Drugs that inhibit CYP3A4 such as ketoconazole can inicrease tadalafil exposure HIV protease inhibitor (Ritonovir) increased tadalafil 20mg single exposure (AUC) by 124% with no change in Cmax. relative to the values for tadalafil 20mg alone.

Based upon these results in patients taking concomittant potent CYP3A4 inhibitors. The dose of tadalafil should not exceed 10mg and tadalafil should not taken more frequently than once in every 72 hours Other cytochrome P450 inhibitors like erythromycin, itraconazole and graprfriut juice would likely increase tadalafil exposure. Studies have shown that drugs that induce CYP3A4 such as rifampicin can decrease tadalafil exposure. Simultaneous administration of an antacid (magnesium hydroxide/aluminium hydroxide ) and tadalafil reduced the apparent rate of absorption of tadlafil without altering exposure (AUC) totadalafil.

Alcohol and PDES inhibitors, including are mild systemic vasodilators. When tadlifil 20mg was administred to healthy subjects taking doxazosin (8mg daily) an alpha1- adrenergic blocker there is a significant augementation of the blood-pressure lowering effect of doxazosin.

Erectile dysfunction

Headache, dyspepsia, back pain, myalgia, nasal congestion, flushing and pain in limb.

In patients who are using any organic nitrate either regularly and/ or intermittently is contraindicated. In patients talking any alpha adrenergic antagonist other trhan 0.4mg o.d. tamsulosin is contraindicated. Known hypersentivity to tadalafil or any component of the tablet.

Special precaution-

Tadalafil should be used with caution in patients who have conditions that might prtedispose them to priapism (such as sickle cell anemia, multiple myeloma or leukemia) or in patients with anatomical deformation of the penis (such as angulation, cervemosal fibrosis or Peyronies disease.

10 to 20mg taken prior to anticipated sexual activity and without regard to food. Maximum recommended dosing frequency is once per day.

Pharmacology-

Tadalafil inhibits phosphodiesterase type 5 -an enzyme which hydrolysis cyclic guanosine monophosphate (cGMP) in the penis corpus carvenosium. When sexual stimulation causes the local release of nitrocoxide, inhibition of PDE5 enhances the concentration of penile cGMP and potentiates smooth muscle relaxation in the corpus cavernosium. The resultant increased arterial blood flow leads to enlargement of the corpus cavernosium and the tunica albuginea as a result of the increased tumescene, and the outflow of blood is reduced.

Consequently, intracaveernosal pressure increases and erection occurs.

Pharmacokinetics-

Tadalfil is eliminated by hepatic metabolism, mainly by cytochrome P450 3A (CYP3A4).

After single oral-dose administration the maximum observed plasma concentration Cmax of tadalafil is acheived between 30 minutes and 6 hours(median time 2 hours) The rate and extent of absorption are not influenced by food. The mean oral clearance for tadalafil is 2.5L/hr and the mean terminal half-life is 17.5hours in healthy subjects. Tadalafil is excreted predominently as metabolites ,mainly in the feces (approximately 61%of the dose) and to a lesser extent in the urine (aproximately 36% of the dose).

The rate and extent of absorption are not influenced by food.