Brand names: Cialis, Entadfi
Drug class: Phosphodiesterase Type 5 Inhibitors

Medically reviewed by Drugs.com on Apr 10, 2024. Written by ASHP.

Introduction

Vasodilating agent; a selective phosphodiesterase (PDE) type 5 inhibitor.

Uses for Tadalafil (Erectile Dysfunction, Benign Prostatic Hyperplasia)

Erectile Dysfunction

Used for the treatment of erectile dysfunction (ED, impotence).

May be used as needed (on demand) or on a daily basis (without regard to timing of sexual activity).

Experts recommend a selective PDE type 5 inhibitor as first-line therapy for ED unless contraindicated. Evidence currently insufficient to support superiority of one selective PDE type 5 inhibitor over another.

Benign Prostatic Hyperplasia

Used as monotherapy or in fixed combination with finasteride (finasteride/tadalafil) for symptomatic management (e.g., to improve lower urinary tract symptoms) of benign prostatic hyperplasia (BPH, benign prostatic hypertrophy).

Not recommended for use in combination with an α-adrenergic blocking agent (e.g., doxazosin, terazosin); inadequate data and potential for additive hypotensive effects.

Concomitant ED and BPH

Treatment of both ED and symptomatic BPH in men with such coexisting conditions.

Tadalafil (Erectile Dysfunction, Benign Prostatic Hyperplasia) Dosage and Administration

General

Pretreatment Screening

• Finasteride/tadalafil: Consider whether the patient has other urological conditions that may cause symptoms similar to BPH; prostate cancer and BPH may coexist.

Patient Monitoring

• Finasteride/tadalafil: Monitor patients with large residual urinary volume and/or severely diminished urinary flow for obstructive uropathy.

• Finasteride/tadalafil: Obtain prostate-specific antigen (PSA) level 6 months after starting treatment to establish a new PSA baseline; monitor PSA periodically thereafter.

Dispensing and Administration Precautions

Handling and Disposal

• Finasteride/tadalafil: Pregnant females should not handle crushed or open finasteride/tadalafil capsules because of the potential for absorption of finasteride and the subsequent potential risk to a male fetus. Wash the contact area immediately with soap and water if contact occurs with crushed or broken capsules.

Administration

Oral Administration

Tadalafil Monotherapy

Administer orally without regard to meals.

May be administered as needed (just prior to [e.g., ≥0.5 hours before] anticipated sexual activity) or on a daily basis (at approximately the same time every day) for treatment of ED; take entire dose and do not split tablets. Because of prolonged duration of action (up to 36 hours), timing of administration relative to anticipated sexual activity is less important than with relatively short-acting drugs for ED.

Administer as a once-daily dose at approximately the same time every day in patients with BPH with or without coexisting ED. When tadalafil is initiated with finasteride, administer as a once-daily dose at approximately the same time every day. The incremental benefit of tadalafil beyond 26 weeks in such patients is unknown.

If a dose is missed, take the dose as soon as it is remembered but do not take more than one dose per day.

Finasteride/Tadalafil Fixed-combination Therapy

Administer orally on an empty stomach.

Administer fixed-combination capsule as a once-daily dose at approximately the same time every day for treatment of BPH. The incremental benefit of tadalafil beyond 26 weeks is unknown.

If a dose is missed, take the dose as soon as it is remembered but do not take more than one dose per day.

Dosage

Adults

ED

Oral

As-needed therapy: Usual initial dose is 10 mg just prior (e.g., at least 0.5 hours before) to anticipated sexual activity. Depending on effectiveness and tolerance, may increase dose to 20 mg or decrease to 5 mg. Maximum recommended dosing frequency is once daily for most patients. Concomitant use with HIV protease inhibitors or with potent CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) requires dosage adjustment (see Drug Interactions).

Once-daily therapy: Initially, 2.5 mg once daily. Depending on effectiveness and tolerance, may increase dosage to 5 mg once daily. Concomitant use with potent CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) requires dosage adjustment (see Drug Interactions).

BPH

Oral

5 mg once daily.

Concomitant use with potent CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) requires dosage adjustment (see Drug Interactions).

Finasteride/tadalafil fixed-combination therapy: 5 mg of finasteride and 5 mg of tadalafil once daily as the fixed combination for up to 26 weeks.

Concomitant ED and BPH

Oral

5 mg once daily.

Concomitant use with potent CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) requires dosage adjustment (see Drug Interactions).

Special Populations

Hepatic Impairment

As-needed use for ED: In patients with mild or moderate hepatic impairment (Child-Pugh class A or B), maximum dosage is 10 mg once per day.

Once-daily use for BPH and/or ED: Use with caution in patients with mild or moderate hepatic impairment.

Finasteride/tadalafil fixed-combination therapy: Caution advised for mild or moderate hepatic impairment (Child-Pugh class A or B); not recommended for severe hepatic impairment (Child-Pugh class C).

Renal Impairment

As-needed use for ED: In patients with Cl_cr 30–50 mL/minute, reduce initial dose to 5 mg, administered no more frequently than once daily; maximum dose 10 mg, administered no more frequently than once every 48 hours. For patients with Cl_cr<30 mL/minute or those undergoing hemodialysis, maximum dose 5 mg, administered no more frequently than once every 72 hours.

Once-daily use for ED: Dosage adjustments not necessary in patients with Cl_cr ≥30 mL/minute. Use not recommended in patients with Cl_cr <30 mL/minute or those on hemodialysis.

Once-daily use for BPH with or without ED: For Cl_cr 30–50 mL/minute, initial dosage of 2.5 mg once daily recommended; may increase to 5 mg once daily based on patient response and tolerance. Use not recommended in patients with Cl_cr <30 mL/minute or those on hemodialysis.

Finasteride/tadalafil fixed combination: Not recommended in patients with Cl_cr <50 mL/minute or on hemodialysis.

Geriatric Patients

No dosage adjustments necessary based solely on age.

Cautions for Tadalafil (Erectile Dysfunction, Benign Prostatic Hyperplasia)

Contraindications

• Known hypersensitivity to tadalafil, finasteride, or any ingredient in the formulations.

• Concomitant use of organic nitrates, either regularly or intermittently.

• Concomitant use of guanylate cyclase stimulators (e.g., riociguat).

• Finasteride/tadalafil fixed combination: Pregnancy.

Warnings/Precautions

Patient Assessment

Thorough medical history and physical examination is recommended to determine potential underlying causes and identify appropriate treatment options for ED and/or BPH.

Prior to initiating therapy in patients with BPH, consider possibility of other urologic conditions, including prostate cancer, that may cause similar symptoms.

Carefully monitor patients with large residual urinary volume and/or severely diminished urinary flow for obstructive uropathy; these patients may not be candidates for finasteride/tadalafil.

Cardiovascular Effects

Safety and efficacy for treatment of ED not established and use not recommended in patients with a recent MI (within 90 days) or stroke (within 6 months); uncontrolled arrhythmias, hypotension (<90/50 mm Hg systolic/diastolic BP) or uncontrolled hypertension; heart failure (>NYHA class II) in the previous 6 months; or those with unstable angina or angina occurring during sexual intercourse.

Possible hypotension, particularly in patients with left-ventricular outflow obstruction (e.g., aortic stenosis, idiopathic hypertrophic subaortic stenosis) and in patients with severely impaired autonomic control of blood pressure. Additive BP-lowering effects may occur when used concomitantly with other vasodilating agents (e.g., α-adrenergic blocking agents or other antihypertensive drugs, alcohol, riociguat).

Potentiation of hypotensive effect with organic nitrates, which may result in life-threatening hypotension and/or hemodynamic compromise; concomitant use contraindicated.

Consider whether patients with underlying cardiovascular disease could be adversely affected by tadalafil’s vasodilatory activity, especially in combination with sexual activity.

Concomitant Administration with α-Adrenergic Blocking Agents

Use with caution in patients receiving α-adrenergic blocking agents; possible potentiation of hypotensive effects due to additive vasodilatory action. In some cases, dosage adjustments are necessary, while in other cases, concomitant administration not recommended.

Safety of concomitant therapy also may be affected by intravascular volume depletion and use of additional antihypertensive agents.

Ocular Effects

Nonarteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, reported rarely during postmarketing experience in temporal association with use of all PDE type 5 inhibitors. Potential increased risk of NAION in the second eye in patients who have already experienced NAION in one eye.

Use not recommended in patients with hereditary degenerative retinal disorders, including retinitis pigmentosa.

Otic Effects

Sudden decrease or loss of hearing reported in temporal association with all PDE type 5 inhibitors.

It is unclear whether such effects are directly related to PDE type 5 inhibitors or to other factors.

Priapism

Possible prolonged erections (>4 hours) and priapism (painful erection >6 hours).

May result in penile tissue damage and permanent loss of potency if priapism is not treated immediately. Use with caution in patients with conditions that may predispose to priapism (e.g., sickle cell anemia, multiple myeloma, leukemia) and in those with anatomic deformation of the penis (e.g., angulation, cavernosal fibrosis, Peyronie’s disease).

Concomitant Administration with Potent CYP3A4 Inhibitors or Inducers

Consider potential for increased or decreased tadalafil concentrations when used concomitantly with potent inhibitors or inducers of CYP3A4; in some cases, dosage adjustments may be necessary, while in other cases, concomitant administration not recommended.

Concomitant Use with Other PDE Type 5 Inhibitors or ED Therapies

Safety and efficacy not established for use in combination with other PDE type 5 inhibitors or other treatments for ED; do not use concomitantly with other PDE type 5 inhibitors.

Hematologic Effects

Tadalafil inhibits PDE type 5, which is found in platelets. Although increase in bleeding time not observed in healthy individuals, manufacturer recommends caution in patients with bleeding disorders or substantial, active peptic ulcers; carefully weigh risks versus benefits of therapy.

Counseling Patients on Sexually Transmitted Diseases

Patients should be advised that use of tadalafil provides no protection against sexually transmitted diseases, including HIV infection, and they should be counseled regarding protective measures to guard against such transmission.

Potential for Drug Interactions with Once-daily Use

Once-daily tadalafil monotherapy or finasteride/tadalafil fixed-combination therapy provides continuous tadalafil plasma drug levels.

Consider potential for interactions with medications (e.g., nitrates, α-adrenergic blocking agents, anti-hypertensives and potent inhibitors of CYP3A4) and substantial consumption of alcohol.

Concomitant Use with Alcohol

Alcohol and PDE type 5 inhibitors are both vasodilators; combined use may have additive BP-lowering effects.

Orthostatic hypotension, manifested by increased heart rate, decreased standing BP, dizziness, and headache may occur with consumption of substantial amounts of alcohol (e.g., ≥ 5 glasses of wine or 5 shots of whiskey).

Use of Fixed Combinations

When tadalafil is used in fixed combination with finasteride, consider the usual cautions, precautions, and contraindications associated with finasteride in addition to those associated with tadalafil.

Effects on Prostate-Specific Antigen (PSA) and the Use of PSA in Prostate Cancer Detection (Finasteride/Tadalafil)

Finasteride causes decreased serum PSA concentrations (approximately 50%) within 6 months; PSA decreases can occur even in those with prostate cancer.

Establish a new PSA baseline at least 6 months after starting finasteride/tadalafil; monitor PSA periodically thereafter.

Carefully evaluate any confirmed increase in serum PSA concentration during therapy, even if PSA is within normal range for men not receiving finasteride.

Noncompliance may affect PSA concentrations; consider when evaluating test results.

Increased Risk of High-Grade Prostate Cancer (Finasteride/Tadalafil)

Finasteride may increase risk of high-grade prostate cancer.

Hypersensitivity Reactions (Finasteride/Tadalafil)

Stevens-Johnson syndrome, exfoliative dermatitis, pruritis, urticaria, and angioedema reported. Contraindicated in patients with a history of hypersensitivity reactions to finasteride or tadalafi.

Risk to Male Fetus from Topical Exposure to Pregnant Females (Finasteride/Tadalafil)

May cause fetal harm; teratogenicity demonstrated in animals.

Abnormal development of external genitalia in a male fetus may occur.

Because of potential for absorption through skin and subsequent potential risk to a male fetus, pregnant females should not handle crushed or open finasteride/tadalafil capsules. If such contact occurs, wash affected area immediately with soap and water.

Specific Populations

Pregnancy

Tadalafil (Cialis) not indicated for use in women.

Finasteride/tadalafil (Entadfi™): Contraindicated in pregnancy; not indicated for use in females. Finasteride may cause fetal harm; teratogenicity demonstrated in animals.

Lactation

Excreted into milk in rats. Not known if tadalafil is excreted into milk in humans.

Tadalafil and finasteride/tadalafil not indicated for use in women.

Females and Males of Reproductive Potential

Decreased sperm concentrations observed in human studies; however, clinical significance unknown.

No studies evaluating the effect of tadalafil on fertility in men or women.

Pediatric Use

Safety and efficacy not established in patients <18 years of age.

Geriatric Use

Safety and efficacy in those >65 years of age is similar to that in younger patients. Possibility exists of greater sensitivity to the drug in some geriatric individuals.

Hepatic Impairment

Insufficient experience in patients with severe hepatic impairment (Child-Pugh C); use not recommended.

Data limited in patients with mild or moderate hepatic impairment (Child-Pugh class A or B) receiving once-daily tadalafil for ED, BPH, or for both conditions; caution advised in such patients. Dosage adjustments recommended in patients with mild or moderate hepatic impairment receiving as-needed therapy for ED.

Finasteride/tadalafil: finasteride is extensively metabolized in liver; effect of hepatic impairment on finasteride not studied.

Renal Impairment

Use of once-daily tadalafil not recommended in any patient with severe renal impairment.

Dosage adjustments recommended in patients with moderate to severe renal impairment receiving once-daily or as-needed tadalafil for ED.

Finasteride/tadalafil: Use not recommended in patients with Cl_cr<50 mL/minute or on hemodialysis.

Common Adverse Effects

Tadalafil (Cialis and generic equivalents): Most common adverse effects (≥2%) include headache, dyspepsia, back pain, myalgia, nasal congestion, flushing, limb pain.

Finasteride/tadalafil: Most common adverse effects (≥1%) include impotence, decreased libido, decreased volume of ejaculate, breast enlargement, breast tenderness, rash.

Drug Interactions

Metabolized principally by CYP3A4. Does not appear to induce or inhibit the clearance of other drugs metabolized by P-glycoprotein (P-gp) or CYP isoforms 1A2, 3A4, 2C9, 2C19, 2D6, or 2E1.

Drugs Affecting or Affected by Hepatic Microsomal Enzymes

Potent inhibitors of CYP3A4: Potential pharmacokinetic interaction (increased tadalafil exposure). In some cases, manufacturer and experts recommend tadalafil dosage adjustments, maximum doses, and/or monitoring for safety or effectiveness during concomitant therapy, while in other cases (i.e., finasteride/tadalafil fixed-combination therapy), concomitant use not recommended.

Potent inducers of CYP3A: Potential pharmacokinetic interaction (decreased tadalafil exposure) and possible decreased efficacy of tadalafil; however, magnitude of such decreased effectiveness is unknown. Some experts recommend tadalafil dose titration based on clinical effect when these drugs are taken concomitantly. Coadministration with finasteride/tadalafil not recommended.

Specific Drugs and Foods

Tadalafil (Erectile Dysfunction, Benign Prostatic Hyperplasia) Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability unknown. Peak plasma concentrations usually attained within 0.5–6 hours.

Onset

Following a single oral dose, effects were obtained within 20 minutes.

Duration

Improved erection up to 24-36 hours.

Food

Food does not appear to affect absorption.

Distribution

Extent

Distributed into tissues.

Plasma Protein Binding

Approximately 94%.

Elimination

Metabolism

Metabolized in the liver, principally by CYP3A4, to inactive metabolites.

Elimination Route

Excreted principally as metabolites in the feces (61%) and urine (36%). Not appreciably removed by hemodialysis.

Half-life

17.5 hours.

Special Populations

In patients with diabetes mellitus, AUC and peak plasma concentrations are decreased compared with healthy individuals.

Clearance reduced in patients ≥65 years of age compared with younger adults, in patients with renal impairment (Cl_cr30-80 mL/minute) including end-stage renal disease on hemodialysis, in patients with mild or moderate hepatic impairment (Child-Pugh class A or class B), and in patients with diabetes mellitus.

Stability

Storage

Oral

Tablets (Tadalafil)

25°C (excursions permitted to 15–30°C).

Capsules (Finasteride/Tadalafil)

20–25°C (excursions permitted to 15–30°C).

Actions

• Selective inhibitor of phosphodiesterases (PDEs), with greatest selectivity for PDE type 5, the principal isoenzyme involved in the metabolism of cGMP to GMP in the corpora cavernosa of the penis.

• PDE type 5 also found in smooth muscle of the prostate and bladder, as well as in vascular and visceral smooth muscle, skeletal muscle, platelets, kidney, lung, cerebellum, and pancreas.

• Potentiates accumulation of cGMP only when cGMP production in the penis is increased by sexual arousal. No effect on erectile function in the absence of sexual stimulation.

• Exact mechanism of action in reducing symptoms of BPH not established, but may be related to smooth muscle relaxation and increased vascular perfusion of the lower urinary tract (i.e., bladder, prostate).

• Modest peripheral vasodilation at usual dosages.

• Although pharmacologically related to other PDE type 5 inhibitors (e.g., sildenafil, vardenafil), tadalafil has a longer elimination half-life and longer duration of action.

Advice to Patients

• Importance of instructing patients to read the manufacturer's patient information before starting tadalafil therapy and each time their prescription is refilled.

• Inform patients that tadalafil is marketed for ED (Cialis and generic equivalents), BPH (Cialis and generic equivalents, Entadfi™), and pulmonary arterial hypertension (Adcirca and generic equivalents, Alyq™, Tadliq); advise patients not to take a combination of these agents or other PDE type 5 inhibitors.

• Risk of symptomatic hypotension (e.g., dizziness, fainting) with concurrent use of α-adrenergic blocking agents or other antihypertensive agents. Advise patients of the potential for tadalafil to augment BP lowering.

• Importance of informing clinician of the presence of risk factors for cardiovascular disease prior to initiating any treatment for ED. Importance of not using tadalafil if underlying cardiovascular disease precludes sexual activity.

• Inform patients taking tadalafil for ED and with potential for cardiac risk of sexual activity (e.g., patients with preexisting cardiovascular risk factors) to refrain from further activity and seek medical attention immediately if they experience symptoms (e.g., chest pain, dizziness, nausea) upon initiation of sexual activity.

• Importance of avoiding concurrent use of organic nitrates or nitrites in any form, including the recreational use of inhaled nitrites (“poppers”) within 48 hours of tadalafil, because of the potential for hypotension and associated dizziness, fainting, or MI or stroke.

• Potential for sudden vision loss or decreased vision (nonarteritic anterior ischemic optic neuropathy [NAION]). Advise patients to seek immediate medical attention if sudden loss of vision in one or both eyes occurs while taking tadalafil or other PDE type 5 inhibitor. Such an event may be a sign of NAION, which can lead to possible permanent loss of vision.

• Risk of sudden hearing impairment; advise patients to seek prompt medical attention in the event of sudden decrease or loss of hearing while taking tadalafil. These events may be accompanied by tinnitus and dizziness.

• Risk of priapism. Advise patients to seek prompt medical attention for an erection that lasts more than 4 hours, whether painful or not. If not treated right away, priapism can permanently damage the penis.

• Advise patients taking tadalafil for ED regarding potential for sexually transmitted diseases and the need to use protective measures to guard against transmission of such diseases.

• Provide instructions regarding proper administration for optimal use. Importance of taking the drug exactly as prescribed and not exceeding recommended doses or frequency of use. Instruct the patient to seek medical attention immediately if they take too much tadalafil.

• Importance of advising patients receiving once-daily therapy to take tadalafil at about the same time each day. Tadalafil may be taken with or without food; tadalafil in fixed combination with finasteride should be taken without food.

• If a dose of once daily tadalafil or finasteride/tadalafil is missed, importance of advising patients to take it as soon as they remember, but to not take more than one dose per day.

• Tadalafil for ED (Cialis and generics): Advise patients to take tadalafil as needed at least 30 minutes (or for up to 36 hours) prior to sexual activity. Do not take tadalafil more than 1 time a day

• Finasteride/tadalafil: Importance of informing patients that finasteride decreases serum prostate-specific antigen (PSA) concentrations. Importance of appropriate medical evaluation of any increase in PSA concentration. If a PSA test is performed, the patient should inform the clinician that he is taking a 5α-reductase inhibitor. Clinicians should also be informed if the patient is not taking the drug daily as prescribed.

• Finasteride/tadalafil: Importance of informing patients that the incidence of high-grade prostate cancer was increased in men receiving 5α-reductase inhibitors (e.g., finasteride) in clinical trials evaluating efficacy of these drugs for prostate cancer prevention.

• Finasteride/tadalafil: Risk to male fetuses. Importance of advising patients that pregnant women or women who may become pregnant should not handle finasteride/tadalafil (i.e. crushed or open capsules); if such contact occurs, wash affected area immediately with soap and water and inform clinician.

• Limit intake of alcohol-containing beverages or products. Instruct patients that consumption of substantial amounts of alcohol (e.g., 5 glasses of wine or 5 shots of whiskey) with tadalafil may increase the potential for orthostatic hypotension, manifested by increased heart rate, decreased standing BP, dizziness, and headache.

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, and alcohol consumption, as well as any concomitant illnesses.

• Importance of informing patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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