Tadalafil

Treatment of pulmonary arterial hypertension (PAH) (WHO Group I) to improve exercise ability.

Oral
Erectile dysfunction
Adult: Initially, 10 mg at least 30 min before sexual activity once daily, up to 20 mg as single dose. Max: Not more than once daily. If used with potent inhibitors of CYP3A4, e.g. azole antifungals or protease inhibitors: max 10 mg once every 72 hr.

Hepatic impairment: Mild-moderate hepatic impairment (Child-Pugh category A or B): Max dose 10 mg. Severe hepatic impairment (Child-Pugh category C): Not recommended.

Special Populations: In hepatic or mild renal impairment (creatinine clearance <30 mL/min), max dose is 10 mg

Regular or intermittent use with any form of organic nitrate, nitrates and nitric oxide donors. Men with cardiac disease for whom sexual activity is inadvisable. Recent MI (within 90 days) or stroke (within last 6 mth), hypotension (<90/50 mm Hg), unstable angina, heart failure, uncontrolled arrhythmias or hypertension. 

Seek immediate medical attention if anginal chest pain, sudden vision loss, decreased or loss of hearing, or erection >4 hrs occurs following use. Transient decrease in BP reported; caution with underlying cardiovascular disease (CVD). Patients with severely impaired autonomic control of BP or left ventricular outflow obstruction may be more sensitive to vasodilatory effects. May worsen cardiovascular (CV) status with pulmonary veno-occlusive disease (PVOD); not recommended with veno-occlusive disease. Avoid use in severe renal impairment (CrCl <30mL/min and on hemodialysis) and hepatic impairment (Child-Pugh Class C). Not recommended with hereditary degenerative retinal disorders (eg, retinal pigmentosa). Non-arteritic anterior ischemic optic neuropathy (NAION) reported. Rare reports of prolonged erections (>4 hrs) and priapism; caution in conditions predisposing to priapism (eg, sickle cell anemia, multiple myeloma, leukemia) or with anatomical deformation of the penis (eg, angulation, cavernosal fibrosis, Peyronie's disease). Assess risk/benefit with bleeding disorders or significant active peptic ulceration.

Headache, myalgia, nasopharyngitis, flushing, respiratory tract infection, pain in extremity, nausea, back pain, dyspepsia, nasal congestion, sudden decrease or loss of hearing, tinnitus.
Potentially Fatal: Stevens-Johnson syndrome, exfoliative dermatitis, severe cardiovascular events e.g. MI, stroke, sudden cardiac death;

Concurrent use increased risk of hypotension with α-blockers; increased risk of priapism with other drugs for erectile dysfunction, e.g. alprostadil; increased heart rate with theophylline; decreased tadalafil serum concentration with CYP 3A4 inducers e.g. rifampicin, efavirenz, carbamazepine, nevirapine, barbiturates, phenobarbital, phenytoin, ribabutin; increased tadalafil serum concentration with CYP3A4 inhibitors e.g. azole antifungals, protease inhibitors, cimetidine, macrolides.
Potentially Fatal: Enhanced hypotensive effect with nitrates and nicorandil.

Concurrent use with grapefruit juice may increase tadalafil levels, while St John's wort may decrease tadalafil levels.

Phosphodiesterase type 5 (PDE5) inhibitor; increases the concentrations of cGMP, resulting in relaxation of pulmonary vascular smooth muscle cells and vasodilation of the pulmonary vascular bed.
Onset: 30 min
Duration: Up to 36 hr.
Absorption: Well absorbed. Peak plasma concentrations reached within 2 hr. Rate and extent of absorption not affected by food.
Distribution: Widely distributed into tissues. 94% bound to plasma proteins.
Metabolism: Metabolised in the liver mainly by the cytochrome P450 isoenzyme CYP3A4 to inactive metabolites. Mean half-life is 17.5 hr.
Excretion: Excreted mainly as metabolites, in the faeces (61% of the dose), and to a lesser extent the urine (36% of the dose).

B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women OR Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester.