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NiMODipine


General


Pronunciation

(nye MOE di peen)


Brand Names: U.S.

  • Nymalize

Indications


Use: Labeled Indications

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)


Contraindications


US labeling:

Concomitant use with strong CYP3A4 inhibitors (eg, clarithromycin, telithromycin, delaviridine, 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


ALERT: U.S. Boxed Warning

Inadvertent intravenous administration:

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.


Dosing and Administration


Dosing: Adult

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.


Dosing: Geriatric

Refer to adult dosing.


Dosing: Renal Impairment

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.


Dosing: Hepatic Impairment

Reduce dosage to 30 mg every 4 hours in patients with cirrhosis.


Administration

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.

Nasogastric (NG) or gastric tube administration:

Oral solution (Nymalize): 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.

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). 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. " � Follow with a flush of 30 mL NS.


Storage

Store at 25 � �C (77 � �F); excursions are permitted to 15 � �C to 30 � �C (59 � �F to 86 � �F). Protect capsules from light and freezing. Protect solution from light and do not refrigerate.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Generic: 30 mg

Solution, Oral:

Nymalize: 60 mg/20 mL (20 mL, 473 mL) [contains alcohol, usp, methylparaben, polyethylene glycol]


Drug Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. 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. 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. Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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). Monitor therapy

Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Monitor therapy

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. Consider therapy modification

Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

CycloSPORINE (Systemic): May decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of NiMODipine. Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of NiMODipine. Avoid combination

CYP3A4 Inducers (Weak): May decrease the serum concentration of NiMODipine. Monitor therapy

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of NiMODipine. Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of NiMODipine. Avoid combination

CYP3A4 Inhibitors (Weak): May increase the serum concentration of NiMODipine. Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dapoxetine: May enhance the orthostatic hypotensive effect of Calcium Channel Blockers. Monitor therapy

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Efavirenz: May decrease the serum concentration of Calcium Channel Blockers. Monitor therapy

Fluconazole: May increase the serum concentration of Calcium Channel Blockers. Monitor therapy

FLUoxetine: May increase the serum concentration of NiMODipine. Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Grapefruit Juice: May increase the serum concentration of NiMODipine. Avoid combination

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Macrolide Antibiotics: May decrease the metabolism of Calcium Channel Blockers. Management: Consider using a noninteracting macrolide. Felodipine Canadian labeling specifically recommends avoiding its use in combination with clarithromycin. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin. 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. Monitor therapy

Melatonin: May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nafcillin: May increase the metabolism of Calcium Channel Blockers. Consider therapy modification

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. 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. Consider therapy modification

Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

QuiNIDine: Calcium Channel Blockers (Dihydropyridine) may decrease the serum concentration of QuiNIDine. Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of QuiNIDine. QuiNIDine may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

St Johns Wort: May decrease the serum concentration of NiMODipine. Avoid combination

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy


Adverse Reactions


1% to 10%:

Cardiovascular: Decreased blood pressure (4% to 5%), bradycardia (1%)

Central nervous system: Headache (1%)

Gastrointestinal: Nausea (1%)

<1% (Limited to important or life-threatening): Anemia, decreased platelet count, disseminated intravascular coagulation, edema, gastrointestinal hemorrhage, gastrointestinal pseudo-obstruction, hematoma, hepatitis, hypertension, increased lactate dehydrogenase, increased serum alkaline phosphatase, increased serum ALT, increased serum glucose, intestinal obstruction, jaundice, rebound vasospasm, thrombocytopenia


Warnings/Precautions


Special Populations: Hepatic Function Impairment

In patients with cirrhosis, bioavailability is increased and Cmax almost doubles; dosage adjustment is recommended.


Special Populations: Elderly

AUC and Cmax were approximately twofold higher in elderly patients as compared to younger patients; this response is not considered clinically significant.


Warnings/Precautions

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 patients 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.

Concurrent drug therapy issues:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

- Inadvertent IV administration: [U.S. 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.


Pregnancy Risk Factor

C


Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Nimodipine crosses the placenta (Belfort, 1994). Nimodipine has been evaluated for the management of pre-eclampsia (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, 2015).


Actions


Pharmacology

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 drugs 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


Metabolism

Extensively hepatic via CYP3A4; undergoes first-pass metabolism


Excretion

Urine (<1% as unchanged drug); feces


Time to Peak

Serum: ~1 hour


Half-Life Elimination

1 to 2 hours; prolonged with renal impairment


Protein Binding

>95%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Have patient report immediately to prescriber severe dizziness or syncope (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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