Embedded Files
Pharmacologic Category
Histamine H1 Antagonist; Histamine H1 Antagonist, Second Generation; Mast Cell Stabilizer; Piperidine Derivative
Dosing: Pediatric
Atopic asthma (prophylactic treatment): Oral:
Infants and Children 6 months to 3 years: Initial: 0.05 mg/kg once daily or in 2 divided doses for 5 days; Maintenance: 0.05 mg/kg/dose twice daily (maximum dose: 1 mg twice daily)
Children >3 years and Adolescents: Initial: 1 mg once daily or in 2 divided doses for 5 days; Maintenance: 1 mg twice daily
Dosing: Renal Impairment: Pediatric
There are no dosage adjustments provided in the manufacturer's labeling.
Dosing: Hepatic Impairment: Pediatric
There are no dosage adjustments provided in the manufacturer's labeling.
Use: Labeled Indications
Note: Not approved in the US
Atopic asthma: Adjunctive therapy in the chronic treatment of mild, atopic asthma in children
Limitations of use: Not indicated for acute prevention or treatment of acute asthma attacks.
Administration: Pediatric
Oral: Administer without regards to meals.
Syrup: Use the measuring device that comes with this drug or a calibrated measuring device.
Dietary Considerations
Syrup contains carbohydrate 4 g/5 mL.
Storage/Stability
Syrup: Store at up to 25°C (up to 77°F).
Tablet: Store at up to 25°C (up to 77°F). Protect from moisture.
Medication Patient Education with HCAHPS Considerations
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience fatigue, weight gain, irritability, dry mouth, dizziness, anxiety, trouble sleeping, nausea, or headache. Have patient report immediately to prescriber seizures (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
Medication Safety Issues
Sound-alike/look-alike issues:
Contraindications
Hypersensitivity to ketotifen or any component of the formulation; use of ketotifen syrup in patients sensitive to benzoate compounds
Warnings/Precautions
Concerns related to adverse effects:
• Sedation: May cause drowsiness early in therapy; initiate therapy at one-half the recommended daily dose and gradually increase over 5 days to maintenance dose; patients must be cautioned about performing tasks which require mental alertness. (eg, operating machinery or driving).
• Thrombocytopenia: Rare cases of thrombocytopenia have been reported in patients concurrently using oral ketotifen and oral antidiabetic agents; manufacturer labeling does not specify associated agents but recommends to monitor platelet counts in patients receiving concomitant therapy.
Disease related concerns:
• Epilepsy: Use with caution in epileptic patients; may lower seizure threshold. Seizures have been reported rarely during therapy.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
• Diabetics: Due to the carbohydrate content of the syrup preparation, diabetic patients may need to use tablet.
Dosage form specific issues:
• Benzoate allergy: Syrup products may contain benzoate compounds.
Other warnings/precautions:
• Appropriate use: Indicated for prophylactic treatment; not effective for the prevention or treatment of acute asthma attacks. Therapy with agents used for prophylaxis or relief of asthma related symptoms (eg, corticosteroids, beta2-agonists, xanthine derivatives), should be maintained for at least 6 to 12 weeks and then gradually reduced as clinically indicated. An immediate increase in corticosteroid dosage may be necessary in patients with severe relapse of symptoms during corticosteroid dose reduction; assess adrenal and pituitary function prior to initiating corticosteroid dose reduction in patients who have received long term therapy Steroid-dependent patients with adrenocortical insufficiency can take up to one year to recover a normal stress related pituitary-adrenal response.
• Delayed clinical response: Therapeutic effects may not be clinically evident until several weeks after the initiation of therapy; maximum effectiveness usually requires duration of therapy ≥10 weeks. Therapy should be maintained for at least 2 to 3 months to determine effectiveness. If therapy requires discontinuation, gradually reduce over 2 to 4 weeks.
Pregnancy Considerations
Adverse events have been observed in some animal studies.
Breast-Feeding Considerations
Breast-feeding is not recommended by the manufacturer.
Adverse Reactions
1% to 10%:
Central nervous system: Disturbed sleep (1%), headache (1%)
Dermatologic: Skin rash (4%), urticaria (1%)
Endocrine & metabolic: Weight gain (5%)
Gastrointestinal: Abdominal pain (1%), increased appetite (1%)
Infection: Influenza (3%)
Ophthalmic: Eyelid edema (1%)
Respiratory: Respiratory tract infection (4%), epistaxis (1%)
<1%, postmarketing, and/or case reports: Cystitis, dizziness, erythema multiforme, excitement, hepatitis, increased serum transaminases, insomnia, irritability, nervousness, Stevens-Johnson syndrome, thrombocytopenia, xerostomia
Toxicology
Metabolism/Transport Effects
None known.
Drug Interactions Open Interactions
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Amezinium: Antihistamines may enhance the stimulatory effect of Amezinium. Risk C: Monitor therapy
Amphetamines: May diminish the sedative effect of Antihistamines. Risk C: Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Risk C: Monitor therapy
Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Risk X: Avoid combination
Benzylpenicilloyl Polylysine: Antihistamines may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Suspend systemic H1 antagonists for benzylpenicilloyl-polylysine skin testing and delay testing until systemic antihistaminic effects have dissipated. A histamine skin test may be used to assess persistent antihistaminic effects. Risk D: Consider therapy modification
Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Risk C: Monitor therapy
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Risk D: Consider therapy modification
Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Cannabis: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination
CloZAPine: Anticholinergic Agents may enhance the constipating effect of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy
Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk D: Consider therapy modification
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Risk D: Consider therapy modification
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination
Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Hyaluronidase: Antihistamines may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving antihistamines (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Risk D: Consider therapy modification
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pitolisant: Antihistamines may diminish the therapeutic effect of Pitolisant. Risk X: Avoid combination
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid combination
Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Risk X: Avoid combination
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk D: Consider therapy modification
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy
Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy
Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Risk D: Consider therapy modification
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination
Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Monitoring Parameters
Manufacturer labeling recommends monitoring of platelet counts in patients receiving oral antidiabetic agents.
Product Availability
Not available in the US
Dosage Forms: Canada
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Syrup, Oral:
Zaditen: 0.2 mg/mL (250 mL) [contains alcohol, usp, methyl hydroxybenzoate, propyl hydroxybenzoate]
Generic: 0.2 mg/mL ([DSC])
Tablet, Oral:
Zaditen: 1 mg
Anatomic Therapeutic Chemical (ATC) Classification
- R06AX17
Generic Available (US)
May be product dependent
Mechanism of Action
Exhibits noncompetitive H1-receptor antagonist and mast cell stabilizer properties. Efficacy in asthma likely results from a combination of anti-inflammatory and antihistaminergic actions including interference with chemokine-induced migration of eosinophils into inflamed airways, inhibition of airway hyper-reactivity due to platelet activating factor (PAF), antagonism of leukotriene-induced bronchoconstriction.
Pharmacodynamics/Kinetics
Absorption: Rapid, ≥60%
Protein binding: 75%
Metabolism: Hepatic via N-glucuronidation to inactive metabolite ketotifen-N-glucoronide; N-demethylation to active metabolite nor-ketotifen; and keto-reduction to hydroxyl derivative
Clearance: Increased in children >3 years; decreased in children ≤3 years
Bioavailability: ~50%
Half-life elimination: Biphasic: Distribution: 3 to 5 hours; Elimination: 21 hours
Time to peak, plasma: 2 to 4 hours
Excretion: Urine (>60% as metabolites, 1% as unchanged drug)
Local Anesthetic/Vasoconstrictor Precautions
No information available to require special precautions
Effects on Dental Treatment
No significant effects or complications reported
Effects on Bleeding
No information available to require special precautions
Index Terms
Ketotifen Fumarate
References
Hung CH, Li CY, Lai YS, et al, “Discrepant Clinical Responses and Blood Chemokine Profiles Between Two Non-Steroidal Anti-Inflammatory Medications for Children With Mild Persistent Asthma,” Pediatr Allergy Immunol, 2005, 16(4):306-9.[PubMed 15943593]
Kabra SK, Pandey RM, Singh R, et al, “Ketotifen for Asthma in Children Aged 5 to 15 Years: A Randomized Placebo-Controlled Trial,” Ann Allergy Asthma Immunol, 2000, 85(1):46-52.[PubMed 10923604]
Zaditen (ketotifen) [product monograph]. Toronto, Ontario, Canada: Teva Canada Limited; October 2010.
Brand Names: International
Allerban (EG); Allerfen (KR); Amitone (HK, MY, SG); Asmafort (BH, QA); Asmaten (MY); Asthafen (IN); Asthan (TW); Asumalife (MY, SG, TH, VN); Azimet (PH); Bronket (VN); Butifeno (CR, DO, GT, HN, NI, PA, SV); Denerel (MY, SG, TW); Dhatifen (MY); Edifen (KR); Eucycline (GR); Gloditen (QA); Ketasma (IN, LK); Ketifen (HK); Keto (TH); Ketof (LK); Ketohexal (ZA); Ketokid (AR); Ketomin (TW); Ketop (RO); Ketosma (TW); Ketotisin (CL); Ketovent (IN); Orpidix (GR); Politifen (TH); Profilar (AE, BH, CY, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE); Profiten (IL); Prophallerge (EG); Prosma 1 (BD); Rui Na Ti (CN); Santiten (TW); Soother (TW); Stafen (BD); Sykofen (TH); Tefanyl (QA); Tokn (BD); Tosma (ID); Totinal (AE, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Zadec (PH); Zadec SRO (PH); Zadin (KR); Zaditen (AE, AR, AT, AU, BE, BF, BG, BH, BJ, BR, CH, CI, CO, CY, CZ, DE, DK, EC, EG, ET, FI, FR, GB, GH, GM, GN, GR, HK, ID, IE, IL, IQ, IR, IT, JO, KE, KR, KW, LB, LR, LY, MA, ML, MR, MT, MU, MW, MY, NE, NG, NL, NO, NZ, OM, PE, PH, PL, PT, PY, QA, RU, SA, SC, SD, SE, SG, SK, SL, SN, SY, TH, TN, TR, TW, TZ, UG, UY, VE, YE, ZM, ZW); Zaditen SDU (HK, TH); Zasten (ES); Zatin (AE, CY, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE); Zatofen (PK); Zerosma (IN); Zylofen (EG); Zytofen (TH)
Last Updated 2/20/20
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