Clinical medicine profile
Verapamil / Trandolapril
Calcium-channel blocker
- Route
- ORAL
- Schedule
- POM
- ATC
- Not assigned
- PPB status
- registered
Safety essentials
The information most likely to change a prescribing or dispensing decision.
Contraindications
- CONTRAINDICATIONS 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.
- Patients with atrial flutter or atrial fibrillation and an accessory bypass tract (e.g., Wolff-Parkinson-White, Lown-Ganong-Levine syndromes) (see WARNINGS ) 6.
- Patients with known hypersensitivity to verapamil hydrochloride.
Precautions
- WARNINGS 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 ).
- Patients with milder ventricular dysfunction should, if possible, be controlled with optimum doses of digitalis and/or diuretics before verapamil treatment.
- ( Note interactions with digoxin under PRECAUTIONS .) Hypotension: Occasionally, the pharmacologic action of verapamil may produce a decrease in blood pressure below normal levels, which may result in dizziness or symptomatic hypotension.
- The incidence of hypotension observed in 4,954 patients enrolled in clinical trials was 2.5%.
- In hypertensive patients, decreases in blood pressure below normal are unusual.
- Tilt-table testing (60 degrees) was not able to induce orthostatic hypotension.
- Elevated liver enzymes: Elevations of transaminases with and without concomitant elevations in alkaline phosphatase and bilirubin have been reported.
- Such elevations have sometimes been transient and may disappear even with continued verapamil treatment.
- Several cases of hepatocellular injury related to verapamil have been proven by rechallenge
- half of these had clinical symptoms (malaise, fever, and/or right upper quadrant pain), in addition to elevation of SGOT, SGPT, and alkaline phosphatase.
Dosing matrix
Population and organ-function guidance, shown together for faster comparison.
DOSAGE AND ADMINISTRATION 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. Consideration should be given to beginning titration at 40 mg three times per day in patients who might respond to lower doses, such as the elderly or people of small stature. The antihypertensive effects of verapamil are evident within the first week of therapy. Upward titration should be based on therapeutic efficacy, assessed at the end of the dosing interval.
Pediatric use: Safety and effectiveness in pediatric patients have not been established.
Generally no major renal dose change for amlodipine; monitor BP response.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Hepatic impairment increases exposure — start low.
Use, effects & interactions
Indications
- INDICATIONS AND USAGE 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.
- Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.
- These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including this drug.
- Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake.
- Many patients will require more than one drug to achieve blood pressure goals.
- For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).
- Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits.
Adverse effects
- ADVERSE REACTIONS 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<50/min) 1.4% Nausea 2.7% AV block total (1°, 2°, 3°) 1.2 % 1.2% Hypotension 2.5% 2° and 3° 0.8% Headache 2.2% Rash 1.2% Edema 1.9% Flushing 0.6% CHF,Pulmonary edema 1.8% Fatigue 1.7% Elevated liver enzymes (see WARNINGS ) In clinical trials related to the control of ventricular response in digitalized patients who had atrial fibrillation or flutter, ventricular rates below 50 at rest occurred in 15% of patients and asymptomatic hypotension occurred in 5% of patients.
- The following reactions, reported in 1% or less of patients, occurred under conditions (open trials, marketing experience) where a causal relationship is uncertain
- they are listed to alert the physician to a possible relationship: Cardiovascular: angina pectoris, atrioventricular dissociation, chest pain, claudication, myocardial infarction, palpitations, purpura (vasculitis), syncope.
- Digestive system: diarrhea, dry mouth, gastrointestinal distress, gingival hyperplasia.
- Hemic and lymphatic: ecchymosis or bruising.
- Nervous system: cerebrovascular accident, confusion, equilibrium disorders, insomnia, muscle cramps, paresthesia, psychotic symptoms, shakiness, somnolence, extrapyramidal symptoms.
- Skin: arthralgia and rash, exanthema, hair loss, hyperkeratosis, macules, sweating, urticaria, Stevens-Johnson syndrome, erythema multiforme.
- Special senses: blurred vision, tinnitus.
- Urogenital: gynecomastia, galactorrhea/hyperprolactinemia, increased urination, spotty menstruation, impotence.
- Treatment of acute cardiovascular adverse reactions: The frequency of cardiovascular adverse reactions that require therapy is rare
- hence, experience with their treatment is limited.
Drug interactions
Open multi-drug checker ↗- Fixed-dose/multi-ingredient product.
- Clinical details partially inherited from component monographs: Verapamil, Trandolapril.
- Confirm combination SmPC for exact dosing.
Mechanism & disposition
Combination product.
Read complete mechanism
Combination product. Component mechanism (Verapamil): Calcium channel blocker. Dihydropyridine CCBs block L-type calcium channels in vascular smooth muscle, causing arterial vasodilation and reduced peripheral resistance. Non-dihydropyridines (verapamil/diltiazem) also depress cardiac conduction and contractility — useful for rate control.
Hours (chronic BP effect over days–weeks)
24 hours (most once-daily DHPs)
ORAL
is increased and plasma clearance reduced to about 30% of normal. Verapamil clearance values suggest that patients with liver dysfunction may attain therapeutic verapamil plasma concentrations with one third of the oral daily dose required for patients with normal liver function....
More than 90% of the orally administered dose of verapamil hydrochloride is absorbed. Because of rapid biotransformation of verapamil during its first pass through the portal circulation, bioavailability ranges from 20% to 35%. Peak plasma concentrations are reached between 1 and...
half-life in single-dose studies ranged from 2.8 to 7.4 hours. In these same studies, after repetitive dosing, the
in single-dose studies ranged from 2.8 to 7.4 hours. In these same studies, after repetitive dosing, the half-life increased to a range from 4.5 to 12 hours (after less than 10 consecutive doses given 6 hours apart). Half-life of verapamil may increase during titration. Aging may...
Pregnancy, lactation & diet
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. In the rat, however, this multiple of the human dose was embryocidal and retarded fetal growth and development, probably because of adverse maternal effects reflected in reduced weight gains of the dams. This oral dose has also been shown to cause hypotension in rats. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Verapamil crosses the placental barrier and can be detected in umbilical vein blood at delivery.
Nursing mothers: Verapamil is excreted in human milk. Because of the potential for adverse reactions in nursing infants from verapamil, nursing should be discontinued while verapamil is administered.
Brands & loaded prices
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Sources & review state
Decision support only. Confirm patient-specific decisions against the current product SmPC, Kenya STG/EML, and professional judgement.