Nimotop

Nimotop (nimodipine) is a calcium channel blocker specifically formulated for the improvement of neurological outcomes by reducing the incidence and severity of ischemic deficits in patients with subarachnoid hemorrhage (SAH) from ruptured congenital intracranial aneurysms. Its cerebroselective mechanism targets cerebral arteries, offering a critical neuroprotective strategy during a vulnerable clinical period. Administered orally, it represents a cornerstone of post-SAH medical management, supported by extensive clinical evidence demonstrating its efficacy in preserving cognitive and motor function when initiated within 96 hours of the hemorrhage.

Features

• Active pharmaceutical ingredient: Nimodipine 30 mg
• Pharmaceutical form: Soft gelatin capsules
• Pharmacotherapeutic group: Selective cerebral calcium channel blocker; class IV antiarrhythmic
• High lipophilicity, facilitating superior blood-brain barrier penetration
• Cerebroselective vasodilation, with preferential activity on cerebral arteries over peripheral vasculature
• Dosing regimen: One 30 mg capsule every 4 hours for 21 consecutive days
• Manufactured under strict GMP (Good Manufacturing Practice) standards

Benefits

• Significantly reduces the risk of cerebral infarction and severe neurological deficits secondary to vasospasm.
• Improves overall neurological outcome and functional recovery following a subarachnoid hemorrhage.
• Helps preserve cognitive functions, including memory and executive function, by mitigating delayed cerebral ischemia.
• Supported by robust clinical trial data establishing a clear mortality and morbidity benefit.
• Oral administration facilitates continued treatment in both inpatient and outpatient settings.
• Targeted mechanism minimizes significant systemic hemodynamic effects compared to non-selective calcium channel blockers.

Common use

Nimotop is exclusively indicated for the improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in patients with subarachnoid hemorrhage (SAH) from ruptured congenital intracranial aneurysms who are in good neurological condition post-ictus (e.g., Hunt and Hess Grades I-III). Its use is prophylactic and therapeutic against cerebral vasospasm, a common and serious complication of SAH that typically manifests 3 to 14 days after the initial bleed. Treatment must be initiated within 96 hours of the onset of SAH and continued for 21 consecutive days.

Dosage and direction

The standard dosage for adults is 60 mg (two 30 mg capsules) every 4 hours for 21 consecutive days.

• Administration: Oral. The capsules should be swallowed whole with a glass of water. They should not be chewed, crushed, or broken.
• Timing: Doses should be administered at approximately the same times each day to maintain consistent plasma levels.
• Duration: The full 21-day course is critical for efficacy and should be completed even if the patient is discharged from the hospital earlier.
• Dosing in Hepatic Impairment: In patients with cirrhosis or severe liver dysfunction, dosage reduction may be necessary due to decreased clearance and increased bioavailability. Dose adjustments should be guided by close monitoring of blood pressure and heart rate.
• Swallowing Difficulties: For patients who cannot swallow the capsule, a hole can be pierced at both ends with a standard 18-gauge needle and the contents emptied into a syringe. The contents can then be administered via nasogastric tube. The tube should then be flushed with 30 mL of normal saline.

Precautions

• Hypotension: Nimotop can cause hypotension, which may be more pronounced in patients with pre-existing low blood pressure or those who are volume-depleted. Blood pressure should be monitored regularly, especially during the initial phase of treatment and after any dose adjustment.
• Liver Function: Nimodipine is extensively metabolized by the liver. Patients with impaired hepatic function will have significantly increased plasma concentrations and require careful monitoring and likely dose reduction.
• CYP3A4 Interactions: Nimodipine is a substrate of the CYP3A4 enzyme system. Concomitant use with strong inhibitors or inducers of this enzyme can drastically alter nimodipine plasma levels.
• Grapefruit Juice: Patients must avoid grapefruit juice during treatment, as it inhibits CYP3A4 metabolism and can lead to potentially toxic increases in nimodipine concentration.
• Pregnancy and Lactation: Use during pregnancy is only recommended if the potential benefit justifies the potential risk to the fetus. It is not known if nimodipine is excreted in human milk; a decision should be made to discontinue nursing or discontinue the drug.
• Pediatric Use: Safety and effectiveness in pediatric patients have not been established.
• Geriatric Use: Elderly patients may exhibit increased bioavailability and a slightly reduced clearance rate; they should be monitored closely for side effects, particularly hypotension.

Contraindications

• Known hypersensitivity to nimodipine, any other calcium channel blocker, or any component of the capsule formulation.
• Concurrent administration with strong CYP3A4 inhibitors in the systemic circulation (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, conivaptan) is contraindicated due to the high risk of severe hypotension and other adverse effects.
• Patients with cardiogenic shock or significant hypotension where a further decrease in blood pressure would be clinically detrimental.

Possible side effect

The most common side effects are related to its pharmacological effect of vasodilation and are generally dose-dependent.

Very Common (≥1/10):

• Decreased blood pressure (hypotension)

Common (≥1/100 to <1/10):

• Headache
• Nausea
• Bradycardia (slow heart rate)
• Gastrointestinal discomfort
• Flushing (feeling of warmth)
• Edema (swelling), primarily peripheral

Uncommon (≥1/1,000 to <1/100):

• Tachycardia (fast heart rate), palpitations
• Rash, pruritus (itching)
• Gastrointestinal hemorrhage (note: this can also be a complication of SAH itself)
• Increased liver enzymes

Rare (<1/1,000):

• Thrombocytopenia (low platelet count)
• Allergic reactions

Drug interaction

Nimodipine’s metabolism via CYP3A4 is the primary source of significant drug interactions.

• Strong CYP3A4 Inhibitors (Systemic): Contraindicated. Concomitant use with drugs like ketoconazole, itraconazole, clarithromycin, ritonavir, and conivaptan can increase nimodipine plasma levels by up to 8-fold, leading to profound hypotension and cardiovascular collapse.
• Moderate CYP3A4 Inhibitors (e.g., diltiazem, verapamil, erythromycin): Use with extreme caution. These drugs can significantly increase nimodipine concentration, necessitating a reduction in the nimodipine dose and intensive monitoring.
• CYP3A4 Inducers (e.g., rifampin, carbamazepine, phenytoin, St. John’s Wort): May decrease the plasma concentration and efficacy of nimodipine. An increase in the nimodipine dose may be required, though this is complicated by its narrow therapeutic index.
• Other Antihypertensives (e.g., beta-blockers, ACE inhibitors, diuretics): Additive hypotensive effects. Blood pressure must be monitored closely.
• Alpha-blockers (e.g., prazosin): May potentiate the hypotensive effect of nimodipine.
• QT-Prolonging Agents: Nimodipine can modestly prolong the QT interval. Caution is advised when co-administering with other drugs known to prolong QT interval (e.g., certain antiarrhythmics, antipsychotics).

Missed dose

• If a dose is missed, it should be taken as soon as it is remembered.
• However, if it is almost time for the next scheduled dose, the missed dose should be skipped.
• The patient should never take a double dose to make up for a missed one.
• The dosing schedule should be re-established with the next due dose.
• Maintaining the 4-hour interval is more important than strictly adhering to the clock time.

Overdose

Symptoms: Overdose would be expected to produce profound and potentially dangerous systemic vasodilation leading to:

• Severe, marked hypotension
• Reflex tachycardia (or bradycardia in some cases)
• Dizziness, palpitations, flushing
• Neurological depression or confusion

Management:

1. Cardiovascular monitoring is essential in a intensive care setting.
2. Symptomatic and supportive measures are the mainstays of treatment.
3. Active cardiovascular support may include:
   • Placing the patient in the Trendelenburg position (head down).
   • Administration of intravenous fluids to maintain vascular volume.
   • Use of vasopressors (e.g., dopamine, norepinephrine) for refractory hypotension.
   • Atropine may be considered for significant bradycardia.
4. As nimodipine is highly protein-bound, dialysis is not likely to be of benefit.

Storage

• Store at or below 25°C (77°F). Do not freeze.
• Keep the blister strips in the outer carton to protect from light and moisture.
• Keep out of the sight and reach of children.
• Do not use after the expiration date printed on the packaging.

Disclaimer

This information is for educational and professional medical reference purposes only and is not a substitute for the professional judgment of a qualified healthcare practitioner in diagnosing and treating patients. The prescribing physician should be familiar with all contraindications, warnings, precautions, adverse reactions, and dosage guidelines as contained in the official prescribing information (SmPC). Dosage and administration must be individualized based on the patient’s specific clinical condition, hepatic function, and concomitant medications.

Reviews

• “Landmark Clinical Trial (1989): The pivotal randomized, double-blind, placebo-controlled study established the efficacy of nimodipine. It demonstrated a significant reduction in cerebral infarction (22% vs 33% in placebo) and poor outcomes (20% vs 33% in placebo) in patients receiving nimodipine following aneurysmal SAH.”
• “Cochrane Systematic Review (Meta-Analysis): Consistent evidence that prophylactic nimodipine therapy produces a statistically significant improvement in outcome for patients with aneurysmal SAH, reducing the risk of poor outcome and secondary ischemia. The number needed to treat (NNT) to prevent one poor outcome is approximately 10-15.”
• Neurocritical Care Society Guidelines: Nimodipine is strongly recommended (Grade A evidence) for the prevention of delayed cerebral ischemia in patients with aneurysmal SAH. It is considered a standard of care in the management of these patients.
• Clinical Neurologist’s Perspective: “Nimotop remains the only pharmacologic agent with a Class I recommendation and Level A evidence for improving neurological outcomes after SAH. Its initiation is a non-negotiable step in our post-hemorrhage protocol for eligible patients.”