Tadalafil

(BAN, USAN, rINN)
Tadalafil Chemical formula
Synonyms: GF-196960; IC-351; Tadalafiili; Tadalafilo; Tadalafilum. (6R,12aR)2,3,6,7,12,12a-Hexahydro-2-methyl-6-[3,4-(methylenedioxy)phenyl]pyrazino[1′,2′:1,6]pyrido[3,4b]indole-1,4-dione.
Cyrillic synonym: Тадалафил.

💊 Chemical information

Chemical formula: C22H19N3O4 = 389.4.
CAS — 171596-29-5.
ATC — G04BE08.
ATC Vet — QG04BE08.
NOTE. The following terms have been used as ‘street names’ or slang names for various forms of tadalafil: Weekend Pill.

💊 Adverse Effects and Precautions

As for Sildenafil. Visual disturbances may occur less frequently with tadalafil than with sildenafil. Dosage reductions may be required in patients with hepatic or renal impairment.
1. Montorsi F, et al. Long-term safety and tolerability of tadalafil in the treatment of erectile dysfunction. Eur Urol 2004; 45: 339–44.

Effects on the cardiovascular system.

References.
1. Kloner RA, et al. Cardiovascular effects of tadalafil. Am J Cardiol 2003; 92: 37M–46M.

💊 Interactions

As for Sildenafil.

Antifungals.

Priapism occurred in a man who took two separate doses of tadalafil 10 mg, at least one month apart, during itraconazole treatment.1 He was able to take sildenafil during itraconazole treatment without adverse effect. See also Uses and Administration, below, for recommended tadalafil dosage when it is taken with inhibitors of the cytochrome P450 isoenzyme CYP3A4.
1. Galatti L, et al. Interaction between tadalafil and itraconazole. Ann Pharmacother 2005; 39: 200.

Nitrates.

Phosphodiesterase type-5 inhibitors may potentiate the hypotensive effects of organic nitrates, and are therefore contra-indicated in patients receiving such drugs. An interaction between tadalafil and sublingual glyceryl trinitrate was reported to occur when glyceryl trinitrate was given within 24 hours after tadalafil but was no longer detectable at 48 hours.1 Licensed product information recommends that if nitrate treatment is needed in a life-threatening situation then it should only be given at least 48 hours after the last dose of tadalafil and under close medical supervision.
1. Kloner RA, et al. Time course of the interaction between tadalafil and nitrates. J Am Coll Cardiol 2003; 42: 1855–60.

💊 Pharmacokinetics

Tadalafil is well absorbed after an oral dose. Peak plasma concentrations are attained within 2 hours; the rate and extent of absorption are not affected by food. Tadalafil is widely distributed into tissues and is about 94% bound to plasma proteins. It is metabolised in the liver mainly by the cytochrome P450 isoenzyme CYP3A4. The major metabolite, the methylcatechol glucuronide, is inactive. The mean half-life of tadalafil is about 17.5 hours. Tadalafil is excreted, mainly as metabolites, in the faeces (61% of the dose), and to a lesser extent the urine (36% of the dose). Clearance may be reduced in the elderly and in patients with renal impairment.
1. Gupta M, et al. The clinical pharmacokinetics of phosphodiesterase-5 inhibitors for erectile dysfunction. J Clin Pharmacol 2005; 45: 987–1003
2. Forgue ST, et al. Tadalafil pharmacokinetics in healthy subjects. Br J Clin Pharmacol 2006; 61: 280–8
3. Forgue ST, et al. Effects of gender, age, diabetes mellitus and renal and hepatic impairment on tadalafil pharmacokinetics. Br J Clin Pharmacol 2007; 63: 24–35.

💊 Uses and Administration

Tadalafil is a phosphodiesterase type-5 inhibitor with actions and uses similar to those of sildenafil. It is used in the management of erectile dysfunction. Tadalafil is given orally in a usual dose of 10 mg at least 30 minutes before sexual intercourse and may be taken with or without food; the dose may be increased to 20 mg, or decreased to 5 mg, if necessary. Efficacy may persist for up to 36 hours after dosing. Tadalafil should not be taken more than once in 24 hours. In the UK, for those who respond to tadalafil when taken as needed, and anticipate frequent use (defined as at least twice weekly), a regular daily regimen may be considered suitable. In these patients, the recommended dose is 5 mg once daily, taken at about the same time each day. The dose may be decreased to 2.5 mg once daily based on individual tolerability. In the USA, the recommended starting dose of tadalafil for daily use is 2.5 mg, taken at about the same time each day, which may then be increased to 5 mg, based on tolerability and efficacy. Dosage adjustments are not necessary in elderly patients; for recommendations in hepatic or renal impairment, see below. Although the use of tadalafil with an alpha blocker is not recommended in the UK, the combination may be used in the USA; in patients stabilised on alpha blocker therapy a starting dose of tadalafil 5 mg may be used. In patients taking potent inhibitors of the cytochrome P450 isoenzyme CYP3A4, such as ketoconazole or ritonavir-boosted HIV-protease inhibitors, the dose of
tadalafil when used as needed should not exceed 10 mg once every 72 hours; when used on a regular daily basis, the dose should not exceed 2.5 mg.
1. Brock GB, et al. Efficacy and safety of tadalafil for the treatment of erectile dysfunction: results of integrated analyses. J Urol (Baltimore) 2002; 168: 1332–6. Correction. ibid. 2005; 173: 664. [dosage error in abstract
2. Brock GB. Tadalafil: a new agent for erectile dysfunction. Can J Urol 2003; 10 (suppl 1): 17–22
3. Bella AJ, Brock GB. Tadalafil in the treatment of erectile dysfunction. Curr Urol Rep 2003; 4: 472–8
4. Curran MP, Keating GM. Tadalafil. Drugs 2003; 63: 2203–12. Correction. ibid.; 2703
5. Meuleman EJ. Review of tadalafil in the treatment of erectile dysfunction. Expert Opin Pharmacother 2003; 4: 2049–56
6. Padma-Nathan H. Efficacy and tolerability of tadalafil, a novel phosphodiesterase 5 inhibitor, in treatment of erectile dysfunction. Am J Cardiol 2003; 92 (suppl 1): 19M–25M
7. Carson CC, et al. The efficacy and safety of tadalafil: an update. BJU Int 2004; 93: 1276–81
8. Doggrell SA. Comparison of clinical trials with sildenafil, vardenafil and tadalafil in erectile dysfunction. Expert Opin Pharmacother 2005; 6: 75–84.
.

Administration in hepatic impairment.

Exposure to tadalafil in patients with mild to moderate hepatic impairment is comparable to healthy subjects when a dose of 10 mg is used. Regular daily dosing has not been evaluated. Licensed product information states the following:
mild to moderate hepatic impairment (Child-Pugh Class A or B): the maximum dose is 10 mg; regular daily dosing has not been evaluated
severe hepatic impairment (Child-Pugh Class C): insufficient data are available; in the UK, caution is advised, and in the USA use in this group is not recommended

Administration in renal impairment.

The clearance of tadalafil is reduced in renal impairment. In the UK, licensed product information recommends the following:
mild to moderate renal impairment: no dose adjustment
severe renal impairment: the maximum dose is 10 mg; regular daily dosing is not recommended in these patients In the USA, the dose recommendations for tadalafil, when used as needed, in patients with renal impairment based on creatinine clearance (CC) are:
mild (CC 51 to 80 mL/minute): no dose adjustment
moderate (CC 31 to 50 mL/minute): an initial dose of 5 mg not more than once daily, with a maximum dose of 10 mg in 48 hours
severe (CC less than 30 mL/minute or on haemodialysis): a maximum dose of 5 mg not more than once in every 72 hours For patients taking tadalafil on a regular daily basis:
mild (CC 51 to 80 mL/minute): no dose adjustment
moderate (CC 31 to 50 mL/minute): no dose adjustment
severe (CC less than 30 mL/minute or on haemodialysis): not recommended

High-altitude disorders.

Hypoxic pulmonary hypertension associated with high altitude may respond to tadalafil. A small study1 has shown some promising results in adults with a history of high-altitude pulmonary oedema.
1. Maggiorini M, et al. Both tadalafil and dexamethasone may reduce the incidence of high-altitude pulmonary edema: a randomized trial. Ann Intern Med 2006; 145: 497–506.

💊 Preparations

Proprietary Preparations

Arg.: Cialis; Austral.: Cialis; Austria: Cialis; Belg.: Cialis; Braz.: Cialis; Canad.: Cialis; Chile: Cialis; Cz.: Cialis; Denm.: Cialis; Fin.: Cialis; Fr.: Cialis; Ger.: Cialis; Gr.: Cialis; Hong Kong: Cialis; Hung.: Cialis; India: Forzest; Sialis†; Tadacip; Zydalis; Indon.: Cialis; Irl.: Cialis; Israel: Cialis; Ital.: Cialis; Malaysia: Cialis; Mex.: Cialis; Neth.: Cialis; Norw.: Cialis; NZ: Cialis; Philipp.: Cialis; Pol.: Cialis; Port.: Cialis; Rus.: Cialis (Сиалис); S.Afr.: Cialis; Singapore: Cialis; Spain: Cialis; Swed.: Cialis; Switz.: Cialis; Thai.: Cialis; UK: Cialis; USA: Cialis; Venez.: Cialis.
Published November 23, 2018.