Cardizem SR

Cardizem SR Tablet (sustained Release), Capsule (sustained Release)

Cardizem SR hydrochloride is a calcium channel antagonist. It is a peripheral and coronary vasodilator with some negative inotropic activity. Cardizem SR inhibits cardiac conduction particularly at the sino-atrial and atrioventricular nodes. Cardizem SR has the following actions:

Antianginal: A direct dilatation of coronary arteries and arterioles proved oxygen supply to myocardial tissues. In addition dilatation of the peripheral vasculature reduces systemic pressure of cardiac "after load" which results in lessened stress and reduced oxygen requirements of the myocardial tissues.

Antiarrhythmic: The inhibited influx of calcium ions in cardiac tissues result in slowed electrophysiological activity through the S-A and A-V nodes without affecting accessory bypass conduction or altering normal atrial action potential or intraventricular conduction.

Antihypertensive: Reduces peripheral vascular resistance as a result of vasodilatation.

Cardizem SR is an antihypertensive and vasodilating agent that works by relaxing the vascular muscle and reducing blood pressure. This is related to the long-term therapeutic effects, as lowering the blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. Cardizem SR inhibits the influx of extracellular calcium ions across the myocardial and vascular smooth muscle cell membranes during depolarization. Cardizem SR is classified as a negative inotrope (decreased force) and negative chronotrope (decreased rate). It is also considered a rate-control drug as it reduces heart rate. Cardizem SR is exerts hemodynamic actions by reducing blood pressure, systemic vascular resistance, the rate-pressure product, and coronary vascular resistance while increasing coronary blood flow. Cardizem SR decreases sinoatrial and atrioventricular conduction in isolated tissues and has a negative inotropic effect in isolated preparations. In supraventricular tachycardia, diltiazem prolongs AV nodal refractories.

As the magnitude of blood pressure reduction is related to the degree of hypertension, the antihypertensive effect of diltiazem is most pronounced in individuals with hypertension. In a randomized, double-blind, parallel-group, dose-response study involving patients with essential hypertension, there was a reduction in the diastolic blood pressure by 1.9, 5.4, 6.1, and 8.6 mmHg in the patients receiving diltiazem at doses of 120, 240, 360, and 540 mg, respectively. In patients receiving placebo, there was a reduction in the diastolic blood pressure by 2.6 mmHg.In a randomized, double-blind study involving patients with chronic stable angina, variable doses of diltiazem administered at night all caused an increased exercise tolerance in the after 21 hours, compared to placebo. In the NORDIL study of patients with hypertension, the therapeutic effectiveness of diltiazem in reducing cardiovascular morbidity and mortality was assessed. When using the combined primary endpoint as fatal and non-fatal stroke, myocardial infarction, and other cardiovascular death, fatal and non-fatal stroke was shown to be reduced by 25% in the diltiazem group. Although the clinical significance to this effect remains unclear, it is suggested that diltiazem may exert a protective role against cerebral stroke in hypertensive patients.

Cardizem SR is an antihypertensive and vasodilating agent that works by relaxing the vascular muscle and reducing blood pressure. This is related to the long-term therapeutic effects, as lowering the blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. Cardizem SR inhibits the influx of extracellular calcium ions across the myocardial and vascular smooth muscle cell membranes during depolarization. Cardizem SR is classified as a negative inotrope (decreased force) and negative chronotrope (decreased rate). It is also considered a rate-control drug as it reduces heart rate. Cardizem SR is exerts hemodynamic actions by reducing blood pressure, systemic vascular resistance, the rate-pressure product, and coronary vascular resistance while increasing coronary blood flow. Cardizem SR decreases sinoatrial and atrioventricular conduction in isolated tissues and has a negative inotropic effect in isolated preparations. In supraventricular tachycardia, diltiazem prolongs AV nodal refractories.

As the magnitude of blood pressure reduction is related to the degree of hypertension, the antihypertensive effect of diltiazem is most pronounced in individuals with hypertension. In a randomized, double-blind, parallel-group, dose-response study involving patients with essential hypertension, there was a reduction in the diastolic blood pressure by 1.9, 5.4, 6.1, and 8.6 mmHg in the patients receiving diltiazem at doses of 120, 240, 360, and 540 mg, respectively. In patients receiving placebo, there was a reduction in the diastolic blood pressure by 2.6 mmHg.In a randomized, double-blind study involving patients with chronic stable angina, variable doses of diltiazem administered at night all caused an increased exercise tolerance in the after 21 hours, compared to placebo. In the NORDIL study of patients with hypertension, the therapeutic effectiveness of diltiazem in reducing cardiovascular morbidity and mortality was assessed. When using the combined primary endpoint as fatal and non-fatal stroke, myocardial infarction, and other cardiovascular death, fatal and non-fatal stroke was shown to be reduced by 25% in the diltiazem group. Although the clinical significance to this effect remains unclear, it is suggested that diltiazem may exert a protective role against cerebral stroke in hypertensive patients.

Uses

Cardizem SR is used for the prophylaxis and treatment of angina pectoris. It is used in the management of classical and vasospastic angina pectoris. It has also been used in the treatment of essential hypertension. It is used for prophylaxis of some selected supraventricular tachyarrhythmias.

Cardizem SR is also used to associated treatment for these conditions: Anal Fissures, Angina Pectoris, Variant, Anginal Pain, Atrial Fibrillation, Chronic Stable Angina Pectoris, Flutter, Atrial, High Blood Pressure (Hypertension), Idiopathic Dilated Cardiomyopathy, Paroxysmal Supraventricular Tachycardia, Proteinuria, Pulmonary Hypertension (PH), Leg cramps, Prophylaxis of migraine headaches

How Cardizem SR works

Excitation of cardiac muscle involves the activation of a slow calcium inward current that is induced by L-type slow calcium channels, which are voltage-sensitive, ion-selective channels associated with a high activation threshold and slow inactivation profile. L-type calcium channels are the main current responsible for the late phase of the pacemaker potential. Acting as the main Ca2+ source for contraction in smooth and cardiac muscle, activation of L-type calcium channels allows the influx of calcium ions into the muscles upon depolarization and excitation of the channel. It is proposed that this cation influx may also trigger the release of additional calcium ions from intracellular storage sites. Cardizem SR is a slow calcium channel blocker that binds to the extracellular site of the alpha-1C subunit of the channel, which is thought to be the S5-6 linker region of the transmembrane domain IV and/or S6 segment of domain III. Cardizem SR can get access to this binding site from either the intracellular or extracellular side, but it requires a voltage-induced conformational changes in the membrane. Cardizem SR inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes. In isolated human atrial and ventricular myocardium, diltiazem suppressed tension over the range of membrane potentials associated with calcium channel activity but had little effect on the tension-voltage relations at more positive potentials. This effect is thought to be mediated by the voltage-dependent block of the L-type calcium channels and inhibition of calcium ion release from the ER stores, without altering the sodium-calcium coupled transport or calcium sensitivity of myofilaments. Through inhibition of inward calcium current, diltiazem exerts a direct ionotropic and energy sparing effect on the myocardium. Cardizem SR fslows atrioventricular nodal conduction, which is due to its ability to impede slow channel function.

Reduced intracellular calcium concentrations equate to increased smooth muscle relaxation resulting in arterial vasodilation and therefore, decreased blood pressure. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload. Through its actions on reducing calcium levels in cardiac and vascular smooth muscles, diltiazem causes a reduction in the contractile processes of the myocardial smooth muscle cells and vasodilation of the coronary and systemic arteries, including epicardial and subendocardial. This subsequently leads to increased oxygen delivery to the myocardial tissue, improved cardiac output due to increased stroke volume, decreased total peripheral resistance, decreased systemic blood pressure and heart rate, and decreased afterload. Cardizem SR lowers myocardial oxygen demand through a reduction in heart rate, blood pressure, and cardiac contractility; this leads to a therapeutic effect in improving exercise tolerance in chronic stable angina.

Cardizem SR

Trade Name Cardizem SR
Availability Prescription only
Generic Diltiazem
Diltiazem Other Names d-cis-diltiazem, Diltiazem, Diltiazemum
Related Drugs amlodipine, aspirin, lisinopril, metoprolol, losartan, furosemide, carvedilol, hydrochlorothiazide, propranolol, Xarelto
Weight 90mg, 120mg
Type Tablet (sustained Release), Capsule (sustained Release)
Formula C22H26N2O4S
Weight Average: 414.518
Monoisotopic: 414.16132802
Protein binding

Diltiazem is about 70-80% bound to plasma proteins, according to in vitro binding studies. About 40% of the drug is thought to bind to alpha-1-glycoprotein at clinically significant concentrations while about 30% of the drug is bound to albumin.

Groups Approved, Investigational
Therapeutic Class Calcium-channel blockers
Manufacturer Drug International Ltd
Available Country Bangladesh
Last Updated: June 7, 2022 at 8:54 pm

Structure

Cardizem SR
Diltiazem Structure

Dosage

Cardizem SR dosage

Hypertension: Dosage needs to be adjusted by titration to individual patient needs. When used as monotherapy, usual starting doses are 120 to 240 mg once daily. Maximum antihypertensive effect is usually observed by 14 days of chronic therapy; therefore, dosage adjustments should be scheduled accordingly. The usual dosage range studied in clinical trials was 120 to 540 mg once daily. Current clinical experience with 540 mg dose is limited; however, the dose may be increased to 540 mg once daily.

Angina: Dosages for the treatment of angina should be adjusted to each patient's needs, starting with a dose of 120 mg to 180 mg once daily. Individual patients may respond to higher doses of up to 540 mg once daily. When necessary, titration should be carried out over 7 to 14 days.

Dilute with appropriate solution either dextrose 5% in water, normal saline, dextrose 5% in water with NaCl 0.45% to achieve desired vol of concentration.

Side Effects

Cardizem SR Hydrochloride produces few side effects and these are usually mild. Oedema, nausea, headache, finger swelling, skin rash, dizziness and asthenia have been reported. Other adverse effects include bradycardia, AV block, hypotension, gastrointestinal symptom, hyperactivity with associated psychiatric symptoms and mild elevation of liver function tests.

Toxicity

Clinical Toxicity and Overdose

The oral LD50 ranges from 415 to 740mg/kg in mice and 560 to 810 mg/kg in rats. The oral LD50 in dogs is considered to be in excess of 50 mg/kg. A dose of 360 mg/kg resulted in lethality in monkeys. The intravenous LD50 is 60 mg/kg in mice and 38 mg/kg in rats.

Cases of overdose from doses ranging from less than 1 g to 18 g have been reported with diltiazem, with several cases involving multiple drug ingestions resulting in death. Overdoses were associated with bradycardia, hypotension, heart block, and cardiac failure that may manifest as dizziness, lightheadedness, and fatigue. Actual treatment and dosage should depend on the severity of the clinical situation and the judgment and experience of the treating physician. Cardizem SR overdose should be responded with appropriate supportive measures and gastrointestinal decontamination. Bradycardia and heart block can be treated with atropine at doses ranging from 0.60 to 1.0 mg. In the case of bradycardia, if there is no response to vagal blockage, cautious administration of isoproterenol should be considered. Cardiac pacing can also be used to treat fixed high-degree AV block. In the case of heart failure, blood pressure may be maintained with the use of fluids and vasopressors, as well as inotropic agents such as isoproterenol, dopamine, or dobutamine. Other appropriate measures include ventilatory support, gastric lavage, activated charcoal, and/or intravenous calcium. Cardizem SR does not appear to be removed by peritoneal or hemodialysis.

Non-clinical toxicity

In a 24-month study in rats receiving oral doses of up to 100 mg/kg/day, there was no evidence of carcinogenicity. There was also no mutagenic response in vitro or in vivo in mammalian cell assays or in vitro bacterial assays. No evidence of impaired fertility was observed in a study performed in male and female rats receiving oral doses of up to 100 mg/kg/day.

Pregnancy and Lactation

In reproduction studies in animals, administration of diltiazem at doses ranging from five to twenty times the daily recommended human therapeutic dose resulted in cases of the embryo and fetal lethality and skeletal abnormalities, and an increase in the risk of stillbirths. There have been no up-to-date controlled studies that investigated the use of diltiazem in pregnant women. The use of diltiazem in pregnant women should be undertaken only if the potential benefit justifies the risk to the fetus. Cardizem SR is excreted in human milk, where one report suggests that the concentrations in breast milk may approximate serum levels; therefore, the decision should be made to either discontinue nursing or the use of the drug after careful consideration of the clinical necessity of diltiazem therapy in the nursing mother.

Use in special populations

As there is limited information on the variable effects of diltiazem in geriatric patients, the initial therapy of diltiazem should involve the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Currently, there are no specific dosing guidelines for patients with renal or hepatic impairment.

Precaution

Patients with mild bradycardia or a prolonged PR interval should be observed closely. Cardizem SR does not have a significant myocardial depressant effect and is well tolerated in patients with poor left ventricular function. The drug should be used with caution in patients with impaired hepatic or renal function.

Interaction

Cardizem SR Hydrochloride should be carefully administered in case of concomitant use with the following drugs.

  • Anti-hypertensive agents : effects of anti-hypertensive agents are enhanced
  • Propranolol : concentration of propranolol may be increased
  • Carbamazepine : plasma level of Carbamazepine may be increased and it may cause Carbamazepine induced toxic symptoms such as sleepiness, nausea, vomiting, vertigo etc.
  • Digoxin preparations : plasma level of Digoxin is increased
  • Cyclosporin : may increase serum cyclosporin concentration by 75% or more.

Food Interaction

  • Avoid natural licorice. The risk of cardiovascular adverse effects may be increased.

[Moderate] MONITOR: Like many CNS-active agents, alcohol can exhibit hypotensive effects.

Coadministration with antihypertensive agents including diltiazem may result in additive effects on blood pressure and orthostasis.

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered diltiazem in some patients.

The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

In a study of ten healthy male volunteers, administration of a single 120 mg oral dose of immediate-release diltiazem in combination with 250 mL of grapefruit juice increased the diltiazem peak plasma concentration (Cmax) and systemic exposure (AUC) by an average of 22% and 20%, respectively, compared to administration with water.

The time to reach Cmax (Tmax) and the terminal half-life were not affected, and no statistically significant differences in blood pressure and heart rate were observed during administration with grapefruit juice relative to water.

In a different study, repeated administration of 200 mL of grapefruit juice at 0, 2, 4, 8 and 12 hours had no significant effect on the Cmax or AUC of a single 120 mg oral dose of diltiazem, but increased its half-life from 4.1 to 5.1 hours.

The ratios for the N-demethyl and deacetyl metabolites to diltiazem were also not affected by grapefruit juice.

However, because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients should be advised that alcohol may potentiate the hypotensive effects of diltiazem, especially during the initiation of therapy and following a dosage increase.

Caution should be exercised when rising from a sitting or recumbent position, and patients should notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

Patients who regularly consume grapefruit or grapefruit juice should be monitored for increased adverse effects of diltiazem such as such as headache, irregular heartbeat, edema, unexplained weight gain, and chest pain.

Grapefruit and grapefruit juice should be avoided if an interaction is suspected.

Cardizem SR Drug Interaction

Moderate: aspirin, aspirin, apixaban, apixaban, rivaroxaban, rivaroxaban

Unknown: omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, furosemide, furosemide, levothyroxine, levothyroxine, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol

Cardizem SR Disease Interaction

Major: aortic stenosis, bradyarrhythmia/AV block, cardiogenic shock/hypotension, coronary artery disease, liver disease, CHF/AMI, accessory AV tracts, ventricular tachycardia

Moderate: renal dysfunction

Volume of Distribution

The apparent volume of distribution of diltiazem was approximately 305 L following a single intravenous injection in healthy male volunteers.

Elimination Route

Cardizem SR is readily absorbed from the gastrointestinal tract. Minimum therapeutic plasma diltiazem concentrations appear to be in the range of 50 to 200 ng/mL. Following oral administration of extended formulations of 360 mg diltiazem, the drug in plasma was detectable within 3 to 4 hours and the peak plasma concentrations were reached between 11 and 18 hours post-dose. Cardizem SR peak and systemic exposures were not affected by concurrent food intake. Due to hepatic first-pass metabolism, the absolute bioavailability following oral administration is about 40%, with the value ranging from 24 to 74% due to high interindividual variation in the first pass effect. The bioavailability may increase in patients with hepatic impairment.

Half Life

The plasma elimination half-life is approximately 3.0 to 4.5 hours following single and multiple oral doses. The half-life may slightly increase with dose and the extent of hepatic impairment. The apparent elimination half-life for diltiazem as extended-release tablets after single or multiple dosing is 6 to 9 hours. The plasma elimination half-life is approximately 3.4 hours following administration of a single intravenous injection. The elimination half-lives of pharmacologically active metabolites are longer than that of diltiazem.

Clearance

Following a single intravenous injection in healthy male volunteers, the systemic clearance of diltiazem was approximately 65 L/h. After constant rate intravenous infusion, the systemic clearance decreased to 48 L/h.

Elimination Route

Due to its extensive metabolism, only 2% to 4% of the unchanged drug can be detected in the urine. The major urinary metabolite in healthy volunnteers was N-monodesmethyl diltiazem, followed by deacetyl N,O-didesmethyl diltiazem, deacetyl N-monodesmethyl diltiazem, and deacetyl diltiazem; however, there seems to be large inter-individual variability in the urinary excretion of DTZ and its metabolites.

Pregnancy & Breastfeeding use

Pregnancy: There are no adequate and controlled studies to date with diltiazem in pregnant women, and the drug should be used during pregnancy only when the potential benefits justify the possible risk to the fetus.

Lactation: Because diltiazem is distributed into milk, women receiving the drug should not breastfeed their infants; an alternative method of infant feeding should be used if diltiazem therapy is considered necessary in nursing women.

Contraindication

Cardizem SR Hydrochloride is contraindicated in pregnant women or those of child bearing potential, patients with Sick Sinus syndromes, patients with second or third degree AV block, patients with severe bradycardia and patients who demonstrated hypersensitivity to the drug.

Special Warning

Elderly and patients with impaired hepatic or renal function: The recommended starting dose is 60 mg twice daily. The heart rate should be measured regularly in these groups of patients and the dose should not be increased if the heart rate falls below 50 beats per minute.

Children: Not recommended.

Acute Overdose

Symptoms: Hypotension, bradycardia, heart block, heart failure, impaired conduction, ECG changes, arrhythmias, shock, altered mental status, cardiac arrest. 

Management: Symptomatic and supportive treatment. Gastric lavage and admin of activated charcoal may be initiated. Maintain appropriate ventilation. Charcoal hemoperfusion may be useful. Hypotension may be treated with fluids and vasopressor agents. Bradycardia, 2nd- or 3rd-degree AV block may be treated with IV atropine sulfate.

Storage Condition

Tablet/ capsule: Store at 25°C. Protect from light. 

Solution for injection: Store between 2-8°C. Do not freeze.

Innovators Monograph

Cardizem SR contains Diltiazem see full prescribing information from innovator Cardizem SR Monograph, Cardizem SR MSDS, Cardizem SR FDA label

FAQ

What is Cardizem SR used for?

Cardizem SR is a medicine used to treat high blood pressure. If you have high blood pressure, taking diltiazem helps to prevent future heart disease, heart attacks and strokes. Cardizem SR is also used to prevent chest pain caused by angina as well as Raynaud's phenomenon.

How safe is Cardizem SR?

Cardizem SR can be taken by adults and children aged 12 years and over. Cardizem SR is not suitable for some people. To make sure Cardizem SR is safe for you, tell your doctor if you: have had an allergic reaction to diltiazem or any other medicines in the past.

How does Cardizem SR work?

Cardizem SR works by lowering your blood pressure and makes it easier for your heart to pump blood around your body.

What are the common side effects of Cardizem SR?

Common side effects of Cardizem SR are include:

  • swollen hands, ankles or feet.
  • headaches.
  • feeling dizzy and lightheaded.
  • feeling tired, weak and generally unwell.
  • feeling hot (flushing) and redness of the skin.
  • itching or burning on the skin where you use the cream or ointment.
  • stomach pain, indigestion and constipation.


Is Cardizem SR safe during pregnancy?

Cardizem SR, are considered to be relatively safe.This drug may result in decreased contraction of the uterus and decreased uterine perfusion due to peripheral vasodilation. There are no controlled data in human pregnancy.

Is Cardizem SR safe during breastfeeding?

Based on limited data, amounts of Cardizem SR ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants.

Can I drink alcohol with Cardizem SR?

Yes, you can drink alcohol with Cardizem SR. However, it's best to not drink alcohol for a few days after starting Cardizem SR or if your doctor increases your dose.

Can I drive after taking Cardizem SR?

If Cardizem SR makes you feel dizzy, stop what you're doing and sit or lie down until you feel better. Do not drive, ride a bike or operate tools or machinery until you feel safe.

What is the best time to take Cardizem SR?

Extended-release Cardizem SR capsules should be taken on an empty stomach. Most other Cardizem SR formulations can be taken either with or without food; however, you should always check the instructions on the label.

How long does Cardizem SR take to work ?

Cardizem SR starts to work on the day you start taking it, but for high blood pressure and angina it may take a couple of weeks to work fully. If you're taking Cardizem SR for high blood pressure, you may not have had any symptoms before.

How quickly does Cardizem SR lower blood pressure?

The peak blood pressure-reducing and blood vessel-widening effects occur three to six hours after oral administration of Cardizem SR extended-release capsules, and at least 50% of the effect is still present after 24 hours.

Does Cardizem SR make me tired?

Cardizem SR can cause dizziness or fatigue when first started, or when the dose is increased.

How long does Cardizem SR stay in the system?

A single 360 mg dose of Cardizem SR results in detectable plasma levels within 3 to 4 hours and peak plasma levels between 11 and 18 hours; absorption occurs throughout the dosing interval. The apparent elimination half-life for Cardizem SR Tablets after single or multiple dosing is 6 to 9 hours.

Can I take Cardizem SR for a long time?

Cardizem SR can be safely given for long periods to patients with hypertension.

Is Cardizem SR hard on the liver?

Cardizem SR can cause mild increases in your liver function enzymes. In rare cases, it may cause sudden harm to your liver. This liver damage often goes away when you stop taking the medication.

How long should I take Cardizem SR?

It may take up to 2 weeks before you feel the full benefit of Cardizem SR. Continue to take Cardizem SR even if you feel well.

Is Cardizem SR hard on the kidneys?

barnd monotherapy was confirmed to be an effective antihypertensive agent. Although mean arterial pressure was reduced from 121 to 108 mm Hg, Cardizem SR had no overall effect on glomerular filtration rate, renal plasma blood flow, salt and water excretion, or body fluid composition.

Who should not take Cardizem SR?

May not be suitable for people with certain preexisting heart conditions, and in those with low blood pressure. Caution should be used when giving Cardizem SR to people with kidney or liver disease, because not many studies have been done in people with these conditions.

What happen if I take too much Cardizem SR?

If you take too much You could have dangerous levels of the drug in your body. If you take too much, you may have the following symptoms: low blood pressure. very slow heartbeat.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What should if I overdose?

Seek emergency medical attention  An overdose of diltiazem can be fatal. Overdose symptoms may include slow heartbeat, weakness, chest pain, shortness of breath, or fainting.

What happen If I suddenly stop taking Cardizem SR?

Stopping Cardizem SR may cause your blood pressure to rise and this may increase your risk of a heart attack or stroke.

Will Cardizem SR affect my fertility?

Cardizem SR may increase the risk of embryolethality.