Verapamil Hydrochloride
Isoptin SR
- Dosage form
- Tablet
- Available strengths
- 120 mg, 180 mg, and 240 mg
- Drug class
- Non-dihydropyridine calcium channel blocker (antihypertensive agent)
- Common brand
- Isoptin SR
Clinical overview. Isoptin SR (verapamil hydrochloride) is a sustained-release, non-dihydropyridine calcium channel blocker used to treat mild to moderate essential hypertension, typically in patients who cannot tolerate diuretics or beta-blockers. It should not be combined with beta-blockers for blood pressure treatment and is contraindicated in significant cardiac conduction disease, severe heart failure, cardiogenic shock, and Wolff-Parkinson-White syndrome with atrial fibrillation or flutter. Verapamil is extensively metabolized by CYP3A4, giving it a broad interaction profile that includes digoxin, statins, immunosuppressants, and grapefruit juice, and it requires cautious use in hepatic or renal impairment and in elderly patients.
Indication
Common therapeutic uses
- Used to treat mild to moderate essential high blood pressure, generally in patients who have had unacceptable side effects from diuretics or beta-blockers.
- May be tried as an initial blood-pressure-lowering medication when diuretics or beta-blockers are contraindicated or poorly tolerated.
- Can be combined with a diuretic or an ACE inhibitor for an additive blood-pressure-lowering effect, but should not be combined with beta-blockers for treating high blood pressure.
Pregnancy
Risk assessment and monitoring considerations
- No well-controlled studies exist in pregnant women; the drug crosses the placenta and can be detected in umbilical cord blood at delivery, so it is not recommended during pregnancy unless the expected benefit to the mother outweighs the potential risk to the fetus.
- In animal studies, high doses similar to the maximum human dose slowed fetal growth and increased pregnancy loss, though these effects occurred alongside toxicity in the mother and no birth defects were seen at any dose tested.
Breastfeeding
Infant exposure considerations
- Passes into human breast milk, and because of the potential for effects in a nursing infant, breastfeeding should be discontinued while taking this medication.
Geriatrics
Dosing and tolerability considerations
- Caution should be used in elderly patients, particularly those prone to low blood pressure or with a history of poor blood flow to the brain, as this medication is processed more slowly and drug exposure is higher in older adults.
- Side effects such as dizziness and constipation occur more often in the elderly, and serious heart block has been reported in this age group, so a lower starting dose is often appropriate.
Pediatrics
Use in children and adolescents
- Safety and the appropriate dosing regimen have not been established in patients under 18 years of age, so use in this age group is not recommended.
Dosage & Administration
Practical dosing and administration
- The usual starting dose for adults is 180 to 240 milligrams once daily, adjusted upward as needed based on individualized response and tolerance, up to a maximum of 480 milligrams per day divided into a morning and evening dose.
- A lower starting dose of around 120 milligrams daily may be appropriate for elderly patients, with gradual, careful adjustment.
- Tablets should be taken with food and swallowed whole, since crushing or chewing destroys the sustained-release mechanism; the 240 milligram tablet may be split in half if needed, but the other strengths should not be split.
Common side effects
Frequently reported tolerability concerns
- Constipation is the most commonly reported side effect.
- Dizziness may occur.
- Headache may occur.
- Fatigue may occur.
- Nausea may occur.
- Mild swelling (edema), particularly of the ankles, may occur.
- Shortness of breath may occur.
- A slower than usual heart rate (bradycardia) may occur.
- Flushing may occur.
- Increased frequency of urination may occur.
Serious side effects
Findings that may require urgent assessment
Serious side effects require immediate discussion with the prescriber or emergency care.
- Heart failure or fluid buildup in the lungs may occur, particularly in patients with underlying heart disease.
- Severe low blood pressure may occur.
- Serious slowing of electrical conduction in the heart, including second- or third-degree heart block, may occur.
- The heart may stop beating briefly (asystole) or the sinus node may pause, especially in patients with underlying conduction disease.
- In patients with certain abnormal heart rhythm pathways, this medication can dangerously speed up the heart rate if atrial fibrillation or flutter is present.
- Liver injury, including elevated liver enzymes, jaundice, and hepatitis, has been reported and can be serious.
- Severe skin reactions, including Stevens-Johnson syndrome and erythema multiforme, have been reported rarely.
- Swelling of the face, lips, tongue, or throat (angioedema) may occur and can affect breathing.
- Seizures have been reported rarely after this medication was marketed.
- Seek immediate medical attention for fainting, a very slow or irregular heartbeat, severe swelling, difficulty breathing, or yellowing of the skin or eyes.
Use with caution
Situations requiring closer assessment
- Should be used with caution in patients with impaired liver function, since the drug is extensively processed by the liver and its clearance is significantly slower in this population.
- Should be used with caution in patients with impaired kidney function.
- Should be used with caution in patients with first-degree heart block, since this can occasionally progress to a higher degree of block.
- Should be used with caution in patients with conditions affecting nerve-to-muscle signaling, such as myasthenia gravis or muscular dystrophy.
- Should be used with caution, and generally avoided, in combination with other heart-rate-lowering drugs such as beta-blockers or certain antiarrhythmics, due to additive effects on heart rate and conduction.
- Patients with hypertrophic cardiomyopathy who are treated with this medication have experienced serious adverse effects, including severe low blood pressure and fluid in the lungs, particularly at high doses.
Contraindications
Situations where therapy may be inappropriate
- Known hypersensitivity to verapamil or to any ingredient in the formulation.
- A recent heart attack complicated by fluid in the lungs from heart failure.
- Severe weakening of the heart's pumping ability (severe left ventricular dysfunction).
- Cardiogenic shock.
- Severely low blood pressure.
- Second- or third-degree heart block, unless a pacemaker is in place.
- Sick sinus syndrome, unless a pacemaker is in place.
- Markedly slow heart rate.
- Atrial flutter or atrial fibrillation in patients with an accessory conduction pathway in the heart, such as Wolff-Parkinson-White syndrome, due to the risk of dangerous rapid heart rhythms.
- Concurrent use of ivabradine, due to the risk of significantly increased ivabradine levels and excessive heart rate slowing.
- Concurrent use of flibanserin, due to the risk of severe low blood pressure and fainting.
Drug interactions
Clinically relevant combinations
- Should not be combined with beta-blockers for treating high blood pressure, as the combination can have additive negative effects on heart rate, conduction, and heart muscle contraction.
- Raises blood levels of digoxin, so the digoxin dose usually needs to be reduced and the patient monitored closely.
- Certain antibiotics, including clarithromycin and erythromycin, may raise verapamil levels and have been linked to severe low blood pressure and slow heart rate when combined.
- Rifampin can substantially reduce the blood-pressure-lowering effect of this medication by speeding up its breakdown.
- Raises blood levels of statins that are processed by the same liver pathway, such as simvastatin, lovastatin, and atorvastatin, so lower statin doses are generally recommended when combined.
- Raises blood levels of certain immunosuppressant medications, including cyclosporine, tacrolimus, sirolimus, and everolimus, requiring dose adjustment and monitoring.
- May increase blood levels of certain blood thinners, including dabigatran and other direct oral anticoagulants, which can raise the risk of bleeding.
- May raise carbamazepine levels and increase the risk of carbamazepine-related nervous system side effects.
- Phenytoin can reduce verapamil blood levels and its blood-pressure-lowering effect.
- Increases exposure to colchicine and combined use is not recommended, as it has been linked to a rare but serious risk of muscle weakness and paralysis.
- May increase blood alcohol concentration and prolong its effects.
Food interactions
Meal-related administration
- Grapefruit and grapefruit juice should be avoided, as they can raise blood levels of this medication.
- Tablets should be taken with food, as this affects the timing and extent of drug absorption from the sustained-release formulation.
Time of administration
Practical scheduling
- Taken once daily in the morning with food for lower total daily doses, or split into a morning and evening dose with food for higher total daily doses, at consistent times each day.
Storage
Product handling
- Store at room temperature between 15 and 25 degrees Celsius.
Patient take-away
Key counselling points for a quick closing summary
- This medication is a calcium channel blocker used to control high blood pressure, often in patients who cannot tolerate diuretics or beta-blockers.
- The usual dose starts at 180 to 240 milligrams once daily with food and may be increased up to a maximum of 480 milligrams a day, taken as a whole tablet without crushing or chewing (though the 240 milligram tablet can be split in half).
- Common effects include constipation, dizziness, headache, fatigue, and mild ankle swelling.
- Contact your doctor's office right away if you notice a very slow or irregular heartbeat, fainting, shortness of breath, significant swelling, or signs of liver problems such as yellowing of the skin or eyes or unusual fatigue.
- Avoid grapefruit juice and St John's wort while taking this medication, and make sure your pharmacist knows about all your other medications, especially digoxin, statins, and beta-blockers.
- Do not stop this medication suddenly without talking to your doctor, and store it at room temperature.
References
Source material and product information
For professional reference. Confirm patient-specific decisions against the current approved product monograph and applicable clinical guidance.