Monotate

Approved Indications:

• Prophylaxis of Angina Pectoris:
• Indicated for the prevention of chronic stable angina due to coronary artery disease.
• Not intended for acute relief of anginal attacks.

Clinically Accepted Off-label Uses:

• Heart Failure (HFrEF):
• Used as part of combination vasodilator therapy (e.g., with Hydralazine) for patients with heart failure with reduced ejection fraction, particularly in those intolerant to ACE inhibitors/ARBs.
• Pulmonary Hypertension (Adjunct):
• Occasionally used off-label in select cases of pulmonary arterial hypertension for its vasodilatory effects.
• Esophageal Spasm:
• Off-label use in diffuse esophageal spasm or achalasia, due to smooth muscle relaxation properties.
• Raynaud's Phenomenon (severe cases):
• Used in selected cases to promote peripheral vasodilation.

Route of Administration:

• Oral (tablet or extended-release tablet)

Adult Dosage (Angina Prophylaxis):

• Immediate-Release Tablets:
• Initial dose: 5–20 mg twice daily
• Administer doses 7 hours apart to minimize nitrate tolerance
• Extended-Release Tablets:
• Initial dose: 30–60 mg once daily, taken in the morning
• Maintenance dose: May be increased up to 120 mg once daily as needed
• Swallow whole; do not crush or chew

Elderly:

• Start at the lower end of the dosage range due to increased sensitivity to hypotension

Renal Impairment:

• No specific adjustment required, but monitor blood pressure closely

Hepatic Impairment:

• Use with caution; potential for altered metabolism

Pediatric Use:

• Not recommended; safety and efficacy have not been established

Note:

• Not suitable for acute anginal episodes; sublingual nitroglycerin should be used in acute cases

Isosorbide Mononitrate is the active metabolite of Isosorbide Dinitrate, and it acts as a nitric oxide donor, leading to relaxation of vascular smooth muscle. This effect primarily results in venous dilation, which reduces preload (venous return to the heart), and to a lesser extent, arterial dilation, which reduces afterload. These actions collectively decrease myocardial oxygen demand, alleviate myocardial ischemia, and prevent anginal episodes. The drug does not affect inotropy or chronotropy, preserving cardiac output.

• Absorption:
• Rapidly and completely absorbed after oral administration
• Bioavailability: ~100% (no significant first-pass effect)
• Onset of Action:
• Immediate-release: ~30 minutes
• Extended-release: 1–2 hours
• Peak Plasma Time:
• Immediate-release: 1 hour
• Extended-release: 4–5 hours
• Distribution: Widely distributed; plasma protein binding <5%
• Metabolism:
• Metabolized in the liver to inactive compounds
• Not dependent on cytochrome P450 enzymes
• Half-life:
• ~5 hours (immediate-release); may be prolonged in hepatic dysfunction
• Elimination:
• Primarily renal (as inactive metabolites)

Pregnancy:

• FDA Classification: Not assigned (previously Category C)
• Use in Pregnancy:
• No adequate human studies; animal studies show potential fetal harm
• Should only be used if potential benefit outweighs risk

Lactation:

• Unknown if excreted in human milk
• Use with caution; consider risk-benefit if breastfeeding

Recommendation:

• Monitor infant for signs of hypotension or cyanosis if used during breastfeeding
• Avoid if safer alternatives are available

• Primary Class: Nitrate Vasodilator
• Subclass: Long-acting Organic Nitrate
• Pharmacologic Category: Antianginal Agent

• Known hypersensitivity to isosorbide mononitrate or any nitrate
• Concomitant use with PDE-5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)
• Acute circulatory failure or shock
• Severe hypotension or uncorrected hypovolemia
• Increased intracranial pressure
• Severe anemia

• Hypotension and Syncope: Especially in volume-depleted or elderly patients
• Headache: Common and may be severe; may improve with continued use
• Tolerance (tachyphylaxis):
• May develop with continuous exposure
• Requires a nitrate-free interval of 10–14 hours daily to maintain efficacy
• Worsening of Angina During Drug-Free Interval: Rare but possible
• Use in Hypertrophic Cardiomyopathy: May worsen outflow obstruction
• Alcohol Use: May enhance hypotensive effects

Monitoring Parameters:

• Blood pressure (especially postural)
• Heart rate
• Frequency of angina episodes

Common Side Effects:

• Central Nervous System: Headache, dizziness, lightheadedness
• Cardiovascular: Hypotension, tachycardia, palpitations
• Gastrointestinal: Nausea, vomiting
• General: Fatigue, flushing

Serious or Rare Side Effects:

• Severe hypotension
• Syncope
• Paradoxical bradycardia
• Worsening of angina (due to nitrate-free interval)
• Rash or allergic reactions (rare)

Timing & Severity:

• Headaches and flushing most common in the first few days of therapy
• Severity often dose-dependent and may diminish with continued use

Major Drug Interactions:

• PDE-5 Inhibitors (e.g., Sildenafil, Tadalafil):
• Contraindicated due to severe risk of hypotension, syncope, or myocardial infarction
• Alcohol:
• Increases risk of orthostatic hypotension and dizziness
• Calcium Channel Blockers & Beta-Blockers:
• May enhance hypotensive effects; monitor closely
• Other Antihypertensives or Diuretics:
• Additive effects on blood pressure lowering

Enzyme Systems:

• Does not involve significant CYP450 metabolism
• Low potential for hepatic enzyme interaction

• Latest Clinical Guidelines:
• Remain recommended as first-line prophylaxis for chronic stable angina
• Nitrate tolerance continues to be addressed in guidelines with emphasis on dosing strategies to avoid tolerance
• No new FDA label changes or safety warnings have been introduced in the last 12 months.

• Standard Storage Temperature:
• Store at 20°C to 25°C (68°F to 77°F)
• Allowable excursions between 15°C and 30°C
• Humidity & Light:
• Protect from moisture and direct sunlight
• Handling Precautions:
• Keep in tightly closed containers
• Do not crush or split extended-release tablets
• Reconstitution or Refrigeration:
• Not required
• No special preparation needed