NYMALIZE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NYMALIZE (NYMALIZE).
NMDA receptor antagonist; acts as a neuroprotective agent by reducing excitotoxicity and modulating calcium influx. Also binds to sigma-1 receptors, possibly contributing to neuroprotection.
| Metabolism | Primarily metabolized by CYP3A4 and to a lesser extent by CYP2D6; forms active metabolites (e.g., dextrorphan and 3-methoxymorphinan). |
| Excretion | Nymalize (nimodipine) is primarily eliminated via hepatic metabolism. Approximately 50% of the dose is excreted in urine as metabolites and <1% as unchanged drug. Fecal excretion accounts for ~20% of metabolites. Less than 1% is excreted unchanged in bile. Renal clearance is negligible for parent compound. |
| Half-life | Terminal elimination half-life is approximately 8–9 hours (range 5–12 hours) in patients with subarachnoid hemorrhage. In elderly or hepatically impaired patients, half-life may be prolonged. Clinically, steady-state is achieved after 3–5 days of oral dosing. |
| Protein binding | Nimodipine is 97–99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 0.8–1.6 L/kg. This large Vd indicates extensive tissue distribution, including penetration into the brain (cerebrospinal fluid concentrations are about 10% of plasma levels). |
| Bioavailability | Oral bioavailability is approximately 13% (range 3–30%) due to extensive first-pass hepatic metabolism. Intravenous administration yields 100% bioavailability. |
| Onset of Action | Oral: Onset of action occurs within 30–60 minutes after oral administration. Intravenous: Onset is immediate with infusion; however, therapeutic effects on vasospasm prevention are delayed (days). |
| Duration of Action | Oral: Duration of action is approximately 4–6 hours for hemodynamic effects, but clinical effect on vasospasm prevention is sustained over the treatment course (21 days). Intravenous: Duration parallels infusion time; hemodynamic effects cease shortly after discontinuation. |
10 mg (5 mL) intravenously over 5-15 minutes, may repeat after 15 minutes if needed; followed by continuous infusion of 0.9-2.0 mg/hour (5-10 mL/hour).
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for renal impairment; not removed by hemodialysis. |
| Liver impairment | Child-Pugh B or C: reduce dose by 50%; consider alternative therapy in severe hepatic impairment. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; monitor for hypotension due to age-related decreased baroreceptor sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NYMALIZE (NYMALIZE).
| Breastfeeding | Nimodipine is excreted in human milk. The M/P ratio is not established. Due to potential for serious adverse reactions in nursing infants, discontinue breast-feeding or discontinue drug, taking into account the importance of the drug to the mother. |
| Teratogenic Risk | First trimester: Cases of metabolic acidosis and respiratory depression in the neonate have been reported with intravenous nimodipine during pregnancy; however, oral nimodipine (NYMALIZE) lacks adequate studies. Second and third trimesters: Potential for maternal hypotension and reduced uteroplacental perfusion. Overall, nimodipine is an FDA Pregnancy Category C drug. Use only if potential benefit justifies risk to the fetus. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to the drug; concomitant use with other NMDA antagonists (e.g., ketamine, methoxetamine); monotherapy for schizophrenia; severe hepatic impairment (Child-Pugh class C).
| Precautions | Risk of abuse, dependence, and withdrawal; may cause cognitive and motor impairment; contraindicated in combination with other NMDA antagonists; use caution in patients with respiratory depression, severe hepatic impairment, or recent myocardial infarction. |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate periodically. Assess fetal heart rate patterns if used near term or during labor. In neonates, observe for signs of metabolic acidosis and respiratory depression if exposure occurred near delivery. |
| Fertility Effects | In animal studies, reduced fertility and increased post-implantation loss were observed at high doses. Human data are insufficient to determine effects on fertility. |