Do not administer nimodipine intravenously (IV) or by other parenteral routes. Deaths and serious, life-threatening adverse reactions have occurred when the contents of nimodipine capsules have been injected parenterally.
Note: Nimodipine oral solution (3 mg/mL) has been discontinued in the United States for >1 year.
Note: For oral administration ONLY.
Subarachnoid hemorrhage: Oral: 60 mg every 4 hours for 21 consecutive days. Note: Start therapy within 96 hours of the onset of subarachnoid hemorrhage.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment provided in manufacturer's labeling. However, nimodipine undergoes minimal renal elimination and dose adjustment may not be necessary. Not removed by hemo- or peritoneal dialysis; supplemental dose is not necessary.
Reduce dosage to 30 mg every 4 hours in patients with cirrhosis.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Generic: 30 mg
Solution, Oral:
Nymalize: 30 mg/10 mL (10 mL [DSC]); 60 mg/20 mL (20 mL [DSC], 473 mL [DSC]); 6 mg/mL (5 mL, 10 mL, 237 mL) [contains alcohol, usp, methylparaben, polyethylene glycol]
May be product dependent
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Nimotop: 30 mg
Nimodipine oral solution (3 mg/mL) has been discontinued in the United States for >1 year.
For enteral administration ONLY. Life-threatening adverse events have occurred when administered parenterally. Administer on an empty stomach at least 1 hour before or 2 hours after meals.
Oral:
US labeling: Administer on an empty stomach at least 1 hour before or 2 hours after meals.
Canadian labeling: Administer without regards to meals; but administer consistently with or without meals. Tablet should be swallowed whole with an adequate amount of fluid (eg, glass of water). Do not crush tablet. Avoid alkaline mixtures for 2 hours before or after administration. Patient should not be lying down during administration.
NG or gastric tube administration:
Oral solution (Nymalize): Note: Oral solution is available as a 3 mg/mL concentration supplied in a bulk bottle or unit-dose cup or as a 6 mg/mL concentration supplied in a prefilled oral syringe.
If using 3 mg/mL concentration (bulk bottle or unit-dose cup): Administer using the supplied oral syringe labeled "ORAL USE ONLY". Following administration, refill the oral syringe with 20 mL of NS and flush any remaining contents from NG or gastric tube into the stomach.
If using 6 mg/mL concentration (prefilled oral syringe): Following administration, refill the oral syringe with 10 mL of NS and flush any remaining contents from NG or gastric tube into the stomach.
Capsules: 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 for storage). It is strongly recommended that preparation be done in the pharmacy. Label oral syringe with "WARNING: For ORAL use only” or “Not for IV use” (Green 2004). Follow administration with a flush of 30 mL NS.
Subarachnoid hemorrhage: For the improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in adult patients with subarachnoid hemorrhage (SAH) from ruptured intracranial berry aneurysms regardless of their postictus neurological condition (ie, Hunt and Hess grades I to V)
NiMODipine may be confused with niCARdipine, NIFEdipine, nisoldipine
Inadvertent intravenous administration; For patients unable to swallow a capsule, the drug should be dispensed in an oral syringe (preferably amber in color) labeled "WARNING: For ORAL use only" or "Not for IV use." Nimodipine has inadvertently been administered IV when withdrawn from capsules into a syringe for subsequent nasogastric tube administration. Severe cardiovascular adverse events, including fatalities, have resulted. Employ precautions against such an event.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Cardiovascular: Decreased blood pressure (4% to 5%), bradycardia (1%)
Central nervous system: Headache (1%)
Gastrointestinal: Nausea (1%)
<1%, postmarketing, and/or case reports: Anemia, decreased platelet count, diaphoresis, disseminated intravascular coagulation, dizziness, edema, flushing, gastrointestinal hemorrhage, gastrointestinal pseudo-obstruction, hematoma, hepatitis, hypertension, increased lactate dehydrogenase, increased serum alkaline phosphatase, increased serum ALT, increased serum glucose, intestinal obstruction, jaundice, muscle cramps, palpitations, pruritus, psoriasis (Song 2021), rebound vasospasm, thrombocytopenia, vomiting, wheezing
US labeling:
Concomitant use with strong CYP3A4 inhibitors (eg, clarithromycin, telithromycin, delavirdine, indinavir, nelfinavir, ritonavir, saquinavir, ketoconazole, itraconazole, voriconazole, and nefazodone).
Nymalize: There are no contraindications listed in the manufacturer’s labeling.
Canadian labeling: Hypersensitivity to nimodipine or any component of the formulation; concomitant use with phenobarbital, phenytoin, carbamazepine, or rifampin
Concerns related to adverse effects:
• Angina/MI: Increased angina and/or MI have 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.
• Gastrointestinal events: Intestinal pseudo-obstruction and ileus have been reported (rarely) during therapy.
• Hypotension/syncope: Symptomatic hypotension with or without syncope can occur; blood pressure must be lowered at a rate appropriate for the patient's clinical condition. Monitor blood pressure closely during treatment.
• Peripheral edema: Peripheral edema is a common adverse event; occurs within 2-3 weeks of starting therapy.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with cirrhosis due to the increased plasma concentrations of nimodipine and an increased risk of adverse reactions; a lower dose and close monitoring of blood pressure and heart rate are required.
• Hypertrophic cardiomyopathy with outflow tract obstruction: Use with caution in patients with hypertrophic cardiomyopathy with outflow tract obstruction.
Other warnings/precautions:
• Inadvertent IV administration: [US Boxed Warning]: Nimodipine has inadvertently been administered IV 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.
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Atosiban: Calcium Channel Blockers may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy
Cimetidine: May increase the serum concentration of Calcium Channel Blockers. Risk C: Monitor therapy
Cladribine: Inhibitors of Equilibrative Nucleoside (ENT1) and Concentrative Nucleoside (CNT3) Transport Proteins may increase the serum concentration of Cladribine. Management: Avoid concomitant use of ENT1 or CNT3 inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider an ENT1 or CNT3 inhibitor dose reduction and separation in the timing of administration. Risk D: Consider therapy modification
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Risk C: Monitor therapy
CycloSPORINE (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of NiMODipine. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of NiMODipine. Risk X: Avoid combination
CYP3A4 Inducers (Weak): May decrease the serum concentration of NiMODipine. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of NiMODipine. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of NiMODipine. Risk X: Avoid combination
CYP3A4 Inhibitors (Weak): May increase the serum concentration of NiMODipine. Risk C: Monitor therapy
Dantrolene: May enhance the hyperkalemic effect of Calcium Channel Blockers. Dantrolene may enhance the negative inotropic effect of Calcium Channel Blockers. Risk X: Avoid combination
Dapoxetine: May enhance the orthostatic hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
FLUoxetine: May increase the serum concentration of NiMODipine. Risk C: Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Grapefruit Juice: May increase the serum concentration of NiMODipine. Risk X: Avoid combination
Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the adverse/toxic effect of Calcium Channel Blockers (Dihydropyridine). Specifically, the risk of hypotension or muscle weakness may be increased. Risk C: Monitor therapy
Melatonin: May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification
St John's Wort: May decrease the serum concentration of NiMODipine. Risk X: Avoid combination
Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Administration of capsules with a standard breakfast results in a 68% lower maximum plasma concentration and 38% lower bioavailability as compared to administration under fasted conditions. In addition, AUC and maximum plasma concentration were increased by an average of 51% and 24%, respectively, following administration of nimodipine with grapefruit juice (Fuhr 1998). Management: Administer capsules on an empty stomach, at least 1 hour before or 2 hours after meals. Avoid concurrent use of grapefruit juice and nimodipine capsules or tablets [Canadian product].
Nimodipine crosses the placenta (Belfort 1994).
Nimodipine has been evaluated for the management of preeclampsia (Belfort 1994; Belfort 2003), but it is not one of the agents currently recommended for severe intrapartum or postpartum hypertension associated with preeclampsia or eclampsia (ACOG 767 2019).
Nimodipine is present in breast milk (Carcas 1996; Tonks 1995).
Based on 2 case reports, the relative infant dose (RID) of nimodipine is <1% of the weight-adjusted maternal dose.
In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).
The RID of nimodipine was calculated following both oral and IV administration. Oral nimodipine 60 mg every 4 hours for 10 days was administered to a woman ~3 days postpartum. Breast milk was sampled after 7 days of therapy. Using the highest milk concentration (16 ng/mL), the RID of nimodipine was 0.05%, providing an estimated daily infant dose via breast milk of 2.4 mcg/kg/day (Tonks 1995). Nimodipine was administered IV to a woman ~3 weeks postpartum as an infusion of 1 mg/hour over 2 hours, then 2 mg/hour up to 24 hours (total dose 46 mg). The highest milk concentration (4.7 ng/mL) occurred ~2 hours after the infusion was completed. Authors of the study calculated the RID of nimodipine to be between 0.008% and 0.092%, providing an estimated daily infant dose via breast milk of 0.063 and 0.705 mcg/kg/day (Carcas 1996). In both cases, breast milk concentrations were variable but correlated with maternal serum concentrations.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Monitor BP and heart rate.
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
Protein binding: >95%.
Metabolism: Extensively hepatic via CYP3A4; undergoes first-pass metabolism.
Bioavailability: Capsule/oral solution: 13%; Tablet [Canadian product]: 16% (range: 3% to 30%).
Half-life elimination: 1 to 2 hours; prolonged with renal impairment.
Time to peak, serum: 0.25 to 1.05 hours.
Excretion: Urine (<1% as unchanged drug); feces.
Hepatic function impairment: In patients with cirrhosis, bioavailability is increased and Cmax almost doubles.
Geriatric: AUC and Cmax were ~2-fold higher in elderly patients compared with younger patients; this response is not considered clinically significant.
Capsules (niMODipine Oral)
30 mg (per each): $15.85 - $18.41
Solution (Nymalize Oral)
6 mg/mL (per mL): $10.41
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