Nimodi

Approved Indications:

• Prevention of ischemic neurological deficits following aneurysmal subarachnoid hemorrhage (SAH)
  Specifically indicated to reduce the incidence and severity of delayed cerebral ischemia caused by cerebral vasospasm after SAH due to ruptured intracranial aneurysms.

Clinically Accepted Off-Label Uses:

• Prevention of cerebral vasospasm following traumatic SAH (not caused by aneurysm)
• Adjunctive therapy in acute ischemic stroke to improve cerebral blood flow (investigational)
• Migraine prophylaxis (limited clinical evidence)

Route of Administration: Oral only (capsules or oral solution via nasogastric tube)
Do not administer intravenously — this is contraindicated and can be fatal.

Adults:

• Dose: 60 mg orally every 4 hours (i.e., 360 mg per day)
• Duration: For 21 consecutive days
• Initiation Timing: Start within 96 hours (4 days) of the onset of SAH

Elderly:

• No dosage adjustment necessary, but monitor blood pressure closely due to heightened sensitivity to hypotension.

Pediatrics:

• Safety and efficacy have not been established in children.

Renal Impairment:

• No specific dose adjustment established; use with caution and monitor for hypotension.

Hepatic Impairment:

• Mild to moderate: Use cautiously, monitor blood pressure and liver function.
• Severe impairment: Contraindicated due to increased plasma levels and higher risk of hypotension.

Nasogastric Administration:

• Oral solution may be withdrawn with a syringe and administered through a nasogastric or gastric tube.
• Rinse the tube with 30 mL of normal saline afterward.

Nimodipine is a dihydropyridine calcium channel blocker that selectively inhibits L-type voltage-gated calcium channels in vascular smooth muscle. It exhibits a high affinity for cerebral blood vessels due to its lipophilic nature. By blocking calcium influx into vascular smooth muscle cells, nimodipine promotes vasodilation, particularly in cerebral arteries, which helps counteract cerebral vasospasm and enhances blood flow to ischemic brain tissues. This mechanism reduces the risk of delayed ischemic deficits following aneurysmal SAH.

• Absorption: Rapidly absorbed orally; peak concentration in 0.5–1 hour
• Bioavailability: Approximately 13% due to significant first-pass metabolism
• Distribution: Highly lipophilic; ~95% bound to plasma proteins
• Metabolism: Extensively metabolized in the liver via CYP3A4 enzymes
• Half-life: ~8–9 hours
• Excretion: Predominantly via feces (60–80%); <5% excreted in urine
• Steady-state: Reached within 2–3 days of consistent dosing

Pregnancy:

• FDA Pregnancy Category C
• Animal studies have shown fetal harm; no adequate data in humans.
• Use only if the potential benefit justifies the potential risk.

Lactation:

• It is unknown whether nimodipine is excreted into human milk.
• Caution is advised; consider discontinuing breastfeeding or the drug, depending on the importance to the mother.

• Class: Calcium Channel Blocker
• Subclass: Dihydropyridine, Cerebroselective

• Known hypersensitivity to nimodipine or formulation excipients
• Severe hepatic impairment
• Intravenous administration (contraindicated; black box warning)
• Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, clarithromycin)

• Black Box Warning: Intravenous administration can cause serious adverse effects, including death, cardiac arrest, and profound hypotension.
• Hypotension Risk: Monitor closely, especially in elderly, hepatic-impaired, or polypharmacy patients.
• CYP3A4 Interactions: Avoid concurrent use with strong CYP3A4 inhibitors or inducers.
• Hepatic Monitoring: In patients with hepatic impairment, use with extreme caution.
• Neurological Monitoring: Assess regularly for signs of increased intracranial pressure or neurologic deterioration.

Common Adverse Effects:

• Cardiovascular: Hypotension, flushing, bradycardia, tachycardia
• Neurologic: Dizziness, headache, somnolence
• Gastrointestinal: Nausea, abdominal discomfort

Serious or Rare Effects:

• Severe hypotension and syncope
• Elevated hepatic enzymes
• Allergic reactions (rash, anaphylaxis – rare)
• Gastrointestinal bleeding (rare)
• Arrhythmias in susceptible patients

Major Interactions:

• CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin, ritonavir): Increase nimodipine levels → risk of severe hypotension → avoid
• CYP3A4 Inducers (e.g., rifampin, carbamazepine, phenytoin): Reduce nimodipine levels → avoid
• Grapefruit Juice: Inhibits CYP3A4 → increases serum levels → avoid
• Beta-blockers and antihypertensives: Additive hypotensive effects

Metabolism Note: Nimodipine is metabolized almost exclusively via CYP3A4; caution with any co-administered drugs affecting this enzyme.

• FDA Reminder (2024): Reinforced the black box warning against IV use due to continued misuse reports.
• American Heart Association (AHA) 2023 Guidelines: Nimodipine remains the only recommended drug for preventing delayed cerebral ischemia after aneurysmal SAH.
• European Stroke Organisation (ESO): Continues recommending nimodipine for 21 days post-SAH to reduce morbidity and mortality.

• Temperature: Store between 20°C and 25°C (68°F to 77°F); brief excursions permitted between 15°C and 30°C
• Humidity: Store in a dry environment
• Light Protection: Protect from light; store in original container
• Handling Instructions:
• Do not refrigerate or freeze
• Capsules must be swallowed whole; do not crush or chew
• Use oral solution only via oral or nasogastric administration (never intravenous)