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: For enteral 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.
Cirrhosis: 30 mg every 4 hours for 21 consecutive days.
Hypotension:
Note: Optimal management is not clearly defined (Ref).
May consider halving dose and administering more frequently (eg, 30 mg every 2 hours); discontinuation of therapy may be necessary if hypotension persists (Ref).
Refer to adult dosing; use with caution.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Cardiovascular: Bradycardia (1%), decreased blood pressure (4%)
Gastrointestinal: Nausea (1%)
Nervous system: Headache (1%)
<1%:
Cardiovascular: Flushing, hypertension, palpitations, rebound vasospasm
Dermatologic: Diaphoresis, pruritus
Endocrine & metabolic: Increased lactate dehydrogenase, increased serum glucose
Gastrointestinal: Gastrointestinal hemorrhage, vomiting
Hematologic & oncologic: Anemia, hematoma, thrombocytopenia
Hepatic: Hepatitis, increased serum alanine aminotransferase, increased serum alkaline phosphatase, jaundice
Nervous system: Dizziness
Neuromuscular & skeletal: Muscle cramps, myalgia
Respiratory: Wheezing
Postmarketing:
Dermatologic: Psoriasis (Song 2021)
Gastrointestinal: Gastrointestinal pseudo-obstruction (including Ogilvie syndrome) (De Jesus 2022, Fahy 1996), intestinal obstruction
Respiratory: Hypoxemia (Baker 2015)
Capsules: Concomitant use with strong CYP3A4 inhibitors (eg, clarithromycin, telithromycin, delavirdine, indinavir, nelfinavir, ritonavir, saquinavir, ketoconazole, itraconazole, voriconazole, nefazodone).
Oral solution: There are no contraindications listed in the manufacturer’s labeling.
Tablets [Canadian product]: Hypersensitivity to nimodipine or any component of the formulation; concomitant use with phenobarbital, phenytoin, carbamazepine, or rifampin.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
• 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.
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: When inadvertently administered IV, fatality may occur; precautions (eg, adequate labeling, use of oral syringes) should be employed against such an event.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Generic: 30 mg
Solution, Oral:
Nymalize: 6 mg/mL (5 mL, 10 mL, 237 mL) [contains alcohol, usp, methylparaben, polyethylene glycol (macrogol)]
Generic: 60 mg/20 mL (473 mL)
Yes
Capsules (niMODipine Oral)
30 mg (per each): $19.23
Solution (niMODipine Oral)
60 mg/20 mL (per mL): $5.93
Solution (Nymalize Oral)
6 mg/mL (per mL): $12.82
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Nimotop: 30 mg
For enteral administration ONLY. Life-threatening adverse events have occurred when administered parenterally.
Oral:
Capsules, oral solution: Administer at least 1 hour before or 2 hours after meals.
Tablets [Canadian product]: Administer without regards to meals; but administer consistently either 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: Administer at least 1 hour before or 2 hours after meals. Administer using the supplied oral syringe labeled “ORAL USE ONLY.” Following administration, refill oral syringe with 10 mL of NS and flush any remaining contents from NG or gastric tube into the stomach.
Capsules: Administer at least 1 hour before or 2 hours after meals. 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” (Ref). 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 from ruptured intracranial aneurysms regardless of post-ictus neurological condition (ie, Hunt and Hess grades I to V) (AHA/ASA [Hoh 2023]; NCS [Treggiari 2023]; manufacturer’s labeling).
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." 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.
Substrate of CYP3A4 (Major with inhibitors), CYP3A4 (Minor with inducers); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits ENT1 and CNT3;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Amifostine: Blood Pressure Lowering Agents may increase hypotensive effects 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 decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor
Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Atosiban: Calcium Channel Blockers may increase adverse/toxic effects of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Risk C: Monitor
Barbiturates: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Benperidol: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Brigatinib: May decrease antihypertensive effects of Antihypertensive Agents. Brigatinib may increase bradycardic effects of Antihypertensive Agents. Risk C: Monitor
Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Bromperidol: May decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid
Calcium Salts: May decrease therapeutic effects of Calcium Channel Blockers. Risk C: Monitor
Cimetidine: May increase serum concentration of Calcium Channel Blockers. Risk C: Monitor
Cladribine: Inhibitors of Equilibrative Nucleoside (ENT1) and Concentrative Nucleoside (CNT3) Transporters may increase 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 serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CycloSPORINE (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase serum concentration of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of NiMODipine. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of NiMODipine. Risk X: Avoid
CYP3A4 Inducers (Weak): May decrease serum concentration of NiMODipine. Risk C: Monitor
CYP3A4 Inhibitors (Moderate): May increase serum concentration of NiMODipine. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of NiMODipine. Risk X: Avoid
CYP3A4 Inhibitors (Weak): May increase serum concentration of NiMODipine. Risk C: Monitor
Dantrolene: May increase hyperkalemic effects of Calcium Channel Blockers. Dantrolene may increase negative inotropic effects of Calcium Channel Blockers. Risk X: Avoid
Dapoxetine: May increase orthostatic hypotensive effects of Calcium Channel Blockers. Risk C: Monitor
Dexmethylphenidate: May decrease therapeutic effects of Antihypertensive Agents. Risk C: Monitor
Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
DULoxetine: Blood Pressure Lowering Agents may increase hypotensive effects of DULoxetine. Risk C: Monitor
Flunarizine: May increase therapeutic effects of Antihypertensive Agents. Risk C: Monitor
FLUoxetine: May increase serum concentration of NiMODipine. Risk C: Monitor
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Grapefruit Juice: May increase serum concentration of NiMODipine. Risk X: Avoid
Herbal Products with Blood Pressure Increasing Effects: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Iloperidone: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Indoramin: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Inhalational Anesthetics: May increase hypotensive effects of Calcium Channel Blockers. Risk C: Monitor
Isocarboxazid: May increase antihypertensive effects of Antihypertensive Agents. Risk X: Avoid
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor
Loop Diuretics: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Magnesium Sulfate: May increase adverse/toxic effects of Calcium Channel Blockers (Dihydropyridine). Specifically, the risk of hypotension or muscle weakness may be increased. Risk C: Monitor
Melatonin: May decrease antihypertensive effects of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor
Metergoline: May decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. Risk C: Monitor
Methylphenidate: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may increase neuromuscular-blocking effects of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor
Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor
Obinutuzumab: May increase hypotensive effects 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 increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Perazine: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Phenobarbital-Primidone: May decrease serum concentration of NiMODipine. Risk X: Avoid
Pholcodine: Blood Pressure Lowering Agents may increase hypotensive effects of Pholcodine. Risk C: Monitor
Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Prazosin: Antihypertensive Agents may increase hypotensive effects of Prazosin. Risk C: Monitor
Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Sincalide: Drugs that Affect Gallbladder Function may decrease therapeutic effects 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 serum concentration of NiMODipine. Risk X: Avoid
Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Terazosin: Antihypertensive Agents may increase hypotensive effects of Terazosin. Risk C: Monitor
Urapidil: Antihypertensive Agents may increase hypotensive effects of Urapidil. Risk C: Monitor
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 or oral solution on an empty stomach, at least 1 hour before or 2 hours after meals. Avoid concurrent use of grapefruit juice and nimodipine capsules, oral solution, or tablets [Canadian product].
Nimodipine crosses the placenta (Belfort 1994).
Fetal outcome data following maternal use of nimodipine during pregnancy are limited (Magee 1996; Weber-Schoendorfer 2008).
The management of subarachnoid hemorrhage in pregnant patients is generally managed the same as nonpregnant patients, considering the trimester at presentation. However, data describing use of nimodipine are limited and use should consider the fetal risks of maternal hypotension (Ascanio 2019; Beighley 2021; Fritzsche 2017; Robba 2016; Toossi 2019; Wilson 2005).
Nimodipine is known to cause cerebral vasodilation and hypotension, and therefore has been evaluated for the treatment of hypertension and prevention of seizures in patients with preeclampsia (Belfort 1994; Belfort 2003). However, nimodipine is not as effective as other agents in reducing high BP or reducing the risk of developing eclampsia and is not currently recommended for the management of preeclampsia (ACOG 2020; Duley 2013).
Nimodipine is present in breast milk (Carcas 1996; Tonks 1995).
Data related to the presence of nimodipine in breast milk are available from 2 case reports. Oral nimodipine 60 mg every 4 hours for 10 days was administered to a woman ~3 days postpartum for the treatment of a subarachnoid hemorrhage. Breast milk and maternal serum were sampled every 3 hours for 24 hours, following 7 days of therapy. Although variable, nimodipine breast milk levels were approximately one-third of the maternal plasma concentrations. The highest breast milk concentration was ~3.5 ng/mL (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 relative infant dose (RID) of nimodipine to be between 0.008% and 0.092% of the weight adjusted maternal dose, providing an estimated daily infant dose via breast milk of 0.063 and 0.705 mcg/kg/day (Carcas 1996). In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).
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.
BP and heart rate.
Nimodipine shares the pharmacology of other calcium channel blockers; animal studies indicate that nimodipine has a greater effect on cerebral arteries 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.
Older adult: AUC and Cmax were ~2-fold higher in elderly patients compared with younger patients; this response is not considered clinically significant.