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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(nye MOE di peen)
Generic Available (U.S.)
Yes
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Vasospasm following subarachnoid hemorrhage from ruptured intracranial aneurysms
Use: Unlabeled
Prevention of migraines (inconsistent data)
Pregnancy Risk Factor
C
Pregnancy Considerations
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
Boxed warnings:
• Inadvertent I.V. administration: See “Other warnings/precautions” below.
Concerns related to adverse effects:
• Angina/MI: Increased angina and/or MI has occurred with initiation or dosage titration of dihydropyridine calcium channel blockers. Reflex tachycardia may occur resulting in angina and/or MI in patients with obstructive coronary disease, especially in the absence of concurrent beta-blockade.
• Hypotension/syncope: Symptomatic hypotension with or without syncope can rarely occur; blood pressure must be lowered at a rate appropriate for the patient's clinical condition.
• Ileus/ pseudo-obstruction: Intestinal pseudo-obstruction and ileus have been reported during therapy; use caution in patients with decreased GI motility of a history of bowel obstruction.
• Peripheral edema: The most common side effect is peripheral edema; occurs within 2-3 weeks of starting therapy.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment; may require lower starting dose.
• Idiopathic hypertrophic subaortic stenosis (IHSS): Use with caution in patients with IHSS.
Other warnings/precautions:
• Inadvertent I.V. administration: [U.S. Boxed Warning]: Nimodipine has inadvertently been administered I.V. when withdrawn from capsules into a syringe for subsequent nasogastric administration. Severe cardiovascular adverse events, including fatalities, have resulted; precautions (eg, adequate labeling, use of oral syringes) should be employed against such an event.
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)
Metabolism/Transport Effects
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Drug Interactions
Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Calcium Channel Blockers. Risk D: Consider therapy modification
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Barbiturates: May increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. Risk C: Monitor therapy
Beta-Blockers: Calcium Channel Blockers (Dihydropyridine) may enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): Calcium Channel Blockers (Dihydropyridine) may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy
Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Calcium Channel Blockers (Dihydropyridine). Management: Consider calcium channel blocker (CCB) dose adjustments or alternative therapy in patients receiving concomitant carbamazepine. Nimodipine Canadian labeling contraindicates concurrent use with carbamazepine. Risk D: Consider therapy modification
Cimetidine: May increase the serum concentration of Calcium Channel Blockers. Management: Consider alternatives to cimetidine. If no suitable alternative exists, monitor for increased effects of calcium channel blockers following cimetidine initiation/dose increase, and decreased effects following cimetidine discontinuation/dose decrease. Risk D: Consider therapy modification
Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination
CycloSPORINE: May decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Nicardipine may likewise inhibit the metabolism of cyclosporine. Cyclosporine dosage adjustments might be needed. Risk C: Monitor therapy
CycloSPORINE (Systemic): May decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Fluconazole: May decrease the metabolism of Calcium Channel Blockers. Risk C: Monitor therapy
FLUoxetine: May increase the serum concentration of NiMODipine. Risk C: Monitor therapy
Fosphenytoin: Calcium Channel Blockers may increase the serum concentration of Fosphenytoin. Management: Monitor for phenytoin toxicity with concomitant use of a calcium channel blocker (CCB) or decreased phenytoin effects with CCB discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian labeling contraindicates use with phenytoin. Risk D: Consider therapy modification
Grapefruit Juice: May increase the serum concentration of NiMODipine. Risk X: Avoid combination
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Macrolide Antibiotics: May decrease the metabolism of Calcium Channel Blockers. Management: Consider using a noninteracting macrolide. Monitor for increased therapeutic effects of calcium channel blockers if an interacting macrolide antibiotic is initiated, or decreased effects if a macrolide is discontinued. Exceptions: Azithromycin; Azithromycin (Systemic); Fidaxomicin; Spiramycin. Risk D: Consider therapy modification
Magnesium Salts: Calcium Channel Blockers may enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
MAO Inhibitors: May enhance the hypotensive effect of Antihypertensives. MAO Inhibitors may enhance the orthostatic hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Nafcillin: May increase the metabolism of Calcium Channel Blockers. Risk D: Consider therapy modification
Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Nitroprusside: Calcium Channel Blockers may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phenytoin: Calcium Channel Blockers may increase the serum concentration of Phenytoin. Management: Monitor for phenytoin toxicity with concomitant use of a calcium channel blocker (CCB) or decreased phenytoin effects with CCB discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian labeling contraindicates use with phenytoin. Risk D: Consider therapy modification
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Protease Inhibitors: May decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Risk D: Consider therapy modification
QuiNIDine: May increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Calcium Channel Blockers (Dihydropyridine) may decrease the serum concentration of QuiNIDine. Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of QuiNIDine. Risk C: Monitor therapy
Rifamycin Derivatives: May increase the metabolism of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Management: The labeling for some U.S. and Canadian calcium channel blockers contraindicate use with rifampin however recommendations vary. Consult appropriate labeling. Risk D: Consider therapy modification
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Tacrolimus: Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus. Risk C: Monitor therapy
Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Food: Nimodipine has shown a 1.5-fold increase in bioavailability when taken with grapefruit juice. Management: Avoid concurrent use of grapefruit juice and nimodipine.
Herb/Nutraceutical: St John's wort may decrease levels. Dong quai has estrogenic activity. Some herbal medications may worsen hypertension (eg, ephedra); garlic may increase antihypertensive effects of nimodipine. Management: Avoid dong quai if using for hypertension. Avoid St John's wort, ephedra, yohimbe, ginseng, and garlic.
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: 1-2 hours; prolonged with renal impairment
Time to peak, serum: ~1 hour
Excretion: Urine (50%) and feces (32%) within 4 days
Dosage
Note: Capsules and contents are for oral/NG tube administration ONLY.
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: Oral
For oral administration ONLY. Life-threatening adverse events have occurred when administered parenterally. Administer on an empty stomach.
Nasogastric (NG) tube 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; transfer these contents into an oral syringe (amber-colored oral syringe preferred). It is strongly recommended that preparation be done in the pharmacy. Label oral syringe with "WARNING: For ORAL use only” or “Not for I.V. use.” Follow with a flush of 30 mL NS.
Patient Education
May cause orthostatic hypotension, headache, or constipation. Report chest pain, palpitations, severe constipation, ankle swelling, or respiratory difficulty.
Geriatric Considerations
Elderly may experience a greater hypotensive response. Constipation may be more of a problem in the elderly. Studies in the treatment of Alzheimer's disease have not demonstrated clear clinical effect.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: Studies suggest nimodipine has preferential action on cerebral arterioles, possibly due to its lipophilicity which may increase 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
Nursing: Physical Assessment/Monitoring
Assess blood pressure and cardiac status. Monitor for rash, hypotension, constipation, and peripheral edema when starting or adjusting dose and periodically during therapy.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, liquid filled, oral: 30 mg
Capsule, softgel, oral: 30 mg
Pricing: U.S. (www.drugstore.com)
Capsules (NiMODipine)
30 mg (100): $599.99
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
Lexi-Comp.com
Last full review/revision March 2012
Content last modified March 2012
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