K

Ketamine

Ability to drive, ketamine [2] ---> SmPC of [2] of eMC

Patients should be cautioned that driving a car, operating hazardous machinery or engaging in hazardous activities should not be undertaken for 24 hours or more after anaesthesia.

Alcohol, ketamine [2] ---> SmPC of [2] of eMC

The use of ketamine with other central nervous system (CNS) depressants can potentiate CNS depression and/or increase risk of developing respiratory depression.

Aminophylline, ketamine [2] ---> SmPC of [2] of eMC

When ketamine and theophylline are given concurrently, a clinically significant reduction in the seizure threshold is observed. Unpredictable extensor-type seizures have been reported with concurrent administration of these agents.

Anticholinergics, ketamine

The anticholinergic effects may be enhanced

Antihypertensives, ketamine [2] ---> SmPC of [2] of eMC

Concomitant use of antihypertensive agents and ketamine increases the risk of developing hypotension.

Anxiolytics, ketamine [2] ---> SmPC of [2] of eMC

Reduced doses of ketamine may be required with concurrent administration of other anxiolytics, sedatives and hypnotics.

Atracurium, ketamine [2] ---> SmPC of [2] of eMC

Ketamine may potentiate the neuromuscular blocking effects of atracurium and tubocurarine including respiratory depression with apnoea.

Barbiturates, ketamine [2] ---> SmPC of [2] of eMC

Prolonged recovery time may occur if barbiturates are used concurrently with ketamine.

Benzodiazepines, ketamine

The co-administration may prolong the ketamine duration of effect and weaken the adverse effects

Breast-feeding, ketamine [2] ---> SmPC of [2] of eMC

The safe use in lactation has not been established and such use is not recommended.

Chloramphenicol, ketamine

Cloramfenicol prolongs the effect of ketamine

Cisatracurium [1], ketamine ---> SmPC of [1] of eMC

Anaesthetics increase the magnitude and/or duration of action of non-depolarising neuromuscular blocking agents

CNS depressants, ketamine [2] ---> SmPC of [2] of eMC

The use of ketamine with other central nervous system (CNS) depressants can potentiate CNS depression and/or increase risk of developing respiratory depression.

Diazepam, ketamine

Increased pharmacodynamic effect of ketamine

Dopamine agonists, ketamine

The effects of dopaminergic agonist may be enhanced

Etomidate [1], ketamine ---> SmPC of [1] of eMC

Co-administration of etomidate and ketamine appears to have no significant effect on the plasma concentrations or pharmacokinetic parameters of ketamine or its principal metabolite, norketamine.

Halogenated anaesthetics, ketamine [2] ---> SmPC of [2] of eMC

The use of halogenated anaesthetics concomitantly with ketamine can lengthen the elimination half-life of ketamine and delay recovery from anaesthesia.

Halothane, ketamine

Ketamine enhances the anaesthetic effect of halothane

Hypnotics, ketamine [2] ---> SmPC of [2] of eMC

Reduced doses of ketamine may be required with concurrent administration of other anxiolytics, sedatives and hypnotics.

Ketamine [1], muscle relaxants ---> SmPC of [1] of eMC

The use of ketamine with other central nervous system (CNS) depressants can potentiate CNS depression and/or increase risk of developing respiratory depression.

Ketamine [1], opiate agonists ---> SmPC of [1] of eMC

Prolonged recovery time may occur if narcotics are used concurrently with ketamine.

Ketamine [1], phenothiazines ---> SmPC of [1] of eMC

The use of ketamine with other central nervous system (CNS) depressants can potentiate CNS depression and/or increase risk of developing respiratory depression.

Ketamine [1], pregnancy ---> SmPC of [1] of eMC

Ketamine crosses the placenta. The safe use in pregnancy has not been established and such use is not recommended.

Ketamine [1], sedating antihistamines ---> SmPC of [1] of eMC

The use of ketamine with other central nervous system (CNS) depressants can potentiate CNS depression and/or increase risk of developing respiratory depression.

Ketamine [1], sedatives ---> SmPC of [1] of eMC

Reduced doses of ketamine may be required with concurrent administration of other anxiolytics, sedatives and hypnotics.

Ketamine [1], theophylline ---> SmPC of [1] of eMC

When ketamine and theophylline are given concurrently, a clinically significant reduction in the seizure threshold is observed. Unpredictable extensor-type seizures have been reported with concurrent administration of these agents.

Ketamine [1], thiopental ---> SmPC of [1] of eMC

Ketamine has been reported to antagonise the hypnotic effect of thiopental.

Ketamine [1], thyroid hormones ---> SmPC of [1] of eMC

Patients taking thyroid hormones have an increased risk of developing hypertension and tachycardia when given ketamine.

Ketamine [1], tubocuranine ---> SmPC of [1] of eMC

Ketamine may potentiate the neuromuscular blocking effects of atracurium and tubocurarine including respiratory depression with apnoea.

Ketamine, memantin [2] ---> SmPC of [2] of EMA

Concomitant use should be avoided, owing to the risk of pharmacotoxic psychosis

Ketamine, mivacurium [2] ---> SmPC of [2] of eMC

As all non-depolarising neuromuscular blocking agents, the magnitude and/or duration of non-depolarising neuromuscular block may be increased and infusion requirements may be reduced as a result of interaction with ketamine

Ketamine, muscle relaxants (non-depolarizing) ---> SmPC of [atracurium] of eMC

As with all non-depolarising neuromuscular blocking agents the magnitude and/or duration of a non-depolarising neuromuscular block may be increased as a result of interaction with ketamine

Ketamine, neuroleptics

The co-administration may prolong the ketamine duration of effect and weaken the adverse effects

           CONTRAINDICATIONS of Ketamine

           - Ketamine is contra-indicated in persons in whom an elevation of blood pressure would constitute a serious hazard

           - Ketamine hydrochloride is contraindicated in patients who have shown hypersensitivity to the drug or its components.

           - Ketamine should not be used in patients with eclampsia or pre-eclampsia, severe coronary or myocardial disease, cerebrovascular accident or cerebral trauma.

           http://www.medicines.org.uk/emc/

Ketoconazole (Ketoconazole HRA)

Abemaciclib [1], ketoconazole ---> SmPC of [1] of EMA

Use of strong CYP3A4 inhibitors together with abemaciclib should be avoided. If strong CYP3A4 inhibitors need to be co-administered, the dose of abemaciclib should be reduced, followed by careful monitoring of toxicity.

Ability to drive, ketoconazole [2] ---> SmPC of [2] of EMA

Patients should be warned about the potential for dizziness and somnolence and should be advised not to drive or operate machines if any of these symptoms occur.

Abiraterone [1], ketoconazole ---> SmPC of [1] of EMA

Co-administration of abiraterone and ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone.

Abiraterone/niraparib [1], ketoconazole ---> SmPC of [1] of EMA

In a separate clinical study in healthy subjects, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone.

Acalabrutinib [1], ketoconazole ---> SmPC of [1] of EMA

If the strong CYP3A/P-gp inhibitors (e.g., ketoconazole, conivaptan, clarithromycin, indinavir, itraconazole, ritonavir, telaprevir, posaconazole, voriconazole) will be used short-term, treatment with Calquence should be interrupted

Acenocoumarol, ketoconazole

The co-administration may enhance the anticoagulant effect of acenocoumarol and increase the bleeding risk

Afatinib [1], ketoconazole ---> SmPC of [1] of EMA

Therefore, it is recommended to administer strong P-gp inhibitors using staggered dosing, preferably 6 hours or 12 hours apart from GIOTRIF (see section 4.2).

Alcohol, ketoconazole [2] ---> SmPC of [2] of EMA

Exceptional cases of a disulfiram-like reaction have been reported when ketoconazole was co-administered with alcohol. Patients should be advised against alcohol consumption while on treatment

Alectinib [1], ketoconazole ---> SmPC of [1] of EMA

Appropriate monitoring is recommended for patients taking concomitant strong CYP3A inhibitors

Alfentanyl [1], ketoconazole ---> SmPC of [1] of eMC

Alfentanil is metabolised mainly via the human cytochrome P450 3A4 enzyme. In vitro data suggest that cytochrome P450 3A4 enzyme inhibitors may inhibit the metabolism of alfentanil

Alfentanyl, ketoconazole [2] ---> SmPC of [2] of EMA

Potential increase in plasma concentrations of alfentanil and fentanyl. Careful monitoring of adverse reactions (respiratory depression, sedation) is recommended. It may be necessary to lower the dose of alfentanil and fentanyl.

Alfuzosin [1], ketoconazole ---> SmPC of [1] of eMC

The strong CYP3A4 inhibition may increase the plasma concentrations of alfuzosin

Algeldrate/magnesium hydroxide, ketoconazole

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Aliskiren [1], ketoconazole ---> SmPC of [1] of EMA

The moderate inhibition of P-glycoprotein may increase aliskiren gastrointestinal absorption and decrease its biliary excretion. Caution is recommended

Aliskiren, ketoconazole [2] ---> SmPC of [2] of EMA

Careful monitoring. Dose adjustment of aliskiren may be required.

Aliskiren/amlodipine [1], ketoconazole ---> SmPC of [1] of EMA

Aliskiren and ketoconazole co-administration enhances aliskiren gastrointestinal absorption and decreases biliary excretion. Caution should be exercised when aliskiren is administered with ketoconazole, verapamil or other moderate P-gp inhibitors

Aliskiren/amlodipine/hydrochlorothiazide [1], ketoconazole ---> SmPC of [1] of EMA

The moderate inhibition of P-glycoprotein may increase aliskiren gastrointestinal absorption and decrease its biliary excretion. Caution is recommended

Aliskiren/hydrochlorothiazide [1], ketoconazole ---> SmPC of [1] of EMA

The moderate inhibition of P-glycoprotein may increase aliskiren gastrointestinal absorption and decrease its biliary excretion. Caution is recommended

Alitretinoin [1], ketoconazole ---> SmPC of [1] of eMC

Co-administration of alitretinoin with CYP3A4 inhibitors such as ketoconazole increases the plasma level of alitretinoin and dose reduction may be required. The effects of other inhibitors of CYP3A4 have not been studied.

Almasilate, ketoconazole

Possible decrease in ketoconazole absorption due to pH gastrointestinal changes

Alprazolam, ketoconazole [2] ---> SmPC of [2] of EMA

triazolam, oral midazolam and alprazolam are contraindicated with ketoconazole due to potential for prolonged or increased sedation and respiratory depression;

Aluminium hydroxide, ketoconazole [2] ---> SmPC of [2] of EMA

Acid-neutralising medicines should not be administered for at least 2 hours after the intake of ketoconazole.

Aluminium oxide/magnesium hydroxide, ketoconazole

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Aluminium, ketoconazole

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Ambrisentan [1], ketoconazole ---> SmPC of [1] of EMA

Steady-state administration of ketoconazole (a strong inhibitor of CYP3A4) did not result in a clinically significant increase in exposure to ambrisentan

Amifampridine [1], ketoconazole ---> SmPC of [1] of EMA

The concomitant use with sultopride or other medicinal products known to cause QT prolongation is contraindicated as this combination may lead to an enhanced risk of ventricular tachycardia, notably torsade de pointes

Amitriptyline, ketoconazole

The strong CYP3A4 inhibition may increase the plasma concentrations of amitriptyline

Amlodipine, ketoconazole ---> SmPC of [amlodipine/valsartan] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure. Clinical monitoring and dose adjustment may thus be required.

Amlodipine/valsartan [1], ketoconazole ---> SmPC of [1] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure. Clinical monitoring and dose adjustment may thus be required.

Amlodipine/valsartan/hydrochlorothiazide [1], ketoconazole ---> SmPC of [1] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure.

Amprenavir [1], ketoconazole ---> SmPC of [1] of EMA

The CYP3A4 inhibition by amprenavir may increase the plasma concentrations of ketoconazole

Amprenavir/ritonavir, ketoconazole ---> SmPC of [amprenavir] of EMA

The CYP3A4 inhibition by amprenavir may increase the plasma concentrations of itraconazole

Antacids, ketoconazole [2] ---> SmPC of [2] of EMA

Acid-neutralising medicines should not be administered for at least 2 hours after the intake of ketoconazole.

Anticholinergics, ketoconazole ---> SmPC of [procyclidine] of eMC

Anticholinergics may reduce the absorption of ketoconazole.

Apalutamide [1], ketoconazole ---> SmPC of [1] of EMA

No initial dose adjustment is necessary when Erleada is co-administered with a strong inhibitor of CYP3A4 (e.g., ketoconazole, ritonavir, clarithromycin) however, a reduction of the Erleada dose based on tolerability should be considered

Apixaban [1], ketoconazole ---> SmPC of [1] of EMA

The use of apixaban is not recommended in patients receiving concomitant systemic treatment with strong inhibitors of both CYP3A4 and P-gp

Apixaban, ketoconazole [2] ---> SmPC of [2] of EMA

Not recommended due to an increased bleeding risk.

Apremilast [1], ketoconazole ---> SmPC of [1] of EMA

There was no clinically meaningful interaction between ketoconazole and apremilast. Apremilast can be co-administered with a potent CYP3A4 inhibitor such as ketoconazole.

Aprepitant [1], ketoconazole ---> SmPC of [1] of EMA

Concomitant administration of aprepitant with active substances that inhibit CYP3A4 activity should be approached cautiously, as the combination is expected to result several-fold in increased plasma concentrations of aprepitant

Aprepitant, ketoconazole [2] ---> SmPC of [2] of EMA

Careful monitoring. Dose adjustment of aprepitant may be required

Aripiprazole [1], ketoconazole ---> SmPC of [1] of EMA

Strong inhibitors of CYP3A4 may increase the AUC of aripiprazole. A dose reduction should, therefore, be applied

Aripiprazole, ketoconazole [2] ---> SmPC of [2] of EMA

Careful monitoring. Aripiprazole dose should be reduced to approximatively one-half of its prescribed dose.

Artemether/lumefantrine [1], ketoconazole ---> SmPC of [1] of eMC

The concurrent oral administration of potent CYP3A4 inhibitors with artemether/lumefantrine led to a modest increase in artemether, DHA, and lumefantrine exposure. A dose adjustment is considered unnecessary

Astemizole, ketoconazole

The strong CYP3A4 inhibition may increase the plasma concentrations of astemizole and prolong the QT interval. The co-administration is contraindicated

Atazanavir/cobicistat [1], ketoconazole ---> SmPC of [1] of EMA

Ketoconazole is a potent inhibitor and a substrate of CYP3A4. Ketoconazole, and/or cobicistat levels may be increased with coadministration of ketoconazole with EVOTAZ. The mechanism is CYP3A4 inhibition by atazanavir, cobicistat and ketoconazole.

Atazanavir/ritonavir, ketoconazole ---> SmPC of [atazanavir] of EMA

Atazanavir/ritonavir is expected to increase ketoconazole concentrations.

Atenolol/nifedipine [1], ketoconazole ---> SmPC of [1] of eMC

Drugs known to inhibit the cytochrome P450 3A4 system when administered orally with nifedipine may substantial increase the systemic bioavailability of nifedipine due to a decreased first pass metabolism and a decreased elimination

Atogepant [1], ketoconazole ---> SmPC of [1] of EMA

Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir) can significantly increase systemic exposure to atogepant.

Atorvastatin, ketoconazole [2] ---> SmPC of [2] of EMA

Concomitant therapy of ketoconazole with CYP3A4 metabolised HMG-CoA reductase inhibitors is contraindicated due to an increased risk of skeletal muscle toxicity including rhabdomyolysis

Avacopan [1], ketoconazole ---> SmPC of [1] of EMA

Strong CYP3A4 enzyme inhibitors should be used with caution in patients who are being treated with avacopan.

Avanafil [1], ketoconazole ---> SmPC of [1] of EMA

Avanafil is predominantly metabolised by CYP3A4. The strong CYP3A4 inhibitors may increase the exposition of avanafil. Co-administration of avanafil with potent CYP3A4 inhibitors is contraindicated

Avapritinib [1], ketoconazole ---> SmPC of [1] of EMA

Co-administration with strong or moderate CYP3A inhibitors should be avoided because it may increase the plasma concentration of avapritinib

Axitinib [1], ketoconazole ---> SmPC of [1] of EMA

Co-administration of axitinib with strong CYP3A4/5 inhibitors may increase axitinib plasma concentrations. Selection of concomitant medicinal products with no or minimal CYP3A4/5 inhibition potential is recommended.

Azilsartan medoxomil [1], ketoconazole ---> SmPC of [1] of EMA

No clinically significant interactions have been reported in studies of azilsartan medoxomil or azilsartan given with amlodipine, antacids, chlortalidone, digoxin, fluconazole, glyburide, ketoconazole, metformin, and warfarin.

Barnidipine, ketoconazole

The strong CYP3A4 inhibition may increase the plasma concentrations of barnidipine. Barnidipine should not be concomitantly prescribed with strong CYP3A4 inhibitors.

BCRP substrates, ketoconazole [2] ---> SmPC of [2] of EMA

Ketoconazole may be an inhibitor of BCRP at the intestinal level at clinically relevant concentrations. Considering the rapid absorption of ketoconazole, intake of BCRP substrates should be postponed for 2 hours after ketoconazole intake.

Bedaquiline [1], ketoconazole ---> SmPC of [1] of EMA

Due to the potential risk of adverse reactions due to an increase in systemic exposure, prolonged co-administration of bedaquiline and moderate or strong CYP3A4 inhibitors used systemically for more than 14 consecutive days should be avoided.

Bexarotene [1], ketoconazole ---> SmPC of [1] of EMA

On the basis of the oxidative metabolism of bexarotene by cytochrome P450 3A4 (CYP3A4), coadministration with other CYP3A4 substrates may theoretically lead to an increase in plasma bexarotene concentrations.

Bicalutamide [1], ketoconazole ---> SmPC of [1] of eMC

Caution should be exercised when administering bicalutamide to patients taking medicinal products that inhibit the oxidation processes in the liver

Bilastine [1], ketoconazole ---> SmPC of [1] of eMC

Concomitant intake of bilastine, substrate for P-gp, may likewise have the potential to increase plasma concentrations of bilastine.

Boceprevir [1], ketoconazole ---> SmPC of [1] of EMA

The inhibition of CYP3A4 and P-glycoprotein may increase the plasma concentrations of boceprevir. Caution should be exercised when boceprevir is combined with azole antifungals

Bortezomib [1], ketoconazole ---> SmPC of [1] of EMA

The strong CYP3A4 inhibition may increase the AUC of bortezomib. Patients should be closely monitored when given bortezomib in combination with potent CYP3A4 inhibitors

Bortezomib, ketoconazole [2] ---> SmPC of [2] of EMA

Careful monitoring. Dose adjustment of each medicinal product may be required.

Bosentan [1], ketoconazole ---> SmPC of [1] of EMA

For the same reason, concomitant administration of both a potent CYP3A4 inhibitor (such as ketoconazole, itraconazole or ritonavir) and a CYP2C9 inhibitor (such as voriconazole) with Tracleer is not recommended.

Bosentan, ketoconazole [2] ---> SmPC of [2] of EMA

Not recommended due to the potential for hepatic toxicity (see section 4.3).

Bosutinib [1], ketoconazole ---> SmPC of [1] of EMA

The concomitant use of bosutinib with potent CYP3A inhibitors should be avoided, as an increase in bosutinib plasma levels will occur. Selection of an alternate concomitant medicine with no or minimal CYP3A enzyme inhibition potential is recommended.

Breast-feeding, ketoconazole [2] ---> SmPC of [2] of EMA

Since ketoconazole is excreted in the milk, mothers who are under treatment must not breast-feed whilst being treated with Ketoconazole HRA

Brentuximab vedotin [1], ketoconazole ---> SmPC of [1] of EMA

The combination of brentuximab with a strong CYP3A4 and P glycoprotein inhibitor increased the exposure to the antimicrotubule agent MMAE and may increase the incidence of neutropenia.

Brexpiprazole [1], ketoconazole ---> SmPC of [1] of EMA

Based on results of interaction studies, dose adjustment of brexpiprazole to half the dose is recommended when administered concomitantly with strong CYP3A4 inhibitors

Brigatinib [1], ketoconazole ---> SmPC of [1] of EMA

The concomitant use of strong CYP3A inhibitors with Alunbrig should be avoided

Brinzolamide [1], ketoconazole ---> SmPC of [1] of EMA

It is expected that inhibitors of CYP3A4 will inhibit the metabolism of brinzolamide by CYP3A4. Caution is advised if CYP3A4 inhibitors are given concomitantly.

Brinzolamide/brimonidine [1], ketoconazole ---> SmPC of [1] of EMA

It is expected that inhibitors of CYP3A4 will inhibit the metabolism of brinzolamide by CYP3A4. Caution is advised if CYP3A4 inhibitors are given concomitantly.

Brinzolamide/timolol [1], ketoconazole ---> SmPC of [1] of EMA

It is expected that inhibitors of CYP3A4 will inhibit the metabolism of brinzolamide by CYP3A4. Caution is advised if CYP3A4 inhibitors are given concomitantly.

Brotizolam, ketoconazole

The strong CYP3A4 inhibition may increase the plasma concentrations of brotizolam

Budesonide, ketoconazole [2] ---> SmPC of [2] of EMA

Increased in plasma concentrations of budesonide have been observed. Not recommended unless necessary. Careful monitoring and dose adjustment of this drug may be required

Budesonide/formoterol [1], ketoconazole ---> SmPC of [1] of EMA

Potent inhibitors of CYP3A4 are likely to markedly increase plasma levels of budesonide and concomitant use should be avoided.

Budipine, ketoconazole

The co-administration of budipine with drugs known to prolong QT interval is contraindicated

Buprenorphine [1], ketoconazole ---> SmPC of [1] of EMA

CYP3A4 inhibitors may inhibit the metabolism of buprenorphine resulting in increased Cmax and AUC of buprenorphine and norbuprenorphine.

Buprenorphine, ketoconazole [2] ---> SmPC of [2] of EMA

Careful monitoring. The buprenorphine dose should be adjusted.

Buprenorphine/naloxone [1], ketoconazole ---> SmPC of [1] of EMA

Medicines that inhibit the enzyme CYP3A4 may give rise to increased concentrations of buprenorphine. A reduction of the buprenorphine/naloxone dose may be needed.

Buspirone, ketoconazole [2] ---> SmPC of [2] of EMA

Potential increased in plasma concentrations of buspirone. Careful monitoring. Dose adjustement of buspirone may be required.

Busulfan, ketoconazole [2] ---> SmPC of [2] of EMA

Potential increase in plasma concentrations of busulfan. Careful monitoring. Dose adjustment may be required.

Cabazitaxel [1], ketoconazole ---> SmPC of [1] of EMA

Repeated administration of ketoconazole, a strong CYP3A inhibitor, decreased cabazitaxel clearance. Therefore concomitant administration of strong CYP3A inhibitors should be avoided as an increase of plasma concentrations of cabazitaxel may occur

Cabazitaxel, ketoconazole [2] ---> SmPC of [2] of EMA

Careful monitoring. Dose adjustment of each medicinal product may be required.

Cabergoline, ketoconazole

The strong CYP3A4 inhibition may increase the plasma concentrations of cabergoline. The co-administration is contraindicated

Cabozantinib [1], ketoconazole ---> SmPC of [1] of EMA

Co-administration of cabozantinib with strong CYP3A4 inhibitors (increased plasma cabozantinib exposure (AUC) should be approached with caution.

Cabozantinib, ketoconazole [2] ---> SmPC of [2] of EMA

Not recommended due to the risk of increased exposure to these medicinal products and QT prolongation.

Caffeine [1], ketoconazole ---> SmPC of [1] of EMA

Lower doses of caffeine citrate may be needed following co-administration of active substances which are reported to decrease caffeine elimination in adults (e.g., cimetidine and ketoconazole)

Calcium carbonate, ketoconazole

Decreased absorption of ketoconazole. It is recommended to administer the two substances at least 3 hours apart.

Calcium citrate, ketoconazole

Decreased absorption of ketoconazole. It is recommended to administer the two substances at least 3 hours apart.

Calcium, ketoconazole

Decreased absorption of ketoconazole. It is recommended to administer the two substances at least 3 hours apart.

Capivasertib [1], ketoconazole ---> SmPC of [1] of EMA

Co-administration of TRUQAP with strong CYP3A4 inhibitors increases capivasertib concentration, which may increase the risk of TRUQAP toxicity. Co-administration with strong CYP3A4 inhibitors should be avoided

Capmatinib [1], ketoconazole ---> SmPC of [1] of EMA

Patients should be closely monitored for adverse reactions during co-administration of Tabrecta with strong CYP3A inhibitors

Carbaldrate, ketoconazole

The aluminium salt decreases the absorption of the co-administered active principle. Separate administration by at least 2 hours

Carbamazepine, ketoconazole [2] ---> SmPC of [2] of EMA

Ketoconazole is mainly metabolised by cytochrome CYP3A4. Enzyme-inducing medicines may significantly reduce the bioavailability of ketoconazole. Use of ketoconazole with potent enzyme inducers is not recommended.

Cariprazine [1], ketoconazole ---> SmPC of [1] of EMA

Therefore, co-administration of cariprazine with strong CYP3A4 inhibitors (e.g. boceprevir, clarithromycin, cobicistat, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole

Carvedilol [1], ketoconazole ---> SmPC of [1] of eMC

The enzymatic inhibition may increase the plasma levels of carvedilol

Ceritinib [1], ketoconazole ---> SmPC of [1] of EMA

If it is not possible to avoid concomitant use with strong CYP3A inhibitors, reduce the ceritinib dose by approximately one third, rounded to the nearest multiple of the 150 mg dosage strength.

Chloroquine, ketoconazole

The co-administration of chloroquine with hepatotoxic medicinal products is not recommended

Chlorpromazine [1], ketoconazole ---> SmPC of [1] of eMC

There is an increased risk of arrhythmias when chlorpromazine is used concomitant with QT prolonging drugs. The combination is not recommended

Ciclesonide, ketoconazole [2] ---> SmPC of [2] of EMA

Increased in plasma concentrations of Ciclesonide have been observed. Not recommended unless necessary. Careful monitoring and dose adjustment of this drug may be required

Cilostazol, ketoconazole [2] ---> SmPC of [2] of EMA

The overall pharmacological activity of cilostazol increases 35% when co-administered with ketoconazole. Careful monitoring.

Cimetidine [1], ketoconazole ---> SmPC of [1] of eMC

Cimetidine increases the pH und decreases the absorption of ketoconazole.

Cinacalcet [1], ketoconazole ---> SmPC of [1] of EMA

Cinacalcet is metabolised in part by the enzyme CYP3A4. Co-administration of a strong inhibitor of CYP3A4 may increase cinacalcet levels. Dose adjustment of cinacalcet may be required

Cinacalcet, ketoconazole [2] ---> SmPC of [2] of EMA

Careful monitoring. Dose adjustment of cinacalcet may be required.

Cinitapride, ketoconazole

The strong CYP3A4 inhibition may increase the plasma concentrations of cinitapride

Cisapride, ketoconazole

The strong CYP3A4 inhibition may increase the plasma concentrations of cisapride and prolong the QT interval. The co-administration is contraindicated

Clarithromycin, ketoconazole [2] ---> SmPC of [2] of EMA

Concomitant therapy of ketoconazole with clarithromycin in patients with severe renal impairment is contraindicated due to an increased risk of hepatotoxicity and QT interval prolongation

Cloprednol, ketoconazole

The strong CYP3A4 inhibition may increase the plasma concentrations of cloprednol

Cobicistat [1], ketoconazole ---> SmPC of [1] of EMA

Co-administration of cobicistat with medicinal products that inhibit CYP3A may result in increased plasma concentration of cobicistat. Some examples include, but are not limited to, itraconazole, ketoconazole, and voriconazole (see Table 3).

Colchicine, ketoconazole [2] ---> SmPC of [2] of EMA

The co-administration is contraindicated in patients with renal impairment due to an increased risk of severe adverse reactions;

Contraceptives, ketoconazole [2] ---> SmPC of [2] of EMA

Women must be provided with comprehensive information on pregnancy prevention. As a minimum requirement, women of childbearing potential must use an effective method of contraception

Coumarin anticoagulants, ketoconazole [2] ---> SmPC of [2] of EMA

Potential increase in plasma concentrations of warfarin. Careful monitoring. INR (international normalised ratio) monitoring recommended.

Crisaborole [1], ketoconazole ---> SmPC of [1] of EMA

Based on in vitro data, concomitant administration of Staquis and CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, erythromycin, clarithromycin, ritonavir) can increase systemic crisaborole concentrations

Crizotinib [1], ketoconazole ---> SmPC of [1] of EMA

Coadministration of crizotinib with strong CYP3A inhibitors may increase crizotinib plasma concentrations. Therefore, the concomitant use of strong CYP3A inhibitors should be avoided.

Crizotinib, ketoconazole [2] ---> SmPC of [2] of EMA

Not recommended due to the risk of QT interval prolongation and serious hepatic adverse reactions. Monitoring of QT-prolongation if used concomitantly.

Cyclosporine, ketoconazole [2] ---> SmPC of [2] of EMA

Increased in plasma concentrations of Ciclosporin have been observed. Not recommended unless necessary. Careful monitoring and dose adjustment of this drug may be required

Cyproterone [1], ketoconazole ---> SmPC of [1] of eMC

Since cyproterone acetate is metabolised by CYP3A4, it is expected strong inhibitors of CYP3A4 inhibit the metabolism of cyproterone acetate.

Dabigatran etexilate [1], ketoconazole ---> SmPC of [1] of EMA

Dabigatran is a substrate for the efflux transporter P-gp. Concomitant administration of strong P-gp inhibitors is expected to result in increased dabigatran plasma concentrations. The coadministration with systemic ketoconazole is contraindicated

Dabigatran [1], ketoconazole ---> SmPC of [1] of EMA

Dabigatran is a substrate for the efflux transporter P-gp. Concomitant administration of strong P-gp inhibitors is expected to result in increased dabigatran plasma concentrations. The coadministration with systemic ketoconazole is contraindicated

Dabigatran, ketoconazole [2] ---> SmPC of [2] of EMA

The coadministration with dabigatran is contraindicated due to an increased bleeding risk;

Dabrafenib [1], ketoconazole ---> SmPC of [1] of EMA

Administration of ketoconazole (a CYP3A4 inhibitor) 400 mg once daily, with dabrafenib 75 mg twice daily, resulted in a 71% increase in dabrafenib AUC and a 33% increase in dabrafenib Cmax relative to administration of dabrafenib 75 mg twice daily alone.

Dabrafenib, ketoconazole [2] ---> SmPC of [2] of EMA

Not recommended due to the risk of increased exposure to these medicinal products and QT prolongation.

Daclatasvir [1], ketoconazole ---> SmPC of [1] of EMA

Strong inhibitors of CYP3A4 may increase the plasma levels of daclatasvir. Dose adjustment of daclatasvir is recommended when coadministered with strong inhibitors of CYP3A4

Dapoxetine [1], ketoconazole ---> SmPC of [1] of eMC

The strong CYP3A4 inhibition may increase the plasma concentrations of dapoxetine. Concomitant use of dapoxetine and potent CYP3A4 inhibitors is contraindicated

Darifenacin [1], ketoconazole ---> SmPC of [1] of EMA

Darifenacin should not be used together with potent CYP3A4 inhibitors (see section 4.3) such as protease inhibitors (e.g. ritonavir), ketoconazole and itraconazole.

Darunavir/cobicistat [1], ketoconazole ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the antifungal plasma concentrations, and darunavir and/or cobicistat plasma concentrations may be increased by the antifungal (CYP3A inhibition)

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], ketoconazole ---> SmPC of [1] of EMA

Co-administration of Symtuza and other medicinal products that inhibit CYP3A may decrease the clearance of darunavir and cobicistat and may result in increased plasma concentrations of darunavir and cobicistat

Darunavir/ritonavir, ketoconazole

Potent inhibitors of CYP3A4 may increase the bioavailability of ketoconazole, these medicinal products should be used with caution when co-administered with ketoconazole and patients should be monitored closely

Darunavir/ritonavir, ketoconazole ---> SmPC of [darunavir] of EMA

Co-administration of darunavir and ritonavir with other medicinal products that inhibit CYP3A may decrease the clearance of darunavir and ritonavir. Co-administration with strong CYP3A4 inhibitors is not recommended and caution is warranted

Dasabuvir with ombitasvir/paritaprevir/ritonavir, ketoconazole ---> SmPC of [dasabuvir] of EMA

CYP3A4/Pgp inhibition by ketoconazole and ombitasvir/paritaprevir/ritonavir may increase the plasma concentrations of ketoconazole and dasabuvir. Concomitant use is contraindicated

Dasatinib [1], ketoconazole ---> SmPC of [1] of EMA

Concomitant use of dasatinib and medicinal products or substances which potently inhibit CYP3A4 may increase exposure to dasatinib. Therefore, in patients receiving dasatinib, systemic administration of a potent CYP3A4 inhibitor is not recommended

Dasatinib, ketoconazole [2] ---> SmPC of [2] of EMA

Not recommended due to the risk of increased exposure to these medicinal products and QT prolongation.

Deflazacort, ketoconazole

The strong CYP3A4 inhibition may increase the plasma concentrations of glucocorticoid

Desloratadine [1], ketoconazole ---> SmPC of [1] of EMA

No clinically relevant interactions were observed in clinical trials with desloratadine in which ketoconazole were co-administered.

Desloratadine/pseudoephedrine [1], ketoconazole ---> SmPC of [1] of EMA

No clinically relevant interactions were observed in clinical trials with desloratadine in which ketoconazole were co-administered.

Dexamethasone, ketoconazole [2] ---> SmPC of [2] of EMA

Potential increase in plasma concentrations of dexamethasone. Careful monitoring. Dose adjustment of dexamethasone may be required.

Dextromethorphan/quinidine [1], ketoconazole ---> SmPC of [1] of EMA

Concomitant administration of medicines that inhibit CYP3A4 can be expected to increase plasma levels of quinidine, which could increase risk relating to QTc prolongation. Strong and moderate CYP3A4 inhibitors should be avoided during treatment.

Diazepam [1], ketoconazole ---> SmPC of [1] of eMC

The CYP3A4 and CYP 2C19 inhibition may increase the plasma levels of diazepam

Didanosine, ketoconazole

Ketoconazole should be administered 2 hours before didanosine

Dienogest, ketoconazole

The CYP3A4 inhibition may increase the plasma levels of dienogest

Digitoxin, ketoconazole

The CYP3A4 inhibition may increase the plasma levels of digitoxin

Digoxin, ketoconazole [2] ---> SmPC of [2] of EMA

Potential increase in plasma concentrations of digoxine. Careful monitoring of digoxin levels is recommended.

Dihydroergotamine, ketoconazole [2] ---> SmPC of [2] of EMA

Concomitant therapy of ketoconazole with ergot alkaloids is contraindicated due to an increased risk of ergotism and other serious vasospastic adverse events

Dihydropyridines, ketoconazole [2] ---> SmPC of [2] of EMA

Potential increase in plasma concentrations of dihydropyridines. Careful monitoring. Dose adjustment of dihydropyridines may be required.

Disopyramide, ketoconazole [2] ---> SmPC of [2] of EMA

Concomitant therapy of ketoconazole with substances that may have their plasma concentrations increased and have QT prolonging potential is contraindicated

Docetaxel [1], ketoconazole ---> SmPC of [1] of EMA

If the concomitant use of a strong CYP3A4 cannot be avoided, a close clinical surveillance is warranted and a dose-adjustment of docetaxel may be suitable during the treatment with the strong CYP3A4 inhibitor

Docetaxel [1], ketoconazole ---> SmPC of [1] of EMA

In a pharmacokinetic study with 7 patients, the co-administration of docetaxel with the strong CYP3A4 inhibitor ketoconazole leads to a significant decrease in docetaxel clearance by 49%.

Docetaxel, ketoconazole [2] ---> SmPC of [2] of EMA

Careful monitoring. Dose adjustment of each medicinal product may be required.

Dofetilide [1], ketoconazole ---> SmPC of [1] of EMA

The strong CYP3A4 inhibition may increase the plasma concentrations of dofetilide and prolong the QT interval. The co-administration is contraindicated

Dolutegravir [1], ketoconazole ---> SmPC of [1] of EMA

The inhibition of CYP3A4 may increase plasma levels of dolutegravir. No dose adjustment is necessary. Based on data from other CYP3A4 inhibitors, a marked increase is not expected.

Dolutegravir/rilpivirine [1], ketoconazole ---> SmPC of [1] of EMA

Induction of CYP3A due to high rilpivirine dose in the study. No dose adjustment is required.

Domperidone, ketoconazole [2] ---> SmPC of [2] of EMA

Not recommended due to an increased risk in QT prolongation.

Donepezil [1], ketoconazole ---> SmPC of [1] of eMC

The strong CYP3A4-inhibition may increase the plasma levels of donepezil

Doravirine [1], ketoconazole ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], ketoconazole ---> SmPC of [1] of EMA

No dose adjustment is required.

Dronedarone [1], ketoconazole ---> SmPC of [1] of EMA

Concomitant use of dronedarone with strong CYP3A4 inhibitors increases dronedarone exposure. The combination of dronedarone with strong CYP3A4 inhibitors is contraindicated

Dronedarone, ketoconazole [2] ---> SmPC of [2] of EMA

Concomitant therapy of ketoconazole with substances that may have their plasma concentrations increased and have QT prolonging potential is contraindicated

Droperidol [1], ketoconazole ---> SmPC of [1] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzyme CYP3A4 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Drugs primarily metabolised by CYP3A4, ketoconazole [2] ---> SmPC of [2] of EMA

Ketoconazole is a potent inhibitor of CYP3A4 and can inhibit the metabolism of medicinal products metabolised by this enzyme. This can result in an increase and/or prolongation of their effects, including adverse reactions.

Dutasteride [1], ketoconazole ---> SmPC of [1] of eMC

Long-term combination of dutasteride with drugs that are potent inhibitors of the enzyme CYP3A4 may increase serum concentrations of dutasteride.

Duvelisib [1], ketoconazole ---> SmPC of [1] of EMA

Duvelisib dose should be reduced to 15 mg twice daily when co-administered with a strong CYP3A4 inhibitor

Ebastine, ketoconazole [2] ---> SmPC of [2] of EMA

Increasing in plasma concentrations of ebastine have been observed. Not recommended due to an increased risk in QT prolongation

Edoxaban [1], ketoconazole ---> SmPC of [1] of EMA

Edoxaban is a substrate for the efflux transporter P-gp. In pharmacokinetic (PK) studies, concomitant administration of edoxaban with the P-gp inhibitor resulted in increased plasma concentrations of edoxaban.

Edoxaban, ketoconazole [2] ---> SmPC of [2] of EMA

Dose of edoxaban needs to be reduced when used concomitantly, please consult edoxaban SmPC.

Elacestrant [1], ketoconazole ---> SmPC of [1] of EMA

Concomitant administration of ORSERDU with strong CYP3A4 inhibitors should be avoided which may increase the risk of adverse reactions

Elbasvir/grazoprevir [1], ketoconazole ---> SmPC of [1] of EMA

CYP3A inhibition. Co-administration is not recommended.

Eletriptan [1], ketoconazole ---> SmPC of [1] of eMC

In clinical studies with potent inhibitors of CYP3A4 significant increases in eletriptan Cmax and AUC were observed. Eletriptan should not be used together with potent CYP3A4 inhibitors

Eletriptan, ketoconazole [2] ---> SmPC of [2] of EMA

Not recommended.

Eliglustat [1], ketoconazole ---> SmPC of [1] of EMA

Increased eliglustat exposition would be expected for strong inhibitors of CYP3A. Caution should be used with strong CYP3A inhibitors in intermediate and extensive metabolisers.

Elvitegravir [1], ketoconazole ---> SmPC of [1] of EMA

No dose adjustment is required when Vitekta is co-administered with ketoconazole.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [1], ketoconazole ---> SmPC of [1] of EMA

Concentrations of ketoconazole and/or cobicistat may increase with co-administration of Genvoya. When administering with Genvoya, the maximum daily dose of ketoconazole should not exceed 200 mg per day.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], ketoconazole ---> SmPC of [1] of EMA

Concentrations of ketoconazole and/or cobicistat may increase with co-administration of elvitegravir/cobicistat/emtricitabine/tenofovir. Caution is warranted

Elvitegravir/ritonavir, ketoconazole ---> SmPC of [elvitegravir] of EMA

No dose adjustment is required when elvitegravir is co-administered with ketoconazole. Due to inhibition of CYP3A by ritonavir, ketoconazole exposure is increased.

Emtricitabine/rilpivirine/tenofovir alafenamide [1], ketoconazole ---> SmPC of [1] of EMA

Co-administration of this antifungal agent is expected to increase plasma concentrations of rilpivirine (inhibition of CYP3A) and tenofovir alafenamide (inhibition of P-gp). Co-administration is not recommended.

Emtricitabine/rilpivirine/tenofovir disoproxil [1], ketoconazole ---> SmPC of [1] of EMA

Concomitant use of Eviplera with azole antifungal agents may cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes). At a dose of 25 mg of rilpivirine, dose adjustment is required.

Emtricitabine/tenofovir alafenamide [1], ketoconazole ---> SmPC of [1] of EMA

Co-administration of ketoconazole or itraconazole, which are potent P-gp inhibitors, is expected to increase plasma concentrations of tenofovir alafenamide.

Encorafenib [1], ketoconazole ---> SmPC of [1] of EMA

Concomitant administration of encorafenib with strong CYP3A4 inhibitors should be avoided (due to increased encorafenib exposure and potential increase in toxicity, see section 5.2).

Enfortumab vedotin [1], ketoconazole ---> SmPC of [1] of EMA

Patients receiving concomitant strong CYP3A4 inhibitors should be monitored more closely for signs of toxicities.

Entrectinib [1], ketoconazole ---> SmPC of [1] of EMA

Co-administration of strong and moderate CYP3A inhibitors (including, but not limited to, ritonavir, saquinavir, ketoconazole, itraconazole, voriconazole, posaconazole, grapefruit or Seville oranges) should be avoided.

Eplerenone, ketoconazole [2] ---> SmPC of [2] of EMA

Contraindicated due to the increased risk of hyperkalaemia and hypotension

Ergometrine, ketoconazole [2] ---> SmPC of [2] of EMA

Concomitant therapy of ketoconazole with ergot alkaloids is contraindicated due to an increased risk of ergotism and other serious vasospastic adverse events

Ergot derivatives, ketoconazole [2] ---> SmPC of [2] of EMA

Concomitant therapy of ketoconazole with ergot alkaloids is contraindicated due to an increased risk of ergotism and other serious vasospastic adverse events

Ergotamine, ketoconazole [2] ---> SmPC of [2] of EMA

Concomitant therapy of ketoconazole with ergot alkaloids is contraindicated due to an increased risk of ergotism and other serious vasospastic adverse events

Eribulin [1], ketoconazole ---> SmPC of [1] of EMA

No drug-drug interactions are expected with CYP3A4 inhibitors and inducers. Eribulin exposure (AUC and Cmax) was unaffected by ketoconazole, a CYP3A4 and P glycoprotein (Pgp) inhibitor, and rifampicin, a CYP3A4 inducer.

Erlotinib [1], ketoconazole ---> SmPC of [1] of EMA

Erlotinib is metabolised in the liver by the hepatic cytochromes in humans, primarily CYP3A4 and to a lesser extent by CYP1A2. Potent inhibitors of CYP3A4 activity decrease erlotinib metabolism and increase erlotinib plasma concentrations.

Erlotinib, ketoconazole [2] ---> SmPC of [2] of EMA

Not recommended due to the risk of increased exposure to these medicinal products and QT prolongation.

Ertugliflozin/sitagliptin [1], ketoconazole ---> SmPC of [1] of EMA

it is possible that potent CYP3A4 inhibitors (i.e., ketoconazole, itraconazole, ritonavir, clarithromycin) could alter the pharmacokinetics of sitagliptin in patients with severe renal impairment or ESRD.

Esomeprazole [1], ketoconazole ---> SmPC of [1] of EMA

The absorption of medicinal products taken orally such as ketoconazole, itraconazole and erlotinib can decrease during treatment with esomeprazole

Estradiol/norethisterone [1], ketoconazole ---> SmPC of [1] of eMC

Drugs that inhibit the activity of hepatic microsomal drug metabolising enzymes, e.g. ketoconazole, may increase circulating levels of the active substances

Estrogens, ketoconazole ---> SmPC of [conjugated oestrogens/bazedoxifene] of EMA

Inhibitors of CYP3A4 may increase plasma concentrations of oestrogens and may result in adverse reactions

Ethinylestradiol/norgestimate [1], ketoconazole ---> SmPC of [1] of eMC

Increase in plasma hormone levels associated with co-administered drug

Etonogestrel, ketoconazole

The strong CYP3A4 inhibition may increase the plasma concentrations of etonogestrel

Etoricoxib [1], ketoconazole ---> SmPC of [1] of eMC

Ketoconazole, a potent inhibitor of CYP3A4, dosed at 400 mg once a day for 11 days to healthy volunteers, did not have any clinically important effect on the single-dose pharmacokinetics of 60 mg etoricoxib (43% increase in AUC).

Etravirine [1], ketoconazole ---> SmPC of [1] of EMA

Possible increase of plasma concentrations of etravirine and decreased plasma concentrations of ketoconazole. The co-administration can be used without dose adjustments.

Everolimus [1], ketoconazole ---> SmPC of [1] of EMA

Large increase in everolimus concentration is expected. Concomitant treatment of everolimus and potent CYP3A4 inhibitors is not recommended.

Everolimus, ketoconazole [2] ---> SmPC of [2] of EMA

The coadministration the everolimus or sirolimus (also known as rapamycin) with ketoconazole is contraindicated due to an increase of the plasma concentrations of these medicinal products;

Exemestane [1], ketoconazole ---> SmPC of [1] of eMC

In a clinical pharmacokinetic study, the specific inhibition of CYP 3A4 showed no significant effects on the pharmacokinetics of exemestane.

Ezetimibe/atorvastatin [1], ketoconazole ---> SmPC of [1] of eMC

Potent CYP3A4 inhibitors have been shown to lead to markedly increased concentrations of atorvastatin. Coadministration of potent CYP3A4 inhibitors should be avoided if possible.

Ezetimibe/simvastatine [1], ketoconazole ---> SmPC of [1] of eMC

Potent inhibitors of cytochrome P450 3A4 with simvastatine increase the risk of myopathy and rhabdomyolysis. The co-administration of simvastatine with potent inhibitors of CYP3A4 is contraindicated

Famotidine, ketoconazole

Decreased absorption of ketoconazole. Ketoconazole should be administered 2 hours before famotidine

Fedratinib [1], ketoconazole ---> SmPC of [1] of EMA

If strong CYP3A4 inhibitors cannot be replaced, the dose of Inrebic should be reduced when administering with strong CYP3A4 inhibitors, (e.g. ketoconazole, ritonavir).

Felodipine, ketoconazole [2] ---> SmPC of [2] of EMA

Concomitant therapy of ketoconazole with felodipine is contraindicated due to an increased risk of oedema and congestive heart failure

Felodipine/metoprolol, ketoconazole

It has been shown that inhibitors of cytochrome P450-3A4 system increase the plasma concentrations of felodipine. The concomitant use with strong CYP3A4 inhibitors should be avoided

Fenofibrate/simvastatin [1], ketoconazole ---> SmPC of [1] of EMA

Potent inhibitors of cytochrome P450 3A4 increase the risk of myopathy and rhabdomyolysis by increasing the concentration of HMG-CoA reductase inhibitory activity in plasma during simvastatin therapy. Concomitant use is contraindicated

Fentanyl [1], ketoconazole ---> SmPC of [1] of EMA

The concomitant use of Effentora with strong CYP3A4 inhibitors or moderate CYP3A4 inhibitors may result in increased fentanyl plasma concentrations, potentially causing serious adverse drug reactions including fatal respiratory depression.

Fentanyl, ketoconazole [2] ---> SmPC of [2] of EMA

Potential increase in plasma concentrations of alfentanil and fentanyl. Careful monitoring of adverse reactions (respiratory depression, sedation) is recommended. It may be necessary to lower the dose of alfentanil and fentanyl.

Fertility, ketoconazole [2] ---> SmPC of [2] of EMA

Studies in animals have shown effects on male and female reproductive parameters (see section 5.3).

Fesoterodine [1], ketoconazole ---> SmPC of [1] of EMA

The maximum dose of fesoterodine should be restricted to 4 mg when used concomitantly with potent CYP3A4 inhibitors

Fesoterodine, ketoconazole [2] ---> SmPC of [2] of EMA

The coadministration of fesoterodine or solifenacin with ketoconazole is contraindicated in patients with renal impairment;

Fexofenadine [1], ketoconazole ---> SmPC of [1] of eMC

The co-administration increases the plasma levels of fexofenadine

Fidaxomicin [1], ketoconazole ---> SmPC of [1] of EMA

Fidaxomicin is a substrate of P-gp. Co-administration of potent inhibitors of P-gp increases fidaxomicin exposure. Co-administration of potent inhibitors of P-gp is not recommended.

Finerenone [1], ketoconazole ---> SmPC of [1] of EMA

Concomitant use of Kerendia with strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, nelfinavir, cobicistat, telithromycin or nefazodone) is contraindicated (see section 4.3), since a marked increase in finerenone exposure is expected.

Fingolimod [1], ketoconazole ---> SmPC of [1] of EMA

Co-administration of fingolimod with CYP3A4 inhibitors may increase the fingolimod exposure. Caution should be exercised with substances that may inhibit CYP3A4

Fludrocortisone [1], ketoconazole ---> SmPC of [1] of eMC

Corticosteroid clearance may be decreased, resulting in increased effects.

Flunitrazepam, ketoconazole

Substances that inhibit hepatic enzymes may enhance the effect of benzodiazepines. Interactions with strong CYP3A4 inhibitors cannot be excluded

Fluticasone furoate [1], ketoconazole ---> SmPC of [1] of EMA

This small increase in exposure did not result in a statistically significant difference in 24 hour serum cortisol levels between the two groups.

Fluticasone furoate/umeclidinium/vilanterol [1], ketoconazole ---> SmPC of [1] of EMA

Caution is advised when co-administering with strong CYP 3A4 inhibitors (e.g. ketoconazole, ritonavir, cobicistat-containing products) as there is potential for increased systemic exposure to both fluticasone furoate and vilanterol.

Fluticasone furoate/vilanterol [1], ketoconazole ---> SmPC of [1] of EMA

Caution is advised when co-administering with strong CYP 3A4 inhibitors as there is potential for increased systemic exposure to both fluticasone furoate and vilanterol, and concomitant use should be avoided.

Fluticasone, ketoconazole

Potential increase in plasma concentrations of fluticasone. Careful monitoring. Dose adjustment of fluticasone may be required.

Fluticasone, ketoconazole [2] ---> SmPC of [2] of EMA

Potential increase in plasma concentrations of fluticasone. Careful monitoring. Dose adjustment of fluticasone may be required.

Formoterol/glycopyrronium/budesonide [1], ketoconazole ---> SmPC of [1] of EMA

The metabolism of budesonide is primarily mediated by CYP3A4. Co-treatment with strong CYP3A inhibitors are expected to increase the risk of systemic side effects, and should be avoided

Fosamprenavir/ritonavir, ketoconazole

Potent inhibitors of CYP3A4 may increase the bioavailability of ketoconazole, these medicinal products should be used with caution when co-administered with ketoconazole and patients should be monitored closely

Fosamprenavir/ritonavir, ketoconazole ---> SmPC of [fosamprenavir] of EMA

The CYP3A4 inhibition by fosamprenavir/ritonavir may increase the plasma concentrations of ketoconazole

Fosaprepitant [1], ketoconazole ---> SmPC of [1] of EMA

Concomitant administration of fosaprepitant with active substances that inhibit CYP3A4 activity should be approached cautiously as the combination is expected to result in increased plasma concentrations of aprepitant

Fosphenytoin [1], ketoconazole ---> SmPC of [1] of eMC

CYP2C9 inhibition may increase plasma phenytoin concentrations

Fostamatinib [1], ketoconazole ---> SmPC of [1] of EMA

Concomitant use of fostamatinib with strong CYP3A4 inhibitors increases exposure to R406 (the major active metabolite), which may increase the risk of adverse reactions.

Fulvestrant [1], ketoconazole ---> SmPC of [1] of EMA

Clinical interaction studies with rifampicin (inducer of CYP3A4) and ketoconazole (inhibitor of CYP3A4) showed no clinically relevant change in fulvestrant clearance.

Galantamine [1], ketoconazole ---> SmPC of [1] of eMC

The co-administration of galantamine with strong CYP3A4 inhibitors may increase the bioavailability of galantamine and the incidence of cholinergic adverse reactions, predominantly nausea and vomiting.

Gastric pH increasing medication, ketoconazole [2] ---> SmPC of [2] of EMA

Acid-neutralising medicines should not be administered for at least 2 hours after the intake of ketoconazole.

Gefitinib [1], ketoconazole ---> SmPC of [1] of EMA

Concomitant administration with potent inhibitors of CYP3A4 activity may increase gefitinib plasma concentrations. The increase may be clinically relevant since adverse reactions are related to dose and exposure.

Glasdegib [1], ketoconazole ---> SmPC of [1] of EMA

Caution should be used when administering concomitantly with strong CYP3A4 inhibitors as an increase in glasdegib plasma concentration may occur.

Glecaprevir/pibrentasvir [1], ketoconazole ---> SmPC of [1] of EMA

Co-administration of Maviret with medicinal products that inhibit P-gp and BCRP may slow elimination of glecaprevir and pibrentasvir and thereby increase plasma exposure of the antivirals.

Glucocorticoids, ketoconazole

The enzymatic inhibition may increase the plasma concentrations of glucocorticoid

Glycopyrronium/indacaterol/mometasone [1], ketoconazole ---> SmPC of [1] of EMA

However, there may be a potential for increased systemic exposure to mometasone furoate when strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, nelfinavir, ritonavir, cobicistat) are co-administered.

Granisetron [1], ketoconazole ---> SmPC of [1] of EMA

In vitro studies have shown that ketoconazole may inhibit the metabolism of granisetron via the cytochrome P450 3A isoenzyme family. The clinical significance of this is unknown.

Guanfacin [1], ketoconazole ---> SmPC of [1] of EMA

Co-administration of Intuniv with moderate and strong CYP3A4/5 inhibitors elevates plasma guanfacine concentrations and increases the risk of adverse reactions such as hypotension, bradycardia, and sedation.

H2 antagonists, ketoconazole [2] ---> SmPC of [2] of EMA

Acid-neutralising medicines should not be administered for at least 2 hours after the intake of ketoconazole. It is advised to administer ketoconazole with an acidic beverage eg cola beverage, orange juice.

Halofantrine, ketoconazole [2] ---> SmPC of [2] of EMA

Concomitant therapy of ketoconazole with substances that may have their plasma concentrations increased and have QT prolonging potential is contraindicated

Haloperidol, ketoconazole [2] ---> SmPC of [2] of EMA

Potential increased in plasma concentrations of haloperidol. Not recommended due to the increased risk of QT prolongation and extrapyramidal symptoms. It may be necessary to reduce haloperidol dosage.

Hemp extract, ketoconazole

The co-administration may increase the Cmax and THC and CBD.

Hepatotoxic drugs, ketoconazole [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole and other medications known to have potentially hepatotoxic effect (eg paracetamol) is not recommended since the combination may lead to increased risk of liver damage.

HMG-CoA reductase inhibitors, ketoconazole [2] ---> SmPC of [2] of EMA

Concomitant therapy of ketoconazole with CYP3A4 metabolised HMG-CoA reductase inhibitors is contraindicated due to an increased risk of skeletal muscle toxicity including rhabdomyolysis

Hydrocortisone [1], ketoconazole ---> SmPC of [1] of EMA

Potent CYP 3A4 inhibitors can inhibit the metabolism of hydrocortisone, and thus increase blood levels.

Hydrotalcite, ketoconazole

The co-administration of hydrotalcite with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 1-2 hours

Ibrutinib [1], ketoconazole ---> SmPC of [1] of EMA

Concomitant use of IMBRUVICA and medicinal products that strongly or moderately inhibit CYP3A4 can increase ibrutinib exposure and strong CYP3A4 inhibitors should be avoided.

Ibrutinib, ketoconazole [2] ---> SmPC of [2] of EMA

Not recommended as it may increase ibrutinib-related toxicity.

Idelalisib [1], ketoconazole ---> SmPC of [1] of EMA

No initial dose adjustment of idelalisib is considered necessary when administered with CYP3A/P-gp inhibitors, but an intensified monitoring of adverse reactions is recommended.

Imatinib [1], ketoconazole ---> SmPC of [1] of EMA

There was a significant increase in exposure to imatinib (the mean Cmax and AUC of imatinib rose by 26% and 40%, respectively) in healthy subjects when it was co-administered with a single dose of ketoconazole (a CYP3A4 inhibitor).

Imatinib, ketoconazole [2] ---> SmPC of [2] of EMA

Careful monitoring. Dose adjustment of each medicinal product may be required.

Indacaterol/mometasone [1], ketoconazole ---> SmPC of [1] of EMA

There may be a potential for increased systemic exposure to mometasone furoate when strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, nelfinavir, ritonavir, cobicistat) are co-administered.

Indinavir [1], ketoconazole ---> SmPC of [1] of EMA

Dose reduction of CRIXIVAN to 600 mg every 8 hours should be considered.

Indinavir, ketoconazole [2] ---> SmPC of [2] of EMA

Careful monitoring. Dose reduction of indinavir to 600 mg every 8 hours should be considered.

Indinavir/ritonavir, ketoconazole ---> SmPC of [indinavir] of EMA

Indinavir and ritonavir inhibit CYP3A4 and as a result are expected to increase the plasma concentrations of ketoconazole. Coadministration of ritonavir and ketoconazole caused an increased incidence of gastrointestinal and hepatic adverse events.

Irinotecan [1], ketoconazole ---> SmPC of [1] of EMA

Patients receiving concomitant non-liposomal irinotecan and ketoconazole, a CYP3A4 and UGT1A1 inhibitor, have increased SN-38 exposure by 109%.

Irinotecan, ketoconazole [2] ---> SmPC of [2] of EMA

The co-administration with irinotecan due to an alteration of the metabolism of this medicinal product;

Isavuconazole [1], ketoconazole ---> SmPC of [1] of EMA

Co-administration of CRESEMBA with the strong CYP3A4/5 inhibitor ketoconazole is contraindicated, since this medicinal product can significantly increase plasma concentrations of isavuconazole

Isavuconazole, ketoconazole [2] ---> SmPC of [2] of EMA

Not recommended due to increased risk of isavuconazole adverse reactions, please consult isavuconazole SmPC

Isoniazid, ketoconazole [2] ---> SmPC of [2] of EMA

Ketoconazole is mainly metabolised by cytochrome CYP3A4. Enzyme-inducing medicines may significantly reduce the bioavailability of ketoconazole. Use of ketoconazole with potent enzyme inducers is not recommended.

Isradipine [1], ketoconazole ---> SmPC of [1] of eMC

Caution should be exercised when co-administering isradipine with strong CYP3A inhibitors

Ivabradine [1], ketoconazole ---> SmPC of [1] of EMA

The concomitant use of ivabradine and potent CYP3A4 inhibitors increases plasma concentrations of ivabradine (may be associated with the risk of excessive bradycardia). The concomitant use of ivabradine with these medicinal products is contraindicated

Ivacaftor [1], ketoconazole ---> SmPC of [1] of EMA

A reduction of the ivacaftor dose is recommended for co-administration with strong CYP3A inhibitors, such as ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin and clarithromycin (see Table 2 in section 4.2 and section 4.4).

Ivacaftor/tezacaftor/elexacaftor [1], ketoconazole ---> SmPC of [1] of EMA

The dose of IVA/TEZ/ELX and ivacaftor should be reduced when co-administered with strong CYP3A inhibitors (see Table 1 in section 4.2 and section 4.4).

Ivosidenib [1], ketoconazole ---> SmPC of [1] of EMA

Ivosidenib induces CYP3A4 and it may, therefore, decrease systemic exposure to CYP3A4 substrates. Patients should be monitored for loss of antifungal efficacy if use of itraconazole or ketoconazole cannot be avoided (see section 4.5).

Ivosidenib [1], ketoconazole* ---> SmPC of [1] of EMA

Coadministration of moderate or strong CYP3A4 inhibitors increases ivosidenib plasma levels. This may increase the risk of QTc interval prolongation and suitable alternatives that are not moderate or strong CYP3A4 inhibitors should be considered

Ixabepilone, ketoconazole

The strong CYP3A4 inhibition may increase the plasma concentrations of ixabepilone. The coadministration should be avoided

Ketoconazole [1], lapatinib ---> SmPC of [1] of EMA

Not recommended due to the risk of increased exposure to these medicinal products and QT prolongation.

Ketoconazole [1], lovastatine ---> SmPC of [1] of EMA

Concomitant therapy of ketoconazole with CYP3A4 metabolised HMG-CoA reductase inhibitors is contraindicated due to an increased risk of skeletal muscle toxicity including rhabdomyolysis

Ketoconazole [1], lurasidone ---> SmPC of [1] of EMA

Contraindicated due to the increased risk of adverse reactions (see section 4.3).

Ketoconazole [1], maraviroc ---> SmPC of [1] of EMA

Careful monitoring. Maraviroc dose should be decreased to 150 mg twice daily.

Ketoconazole [1], metabolized by CYP3A4 and prolong QT ---> SmPC of [1] of EMA

CYP3A4-metabolised known to prolong the QT interval may be contraindicated with ketoconazole, since the combination may lead to an increased risk of ventricular tachyarrhythmias, including occurrences of torsade de pointes, a potentially fatal arrhythmia

Ketoconazole [1], methadone ---> SmPC of [1] of EMA

Concomitant therapy of ketoconazole with substances that may have their plasma concentrations increased and have QT prolonging potential is contraindicated

Ketoconazole [1], methylergometrine ---> SmPC of [1] of EMA

Concomitant therapy of ketoconazole with ergot alkaloids is contraindicated due to an increased risk of ergotism and other serious vasospastic adverse events

Ketoconazole [1], methylprednisolone ---> SmPC of [1] of EMA

Potential increase in plasma concentrations of methylprednisolone. Careful monitoring. Dose adjustment of methylprednisolone may be required.

Ketoconazole [1], metyrapone ---> SmPC of [1] of EMA

There is no evidence to suggest that there is an interaction between ketoconazole and other steroidogenesis inhibitors (ie metyrapone)

Ketoconazole [1], midazolam ---> SmPC of [1] of EMA

triazolam, oral midazolam and alprazolam are contraindicated with ketoconazole due to potential for prolonged or increased sedation and respiratory depression;

Ketoconazole [1], mitotane ---> SmPC of [1] of EMA

Ketoconazole is mainly metabolised by cytochrome CYP3A4. Enzyme-inducing medicines may significantly reduce the bioavailability of ketoconazole. Use of ketoconazole with potent enzyme inducers is not recommended.

Ketoconazole [1], mizolastine ---> SmPC of [1] of EMA

Concomitant therapy of ketoconazole with substances that may have their plasma concentrations increased and have QT prolonging potential is contraindicated

Ketoconazole [1], nadolol ---> SmPC of [1] of EMA

Increase in plasma concentrations of nadolol have been observed. Careful monitoring. Dose adjustment of nadolol may be required.

Ketoconazole [1], naloxegol ---> SmPC of [1] of EMA

Not recommended

Ketoconazole [1], nevirapine ---> SmPC of [1] of EMA

Ketoconazole is mainly metabolised by cytochrome CYP3A4. Enzyme-inducing medicines may significantly reduce the bioavailability of ketoconazole. Use of ketoconazole with potent enzyme inducers is not recommended.

Ketoconazole [1], nilotinib ---> SmPC of [1] of EMA

Not recommended due to the risk of increased exposure to these medicinal products and QT prolongation.

Ketoconazole [1], nisoldipine ---> SmPC of [1] of EMA

Concomitant therapy of ketoconazole with nisoldipine is contraindicated due to an increased risk of oedema and congestive heart failure

Ketoconazole [1], oxycodone ---> SmPC of [1] of EMA

Increasing in plasma concentrations of oxycodone have been observed. Careful monitoring. The oxycodone dose may be adjusted.

Ketoconazole [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

Ketoconazole is a potent inhibitor of P-gp: inhibition of P-gp by ketoconazole can increase patients' exposure to medicinal products which are P-gp substrates

Ketoconazole [1], P-gp substrates and prolong QT interval ---> SmPC of [1] of EMA

P-gp substrates known to prolong the QT interval may be contraindicated with ketoconazole, since the combination may lead to an increased risk of ventricular tachyarrhythmias, including occurrences of torsade de pointes, a potentially fatal arrhythmia

Ketoconazole [1], paclitaxel ---> SmPC of [1] of EMA

No change in plasma concentration were shown with paclitaxel concentrate. No studies were performed with albumin bound nanoparticles. Careful monitoring. Dose adjustment of paclitaxel may be required.

Ketoconazole [1], paritaprevir/ombitasvir ---> SmPC of [1] of EMA

Contraindicated due to the increased risk of adverse reactions

Ketoconazole [1], pasireotide ---> SmPC of [1] of EMA

Co-administration of ketoconazole and pasireotide is not recommended since the combination can lead to a QT prolongation in patients with known cardiac rhythm disorders.

Ketoconazole [1], phenytoin ---> SmPC of [1] of EMA

Ketoconazole is mainly metabolised by cytochrome CYP3A4. Enzyme-inducing medicines may significantly reduce the bioavailability of ketoconazole. Use of ketoconazole with potent enzyme inducers is not recommended.

Ketoconazole [1], pimozide ---> SmPC of [1] of EMA

Concomitant therapy of ketoconazole with substances that may have their plasma concentrations increased and have QT prolonging potential is contraindicated

Ketoconazole [1], praziquantel ---> SmPC of [1] of EMA

Potential increase in plasma concentrations of praziquantel have been observed. Careful monitoring. Dose adjustment of praziquantel may be required.

Ketoconazole [1], pregnancy ---> SmPC of [1] of EMA

Ketoconazole is contraindicated during pregnancy and it should not be used in women of childbearing potential not using an effective method of contraception

Ketoconazole [1], proton pump inhibitors ---> SmPC of [1] of EMA

Acid-neutralising medicines should not be administered for at least 2 hours after the intake of ketoconazole. It is advised to administer ketoconazole with an acidic beverage eg cola beverage, orange juice.

Ketoconazole [1], QT interval prolonging drugs ---> SmPC of [1] of EMA

Concomitant therapy of ketoconazole with substances that may have their plasma concentrations increased and have QT prolonging potential is contraindicated

Ketoconazole [1], quetiapine ---> SmPC of [1] of EMA

Contraindicated as it may increase quetiapine-related toxicity

Ketoconazole [1], quinidine ---> SmPC of [1] of EMA

Concomitant therapy of ketoconazole with substances that may have their plasma concentrations increased and have QT prolonging potential is contraindicated

Ketoconazole [1], ranolazine ---> SmPC of [1] of EMA

Concomitant therapy of ketoconazole with substances that may have their plasma concentrations increased and have QT prolonging potential is contraindicated

Ketoconazole [1], reboxetine ---> SmPC of [1] of EMA

Not recommended because of reboxetine narrow's therapeutic margin.

Ketoconazole [1], repaglinide ---> SmPC of [1] of EMA

Careful monitoring. Dose adjustement of repaglinide may be required.

Ketoconazole [1], rifabutin ---> SmPC of [1] of EMA

Ketoconazole is mainly metabolised by cytochrome CYP3A4. Enzyme-inducing medicines may significantly reduce the bioavailability of ketoconazole. Use of ketoconazole with potent enzyme inducers is not recommended.

Ketoconazole [1], rifampicin ---> SmPC of [1] of EMA

Ketoconazole is mainly metabolised by cytochrome CYP3A4. Enzyme-inducing medicines may significantly reduce the bioavailability of ketoconazole. Use of ketoconazole with potent enzyme inducers is not recommended.

Ketoconazole [1], risperidone ---> SmPC of [1] of EMA

Careful monitoring. Dose adjustment of risperidone may be required.

Ketoconazole [1], ritonavir ---> SmPC of [1] of EMA

A dose reduction of ketoconazole should be considered when coadministered with ritonavir dosed as an antiretroviral medicine or as a pharmacokinetic enhancer. (See also "Effects of other medicinal products on the metabolism of ketoconazole HRA ").

Ketoconazole [1], rivaroxaban ---> SmPC of [1] of EMA

Not recommended due to an increased bleeding risk.

Ketoconazole [1], salmeterol ---> SmPC of [1] of EMA

Not recommended due to an increased risk in QT prolongation.

Ketoconazole [1], saquinavir ---> SmPC of [1] of EMA

Concomitant therapy of ketoconazole with substances that may have their plasma concentrations increased and have QT prolonging potential is contraindicated

Ketoconazole [1], saxagliptin ---> SmPC of [1] of EMA

Associated with a decrease in corresponding values for the active metabolite. Careful monitoring. Dose adjustment of saxagliptin may be required.

Ketoconazole [1], sertindole ---> SmPC of [1] of EMA

Concomitant therapy of ketoconazole with substances that may have their plasma concentrations increased and have QT prolonging potential is contraindicated

Ketoconazole [1], sildenafil ---> SmPC of [1] of EMA

Not recommended due to the increased risk of adverse reactions.

Ketoconazole [1], simvastatine ---> SmPC of [1] of EMA

Concomitant therapy of ketoconazole with CYP3A4 metabolised HMG-CoA reductase inhibitors is contraindicated due to an increased risk of skeletal muscle toxicity including rhabdomyolysis

Ketoconazole [1], sirolimus ---> SmPC of [1] of EMA

The coadministration the everolimus or sirolimus (also known as rapamycin) with ketoconazole is contraindicated due to an increase of the plasma concentrations of these medicinal products;

Ketoconazole [1], solifenacin ---> SmPC of [1] of EMA

The coadministration of fesoterodine or solifenacin with ketoconazole is contraindicated in patients with renal impairment;

Ketoconazole [1], statins metabolised by CYP3A4 ---> SmPC of [1] of EMA

Concomitant therapy of ketoconazole with CYP3A4 metabolised HMG-CoA reductase inhibitors is contraindicated due to an increased risk of skeletal muscle toxicity including rhabdomyolysis

Ketoconazole [1], Steroidogenese ---> SmPC of [1] of EMA

There is no evidence to suggest that there is an interaction between ketoconazole and other steroidogenesis inhibitors (ie metyrapone)

Ketoconazole [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Ketoconazole is mainly metabolised by cytochrome CYP3A4. Enzyme-inducing medicines may significantly reduce the bioavailability of ketoconazole. Use of ketoconazole with potent enzyme inducers is not recommended.

Ketoconazole [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Potent inhibitors of CYP3A4 may increase the bioavailability of ketoconazole, these medicinal products should be used with caution when co-administered with ketoconazole and patients should be monitored closely

Ketoconazole [1], sunitinib ---> SmPC of [1] of EMA

Not recommended due to the risk of increased exposure to these medicinal products and QT prolongation.

Ketoconazole [1], tacrolimus ---> SmPC of [1] of EMA

Increased in plasma concentrations of tacrolimus have been observed. Not recommended unless necessary. Careful monitoring and dose adjustment of this drug may be required

Ketoconazole [1], tadalafil ---> SmPC of [1] of EMA

Not recommended due to the increased risk of adverse reactions.

Ketoconazole [1], telithromycin ---> SmPC of [1] of EMA

Concomitant therapy of ketoconazole with telithromycin in patients with severe renal impairment is contraindicated due to an increased risk of hepatotoxicity and QT interval prolongation

Ketoconazole [1], tolbutamide ---> SmPC of [1] of EMA

Careful monitoring. Dose adjustment of tolbutamide may be required.

Ketoconazole [1], tolvaptan ---> SmPC of [1] of EMA

The coadministration of ketoconazole with tolvaptan used for a specific disease called "syndrome of inappropriate antidiuretic hormone secretion" is contraindicated.

Ketoconazole [1], triazolam ---> SmPC of [1] of EMA

triazolam, oral midazolam and alprazolam are contraindicated with ketoconazole due to potential for prolonged or increased sedation and respiratory depression;

Ketoconazole [1], vardenafil ---> SmPC of [1] of EMA

The coadministration of ketoconazole with vardenafil is contraindicated in men older than 75-years due to increased risk of adverse reactions;

Ketoconazole [1], verapamil ---> SmPC of [1] of EMA

Potential increased in plasma concentrations of verapamil. Careful monitoring. Dose adjustment of verapamil may be required.

Ketoconazole [1], vinblastine ---> SmPC of [1] of EMA

Potential increase in plasma concentrations of vinca alkaloid. Careful monitoring as it may cause an earlier onset and/or an increased severity of side-effects.

Ketoconazole [1], vincristine ---> SmPC of [1] of EMA

Potential increase in plasma concentrations of vinca alkaloid. Careful monitoring as it may cause an earlier onset and/or an increased severity of side-effects.

Ketoconazole [1], warfarin ---> SmPC of [1] of EMA

Potential increase in plasma concentrations of warfarin. Careful monitoring. INR (international normalised ratio) monitoring recommended.

Ketoconazole, lacosamide [2] ---> SmPC of [2] of EMA

Caution is recommended in concomitant treatment of lacosamide with strong inhibitors of CYP3A4, which may lead to increased systemic exposure of lacosamide.

Ketoconazole, lansoprazole [2] ---> SmPC of [2] of eMC

Administration of lansoprazole may result in subtherapeutic concentrations of ketoconazole and the combination should be avoided.

Ketoconazole, lanthanum carbonate [2] ---> SmPC of [2] of eMC

The lanthanum carbonate decreases absorption of ketoconazole. Separate administration by at least 2 hours

Ketoconazole, lapatinib [2] ---> SmPC of [2] of EMA

In healthy volunteers receiving ketoconazole, a strong CYP3A4 inhibitor, at 200 mg twice daily for 7 days, systemic exposure to lapatinib (100 mg daily) was increased approximately 3.6-fold, and half-life increased 1.7-fold.

Ketoconazole, larotrectinib [2] ---> SmPC of [2] of EMA

Co-administration of VITRAKVI with strong or moderate CYP3A inhibitors, P-gp and BCRP inhibitors may increase larotrectinib plasma concentrations (see section 4.2).

Ketoconazole, lefamulin [2] ---> SmPC of [2] of EMA

Strong inhibition of CYP3A4. Co-administration with strong CYP3A inhibitors like ketoconazole may lead to increased exposures of lefamulin and is contraindicated

Ketoconazole, lenacapavir [2] ---> SmPC of [2] of EMA

Plasma concentration of lenacapavir may be increased when co-administered with itraconazole or ketoconazole.

Ketoconazole, lercanidipine [2] ---> SmPC of [2] of eMC

The strong CYP3A4 inhibition increases plasma concentrations of lercanidipine. Co-administration of lercanidipine with inhibitors of CYP3A4 should be avoided

Ketoconazole, levobupivacaine [2] ---> SmPC of [2] of eMC

In vitro studies indicate that the CYP3A4 isoform and CYP1A2 isoform mediate the metabolism of levobupivacaine. Metabolism of levobupivacaine may be affected by CYP3A4 inhibitors and CYP1A2 inhibitors

Ketoconazole, levomepromazine [2] ---> SmPC of [2] of eMC

There is an increased risk of arrhythmias when neuroleptics are used with drugs that prolong the QT interval

Ketoconazole, lomitapide [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase lomitapide AUC. The combination of lomitapide with strong CYP3A4 inhibitors is contra-indicated

Ketoconazole, lonafarnib [2] ---> SmPC of [2] of EMA

This may lead to an increased risk of adverse reactions. Therefore, concomitant use of lonafarnib and strong CYP3A inhibitors is contraindicated

Ketoconazole, loperamide [2] ---> SmPC of [2] of eMC

The concomitant administration of loperamide (16 mg single dose) and ketoconazole, an inhibitor of CYP3A4 and P-glycoprotein, resulted in a 5-fold increase in loperamide plasma concentrations.

Ketoconazole, lopinavir/ritonavir [2] ---> SmPC of [2] of EMA

Lopinavir/ritonavir, CYP3A4 inhibitors, may increase the plasma levels of ketoconazole. High doses of ketoconazole are not recommended.

Ketoconazole, loratadine

The strong CYP3A4 inhibition may increase the plasma concentrations of loratadine

Ketoconazole, lorlatinib [2] ---> SmPC of [2] of EMA

CYP3A4/5 inhibitors may increase lorlatinib plasma concentrations and should be avoided

Ketoconazole, lumacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

No dose adjustment of lumacaftor/ivacaftor is recommended when these antifungals are initiated in patients currently taking lumacaftor/ivacaftor.

Ketoconazole, lumefantrine

The strong CYP3A4 inhibition may increase the plasma concentrations of lumefantrine

Ketoconazole, lurasidone [2] ---> SmPC of [2] of EMA

Lurasidone and its active metabolite ID-14283 are primarily metabolised by CYP3A4. Lurasidone is contraindicated with strong CYP3A4 inhibitors

Ketoconazole, magnesium hydroxide

The magnesium hydroxide may decrease the absorption of ketoconazole. Separate administration by 2-3 hours

Ketoconazole, manidipine

Manidipine should not be administered with CYP3A4 inhibitors

Ketoconazole, maraviroc [2] ---> SmPC of [2] of EMA

Maraviroc dose should be decreased when co-administered with ketoconazole.

Ketoconazole, maribavir [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Ketoconazole, mefloquine

The combination (ketoconazole inhibits CYP3A4) may increase the mefloquine levels and prolong the QT-interval (also within 15 weeks after the last dose of mefloquine)

Ketoconazole, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Co-administration of saxagliptin with the potent inhibitor of CYP3A4/5 ketoconazole, increased the Cmax and AUC of saxagliptin by 62% and 2.5-fold. These pharmacokinetic effects are not clinically meaningful and do not require dose adjustment.

Ketoconazole, methysergide [2] ---> SmPC of [2] of eMC

The concomitant use of cytochrome P450 3A (CYP3A) inhibitors, since this can result in an elevated exposure to methysergide and ergot toxicity (vasospasm and ischemia of the extremities and other tissues).

Ketoconazole, mianserin

The strong CYP3A4 inhibition may increase the plasma concentrations of mianserin

Ketoconazole, miconazole

Oral miconazole is contraindicated with medicinal products that are metabolised by CYP3A4 and may prolong also the QT interval

Ketoconazole, midostaurin [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inhibitors may increase midostaurin blood concentrations.

Ketoconazole, mifepristone [2] ---> SmPC of [2] of eMC

On the basis of this drug's metabolism by CYP3A4, it is possible that strong CYP3A4 inhibitors may inhibit its metabolism (increasing serum levels of mifepristone).

Ketoconazole, mirabegron [2] ---> SmPC of [2] of EMA

Betmiga is not recommended in patients with severe renal impairment (GFR 15 to 29 mL/min/1.73 m2) or patients with moderate hepatic impairment (Child-Pugh Class B) concomitantly receiving strong CYP3A inhibitors

Ketoconazole, mirtazapine [2] ---> SmPC of [2] of eMC

The strong CYP3A4 inhibition may increase the plasma concentrations of mirtazapine

Ketoconazole, mometasone [2] ---> SmPC of [2] of eMC

There may be a potential for increased systemic exposure to mometasone furoate when strong CYP3A4 inhibitors are co-administered

Ketoconazole, naldemedine [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A inhibitors should be avoided. If use with strong CYP3A inhibitors is unavoidable, monitor for adverse reactions

Ketoconazole, naloxegol [2] ---> SmPC of [2] of EMA

Concomitant use of naloxegol with CYP3A4 inhibitors increases naloxegol exposition. Concomitant use of naloxegol with strong CYP3A4 inhibitors is contraindicated

Ketoconazole, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

Like with other drugs that decrease the intragastric acidity, the absorption of ketoconazole can decrease

Ketoconazole, nelfinavir [2] ---> SmPC of [2] of EMA

Coadministration of nelfinavir and a strong inhibitor of CYP3A, ketoconazole, resulted in a 35 % increase in nelfinavir plasma AUC. The changes in nelfinavir concentrations are not considered clinically significant and no dose adjustment is needed

Ketoconazole, neratinib [2] ---> SmPC of [2] of EMA

Concomitant use of strong or moderate CYP3A4/P-gp inhibitors significantly increased neratinib systemic exposure, therefore, concomitant use of neratinib with strong and moderate CYP3A4/P-gp inhibitors is not recommended

Ketoconazole, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Netupitant is mainly metabolized by CYP3A4; therefore, co-administration with medicinal products that inhibit CYP3A4 may increase netupitant plasma levels. Consequently, co-administration with strong CYP3A4 inhibitors should be approached with caution

Ketoconazole, nifedipine [2] ---> SmPC of [2] of eMC

Nifedipine is metabolised via the cytochrome P450 3A4 system. Therefore, there are theoretical interactions with drugs known to inhibit this enzyme system.

Ketoconazole, nilotinib [2] ---> SmPC of [2] of EMA

Significant prolongation of the QT interval may occur when nilotinib is inappropriately taken with strong CYP3A4 inhibitors. Prolongation of the QT interval may expose patients to the risk of fatal outcome.

Ketoconazole, nilvadipine

The strong CYP3A4 inhibition may increase the plasma concentrations of nilvadipine. Caution is recommended

Ketoconazole, nimodipine [2] ---> SmPC of [2] of eMC

Upon co-administration of nimodipine with CYP3A4 inhibitors the blood pressure should be monitored and, if necessary, an adaptation in the nimodipine dose should be considered.

Ketoconazole, nintedanib [2] ---> SmPC of [2] of EMA

If co-administered with nintedanib, potent P-gp inhibitors may increase exposure to nintedanib. In such cases, patients should be monitored closely for tolerability of nintedanib.

Ketoconazole, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir inhibits CYP3A-mediated metabolism of ketoconazole. Due to an increased incidence of gastrointestinal and hepatic adverse reactions, a dose reduction of ketoconazole should be considered when coadministered with ritonavir.

Ketoconazole, nitrendipine

The strong CYP3A4 inhibition may increase the plasma concentrations of nitrendipine. Caution is recommended

Ketoconazole, nomegestrol/estradiol [2] ---> SmPC of [2] of EMA

Concomitant administration of strong (e.g. ketoconazole, itraconazole, clarithromycin) or moderate (e.g. fluconazole, diltiazem, erythromycin) CYP3A4 inhibitors may increase the serum concentrations of oestrogens or progestogens.

Ketoconazole, norgestimate

The strong CYP3A4 inhibition may increase the plasma concentrations of norgestimate

Ketoconazole, omaveloxolone [2] ---> SmPC of [2] of EMA

Omaveloxolone is primarily metabolised by CYP3A4 (see section 5.2). Concomitant use of strong or moderate CYP3A4 inhibitors may significantly increase the systemic exposure of omaveloxolone (see section 4.5).

Ketoconazole, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

CYP3A4/P-gp inhibition by ketoconazole and paritaprevir/ ritonavir/ ombitasvir. Concomitant use is contraindicated

Ketoconazole, omeprazole [2] ---> SmPC of [2] of eMC

Due to the decreased intragastric acidity the absorption of ketoconazole may be reduced during omeprazole treatment

Ketoconazole, osilodrostat [2] ---> SmPC of [2] of EMA

A washout period should be considered when switching from other products known to affect the QT interval such as pasireotide or ketoconazole.

Ketoconazole, ospemifene [2] ---> SmPC of [2] of EMA

Ketoconazole, a strong CYP3A4 inhibitor and moderate P-glycoprotein inhibitor, increased the AUC of ospemifene by 1.4-fold. This increase is not considered to be clinically significant given the inherent pharmacokinetic variability of ospemifene.

Ketoconazole, oxybutynine [2] ---> SmPC of [2] of EMA

As oxybutynin is metabolised by cytochrome P 450 isoenzyme CYP 3A4, interactions with medicinal products that inhibit this isoenzyme cannot be ruled out.

Ketoconazole, paclitaxel [2] ---> SmPC of [2] of EMA

Caution should be exercised when administering paclitaxel concomitantly with medicines known to inhibit either CYP2C8 or CYP3A4 because toxicity of paclitaxel may be increased due to higher paclitaxel exposure.

Ketoconazole, palbociclib [2] ---> SmPC of [2] of EMA

The concomitant use of strong CYP3A inhibitors and grapefruit or grapefruit juice, should be avoided (see sections 4.2 and 4.4)

Ketoconazole, palonosetron ---> SmPC of [netupitant/palonosetron] of EMA

Co-administration with ketoconazole did not affect the pharmacokinetics of palonosetron.

Ketoconazole, panobinostat [2] ---> SmPC of [2] of EMA

In patients who take concomitant medicinal products which are strong CYP3A and/or Pgp inhibitors, the dose of panobinostat should be reduced

Ketoconazole, pantoprazole [2] ---> SmPC of [2] of EMA

Pantoprazole may reduce the absorption of active substances whose bioavailability is dependent on the gastric pH (e.g. ketoconazole).

Ketoconazole, parecoxib [2] ---> SmPC of [2] of EMA

Plasma exposure (AUC and Cmax) to valdecoxib was increased (38% and 24%, respectively) when co-administered with ketoconazole (CYP3A4 inhibitor); however, a dosage adjustment should not generally be necessary

Ketoconazole, paricalcitol [2] ---> SmPC of [2] of eMC

Ketoconazole, enzymatic inhibitor, may increase the mean half-life of paricalcitol. Caution is recommended.

Ketoconazole, pasireotide [2] ---> SmPC of [2] of EMA

Pasireotide should be used with caution in patients who are concomitantly receiving medicinal products that prolong the QT interval

Ketoconazole, pazopanib [2] ---> SmPC of [2] of EMA

The possible strong inhibition of CYP3A4, BCRP and P-glycoprotein may increase the plasma concentrations of pazopanib. The combination should be avoided

Ketoconazole, perampanel [2] ---> SmPC of [2] of EMA

In healthy subjects, the CYP3A4 inhibitor ketoconazole (400 mg once daily for 10 days) increased perampanel AUC by 20% and prolonged perampanel half-life by 15% (67.8 h vs 58.4 h).

Ketoconazole, phenazone

Concomitant use of phenazone and ketoconazole delays the elimination of phenazone. There is the possibility of an accumulation

Ketoconazole, polatuzumab vedotin [2] ---> SmPC of [2] of EMA

Strong CYP3A4 and P-gp inhibitors (e.g., ketoconazole) may increase the area under the concentration-time curve (AUC) of unconjugated MMAE by 48%.

Ketoconazole, pomalidomide [2] ---> SmPC of [2] of EMA

Co-administration of pomalidomide with the strong CYP3A4/5 and P-gp inhibitor ketoconazole had no clinically relevant effect on exposure to pomalidomide.

Ketoconazole, ponatinib [2] ---> SmPC of [2] of EMA

Caution should be exercised and a reduction of the starting dose of Iclusig to 30 mg should be considered with concurrent use of strong CYP3A inhibitors

Ketoconazole, pralsetinib [2] ---> SmPC of [2] of EMA

Therefore, co-administration of pralsetinib with strong CYP3A4 inhibitors or combined P-gp and strong CYP3A4 inhibitors should be avoided. If co-administration cannot be avoided, reduce the current dose of pralsetinib

Ketoconazole, prasugrel [2] ---> SmPC of [2] of EMA

Ketoconazole (400 mg daily), a selective and potent inhibitor of CYP3A4 and CYP3A5, did not affect prasugrel-mediated inhibition of platelet aggregation or the prasugrel active metabolite's AUC and Tmax, but decreased the Cmax by 34% to 46%.

Ketoconazole, pravastatine/fenofibrate [2] ---> SmPC of [2] of EMA

Absence of a significant pharmacokinetic interaction with pravastatin

Ketoconazole, prednisolone

Increase of effects and adverse reactions of prednisolone

Ketoconazole, prednisone

The strong CYP3A4 inhibition may increase the plasma concentrations of prednisone

Ketoconazole, procyclidine [2] ---> SmPC of [2] of eMC

Anticholinergics may reduce the absorption of ketoconazole.

Ketoconazole, progesterone

The strong CYP3A4 inhibition may increase the plasma concentrations of progesterone

Ketoconazole, propafenone [2] ---> SmPC of [2] of eMC

Drugs that inhibit CYP2D6, CYP1A2 and CYP3A4 may lead to increased levels of propafenone. When propafenone is administered with inhibitors of these enzymes, the patients should be closely monitored and the dose adjusted accordingly.

Ketoconazole, propiverine

Clinically relevant increases in serum propiverine may cause the coadministration of propiverine with CYP3A4 inhibitors (e. g. ketoconazole)

Ketoconazole, protease inhibitors

The co-administration may increase the plasma levels of protease inhibitor. The dosage should be reduced if necessary

Ketoconazole, prucalopride [2] ---> SmPC of [2] of EMA

Ketoconazole (200 mg twice daily), a potent inhibitor of CYP3A4 and of P-gp, increased the systemic exposure to prucalopride by approximately 40%. This effect is too small to be clinically relevant.

Ketoconazole, pyrazinamide

The co-administration may increase the risk of hepatotoxicity

Ketoconazole, quizartinib [2] ---> SmPC of [2] of EMA

Increased quizartinib maximum plasma concentration. Increased quizartinib exposure may increase the risk of toxicity.

Ketoconazole, rabeprazole [2] ---> SmPC of [2] of eMC

Co-administration of rabeprazole sodium with ketoconazole may result in a significant decrease in antifungal plasma levels.

Ketoconazole, ranitidine

Decreased absorption of ketoconazole. Separate administration by at least 2 hours

Ketoconazole, ranolazine [2] ---> SmPC of [2] of EMA

Ranolazine is a substrate of cytochrome CYP3A4. Inhibitors of CYP3A4 increase plasma concentrations of ranolazine. Combining ranolazine with potent CYP3A4 inhibitors is contraindicated

Ketoconazole, regorafenib [2] ---> SmPC of [2] of EMA

It is recommended to avoid concomitant use of strong inhibitors of CYP3A4 activity as their influence on the steady-state exposure of regorafenib and its metabolites has not been studied.

Ketoconazole, repaglinide [2] ---> SmPC of [2] of EMA

Co-administration of 200 mg ketoconazole increased the repaglinide (AUC and Cmax) by 1.2-fold with profiles of blood glucose concentrations altered by less than 8% when administered concomitantly (a single dose of 4 mg repaglinide).

Ketoconazole, retapamulin [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the plasma concentrations of retapamulin. Caution is advised

Ketoconazole, ribociclib [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inhibitors should be avoided and an alternative concomitant medicinal product with less potential to inhibit CYP3A4 inhibition should be considered.

Ketoconazole, rilpivirine [2] ---> SmPC of [2] of EMA

Concomitant use of ketoconazole (inhibition of CYP3A enzymes) with rilpivirine (induction of CYP3A due to high rilpivirine dose in the study) decreases ketoconazole plasma levels and increases rilpivirine plasma levels. No dose adjustment is required.

Ketoconazole, rimonabant [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the exposition of rimonabant. Caution is advised during concomitant use of rimonabant and potent CYP3A4 inhibitors

Ketoconazole, riociguat [2] ---> SmPC of [2] of EMA

Concomitant use of riociguat with strong multi-pathway CYP and P-gp/BCRP inhibitors is not recommended

Ketoconazole, ripretinib [2] ---> SmPC of [2] of EMA

Strong inhibitors of CYP3A/P-gp (e.g. ketoconazole, erythromycin, clarithromycin, itraconazole, ritonavir, posaconazole, and voriconazole) are to be used with caution and patients should be monitored.

Ketoconazole, risperidone [2] ---> SmPC of [2] of EMA

Ketoconazole, a strong CYP3A4 inhibitor and a P-gp inhibitor, at a dosage of 200 mg/day increased the plasma concentrations of risperidone and decreased the plasma concentrations of 9-hydroxy-risperidone.

Ketoconazole, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir inhibits CYP3A-mediated metabolism of ketoconazole. Due to an increased incidence of gastrointestinal and hepatic adverse reactions, a dose reduction of ketoconazole should be considered

Ketoconazole, rivaroxaban [2] ---> SmPC of [2] of EMA

Co-administration of rivaroxaban with ketoconazole (400 mg once a day) or ritonavir (600 mg twice a day) led to a 2.6 fold / 2.5 fold increase in mean rivaroxaban AUC and a 1.7 fold / 1.6 fold increase in mean rivaroxaban Cmax

Ketoconazole, roflumilast [2] ---> SmPC of [2] of EMA

Clinical interaction studies with CYP3A4 inhibitor ketoconazole showed increases of 9% of the total PDE4 inhibitory activity. No dose adjustment is necessary

Ketoconazole, rolapitant [2] ---> SmPC of [2] of EMA

No clinically significant effect was seen on the pharmacokinetics of rolapitant when ketoconazole, a strong CYP3A4 inhibitor was administered with rolapitant.

Ketoconazole, rosiglitazone

Ketoconazole increases the effect of rosiglitazone

Ketoconazole, rosuvastatin [2] ---> SmPC of [2] of eMC

No clinically relevant interactions have been observed between rosuvastatin and ketoconazole (an inhibitor of CYP2A6 and CYP3A4).

Ketoconazole, roxatidine

Decreased absorption of ketoconazole. Separate administration by at least 2 hours

Ketoconazole, rupatadine [2] ---> SmPC of [2] of eMC

The concomitant administration of rupatadine with inhibitors of the isozyme CYP3A4 increases the systemic exposure to rupatadine. Rupatadine should be used with caution when it is administered concomitantly with inhibitors of CYP3A4.

Ketoconazole, ruxolitinib [2] ---> SmPC of [2] of EMA

When administering ruxolitinib with strong CYP3A4 inhibitors the unit dose of ruxolitinib should be reduced by approximately 50%, to be administered twice daily.

Ketoconazole, sacituzumab govitecan [2] ---> SmPC of [2] of EMA

Sacituzumab govitecan should be used with caution in patients receiving UGT1A1 inhibitors (e.g. propofol, ketoconazole, EGFR tyrosine kinase inhibitors).

Ketoconazole, safinamide [2] ---> SmPC of [2] of EMA

Safinamide is eliminated mainly in the urine. In human liver microsomes (HLM), the N-dealkylation step appears to be catalysed by CYP3A4, as safinamide clearance in HLM was inhibited by ketoconazole by 90%.

Ketoconazole, salmeterol [2] ---> SmPC of [2] of eMC

The co-administration with strong CYP3A4 inhibitors with salmeterol may significant increase the plasma salmeterol exposure, what may cause a QTc interval prolongation. The co-administration should be avoided

Ketoconazole, salmeterol/fluticasone propionate [2] ---> SmPC of [2] of EMA

This may lead to an increase in the incidence of other systemic effects of salmeterol treatment (e.g. prolongation of QTc interval and palpitations) compared with salmeterol or ketoconazole treatment alone (see section 4.4).

Ketoconazole, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

No dose adjustment required when saquinavir/ritonavir combined with ≤ 200 mg/day ketoconazole. High doses of ketoconazole (> 200 mg/day) are not recommended.

Ketoconazole, saxagliptin [2] ---> SmPC of [2] of EMA

Concomitant administration of saxagliptin with the potent inhibitor of CYP3A4/5 ketoconazole, increased the Cmax and AUC of saxagliptin by 62% and 2.5-fold, respectively, and the corresponding values for the active metabolite were decreased by 95% and 88

Ketoconazole, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

The pharmacokinetic effects are not clinically meaningful and do not require dose adjustment.

Ketoconazole, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Co-administration of saxagliptin with the potent inhibitor of CYP3A4/5 ketoconazole, increased the Cmax and AUC of saxagliptin by 62% and 2.5-fold, respectively, and the corresponding values for the active metabolite were decreased by 95% and 88%.

Ketoconazole, selpercatinib [2] ---> SmPC of [2] of EMA

If strong CYP3A and/or P-gp inhibitors, e. g. ketoconazole, itraconazole, voriconazole, ritonavir, saquinavir, telithromycin, posaconazole and nefazodone, have to be coadministered, the dose of selpercatinib should be reduced

Ketoconazole, selumetinib [2] ---> SmPC of [2] of EMA

Co-administration with medicinal products that are strong inhibitors of CYP3A4 (e.g., clarithromycin, grapefruit juice, oral ketoconazole) or CYP2C19 (e.g., ticlopidine) should be avoided.

Ketoconazole, sibutramine [2] ---> SmPC of [2] of eMC

Caution should be exercised on concomitant administration of sibutramine with drugs which affect CYP3A4 enzyme activity (increased plasma concentrations (AUC) of sibutramine active metabolites)

Ketoconazole, sildenafil [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analysis of clinical trial data indicated a reduction in sildenafil clearance when co-administered with CYP3A4 inhibitors

Ketoconazole, silodosin [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the plasma levels of silodosin. Concomitant use of silodosin with potent CYP3A4 inhibitors is not recommended

Ketoconazole, simeprevir [2] ---> SmPC of [2] of EMA

Co-administration of simeprevir with moderate or strong inhibitors of CYP3A4 may significantly increase the plasma exposure of simeprevir. Co-administration of simeprevir with these inhibitors is not recommended.

Ketoconazole, sirolimus [2] ---> SmPC of [2] of EMA

Multiple-dose ketoconazole administration significantly affected the rate and extent of absorption and sirolimus exposure from Rapamune oral solution. Co-administration of sirolimus and ketoconazole is not recommended (see section 4.4).

Ketoconazole, sitagliptin [2] ---> SmPC of [2] of EMA

It is possible that potent CYP3A4 inhibitors (i.e. ketoconazole, itraconazole, ritonavir, clarithromycin) could alter the pharmacokinetics of sitagliptin in patients with severe renal impairment or ESRD.

Ketoconazole, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

For this reason, it is possible that potent CYP3A4 inhibitors (i.e., ketoconazole, itraconazole, ritonavir, clarithromycin) could alter the pharmacokinetics of sitagliptin in patients with severe renal impairment or ESRD.

Ketoconazole, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

Ketoconazole, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Inhibition of P-gp and CYPs. No dose adjustment of Epclusa or ketoconazole is required.

Ketoconazole, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Inhibition of P-gp and CYP3A. No dose adjustment of Vosevi or ketoconazole is required.

Ketoconazole, solifenacin [2] ---> SmPC of [2] of eMC

The CYP3A4 inhibition may increase the plasma levels of solifenacin. Simultaneous treatment of solifenacin and a potent CYP3A4 inhibitor is contra-indicated in patients with severe renal impairment or moderate hepatic impairment

Ketoconazole, sonidegib [2] ---> SmPC of [2] of EMA

Sonidegib undergoes metabolism primarily by CYP3A4, and concomitant administration of strong inhibitors of CYP3A4 can increase sonidegib concentrations significantly. The sonidegib dose should be reduced to 200 mg every other day

Ketoconazole, sorafenib [2] ---> SmPC of [2] of EMA

Clinical pharmacokinetic interactions of sorafenib with CYP3A4 inhibitors are unlikely.

Ketoconazole, St. John's wort

The strong CYP3A4 induction significantly decreases the bioavailability of ketoconazole. St. John's Wort should be avoided

Ketoconazole, sucralfate [2] ---> SmPC of [2] of eMC

Concomitant administration of sucralfate may reduce the bioavailability of ketoconazole. The bioavailability may be restored by separating the administration from sucralfate by 2 hours.

Ketoconazole, sufentanil [2] ---> SmPC of [2] of EMA

Sufentanil is primarily metabolised by the CYP3A4. Ketoconazole, a potent CYP3A4 inhibitor, can significantly increase the systemic exposure to sublingual sufentanil. Similar effects with other potent CYP3A4 inhibitors cannot be excluded.

Ketoconazole, sunitinib [2] ---> SmPC of [2] of EMA

Administration of sunitinib with potent CYP3A4 inhibitors may increase sunitinib concentrations. Combination with CYP3A4 inhibitors should therefore be avoided

Ketoconazole, tadalafil [2] ---> SmPC of [2] of EMA

Tadalafil is principally metabolised by CYP3A4. CYP3A4 inhibitors should be co-administered with caution as they would be expected to increase plasma concentrations of tadalafil

Ketoconazole, talazoparib [2] ---> SmPC of [2] of EMA

Concomitant use of strong P-gp inhibitors should be avoided. If co-administration with a strong P-gp inhibitor is unavoidable, the Talzenna dose should be reduced (see section 4.2).

Ketoconazole, tamsulosin

The strong CYP3A4 inhibition may increase the plasma concentrations of tamsulosin

Ketoconazole, tasimelteon [2] ---> SmPC of [2] of EMA

Tasimelteon exposure was increased by approximately 50% when co-administered with ketoconazole 400 mg (after 5 days of ketoconazole 400 mg per day). The clinical relevance of this single factor is unclear

Ketoconazole, tegafur

The co-administration of a CYP2A6 inhibitor and tegafur should be avoided as effectiveness of tegafur can be decreased

Ketoconazole, telaprevir [2] ---> SmPC of [2] of EMA

Caution is recommended when prescribing telaprevir concurrently with medicinal products known to induce QT prolongation and which are CYP3A substrates

Ketoconazole, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure resulting in an increased risk of hypotension.

Ketoconazole, temsirolimus [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inhibitors may increase blood concentrations of the active drug substances, temsirolimus and its metabolite, sirolimus. Therefore, concomitant treatment with agents that have strong CYP3A4 inhibition potential should be avoided.

Ketoconazole, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Co-administration of Vemlidy with strong inhibitors of P-gp (e.g. itraconazole and ketoconazole) may increase tenofovir alafenamide plasma concentrations. Co-administration is not recommended.

Ketoconazole, tepotinib [2] ---> SmPC of [2] of EMA

Concomitant use of TEPMETKO with dual strong CYP3A and P-gp inhibitors (e.g. itraconazole, ketoconazole, ritonavir, saquinavir, nelfinavir) should be avoided.

Ketoconazole, terbinafine [2] ---> SmPC of [2] of eMC

Co-administration of terbinafine with drugs that inhibit CYP2C9 and CYP3A4 may increase the exposure to terbinafine

Ketoconazole, terfenadine

The strong CYP3A4 inhibition may increase the terfenadine plasma levels and prolong the QT interval (risk of life-threatening arrythmias). The combination is contraindicated

Ketoconazole, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

When co-administered with strong CYP3A inhibitors, the dose should be adjusted to one Symkevi tablet twice a week, taken approximately 3 to 4 days apart.

Ketoconazole, ticagrelor [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inhibitors - Co-administration of ketoconazole with ticagrelor increased the ticagrelor Cmax and AUC equal to 2.4-fold and 7.3-fold, respectively.

Ketoconazole, tigecycline [2] ---> SmPC of [2] of EMA

Based on an in vitro study tigecycline is a P-gp substrate. Co-administration of P-gp inhibitors (e.g., ketoconazole or cyclosporine) or P-gp inducers (e.g., rifampicin) could affect the pharmacokinetics of tigecycline

Ketoconazole, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Based on theoretical considerations tipranavir, is expected to increase plasma concentrations of the active principles

Ketoconazole, tivozanib [2] ---> SmPC of [2] of EMA

The co-administration of tivozanib with a potent CYP3A4 inhibitor, ketoconazole (400 mg once daily), had no influence on tivozanib serum concentrations (Cmax or AUC); therefore, tivozanib exposure is unlikely to be altered by CYP3A4 inhibitors.

Ketoconazole, tofacitinib [2] ---> SmPC of [2] of EMA

Tofacitinib exposure is increased when coadministered with potent inhibitors of CYP3A4 (e.g., ketoconazole)

Ketoconazole, tolterodine [2] ---> SmPC of [2] of eMC

Concomitant systemic medication with potent CYP3A4 inhibitors is not recommended due to increased serum concentrations of tolterodine in poor CYP2D6 metabolisers with (subsequent) risk of overdosage

Ketoconazole, tolvaptan [2] ---> SmPC of [2] of EMA

Tolvaptan plasma concentrations have been increased by up to 5.4-fold area under time-concentration curve (AUC) after the administration of strong CYP3A4 inhibitors.

Ketoconazole, toremifene [2] ---> SmPC of [2] of EMA

Theoretically the metabolism of toremifene is inhibited by drugs known to inhibit the CYP3A enzyme system which is reported to be responsible for its main metabolic pathways. Concomitant use should be carefully considered.

Ketoconazole, trabectedin [2] ---> SmPC of [2] of EMA

Concomitant use of a strong CYP3A4 inhibitor with trabectedin may increase the plasma exposure of trabectedin. Concomitant use should be avoided. If the combination is needed, close monitoring of toxicities

Ketoconazole, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inhibitors with trastuzumab emtansine should be avoided due to the potential for an increase in DM1 exposure and toxicity.

Ketoconazole, trazodone [2] ---> SmPC of [2] of eMC

It is likely that potent CYP3A4 inhibitors may lead to substantial increases in trazodone plasma concentrations. The co-administration of trazodone and potent CYP3A4 inhibitors should be avoided where possible.

Ketoconazole, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Corticosteroid clearance may be decreased, resulting in increased effects.

Ketoconazole, triamcinolone [2] ---> SmPC of [2] of eMC

Corticosteroid clearance may be decreased, resulting in increased effects.

Ketoconazole, trihexyphenidyl

The anticholinergic agent increases the pH value and may decrease the absorption of ketoconazole

Ketoconazole, trofosfamide

The inhibition of CYP3A4 may increase the formation of a trofosfamide metabolite which is related with nephrotoxicity and CNS toxicity

Ketoconazole, ulipristal [2] ---> SmPC of [2] of EMA

Following administration of the potent CYP3A4 inhibitor ketoconazole (400 mg once daily for 7 days) to healthy female volunteers, Cmax and AUC of ulipristal acetate increased 2 and 5.9 fold, respectively

Ketoconazole, umeclidinium/vilanterol [2] ---> SmPC of [2] of EMA

Care is advised when co-administering umeclidinium/vilanterol with ketoconazole and other known strong CYP3A4 inhibitors as there is potential for an increased systemic exposure to vilanterol

Ketoconazole, upadacitinib [2] ---> SmPC of [2] of EMA

Upadacitinib exposure is increased when co-administered with strong CYP3A4 inhibitors. Consider alternatives to strong CYP3A4 inhibitor medications when used in the long-term.

Ketoconazole, valdecoxib [2] ---> SmPC of [2] of EMA

Plasma exposure (AUC) to valdecoxib was increased 38% when co-administered with ketoconazole (CYP3A4 inhibitor).

Ketoconazole, vardenafil [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole (200 mg), a potent CYP3A4 inhibitor, with vardenafil (5 mg) resulted in a 10-fold increase in vardenafil AUC and a 4-fold increase in vardenafil Cmax (see section 4.4).

Ketoconazole, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib should be used with caution in combination with potent inhibitors of CYP3A4, glucuronidation and/or transport proteins

Ketoconazole, venetoclax [2] ---> SmPC of [2] of EMA

For patients requiring concomitant use of venetoclax with strong CYP3A inhibitors or moderate CYP3A inhibitors, venetoclax dosing should be administered according to Table 7

Ketoconazole, venlafaxine [2] ---> SmPC of [2] of eMC

Concomitant use of CYP3A4 inhibitors and venlafaxine may increase levels of venlafaxine and O-desmethylvenlafaxine. Therefore, caution is advised if a patient's therapy includes a CYP3A4 inhibitor and venlafaxine concomitantly.

Ketoconazole, vericiguat [2] ---> SmPC of [2] of EMA

No clinically meaningful effect on vericiguat exposure was observed when vericiguat was co-administered with ketoconazole (multi-pathway CYP and transporter inhibitor),

Ketoconazole, vilanterol ---> SmPC of [umeclidinium/vilanterol] of EMA

Concomitant administration of strong CYP3A4 inhibitors may inhibit the metabolism of, and increase the systemic exposure to, vilanterol. Care is advised

Ketoconazole, vinca alkaloids ---> SmPC of [vincristine] of eMC

The metabolism of vinca alkaloids has been shown to be mediated by hepatic cytochrome P450 isoenzymes in the CYP3A subfamily. This metabolic pathway may be impaired in patients who are taking concomitant potent inhibitors of these isoenzymes

Ketoconazole, vinflunine [2] ---> SmPC of [2] of EMA

The concomitant use of vinflunine and potent CYP3A4 inhibitors should be avoided since they may increase vinflunine and DVFL concentrations

Ketoconazole, vinorelbine [2] ---> SmPC of [2] of eMC

CYP3A4 is the main enzyme involved in the metabolism of vinorelbine, and the combination with a drug that inhibits this iso-enzyme can affect the concentration of vinorelbine

Ketoconazole, voclosporine [2] ---> SmPC of [2] of EMA

Voclosporin exposure was 18.6-fold higher in the presence of the strong CYP3A4 inhibitor ketoconazole compared to voclosporin administered alone.

Ketoconazole, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole with vorapaxar significantly increased the vorapaxar exposition. Concomitant use of vorapaxar with strong inhibitors of CYP3A should be avoided.

Ketoconazole, vortioxetine [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the AUC of vortioxetine. No dosage adjustment necessary. It is caution recommended with CYP2D6 poor metabolisers

Ketoconazole, zanubrutinib [2] ---> SmPC of [2] of EMA

If a strong CYP3A inhibitor must be used (e.g., posaconazole, voriconazole, ketoconazole, itraconazole, clarithromycin, indinavir, lopinavir, ritonavir, telaprevir), reduce the BRUKINSA dose to 80 mg (one capsule) for the duration of the inhibitor use.

Ketoconazole, ziprasidone

It is unlikely that changes in pharmacokinetics (with the concomitant use of strong CYP3A4 inhibitors) be of clinical relevance. No dose adjustment is required

Ketoconazole, zolpidem [2] ---> SmPC of [2] of eMC

Co-administration with ketoconazole increased total AUC, and decreased apparent oral clearance of zolpidem. A routine dosage adjustment of zolpidem is not considered necessary. The use of zolpidem with ketoconazole may enhance the sedative effects.

Ketoconazole, zonisamide [2] ---> SmPC of [2] of EMA

Steady-state dosing of either ketoconazole (400 mg/day) or cimetidine (1200 mg/day) had no clinically relevant effects on the single-dose pharmacokinetics of zonisamide given to healthy subjects.

Ketoconazole, zopiclone [2] ---> SmPC of [2] of eMC

Since zopiclone is metabolised by the cytochrome P450 (CYP) 3A4, plasma levels of zopiclone may be increased when co-administered with CYP3A4 inhibitors

            CONTRAINDICATIONS of Ketoconazole (Ketoconazole HRA)      

            - Hypersensitivity to ketoconazole and/or to any imidazole antifungal medication, or to any of the excipients listed in section 6.1          

            - Hypersensitivity to any imidazole antifungal medicinal product;             

            - Acute or chronic liver disease and/or if pre-treatment liver enzymes levels are above 2 times the upper limit of normal (see sections 4.2 and 4.4):       

            - Pregnancy (see section 4.6);   

            - Breastfeeding (see section 4.6);           

            - Congenital or documented acquired QTc prolongation ;            

            - Concomitant therapy with any of the following medicinal products which may interact and result in potentially life-threatening adverse reactions (see section 4.5):    

              - CYP3A4 metabolised HMG-CoA reductase inhibitors (e.g. simvastatin, atorvastatin and lovastatin) due to an increased risk of skeletal muscle toxicity including rhabdomyolysis;    

              - eplerenone due to an increased risk of hyperkalemia and hypotension;            

              - substances that may have their plasma concentrations increased and have QT prolonging potential: methadone, disopyramide, quinidine, dronedarone, pimozide, sertindole, saquinavir (saquinavir/ritonavir 1000/100 mg bid), ranolazine, mizolastine, halofantrine;    

              - dabigatran due to an increased bleeding risk;    

              - triazolam, oral midazolam and alprazolam due to potential for prolonged or increased sedation and respiratory depression;    

              - ergot alkaloids (eg dihydroergotamine, ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine) due to an increased risk of ergotism and other serious vasospastic adverse reactions;     

              - lurasidone;  

              - quetiapine due to an increased risk of toxicity;            

              - telithromycin and clarithromycin in patients with severe renal impairment due to an increased risk of hepatotoxicity and QT interval prolongation;   

              - felodipine, nisoldipine due to an increased risk of oedema and congestive heart failure;

              - colchicine in patients with renal impairment due to an increased risk of severe adverse reactions;        

              - irinotecan due to an alteration of the metabolism of this medicinal product;  

              - everolimus, sirolimus (also known as rapamycin) due to an increase of the plasma concentrations of these medicinal products;     

              - vardenafil in men older than 75-years due to increased risk of adverse reactions;         

              - paritaprevir/ombitasvir (ritonavir) due to increased risk of adverse reactions;     

              - fesoterodine and solifenacin in patients with renal impairment;           

              - tolvaptan used for a specific disease called "syndrome of inappropriate antidiuretic hormone secretion".    

            The list above is not an inclusive list of compounds that may interact with ketoconazole and result in potentially life-threatening reactions.  

            https://www.ema.europa.eu/en/documents/product-information/ketoconazole-hra-epar-product-information_en.pdf 28/11/2024            

Ketoprofen

Ability to drive, ketoprofen [2] ---> SmPC of [2] of eMC

Patients should be warned about the potential for somnolence, dizziness or convulsions, drowsiness, fatigue and visual disturbances and be advised not to drive or operate machinery if these symptoms occur.

ACE inhibitors, ketoprofen [2] ---> SmPC of [2] of eMC

In patients with compromised renal function the co-administration of an ACE inhibitor and agents that inhibit cyclooxygenase may result in further deterioration of renal function, including possible acute renal failure.

AIIRA, ketoprofen [2] ---> SmPC of [2] of eMC

In patients with compromised renal function the co-administration of an angiotensin II antagonist and agents that inhibit cyclooxygenase may result in further deterioration of renal function, including possible acute renal failure.

Alcohol, ketoprofen

Enhancement of the adverse effects of the NSAID, especially those of the gastrointestinal tract and CNS

Antacids, ketoprofen

Antacid decreases the absorption of NSAID. Separate administration by at least 2 hours

Anticoagulants, ketoprofen [2] ---> SmPC of [2] of eMC

Increased risk of bleeding

Antihypertensives, ketoprofen [2] ---> SmPC of [2] of eMC

Risk of decreased antihypertensive potency (inhibition of vasodilator prostaglandins by NSAIDs).

Betablockers, ketoprofen [2] ---> SmPC of [2] of eMC

Risk of decreased antihypertensive potency (inhibition of vasodilator prostaglandins by NSAIDs).

Breast-feeding, ketoprofen [2] ---> SmPC of [2] of eMC

No data are available on excretion of ketoprofen in human milk. Ketoprofen is not recommended in nursing mothers.

Cardiac glycosides, ketoprofen [2] ---> SmPC of [2] of eMC

NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.

Clopidogrel, ketoprofen [2] ---> SmPC of [2] of eMC

Increased risk of bleeding

Corticosteroids, ketoprofen [2] ---> SmPC of [2] of eMC

Increased risk of gastrointestinal ulceration or bleeding.

Coxibs, ketoprofen [2] ---> SmPC of [2] of eMC

Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects, particularly gastrointestinal ulceration and bleeding.

Cyclosporine, ketoprofen ---> SmPC of [piroxicam] of eMC

Possible increased risk of nephrotoxicity when NSAIDs are given with ciclosporin

Digoxin, ketoprofen

The co-administration of ketoprofen with digoxin may increase the plasma levels of digoxin

Diuretics, ketoprofen [2] ---> SmPC of [2] of eMC

Risk of reduced diuretic effect. Patients and particularly dehydrated patients taking diuretics are at a greater risk of developing renal failure secondary to a decrease in renal blood flow caused by prostaglandin inhibition.

Heparin, ketoprofen [2] ---> SmPC of [2] of eMC

Increased risk of bleeding

Ketoprofen [1], lithium ---> SmPC of [1] of eMC

Risk of elevation of lithium plasma levels, sometimes reaching toxic levels due to decreased lithium renal excretion.

Ketoprofen [1], loop diuretics ---> SmPC of [1] of eMC

Risk of reduced diuretic effect. Patients and particularly dehydrated patients taking diuretics are at a greater risk of developing renal failure secondary to a decrease in renal blood flow caused by prostaglandin inhibition.

Ketoprofen [1], methotrexate ---> SmPC of [1] of eMC

Serious interactions have been recorded after the use of high dose methotrexate with NSAIDs, including ketoprofen, due to decreased elimination of methotrexate.

Ketoprofen [1], NSAID ---> SmPC of [1] of eMC

Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects, particularly gastrointestinal ulceration and bleeding.

Ketoprofen [1], pentoxifylline ---> SmPC of [1] of eMC

There is an increased risk of bleeding. More frequent clinical monitoring and monitoring of bleeding time is required.

Ketoprofen [1], platelet aggregation inhibitors ---> SmPC of [1] of eMC

Increased risk of gastrointestinal bleeding

Ketoprofen [1], pregnancy ---> SmPC of [1] of eMC

During the first and second trimester of pregnancy, ketoprofen should not be given unless clearly necessary. Ketoprofen is contraindicated during the third trimester of pregnancy.

Ketoprofen [1], probenecide ---> SmPC of [1] of eMC

Concomitant administration of probenecid may markedly reduce the plasma clearance of ketoprofen.

Ketoprofen [1], quinolones ---> SmPC of [1] of eMC

Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.

Ketoprofen [1], salicylates ---> SmPC of [1] of eMC

Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects, particularly gastrointestinal ulceration and bleeding.

Ketoprofen [1], SSRI ---> SmPC of [1] of eMC

Increased risk of gastrointestinal bleeding

Ketoprofen [1], thrombolytics ---> SmPC of [1] of eMC

Increased risk of bleeding.

Ketoprofen [1], ticlopidine ---> SmPC of [1] of eMC

Increased risk of bleeding

Ketoprofen [1], zidovudine ---> SmPC of [1] of eMC

Increased risk of haematological toxicity when NSAIDs are given with zidovudine.

Ketoprofen, leflunomide [2] ---> SmPC of [2] of EMA

A771726 is an inhibitor of OAT3 in vivo .Therefore, when co-administered leflunomide with substrates of OAT3 caution is recommended.

Ketoprofen, phenytoin

The co-administration of ketoprofen with phenytoin may increase the plasma levels of phenytoin

Ketoprofen, potassium-sparing diuretics

The co-administration may decrease the diuretic effect, increase the risk of renal failure due to a reduction in renal blood flow and cause hypercaliemia.

Ketoprofen, sulfinpyrazone

Sulfinpyrazone delays the elimination of NSAID

Ketoprofen, tacrolimus ---> SmPC of [piroxicam] of eMC

Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.

Ketoprofen, teriflunomide [2] ---> SmPC of [2] of EMA

When teriflunomide (OAT3 inhibitor) is coadministered with substrates of OAT3 caution is recommended.

Ketoprofen, warfarin

Increased risk of bleeding

           CONTRAINDICATIONS of Ketoprofen

           - Ketoprofen is contraindicated in patients who have a history of hypersensitivity reactions such as bronchospasm, asthmatic attacks, rhinitis, angioedema, urticaria or other allergic-type reactions to ketoprofen, any other ingredients in this medicine, ASA or other NSAIDs. Severe, rarely fatal, anaphylactic reactions have been reported in such patients

           - Ketoprofen is contraindicated in patients with hypersensitivity to any of the excipients of the drug.

           - Ketoprofen is also contraindicated in the third trimester of pregnancy.

           - Ketoprofen is contraindicated in the following cases:

           - Severe heart failure

           - active peptic ulcer, or any history of gastrointestinal bleeding, ulceration or perforation

           - haemorrhagic diathesis

           - severe hepatic insufficiency

           - severe renal insufficiency

           http://www.medicines.org.uk/emc/

Ketorolac

Ability to drive, ketorolac [2] ---> SmPC of [2] of eMC

Some patients may experience dizziness, drowsiness, fatigue, visual disturbances, headaches, vertigo, insomnia or depression.

ACE inhibitors, ketorolac [2] ---> SmPC of [2] of eMC

The risk of acute renal insufficiency, which is usually reversible, may be increased in some patients with compromised renal function when ACE inhibitors are combined with NSAIDs.

Acetylsalicylic acid, ketorolac [2] ---> SmPC of [2] of eMC

There is an increased risk of gastrointestinal bleeding when anti-platelet agents are combined with NSAIDs.

AIIRA, ketorolac [2] ---> SmPC of [2] of eMC

The risk of acute renal insufficiency, which is usually reversible, may be increased in some patients with compromised renal function when angiotensin II receptor antagonists are combined with NSAIDs.

Anticoagulants, ketorolac [2] ---> SmPC of [2] of eMC

Ketorolac is contraindicated in combination with anti-coagulants, such as warfarin since co-administration of NSAIDs and anti-coagulants may cause an enhanced anti-coagulant effect

Antihypertensives, ketorolac [2] ---> SmPC of [2] of eMC

NSAIDs may reduce the effect of anti-hypertensive medicinal products.

Betablockers, ketorolac

NSAIDs may reduce the effect of anti-hypertensive medicinal products.

Breast-feeding, ketorolac [2] ---> SmPC of [2] of eMC

Ketorolac is contraindicated in mothers who are breast-feeding.

Cardiac glycosides, ketorolac [2] ---> SmPC of [2] of eMC

NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels when co-administered with cardiac glycosides.

Clopidogrel, ketorolac [2] ---> SmPC of [2] of eMC

There is an increased risk of gastrointestinal bleeding when anti-platelet agents are combined with NSAIDs.

Corticosteroids, ketorolac [2] ---> SmPC of [2] of eMC

As with all NSAIDs, caution should be taken when co-administering with corticosteroids because of the increased risk of gastrointestinal ulceration or bleeding

Coumarin anticoagulants, ketorolac [2] ---> SmPC of [2] of eMC

Ketorolac is contraindicated in combination with anti-coagulants, such as warfarin since co-administration of NSAIDs and anti-coagulants may cause an enhanced anti-coagulant effect

Coxibs, ketorolac [2] ---> SmPC of [2] of eMC

Concomitant use of several NSAIDs should be avoided due to an increased risk of adverse effects, particularly upper gastrointestinal disorders.

Cyclosporine, ketorolac ---> SmPC of [piroxicam] of eMC

Possible increased risk of nephrotoxicity when NSAIDs are given with ciclosporin

Digoxin, ketorolac [2] ---> SmPC of [2] of eMC

Ketorolac does not alter digoxin protein binding.

Diuretics, ketorolac [2] ---> SmPC of [2] of eMC

NSAIDs may reduce the effect of diuretics medicinal products.

Enoxaparin sodium [1], ketorolac ---> SmPC of [1] of EMA

It is recommended that agents which affect haemostasis should be discontinued prior to enoxaparin therapy unless their use is essential.

Enoxaparin [1], ketorolac ---> SmPC of [1] of eMC

The co-administration may enhance the pharmacologic effect and increase the bleeding risk. A close clinical and laboratory monitoring is recommended

Ketorolac [1], lithium ---> SmPC of [1] of eMC

Inhibition of renal lithium clearance, leading to an increase in plasma lithium concentration, has been reported with some prostaglandin synthesis-inhibiting drugs. Cases of increased lithium plasma levels during ketorolac therapy have been reported.

Ketorolac [1], methotrexate ---> SmPC of [1] of eMC

Caution is advised when methotrexate is administered concurrently with ketorolac since some prostaglandin synthesis-inhibiting drugs have been reported to reduce the clearance of methotrexate, and thus possibly enhance its toxicity.

Ketorolac [1], NSAID ---> SmPC of [1] of eMC

Concomitant use of several NSAIDs should be avoided due to an increased risk of adverse effects, particularly upper gastrointestinal disorders.

Ketorolac [1], opioid analgesics ---> SmPC of [1] of eMC

Ketorolac has been shown to reduce the need for concomitant opioid analgesia when it is given for the relief of postoperative pain.

Ketorolac [1], pentoxifylline ---> SmPC of [1] of eMC

When ketorolac is administered concurrently with oxpentifylline, there is an increased tendency to bleeding.

Ketorolac [1], pentoxifylline ---> SmPC of [1] of eMC

Pentoxifylline should not be given concomitantly with ketorolac as there is increased risk of bleeding and/or prolongation of prothrombin time.

Ketorolac [1], platelet aggregation inhibitors ---> SmPC of [1] of eMC

There is an increased risk of gastrointestinal bleeding when anti-platelet agents are combined with NSAIDs.

Ketorolac [1], pregnancy ---> SmPC of [1] of eMC

Ketorolac crosses the placenta to the extent of approximately 10%. Ketorolac is contraindicated in pregnancy, labour or delivery

Ketorolac [1], probenecide ---> SmPC of [1] of eMC

Probenecid should not be administered concurrently with ketorolac because of increases in ketorolac plasma concentrations and half-life.

Ketorolac [1], quinolones ---> SmPC of [1] of eMC

Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.

Ketorolac [1], SSRI ---> SmPC of [1] of eMC

There is an increased risk of gastrointestinal bleeding when selective serotonin reuptake inhibitors (SSRIs) are combined with NSAIDs.

Ketorolac [1], ticlopidine ---> SmPC of [1] of eMC

There is an increased risk of gastrointestinal bleeding when anti-platelet agents are combined with NSAIDs.

Ketorolac, thrombolytics

Thrombolytic agents may increase the risk of bleeding

Ketorolac, triamterene [2] ---> SmPC of [2] of eMC

Effects of diuretics are antagonized by ketorolac

Ketorolac, warfarin

Ketorolac is contraindicated in combination with anti-coagulants, such as warfarin since co-administration of NSAIDs and anti-coagulants may cause an enhanced anti-coagulant effect

           CONTRAINDICATIONS of Ketorolac

           - Ketorolac is contraindicated in patients with previously demonstrated hypersensitivity to ketorolac, any of its excipients, or other NSAIDs and patients in whom aspirin or other prostaglandin synthesis inhibitors induce allergic reactions (severe anaphylactic-like reactions have been observed in such patients). Such reactions have included asthma, rhinitis, angioedema or urticaria.

           Ketorolac is also contraindicated in

             - those with a history of asthma

             - children under 16 years of age.

           - Ketorolac is contraindicated in patients with active peptic ulcer, or any history of gastrointestinal bleeding, ulceration or perforation.

           - As with other NSAIDs, ketorolac is contraindicated in patients with severe heart failure, hepatic failure and renal failure

           - Ketorolac is contraindicated in patients with moderate or severe renal impairment (serum creatinine >160 µmol/l) or in patients at risk for renal failure due to volume depletion or dehydration.

           - Ketorolac is contraindicated in pregnancy, labour, delivery or lactation

           - Ketorolac is contraindicated as prophylactic analgesia before surgery due to inhibition of platelet aggregation and is contraindicated intra-operatively because of the increased risk of bleeding.

           - Ketorolac inhibits platelet function and is, therefore, contraindicated in patients with suspected or confirmed cerebrovascular bleeding, patients who have had operations with a high risk of haemorrhage or incomplete haemostasis and those at high risk of bleeding such as those with haemorrhagic diatheses, including coagulation disorders.

           - It is also contraindicated in patients on anti-coagulants, including warfarin and low dose heparin (2500 - 5000 units 12 hourly).

           - Ketorolac is contraindicated in patients currently receiving ASA or other NSAIDs (including cyclooxygenase-2 selective inhibitors).

           - Ketorolac Solution for injection is contraindicated for neuraxial (epidural or intrathecal) administration due to its alcohol content.

           - The combination of ketorolac with oxpentifylline is contraindicated.

           - Concurrent treatment with ketorolac and probenecid or lithium salts is contraindicated.

           - Ketorolac is contraindicated in patients with the complete or partial syndrome of nasal polyps, angioedema or bronchospasm.

           http://www.medicines.org.uk/emc/

Ketotifen

Ability to drive, ketotifen [2] ---> SmPC of [2] of eMC

During the first few days of treatment with ketotifen reactions may be impaired. Patients should be warned not to take charge of vehicles or machinery until the effect of ketotifen treatment on the individual is known.

Alcohol, ketotifen [2] ---> SmPC of [2] of eMC

Ketotifen may potentiate the effects of alcohol

Anticoagulants, ketotifen

Ketotifen may potentiate the effects of anticoagulants

Antihistamines, ketotifen [2] ---> SmPC of [2] of eMC

Ketotifen may potentiate the effects of antihistamines

Breast-feeding, ketotifen [2] ---> SmPC of [2] of eMC

Ketotifen is excreted in breast milk, therefore mothers receiving ketotifen should not breast feed.

CNS depressants, ketotifen

Ketotifen may potentiate the effects of CNS depressants

Ketotifen [1], pregnancy ---> SmPC of [1] of eMC

Although there is no evidence of any teratogenic effect, recommendation for ketotifen in pregnancy cannot be given.

Ketotifen, oral antidiabetics

The co-administration may decrease the platelet count

           CONTRAINDICATIONS of Ketotifen

           Hypersensitivity to ketotifen or any of the excipients. A reversible fall in the thrombocyte count in patients receiving ZADITEN® concomitantly with oral anti-diabetic agents has been observed in a few cases. This combination of drugs should therefore be avoided until this phenomenon has been satisfactorily explained.

           http://www.medicines.org.uk/emc/