Class: Dihydropyridines
VA Class: CV200
Chemical Name: 1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester
Molecular Formula: C21H26N2O7
CAS Number: 66085-59-4
Brands: Nimotop
Do not administer contents of nimodipine oral capsules by IV or other parenteral routes.1 245 246 248 249 250
Death and serious, life-threatening adverse effects reported following parenteral injection of the contents of nimodipine capsules.1 245 246 248 249 250 (See Parenteral Administration under Cautions and see Hypotension and Other Cardiovascular Effects under Cautions and see Oral Administration under Dosage and Administration.)
Introduction
A dihydropyridine-derivative calcium-channel blocking agent that affects the CNS preferentially.1 4 5 13 22 96 d
Uses for Nimodipine
Subarachnoid Hemorrhage
Used to improve neurologic outcome by reducing the incidence and severity of ischemic deficits in patients with subarachnoid hemorrhage resulting from ruptured intracranial berry aneurysms regardless of the patient’s postictal neurologic condition (e.g., Hunt and Hess grades I–V).1 2 4 5 8 20 21 22 23 69 95 109 230 231
Decreases severity and incidence of delayed ischemic neurologic deficits associated with subarachnoid hemorrhage.1 2 5 20 21 22 23 40 82 95 231
Efficacy in reducing mortality from subarachnoid hemorrhage after oral administration not fully established.1 20 69 95
Acute Ischemic Stroke
Limited evidence suggests that nimodipine may improve neurologic recovery and reduce mortality compared with plasma volume expansion therapy or placebo in some patients with acute ischemic stroke†.4 10 76 77 220 240 241 247
Migraine
Has been used with equivocal results for reduction of frequency and possibly severity and duration of vascular headaches (e.g., migraine attacks) in patients with classic or common migraine†.4 8 11 12 78 79 80 90 101 114 206 233 244
Also has been used in a few patients with cluster headache†.90 100 114
Additional studies are needed to determine the role of nimodipine relative to that of other therapies used in the management of migraine headaches78 79 80 206 230 231 and to determine whether tolerance to the prophylactic effects of the drug develops during chronic therapy.206
Nimodipine Dosage and Administration
Administration
Oral Administration
Nimodipine capsules are for oral administration only.1 245 246 248 249 250 (See Boxed Warning.)
Administer orally every 4 hours, preferably at least 1 hour before or 2 hours after meals.1
Nasogastric Tube
If the oral capsule cannot be swallowed (e.g., when administered at the time of surgery or to an unconscious patient), puncture the capsule at both ends with an 18-gauge needle and empty the contents into a syringe,1 249 250 preferably using a syringe designed for nasogastric or percutaneous endoscopic gastrostomy administration (e.g., Toomey syringe).246 250 To help minimize administration errors, label the syringe for oral use only; not for IV use.1 245 248 249 250 The contents of the capsule should then be emptied into the patient’s nasogastric tube.1 249 250 Following administration, flush with 30 mL of 0.9% sodium chloride solution.1 245 246 249
Reinforce awareness among health-care professionals of potential medical errors that may result in inadvertent injection of syringe contents into an IV line or via other parenteral routes.246 248 249 250 (See Parenteral Administration under Cautions, see Hypotension and Other Cardiovascular Effects under Cautions, and see Boxed Warning.)
If inadvertent IV administration of contents of nimodipine capsules occurs, administer vasopressor agents for cardiovascular support if required for clinically important hypotension and promptly administer specific treatment for overdosage associated with calcium-channel blocking agents.1 246
The contents of the capsule should not be admixed with any solution prior to oral administration because of the possibility of drug decomposition.230
IV Administration
The contents of nimodipine capsules must not be administered by IV injection or any other parenteral route; serious adverse effects such as hypotension, cardiovascular collapse, and cardiac arrest have occurred with such administration.1 248 249 250 Report adverse events or medication errors involving nimodipine capsules to the FDA MedWatch program.248 250
Has been administered by IV infusion† (IV dosage form currently is not commercially available in the US)d in patients with subarachnoid hemorrhage, often in conjunction with intracisternal† application during surgery67 117 119 120 214 and usually followed by oral therapy.5 67 93 116 117 118 119 120 214
Dosage
Adults
Subarachnoid Hemorrhage
Oral
60 mg every 4 hours for 21 consecutive days.1 5 Initiate therapy as soon as possible after the occurrence of subarachnoid hemorrhage, preferably within 96 hours.1 4 5 20 230 231
It has been suggested that the drug may be discontinued after 14 consecutive days (but not earlier) in some uncomplicated cases in which early aneurysm surgery is performed.231
In patients in whom surgical repair of the aneurysm is performed relatively late (e.g., day 20), some clinicians suggest continuation of therapy for ≥5 days after surgery to minimize the possibility of postoperative vasospasm.4 231
It has been suggested that patients with unstable BP receive a lower dosage (e.g., 30 mg every 4 hours);4 231 however, the manufacturer states that the usual adult dosage should be used in such patients.230 (See Hypotension and Other Cardiovascular Effects under Cautions.)
Acute Ischemic Stroke†
Oral
120 mg daily given in divided doses for 21 or 28 days has been used.76 77 242 247
Migraine†
Prophylaxis of Classic or Common Migraine†
Oral
120 mg daily given in divided doses has been used.4 8 11 12 78 79 80 101 114 206
Special Populations
Hepatic Impairment
Subarachnoid Hemorrhage
Oral
Initially, 30 mg every 4 hours.1 5 89
Monitor BP and heart rate closely.1 5 89 May use pharmacologic support of BP (e.g., vasopressors such as norepinephrine or dopamine), if necessary.230 231
Renal Impairment
No specific dosage recommendations.1
Geriatric Patients
Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1
Cautions for Nimodipine
Contraindications
No known contraindications in patients with subarachnoid hemorrhage.1
Warnings/Precautions
Warnings
Parenteral Administration
Do not administer contents of nimodipine oral capsules by IV or other parenteral routes.1 245 246 248 249 250 Death and serious life-threatening adverse effects (e.g., cardiac arrest, cardiovascular collapse, hypotension, bradycardia) reported following parenteral injection of nimodipine capsule contents.1 245 246 248 249 250 (See Hypotension and Other Cardiovascular Effects under Cautions and see Boxed Warning.)
IV use of nimodipine, with serious and sometimes fatal outcomes, continues to be reported despite revisions to the drug’s labeling (including addition of a boxed warning) that warn against such use.248 249 250
Factors identified by FDA as contributing to this error include use of IV syringes to administer the drug by NG tube (IV syringes sometimes are used to remove the liquid contents from the capsules) and the fact that most patients receiving the drug are in critical care settings and are receiving other IV therapy.249 250
Report adverse events or medication errors involving nimodipine capsules to the FDA MedWatch program.248 250
General Precautions
Hypotension and Other Cardiovascular Effects
IV administration of the contents of nimodipine capsules† has resulted in serious cardiovascular effects.1 248 249 250 (See Parenteral Administration under Cautions and see Boxed Warning.)
Possible decreased systemic BP;1 decreases generally are not marked with usual oral dosages.1 2 6 7 20 21 22 23 54 69 132
Monitor BP closely during therapy.1 In patients with unstable BP, frequently monitor BP and heart rate; a lower dosage has been suggested.231 (See Subarachnoid Hemorrhage under Dosage and Administration.)
Shares the toxic potentials of other calcium-channel blocking agents; consider possible occurrence of other adverse effects associated with these drugs (e.g., AV-conduction disturbances).1 7 128 230 231
GI Effects
Intestinal pseudo-obstruction and ileus responsive to conservative management has been reported rarely.1 127
Specific Populations
Pregnancy
Category C.1
Lactation
Distributed into milk in rats;1 91 not known whether distributed into human milk.1 Discontinue nursing because of potential risk to nursing infants.1
Pediatric Use
Safety and efficacy not established in children <18 years of age.1 230
Geriatric Use
Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; select dosage with caution.1
Hepatic Impairment
Possible decreased metabolism, substantially reduced clearance, and increased peak plasma concentrations.1 89 (See Absorption: Special Populations and see also Elimination: Special Populations, under Pharmacokinetics.)
Possible hypotension.1 4 90 230 231 Use with caution; monitor BP and pulse rate closely; dosage adjustment recommended.1 (See Hepatic Impairment under Dosage and Administration.)
Renal Impairment
Clearance may be decreased.88 (See Elimination: Special Populations, under Pharmacokinetics.)
Common Adverse Effects
Decreased BP, headache.1 4 5 23 112 122 154 230 231
Interactions for Nimodipine
Specific Drugs
Drug | Interaction | Comments |
|---|---|---|
Anesthetic agents | Does not appear to potentiate hemodynamic effects of anesthetic agents during surgery54 230 231 | |
Antineoplastic agents | Risk of enhanced cytotoxic effects of certain antineoplastic agents140 141 190 191 192 193 195 215 216 217 218 219 | Clinical importance not known230 231 |
Antihypertensive agents | Possible additive antihypertensive effects1 93 | Monitor BP carefully if used concomitantly; when possible use short-acting antihypertensive agents231 Reduced dosage or cautious discontinuance of the antihypertensive agent and/or initiation of pharmacologic support of BP may be required230 231 |
Calcium-channel blockers (e.g., diltiazem) | Possible potentiation of cardiovascular effects of nimodipine (e.g., negative inotropic effect)155 | Clinical importance not known;1 230 231 avoid combined therapy if possible231 |
Cimetidine | Decreased clearance and increased plasma nimodipine concentrations1 243 | Clinical importance not known243 |
Digoxin | Low doses (i.e., 30 mg twice daily) of nimodipine do not alter the pharmacokinetics or hemodynamic effects of digoxin137 | |
Fentanyl | Possible potentiation of analgesia in patients undergoing heart surgery154 | |
Phenytoin | Possible decreased phenytoin metabolism1 179 | Monitor plasma phenytoin concentrations when nimodipine is initiated or discontinued179 No drug interactions reported in patients with subarachnoid hemorrhage receiving concomitant therapy 230 |
Nimodipine Pharmacokinetics
Absorption
Bioavailability
Rapidly1 46 85 89 213 and almost completely4 5 213 absorbed following oral administration, with peak concentrations attained within 1 hour.1 46 89 213
Bioavailability is about 13% and variable due to extensive first-pass metabolism in the liver.1 46 85 213 230
Food
Food substantially decreases the extent of absorption; peak plasma concentrations reduced by 68% and bioavailability by 38%.1
Special Populations
In patients with hepatic cirrhosis, systemic availability, peak serum drug concentrations, and AUCs may be increased substantially.1 89 230
Distribution
Extent
Widely distributed into body tissues after oral or IV administration in animals.87
Distributes to a limited extent into CSF.4 22 86 231
May distribute more extensively into CSF in patients with subarachnoid hemorrhage.1 230
In animals, nimodipine crosses the placenta4 87 and is distributed into milk.1 91
Plasma Protein Binding
>95%.1 4 213
Elimination
Metabolism
Extensively metabolized in the liver1 5 4 88 89 213 to either inactive or substantially less active metabolites1 124 125 213 principally via demethylation followed by dehydrogenation.4 85 86
Elimination Route
Following oral administration, approximately 50% excreted in urine as metabolites and to a lesser extent in feces (possibly secondary to biliary excretion).4
In animals, nimodipine and/or its metabolites appear to undergo extensive enterohepatic circulation;123 possible enterohepatic circulation in humans.89
Half-life
Following oral administration: 1.7–9 hours.1 4 5 46 85 86 88 89 213
Following IV (IV dosage form currently is not commercially available in the US)d administration: 0.9–1.5 hours.4 46 85 86 213
Special Populations
Substantially decreased clearance in patients with hepatic dysfunction.4 89 231 Mean clearance rates in patients with hepatic cirrhosis were decreased by >50% in one study.89
Increased half-life and reduced plasma clearance reported in patients with renal impairment; findings may have been related in part to age-related reductions in liver function.88
Hemodialysis or peritoneal dialysis not likely to affect elimination.1 230 231
Stability
Storage
Oral
Capsules
25°C (may be exposed to 15–30°C) in the original container.1 Do not freeze; protect from light.1 129
ActionsActions
Inhibits transmembrane influx of extracellular calcium ions across the membranes of myocardial, vascular smooth muscle, and neuronal cells.1 4 7 10 14 41 48 49 53 126 128 132 133 236
Appears to affect the CNS preferentially.1 4 7 8 13 17 35 42 45 55 82 155 185 206 229 230
Mechanism of selectivity for cerebral tissue is complex and has not been fully elucidated; tissue selectivity of 1,4-dihydropyridine calcium-channel blockers may be related to differences in chemical structure, binding site characteristics, and/or calcium-channel gating behavior.47 48 210
Mechanism(s) of clinical benefit in patients with subarachnoid hemorrhage has not been fully elucidated;1 4 20 69 102 current evidence suggests that dilation of small cerebral resistance vessels,2 23 36 102 131 with a resultant increase in collateral circulation,4 5 23 52 67 83 98 131 and/or a direct effect involving prevention of calcium overload in neurons2 4 5 13 23 68 69 82 83 96 102 104 132 206 may be responsible.
Advice to Patients
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of advising patients of other important precautionary information.1 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Capsules, liquid-filled | 30 mg | Nimotop | Bayer |
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions February 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
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