Tadalafil

Tadalafil is a phosphodiesterase inhibitor used for treating impotence (erectile dysfunction, or ED), benign prostatic hyperplasia (BPH), and pulmonary arterial hypertension (PAH).

Tadalafil is available under the following different brand names: Adcirca, and Cialis.

Dosage Forms and Strengths

Tablet (Adcirca)

20 mg

Tablet (Cialis)

2.5 mg

5 mg

10 mg

20 mg

Dosage Considerations – Should be Given as Follows:

Erectile Dysfunction (ED)

Cialis

As needed use: 10 mg orally initially before sexual activity, with or without food; may be increased to 20 mg or reduced to 5 mg on basis of efficacy and tolerability; in most patients, maximum dosing frequency is once daily

Once-daily use: 2.5 mg/day orally in single daily dose, without regard to timing of sexual activity, with or without food; may be increased to 5 mg/day on basis of efficacy and tolerability

Dosing considerations

As needed use: Decrease dose with concomitant use of potent CYP3A4 inhibitor (e.g., ritonavir, ketoconazole, itraconazole); not to exceed 10 mg/72 hours

Once-daily use: Decrease dose with concomitant use of potent CYP3A4 inhibitor (e.g., ritonavir, ketoconazole, itraconazole); not to exceed 2.5 mg/day

Benign Prostatic Hyperplasia

Treatment of signs and symptoms of benign prostatic hyperplasia (BPH); daily use also indicated for treatment of patients with both BPH and erectile dysfunction

Cialis

BPH: 5 mg orally once daily

BPH with erectile dysfunction: 5 mg orally once daily, taken at approximately same time each day without regard to timing of sexual activity

With finasteride for BPH: tadalafil 5 mg plus finasteride 5 mg orally once daily for up to 26 weeks

Pulmonary Arterial Hypertension (PAH)

Adcirca

40 mg orally once daily; dividing dose for more frequent dosing is not recommended

Patients also taking ritonavir: 20 mg orally once daily initially for 1 week or more; may be increased to 40 mg/day on basis of tolerability

Dosing considerations

If possible, avoid coadministration with CYP3A4 inhibitors; if coadministration is essential, long-term therapy is indicated, or strong CYP3A4 inhibitors are required, modify or hold dose

Patients already taking strong CYP3A4 inhibitor who require tadalafil: 20 mg orally once daily; may be increased to 40 mg/day on basis of tolerability

Patients already taking tadalafil who require strong CYP3A4 inhibitor: Avoid using tadalafil while starting strong CYP3A4 inhibitor; stop tadalafil 24 hours or more before starting strong CYP3A4 inhibitor; after 1 week, resume tadalafil at 20 mg orally once daily; may be increased to 40 mg/day on basis of tolerability

Geriatric Dosing

Erectile Dysfunction (ED)

Cialis: No dosage adjustment is warranted solely on basis of age; however, greater sensitivity to medications in some older individuals should be considered

Pulmonary Arterial Hypertension (PAH)

Adcirca: Lower dose or reduced dosing frequency may be required in elderly because of decreased renal or hepatic clearance

Dosing Modifications

Pediatric: Safety and efficacy not established

Renal impairment (ED)

Cialis (as needed use)

Mild (CrCl 51 mL/min or more): No dosage adjustment needed

Moderate (CrCl 30-50 mL/min): Not to exceed 5 mg orally once daily initially; maximum dosage, 10 mg orally every 48 hours

Severe (CrCl less than 30 mL/min and on hemodialysis): Not to exceed 5 mg orally every 72 hours

Cialis (once daily use)

CrCl 30 mL/min or more: No dosage adjustment needed

CrCl less than 30 mL/min: Not recommended

Renal impairment (PAH)

Adcirca

Mild-to-moderate (CrCl 31-80 mL/min): 20 mg orally once daily initially; may be increased to 40 mg once daily on basis of tolerability

Severe (CrCl less than 30 mL/min and on hemodialysis): Avoid use

Hepatic impairment (ED)

Cialis (as needed use)

Mild-to-moderate (Child-Pugh class A or B): Not to exceed 10 mg orally once daily

Severe (Child-Pugh class C): Not recommended

Cialis (once daily use)

Mild-to-moderate (Child-Pugh class A or B): Data limited; caution advised

Severe (Child-Pugh class C): Not recommended

Hepatic impairment (PAH)

Adcirca

Mild-to-moderate (Child-Pugh class A or B): Consider starting dosage of 20 mg orally once daily

Severe (Child-Pugh class C): Avoid use

Common side effects or health problems may include:

• Headache
• Muscle pain
• Respiratory tract infection
• Runny or stuffy nose
• Indigestion
• Flushing (redness or warmth of the face, neck, or chest)
• Back pain
• Nausea
• Gastroesophageal reflux disease (GERD)
• High blood pressure (hypertension)
• Bronchitis
• Genitourinary tract infection
• Stomach upset
• Diarrhea
• Flu-like symptoms (such as stuffy nose, sneezing, or sore throat)
• Memory problems
• Low blood pressure (hypotension)
• Blurred vision
• Abnormal ejaculation
• Prolonged erections (priapism)

Less common side effects of tadalafil include:

• Amnesia
• Change in color vision
• Chest pain (angina)
• Conjunctival hyperemia
• Joint pain
• Nosebleed
• Shortness of breath

Postmarketing side effects of tadalafil reported include:

• Visual Loss
• Hearing loss

This is not a complete list of side effects and other serious side effects or health problems may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of this medicine or any drug before seeking medical advice from your doctor, healthcare provider or pharmacist first. To do so may result in serious consequences or side effects.

Severe Interactions of tadalafil include:

• boceprevir
• isosorbide dinitrate
• isosorbide mononitrate
• nitroglycerin IV
• nitroglycerin PO
• nitroglycerin rectal
• nitroglycerin sublingual
• nitroglycerin topical
• nitroglycerin transdermal
• nitroglycerin translingual
• riociguat
• telaprevir

Tadalafil has serious interactions with at least 21 different drugs.

Tadalafil has moderate interactions with at least 152different drugs.

Mild Interactions of tadalafil include:

• ranolazine

This document does not contain all possible interactions from the use of this medication. Therefore, before using this drug, tell your doctor or pharmacist of all the drugs you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

• This medication contains tadalafil. Do not take Adcirca or Cialis if you are allergic to tadalafil or any ingredients contained in this drug.
• Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• Hypersensitivity, including Stevens-Johnson syndrome and exfoliative dermatitis
• Soluble guanylate cyclase (sGC) stimulators (e.g., riociguat); concomitant use can cause hypotension
• Coadministration with nitrates
• Coadministration with nitrates (either regularly and/or intermittently) and nitric oxide donors
• Consistent with the effects of PDE5 inhibition on the nitric oxide/cyclic guanosine monophosphate pathway, PDE5 inhibitors may potentiate the hypotensive effects of nitrates
• A suitable time interval following PDE5 dosing for the safe administration of nitrates or nitric oxide donors has not been determined

Effects of Drug Abuse

• No information provided

Short-Term Effects

• See "What Are Side Effects Associated with Using Tadalafil?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Tadalafil?"

Cautions

• Use caution in patients with anatomic deformation of penis, cardiovascular disease, left ventricular outflow obstruction, myocardial infarction in preceding 90 days, unstable angina, angina occurring during sexual intercourse, NYHA class 2 or greater heart failure in preceding 6 months, uncontrolled arrhythmias, hypotension, uncontrolled hypertension, cerebrovascular accident in preceding 6 months, bleeding disorders, active peptic ulcer disease, liver disease, renal impairment, conditions predisposing to priapism, concomitant use of CYP3A4 inhibitors.
• May cause dose-related impairment of color discrimination; use caution in patients with retinitis pigmentosa.
• Evaluate underlying causes of erectile dysfunction or benign prostatic hyperplasia (BPH) before initiating therapy.
• May increase risk of sudden vision loss attributed to non-arteritic ischemic optic neuropathy; if vision problems arise, discontinue, and contact physician.
• Risk of sudden hearing loss.
• CYP3A4 inhibitors (e.g., erythromycin, ketoconazole, itraconazole, indinavir, ritonavir) may significantly increase tadalafil serum levels.
• CYP3A4 inducers (e.g., rifampin, St John's wort) may decrease tadalafil serum levels.
• Potentiates hypotensive effect of nitrates.
• Concomitant use with alpha-blockers (other than tamsulosin 0.4 mg/day) should be stabilized before initiation of phosphodiesterase (PDE)-5 inhibitors; patients with instability on alpha-blocker therapy alone are at increased risk for symptomatic hypotension with concurrent PDE-5 inhibitor therapy.
• Not to be taken with other PDE-5 inhibitors (e.g., sildenafil, vardenafil).
• Not recommended in patients with pulmonary veno-occlusive disease.
• Advise patients to seek emergency treatment if an erection lasts more than 4 hours.

Pregnancy and Lactation

• Tadalafil may be acceptable for use during pregnancy. Either animal studies show no risk but human studies are not available or animal studies showed minor risks and human studies were done and showed no risk.
• Tadalafil use is not recommended in nursing women.