Nimodipine

Pronunciation

(nye MOE di peen)

U.S. Brand Names

Nimotop®

Generic Available

Canadian Brand Names

Nimotop®

Use

Spasm following subarachnoid hemorrhage from ruptured intracranial aneurysms regardless of the patients neurological condition postictus (Hunt and Hess grades I-V)

Pregnancy Risk Factor

Pregnancy Implications

Use in pregnancy only when clearly needed and when the benefits outweigh the potential hazard to the fetus. Teratogenic and embryotoxic effects have been demonstrated in small animals. No well-controlled studies have been conducted in pregnant women.

Lactation

Enters breast milk/not recommended

Contraindications

Hypersensitivity to nimodipine or any component of the formulation

Warnings/Precautions

May cause reductions in blood pressure. Use caution in hepatic impairment. Intestinal pseudo-obstruction and ileus have been reported during the use of nimodipine. Use caution in patients with decreased GI motility of a history of bowel obstruction. Use caution when treating patients with increased intracranial pressure.

Adverse Reactions

1% to 10%:

Cardiovascular: Reductions in systemic blood pressure (1% to 8%)

Central nervous system: Headache (1% to 4%)

Dermatologic: Rash (1% to 2%)

Gastrointestinal: Diarrhea (2% to 4%), abdominal discomfort (2%)

<1% (Limited to important or life-threatening): Edema ( 1%), ECG abnormalities ( 1%), tachycardia (0% to 1%), bradycardia ( 1%), depression ( 1%), acne ( 1%), nausea ( 1%), hemorrhage, hepatitis, muscle cramps/pain ( 1%), dyspnea ( 1%). itching, GI hemorrhage, thrombocytopenia, anemia, palpitation, vomiting, flushing, diaphoresis, wheezing, lightheadedness, dizziness, rebound vasospasm, jaundice, hypertension, hematoma, neurological deterioration, CHF, hyponatremia, disseminated intravascular coagulation, deep vein thrombosis

Case report: Disseminated intravascular coagulation (DIC)

Overdosage/Toxicology

Primary cardiac symptoms of calcium blocker overdose include hypotension and bradycardia. Noncardiac symptoms include confusion, stupor, nausea, vomiting, metabolic acidosis and hyperglycemia. Treat symptomatically.

Drug Interactions

Substrate of CYP3A4 (major)

Antihypertensive agents: Effects may be potentiated by nimodipine.

Azole antifungals may inhibit the calcium channel blocker's metabolism; avoid this combination. Try an antifungal like terbinafine (if appropriate) or monitor closely for altered effect of the calcium channel blocker.

Calcium may reduce the calcium channel blocker's effects, particularly hypotension.

Calcium channel blockers: The effects of other calcium channel blockers may be potentiated by nimodipine.

CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of nimodipine. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.

CYP3A4 inhibitors: May increase the levels/effects of nimodipine. Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.

Grapefruit juice increases the bioavailability of nimodipine; monitor for altered nimodipine effects.

Protease inhibitor like amprenavir and ritonavir may increase nimodipine's serum concentration.

Rifampin increases the metabolism of the calcium channel blocker; adjust the dose of the calcium channel blocker to maintain efficacy.

Sildenafil, tadalafil, vardenafil: Blood pressure-lowering effects may be additive; use caution.

Valproic acid increased nimodipine's serum concentration; monitor altered effect of nimodipine.

Ethanol/Nutrition/Herb Interactions

Food: Nimodipine has shown a 1.5-fold increase in bioavailability when taken with grapefruit juice; avoid concurrent use.

Herb/Nutraceutical: St John's wort may decrease levels. Avoid dong quai if using for hypertension (has estrogenic activity). Avoid ephedra, yohimbe, ginseng (may worsen hypertension). Avoid garlic (may have increased antihypertensive effect).

Mechanism of Action

Nimodipine shares the pharmacology of other calcium channel blockers; animal studies indicate that nimodipine has a greater effect on cerebral arterials than other arterials; this increased specificity may be due to the drug's increased lipophilicity and cerebral distribution as compared to nifedipine; inhibits calcium ion from entering the "slow channels" or select voltage sensitive areas of vascular smooth muscle and myocardium during depolarization

Pharmacodynamics/Kinetics

Protein binding: >95%

Metabolism: Extensively hepatic

Bioavailability: 13%

Half-life elimination: 3 hours; prolonged with renal impairment

Time to peak, serum: ~1 hour

Excretion: Urine (50%) and feces (32%) within 4 days

Dosage

Adults: Oral: 60 mg every 4 hours for 21 days, start therapy within 96 hours after subarachnoid hemorrhage.

Dialysis: Not removed by hemo- or peritoneal dialysis; supplemental dose is not necessary.

Dosing adjustment in hepatic impairment: Reduce dosage to 30 mg every 4 hours in patients with liver failure.

Administration

If the capsules cannot be swallowed, the liquid may be removed by making a hole in each end of the capsule with an 18-gauge needle and extracting the contents into a syringe. If administered via NG tube, follow with a flush of 30 mL NS.

Patient Education

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Take as directed; do not alter dose or decrease without consulting prescriber. Avoid grapefruit juice. May cause orthostatic hypotension (change position slowly from sitting or lying to standing, or when climbing stairs); headache (consult prescriber for approved analgesic); or diarrhea (buttermilk, boiled milk, or yogurt may help). Report chest pain, palpitations, slow heartbeat, respiratory difficulty, or other persistent adverse effects. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Breast-feeding is not recommended.

Anesthesia and Critical Care Concerns/Other Considerations

Animal studies suggest nimodipine may have a greater effect on cerebral arterioles, possibly due to its lipophilicity which increases cerebral distribution.

Cardiovascular Considerations

Nimodipine is primarily used in the treatment of subarachnoid hemorrhage and is not used in the management of essential hypertension or angina.

Dental Health: Effects on Dental Treatment

Other drugs of this class can cause gingival hyperplasia (ie, nifedipine) but there have been no reports for nimodipine.

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

May cause dizziness; may rarely cause depression

Mental Health: Effects on Psychiatric Treatment

None reported

Dosage Forms

Capsule, liquid filled: 30 mg

References

Ramoska EA, Spiller HA, and Myers A, "Calcium Channel Blocker Toxicity," Ann Emerg Med , 1990, 19(6):649-53.

Steele RM, Schuna AA, and Schreiber RT, "Calcium Antagonist-Induced Gingival Hyperplasia," Ann Intern Med , 1994, 120(8):663-4.

International Brand Names

Acival® (AR); AC Vascular® (AR); Admon® (ES); Aniduv® (AR); Brainal® (CL, CZ, EC, ES, RO, RU); Brainox® (PT); Calnit® (ES); Cebrofort® (AR); Cletonol® (AR); Dilceren® (CZ); Eugerial® (AR, BR, CO); Explaner® (AR); Grifonimod® (CL); Kenesil® (ES); Macobal® (AR); Modina® (PT); Modus® (ES); Nemotan® (RO, RU, SK, UA); Neurogeron® (CL); Nidip® (CO); Nimodilat® (AR); Nimodipina Labinca® (AR); Nimodipin Hexal® (DE); Nimodipin-ISIS® (DE); Nimodipino Bayvit® (ES); Nimodipino® (BR); Nimodipin® (RO); Nimopin® (DO); Nimotop® (AR, AT, AU, BE, BR, CA, CH, CL, CO, CZ, DE, DK, EC, ES, FI, FR, GB, HK, HR, HU, ID, IE, IL, IT, LU, MX, NL, NO, NZ, PL, RO, RU, SE, SG, SI, TH, TR, YU, ZA); Nisom® (CO); Nivas® (AR); Noodipina® (BR); Norton® (BR); Optisel® (CL); Oxigen® (BR); Periplum® (IT); Regental® (CL); Remontal® (ES); Sobrepina® (PT); Tenocard® (AR); Trinalion® (PT); Tropocer® (CR, DO, GT, HN, PA, SV); Vasoflex® (CL); Vasotop® (IN)

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