Cardizem-SR120 mg

Cardizem-SR is a non-dihydropyridine calcium channel blocker indicated for the following conditions, classified by strength of evidence:

Established / FDA-approved uses

• Hypertension: Extended-release formulations of Cardizem-SR are indicated for the management of hypertension, alone or in combination with other antihypertensive agents.
• Chronic stable angina pectoris: Cardizem-SR is indicated for the management of chronic stable angina.
• Vasospastic (Prinzmetal's) angina: Cardizem-SR is indicated for the management of angina due to coronary artery spasm.
• Rate control in atrial fibrillation/atrial flutter: Intravenous Cardizem-SR is indicated for temporary control of rapid ventricular rate in atrial fibrillation or atrial flutter; oral Cardizem-SR is used for chronic rate control once the patient is stabilized.

Guideline-supported / adjunct uses

• As an adjunct to conventional antianginal therapy (e.g. nitrates) when a single agent does not provide adequate symptom control.

Use of Cardizem-SR should always be individualized and guided by a physician's assessment.

Each tablet/capsule of Diltiazem Hydrochloride contains diltiazem hydrochloride as the active pharmaceutical ingredient. Diltiazem Hydrochloride is available in several dosage forms and strengths, including immediate-release tablets (30 mg, 60 mg), sustained-release/extended-release tablets or capsules (90 mg, 120 mg, 180 mg, 240 mg, 300 mg), and an intravenous injection form for hospital use. Exact strengths and available brands vary by market; consult the product label for the specific formulation dispensed.

Cardizem-SR is a non-dihydropyridine calcium channel blocker belonging to the benzothiazepine class. It works by inhibiting the influx of calcium ions into cardiac and vascular smooth muscle cells, resulting in coronary and peripheral vasodilation, reduced myocardial oxygen demand, and slowed conduction through the sinoatrial (SA) and atrioventricular (AV) nodes.

Cardizem-SR is widely used in the long-term management of hypertension and chronic angina, and for controlling fast heart rates associated with atrial fibrillation or atrial flutter. It is available as immediate-release and extended/sustained-release oral formulations, as well as an intravenous formulation for acute in-hospital rate control.

Cardizem-SR belongs to the following therapeutic classes:

• Calcium channel blocker (non-dihydropyridine, benzothiazepine derivative)
• Antianginal agent
• Antihypertensive agent
• Antiarrhythmic agent (used for rate control, not classified among the traditional Vaughan-Williams antiarrhythmic classes but functionally a Class IV antiarrhythmic)

Mechanism of action: Diltiazem Hydrochloride inhibits the transmembrane influx of calcium ions during depolarization of cardiac and vascular smooth muscle. This produces:

• Vasodilation: Relaxation of coronary and peripheral vascular smooth muscle, reducing peripheral vascular resistance and increasing coronary blood flow.
• Reduced myocardial oxygen demand: Through afterload reduction and mild negative inotropy.
• Slowed AV/SA nodal conduction: Diltiazem Hydrochloride slows conduction through the SA and AV nodes, decreasing ventricular response rate in atrial fibrillation/flutter and terminating re-entrant supraventricular tachycardias involving the AV node.

Pharmacokinetics: Diltiazem Hydrochloride is well absorbed orally, with peak plasma concentrations reached within 30 minutes to a few hours depending on formulation (immediate- vs extended-release). It undergoes extensive first-pass hepatic metabolism (primarily via CYP3A4) to form active and inactive metabolites, is highly protein-bound (approximately 70-80%), and is eliminated mainly via biliary/fecal excretion with a smaller renal component. Elimination half-life is approximately 3.5-9 hours for immediate-release forms, longer for extended-release formulations.

Oral Cardizem-SR tablets/capsules should be swallowed whole with water. Extended/sustained-release formulations must not be crushed, chewed, or split, as this can cause rapid release of the drug and increase the risk of adverse effects. Cardizem-SR may be taken with or without food, but should be taken consistently the same way each day. Intravenous Cardizem-SR is administered only in a hospital or clinical setting under continuous cardiac monitoring by trained healthcare professionals.

Cardizem-SR has several clinically significant drug interactions:

• Beta-blockers: Concomitant use, especially intravenous beta-blockers with intravenous Cardizem-SR, can cause additive bradycardia, AV block, and depressed cardiac contractility; this combination is contraindicated for IV-IV use and requires caution otherwise.
• Digoxin: Cardizem-SR can increase serum digoxin concentrations; monitoring of digoxin levels is recommended.
• CYP3A4 substrates: Cardizem-SR is a moderate inhibitor of CYP3A4 and can increase plasma levels of drugs metabolized by this enzyme, including certain statins (e.g. simvastatin, lovastatin), cyclosporine, midazolam and other benzodiazepines, and some other drugs; dose adjustment or avoidance of the interacting drug may be required.
• Other antihypertensive or negative chronotropic agents: Additive hypotensive or bradycardic effects may occur with other blood-pressure-lowering drugs.
• Grapefruit juice: May increase plasma concentrations of Cardizem-SR; avoid concurrent consumption.
• CYP3A4 inducers (e.g. rifampin): May reduce the effectiveness of Cardizem-SR by increasing its metabolism.

Common and serious side effects reported with Cardizem-SR include:

Common

• Peripheral edema (swelling of the ankles/legs)
• Headache
• Dizziness or lightheadedness
• Bradycardia (slow heart rate)
• Constipation
• Flushing
• Nausea

Less common but serious

• Hypotension
• AV block (including first-, second-, or third-degree)
• Worsening of heart failure symptoms
• Elevated liver enzymes / rare hepatic injury
• Skin reactions, including rare severe reactions

Patients should seek prompt medical attention for symptoms such as fainting, severe dizziness, very slow heartbeat, or signs of an allergic reaction.

Pregnancy: There are no adequate and well-controlled studies of Cardizem-SR in pregnant women. Cardizem-SR should be used during pregnancy only if the potential benefit to the mother clearly justifies the potential risk to the fetus. A physician should be consulted before use in pregnancy.

Lactation: Cardizem-SR is excreted into human breast milk. Because of the potential for adverse effects in nursing infants, a decision should be made whether to discontinue breastfeeding or discontinue Cardizem-SR, taking into account the importance of the drug to the mother, and only under medical supervision.

The following precautions apply to the use of Cardizem-SR:

• Cardiac conduction abnormalities: Cardizem-SR slows AV nodal conduction and may rarely cause first-, second-, or third-degree AV block or symptomatic bradycardia; use with caution in patients with pre-existing conduction abnormalities.
• Heart failure: Use with caution in patients with impaired left ventricular function due to the drug's negative inotropic effect.
• Hypotension: May cause symptomatic low blood pressure, particularly when combined with other antihypertensive drugs.
• Hepatic impairment: Cardizem-SR is extensively metabolized in the liver; use with caution and reduced starting dose in hepatic impairment, with monitoring of liver function periodically.
• Renal impairment: Use with caution; clinical monitoring is advised.
• Acute alcohol intoxication and abrupt discontinuation: Avoid abrupt discontinuation; dose should be tapered under medical supervision where feasible.
• Skin reactions: Discontinue if a dermatologic reaction occurs and persists.

See Contraindications for absolute restrictions on the use of Cardizem-SR.

Overdose of Cardizem-SR can cause severe hypotension, marked bradycardia, AV block, and cardiogenic shock, which may be life-threatening. In case of suspected overdose, seek immediate emergency medical attention or contact a poison control center right away. Do not attempt to manage an overdose at home. Hospital-based supportive care (cardiac monitoring, and treatment directed at hemodynamic and rhythm abnormalities as determined by treating physicians) is required.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Pediatric use: Safety and efficacy of Cardizem-SR in pediatric patients have not been established. Use in children is generally not recommended outside of specialist supervision.

Elderly: Elderly patients may have reduced clearance of Cardizem-SR and may be more sensitive to its hypotensive and bradycardic effects; a lower starting dose with careful titration and monitoring is recommended.

Hepatic/renal impairment: See Dosage and Administration and Precautions and Warnings for dose adjustment guidance.

Cardizem-SR is typically used as a long-term, ongoing therapy for chronic conditions such as hypertension and chronic stable angina, with duration determined by the treating physician based on response and tolerability. For acute intravenous use in atrial fibrillation/flutter rate control, treatment duration is short-term and limited to the hospital setting until the patient is transitioned to oral therapy or the arrhythmia is otherwise managed. Patients should not stop Cardizem-SR abruptly without consulting their physician.

Calcium channel blocker (non-dihydropyridine); Antianginal agent; Antihypertensive agent; Antiarrhythmic (rate-control) agent

Diltiazem Hydrochloride blocks the influx of calcium ions through voltage-gated L-type calcium channels in cardiac and vascular smooth muscle cells. This relaxes vascular smooth muscle (producing coronary and peripheral vasodilation), reduces myocardial contractility and oxygen demand, and slows conduction through the SA and AV nodes, thereby reducing heart rate and controlling ventricular response in supraventricular tachyarrhythmias.

C

The safety and efficacy of Cardizem-SR in pediatric patients have not been established. Cardizem-SR is generally not recommended for use in children outside of specialist cardiology guidance, and should only be considered when no suitable alternative exists and under close medical supervision.