NDC 0904-6566 Nimodipine

Nimodipine

NDC Product Code 0904-6566

NDC Code: 0904-6566

Proprietary Name: Nimodipine What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Nimodipine What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Product Characteristics

Color(s):
GRAY (C48324 - GRAY OPAQUE)
Shape: CAPSULE (C48336)
Size(s):
15 MM
Imprint(s):
A297
Score: 1

NDC Code Structure

  • 0904 - Major Pharmaceuticals

NDC 0904-6566-61

Package Description: 100 BLISTER PACK in 1 BOX, UNIT-DOSE > 1 CAPSULE, LIQUID FILLED in 1 BLISTER PACK

NDC Product Information

Nimodipine with NDC 0904-6566 is a a human prescription drug product labeled by Major Pharmaceuticals. The generic name of Nimodipine is nimodipine. The product's dosage form is capsule, liquid filled and is administered via oral form.

Labeler Name: Major Pharmaceuticals

Dosage Form: Capsule, Liquid Filled - A solid dosage form in which the drug is enclosed within a soluble, gelatin shell which is plasticized by the addition of a polyol, such as sorbitol or glycerin, and is therefore of a somewhat thicker consistency than that of a hard shell capsule; typically, the active ingredients are dissolved or suspended in a liquid vehicle.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Nimodipine Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • NIMODIPINE 30 mg/1

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • GLYCERIN (UNII: PDC6A3C0OX)
  • PEPPERMINT OIL (UNII: AV092KU4JH)
  • WATER (UNII: 059QF0KO0R)
  • POLYETHYLENE GLYCOL 400 (UNII: B697894SGQ)
  • GELATIN (UNII: 2G86QN327L)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • FERROSOFERRIC OXIDE (UNII: XM0M87F357)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Calcium Channel Antagonists - [MoA] (Mechanism of Action)
  • Dihydropyridine Calcium Channel Blocker - [EPC] (Established Pharmacologic Class)
  • Dihydropyridines - [CS]

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Major Pharmaceuticals
Labeler Code: 0904
FDA Application Number: ANDA090103 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 01-01-2015 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

End Marketing Date: 12-16-2019 What is the End Marketing Date?
This is the date the product will no longer be available on the market. If a product is no longer being manufactured, in most cases, the FDA recommends firms use the expiration date of the last lot produced as the EndMarketingDate, to reflect the potential for drug product to remain available after manufacturing has ceased. Products that are the subject of ongoing manufacturing will not ordinarily have any EndMarketingDate. Products with a value in the EndMarketingDate will be removed from the NDC Directory when the EndMarketingDate is reached.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Information for Patients

Nimodipine

Nimodipine is pronounced as (nye moe' di peen)

Why is nimodipine medication prescribed?
Nimodipine is used to decrease brain damage that may be caused by a subarachnoid hemorrhage (bleeding in the space surrounding the brain that occurs when a weakened blood...
[Read More]

* Please review the disclaimer below.

Nimodipine Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Rx Only

Ascend Laboratories, LLC

Description

Nimodipine capsules belongs to the class of pharmacological agents known as calcium channel blockers. Nimodipine is isopropyl 2 – methoxyethyl 1, 4 – dihydro – 2, 6 – dimethyl – 4 – (m-nitrophenyl) – 3, 5 – pyridinedicarboxylate. It has a molecular weight of 418.5 and a molecular formula of C21H26N2O7. The structural formula is:Nimodipine is a yellow crystalline substance, practically insoluble in water.Nimodipine capsules are formulated as soft gelatin capsules for oral administration. Each liquid filled capsule contains 30 mg of nimodipine in a vehicle of glycerin, peppermint oil, purified water and polyethylene glycol 400. The soft gelatin capsule shell contains gelatin, glycerin, purified water, titanium dioxide and iron oxide black.

Mechanism Of Action

Mechanism of Action: Nimodipine is a calcium channel blocker. The contractile processes of smooth muscle cells are dependent upon calcium ions, which enter these cells during depolarization as slow ionic transmembrane currents. Nimodipine inhibits calcium ion transfer into these cells and thus inhibits contractions of vascular smooth muscle. In animal experiments, nimodipine had a greater effect on cerebral arteries than on arteries elsewhere in the body perhaps because it is highly liphophilic, allowing it to cross the blood-brain barrier; concentrations of nimodipine as high as 12.5 ng/mL have been detected in the cerebrospinal fluid of nimodipine-treated subarachnoid hemorrhage (SAH) patients.The precise mechanism of action of nimodipine in humans is unknown. Although the clinical studies described below demonstrate a favorable effect of nimodipine on the severity of neurological deficits caused by cerebral vasospasm following SAH, there is no arteriographic evidence that the drug either prevents or relieves the spasm of these arteries. However, whether or not the arteriographic methodology utilized was adequate to detect a clinically meaningful effect, if any, on vasospasm is unknown.

Pharmacokinetics

Pharmacokinetics and Metabolism: In man, nimodipine is rapidly absorbed after oral administration, and peak concentrations are generally attained within one hour. The terminal elimination half-life is approximately 8 to 9 hours but earlier elimination rates are much more rapid, equivalent to a half-life of 1-2 hours; a consequence is the need for frequent (every 4 hours) dosing. There were no signs of accumulation when nimodipine was given three times a day for seven days. Nimodipine is over 95% bound to plasma proteins. The binding was concentration independent over the range of 10 ng/mL to 10 μg/mL. 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. Because of a high first-pass metabolism, the bioavailability of nimodipine averages 13% after oral administration. The bioavailability is significantly increased in patients with hepatic cirrhosis, with Cmax approximately double that in normals which necessitates lowering the dose in this group of patients (see Dosage and Administration). In a study of 24 healthy male volunteers, administration of nimodipine capsules following a standard breakfast resulted in a 68% lower peak plasma concentration and 38% lower bioavailability relative to dosing under fasted conditions. In a single parallel-group study involving 24 elderly subjects (aged 59-79) and 24 younger subjects (aged 22-40), the observed AUC and Cmax of nimodipine was approximately 2-fold higher in the elderly population compared to the younger study subjects following oral administration (given as a single dose of 30 mg and dosed to steady-state with 30 mg t.i.d. for 6 days). The clinical response to these age-related pharmacokinetic differences, however, was not considered significant. (See PRECAUTIONS: Geriatric Use.)

Clinical Studies

Clinical Trials: Nimodipine has been shown, in 4 randomized, double-blind, placebo-controlled trials, to reduce the severity of neurological deficits resulting from vasospasm in patients who have had a recent subarachnoid hemorrhage (SAH). The trials used doses ranging from 20-30 mg to 90 mg every 4 hours, with drug given for 21 days in 3 studies, and for at least 18 days in the other. Three of the four trials followed patients for 3-6 months. Three of the trials studied relatively well patients, with all or most patients in Hunt and Hess Grades I-III (essentially free of focal deficits after the initial bleed) the fourth studied much sicker patients, Hunt and Hess Grades III-V. Two studies, one U.S., one French, were similar in design, with relatively unimpaired SAH patients randomized to nimodipine or placebo. In each, a judgment was made as to whether any late-developing deficit was due to spasm or other causes, and the deficits were graded. Both studies showed significantly fewer severe deficits due to spasm in nimodipine group; the second (French) study showed fewer spasm-related deficits of all severities. No effect was seen on deficits not related to spasm.PatientsStudyDoseGradeHunt and Hess GradeNumberAnalyzedAny DeficitDue to SpasmNumbers withSevere DeficitU.S.20-30 mgI-IIINimodipinePlacebo56 60131618p=0.03French60 mgI-IIINimodipinePlacebo3139411 210A third, large, study was performed in the United Kingdom in SAH patients with all grades of severity (but 89% were in Grades I-III). Nimodipine was dosed 60mg every 4 hours. Outcomes were not defined as spasm related or not but there was a significant reduction in the overall rate of infarction and severely disabling neurological outcome at 3 months:NimodipinePlaceboTotal patients278276Good recovery199p = 0.0444 – good and moderate vs severe and dead169Moderate disability2416Severe disability12p = 0.001 – severe disability31Death43p = 0.056 – death60A Canadian study entered much sicker patients, (Hunt and Hess Grades III-V), who had a high rate of death and disability, and used a dose of 90 mg every 4 hours, but was otherwise similar to the first two studies. Analysis of delayed ischemic deficits, many of which result from spasm, showed a significant reduction in spasm-related deficits. Among analyzed patients (72 nimodipine, 82 placebo), there were the following outcomes.Delayed IschemicDeficits (DID)PermanentDeficitsNimodipinen (%)Placebon (%)Nimodipinen (%)Placebon (%)DID Spasm Alone8 (11)p=0.001, nimodipine vs placebo25 (31)5 (7)22 (27)DID Spasm Contributing18 (25)21 (26)16 (22)17 (21)DID Without Spasm7 (10)8 (10)6 (8)7 (9)No DID39 (54)28 (34)45 (63)36 (44)When data were combined for the Canadian and the United Kingdom studies, the treatment difference on success rate (i.e. good recovery) on the Glasgow Outcome Scale was 25.3% (nimodipine) versus 10.9% (placebo) for Hunt and Hess Grades IV or V. The table below demonstrates that nimodipine tends to improve good recovery of SAH patients with poor neurological status post-ictus, while decreasing the numbers with severe disability and vegetative survival.Glasgow Outcomep=0.045, nimodipine vs placeboNimodipine(n=87)Placebo(n=101)Good Recovery22 (25.3%)11 (10.9%)Moderate Disability8 (9.2%)12 (11.9%)Severe Disability6 (6.9%)15 (14.9%)Vegetative Survival4 (4.6%)9 (8.9%)Death47 (54.0%)54 (53.5%)A dose-ranging study comparing 30, 60 and 90 mg doses found a generally low rate of spasm-related neurological deficits but no dose response relationship.

Indications And Usage

Nimodipine is indicated 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 (i.e., Hunt and Hess Grades I-V).

Contraindications

The concomitant use of nimodipine with strong inhibitors of CYP3A4 such as some macrolide antibiotics (e.g., clarithromycin, telithromycin), some anti-HIV protease inhibitors (e.g., delaviridine, indinavir, nelfinavir, ritonavir, saquinavir), some azole antimycotics (e.g., ketoconazole, itraconazole, voriconazole) and some antidepressants (e.g., nefazadone) is contraindicated because of a risk of significant hypotension (see PRECAUTIONS, Drug Interactions).

Warnings

DEATH DUE TO INADVERTENT INTRAVENOUS ADMINISTRATION:DO NOT ADMINISTER NIMODIPINE INTRAVENOUSLY OR BY OTHER PARENTERAL ROUTES. DEATHS AND SERIOUS, LIFE THREATENING ADVERSE EVENTS, INCLUDING CARDIAC ARREST, CARDIOVASCULAR COLLAPSE, HYPOTENSION, AND BRADYCARDIA, HAVE OCCURRED WHEN THE CONTENTS OF NIMODIPINE CAPSULES HAVE BEEN INJECTED PARENTERALLY (SEE DOSAGE AND ADMINISTRATION).Reduced Efficacy with CYP3A4 InducersConcomitant use of strong CYP3A4 inducers (e.g., rifampin, phenobarbital, phenytoin, carbamazepine, St John’s wort) and nimodipine should generally be avoided, as nimodipine plasma concentration and efficacy may be very significantly reduced (see PRECAUTIONS, Drug Interactions).Moderate and weak inducers of CYP3A4 may also reduce the efficacy of nimodipine to a lesser extent. Patients on these should be closely monitored for lack of effectiveness, and a nimodipine dosage increase may be required.Moderate and weak CYP3A4 inhibitors include, for example: amprenavir, aprepitant, armodafinil, bosentan, efavirenz, etravirine, echinacea, modafinil, nafcillin, pioglitazone, prednisone and rufinamide.

General Precautions

General:Blood Pressure: Nimodipine has the hemodynamic effects expected of a calcium channel blocker, although they are generally not marked. However, intravenous administration of the contents of nimodipine capsules has resulted in serious adverse consequences including death, cardiac arrest, cardiovascular collapse, hypotension, and bradycardia. In patients with subarachnoid hemorrhage given nimodipine capsules in clinical studies, about 5% were reported to have had lowering of the blood pressure and about 1% left the study because of this (not all could be attributed to nimodipine). Nevertheless, blood pressure should be carefully monitored during treatment with nimodipine capsules based on its known pharmacology and the known effects of calcium channel blockers. (see WARNINGS and DOSAGE AND ADMINISTRATION).

Other

Hepatic Disease:The metabolism of nimodipine capsules is decreased in patients with impaired hepatic function. Such patients should have their blood pressure and pulse rate monitored closely and should be given a lower dose (see DOSAGE AND ADMINISTRATION).Intestinal pseudo-obstruction and ileus have been reported rarely in patients treated with nimodipine. A causal relationship has not been established. The condition has responded to conservative management.

  • Distributed by:Ascend Laboratories, LLC180 Summit AvenueMontvale, NJ 07645 Manufactured in Switzerland by:Swiss Caps AGKirchberg, Switzerland CH-9533Distributed by:Major® Pharmaceuticals31778 Enterprise DriveLivonia, MI 48150REFER TO PACKAGE LABEL FORDISTRIBUTOR’S NDC NUMBER12/2015                                                                                       Printed in USA

Laboratory Tests

Laboratory Test Interactions: None known.

Drug Interactions

Drug Interaction:Nimodipine is metabolized via the cytochrome P450 3A4 system located both in the intestinal mucosa and in the liver. Drugs that are known to either inhibit or to induce this enzyme system may therefore alter the first pass or the clearance of nimodipine.In addition, the blood pressure lowering effects of antihypertensives could be enhanced when taken concomitantly with nimodipine.Inducers of CYP3A4Nimodipine plasma concentration and efficacy may be significantly reduced when concomitantly administered with strong CYP3A4 inducers. Therefore strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenobarbital, phenytoin, St. John’s Wort) should generally not be administered concomitantly with nimodipine (see WARNINGS). Other moderate and weak inducers of CYP3A4 may also reduce the efficacy of nimodipine, although the magnitude of decrease in nimodipine plasma concentrations is not known. Patients on these should be closely monitored for lack of effectiveness, and a nimodipine dosage increase may be required. Moderate and weak CYP3A4 inducers include: amprenavir, aprepitant, armodafinil, bosentan, efavirenz, etravirine, Echinacea, modafinil, nafcillin, pioglitazone, prednisone and rufinamide.Inhibitors of CYP3A4Nimodipine plasma concentration can be significantly increased when concomitantly administered with strong inhibitors of the CYP3A4 system. As a consequence, the blood pressure lowering effect may be increased. Therefore strong CYP3A4 inhibitors should not be coadministered with nimodipine (see CONTRAINDICATIONS). Strong CYP3A4 inhibitors include some members of the following classes: - macrolide antibiotics (e.g., clarithromycin, telithromycin,), - HIV protease inhibitors (e.g., delavirdine, indinavir, nelfinavir, ritonavir, saquinavir), - azole antimycotics (e.g., ketoconazole, itraconazole, voriconazole), - antidepressants (e.g., nefazodone) - grapefruit juice: after intake of grapefruit juice and nimodipine, the blood pressure lowering effect may last for at least 4 days after the last ingestion of grapefruit juice. Ingestion of grapefruit / grapefruit juice is therefore not recommended while taking nimodipine (see DOSAGE AND ADMINISTRATION).Nimodipine plasma concentration can also be increased in the presence of moderate and weak inhibitors of CYP3A4. If nimodipine is concomitantly administered with these drugs, blood pressure should be monitored, and a reduction of the nimodipine dose may be necessary. Moderate and weak CYP3A4 inhibitors include amprenavir, aprepitant, atazanavir, amiodarone, alprozalam, cyclosporine, cimetidine, erythromycin, fluconazole, fluoxetine, isoniazid, oral contraceptives, quinuprestin/dalforpristin, and valproic acid.Blood pressure lowering drugsNimodipine may increase the blood pressure lowering effect of concomitantly administered anti-hypertensives, such as:- diuretics,                      - other calcium antagonists,- β-blockers,                   - α-adrenergic blocking agents,- ACE inhibitors,             - PDE5 inhibitors,- A1-antagonists,            - α-methyldopa.Blood pressure should be carefully monitored, and dose adjustment of the blood pressure lowering drug(s) may be necessary.

Carcinogenesis & Mutagenesis & Impairment Of Fertility

Carcinogenesis, Mutagenesis, Impairment of Fertility:In a two-year study, higher incidences of adenocarcinoma of the uterus and Leydig-cell adenoma of the testes were observed in rats given a diet containing 1800 ppm nimodipine (equivalent to 91 to 121 mg/kg/day nimodipine) than in placebo controls. The differences were not statistically significant, however, and the higher rates were well within historical control range for these tumors in the Wistar strain. Nimodipine was found not to be carcinogenic in a 91-week mouse study but the high dose of 1800 ppm nimodipine-in-feed (546 to 774 mg/kg/day) shortened the life expectancy of the animals. Mutagenicity studies, including the Ames, micronucleus and dominant lethal tests were negative.Nimodipine did not impair the fertility and general reproductive performance of male and female Wistar rats following oral doses of up to 30 mg/kg/day when administered daily for more than 10 weeks in the males and 3 weeks in the females prior to mating and continued to day 7 of pregnancy. This dose in a rat is about 4 times the equivalent clinical dose of 60 mg q4h in a 50 kg patient.

Pregnancy

Pregnancy: Pregnancy Category C. Nimodipine has been shown to have a teratogenic effect in Himalayan rabbits. Incidences of malformations and stunted fetuses were increased at oral doses of 1 and 10 mg/kg/day administered (by gavage) from day 6 through day 18 of pregnancy but not at 3.0 mg/kg/day in one of two identical rabbit studies. In the second study an increased incidence of stunted fetuses was seen at 1.0 mg/kg/day but not at a higher doses. Nimodipine was embryotoxic, causing resorption and stunted growth of fetuses, in Long Evans rats at 100 mg/kg/day administered by gavage from day 6 through day 15 of pregnancy. In two other rat studies, doses of 30 mg/kg/day nimodipine administered by gavage from day 16 of gestation and continued until sacrifice (day 20 of pregnancy or day 21 post partum) were associated with higher incidences of skeletal variation, stunted fetuses and stillbirths but no malformations. There are no adequate and well controlled studies in pregnant women to directly assess the effect on human fetuses. Nimodipine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Nursing Mothers: Nimodipine and/or its metabolites have been shown to appear in rat milk at concentrations much higher than in maternal plasma. It is not known whether the drug is excreted in human milk. Because many drugs are excreted in human milk, nursing mothers are advised not to breast feed their babies when taking the drug.

Pediatric Use

Pediatric Use: Safety and effectiveness in children have not been established.

Geriatric Use

Geriatric Use: Clinical studies of nimodipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dosing in elderly patents should be cautious, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease of other drug therapy.

Adverse Reactions

Adverse experiences were reported by 92 of 823 patients with subarachnoid hemorrhage (11.2%) who were given nimodipine. The most frequently reported adverse experience was decreased blood pressure in 4.4% of these patients. Twenty-nine of 479 (6.1%) placebo treated patients also reported adverse experiences. The events reported with a frequency greater than 1% are displayed below by dose.DOSE q4h Number of Patients (%)NimodipineSign/Symptom0.35 mg/kg(n=82)30 mg(n=71)60 mg(n=494)90 mg(n=172)120 mg(n=4)Placebo(n=479)Decreased Blood Pressure1 (1.2)019 (3.8)14 (8.1)2 (50.0)6 (1.2)Abnormal Liver Function Test1 (1.2)02 (0.4)1 (0.6)07 (1.5)Edema002 (0.4)2 (1.2)03 (0.6)Diarrhea03 (4.2)03 (1.7)03 (0.6)Rash2 (2.4)03 (0.6)2 (1.2)03 (0.6)Headache01 (1.4)6 (1.2)001 (0.2)Gastrointestinal Symptoms2 (2.4)002 (1.2)00Nausea1 (1.2)1 (1.4)6 (1.2)1 (0.6)00Dyspnea1 (1.2)00000EKG Abnormalities01 (1.4)01 (0.6)00Tachycardia01 (1.4)0000Bradycardia005 (1.0)1 (0.6)00Muscle Pain/   Cramp01 (1.4)1 (0.2)1 (0.6)00Acne01 (1.4)0000Depression01 (1.4)0000There were no other adverse experiences reported by the patients who were given 0.35 mg/kg q4h, 30 mg q4h or 120 mg q4h. Adverse experiences with an incidence rate of less than 1% in the 60 mg q4h dose group were: hepatitis; itching; gastrointestinal hemorrhage; thrombocytopenia; anemia; palpitations; vomiting; flushing; diaphoresis; wheezing; phenytoin toxicity; lightheadedness; dizziness; rebound vasospasm; jaundice; hypertension; hematoma.Adverse experience with an incidence rate less than 1% in the 90 mg q4h dose group were: itching, gastrointestinal hemorrhage; thrombocytopenia; neurological deterioration; vomiting; diaphoresis; congestive heart failure; hyponatremia; decreasing platelet count; disseminated intravascular coagulation; deep vein thrombosis.As can be seen from the table, side effects that appear related to nimodipine use based on increased incidence with higher dose or a higher rate compared to placebo control, included decreased blood pressure, edema and headaches which are known pharmacologic actions of calcium channel blockers. It must be noted, however, that SAH is frequently accompanied by alterations in consciousness which lead to an under reporting of adverse experiences. Patients who received nimodipine in clinical trials for other indications reported flushing (2.1%), headache (4.1%) and fluid retention (0.3%), typical responses to calcium channel blockers. As a calcium channel blocker, nimodipine may have the potential to exacerbate heart failure in susceptible patients or to interfere with A-V conduction, but these events were not observed.No clinically significant effects on hematologic factors, renal or hepatic function or carbohydrate metabolism have been causally associated with oral nimodipine. Isolated cases of non-fasting elevated serum glucose levels (0.8%), elevated LDH levels (0.4%), decreased platelet counts (0.3%), elevated alkaline phosphatase levels (0.2%) and elevated SGPT levels (0.2% have been reported rarely.

Drug Abuse And Dependence

There have been no reported instances of drug abuse or dependence with nimodipine capsules.

Overdosage

There have been no reports of overdosage from the oral administration of nimodipine capsules. Symptoms of overdosage would be expected to be related to cardiovascular effects such as excessive peripheral vasodilation with marked systemic hypotension. Clinically significant hypotension due to nimodipine capsules overdosage may require active cardiovascular support with pressor agents. Specific treatments for calcium channel blocker overdose should also be given promptly. Since nimodipine is highly protein-bound, dialysis is not likely to be of benefit.

Dosage And Administration

DO NOT ADMINISTER NIMODIPINE CAPSULES INTRAVENOUSLY OR BY OTHER PARENTERAL ROUTES (see WARNINGS).If nimodipine is inadvertently administered intravenously, clinically significant hypotension may require cardiovascular support with pressor agents. Specific treatments for calcium channel blocker overdose should also be given promptly.Nimodipine capsules are given orally in the form of gray opaque colored, soft gelatin 30 mg capsules for subarachnoid hemorrhage.The recommended oral dose is 60 mg (two 30 mg capsules) every 4 hours for 21 consecutive days. In general, the capsules should be swallowed whole with a little liquid, preferably not less than one hour before or two hours after meals. Grapefruit juice is to be avoided (see PRECAUTIONS, Drug Interactions). Oral nimodipine capsules therapy should commence as soon as possible within 96 hours of the onset of subarachnoid hemorrhage.If the capsule cannot be swallowed, e.g., at the time of surgery, or if the patient is unconscious, a hole should be made in both ends of the capsule with an 18 gauge needle, and the contents of the capsule extracted into a syringe. A parenteral syringe can be used to extract the liquid inside the capsule, but the liquid should always be transferred to a syringe that cannot accept a needle and that is designed for administration orally or via a naso-gastric tube or PEG. To help minimize administration errors, it is recommended that the syringe used for administration be labeled “Not for IV Use”. The contents should then be emptied into the patient’s in situ naso-gastric tube and washed down the tube with 30 mL of normal saline (0.9%).Severely disturbed liver function, particularly liver cirrhosis, may result in an increased bioavailability of nimodipine due to a decreased first pass capacity and a reduced metabolic clearance. The reduction in blood pressure and other adverse effects may be more pronounced in these patients. Dosage should be reduced to one 30 mg capsule every 4 hours with close monitoring of blood pressure and heart rate; if necessary, discontinuation of the treatment should be considered. Strong inhibitors of CYP3A4 should not be administered concomitantly with nimodipine (see CONTRAINDICATIONS).Strong inducers of CYP3A4 should generally not be administered with Nimodipine (see WARNINGS). Patients on moderate and weak inducers of CYP3A4 should be closely monitored for lack of effectiveness, and a nimodipine dose increase may be required. Patients on moderate and weak CYP3A4 inhibitors may require a nimodipine dose reduction in case of hypotension (see PRECAUTIONS, Drug Interactions).

How Supplied

Nimodipine capsules 30 mg are clear yellow solution filled in oblong gray opaque colored softgel capsules, imprinted “A297” in black ink. The capsules are available as follows:                                                Strength        NDC Code              Capsule IdentificationUnit DosePackage of 100 (10 x 10):         30 mg             [0904-6566-61]      A297Unit DosePackage of 30 (3 x 10):             30 mg             [0904-6566-04]      A297

Storage And Handling

Storage: The capsules should be stored in manufacturer’s original foil package at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].Capsules should be protected from light and freezing.

Package/Label Display Panel

Nimodipine Capsules30 mg30 (3 x 10) Unit-dose Capsules

* Please review the disclaimer below.