Verapamil

Verapamil Hydrochloride Tablets are indicated for the treatment of the following: Angina 1. Angina at rest including: – Vasospastic (Prinzmetal’s variant) angina – Unstable (crescendo, pre-infarction) angina 2. Chronic stable angina (classic effort-associated angina) Arrhythmias 1. In association with digitalis for the control of ventricular rate at rest and during stress in patients with chronic atrial flutter and/or atrial fibrillation (see WARNINGS; Accessory bypass tract ) 2. Prophylaxis of repetitive paroxysmal supraventricular tachycardia Essential hypertension: Verapamil is indicated for the treatment of hypertension, to lower blood pressure. …

• The dose of verapamil must be individualized by titration
• The usefulness and safety of dosages exceeding 480 mg/day have not been established; therefore, this daily dosage should not be exceeded
• Since the half-life of verapamil increases during chronic dosing, maximum response may be delayed
• Angina: Clinical trials show that the usual dose is 80 mg to 120 mg three times a day
• However, 40 mg three times a day may be warranted in patients who may have an increased response to verapamil (e.g., decreased hepatic function, elderly, etc.)
• Upward titration should be based on therapeutic efficacy and safety evaluated approximately eight hours after dosing
• Dosage may be increased at daily (e.g., patients with unstable angina) or weekly intervals until optimum clinical response is obtained
• Arrhythmias: The dosage in digitalized patients with chronic atrial fibrillation (see PRECAUTIONS ) ranges from 240 to 320 mg/day in divided (three times a day or four times a day) doses
• The dosage for prophylaxis of PSVT (non-digitalized patients) ranges from 240 to 480 mg/day in divided (three times a day or four times a day) doses
• In general, maximum effects for any given dosage will be apparent during the first 48 hours of therapy
• Essential hypertension: Dose should be individualized by titration
• The usual initial monotherapy dose in clinical trials was 80 mg three times a day (240 mg/day)
• Daily dosages of 360 and 480 mg have been used but there is no evidence that dosages beyond 360 mg provided added effect. …

• Safety and effectiveness
• In pediatric patients have not been established

• Verapamil Hydrochloride Tablets are contraindicated in: 1
• Severe left ventricular dysfunction (see WARNINGS ) 2
• Hypotension (systolic pressure less than 90 mm Hg) or cardiogenic shock 3
• Sick sinus syndrome (except in patients with a functioning artificial ventricular pacemaker) 4
• Second-or-third-degree AV block (except in patients with a functioning artificial ventricular pacemaker) 5. …

Cytochrome inducers/inhibitors: In vitro metabolic studies indicate that verapamil is metabolized by cytochrome P450 CYP3A4, CYP1A2, CYP2C8, CYP2C9, and CYP2C18. Clinically significant interactions have been reported with inhibitors of CYP3A4 (e.g., erythromycin, ritonavir) causing elevation of plasma levels of verapamil while inducers of CYP3A4 (e.g., rifampin) have caused a lowering of plasma levels of verapamil. HMG-CoA reductase inhibitors: The use of HMG-CoA reductase inhibitors that are CYP3A4 substrates in combination with verapamil has been associated with reports of myopathy/rhabdomyolysis. …

Heart failure: Verapamil has a negative inotropic effect, which in most patients is compensated by its afterload reduction (decreased systemic vascular resistance) properties without a net impairment of ventricular performance. In clinical experience with 4,954 patients, 87 (1.8%) developed congestive heart failure or pulmonary edema. Verapamil should be avoided in patients with severe left ventricular dysfunction (e.g., ejection fraction less than 30%) or moderate to severe symptoms of cardiac failure and in patients with any degree of ventricular dysfunction if they are receiving a beta-adrenergic blocker (see PRECAUTIONS, Drug Interactions ). …

Serious adverse reactions are uncommon when verapamil hydrochloride therapy is initiated with upward dose titration within the recommended single and total daily dose. See WARNINGS for discussion of heart failure, hypotension, elevated liver enzymes, AV block, and rapid ventricular response. Reversible (upon discontinuation of verapamil) non-obstructive, paralytic ileus has been infrequently reported in association with the use of verapamil. The following reactions to orally administered verapamil occurred at rates greater than 1% or occurred at lower rates but appeared clearly drug-related in clinical trials in 4,954 patients: Constipation 7.3% Dyspnea 1.4% Dizziness 3.3% Bradycardia (HR

Pregnancy: Pregnancy Category C. Reproduction studies have been performed in rabbits and rats at oral doses up to 1.5 (15 mg/kg/day) and 6 (60 mg/kg/day) times the human oral daily dose, respectively, and have revealed no evidence of teratogenicity. …

Treat all verapamil overdoses as serious and maintain observation for at least 48 hours (especially the extended-release formulation), preferably under continuous hospital care. Delayed pharmacodynamic consequences may occur with the extended-release formulation. Verapamil is known to decrease gastrointestinal transit time. Treatment of overdosage should be supportive. Beta-adrenergic stimulation or parenteral administration of calcium solutions may increase calcium ion flux across the slow channel and have been used effectively in treatment of deliberate overdosage with verapamil. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.