Anxiolytic

Initially 5 mg 2–3 times daily.

Usual range 15–30 mg daily in divided doses (maximum 45 mg daily)

Molecular weight :422

%Protein binding :95

%Excreted unchanged in urine : 0

Volume of distribution (L/kg) :2.69–7.91

half-life – normal/ESRD (hrs) :2–11/Increased by 2 hours1

20 to 50 : Dose as in normal renal function

10 to 20 : Dose as in normal renal function

<10 : Reduce by 25–50% if patient is anuric2

CAPD :Not dialysed. Dose as in GFR <10 mL/min

HD :Not dialysed. Dose as in GFR <10 mL/min

HDF/high flux :Unknown dialysability. Dose as in GFR <10 mL/min

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

Potentially hazardous interactions with other drugs

Antibacterials: concentration increased by erythromycin – reduce dose; concentration reduced by rifampicin

Antidepressants: risk of severe hypertension with MAOIs – avoid concomitant use

Antifungals: concentration increased by itraconazole – reduce dose

Antipsychotics: enhanced sedative effects; haloperidol concentration increased

Antivirals: concentration increased by ritonavir, increased risk of toxicity

Calcium-channel blockers: concentration increased by diltiazem and verapamil – reduce dose

Grapefruit juice: concentration increased by grapefruit juice – reduce dose

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Oral

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Peak plasma levels occur 60–90 minutes after dosing

Steady state plasma concentrations achieved within 2 days, although response to treatment may take 2 weeks

Non-sedative Do not use in patients with severe hepatic disease

Use in severe renal impairment not recommended; risk of accumulation of active metabolites