MONOKET
Clinical safety rating
cautionComprehensive clinical and safety monograph for MONOKET (MONOKET).
Isosorbide mononitrate is a vasodilator that relaxes vascular smooth muscle via the release of nitric oxide (NO), which activates guanylate cyclase, increasing intracellular cGMP. This leads to venous and arterial dilation, reducing preload and afterload, thereby decreasing myocardial oxygen demand.
| Metabolism | Primarily hepatic metabolism via denitration; no significant cytochrome P450 involvement. Metabolites include isosorbide and isosorbide-2-mononitrate (active). |
| Excretion | Renal: approximately 98% of the dose is excreted in urine as metabolites (isosorbide mononitrate and its glucuronide conjugates); fecal excretion is minimal (<2%). |
| Half-life | Terminal elimination half-life is approximately 5 hours (range 4–6 hours) for isosorbide mononitrate, consistent with a sustained duration suitable for once-daily dosing. |
| Protein binding | Isosorbide mononitrate is less than 5% bound to plasma proteins. |
| Volume of Distribution | Volume of distribution is approximately 0.6 L/kg (range 0.5–0.7 L/kg), indicating distribution primarily into total body water and well-perfused tissues. |
| Bioavailability | Oral: nearly 100% (complete absorption with no significant first-pass metabolism, as isosorbide mononitrate is the active metabolite of isosorbide dinitrate). |
| Onset of Action | Oral: measurable hemodynamic effects (e.g., reduction in preload) begin within 30–60 minutes after ingestion. |
| Duration of Action | Oral: Hemodynamic effects (venodilation, reduced preload) persist for approximately 10–12 hours with immediate-release formulations; extended-release preparations provide effect for up to 12–14 hours, permitting once-daily dosing. |
| Molecular Weight | 191.14 |
20 mg orally twice daily, 7 hours apart (e.g., 8 AM and 3 PM) to provide a nitrate-free interval.
| Dosage form | TABLET |
| Renal impairment | No adjustment required for mild to moderate renal impairment. For severe renal impairment (eGFR <30 mL/min/1.73 m²), use with caution and monitor for hypotension. |
| Liver impairment | No specific adjustment for Child-Pugh A or B. For Child-Pugh C, dose reduction is recommended; initial dose 10 mg once daily and titrate carefully. |
| Pediatric use | Safety and efficacy have not been established in pediatric patients (age <18 years). |
| Geriatric use | Start at the low end of the dosing range (20 mg once daily) due to increased sensitivity to hypotension and fall risk; titrate slowly. |
| 1st trimester | Use only if clearly needed; no adequate studies in pregnant women. Animal studies show risk. |
| 2nd trimester | Use only if clearly needed; may cause fetal harm due to hemodynamic effects. |
| 3rd trimester | Use only if clearly needed; may cause fetal bradycardia and other effects. |
Clinical note
Comprehensive clinical and safety monograph for MONOKET (MONOKET).
| Placental transfer | Crosses placenta; degree not well quantified but likely significant due to low molecular weight. |
| Breastfeeding | Excreted into breast milk in low amounts; not expected to cause adverse effects in infants. Caution with high doses or prolonged use. |
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | Isosorbide mononitrate (MONOKET) is a nitrate vasodilator. Animal studies show no evidence of teratogenicity. There are no adequate and well-controlled studies in pregnant women. However, nitrates can cause uterine relaxation, potentially affecting labor. Use only if clearly needed, with caution in the third trimester due to risk of maternal hypotension and reduced placental perfusion. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate, especially during dose initiation and titration. Assess fetal heart rate if used near term due to potential uterine relaxation. Monitor for signs of maternal hypotension and reflex tachycardia. |
| Fertility Effects | No fertility studies with isosorbide mononitrate in humans. Animal studies did not show impaired fertility at clinically relevant doses. No known effect on human fertility. |
■ FDA Black Box Warning
NOT for use in acute myocardial infarction or acute episodes of angina. Do not use with phosphodiesterase-5 (PDE5) inhibitors (e.g., sildenafil, tadalafil) due to risk of severe hypotension.
| Serious Effects |
Hypersensitivity to isosorbide mononitrate or any componentConcomitant use with phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil)Severe hypotension (systolic blood pressure < 90 mmHg)Acute myocardial infarction with low filling pressuresCardiogenic shockHypertrophic obstructive cardiomyopathyConstrictive pericarditisCardiac tamponadeSevere aortic stenosisIncreased intracranial pressure
| Precautions | Hypotension, especially during initial dosing or dose escalation; tolerance development with prolonged use (intermittent dosing required); exacerbation of angina upon abrupt withdrawal; use with caution in patients with volume depletion, hypotension, or hypertrophic cardiomyopathy. |
| Food/Dietary | No significant food interactions. However, alcohol should be avoided due to additive vasodilation and hypotension. |
| Clinical Pearls | Monoket (isosorbide mononitrate) is a long-acting nitrate used for angina prophylaxis, not acute attacks. Tolerance develops with sustained use; use a daily nitrate-free interval of 10-14 hours. Avoid in hypertrophic cardiomyopathy, aortic stenosis, and with phosphodiesterase-5 inhibitors (risk of severe hypotension). Headache is common initially but often subsides. |
| Patient Advice | Take this medication exactly as prescribed to prevent angina attacks, not to relieve an attack already occurring. · Do not take with erectile dysfunction drugs (like sildenafil, tadalafil) — can cause dangerous blood pressure drop. · Headaches may occur initially but often improve with continued use; consult your doctor if persistent. · Avoid alcohol as it may worsen side effects like dizziness and hypotension. · If you miss a dose, skip it; do not double the next dose. Maintain a consistent dosing schedule with a nitrate-free period. |
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