Modus (Nimodipine)

Uses

For the improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in patients with subarachnoid hemorrhage from ruptured intracranial berry aneurysms regardless of their post ictus neurological condition.

Modus (Nimodipine) is also used to associated treatment for these conditions: Hunt and Hess Grades I-V Subarachnoid hemorrhage

How Modus (Nimodipine) works

Although the precise mechanism of action is not known, nimodipine blocks intracellular influx of calcium through voltage-dependent and receptor-operated slow calcium channels across the membranes of myocardial, vascular smooth muscle, and neuronal cells. By specifically binding to L-type voltage-gated calcium channels, nimodipine inhibits the calcium ion transfer, resulting in the inhibition of vascular smooth muscle contraction. Evidence suggests that the dilation of small cerebral resistance vessels, with a resultant increase in collateral circulation, and/or a direct effect involving the prevention of calcium overload in neurons may be responsible for nimodipine's clinical effect in patients with subarachnoid hemorrhage.

Dosage

Modus (Nimodipine) dosage

Adult: Initial dose is 60 mg in every four hours interval for 21 consecutive days, preferably not less than one hour before or two hours after meals. Oral Modus (Nimodipine) therapy should be commence within 96 hours of the subarachnoid hemorrhage.

Use in Pediatric Patients: While there is no specific information on use of this medication in pediatric patients.

Side Effects

Although side effects from nimodipine are not common, the following can occur: headache, dizziness, flushing (feeling of warmth), heartburn, fast heartbeat, slow heartbeat, upset stomach, stomach pain, constipation, depression etc.

Toxicity

Symptoms of overdosage would be expected to be related to cardiovascular effects such as excessive peripheral vasodilation with marked systemic hypotension.

Precaution

Patients with cerebral oedema or severely raised intracranial pressure. Contents of oral capsules should be given only by mouth or through a feeding tube. It must never be administered IV or by any other parenteral route. Hepatic impairment. Pregnancy and lactation.

Interaction

Plasma concentration and efficacy may be significantly reduced when administered with strong CYP3A4 inducers (e.g. rifampicin, carbamazepine, phenobarbital, phenytoin). May increase serum levels and toxicity of phenytoin. Increased plasma concentrations with cimetidine or sodium valproate.

Food Interaction

• Avoid grapefruit products.
• Take with or without food. Take consistently at the same time in regard to meals.

[Moderate] GENERALLY AVOID: The consumption of grapefruit juice may be associated with significantly increased plasma concentrations of some calcium channel blockers (CCBs) when they are administered orally.

The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

The interaction has been reported with the dihydropyridine CCBs (in roughly decreasing order of magnitude) felodipine, nisoldipine, nifedipine, and nimodipine, often with a high degree of interindividual variability.

Grapefruit juice caused more than twofold increases in felodipine, nifedipine, and nisoldipine AUCs.

MANAGEMENT: The manufacturers of nifedipine and nisoldipine recommend avoiding grapefruit juice.

Patients treated orally with other calcium channel blockers should be advised to avoid consumption of large amounts of grapefruits and grapefruit juice to prevent any undue fluctuations in serum drug levels.

Increased effects on blood pressure may persist for up to 4 days after the consumption of grapefruit juice.

Monitoring for calcium channel blocker adverse effects (e.g., headache, hypotension, syncope, tachycardia, edema) is recommended.

Modus (Nimodipine) Alcohol interaction

[Moderate]

Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation.

Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

Caution and close monitoring for development of hypotension is advised during coadministration of these agents.

Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs.

Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

Modus (Nimodipine) multivitamins interaction

[Moderate] Calcium-containing products may decrease the effectiveness of calcium channel blockers by saturating calcium channels with calcium.

Calcium chloride has been used to manage acute severe verapamil toxicity.

Management consists of monitoring the effectiveness of calcium channel blocker therapy during coadministration with calcium products.

Modus (Nimodipine) Drug Interaction

Major: phenytoin, carbamazepineModerate: aspirin, clonazepam, furosemide, metoprololUnknown: amoxicillin / clavulanate, levetiracetam, lamotrigine, insulin glargine, atorvastatin, pregabalin, amlodipine, acetaminophen, clopidogrel, lvp solution with potassium, cyanocobalamin, ascorbic acid, cholecalciferol, phytonadione

Modus (Nimodipine) Disease Interaction

Major: cardiogenic shock/hypotension, coronary artery disease, liver diseaseModerate: CHF/AMI

Elimination Route

In humans, nimodipine is rapidly absorbed after oral administration, and peak concentrations are generally attained within one hour. Bioavailability is 100% following intravenous administration and 3-30% following oral administration due to extensive first-pass metabolism.

Half Life

1.7-9 hours

Elimination Route

Modus (Nimodipine) is eliminated almost exclusively in the form of metabolites and less than 1% is recovered in the urine as unchanged drug. Numerous metabolites, all of which are either inactive or considerably less active than the parent compound, have been identified.

Pregnancy & Breastfeeding use

Use in Pregnancy: Large doses of nimodipine have been shown to cause birth defects in animals. Human studies have not been done. Before you take nimodipine, tell your doctor if you are pregnant or plan to become pregnant.

Use in Nursing Mothers: Modus (Nimodipine) may pass into breast milk but has not been reported to cause problems; caution is advised. Consult your doctor for advice.

Contraindication

Use within 1 mth of MI or an episode of unstable angina. Concomitant use with potent CYP3A4 inhibitors (e.g. clarithromycin, ritonavir, ketoconazole, nefazodone).

Acute Overdose

Symptoms: Excessive peripheral vasodilation, systemic hypotension, tachycardia, bradycardia, GI complaints, nausea.

Management: Symptomatic and supportive treatment. Admin of vasopressor may be necessary if significant hypotension occurs. IV Ca salts have been also used for hypotension.

Storage Condition

Store between 15-30° C. Protect from light.

Innovators Monograph

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