MONOKET

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MONOKET (MONOKET).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for MONOKET (MONOKET).

Breastfeeding	It is not known whether isosorbide mononitrate is excreted into human breast milk. The M/P ratio is not available. Because many drugs are excreted in human milk, caution should be exercised when MONOKET is administered to a nursing woman. Consider the importance of the drug to the mother and potential risk to the infant.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

Concomitant use with PDE5 inhibitors (e.g., sildenafil, tadalafil, vardenafil); severe hypotension (systolic BP <90 mmHg); hypovolemia; increased intracranial pressure; acute myocardial infarction with low filling pressures; severe anemia.

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

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MONOKET

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MONOKET (MONOKET).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for MONOKET (MONOKET).

Breastfeeding	It is not known whether isosorbide mononitrate is excreted into human breast milk. The M/P ratio is not available. Because many drugs are excreted in human milk, caution should be exercised when MONOKET is administered to a nursing woman. Consider the importance of the drug to the mother and potential risk to the infant.
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.

Warnings & precautions

■ 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.