Tadalafil

Pharmacologic Category

Dosing: Adult

Note: Contraindicated in patients taking nitrates (regularly or intermittently) due to potentially severe hypotension. If a patient taking tadalafil develops chest pain, delay therapy with a nitrate for 48 hours. For patients taking an alpha-blocking antihypertensive agent, use tadalafil with caution and consider a lower starting dose, as tadalafil can potentiate hypotensive effects (Khera 2020); some experts recommend against routinely using these drugs together, particularly in patients with cardiovascular disease (Sauer 2020).

Benign prostatic hyperplasia (with or without concomitant erectile dysfunction) (Cialis): Oral: 5 mg once daily. Note: When tadalafil is used with finasteride to initiate BPH therapy, the recommended duration of therapy is ≤26 weeks.

Erectile dysfunction (Cialis):

As-needed dosing: 10 mg at least 30 minutes prior to anticipated sexual activity as one single dose and not more than once daily. Dose may be adjusted based on tolerability (dosing range: 5 to 20 mg). Note: Erectile function may be improved for up to 36 hours following a single dose.

Once-daily dosing: 2.5 mg once daily at approximately the same time daily without regard to timing of sexual activity. Dose may be adjusted based on tolerability (dosage range: 2.5 to 5 mg/day).

Pulmonary arterial hypertension (Adcirca):

Note: A clinician with expertise in pulmonary arterial hypertension should be consulted for all management decisions. Tadalafil is contraindicated in patients taking riociguat due to potentially severe hypotension (ACCP [Klinger 2019]).

Oral: 40 mg once daily. Note: Initiating therapy in combination with ambrisentan has been shown to be beneficial (ACCP [Klinger 2019]; Gaile 2015).

Raynaud phenomenon (alternative agent) (off-label use): Oral: 20 mg every other day (Roustit 2013; Shenoy 2010).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing. No dose adjustment for patients >65 years of age in the absence of renal or hepatic impairment.

Dosing: Renal Impairment: Adult

Benign prostatic hyperplasia (with or without concomitant erectile dysfunction) (Cialis):

CrCl ≥51 mL/minute: No dosage adjustment necessary.

CrCl 30 to 50 mL/minute: Initial: 2.5 mg once daily; maximum: 5 mg once daily.

CrCl <30 mL/minute: Use not recommended.

ESRD requiring hemodialysis: Use not recommended.

Erectile dysfunction (Cialis):

As-needed use:

CrCl ≥51 mL/minute: No dosage adjustment necessary.

CrCl 30 to 50 mL/minute: Initial: 5 mg once daily; maximum: 10 mg (not more frequently than every 48 hours).

CrCl <30 mL/minute: Maximum: 5 mg (not more frequently than every 72 hours).

ESRD requiring hemodialysis: Maximum: 5 mg (not more frequently than every 72 hours).

Once-daily use:

CrCl ≥31 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute: Use not recommended.

ESRD requiring hemodialysis: Use not recommended.

Pulmonary arterial hypertension (Adcirca):

CrCl 31 to 80 mL/minute: Initial: 20 mg once daily; increase to 40 mg once daily based on individual tolerability.

CrCl ≤30 mL/minute: Avoid use due to increased tadalafil exposure, limited clinical experience, and lack of ability to influence clearance by dialysis.

ESRD requiring hemodialysis: Avoid use due to increased tadalafil exposure, limited clinical experience, and lack of ability to influence clearance by dialysis.

Dosing: Hepatic Impairment: Adult

Benign prostatic hyperplasia (with or without concomitant erectile dysfunction) (Cialis):

Mild to moderate hepatic impairment (Child-Pugh class A or B): Use with caution; the use of tadalafil for once-daily use has not been extensively evaluated in patients with hepatic impairment.

Severe hepatic impairment (Child-Pugh class C): Use is not recommended.

Erectile dysfunction (Cialis):

As-needed use:

Mild to moderate impairment (Child-Pugh class A or B): Use with caution; dose should not exceed 10 mg once daily. The use of tadalafil once per day has not been evaluated extensively in patients with hepatic impairment.

Severe impairment (Child-Pugh class C): Use is not recommended.

Once-daily use:

Mild to moderate impairment (Child-Pugh class A or B): Use with caution; the use of tadalafil for once-daily use has not been extensively evaluated in patients with hepatic impairment.

Severe impairment (Child-Pugh class C): Use is not recommended.

Pulmonary arterial hypertension (Adcirca):

Mild to moderate hepatic impairment (Child-Pugh class A or B): Use with caution; consider initial dose of 20 mg once daily.

Severe hepatic impairment (Child-Pugh class C): Avoid use; has not been studied in patients with severe hepatic cirrhosis.

Calculations

Use: Labeled Indications

Benign prostatic hyperplasia (Cialis only): Treatment of the signs and symptoms of benign prostatic hyperplasia (BPH).

Erectile dysfunction (Cialis only): Treatment of erectile dysfunction.

Erectile dysfunction and benign prostatic hyperplasia (Cialis only): Treatment of erectile dysfunction and the signs and symptoms of BPH.

Pulmonary arterial hypertension (Adcirca only): Treatment of pulmonary arterial hypertension (World Health Organization group 1) to improve exercise ability. Studies establishing effectiveness included predominately patients with New York Heart Association (NYHA) functional class II to III symptoms and etiologies of idiopathic or heritable pulmonary arterial hypertension (61%) or pulmonary arterial hypertension associated with connective tissue diseases (23%).

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

Raynaud phenomenonLevel of Evidence [B, G]

Data from a meta-analysis and a small, controlled trial support the use of tadalafil for Raynaud phenomenon related to systemic sclerosis, demonstrating a decrease in the frequency and severity of attacks Ref. In one small controlled trial, tadalafil showed no benefit compared to placebo Ref.

Based on the European League Against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis, phosphodiesterase type 5 (PDE5) inhibitors (eg, tadalafil) have been found to reduce the frequency and severity of systemic sclerosis–related Raynaud phenomenon attacks and should be considered in patients with severe symptoms and/or those who do not respond to first-line treatment Ref. Access Full-Off Label Monograph

Level of Evidence Definitions

Level of Evidence Scale

Class and Related Monographs

Phosphodiesterase Type 5 Inhibitors

Comparative Efficacy

Clinical Practice Guidelines

Benign Prostatic Hyperplasia:

CUA, “Guideline on Male Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia (MLUTS/BPH),” 2018

Erectile Dysfunction:

AUA, “Erectile Dysfunction,” 2018

“The Princeton III consensus recommendations for the management of erectile dysfunction and cardiovascular disease,” August 2012

Pulmonary Arterial Hypertension:

ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension, April 28, 2009

ACCP, “Therapy for Pulmonary Arterial Hypertension in Adults,” January 2019

CHEST Guideline and Expert Panel Report, “Pharmacologic Therapy for Pulmonary Arterial Hypertension in Adults,” August 2014

Sixth World Symposium on Pulmonary Hypertension (WSPH), November 2018

Systemic Sclerosis:

EULAR, “Update of EULAR Recommendations for the Treatment of Systemic Sclerosis” August 2017

Administration: Oral

May be administered with or without food.

Adcirca: Administer daily dose all at once; dividing doses throughout the day is not advised.

Cialis: Do not split tablets; the entire dose should be taken. When used on an as-needed basis, should be taken at least 30 minutes prior to sexual activity. When used on a once-daily basis, should be taken at the same time each day, without regard to timing of sexual activity.

Storage/Stability

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Extemporaneously Prepared

A 5 mg/mL tadalafil oral suspension may be made with tablets in a 1:1 mixture of Ora-Plus® and Ora-Sweet®. Crush fifteen 20 mg tadalafil tablets in a glass mortar and reduce to a fine powder. Prepare the vehicle by mixing 30 mL of Ora-Plus® and 30 mL of Ora-Sweet®; stir vigorously. Add 30 mL of the vehicle in geometric proportions to the powder and mix to form a smooth suspension. Transfer the mixture to a 2 ounce amber plastic prescription bottle. Rinse mortar with a quantity of the vehicle sufficient to make a final volume of 60 mL. Label “shake well.” Stable for 91 days when stored in amber plastic prescription bottles at room temperature.

Pettit RS, Johnson CE, and Caruthers RL, “Stability of an Extemporaneously Prepared Tadalafil Suspension,” Am J Health Syst Pharm, 2012, 69(7):592-4.[PubMed 22441791]

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat erectile dysfunction (ED).

• In men, it is used to treat the signs of an enlarged prostate.

• It is used to treat raised pressure in the lungs.

• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Flushing

• Nausea

• Throat irritation

• Nose irritation

• Back pain

• Muscle pain

• Common cold symptoms

• Painful extremities

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe cerebrovascular disease like change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or vision changes

• Chest pain

• Fast heartbeat

• Abnormal heartbeat

• Dizziness

• Passing out

• Severe headache

• Vision changes

• Blindness

• Hearing loss

• Change in hearing

• Noise or ringing in the ears

• Erection that lasts more than 4 hours

• Signs of a significant reaction like 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. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Sound-alike/look-alike issues:

Contraindications

Serious hypersensitivity to tadalafil or any component of the formulation; concurrent use of organic nitrate (regularly and/or intermittently) or guanylate cyclase stimulators (eg, riociguat).

Canadian labeling: Additional contraindications (not in US labeling): Previous episode of nonarteritic anterior ischemic optic neuropathy

Warnings/Precautions

Concerns related to adverse effects:

• Anginal chest pain: Patients experiencing anginal chest pain after tadalafil administration should seek immediate medical attention.

• Color discrimination: May cause dose-related impairment of color discrimination. Use caution in patients with retinitis pigmentosa; a minority have genetic disorders of retinal phosphodiesterases (no safety information available).

• Hearing loss: Sudden decrease or loss of hearing has been reported rarely; hearing changes may be accompanied by tinnitus and dizziness. Instruct patients to seek medical assistance for sudden decrease in hearing or loss of hearing. A direct relationship between therapy and hearing loss has not been determined.

• Hypotension: Decreases in blood pressure may occur due to vasodilator effects; use with caution in patients with left ventricular outflow obstruction (aortic stenosis or hypertrophic obstructive cardiomyopathy); may be more sensitive to hypotensive actions. Concurrent use with alpha-adrenergic antagonist therapy may cause symptomatic hypotension; patients should be hemodynamically stable prior to initiating therapy at the lowest possible dose. Patients should avoid or limit concurrent substantial ethanol consumption as this may increase the risk of symptomatic hypotension.

• Priapism: Painful erection >6 hours in duration has been reported (rarely). Instruct patient to seek medical assistance for erection lasting >4 hours. Use with caution in patients who have conditions which may predispose them to priapism (eg, sickle cell anemia, multiple myeloma, leukemia).

• Vision loss: Vision loss (rare) may be a sign of nonarteritic anterior ischemic optic neuropathy (NAION); causal relationship to PDE5 inhibitors not established. Instruct patients to discontinue therapy and seek medical assistance for sudden loss of vision in one or both eyes. Patients who have already experienced NAION are at an increased risk of recurrence. Other risk factors for NAION include low cup-to-disc ratio ("crowded disc"), CAD, diabetes, hypertension, hyperlipidemia, smoking, and >50 years of age. Use with caution in these patients and only when the benefits outweigh the risks. Safety has not been evaluated in patients with known hereditary degenerative retinal disorders (eg, retinitis pigmentosa); use is not recommended.

Disease-related concerns:

• Anatomical penis deformation: Use with caution in patients with anatomical deformation of the penis (angulation, cavernosal fibrosis, or Peyronie disease).

• Bleeding disorders: Use with caution in patients with bleeding disorders; safety and efficacy have not been established. In vitro studies have suggested a decreased effect on platelet aggregation.

• Cardiovascular disease: Use is not recommended in patients with hypotension (<90/50 mm Hg), uncontrolled hypertension (>170/100 mm Hg), NYHA class II-IV heart failure within the last 6 months, uncontrolled arrhythmias, stroke within the last 6 months, MI within the last 3 months, unstable angina or angina during sexual intercourse; safety and efficacy have not been evaluated in these patients. Safety and efficacy in PAH have not been evaluated in patients with clinically significant aortic and/or mitral valve disease, life-threatening arrhythmias, hypotension (<90/50 mm Hg), uncontrolled hypertension, significant left ventricular dysfunction, pericardial constriction, restrictive or congestive cardiomyopathy, symptomatic coronary artery disease. Use caution in patients with left ventricular outflow obstruction (eg, aortic stenosis, hypertrophic obstructive cardiomyopathy); may be more sensitive to vasodilator effects. There is a degree of cardiac risk associated with sexual activity; therefore, physicians may wish to consider the cardiovascular status of their patients prior to initiating any treatment for erectile dysfunction.

• Hepatic impairment: Use with caution in patients with mild to moderate hepatic impairment; dosage adjustment/limitation is needed. Use is not recommended in patients with severe hepatic impairment or cirrhosis.

• Peptic ulcer disease: Use with caution in patients with active peptic ulcer disease because of effect on platelets (bleeding); safety and efficacy have not been established.

• Pulmonary veno-occlusive disease (PVOD): Pulmonary vasodilators may exacerbate the cardiovascular status in patients with PVOD. Use is not recommended; no clinical data exists in patients with PVOD. In patients with unrecognized PVOD, signs of pulmonary edema should prompt investigation into this diagnosis.

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment/limitation is needed.

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.

• Nitrates: Concomitant use (regularly/intermittently) with all forms of nitrates is contraindicated. Nitrate-mediated vasodilation is markedly exaggerated and prolonged in the presence of PDE-5 inhibitors. When tadalafil is used for BPH, erectile dysfunction, or PAH and nitrate administration is medically necessary (eg, chest pain refractory to other treatments) following the use of tadalafil, at least 48 hours should elapse after the tadalafil dose and nitrate administration. When used for PAH, per the manufacturer, nitrate may be administered within 48 hours of tadalafil. For both situations, administration of nitrates should only be done under close medical supervision with hemodynamic monitoring.

Other warnings/precautions:

• Appropriate use: Potential underlying causes of erectile dysfunction or BPH should be evaluated prior to treatment.

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

No significant differences in pharmacokinetics were seen in elderly men versus younger men. Dosing should be adjusted for renal function. Since older adults often have concomitant diseases, many of which may be contraindicated with the use of tadalafil, prescriber should complete a thorough review of diseases and medications prior to prescribing tadalafil.

Reproductive Considerations

Less than 0.0005% is found in the semen of healthy males.

Pregnancy Considerations

Tadalafil likely crosses the placenta (Sakamoto 2016). Women with pulmonary arterial hypertension are encouraged to avoid pregnancy (McLaughlin 2009; Taichman 2014).

Breast-Feeding Considerations

It is not known if tadalafil is present in breast milk. The manufacturer recommends that caution be exercised when administering tadalafil to breastfeeding women.

Adverse Reactions

>10%:

Cardiovascular: Flushing (2% to 13%)

Central nervous system: Headache (4% to 42%)

Gastrointestinal: Nausea (≤11%)

Neuromuscular & skeletal: Myalgia (1% to 14%), limb pain (1% to 11%)

Respiratory: Respiratory tract infection (13%), nasopharyngitis (6% to 13%)

1% to 10%:

Cardiovascular: Hypertension (1% to 3%), angina pectoris (<2%), chest pain (<2%), facial edema (<2%), hypotension (<2%), myocardial infarction (<2%), orthostatic hypotension (<2%), palpitations (<2%), peripheral edema (<2%), syncope (<2%), tachycardia (<2%)

Central nervous system: Dizziness (<2%), drowsiness (<2%), fatigue (<2%), hypoesthesia (<2%), insomnia (<2%), pain (<2%), paresthesia (<2%), vertigo (<2%)

Dermatologic: Diaphoresis (<2%), pruritus (<2%), skin rash (<2%)

Endocrine & metabolic: Increased gamma-glutamyl transferase (<2%)

Gastrointestinal: Dyspepsia (2% to 10%), gastroenteritis (3% to 5%), gastroesophageal reflux disease (≤3%), diarrhea (1% to 3%), abdominal pain (1% to 2%), dysphagia (<2%), esophagitis (<2%), gastritis (<2%), hemorrhoidal bleeding (<2%), loose stools (<2%), upper abdominal pain (<2%), vomiting (<2%), xerostomia (<2%)

Genitourinary: Urinary tract infection (2%), prolonged erection (<2%), spontaneous erections (<2%)

Hematologic & oncologic: Rectal hemorrhage (<2%)

Hepatic: Abnormal hepatic function tests (<2%)

Neuromuscular & skeletal: Back pain (2% to 10%), arthralgia (<2%), asthenia (<2%), neck pain (<2%)

Ophthalmic: Blurred vision (<2%), conjunctival hyperemia (<2%), conjunctivitis (<2%), eyelid edema (<2%), eye pain (<2%), increased lacrimation (<2%), vision color changes (<2%)

Otic: Hearing loss (<2%), tinnitus (<2%)

Renal: Renal insufficiency (<2%)

Respiratory: Nasal congestion (≤9%), paranasal sinus congestion (≤9%), upper respiratory tract infection (3% to 4%), cough (2% to 4%), dyspnea (<2%), epistaxis (<2%), pharyngitis (<2%)

<1%, postmarketing, and/or case reports: Amnesia (transient global), anterior ischemic optic neuropathy (nonarteritic), basal cell carcinoma (Loeb 2015), cardiovascular toxicity, cerebrovascular accident, hypersensitivity reaction, malignant melanoma (Loeb 2015), migraine, muscle spasm, permanent vision loss, priapism, retinal artery occlusion, retinal vein occlusion, seizure, Stevens-Johnson syndrome, vision loss, visual field loss

* See Cautions in AHFS Essentials for additional information.

Metabolism/Transport Effects

Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions Open Interactions

Alcohol (Ethyl): May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors. Risk C: Monitor therapy

Alpha1-Blockers (Nonselective): Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Alpha1-Blockers (Nonselective). Management: Ensure patient is stable on one agent prior to initiating the other, and always initiate combination using the lowest possible dose of the drug being added. When tadalafil is used for treatment of BPH, concurrent alpha 1-blockers are not recommended. Risk D: Consider therapy modification

Alpha1-Blockers (Uroselective): May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors. Risk C: Monitor therapy

Alprostadil: Phosphodiesterase 5 Inhibitors may enhance the adverse/toxic effect of Alprostadil. Risk X: Avoid combination

Amyl Nitrite: Phosphodiesterase 5 Inhibitors may enhance the vasodilatory effect of Amyl Nitrite. Risk X: Avoid combination

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Blood Pressure Lowering Agents: Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bosentan: May decrease the serum concentration of Phosphodiesterase 5 Inhibitors. Phosphodiesterase 5 Inhibitors may increase the serum concentration of Bosentan. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

CYP3A4 Inducers (Strong): May decrease the serum concentration of Tadalafil. Management: Erectile dysfunction: monitor for decreased effectiveness - no standard dose adjustments recommended. Avoid use of tadalafil for pulmonary arterial hypertension in patients receiving a strong CYP3A4 inducer. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Tadalafil. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Tadalafil. Management: Avoid this combination in patients taking tadalafil for pulmonary arterial hypertension. In patients taking tadalafil for ED or BPH, max tadalafil dose is 2.5 mg if taking daily or 10 mg no more frequently than every 72 hours if used as needed. Exceptions: Ritonavir. Risk D: Consider therapy modification

Dapoxetine: May enhance the orthostatic hypotensive effect of Phosphodiesterase 5 Inhibitors. Risk X: Avoid combination

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Etravirine: May decrease the serum concentration of Phosphodiesterase 5 Inhibitors. Risk C: Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Lorcaserin (Withdrawn From US Market): May enhance the adverse/toxic effect of Phosphodiesterase 5 Inhibitors. Specifically, the risk of developing priapism may be increased. Risk C: Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Risk D: Consider therapy modification

Molsidomine: May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors. Risk X: Avoid combination

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Nitroprusside: Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Nitroprusside. Risk X: Avoid combination

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the adverse/toxic effect of other Phosphodiesterase 5 Inhibitors. Risk X: Avoid combination

Riociguat: Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Riociguat. Risk X: Avoid combination

Ritonavir: May increase the serum concentration of Tadalafil. Management: In patients treated for pulmonary arterial hypertension avoid initiating ritonavir in patients taking tadalafil; dose adjustments are required. For ED or BPH treatment, decrease tadalafil max dose and frequency. See full monograph for details. Risk D: Consider therapy modification

Sapropterin: May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors. Risk C: Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Simeprevir: May increase the serum concentration of Phosphodiesterase 5 Inhibitors. Risk C: Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Risk D: Consider therapy modification

Vasodilators (Organic Nitrates): Phosphodiesterase 5 Inhibitors may enhance the vasodilatory effect of Vasodilators (Organic Nitrates). Risk X: Avoid combination

Food Interactions

Rate and extent of absorption are not affected by food. Grapefruit juice may increase serum levels/toxicity of tadalafil. Management: Monitor for increased effects/toxicity with concomitant use.

Genes of Interest

Cytochrome P450 3A4

Monitoring Parameters

Blood pressure, response and adverse effects; urine flow, PSA

Advanced Practitioners Physical Assessment/Monitoring

Monitor for postural hypotension.

Nursing Physical Assessment/Monitoring

Monitor for postural hypotension.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Adcirca: 20 mg

Alyq: 20 mg

Cialis: 2.5 mg, 5 mg, 10 mg, 20 mg

Generic: 2.5 mg, 5 mg, 10 mg, 20 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Adcirca: 20 mg

Cialis: 2.5 mg, 5 mg, 10 mg, 20 mg

Generic: 2.5 mg, 5 mg, 10 mg, 20 mg

Anatomic Therapeutic Chemical (ATC) Classification

G04BE08

Generic Available (US)

Yes

Pricing: US

Tablets (Adcirca Oral)

20 mg (per each): $83.40

Tablets (Alyq Oral)

20 mg (per each): $76.15

Tablets (Cialis Oral)

2.5 mg (per each): $14.23

5 mg (per each): $14.23

10 mg (per each): $83.40

20 mg (per each): $83.40

Tablets (Tadalafil (PAH) Oral)

20 mg (per each): $72.14 - $76.15

Tablets (Tadalafil Oral)

2.5 mg (per each): $12.26 - $13.00

5 mg (per each): $12.26 - $13.00

10 mg (per each): $71.81 - $76.15

20 mg (per each): $71.81 - $76.15

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

BPH: Exact mechanism unknown; effects likely due to PDE-5 mediated reduction in smooth muscle and endothelial cell proliferation, decreased nerve activity, and increased smooth muscle relaxation and tissue perfusion of the prostate and bladder

Erectile dysfunction: Does not directly cause penile erections, but affects the response to sexual stimulation. The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation and inflow of blood to the corpus cavernosum. Tadalafil enhances the effect of NO by inhibiting phosphodiesterase type 5 (PDE-5), which is responsible for degradation of cGMP in the corpus cavernosum; when sexual stimulation causes local release of NO, inhibition of PDE-5 by tadalafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum. At recommended doses, it has no effect in the absence of sexual stimulation.

PAH: Inhibits phosphodiesterase type 5 (PDE-5) in smooth muscle of pulmonary vasculature where PDE-5 is responsible for the degradation of cyclic guanosine monophosphate (cGMP). Increased cGMP concentration results in pulmonary vasculature relaxation; vasodilation in the pulmonary bed and the systemic circulation (to a lesser degree) may occur.

Pharmacodynamics/Kinetics

Onset of action: Within 1 hour

Peak effect (pulmonary artery vasodilation): 75 to 90 minutes (Ghofrani 2004)

Duration: Erectile dysfunction: Up to 36 hours

Distribution: Vd: 63 to 77 L

Protein binding: 94%

Metabolism: Hepatic, via CYP3A4 to metabolites (inactive)

Half-life elimination: 15 to 17.5 hours; Pulmonary hypertension (not receiving bosentan): 35 hours

Time to peak, plasma: ~2 hours (range: 30 minutes to 6 hours)

Excretion: Feces (~61%, predominantly as metabolites); urine (~36%, predominantly as metabolites)

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: Tadalafil AUC doubled in subjects with CrCl 31 to 80 mL/minute. In patients with ESRD on hemodialysis, there was a 2-fold increase in Cmax and 2.7- to 4.8-fold increase in AUC.

Hepatic function impairment: Tadalafil AUC after a 10 mg dose in patients with mild or moderate hepatic impairment (Child-Pugh class A or B) was comparable with exposure in healthy subjects. There are insufficient data for subjects with severe hepatic impairment.

Geriatric: Subjects >65 years of age have a 25% higher exposure compared with subjects 19 to 45 years of age.

Diabetes mellitus: The AUC was reduced approximately 19% and Cmax was 5% lower in patients with diabetes mellitus than in healthy subjects.

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

GF196960

FDA Approval Date

November 21, 2003

References

Adcirca (tadalafil) [prescribing information]. Indianapolis, IN: Eli Lilly and Company; December 2019.

Adcirca (tadalafil) [product monograph]. Toronto, Ontario, Canada: Eli Lilly Canada Inc; January 2015.

Andersson KE, de Groat WC, McVary KT, et al, "Tadalafil for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: Pathophysiology and Mechanism(s) of Action," Neurourol Urodyn, 2011, 30(3):292-301.

Anderson JL, Adams CD, Antman EM, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(23):e663-e828. doi: 10.1161/CIR.0b013e31828478ac.[PubMed 23630129]10.1161/CIR.0b013e31828478ac

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Brand Names: International

36 Horas (PY); Adafil (BD); Adcirca (AT, AU, BB, BE, BR, CZ, DK, EE, ES, FR, GB, HR, HU, IE, IL, IS, JP, LT, LU, MT, MX, NL, NO, PL, PT, RO, SE, SI, SK); Cendom (KR); Cendom Orally Soluble Film (KR); Cialis (AE, AR, AT, AU, BB, BE, BF, BG, BH, BJ, BR, BS, CH, CI, CL, CN, CO, CR, CY, CZ, DE, DK, DO, EE, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, GT, HK, HN, HR, HU, IE, IL, IS, IT, JM, JO, JP, KE, KR, KW, LB, LR, LT, LU, LV, MA, ML, MR, MT, MU, MW, MX, MY, NE, NG, NI, NL, NO, NZ, PA, PE, PH, PL, PT, QA, RO, RU, SA, SC, SD, SE, SG, SI, SK, SL, SN, SV, TH, TN, TR, TT, TW, TZ, UA, UG, VE, VN, ZA, ZM, ZW); Ciaton (BD); Digram (PY); Duralis (LB); Erectalis (EG); Eredys 10 (VN); Erotadil (VN); Exerdya (HU); Forzest (IN); Glodafil (VN); Glofil (LK); GODN Orodispersible Film (KR); Greseo Powd. (KR); Gugu Chew (KR); Jovan T 20 (ZW); Lanrextan (AT); Link (LB); Mega Joy (BD); Megafil (LK); Megafort (VN); Mplify (ZW); Pasport (TR); Snafi (AE, BH, EG, KW, QA, SA); Spciafil (VN); Sunka (KR); Tadacip (LK); Tadaf (LK); Tadair (IL); Tadam (IL); Taderect (EG); Tagra (LB); Talmanco (BE); Tyra (BH); Viev (BD); Yesgra (KR); Zenavil (MT); Zydalis (IN)

Last Updated 5/7/20

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