verapamil hydrochloride

CLINICAL USE

Calcium-channel blocker: Supraventricular arrhythmias Angina Hypertension

DOSE IN NORMAL RENAL FUNCTION

Oral: Supraventricular arrhythmias: 40–120 mg 3 times daily Angina: 80–120 mg 3 times daily Hypertension: 240–480 mg daily in 2–3 divided doses IV: 5–10 mg followed by 5 mg, 5–10 minutes later if required

PHARMACOKINETICS

Molecular weight : 491.1

%Protein binding : 90

%Excreted unchanged in urine : <4

Volume of distribution (L/kg) : 3–6

half-life – normal/ESRD (hrs) : 4.5–12/Increased

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Dose as in normal renal function. Monitor carefully

10 to 20 : Dose as in normal renal function. Monitor carefully

<10 : Dose as in normal renal function. Monitor carefully

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

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 : Dialysability minimal. Dose as in GFR 10 to 20 mL/min

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Anaesthetics: increased hypotensive effect

Anti-arrhythmics: increased risk of amiodarone-induced bradycardia, AV block and myocardial depression; increased risk of myocardial depression and asystole with disopyramide and flecainide

Antibacterials: metabolism increased by rifampicin; metabolism possibly inhibited by erythromycin and clarithromycin (increased risk of toxicity)

Anti-epileptics: effect probably reduced by barbiturates, phenytoin and primidone; enhanced effect of carbamazepine Antihypertensives: enhanced hypotensive effect, increased risk of first dose hypotensive effect of post-synaptic alpha- blockers

Antivirals: concentration possibly increased by atazanavir and ritonavir

Beta-blockers: enhanced hypotensive effect; risk of asystole, severe hypotension and heart failure if co-prescribed with beta-blockers Cardiac glycosides: increased levels of digoxin. Increased AV block and bradycardia

Ciclosporin: variable reports of decreased nephrotoxicity and potentiated effect; may also increase ciclosporin levels

Grapefruit juice: concentration increased – avoid concomitant use Ivabradine: avoid concomitant use Sirolimus: concentration of both drugs increased Statins: increased myopathy with simvastatin – do not exceed 20 mg of simvastatin.1

Tacrolimus: may increase tacrolimus levels Theophylline: enhanced effect of theophylline Verapamil hydrochloride .