Bosentan

CLINICAL USE

Treatment of primary arterial pulmonary hypertension (PAH), and PAH secondary to scleroderma without significant interstitial pulmonary disease

DOSE IN NORMAL RENAL FUNCTION

62.5–250 mg twice daily

PHARMACOKINETICS

Molecular weight &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :551.6

%Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :>98

%Excreted unchanged in urine &nbsp &nbsp : <3

Volume of distribution (L/kg) &nbsp &nbsp &nbsp :18 litres

half-life – normal/ESRD (hrs)&nbsp &nbsp &nbsp :5–8/Unchanged

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 &nbsp &nbsp : Dose as in normal renal function

10 to 20 &nbsp &nbsp : Dose as in normal renal function

<10 &nbsp &nbsp &nbsp &nbsp &nbsp : Dose as in normal renal function

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp:Not dialysed. Dose as in normal renal function

HD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :Not dialysed. Dose as in normal renal function

HDF/high flux &nbsp :Not dialysed. Dose as in normal renal function

CAV/VVHD &nbsp &nbsp &nbsp:Not dialysed. Dose as in normal renal function

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Antibacterials: concentration reduced by rifampicin – avoid concomitant use

Antidiabetics: increased risk of hepatoxicity with glibenclamide – avoid concomitant useAntifungals: fluconazole, ketoconazole and itraconazole cause large increases in plasma concentrations of bosentan – avoid concomitant useAntivirals: ritonavir causes greatly increased bosentan levels – avoid concomitant use

Ciclosporin: co-administration of ciclosporin and bosentan is contraindicated. When ciclosporin and bosentan are co-administered, initial trough concentrations of bosentan are 30 times higher than normal. At steady state, trough levels are 3–4 times higher than normal. Blood concentrations of ciclosporin decreased by 50%

Lipid lowering agents: concentration of simvastatin reduced by 45% – monitor cholesterol levels and adjust dose of statin

Oestrogens and progestogens: may be failure of contraception – use alternative method

ADMINISTRATION

Reconstition

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Route

Oral

Rate of Administration

–

Comments

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OTHER INFORMATION

Bosentan should only be used if the systemic systolic blood pressure is >85 mm/Hg

Treatment with bosentan is associated with a dose-related, modest decrease in haemoglobin concentration

Bosentan is an inducer of CYP 3A4 and CYP 2C9Bosentan has been associated with dose-related elevations in liver aminotransferases

Side effects include leg oedema and hypotension

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