Nimodipine (nimodipine)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Nimodipine is a 1,4-dihydropyridine-derivative calcium-channel blocking agent with greater selectivity for cerebral blood vessels.
Nimodipine is a 1,4-dihydropyridine-derivative calcium-channel blocking agent that has greater selectivity for cerebral blood vessels; it is structurally related to nifedipine. The calcium-channel blocking activity of nimodipine appears to be attributable principally to the levorotatory, S-configuration isomer, this is of unknown clinical relevance. Nimodipine inhibits transmembrane influx of extracellular calcium ions across the membranes of myocardial, vascular smooth muscle, and neuronal cells.
Nimodipine exerts relatively selective pharmacologic effects on cerebral arteries compared with arteries elsewhere in the body, which may be attributable in part to the drug's high lipid solubility, ability to cross the blood-brain barrier, and specific binding to cerebral tissue. The mechanism by which nimodipine provides a favorable effect on the severity of neurologic deficits caused by delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage is not known. It is not clear if nimodipine prevents or relieves cerebral artery vasospasm, however, it has been shown to dilate blood vessels and prevent vasoconstriction in small arterioles (70-100 mcm in diameter).
Nimodipine is rapidly and almost completely absorbed following oral administration; however, because of extensive first-pass metabolism in the liver, oral bioavailability of the drug is low and variable. Limited data indicate that oral bioavailability of nimodipine administered in single doses as capsules to healthy individuals averages approximately 13% (range 3-30%). The bioavailability of nimodipine from commercially available oral solution preparations is comparable to the bioavailability of oral capsules.
Sublingual administration of the contents of the capsule does not appear to alter the degree of first-pass metabolism of nimodipine. Presence of food in the GI tract can substantially decrease the extent of oral absorption of nimodipine. In one study in a limited number of healthy individuals, administration of nimodipine capsules following a standard breakfast decreased peak plasma concentrations 68% and decreased bioavailability 38% compared with administration on an empty stomach.
Limited evidence suggests that the drug may undergo enterohepatic circulation.
Peak nimodipine concentrations are attained within 1 hour after oral administration of single doses of the drug as capsules, tablets, or a solution. In patients with subarachnoid hemorrhage, peak plasma nimodipine concentrations after oral dosing exhibit considerable interindividual variation, but generally occur 1 hour after administration and range from 7-96 ng/mL. Systemic availability of nimodipine may be increased substantially in patients with hepatic disease (e.g., cirrhosis).
In one study, after oral administration of single 60-mg doses of nimodipine as capsules, a mean peak serum nimodipine concentration and AUC were 1.5- and 4-times as high, respectively, in patients with hepatic cirrhosis compared to age-matched healthy individuals receiving the same dose. The manufacturer states nimodipine peak plasma concentrations may approximately double in those with hepatic cirrhosis; a lower nimodipine dosage is recommended.
In a parallel-group study, peak plasma concentration and AUC following administration of nimodipine 30 mg as a single dose and at steady state (3 times daily for 6 days) were about twice as high in geriatric individuals (59-79 years of age) as in younger adults (22-40 years of age). However, the clinical responses associated with these age-related differences were not considered important. Plasma protein binding of unchanged nimodipine averages more than 95% and is independent of concentration over a range of 10 ng/mL to 10 mcg/mL.
Studies in animals indicate that nimodipine is widely distributed into body tissues after oral or IV administration (IV dosage form currently not commercially available in the US). Following IV administration in healthy individuals, nimodipine distributes rapidly into the central compartment with a half-life of approximately 6-7 minutes; the volume of distribution of the central compartment averaged 0.43 L/kg. The steady-state volume of distribution following IV administration has been reported to range from 0.94-2.3 L/kg.
Nimodipine appears to distribute to a limited extent into CSF. However, concentrations as high as 12.5 ng/mL reportedly have been detected in CSF of at least one patient with subarachnoid hemorrhage receiving the drug. Nimodipine has been detected in human milk.
Nimodipine crosses the placenta to a limited extent in animals. Nimodipine and its metabolites are distributed into milk in animals in concentrations substantially exceeding those in maternal plasma. Nimodipine concentrations appear to decline in a biphasic manner; the early elimination and terminal elimination half-life is 1-2 and 8-9 hours, respectively.
No evidence of drug accumulation was noted in patients receiving 40 mg of nimodipine 3 times daily for 7 days.
Nimodipine is extensively metabolized (mediated by CYP3A4) in the liver; less than 1% is recovered as unchanged drug in the urine. All metabolites of nimodipine are either inactive or substantially less active than the parent drug. Approximately 50% of an orally administered dose of nimodipine is excreted almost exclusively as metabolites in the urine within 4 days.
A single study indicated prolongation of nimodipine elimination half-life and a reduction in plasma clearance of the drug in patients with renal impairment, defined as an estimated glomerular filtration rate <60 mL/minute, compared with healthy individuals; however, these findings may have been attributable in part to age-related reductions in liver function in patients with renal impairment, who were substantially older (mean age 65.3 years) than healthy controls (mean age 25.2 years). In a second study, investigators reported variability in nimodipine pharmacokinetics among patients with a creatinine clearance between 51-80 mL/minute. Dialysis is not likely to be beneficial in removing nimodipine from the body due to its extensive protein binding.
USES: Nimodipine is used to decrease problems due to a certain type of bleeding in the brain (subarachnoid hemorrhage-SAH). Nimodipine is called a calcium channel blocker. The body naturally responds to bleeding by narrowing the blood vessel to slow blood flow.
However, when the bleeding is in the brain, stopping blood flow causes more brain damage. Nimodipine is thought to work by relaxing narrowed blood vessels in the brain near the area of bleeding so blood can flow more easily. This effect reduces brain damage.
Generic name: nimodipine
Pronunciation: (nye-MOE-di-peen)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Nimodipine
Indications
The following indications are listed for Nimodipine:
- Subarachnoid Intracranial Hemorrhage
Also known as: Subarachnoid Hemorrhage, Subarachnoid Intracranial Bleeding.
Dosing
No dosing information is available for this tab.
Nimodipine is administered orally only (as capsules or an oral solution). The manufacturer recommends administration at least 1 hour before or 2 hours after meals.
Nimodipine has been administered by IV infusion+ (IV dosage form currently not commercially available in the US) and by intracisternal+ or intraventricular+ surgical application of a nimodipine sustained-release microparticle formulation (dosage form currently not commercially available in the US) in patients with subarachnoid hemorrhage. The manufacturer states that the contents of nimodipine capsules or nimodipine oral solution must not be administered IV or by any other parenteral route; death and serious, life-threatening adverse effects such as cardiac arrest, cardiovascular collapse, hypotension, and bradycardia have occurred with such administration.
Nimodipine oral solution may be administered orally or into a nasogastric or gastric tube following transfer into a designated oral syringe. To minimize administration errors, the syringe should be labeled for oral use only; not for IV use. Refill the oral syringe with 0.9% sodium chloride solution and then flush any remaining contents from the nasogastric or gastric tube into the stomach. Consult the manufacturer's administration instructions for the appropriate volume of flush solution.
If the oral capsule cannot be swallowed (e.g., when administered at the time of surgery or to an unconscious patient) and the oral solution is not available, the liquid-filled capsule may be punctured at both ends with an 18-gauge needle and the contents transferred to an oral syringe that cannot accept a needle and that is designed for naso-gastric or percutaneous endoscopic gastrostomy (PEG) tube administration. To minimize administration errors, the syringe should be labeled for oral use only; not for IV use. The contents of the capsule should then be administered via the patient's nasogastric tube. Following administration, the tubing should be flushed with 30 mL of 0.9% sodium chloride solution.
Nimodipine capsules should be protected from light by storing them in the manufacturer's original unit-dose foil packaging; the capsules also should be protected from freezing and stored at 20-25degreesC (excursions permitted to 15-30degreesC).
Nimodipine 3 and 6 mg/mL oral solution should be stored at 20-25degreesC (excursions permitted to 15-30degreesC); do not refrigerate the oral solution and protect it from light and freezing.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Nimodipine is metabolized by cytochrome P-450 (CYP) isoenzyme 3A4. Inhibitors and inducers of these isoenzymes may reduce or increase nimodipine clearance, respectively.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Concomitant use with strong cytochrome P-450 (CYP) 3A4 inhibitors (e.g., clarithromycin, nelfinavir, ritonavir, ketoconazole, itraconazole, voriconazole, nefazodone) due to the risk of significant hypotension.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Most common reported adverse reactions were hypotension, headache, nausea, and bradycardia.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of nimodipine in children younger than 18 years of age have not been established.
There are no adequate and controlled studies evaluating use of nimodipine in pregnant women. Nimodipine at oral (gavage) dosages of 1 (less than the recommended human dose (RHD) of 360 mg/day on a body surface area (mg/m2) basis) or 10 mg/kg daily, but not at 3 mg/kg daily, was associated with an increased incidence of malformations and stunted fetal growth when given from day 6 through day 18 of pregnancy in rabbits. In a second study, an increased incidence of stunted fetal growth was observed at oral dosages of 1 mg/kg daily but not at the higher dosages. Nimodipine was embryotoxic in rats at oral dosages of 100 mg/kg daily (approximately 3 times the RHD on a mg/m2 basis), causing resorption or stunted fetal growth when administered by gavage from day 6 through 15 of pregnancy. Slight maternotoxicity was observed in one of these studies but may have been attributable to the presence of polyethylene glycol 400 in the gavage solution. When administered in 2 other studies to rats at oral dosages of 30 mg/kg daily (dose similar to the RHD on a mg/m2 basis) from day 16 of gestation until sacrifice (at day 20 of pregnancy or day 21 postpartum), nimodipine was associated with higher incidences of skeletal variation, stunted fetal growth, and stillbirths, but no malformations. In addition, the drug did not impair postnatal development.
Nimodipine should be used during pregnancy only when the potential benefits justify the risks to the fetus.
Nimodipine has been detected in human milk; however, it is not known whether the drug has any effects on milk production or on the breastfed infant. Nimodipine and/or its metabolites are distributed into milk in animals (rats) in concentrations much higher than those in maternal plasma.
Consider the mother's clinical need for nimodipine and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.
The manufacturer recommends cautious dosage selection in geriatric patients, reflecting the greater frequency of decreased hepatic, renal and/or cardiac function, and of concomitant disease or other drug therapy.
The manufacturers state that clinical studies of nimodipine did not include a sufficient number of patients 65 years of age or older to determine whether such patients respond differently than younger individuals, but that other reported clinical experience has not identified differences in response between geriatric and younger patients. In a pharmacokinetic study, peak plasma concentrations and AUC of nimodipine were about twice as high in geriatric individuals as in younger individuals following single and multiple dosing; however, no clinically important age-related differences in response were noted. An appropriate dosage of nimodipine in geriatric patients should be selected with caution because of the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy in these patients.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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