NYMALIZE
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 418.4 |
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 | Avoid; animal studies show teratogenicity (skeletal malformations) and fetal toxicity; no adequate human data. |
| 2nd trimester | Avoid; may cause fetal hypotension, hypoxia, and reduced uteroplacental blood flow. |
| 3rd trimester | Avoid; risk of fetal hypoxia, premature closure of ductus arteriosus, and neonatal adverse effects (hypotension, bradycardia). |
Clinical note
Comprehensive clinical and safety monograph for NYMALIZE (NYMALIZE).
| Placental transfer | Crosses placenta; detectable in fetal plasma after maternal administration. |
| Breastfeeding | Excreted into breast milk in small amounts; use with caution, monitor infant for hypotension and bradycardia; consider alternative agent. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to nimodipine or any componentSevere hypotension (systolic BP <90 mmHg)Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir)Concomitant use with strong CYP3A4 inducers (e.g., rifampin, phenytoin)Recent myocardial infarction or unstable angina (due to risk of reflex tachycardia)
| 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. |
| Food/Dietary | Grapefruit juice increases nimodipine plasma concentrations by inhibiting CYP3A4 metabolism, potentially leading to toxicity. Avoid grapefruit products entirely. Alcohol may exacerbate hypotension and dizziness. No other significant food interactions. |
| Clinical Pearls | Nymalize (nimodipine) is a calcium channel blocker used specifically to prevent vasospasm following subarachnoid hemorrhage (SAH). It must be administered via nasogastric tube if the patient has impaired swallowing or is intubated. Monitor blood pressure closely due to risk of hypotension. Enteral administration is preferred over IV; if IV is used, avoid PVC tubing as nimodipine adsorbs to PVC. Do not administer with grapefruit juice. |
| Patient Advice | Take this medication exactly as prescribed, even if you feel well. · If you cannot swallow the capsule, the liquid can be extracted using a needle and taken orally or via feeding tube. · Do not consume grapefruit or grapefruit juice while taking this medication. · Avoid alcohol as it may increase dizziness or hypotension. · Sit up slowly from lying or sitting position to prevent dizziness from low blood pressure. · Store capsules at room temperature away from light and moisture. |
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