Tadalafil, a selective phosphodiesterase (PDE) type 5 inhibitor, is a vasodilating agent.1
Tadalafil (Cialis® and generic equivalents) is used for the treatment of erectile dysfunction (ED, impotence).1, 3, 4, 6, 7, 8, 9, 59, 60, 61
A thorough medical, sexual and psychosocial history, physical examination, and selective laboratory testing should be undertaken to diagnose ED, determine potential underlying causes, exclude potentially reversible or treatable causes (e.g., hypogonadism with inadequate testosterone replacement, hyperprolactinemia, drug-induced dysfunction, dyslipidemias, alcoholism, other substance abuse, hypertension, thyroid disease, cardiovascular or cerebrovascular disease, neurologic disease, adrenal dysfunction), and identify appropriate treatment in conjunction with or prior to initiating vasoactive therapy (e.g., PDE 5 type inhibitor).161, 189, 601, 602, 603 A review of the patient's current drug regimens should be conducted to detect possible drug-induced ED (e.g., certain antihypertensive, antidepressant, antipsychotic, or antiarrhythmic agents); it may be possible to substitute alternative drug(s) that lessen the risk of such dysfunction.161, 602, 603 In instances where substitution therapy is not feasible, concomitant vasoactive therapy with a PDE 5 type inhibitor may promote patient compliance by counteracting ED as an adverse effect.161, 603
The safety and efficacy of as-needed therapy with tadalafil in men with ED of various etiologies are based principally on the results of 7 randomized, double-blind, placebo-controlled trials of 12 weeks' duration.1, 6, 7, 9 In these and other trials of similar duration in patients with ED, including individuals with diabetes mellitus or those who had undergone bilateral nerve-sparing radical prostatectomy, tadalafil (2.5-20 mg, generally 5, 10, or 20 mg) produced clinically important improvement in erectile function that did not diminish over time.1, 6, 7, 9 In these trials, patients generally were allowed to choose the interval between drug administration and sexual activity.1 In 2 clinical trials specifically evaluating efficacy of tadalafil 20 mg at 24 hours (range: 22-26 hours) and 36 hours (range: 33-39 hours) after administration, the proportion of patients reporting at least 1 successful intercourse at each of these time points was higher with tadalafil (61 or 64% at 24 or 36 hours, respectively) than with placebo (37% of patients at each time point).1, 9
The safety and efficacy of once-daily therapy with tadalafil are based principally on the results of 3 multicenter, double-blind, placebo-controlled trials of 12- or 24-weeks duration in men with ED of various etiologies.1 In 2 of these trials in patients with ED, including those with complications from diabetes mellitus, hypertension, hyperlipidemia, or prostatic disease, tadalafil (2.5, 5, or 10 mg once daily) produced clinically important improvements in erectile function.1, 60, 61 The mean per-patient rate of maintenance of erection to successful completion of intercourse was 50 or 57% with 2.5 or 5 mg of tadalafil, respectively, in the 24-week trial compared with 31% with placebo; the per-patient rate for this efficacy measure in the 12-week trial was 67 or 37% for tadalafil 5 mg or placebo, respectively.1, 60, 61 In the 24-week clinical trial, these effects did not diminish over time.1, 60 In another randomized, double-blind, placebo-controlled trial in patients with ED and diabetes mellitus, the mean per-patient rates of maintenance of erection to successful completion of intercourse were 46 or 41% with 2.5 or 5 mg of tadalafil, respectively, compared with 28% with placebo.1, 59
With the availability of orally active and convenient vasoactive (erectogenic) therapies (e.g., selective phosphodiesterase [PDE] type 5 inhibitors such as sildenafil, tadalafil, avanafil, and vardenafil), most experts (e.g., the American Urological Association [AUA]) now consider these drugs to be first-line therapies for a broad range of patients with ED unless contraindicated.18, 19, 30, 189, 601
Because PDE type 5 inhibitors are administered orally, they are likely to be more acceptable to men with ED than other vasoactive therapies (e.g., intracavernosal injections, intraurethral suppositories) or mechanical or prosthetic devices.602 Alternative therapies (e.g., intracavernosal or intraurethral vasoactive agents, vacuum constriction devices) may be considered for patients who fail to respond to, or are not candidates for, first-line therapy (e.g., patients who require nitrate therapy).161, 189, 601 Ultimately, the choice of therapy for ED should be individualized, taking into account patient response, tolerability, and safety; administration considerations, cost and patient reimbursement factors; experience and judgment of the clinician; and individual patient and partner preference, expectations, and satisfaction.189, 601, 602
PDE type 5 inhibitors are effective only in the presence of adequate sexual stimulation.189, 601, 602 Prior to proceeding to alternative therapies in patients reporting failure of selective PDE type 5 inhibitor therapy, an evaluation to determine whether there was an adequate trial should be undertaken.189, 601, 602 Non-response to PDE type 5 inhibitors is related to factors such as condition severity, medications, and comorbidities (e.g., diabetes mellitus, vascular disease, hypogonadism, psychological factors, neurologic damage [e.g., non-nerve-sparing radical prostatectomy], radiotherapy for prostate cancer).602 Treatment failure may also be attributed to incorrect use of PDE type 5 inhibitor therapy (e.g., lack of sexual stimulation, medication taken with a large meal).189 The possibility that another selective PDE type 5 inhibitor therapy may be effective should be considered in patients who fail an adequate trial with one drug.189, 601, 602 Although differences in the pharmacokinetics of these drugs (onset and duration) may exist, data currently are insufficient to support the superiority of one selective PDE type 5 inhibitor over another.189, 601, 602
Tadalafil (Cialis® and generic equivalents) is used for the treatment of signs and symptoms of benign prostatic hyperplasia (BPH, benign prostatic hypertrophy).1, 81, 82, 83, 84, 89 In clinical studies, tadalafil improved lower urinary tract symptoms associated with BPH (e.g., urinary frequency, urgency, nocturia, straining, incomplete emptying, weak urinary stream) but generally did not affect peak urinary flow rate or postvoid residual volume.1, 81, 82, 83, 84, 89
Tadalafil is also available in fixed combination with finasteride, a 5α-reductase inhibitor; the fixed combination preparation (finasteride/tadalafil; Entadfi®) is used to initiate treatment of the signs and symptoms of BPH in men with an enlarged prostate for up to 26 weeks.2 The incremental benefit of tadalafil beyond 26 weeks is unknown.2
Clinical Experience: Tadalafil Monotherapy
Efficacy and safety of once-daily tadalafil therapy for the symptomatic management of BPH are based principally on the results of 3 multinational, double-blind, placebo-controlled studies of 12 weeks' duration.1, 81, 82 Two of these studies included men with BPH alone; the third study included men with both BPH and ED.1, 81, 82 In the 2 studies evaluating the effects of tadalafil in men with BPH alone (i.e., without ED), treatment with tadalafil 5 mg once daily substantially improved the scores for severity of irritative (e.g., frequency, urgency, nocturia) and obstructive (e.g., incomplete bladder emptying, stopping and starting urination, weak stream, pushing or straining on urination) symptoms of BPH as measured by a 4-week recall questionnaire (International Prostate Symptom Score [IPSS]).1, 81 A reduction in symptoms was observed at 4 weeks and continued throughout the remainder of the study periods.1, 81 Tadalafil therapy also was associated with an improvement in quality of life (e.g., as measured by the Benign Prostatic Hyperplasia Impact Index [BII]); however, changes in peak urinary flow rate and postvoid residual volume with tadalafil were not substantially different from those with placebo.1, 81 Results of an open-label extension study in patients with symptomatic BPH indicate that improvements in lower urinary tract symptoms are maintained during long-term (e.g., 1 year) tadalafil therapy.83
Clinical Experience: Finasteride/Tadalafil Combination
Efficacy and safety of the fixed combination of finasteride and tadalafil (finasteride/tadalafil) for the symptomatic management of BPH are based on the results of a 26-week, double-blind, placebo-controlled study of tadalafil coadministered with finasteride in men with BPH.2 Patients ≥45 years of age with IPSS ≥13 and prostate volume ≥30 mL who did not previously receive treatment with an 5α-reductase inhibitor were randomized to tadalafil 5 mg plus finasteride 5 mg or placebo plus finasteride 5 mg.2, 100 Patients with multiple comorbid conditions such as ED, diabetes mellitus, hypertension, and other cardiovascular diseases were included.2 The mean age of patients was 64 years (range 46-86).2
Treatment with tadalafil plus finasteride resulted in a statistically significant improvement in the signs and symptoms of BPH as measured by the total symptom score (IPSS) at 12 weeks (the primary study endpoint) compared with finasteride plus placebo.2 However, the magnitude of treatment difference between placebo/finasteride and tadalafil/finasteride decreased from 1.7 points at week 4 to 1 point at week 26; the incremental benefit of combination therapy beyond 26 weeks is unknown.2 Statistically significant improvement in erectile dysfunction as measured by the International Index of Erectile Function-Erectile Function (IIEF-EF) in sexually active men was observed at 4-, 12-, and 26-weeks in those taking the combination therapy.100
Randomized controlled clinical trials have demonstrated the efficacy of α-adrenergic blocking agents, 5α-reductase inhibitors, and the long-acting PDE type 5 inhibitor tadalafil for the treatment of BPH.604 Most experts (e.g., the American Urological Association [AUA]) consider α-adrenergic blocking agent monotherapy as first-line therapy unless the patient has comorbid ED, prostate volume >30mL, or prostate specific antigen (PSA) >1.5 ng/dL604, 605 Tadalafil may be considered first-line in those with comorbid ED.604, 605
Experts do not provide a recommendation for the place in therapy of tadalafil in combination with finasteride, however, this combination has been shown to be effective for up to 26 weeks in men with an enlarged prostate (volume >30 mL).2, 604, 605 The incremental benefit of tadalafil when combined with finasteride has been shown to decrease from 4 weeks until 26 weeks, and the incremental benefit of tadalafil beyond 26 weeks is not known.1, 2
The combination of tadalafil and an α-adrenergic blocking agent (e.g., doxazosin, terazosin) currently is not recommended for the treatment of BPH because it offers no advantages in symptom improvement over either agent alone and has the potential for additive vasodilatory and hypotensive effects.1, 2 604
Concomitant Erectile Dysfunction and Benign Prostatic Hyperplasia
Tadalafil (Cialis® and generic equivalents) is used for the treatment of ED and the signs and symptoms of BPH (ED/BPH).1, 82, 89 In a randomized placebo-controlled study,1, 82 tadalafil 5 mg once daily improved ED (as measured principally by the International Index of Erectile Function-Erectile Function [IIEF-EF] domain score) and symptoms of BPH (as measured principally by the total IPSS score) in men with both conditions; a dosage of 2.5 mg once daily improved IIEF-EF but not IPSS.1, 82 Tadalafil 5 mg once daily resulted in substantial improvement in maintenance of erection to successful intercourse.1, 82 In addition, a reduction in the IPSS score was observed at 2 weeks and remained decreased throughout the remainder of the 12-week study.1, 82 Although peak urinary flow rates were increased from baseline with tadalafil in this study, these changes were not substantially different from those with placebo.1, 82
Dispensing and Administration Precautions
Tadalafil is administered orally without regard to meals.1
Tadalafil is administered orally without regard to meals.1
For the treatment of erectile dysfunction (ED), tadalafil may be administered as needed (just prior to sexual activity) or on a daily basis (at approximately the same time every day); the manufacturer states that the entire dose should be taken and that tablets should not be split.1 In patients receiving as-needed therapy with tadalafil, sexual activity may be attempted at 0.5-36 hours after tadalafil administration.1 Because of the prolonged duration of action (up to 36 hours) of tadalafil,1, 4, 7, 9 timing of administration relative to anticipated sexual activity is less important than with shorter-acting drugs for ED.3, 9 In patients receiving once-daily tadalafil therapy for ED, sexual activity may be attempted at any time between doses.1
When used for the treatment of benign prostatic hyperplasia (BPH) with or without coexisting ED, tadalafil is administered once daily at approximately the same time every day.1 When tadalafil is used with finasteride to initiate BPH treatment, the dose is administered once daily at approximately the same time every day for up to 26 weeks.1 The incremental benefit of tadalafil beyond 26 weeks is unknown.2
If a dose is missed, patients may take the dose as soon as it is remembered but should not take more than one dose per day.1
Tadalafil tablets should be stored at 25°C; excursions permitted to 15-30°C.1
Finasteride/Tadalafil Fixed-combination Therapy
Capsules containing tadalafil in fixed combination with finasteride (finasteride/tadalafil) should be administered orally on an empty stomach.2
When finasteride/tadalafil is used for the treatment of BPH in men with an enlarged prostate, the dosage is administered once daily at approximately the same time every day for up to 26 weeks.2 The incremental benefit of tadalafil beyond 26 weeks is unknown.2
If a dose is missed, patients may take the dose as soon as it is remembered but should not take more than one dose per day.2
Store the fixed-combination capsules at 20°C to 25°C; excursions permitted to 15°C to 30°C.2
For as-needed use in patients with ED, the usual initial oral dose of tadalafil is 10 mg taken just prior to (e.g., at least 0.5 hours before) anticipated sexual activity; optimal use should consider that improvement in erectile function may be maintained for up to 36 hours following a dose.1, 4 Depending on effectiveness and tolerance, the dose subsequently may be increased to 20 mg or decreased to 5 mg.1 The maximum recommended dosing frequency is once daily for most patients.1
In patients receiving concomitant therapy with human immunodeficiency virus (HIV) protease inhibitors (e.g., atazanavir, darunavir, fosamprenavir, lopinavir/ritonavir, ritonavir, saquinavir, tipranavir), an initial tadalafil dose of 5 mg is recommended; dosage should not exceed 10 mg once every 72 hours.1, 200 In patients receiving concomitant therapy with potent inhibitors of cytochrome P-450 (CYP) 3A4 (e.g., ketoconazole, ritonavir), dosage of tadalafil should not exceed 10 mg once every 72 hours.1, 200
For once-daily use in patients with ED, the usual initial oral dosage of tadalafil is 2.5 mg once daily taken at approximately the same time every day without regard to timing of sexual activity.1 Depending on effectiveness and tolerance, dosage may be increased to 5 mg once daily.1
In patients receiving concomitant therapy with potent CYP3A4 inhibitors (e.g., ketoconazole, ritonavir), dosage of once-daily tadalafil should not exceed 2.5 mg once daily.1
The usual dosage of tadalafil in patients with BPH is 5 mg once daily taken at approximately the same time every day.1
In patients receiving concomitant therapy with potent CYP3A4 inhibitors (e.g., ketoconazole, ritonavir), dosage of tadalafil should not exceed 2.5 mg once daily.1, 200
Finasteride/Tadalafil Fixed-combination Therapy
The usual dosage of the fixed-combination preparation for the treatment of BPH is 5 mg of finasteride and 5 mg of tadalafil taken once daily at approximately the same time every day for up to 26 weeks.2
Concomitant Benign Prostatic Hyperplasia and Erectile Dysfunction
When used for the treatment of both ED and BPH, the recommended dosage of tadalafil is 5 mg once daily at approximately the same time every day, without regard to timing of sexual activity.1
In patients receiving concomitant therapy with potent CYP3A4 inhibitors (e.g., ketoconazole, ritonavir), dosage of tadalafil should not exceed 2.5 mg once daily.1, 200
In patients with mild or moderate hepatic impairment (Child-Pugh class A or B) receiving as-needed therapy for ED, the maximum dosage of tadalafil should not exceed 10 mg once per day.1 The manufacturer recommends that once-daily tadalafil therapy for ED be used with caution in patients with mild or moderate hepatic impairment because such therapy has not been extensively evaluated in this population.1
The manufacturer states that use of tadalafil is not recommended in patients with severe hepatic impairment (Child-Pugh class C).1
Benign Prostatic Hyperplasia With or Without Erectile Dysfunction
The manufacturer recommends that once-daily tadalafil therapy be used with caution in patients with BPH (with or without ED) and mild or moderate hepatic impairment (Child-Pugh class A or B) because such therapy has not been extensively evaluated in such patients.1
The manufacturer states that use of tadalafil is not recommended in patients with severe hepatic impairment (Child-Pugh class C).1
Finasteride/tadalafil fixed-combination therapy: The manufacturer recommends caution in patients with mild or moderate hepatic impairment (Child-Pugh class A or B); use in patients with severe hepatic impairment (Child-Pugh class C) is not recommended.2
In patients with creatinine clearance of 30-50 mL/minute receiving as-needed therapy for ED, the recommended initial tadalafil dose is 5 mg, administered no more frequently than once daily, and the maximum recommended dose is 10 mg, administered no more frequently than once every 48 hours.1 In patients with creatinine clearance less than 30 mL/minute or those on hemodialysis receiving as-needed therapy for ED, the maximum recommended dose of tadalafil is 5 mg, administered no more frequently than once every 72 hours.1
Once-daily tadalafil therapy is not recommended in patients with ED who have a creatinine clearance less than 30 mL/minute or in those on hemodialysis.1
Benign Prostatic Hyperplasia With or Without Erectile Dysfunction
In patients with creatinine clearance of 30-50 mL/minute receiving once-daily tadalafil therapy for BPH alone or with coexisting ED, an initial tadalafil dosage of 2.5 mg once daily is recommended; dosage may be increased to 5 mg once daily based on patient response and tolerance.1 Once-daily tadalafil therapy is not recommended in patients with creatinine clearance less than 30 mL/minute or those on hemodialysis.1
Finasteride/tadalafil fixed-combination therapy is not recommended in patients with creatinine clearance <50 mL/minute or on hemodialysis due to increased tadalafil exposure, limited clinical experience, and the lack of ability to influence clearance by dialysis.2
Tadalafil or finasteride/tadalafil dosage adjustment based solely on age is not necessary in geriatric patients.1, 2
Concomitant use of organic nitrates or nitrites, either regularly and/or intermittently.1
Concomitant use of guanylate cyclase stimulators (e.g., riociguat).1, 2, 247
Known hypersensitivity to tadalafil, finasteride, or any ingredient in the formulations.1, 2
Finasteride/tadalafil fixed combination: Pregnancy.2
Prior to initiating tadalafil for the treatment of erectile dysfunction (ED) or benign prostatic hyperplasia (BPH), a thorough medical history and physical examination should be undertaken to determine potential underlying causes of the conditions and identify appropriate treatment options.1, 14, 15, 18, 19, 20, 21 In patients with BPH, clinicians should consider the possibility of other urologic conditions, including prostate cancer, that may cause similar symptoms to BPH.1, 2 Carefully monitor patients with large residual urinary volume and/or severely diminished urinary flow for obstructive uropathy; these patients may not be candidates for the fixed combination of finasteride/tadalafil.2
Since sexual activity is associated with a degree of cardiac risk, clinicians should assess the cardiovascular status of their patients prior to initiating tadalafil for the treatment of ED.1 Therapies for ED, including tadalafil, are not recommended for use in men for whom sexual activity is inadvisable because of their underlying cardiovascular status.1
Patients who experience chest pain, dizziness, or nausea during sex should stop sexual activity and seek immediate medical attention.1
Tadalafil induces mild vasodilation, which generally results in only transient modest reductions in systolic and diastolic blood pressure; such blood pressure reductions usually are not clinically important when the drug is taken alone.1, 5 However, additive blood pressure-lowering effects, possibly leading to symptomatic hypotension, may occur when tadalafil is used concomitantly with other vasodilating agents (e.g., α-adrenergic blocking agents or other antihypertensive drugs, alcohol, riociguat).1, 247 Clinicians should consider whether patients with underlying cardiovascular disease could be adversely affected by tadalafil's vasodilatory activity.1 Patients with left-ventricular outflow obstruction (e.g., aortic stenosis, idiopathic hypertrophic subaortic stenosis) or severely impaired autonomic control of blood pressure can be sensitive to vasodilators, including phosphodiesterase (PDE) type 5 inhibitors.1, 2
Tadalafil may potentiate the hypotensive effects of organic nitrates or nitric oxide donors, and concomitant use with these drugs is contraindicated.1, 5, 10 If nitrate administration is deemed medically necessary for a life-threatening condition, at least 48 hours should elapse between tadalafil administration and nitrate use.1, 10 In such circumstances, nitrates should be administered only under close medical supervision with appropriate hemodynamic monitoring.1, 10 If chest pain occurs within 48 hours of taking tadalafil, use of non-nitrate antianginal agents (e.g., β-adrenergic blocking agents, calcium-channel blocking agents) should be considered.10
Because of a lack of controlled clinical data establishing the safety and efficacy of tadalafil in the following subpopulations of patients with ED, the manufacturer does not recommend use of the drug in patients with a recent (within 90 days) myocardial infarction or stroke (within 6 months); those with uncontrolled arrhythmias, hypotension (systolic/diastolic blood pressure less than 90/50 mm Hg) or uncontrolled hypertension; those with heart failure (New York Heart Association [NYHA] class 2 or greater) in the previous 6 months; or those with unstable angina or angina occurring during sexual intercourse.1, 2
Concomitant Administration with Beta-Adrenergic Blocking Agents
Potentiation of hypotensive effects may occur in patients receiving concomitant therapy with α-adrenergic blocking agents due to additive vasodilatory effects.1 Patients who demonstrate hemodynamic instability during therapy with an α-adrenergic blocking agent alone are at increased risk for symptomatic hypotension (e.g., fainting) with concomitant use of a PDE type 5 inhibitor.1 Safety of such concomitant therapy also may be affected by intravascular volume depletion and use of additional antihypertensive agents.1
Use caution during concomitant therapy with PDE type 5 inhibitors and α-adrenergic blocking agents.1 A PDE type 5 inhibitor may be administered at the lowest possible dose in patients who exhibit hemodynamic stability while receiving an α-adrenergic blocking agent.1 In patients receiving an optimized dose of a PDE type 5 inhibitor, concomitant therapy with an α-adrenergic blocking agent may be initiated at the lowest dosage of that drug.1 Incremental increases in the dosage of the α-adrenergic blocking agent during such concomitant therapy may be associated with a further lowering of blood pressure.1
The combination of tadalafil and an α-adrenergic blocking agent (e.g., doxazosin, terazosin) currently is not recommended for the treatment of BPH because it offers no advantages in symptom improvement over either agent alone and has the potential for additive vasodilatory and hypotensive effects.1, 2, 604 For the treatment of BPH, the α-adrenergic blocking agent should be discontinued ≥ 1 day prior to the initiation of tadalafil.1, 2
Nonarteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely during postmarketing experience in temporal association with the use of all PDE type 5 inhibitors for the treatment of ED.1, 2, 37, 38, 39, 43, 44 Most, but not all, of these events occurred in individuals with preexisting vascular risk factors (e.g., age over 50 years, diabetes mellitus, hypertension, coronary artery disease, hyperlipidemia, smoking) or anatomic abnormalities (e.g., low cup to disc ratio [“crowded disc”]).1 Available data suggest that the annual incidence of NAION in the general population of men ≥ 50 years of age is 2.5-11.8 cases per 100,000.1, 2 Results of an observational study in patients with recent, episodic PDE type 5 inhibitor use (typical of ED treatment) suggest an approximately twofold increase in the risk of NAION, with a risk estimate of 2.15, within 5 half-lives of such use.1, 2 A risk estimate of 2.27 was reported in a similar study.1, 2 Other risk factors for NAION, such as the presence of "crowded" optic disc, may have contributed to the occurrence of NAION in these studies.1, 2
Neither the rare postmarketing reports, nor the association of PDE type 5 inhibitor use and NAION in observational studies, substantiate a causal relationship between PDE type 5 inhibitor use and NAION.1, 2
Use of tadalafil currently is not recommended in patients with hereditary degenerative retinal disorders, including retinitis pigmentosa; these patients were not studied in clinical trials.1
Clinicians should discuss the increased risk of NAION with patients who have already experienced NAION in one eye or in those with underlying NAION risk factors, including whether such individuals could be adversely affected by use of vasodilators, such as PDE type 5 inhibitors.1, 2 Use tadalafil with caution in these patients and only when the anticipated benefits outweigh the risks.1, 2 Evidence is insufficient to support screening for "crowded" optic disc in prospective users of PDE type 5 inhibitors.1, 2 If sudden vision loss or decreased vision occurs in one or both eyes while a patient is receiving a PDE type 5 inhibitor, the patient should discontinue the drug and contact a clinician immediately.1, 2
Sudden decrease or loss of hearing, with or without tinnitus or dizzines, has been reported in temporal association with all PDE type 5 inhibitors, including tadalafil.1
Clinicians should advise patients about the possibility of hearing loss with tadalafil therapy and instruct patients to discontinue tadalafil and any other PDE type 5 inhibitor and seek medical attention immediately if sudden hearing loss or decreased hearing occurs.1
Prolonged erections (exceeding 4 hours in duration) and priapism (painful erection exceeding 6 hours) have been observed with PDE type 5 inhibitors.1
Because of the risk of penile tissue damage and permanent loss of potency if priapism is not treated immediately, patients should be warned to seek immediate medical attention if an erection persists for longer than 4 hours (whether painful or not).1 Tadalafil should be used with caution in patients with anatomic deformation of the penis (e.g., angulation, cavernosal fibrosis, Peyronie's disease) and in those with conditions that may predispose to priapism (e.g., sickle cell anemia, multiple myeloma, leukemia).1
Concomitant Administration with Potent CYP3A4 Inhibitors or Inducers
Tadalafil is metabolized principally by cytochrome P-450 (CYP) 3A4; therefore, the potential for drug interactions with strong inhibitors or inducers of CYP3A4 should be considered.1, 200 In some cases, dosage adjustments of tadalafil may be necessary or frequency of use may be restricted (i.e., as needed use for the treatment of ED), while in other cases (i.e., BPH treatment),1, 200 concomitant administration of tadalafil and a strong CYP3A4 inhibitor or inducer is not recommended.2
Concomitant Use with other PDE Type 5 Inhibitors or ED Therapies
Data are lacking regarding the combined use of tadalafil and other PDE type 5 inhibitors or other therapies for ED; the manufacturer recommends that tadalafil not be used concomitantly with other PDE type 5 inhibitors used for the treatment of pulmonary arterial hypertension.1
Tadalafil inhibits PDE type 5, which is found in platelets.1 Although tadalafil has not been shown to increase bleeding times in healthy individuals, data are lacking in patients with bleeding disorders or substantial, active peptic ulcer disease; the manufacturer recommends that tadalafil be used with caution in such patients after carefully weighing the risks versus benefits of therapy.1
Counseling Patients on Sexually Transmitted Diseases
Patients should be advised that use of tadalafil provides no protection against sexually transmitted diseases, including human immunodeficiency virus (HIV) infection, and they should be counseled regarding protective measures to guard against such transmission.1
Potential for Drug Interactions with Once-daily Use
Taking once-daily tadalafil monotherapy or finasteride/tadalafil fixed-combination therapy provides continuous tadalafil plasma drug levels; consider this when evaluating the potential for interactions with medications (e.g., nitrates, α-adrenergic blocking agents, anti-hypertensives and potent inhibitors of CYP3A4) and with substantial consumption of alcohol.1, 2
Alcohol and PDE type 5 inhibitors (e.g., tadalafil) are both vasodilators, and combined use may have additive blood pressure-lowering effects.1, 2 Clinicians should inform 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 blood pressure, dizziness, and headache.1, 2
When tadalafil is used in fixed combination with finasteride, the usual cautions, precautions, and contraindications associated with finasteride must be considered in addition to those associated with tadalafil.2
Effects on Prostate Specific Antigen (PSA) and the Use of PSA in Prostate Cancer Detection (Finasteride/Tadalafil)
Finasteride causes a decrease in serum PSA concentrations of approximately 50% within 6 months in patients with BPH; decreases in PSA can occur even in those with prostate cancer.2, 604 The effect of finasteride on serum PSA concentrations is predictable over the entire range of PSA values, although there is evidence of interindividual variation.2
For interpretation of serial PSAs in men taking finasteride/tadalafil, a new PSA baseline should be established at least 6 months after starting treatment and PSA monitored periodically thereafter.2 Any confirmed increase from the lowest PSA value while taking finasteride/tadalafil may signal the presence of prostate cancer and should be evaluated, even if PSA levels are still within the normal range for men not taking a 5α-reductase inhibitor.2 Noncompliance with finasteride/tadalafil may affect PSA concentrations and should be considered when evaluating test results.2
For clinical interpretation of an isolated PSA value in men who have been receiving finasteride/tadalafil for 6 months or longer, the reported PSA value should be doubled for comparison with normal values in men not receiving the drug.2 This adjustment will preserve the utility of the serum PSA assay and maintain its usefulness in the detection of prostate cancer.2 Finasteride does not substantially alter the ratio of free to total PSA (percentage of free PSA).2 If clinicians elect to use this ratio in the detection of prostate cancer, no adjustment of the reported value of the ratio appears to be necessary.2
Patients should be informed that finasteride decreases serum PSA concentrations and should be advised of the importance of appropriate medical evaluation of any increase in PSA concentration.2
Increased Risk of High-Grade Prostate Cancer (Finasteride/Tadalafil)
Use of 5α-reductase inhibitors may increase the risk of development of high-grade prostate cancer.2
Men ≥55 years of age with baseline serum PSA concentration ≤3 ng/mL and normal digital rectal examinations at baseline taking finasteride had an increased risk of high-grade tumors (Gleason score of 8-10) compared to placebo (1.8 versus 1.1%, respectively) in the 7-year Prostate Cancer Prevention Trial (PCPT).2 Similar results were reported for a 4-year placebo-controlled trial with a different 5α-reductase inhibitor.2
It is not known whether the effect of 5α-reductase inhibitors to reduce prostate volume, or study-related factors, influenced the results of these studies.2
Hypersensitivity Reactions (Finasteride/Tadalafil)
Hypersensitivity reactions such as Stevens-Johnson syndrome, exfoliative dermatitis, pruritis, urticaria, and angioedema have been reported with finasteride/tadalafil; immediately discontinue the drug if a hypersensitivity reaction occurs.2
Risk to Male Fetus from Topical Exposure to Pregnant Females (Finasteride/Tadalafil)
Finasteride/tadalafil is contraindicated in pregnant females and is not indicated for use in females.2 Based on animal studies and the mechanism of action of finasteride, abnormal development of external genitalia in a male fetus may occur if administered to a pregnant female.2
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.2 Wash the contact area immediately with soap and water if contact with crushed or broken capsules occurs.2
The manufacturer of tadalafil (Cialis®) states that the drug is not indicated for use in women.1
Tadalafil and/or its metabolites cross the placenta, resulting in fetal exposure in rats.1, 2 In animal reproduction studies, no adverse developmental effects were observed with oral administration of tadalafil to pregnant rats or mice during organogenesis at exposures up to 11 times the maximum recommended human dose (MRHD) of 20 mg/day.1, 2
Finasteride/tadalafil: Contraindicated in pregnancy and not indicated for use in females.2 Based on animal studies and the mechanism of action of finasteride, finasteride/tadalafil may cause abnormal development of external genitalia in a male fetus if administered to a pregnant female.2
Reproduction studies in pregnant rats receiving finasteride dosages ranging from 0.1 to 86 times the MRHD of 5 mg daily resulted in dose-dependent development of hypospadias in 3.6-100% of male offspring.2 Pregnant rats produced male offspring with decreased prostatic and seminal vesicular weights, delayed preputial separation, and transient nipple development when given dosages 0.03 times the MRHD and decreased anogenital distance in male offspring at maternal doses approximately 0.003 times the MRHD.2 These effects are expected pharmacologic effects of 5α-reductase inhibitors and are similar to those reported in male infants with a genetic deficiency of 5α-reductase.2
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.2 Wash the contact area immediately with soap and water if contact occurs.2
Tadalafil (Cialis®) and finasteride/tadalafil (Entadfi®) are not indicated for use in women.1 Tadalafil and/or its metabolites are present in the milk of lactating rats at concentrations approximately 2.4 times that found in the plasma.1
Females and Males of Reproductive Potential
Based on the data from 3 studies in adult males, tadalafil decreased sperm concentrations in the study of 10 mg tadalafil for 6 months and the study of 20 mg tadalafil for 9 months.1, 2 This effect was not seen in the study of 20 mg tadalafil taken for 6 months.1, 2 There was no adverse effect of tadalafil 10 mg or 20 mg on mean concentrations of testosterone, luteinizing hormone or follicle stimulating hormone.1, 2 The clinical significance of the decreased sperm concentrations in the two studies is unknown.1, 2
There have been no studies evaluating the effect of tadalafil on fertility in men or women.1, 2
No clinically meaningful effects on sperm concentration, mobility, morphology, or pH were reported in a 24-week study in healthy male volunteers treated with finasteride.2 A 0.6 mL (22.1%) median decrease in ejaculate volume with a concomitant reduction in total sperm per ejaculate was observed.2 These parameters remained within the normal range and were reversible upon discontinuation of therapy with an average time to return to baseline of 84 weeks.2
Use of tadalafil has not been evaluated for the treatment of BPH or ED in individuals younger than 18 years of age.1
Safety and efficacy of tadalafil in geriatric patients (older than 65 years of age) are similar to those in younger patients.1, 8 Substantial age-related differences in pharmacokinetics of tadalafil were not observed between patients 65 years of age or older and younger individuals;88 therefore, the manufacturer states that modification of tadalafil dosage is not needed in geriatric patients solely on the basis of age.1 However, the possibility of greater sensitivity in some geriatric individuals should be considered.1
Insufficient data are available in patients with severe hepatic impairment (Child-Pugh class C), and use of tadalafil once daily or on an as-needed basis in such patients currently is not recommended by the manufacturer.1, 88 Although exposure to tadalafil (10 mg) was not appreciably altered by mild or moderate hepatic impairment in a study of individuals with stable liver cirrhosis,88 the manufacturer states that data are limited in patients with mild or moderate hepatic impairment (Child-Pugh class A or B) receiving once-daily therapy with the drug for ED, BPH, or for both conditions; caution is advised in such patients.1 The maximum dosage of tadalafil should not exceed 10 mg once daily in patients with mild or moderate hepatic impairment (Child-Pugh class A or B) receiving tadalafil as needed for ED.1
The pharmacokinetics of finasteride, a drug extensively metabolized in the liver, has not been studied in hepatic impairment.2 Based on tadalafil data, the manufacturer recommends caution in patients with mild or moderate hepatic impairment (Child-Pugh class A or B); use in patients with severe hepatic impairment (Child-Pugh class C) is not recommended due to insufficient data.2
Following a single 5- or 10-mg tadalafil dose, drug exposure (AUC) doubled in patients with mild to moderate (creatinine clearance of 30-80 mL/minute) renal impairment.1, 2 In patients with end-stage renal disease on hemodialysis, there was a two-fold increase in peak plasma concentration and 2.7- to 4.8-fold increase in AUC following single-dose administration of tadalafil 10 or 20 mg.1, 2
Exposure to total methylcatechol (unconjugated plus glucuronide) was 2- to 4-fold higher in subjects with renal impairment, compared to those with normal renal function.1, 2 Hemodialysis performed between 24 and 30 hours post-dose contributed negligibly to tadalafil or metabolite elimination.1, 2 Back pain was reported as a limiting adverse event in male patients with creatinine clearance of 30-50 mL/minute taking a 10 mg tadalafil dose, but not in those taking 5 mg or in patients on hemodialysis taking 10 or 20 mg drug doses.1, 2
Use of once-daily tadalafil therapy is not recommended for any indication in patients with severe renal impairment due to increased tadalafil exposure, limited clinical experience, and the lack of ability to influence clearance by dialysis.1 In those taking once-daily tadalafil for BPH and a creatinine clearance 30-50 mL/minute, the initial tadalafil dosage should be 2.5 mg once daily; dosage may be increased to 5 mg once daily based upon individual response.1
Dosage adjustments are recommended in patients with moderate to severe renal impairment receiving as-needed tadalafil therapy for ED.1 In patients with creatinine clearance 30-50 mL/minute, the initial tadalafil dose should be 5 mg, administered no more than once per day and the maximum dose should be limited to 10 mg, taken no more than once in every 48 hours.1 In patients with creatinine clearance < 30 mL/minute or end-stage renal disease on hemodialysis, tadalafil should be limited to 5 mg, taken no more than once in every 72 hours.1
Use of finasteride/tadalafil is not recommended in patients with creatinine clearance <50 mL/minute or on hemodialysis due to increased tadalafil exposure, limited clinical experience, and the lack of ability to influence clearance by dialysis.2
Tadalafil (Cialis® and generic equivalents): Most common adverse effects reported in at least 2% of patients receiving tadalafil for the treatment of ED and/or BPH include headache, dyspepsia, back pain, myalgia, nasal congestion, flushing, and limb pain.1, 4, 6, 7, 8, 9, 10, 60, 61, 82, 83
Finasteride/tadalafil: Most common adverse effects associated with finasteride monotherapy (≥1%) in a 4-year study were impotence, decreased libido, decreased volume of ejaculate, breast enlargement, breast tenderness, and rash.2 Most common adverse effects (≥2%) associated with tadalafil were headache, dyspepsia, back pain, myalgia, nasal congestion, flushing, and limb pain.2
Tadalafil is metabolized principally via hepatic cytochrome P-450 (CYP) isoenzyme 3A4.1, 2 Inhibitors and inducers of CYP3A4 may increase or decrease tadalafil exposure, respectively.1, 2
Tadalafil 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 2E1.1, 2
When tadalafil in fixed combination with finasteride is used, the drug interactions associated with each drug must be considered.2 The manufacturer states no drug interactions of clinical importance have been identified for finasteride.2
Drugs Affecting or Affected by Hepatic Microsomal Enzymes
Pharmacokinetic interactions (increased tadalafil AUC) has been observed with drugs that are potent inhibitors (e.g., ketoconazole, ritonavir) of CYP3A4.1, 200 In some cases, the 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 is not recommended.1, 200, 2
Although specific drug interaction studies have not been conducted, there is a potential for similar pharmacokinetic interactions when tadalafil is given with other CYP3A4 inhibitors such as erythromycin, itraconazole, grapefruit juice, or human immunodeficiency virus (HIV) protease inhibitors (e.g., atazanavir, darunavir, fosamprenavir, lopinavir/ritonavir, ritonavir, saquinavir, tipranavir).1, 200
Pharmacokinetic interaction (decreased tadalafil exposure) has been observed following concomitant administration of tadalafil and certain CYP3A4 inducers (e.g., rifampin).1 Decreased tadalafil exposure also is likely during concurrent therapy with other CYP3A4 inducers (e.g., carbamazepine, phenytoin, phenobarbital, efavirenz, nevirapine, and etravirine).1, 200 Such reduced drug exposure can be anticipated to decrease the effectiveness of once-daily tadalafil therapy; however, the magnitude of such decreased effectiveness with concurrent CYP3A4 inducers is unknown.1 Some experts recommend tadalafil dose titration based on clinical effect when these drugs are taken concomitantly.200 The manufacturer recommends that patients taking the finasteride/tadalafil fixed-combination preparation should avoid concomitant use of CYP3A4 inducers.2
No clinically meaningful effects on steady-state pharmacokinetics of the P-gp substrate digoxin have been observed with concomitant administration of tadalafil.1, 2
Pharmacodynamic interaction (potentiation of hypotensive effect) has been observed with concurrent use of tadalafil and certain antihypertensive agents (i.e., α-adrenergic blocking agents, amlodipine, angiotensin II receptor antagonists, bendroflumethiazide, enalapril, metoprolol).1 Following concurrent administration of metoprolol, enalapril, amlodipine, or bendroflumethiazide, tadalafil reduced blood pressure marginally compared with placebo.1, 12 Studies suggest that a clinically important decrease in blood pressure is more likely to occur with concurrent use of tadalafil and an α-adrenergic blocking agent.1 Caution is advised when PDE type 5 inhibitors and α-adrenergic blocking agents are used concomitantly.1
In patients with ED, use caution during concomitant therapy with PDE type 5 inhibitors and α-adrenergic blocking agents.1 A PDE type 5 inhibitor may be administered at the lowest possible dose in patients who exhibit hemodynamic stability while receiving an α-adrenergic blocking agent.1 In patients receiving an optimized dose of a PDE type 5 inhibitor, concomitant therapy with an α-adrenergic blocking agent may be initiated at the lowest dosage of that drug.1 Incremental increases in the dosage of the α-adrenergic blocking agent during such concomitant therapy may be associated with a further lowering of blood pressure.1
In patients with BPH, the combination of tadalafil and an α-adrenergic blocking agent (e.g., doxazosin, terazosin) is not currently recommended because it offers no advantages in symptom improvement over either agent alone and has the potential for additive vasodilatory and hypotensive effects.1, 604 The α-adrenergic blocking agent should be discontinued ≥ 1 day prior to the initiation of tadalafil.1
Organic Nitrates and Nitric Oxide Donors
Concomitant use of any form of organic nitrate (e.g., nitroglycerin), including recreational use of inhaled nitrites (amyl nitrate or nitrite, “poppers”), with tadalafil is contraindicated due to the potential pharmacodynamic interaction (increased hypotensive effect).1, 4, 5, 8, 10 If nitrate administration is deemed medically necessary for a life-threatening condition, at least 48 hours should elapse between tadalafil administration and nitrate use; in such situations, nitrates should be administered with caution, under close medical supervision, and with hemodynamic monitoring.1, 10 In a double-blind, placebo-controlled, crossover study, tadalafil 20 mg was administered daily for 7 days to male subjects ≥ 40 years of age.1 Additive hemodynamic effects were observed when sublingual nitroglycerin 0.4 mg was administered at pre-specified time points 2, 4, 8, 24, 48, 72, and 96 hours following the final tadalafil dose; a significant interaction was observed at each timepoint up to and including 24 hours, with most hemodynamic effects no longer detectable after 48 hours.1, 10
Alcohol and PDE type 5 inhibitors are both mild systemic vasodilators.1 Pharmacodynamic effects (orthostatic hypotension manifested by increased heart rate, decreased standing blood pressure, dizziness, headache) have been observed when tadalafil was administered with alcohol (0.7 g/kg, the equivalent to 180 mL of 80-proof vodka in an 80-kg man) ingested over less than 10 minutes.1 Such effects were not observed, or occurred with similar frequency to ingestion of alcohol alone, when tadalafil was given concurrently with a lower dose of alcohol (0.6 g/kg, or the equivalent of 118 mL of 80-proof vodka ingested over less than 10 minutes).1
Alcohol should not be consumed excessively (e.g., 5 glasses of wine or 5 shots of whiskey) when taking tadalafil.1
No clinically meaningful effects on the pharmacokinetics (effects on plasma drug or alcohol concentrations) of either tadalafil or alcohol have been observed.1
Drugs Affecting Gastric Acidity
Concomitant administration of tadalafil and an antacid containing magnesium hydroxide and aluminum hydroxide reduced the rate, but not extent, of tadalafil absorption.1
No significant effect on the pharmacokinetics of tadalafil has been observed wtih concomitant use of nizatidine.1
Increased tadalafil exposure is expected with protease inhibitors alone or in combination with ritonavir (e.g., amprenavir, atazanavir, fosamprenavir, indinavir, lopinavir, nelfinavir, tipranavir, darunavir).200 Indication-based tadalafil dosage interruption, adjustment, or maximum dosage recommendations may be necessary.1 200
If tadalafil is used as needed for the treatment of ED in a patient receiving a protease inhibitor, tadalafil should be initiated with a dose of 5 mg, and the dosage should not exceed 10 mg once every 72 hours.1 200
If tadalafil is used daily for the treatment of ED or BPH in patients receiving protease inhibitors, tadalafil dosage should not exceed 2.5 mg once daily.1
Finasteride/tadalafil: Use with caution in those taking strong CYP3A4 inhibitors.2
The nonnucleoside reverse transcriptase inhibitors efavirenz, nevirapine, and etravirine may decrease tadalafil exposure via CY3A4 induction, and experts state tadalafil dose titration based upon clinical effect may be required.200
Tadalafil does not increase bleeding time in healthy individuals, and concomitant administration of tadalafil and aspirin did not prolong bleeding time relative to aspirin administration alone.1
No clinically meaningful effects on steady-state pharmacokinetics of digoxin (a P-gp substrate) have been observed with concomitant administration of tadalafil.1
Decreased tadalafil concentrations are possible when used concomitantly with etravirine; tadalafil dosage increase may be necessary depending on clinical effect.200
Systemic exposure and peak plasma concentrations of tadalafil were increased by 107-312% and 15-22%, respectively, with concomitant administration of ketoconazole (a potent inhibitor of CYP3A).1 If ketoconazole is used in a patient receiving tadalafil for ED and/or BPH, tadalafil dosage adjustments are necessary.1 The manufacturer states that tadalafil in fixed combination with finasteride is not recommended in patients receiving potent inhibitors of CYP3A4 such as ketoconazole.2
In patients receiving concomitant therapy with ketoconazole, as needed tadalafil dosage should not exceed 10 mg once every 72 hours.1
In patients receiving concomitant therapy with ketoconazole, once-daily tadalafil dosage should not exceed 2.5 mg.1
Systemic exposure of lovastatin was not substantially affected by concomitant use of tadalafil.1
Systemic exposure of midazolam was not substantially affected by concomitant use of tadalafil.1
Coadministration of rifampin, a CYP3A inducer, decreased systemic exposure and peak plasma concentrations of tadalafil by 88 and 46%, respectively.1 Such reduced drug exposure can be anticipated to decrease the effectiveness of once-daily tadalafil therapy; however, the magnitude of such decreased effectiveness with concurrent CYP3A4 inducers is unknown.1 The manufacturer recommends avoiding tadalafil in fixed combination with finasteride in patients receiving CYP3A4 inducers.2
Additive hypotensive effects can occur if PDE type 5 inhibitors are used concomitantly with riociguat.1, 247 Concomitant use of tadalafil and riociguat is contraindicated.1, 247
Ritonavir has an initial inhibitory effect on CYP3A, followed by a late inducing effect on the isoenzyme.1, 87 Concomitant use of tadalafil and ritonavir (200 mg twice daily) increased systemic exposure of tadalafil by more than twofold after the first concurrent dose; however, no change in tadalafil exposure was observed at steady-state concentrations of ritonavir.1, 87 Tadalafil had no substantial effect on the pharmacokinetics of ritonavir.87
If tadalafil is used as needed for the treatment of ED in a patient receiving ritonavir, tadalafil should be initiated with a dose of 5 mg, and the dosage should not exceed 10 mg once every 72 hours.1, 200
If tadalafil is used daily for the treatment of ED or BPH in patients receiving ritonavir, tadalafil dosage should not exceed 2.5 mg once daily.1, 200
Finasteride/tadalafil: Use with caution.2
Pharmacodynamic interaction (small augmentation of theophylline-induced increase in heart rate) has been observed with concurrent use of tadalafil and theophylline; however, tadalafil had no substantial effect on the pharmacokinetics of theophylline.1
No clinically meaningful effects on pharmacokinetics (systemic exposure) and pharmacodynamics (i.e., changes in prothrombin time) of warfarin have been observed with concomitant tadalafil administration.1
Tadalafil is a selective inhibitor of phosphodiesterases (PDEs), with the greatest selectivity for PDE type 5, the principal isoenzyme of PDE involved in the metabolism of cyclic guanosine monophosphate (cGMP) to GMP in the vascular smooth muscle of the prostate, bladder, and corpora cavernosa of the penis.1, 3, 4, 8 During sexual stimulation, nitric oxide is released from nerve endings and endothelial cells in the corpora cavernosa.1, 3, 6, 8 Nitric oxide activates the enzyme guanylate cyclase, which stimulates the synthesis of cGMP.1, 3 cGMP produces smooth muscle relaxation and increased blood flow into the corpora cavernosa.1, 3, 10 By selectively inhibiting PDE type 5, tadalafil increases cGMP concentrations in the corpora cavernosa of the penis, resulting in nitric oxide-stimulated vascular relaxation.1, 3 Tadalafil has no effect on erectile function in the absence of sexual stimulation.1
The exact mechanism of action of tadalafil in reducing symptoms of benign prostatic hyperplasia (BPH) has not been established, but may be related to smooth muscle relaxation and increased vascular perfusion of the lower urinary tract (i.e., bladder, prostate).1, 81, 84, 89
Tadalafil produces modest peripheral vasodilation at usual dosages without affecting heart rate or blood pressure; such changes are not appreciably different from those observed with placebo.1, 4, 5 These effects are potentiated with concurrent use of organic nitrates, and concurrent use is contraindicated.1
Tadalafil also exhibits some activity against other PDE isoenzymes.1, 2 In vitro, tadalafil is >10,000-fold more potent against PDE type 5 than against PDE type 1, PDE type 2, PDE type 4, and PDE type 7 enzymes which are found in the heart, brain, blood vessels, liver, leukocytes, skeletal muscle, and other organs.1, 2 Tadalafil is >10,000-fold more potent for PDE type 5 than for PDE type 3, an enzyme found in the heart and blood vessels.1, 2 Additionally, tadalafil is 700-fold more potent for PDE type 5 than for PDE type 6, which is found in the retina and is responsible for phototransduction.1, 2 Tadalafil also exhibits some affinity for PDE type 11, but the clinical importance currently is unknown.1
When tadalafil is used as needed for erectile dysfunction, onset and duration of action are estimated to be 20 minutes and 24 to 36 hours, respectively.602
Although pharmacologically related to other selective PDE type 5 inhibitors (e.g., sildenafil, vardenafil), tadalafil differs structurally from sildenafil and vardenafil and has a longer elimination half-life and a longer duration of action than these drugs.3, 4
The absolute bioavailability of tadalafil has not been determined.1, 2 The maximum observed plasma concentration is achieved between 30 minutes and 6 hours (median time 2 hours).1 The rate and extent of absorption of tadalafil are not influenced by food, including a high-fat, high-calorie meal; thus tadalafil may be taken with or without food.1, 602 Administration of finasteride/tadalafil with a high-fat, high-calorie meal did not affect tadalafil or finasteride exposure (AUC).2 Tadalafil is distributed into tissues;1, 2, 602 less than 0.0005% of the administered dose appeared in the semen of healthy subjects.1, 2 At therapeutic concentrations, the drug is 94% bound to plasma proteins.1, 2, 602 Tadalafil clearance is reduced in patients ≥65 years of age compared with younger adults, in patients with renal impairment (creatine clearance 30-80 mL/minute) including end-stage renal disease on hemodialysis, and in patients with diabetes mellitus.1, 2
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.
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 2.5 mg | Cialis® | Lilly |
5 mg | Cialis® | Lilly | ||
10 mg | Cialis® | Lilly | ||
20 mg | Cialis® | Lilly |
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Capsules | 5 mg of finasteride with 5 mg of tadalafil | Entadfi® | Veru |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions April 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
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