Monocard-SR50 mg

Established (FDA-approved) Use

Monocard-SR is indicated for the prevention of angina pectoris due to coronary artery disease. It is used for long-term prophylaxis of exertional angina and is intended to reduce the frequency of anginal attacks with regular, scheduled dosing.

Important Limitation of Use

Monocard-SR is not intended to abort an acute anginal attack because its onset of action is too slow for that purpose; a fast-acting sublingual nitrate should be used for acute episodes.

Not Established / Not Recommended

Monocard-SR is not approved for acute coronary syndromes, acute myocardial infarction, or acute decompensated heart failure, and should not be relied upon for these indications.

Monocard-SR is a long-acting organic nitrate vasodilator used in the long-term management of coronary artery disease to prevent episodes of angina pectoris. It is the active metabolite of isosorbide dinitrate and is available in immediate-release and extended-release oral tablet forms.

Monocard-SR works by relaxing vascular smooth muscle, predominantly in the venous system, which reduces the workload of the heart and lowers myocardial oxygen demand.

Long-acting organic nitrate vasodilator; Anti-anginal agent

Pharmacodynamics

Isosorbide Mononitrate is metabolized to release nitric oxide (NO), which activates guanylate cyclase in vascular smooth muscle, increasing intracellular cyclic GMP (cGMP). This causes relaxation of vascular smooth muscle, with a predominant effect on venous capacitance vessels and a lesser effect on arterioles. The resulting venodilation reduces venous return (preload), decreasing left ventricular wall stress and myocardial oxygen demand. At higher doses, mild arterial dilation also reduces afterload and modestly reduces coronary vascular resistance, improving oxygen supply to ischemic myocardium.

Pharmacokinetics

Isosorbide Mononitrate does not undergo first-pass hepatic metabolism (unlike isosorbide dinitrate), giving it essentially 100% oral bioavailability and more predictable plasma levels. It is metabolized in the liver mainly by denitration and glucuronidation, and metabolites are excreted primarily in the urine. Immediate-release tablets have an onset within about 30-60 minutes; extended-release formulations provide sustained plasma levels over approximately 24 hours.

• Monocard-SR tablets may be taken with or without food.
• Extended-release tablets must be swallowed whole with water; do not crush, chew, or break them.
• Take the two immediate-release doses at the prescribed times (approximately 7 hours apart) to preserve a nitrate-free interval; do not take a third dose later in the day.
• Do not stop taking Monocard-SR suddenly after prolonged high-dose therapy without medical advice (see Precautions and Warnings).

Contraindicated Combinations

Concomitant use of Monocard-SR with phosphodiesterase-5 (PDE5) inhibitors (sildenafil, tadalafil, vardenafil) or with the soluble guanylate cyclase stimulator riociguat can cause severe, potentially life-threatening hypotension due to additive nitric oxide/cGMP-mediated vasodilation. This combination must be avoided (see Contraindications).

Other Clinically Significant Interactions

• Alcohol: additive hypotensive effect; may cause severe dizziness or fainting.
• Antihypertensives, other vasodilators, and calcium channel blockers: additive blood-pressure-lowering effect; dose adjustment or closer monitoring may be needed.
• Other nitrates: additive hypotension; concurrent use of multiple nitrate products is generally avoided.

Very common: Headache is very common when starting Monocard-SR, particularly at the beginning of therapy; it often diminishes with continued regular use and may respond to a mild analgesic.

Common: Dizziness, lightheadedness, flushing, orthostatic (postural) hypotension, reflex tachycardia, nausea.

Less common/rare: Syncope (fainting), especially after the first few doses or with dose increases; rash; and, rarely with very high doses, methemoglobinemia.

Pregnancy: Data on the use of Monocard-SR in human pregnancy are limited. Monocard-SR should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the fetus. A physician should be consulted before use in pregnancy.

Lactation: It is not known whether Monocard-SR is excreted in human breast milk. Caution is advised, and a physician should be consulted before use while breastfeeding, weighing the benefits of treatment against potential risk to the infant.

• Tolerance: Continuous, around-the-clock use of Monocard-SR leads to development of tolerance with loss of anti-anginal effect. Dosing regimens are designed to include a daily nitrate-free interval (typically overnight) to help maintain efficacy.
• Rebound angina on abrupt discontinuation: Abruptly stopping Monocard-SR after prolonged, high-dose therapy may precipitate rebound angina. If long-term high-dose therapy is being discontinued, the dose should be tapered gradually under medical supervision.
• Hypotension: Monocard-SR can cause significant hypotension, particularly at the start of therapy or with dose increases, especially in volume-depleted patients, the elderly, or those on other blood-pressure-lowering drugs. Caution when standing up, especially after alcohol.
• Not for acute attacks: Monocard-SR is not suitable for relieving an acute anginal attack in progress; a fast-acting nitrate should be used for that purpose.
• Increased intraocular/intracranial pressure: Use with caution in patients with raised intracranial pressure or narrow-angle glaucoma tendencies.
• Do not combine with PDE5 inhibitors or riociguat (see Contraindications and Interactions).

Overdose with Monocard-SR may cause severe hypotension, reflex tachycardia, throbbing headache, dizziness, flushing, weakness, syncope, and, rarely with very large doses, methemoglobinemia (presenting as cyanosis and shortness of breath despite adequate oxygenation). Seek immediate medical attention or contact a poison control center/emergency services if overdose is suspected. Management is supportive and should be carried out under medical supervision (e.g., positioning to improve venous return, intravenous fluids for hypotension, and specific treatment such as methylene blue for clinically significant methemoglobinemia); do not attempt specific home treatment.

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

Elderly: May be more sensitive to the hypotensive effects of Monocard-SR; start at the lower end of the dosing range and monitor closely.

Renal impairment: No well-established dose adjustment; use with routine monitoring.

Hepatic impairment: Use with caution; bioavailability may be increased, raising the risk of hypotension.

Pediatric patients: Safety and efficacy have not been established (see Pediatric Uses).

Pregnancy and lactation: See Pregnancy and Lactation section.

Monocard-SR is generally used as long-term, ongoing prophylactic therapy for chronic stable angina, with treatment duration determined by the prescribing physician based on continued need for anginal prevention and response to therapy. Periodic clinical review is recommended. If long-term high-dose therapy is to be stopped, the dose should be tapered gradually rather than stopped abruptly (see Precautions and Warnings).

Nitrates / Anti-anginal agents / Vasodilators

Isosorbide Mononitrate is denitrated in tissues to release nitric oxide (NO), which stimulates soluble guanylate cyclase in vascular smooth muscle cells, increasing cyclic guanosine monophosphate (cGMP). Elevated cGMP triggers smooth muscle relaxation, producing predominant venodilation (reducing cardiac preload) and, at higher doses, some arterial dilation (reducing afterload). The net effect is decreased myocardial oxygen demand and improved myocardial oxygen supply, which relieves and helps prevent angina.

C

The safety and efficacy of Monocard-SR in pediatric patients have not been established. Monocard-SR is therefore not recommended for use in children and adolescents outside of specialist supervision.