Ketoconazole, Itraconazole, Voriconazole, Fluconazole Ritronavir Cyclosporin Rifampicin Nimodipine Glibenclamide Tacrolimus, Sirolimus Sidenafil, Simavastatin Warfarin, Digoxin, O.C.

Pulmonary arterial hypertension

Headache, flushing, abnormal hepatic function Leg oedema, Anemia URTIs , Nasopharyngitis, pneumonia Palpitation, dypepsia, dry mouth Hypotension,chest pain, pruritus, fatigue Arthalgia, dizzinees Rarely liver failure, anaphylaxis, neutropenia, leucopenia

Moderate to severe hepatic impairment, Hepatic aminotransferase levels > 3 upper limit. Concomittant cyclosporin, glibenclamide Pregnancy Lactation

Special Precautions-

Raised liver enzymes Monitor prior to and at monthly itervals during therapy and two weeks after any increase in dose.

Advice patients to report any signs suggestive of liver damage Monitor for signs of fluid retention, LV, severe systolic dysfunction

Women of child bearing potential should use non-hormonal contraception during treatment Peform monthly pregnancy tests where appropiate . Hypotension.Withdraw gradually.

Indication-

Pulmonary arterial hypertension

Dosage-

Dosages above Initially 62.5mg twice daily for 4 weeks increasing to maintenance of 125mg twice daily

Maximum dose- dosage above 125mg twice daily did not appear to confer additional benefit to offset the increased risk of liver injury

Children below 12 years- consult doctor

Discuss with patients the importance of monthly monitoring of serum aminotransferases and urine or serum pregnancy testing and of avoidance of pregnancy.

Discuss options of effective contraception and measures to prevent pregnancy with women. Seek input from a gynaecologist or an expert on adequate contraception as needed.

Pharmacology-

Bosentan is a specific and competetive antagonist at endothelin receptor types ETa ETb . Bosantan has a slightly higher affinity for ETa receptors than for ETb receptors

Phamacokinetics-

After oral admin of Bosentan Cmx of bosentan are attained within 3 to 5 hours. Steady state is reached within 3 to 5 days

Contraindicated in pregnancy and lactation