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 have been derived from various trials regarding the use of nimodipine:
During depolarization of smooth muscle cells of blood vessels, there is an influx of calcium ions. The main 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 has to be started 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 are to be 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 is attained 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 drug is well tolerated and there is no hypotension, the dose can be increased 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 be continued for a minimum of 5 days and a maximum of 14 days. If the condition is treated surgically, nimodipine should be continued in the same dose for a minimum of 5 days.
Intravenous nimodipine can be administered with or without pre-treatment with nimodipine tablets. If it is given 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.
Nimodipine is metabolized by the cytochrome P450 3A4 system. Drugs which 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. Grape juice is also an inhibitor of the cytochrome system and should not be given to a patient who is being treated with nimodipine.
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 is associated with some side effects, related to the vasodilating property. The main adverse effects of the drug are a 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 fully safe in pregnancy (Category C) and should be used only if there is a good 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 has to be monitored 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 should be provided. If the toxicity is due to oral intake, gastric lavage can be done, and charcoal can be administered on an emergency basis. Hypotension is managed with inotrope and arrhythmias are treated in conjunction with a cardiologist. No specific antidote is available.
Nurses often use nimodipine in the intensive care unit (ICU) and on the neurosurgical floor. When administering this agent, it is important to be aware that it can produce hypotension. Careful monitoring of blood pressure is required after administration. In patients who cannot be fed orally, it can be given 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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