Nimodipine (3 brand names, 2 dosage forms, 1 route)
Available dosage forms: SOLUTION, CAPSULE.
Routes of administration: ORAL.
Brand Names
- NIMODIPINE
- NIMOTOP
- NYMALIZE
Boxed Warning
DO NOT ADMINISTER NIMODIPINE INTRAVENOUSLY OR BY OTHER PARENTERAL ROUTES. DEATHS AND SERIOUS, LIFE THREATENING ADVERSE EVENTS HAVE OCCURRED WHEN THE CONTENTS OF NIMODIPINE CAPSULES HAVE BEEN INJECTED PARENTERALLY (See WARNINGS and DOSAGE AND ADMINISTRATION).
Indications and Usage
Nimodipine is 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 regardless of their post-ictus neurological condition (i.e., Hunt and Hess Grades I-V).
Dosage and Administration
DO NOT ADMINISTER NIMODIPINE CAPSULES INTRAVENOUSLY OR BY OTHER PARENTERAL ROUTES (see WARNINGS). If Nimodipine is inadvertently administered intravenously, clinically significant hypotension may require cardiovascular support with pressor agents. Specific treatments for calcium channel blocker overdose should also be given promptly. Nimodipine is given orally in the form of soft gelatin 30 mg capsules for subarachnoid hemorrhage. The recommended oral dose is 60 mg (two 30 mg capsules) every 4 hours for 21 consecutive days. In general, the capsules should be swallowed whole with a little liquid, preferably not less than one hour before or two hours after meals. Grapefruit juice is to be avoided (See PRECAUTIONS, Drug Interactions). Oral nimodipine therapy should commence as soon as possible within 96 hours of the onset of subarachnoid hemorrhage. If the capsule cannot be swallowed, e.g., at the time of surgery, or if the patient is unconscious, a hole should be made in both ends of the capsule with an 18 gauge needle, and the contents of the capsule extracted into a syringe. A parenteral syringe can be used to extract the liquid inside the capsule, but the liquid should always be transferred to a syringe that cannot accept a needle and that is designed for administration orally or via a naso-gastric tube or PEG. To help minimize administration errors, it is recommended that the syringe used for administration be labeled “Not for IV Use”. The contents should then be emptied into the patient’s in situnaso-gastric tube and washed down the tube with 30 mL of normal saline (0.9%). Severely disturbed liver function, particularly liver cirrhosis, may result in an increased bioavailability of nimodipine due to a decreased first pass capacity and a reduced metabolic clearance. The reduction in blood pressure and other adverse effects may be more pronounced in these patients. Dosage should be reduced to one 30 mg capsule every 4 hours with close monitoring of blood pressure a
Contraindications
The concomitant use of nimodipine with strong inhibitors of CYP3A4 such as some macrolide antibiotics (e.g., clarithromycin, telithromycin), some anti-HIV protease inhibitors (e.g., delaviridine, indinavir, nelfinavir, ritonavir, saquinavir), some azole antimycotics (e.g., ketoconazole, itraconazole, voriconazole) and some antidepressants (e.g., nefazadone) is contraindicated because of a risk of significant hypotension (See PRECAUTIONS, Drug Interactions).
Adverse Reactions
Adverse experiences were reported by 92 of 823 patients with subarachnoid hemorrhage (11.2%) who were given nimodipine. The most frequently reported adverse experience was decreased blood pressure in 4.4% of these patients. Twenty-nine of 479 (6.1%) placebo treated patients also reported adverse experiences. The events reported with a frequency greater than 1% are displayed below by dose. DOSE q4h Number of Patients (%) Nimodipine Sign/Symptom 0.35 mg/kg (n=82) 30 mg (n=71) 60 mg (n=494) 90 mg (n=172) 120 mg (n=4) Placebo (n=479) Decreased Blood Pressure 1 (1.2) 0 19 (3.8) 14 (8.1) 2 (50.0) 6 (1.2) Abnormal Liver Function Test 1 (1.2) 0 2 (0.4) 1 (0.6) 0 7 (1.5) Edema 0 0 2 (0.4) 2 (1.2) 0 3 (0.6) Diarrhea 0 3 (4.2) 0 3 (1.7) 0 3 (0.6) Rash 2 (2.4) 0 3 (0.6) 2 (1.2) 0 3 (0.6) Headache 0 1 (1.4) 6 (1.2) 0 0 1 (0.2) Gastrointestinal Symptoms 2 (2.4) 0 0 2 (1.2) 0 0 Nausea 1 (1.2) 1 (1.4) 6 (1.2) 1 (0.6) 0 0 Dyspnea 1 (1.2) 0 0 0 0 0 EKG Abnormalities 0 1 (1.4) 0 1 (0.6) 0 0 Tachycardia 0 1 (1.4) 0 0 0 0 Bradycardia 0 0 5 (1.0) 1 (0.6) 0 0 Muscle Pain/Cramp 0 1 (1.4) 1 (0.2) 1 (0.6) 0 0 Acne 0 1 (1.4) 0 0 0 0 Depression 0 1 (1.4) 0 0 0 0 There were no other adverse experiences reported by the patients who were given 0.35 mg/kg q4h, 30 mg q4h or 120 mg q4h. Adverse experiences with an incidence rate of less than 1% in the 60 mg q4h dose group were: hepatitis; itching; gastrointestinal hemorrhage; thrombocytopenia; anemia; palpitations; vomiting; flushing; diaphoresis; wheezing; phenytoin toxicity; lightheadedness; dizziness; rebound vasospasm; jaundice; hypertension; hematoma. Adverse experiences with an incidence rate less than 1% in the 90 mg q4h dose group were: itching, gastrointestinal hemorrhage; thrombocytopenia; neurological deterioration; vomiting; diaphoresis; congestive heart failure; hyponatremia; decreasing platelet count; disseminated intravascular coagulation; deep vein thrombosis. As can be seen from the table, side effects that appear related to nimodip
Drug Interactions
Nimodipine is metabolized via the cytochrome P450 3A4 system located both in the intestinal mucosa and in the liver. Drugs that are known to either inhibit or to induce this enzyme system may therefore alter the first pass or the clearance of nimodipine. In addition, the blood pressure lowering effects of antihypertensives could be enhanced when taken concomitantly with nimodipine.
Mechanism of Action
Nimodipine is a calcium channel blocker. The contractile processes of smooth muscle cells are dependent upon calcium ions, which enter these cells during depolarization as slow ionic transmembrane currents. Nimodipine inhibits calcium ion transfer into these cells and thus inhibits contractions of vascular smooth muscle. In animal experiments, nimodipine had a greater effect on cerebral arteries than on arteries elsewhere in the body perhaps because it is highly lipophilic, allowing it to cross the blood-brain barrier; concentrations of nimodipine as high as 12.5 ng/mL have been detected in the cerebrospinal fluid of nimodipine-treated subarachnoid hemorrhage (SAH) patients. The precise mechanism of action of nimodipine in humans is unknown. Although the clinical studies described below demonstrate a favorable effect of nimodipine on the severity of neurological deficits caused by cerebral vasospasm following SAH, there is no arteriographic evidence that the drug either prevents or relieves the spasm of these arteries. However, whether or not the arteriographic methodology utilized was adequate to detect a clinically meaningful effect, if any, on vasospasm is unknown.
Overdosage
There have been no reports of overdosage from the oral administration of nimodipine. Symptoms of overdosage would be expected to be related to cardiovascular effects such as excessive peripheral vasodilation with marked systemic hypotension. Clinically significant hypotension due to nimodipine overdosage may require active cardiovascular support with pressor agents. Specific treatments for calcium channel blocker overdose should also be given promptly. Since nimodipine is highly protein-bound, dialysis is not likely to be of benefit.