Isosorbide Mononitrate

Today's med: Isosorbide Mononitrate (eye soe SOR bide mon oh NYE trate) 
(brand names: Imdur, Ismo, Monoket [DSC] Index term: ISMN)

Drug Class: Antianginal agent, Nitrate Vasodilator

Other Drugs in this class: Isosorbide,Isosorbide dinitrate, Nitroglycerin

Indications: Prevention of angina pectoris

Action: Nitroglycerin and other nitrates form free radical nitric oxide. In smooth muscle, nitric oxide activates guanylate cyclase which increases guanosine 3’5’ monophosphate (cGMP) leading to dephosphorylation of myosin light chains and smooth muscle relaxation. Produces a vasodilator effect on the peripheral veins and arteries with more prominent effects on the veins. Primarily reduces cardiac oxygen demand by decreasing preload (left ventricular end-diastolic pressure); may modestly reduce afterload; dilates coronary arteries and improves collateral flow to ischemic regions.

Absorption

Nearly complete and low intersubject variability in its pharmacokinetic parameters and plasma concentrations

Contraindications: Hypersensitivity to isosorbide mononitrate or any component of the formulation; hypersensitivity to organic nitrates; concurrent use with phosphodiesterase-5 (PDE-5) inhibitors (sildenafil, tadalafil, or vardenafil).

Adverse Effects: >10%: Central nervous system: Headache (13% to 35%)

1% to 10%:

Cardiovascular: Angina (≤2%), flushing (≤2%)

Central nervous system: Dizziness (≤4%), fatigue (≤4%), pain (≤4%), emotional lability (≤2%)

Dermatologic: Pruritus (≤2%), rash (≤2%)

Gastrointestinal: Nausea (≤3%), abdominal pain (≤2%), diarrhea (≤2%)

Respiratory: Upper respiratory infection (≤4%), cough increased (≤2%)

Miscellaneous: Allergic reaction (≤2%)

<1% (Limited to important or life-threatening): Apoplexy, arrhythmia, bradycardia, dyspnea, edema, hyper-/hypotension, methemoglobinemia (rare, overdose), MI, orthostatic hypotension, pallor, palpitation, paresthesia, tachycardia

Standard Dosing: Oral: Adults: Regular release tablet: Initial: 5-20 mg twice daily with the 2 doses given 7 hours apart (eg, 8 AM and 3 PM) to decrease tolerance development; patients initiating therapy with 5 mg twice daily (eg, small stature) should be titrated up to 10 mg twice daily in first 2-3 days.

Extended release tablet: Initial: 30-60 mg given once daily in the morning; titrate upward as needed, giving at least 3 days between increases; maximum daily single dose: 240 mg

Elderly: Start with lowest recommended adult dose.

Administration

Do not administer around-the-clock. Immediate release tablet should be scheduled twice daily with doses 7 hours apart (8 AM and 3 PM); extended release tablet may be administered once daily in the morning upon rising with a half-glassful of fluid and should not be chewed or crushed.

Note: Tolerance to nitrate effects develops with chronic exposure. Dose escalation does not overcome this effect. Tolerance can only be overcome by short periods of nitrate absence from the body. Short periods of nitrate withdrawal may help minimize tolerance. Recommended twice daily dosage regimens incorporate this interval. Administer sustained release tablet once daily in the morning.

Warnings/Precautions:

• Hypotension/bradycardia: Severe hypotension can occur; paradoxical bradycardia and increased angina pectoris can accompany hypotension. Orthostatic hypotension can also occur; ethanol can accentuate this. Use with caution in volume depletion and moderate hypotension, and with extreme caution with inferior wall MI and suspected right ventricular infarctions.

• Intracranial pressure increased: Nitrates may precipitate or aggravate increased intracranial pressure and subsequently may worsen clinical outcomes in patients with neurologic injury (eg, intracranial hemorrhage, traumatic brain injury).

• Tolerance: Appropriate dosing intervals are needed to minimize tolerance development. Tolerance can only be overcome by short periods of nitrate absence from the body. Dose escalation does not overcome this effect.

Pregnancy Risk Factor: B/C 

Drug interactions: Link: http://www.drugs.com/drug-interactions/isosorbide-mononitrate.html

A total of 265 drugs (1233 brand and generic names) are known to interact with isosorbide mononitrate.

• 11 major drug interactions (26 brand and generic names)
• 250 moderate drug interactions (1195 brand and generic names)
• 4 minor drug interactions (12 brand and generic names)

Show all medications in the database that may interact with isosorbide mononitrate.

CYP3A4 Inducers: May increase the metabolism of CYP3A4 Substrates. 

Major risk: post MI, hypertrophic cardiomyopathy, combined with hemodialysis and head injury/intracranial pressure: AVOID

"I sooooooo sore" (in my heart), gimmy some nitro!

(Disclaimer....I sooo sorry about this one!)