Nimodipine (C21H26N2O7) is a second-generation 1,4-dihydropyridine calcium channel blocker. It was originally invented for the management of systemic hypertension.
The FDA approved the use of nimodipine for the first time in 1988. However, its use is restricted mainly to the management of vasospasm following subarachnoid hemorrhage.
The following findings derive from various trials regarding the use of nimodipine:
During the depolarization of smooth muscle cells of blood vessels, there is an influx of calcium ions. The primary function of nimodipine is to block voltage-gated L-type calcium channels in their inactive conformation, avoiding this influx, to prevent vasoconstriction. It has a preference to act on cerebral blood vessels since it is lipophilic and can cross the blood-brain barrier.
Nimodipine should start as early as possible or within 96 hours of the diagnosis of subarachnoid hemorrhage. Nimodipine is usually available as capsules of 30 mg. 1It has to be given at least 1 hour before or 2 hours after meals. The adult recommended dose for adults is 60 mg (two 30-mg capsules) every 4 hours for 21 consecutive days.
If the patient is not conscious enough to swallow the nimodipine capsule, a hole can be made in both ends of it using an 18-gauge needle, and the contents get extracted into a syringe. Then it can be fed through a nasogastric tube and washed down with 30 ml of normal saline (0.9%).
Bioavailability following parenteral administration is 100%, while that following oral administration is 3% to 30% due to the extensive first-pass metabolism. Bioavailability increases in patients with cirrhosis liver, making it necessary to reduce the dose in such patients. After oral administration, peak plasma concentration occurs within 1 hour. The elimination half-life is longer (8 to 9 hours) as compared to the rate of initial elimination (1 to 2 hours), making the biological half-life 1.7 to 9 hours. Hence the drug has to be administered frequently (every 4 hours). Nimodipine does not accumulate in the body even after continuous administration for a week. It is over 95% attached to plasma proteins, which is concentration-independent. Excretion is via kidneys in the form of metabolites.
Nimodipine should be given intravenously via a central venous catheter at a starting dose of 1 mg/hr (15 mcg/kg per hour equivalent to 5 ml per hour) for the first 2 hours. If the patient tolerates the drug well and there is no hypotension, the dose can increase to 2 mg per hour (30 mcg/kg per hour equivalent to 10 ml per hour) after the first 2 hours. Two hours for 2 mg nimodipine, i.e., 10 ml nimodipine solution per hour (about 30 microgram/kg per hour).
If the patient's body weight is less than 70 kg or the patient has hypotension, nimodipine should be started at a dose of 0.5 mg per hour (2.5 ml of solution per hour) or less, if necessary.
Duration of Treatment
Aneurysmal subarachnoid hemorrhage
Treatment via intravenous route should be started via intravenous route as soon as possible after the onset of clinical vasospasm and should continue for a minimum of 5 days and a maximum of 14 days. If the condition has surgical treatment, nimodipine should be maintained at the same dose for a minimum of 5 days.
Intravenous nimodipine can be administered with or without pre-treatment with nimodipine tablets. If giving the drug following administration of oral form, the total duration of treatment should not exceed a maximum of 21 days. Intravenous nimodipine should not be given for a period longer than 14 days. Intravenous and oral forms of nimodipine should not be used concomitantly.
During surgery, a freshly prepared dilute solution of nimodipine (20 ml of a dilute solution of nimodipine: 1 ml of nimodipine concentrated intravenous infusion solution and 19 ml of Ringer solution) warmed up to blood temperature may be instilled intracisternally. This dilution must be used immediately after preparation.
The cytochrome P450 3A4 system metabolizes nimodipine. Drugs that inhibit this enzyme can lead to increased plasma concentrations of nimodipine. Such drugs include macrolide antibiotics like erythromycin, protease inhibitors like ritonavir, azole antimycotics like ketoconazole, antidepressants like fluoxetine, quinupristin/dalfopristin, cimetidine, and valproic acid. Grapefruit juice is also an inhibitor of the cytochrome system, and a patient who is getting treated with nimodipine should avoid it.
The outcome, dosage, and duration of intraventricular administration of nimodipine are not yet clear. The NEWTON trial is going on to identify these factors.
Nimodipine is usually well tolerated orally, but its use correlates with some side effects, related to the vasodilating property. The main adverse effects of the drug are headache, vertigo, flushing, nausea, diarrhea, pedal edema, rash, and palpitations.
A previous history of a hypersensitivity reaction to nimodipine is an absolute contraindication. Liver failure and hypotension are relative contraindications for administering nimodipine.
The drug is not entirely safe in pregnancy (Category C under the previous FDA system) and should only be used if there is a strong benefit-risk ratio. Breastfeeding is contraindicated while taking the drug due to the chance of harmful effects on the baby. Safety in the pediatric population has not been fully established.
Blood pressure requires monitoring in patients receiving nimodipine as it can cause hypotension.
Sudden toxicity due to overdosage can cause hypotension, cardiac arrhythmias, nausea, and sometimes vomiting.
Stop the drug as the first step. Emergency symptomatic management is necessary. If the toxicity is due to oral intake, gastric lavage is an option, and charcoal can be administered on an emergency basis. Hypotension management is with inotrope, and arrhythmias will receive treatment in conjunction with a cardiologist. No specific antidote is available.
Nimodipine therapy is best when under the direction of an interprofessional team. A cardiologist or internal medicine specialist will most frequently initiate treatment. Nurses often use nimodipine in the intensive care unit (ICU) and on the neurosurgical floor. All practitioners would be well advised to consult a pharmacist on dosing and drug interactions before initiating nimodipine; interprofessional coordination of effort will permit the team to obtain optimal outcomes with minimal adverse events. [Level 5]
When administering this agent, it is essential to be aware that it can produce hypotension. Careful monitoring of blood pressure is necessary after administration. In patients who cannot feed orally, administration is possible after extracting the contents in a syringe and feeding through a nasogastric tube. It should be labeled and kept separate to avoid its administration intravenously.
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