What is the use of Nimodipine (calcium channel blocker) for?

Use of Nimodipine in Aneurysmal Subarachnoid Hemorrhage

Nimodipine is primarily indicated for the improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in patients with subarachnoid hemorrhage from ruptured intracranial berry aneurysms. 1

Mechanism of Action and Pharmacology

• Nimodipine is a dihydropyridine calcium channel blocker that inhibits calcium ion transfer into vascular smooth muscle cells, thus inhibiting contractions 1
• It has greater effect on cerebral arteries than on arteries elsewhere in the body due to its high lipophilicity, allowing it to cross the blood-brain barrier 1
• The drug is rapidly absorbed after oral administration with peak concentrations generally attained within one hour and a terminal elimination half-life of approximately 8-9 hours 1
• Nimodipine is over 95% bound to plasma proteins and is metabolized primarily by CYP3A4 1

Clinical Use in Aneurysmal Subarachnoid Hemorrhage (aSAH)

• Nimodipine is the only FDA-approved drug for neuroprotection in patients with aneurysmal subarachnoid hemorrhage 2
• The standard recommended enteral dose is 60 mg every 4 hours 2
• The 2023 AHA/ASA guidelines strongly recommend continued enteral administration of nimodipine at 60 mg 6 times a day to prevent delayed cerebral ischemia (DCI) and improve functional outcome 3
• Nimodipine's benefit appears to be through neuroprotection rather than preventing angiographic vasospasm, as it has not demonstrated a reduction in angiographic vasospasm despite improving clinical outcomes 3

Clinical Evidence

• The original 1983 clinical trial showed that nimodipine reduced severe neurologic deficits due to cerebral arterial spasm in neurologically normal patients after subarachnoid hemorrhage 4
• A meta-analysis of 16 trials involving 3361 patients confirmed nimodipine's benefit in preventing DCI and improving functional outcomes 3
• Disruption of nimodipine therapy is associated with a greater incidence of DCI, highlighting the importance of consistent administration 3

Important Clinical Considerations

• Up to 78% of patients with aSAH develop systemic arterial hypotension after taking nimodipine at the recommended dose 2
• If nimodipine causes significant blood pressure variability, temporary dose adjustment may be necessary, but consistent administration should be maintained when possible 3
• Hypotension from nimodipine could theoretically limit its neuroprotective role and worsen cerebral perfusion pressure, particularly when concomitant vasospasm is present 2
• Maintenance of euvolemia (not hypervolemia) is recommended alongside nimodipine therapy to prevent DCI and improve outcomes 3

Alternative Administration Routes

• While oral nimodipine is the standard of care, intra-arterial nimodipine has been studied for treatment of symptomatic vasospasm with promising preliminary results 5
• However, there are limited data to make any recommendation for intravenous or intra-arterial routes of nimodipine administration 3

Pitfalls and Caveats

• Nimodipine should not be confused with other calcium channel blockers used for different indications 1
• Unlike its use in aSAH, nimodipine has shown negative results when tested for treatment of acute ischemic stroke 3
• In some ischemic stroke trials, outcomes were worse among patients treated with nimodipine than among control subjects, presumably due to its antihypertensive effects 3
• Bioavailability is significantly increased in patients with hepatic cirrhosis, necessitating dose adjustment in this population 1
• Administration following a standard meal results in 68% lower peak plasma concentration and 38% lower bioavailability compared to fasting conditions 1

Emerging Research

• Recent research is exploring the potential for individualized dosing of nimodipine based on pharmacogenomic factors to minimize hypotensive effects while maintaining neuroprotection 2
• Combination therapy with agents like dexmedetomidine has been studied to reduce nimodipine consumption while maintaining its benefits 6