Nimodipine (Nimotop) is a calcium channel blocker that improves neurological outcomes in patients with subarachnoid hemorrhage (ruptured berry aneurysm).
Nimodipine Uses (indications):
-
Subarachnoid hemorrhage:
- It is used for the improvement of neurological outcome by reducing in adult patients the incidence & severity of ischemic deficits with subarachnoid hemorrhage (SAH) from ruptured intracranial berry aneurysms regardless of their post ictus neurological condition (ie, Hunt and Hess grades I to V)
Nimodipine (Nimotop) Dose in Adults
Note:
- For oral administration ONLY.
Nimodipine (Nimotop) Dose in the treatment of Subarachnoid hemorrhage:
- P/O:
- 60 mg every 4 hours for 21 consecutive doses.
- Note:
- Within 96 hours of the onset of subarachnoid hemorrhage, start therapy.
Use in Children:
Not indicated
Pregnancy Risk Category: C
- Nimodipine crosses over to the placenta
- Nimodipine was evaluated for the management of preeclampsia.
- However, it is not recommended for severe intrapartum hypertension or postpartum hypertension that can be associated with preeclampsia.
Use of Nimodipine while breastfeeding
- Nimodipine can be found in breast milk (Carcas 1996; Tonks 95).
- Based on two case reports, the relative infant dose (RID), of nimodipine was 1%.
- It is generally accepted to breastfeed if the RID of medication falls below 10% (Anderson 2016; Ito2000).
- After both oral and intravenous administration, the RID for nimodipine (or nimodipine) was calculated.
- Oral nimodipine 60mg was given to a woman within 3 days of giving birth. It was taken for 10 days.
- After seven days of therapy, breastmilk was finally obtained.
- The highest possible milk concentration (16 ng/mL), the RID for nimodipine (0.05%) provided an infant dose via breastmilk of 2.4 mg/kg/day.
- A woman received Nimodipine IV at 3 weeks postpartum. It was given as an infusion of 1mg/hour for two hours and then 2mg/hour for 24 hours (total dose 46mg).
- The highest milk concentration of 4.7 ng/mL was reached 2 hours after the infusion had been completed.
- According to the study authors, the RID of Nimodipine was between 0.092% and 0.008%. This gives an infant daily dose via breastmilk of 0.063 and 0.705 mg/kg/day.
- Both cases showed that breast milk concentrations varied but were correlated with maternal serum levels.
- Manufacturer recommends that you decide whether to stop breastfeeding or discontinue using the drug.
- This is taking into consideration the importance of mother's treatment due to the possibility of serious adverse reactions in breastfed babies.
Nimodipine (Nimotop) Dose in Kidney Disease:
- In the manufacturer’s labeling, no dosage adjustment provided.
- However, nimodipine undergoes minimal renal elimination & dose adjustment may not be necessary.
- Not removed by hemo- or peritoneal dialysis.
- The supplemental dose is not necessary.
Dose in Liver disease:
- In patients with cirrhosis, reduce dosage to 30 mg every 4 hours.
Side Effects of Nimodipine (Nimotop):
-
Cardiovascular:
- Decreased blood pressure
- Bradycardia
-
Central nervous system:
- Headache
-
Gastrointestinal:
- Nausea
Contraindication to Nimodipine (Nimotop):
US Labeling
- Use with strong CYP3A4 inhibitors (eg clarithromycin and telithromycin), concomitantly.
Nymalize
- There are no contraindications in the manufacturer's labeling.
Canadian labeling:
- Hypersensitivity to nimodipine and any component of the formulation
- Use phenobarbital or phenytoin with carbamazepine or rifampin.
Warnings and precautions
-
Angina/MI
- Increased angina and MI can occur when dihydropyridine calcium channel blocking agents are commenced or titrated.
- Reflex tachycardia can occur in patients with obstructive heart disease, especially if there is no concurrent beta-blockade.
-
Gastrointestinal events:
- Therapy has rarely been associated with ileus and pseudo-obstruction of the intestines.
-
Syncope and hypotension:
- Hypotension symptoms can be present with or without syncope.
- Blood pressure must be reduced at a pace that is appropriate for the patient's medical condition.
- Monitor blood pressure carefully during treatment.
-
Peripheral edema
- Peripheral swelling is a common side effect.
- Within 2-3 weeks after starting therapy, this happens.
-
Hepatic impairment
- Use caution in patients suffering from cirrhosis, due to increased plasma levels of nimodipine.
- It is necessary to reduce the dose and monitor blood pressure and heart rate closely.
-
Hypertrophic cardiomyopathy and outflow tract obstruction
- Use caution when treating patients suffering from hypertrophic cardiomyopathy and outflow tract obstruction.
Nimodipine: Drug Interaction
|
Risk Factor C (Monitor therapy) |
|
|
Alfuzosin |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Alpha1-Blockers |
May enhance the hypotensive effect of Calcium Channel Blockers. |
|
Amphetamines |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Antipsychotic Agents (Second Generation [Atypical]) |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). |
|
Aprepitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Atosiban |
Calcium Channel Blockers may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. |
|
Barbiturates |
May increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. |
|
Barbiturates |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Benperidol |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Bosentan |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Brigatinib |
May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. |
|
Brimonidine (Topical) |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Calcium Channel Blockers (Nondihydropyridine) |
Calcium Channel Blockers (Dihydropyridine) may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). |
|
Calcium Salts |
May diminish the therapeutic effect of Calcium Channel Blockers. |
|
Clofazimine |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Clopidogrel |
Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. |
|
CycloSPORINE (Systemic) |
Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). |
|
CYP3A4 Inducers (Moderate) |
May decrease the serum concentration of NiMODipine. |
|
CYP3A4 Inducers (Weak) |
May decrease the serum concentration of NiMODipine. |
|
CYP3A4 Inhibitors (Moderate) |
May increase the serum concentration of NiMODipine. |
|
CYP3A4 Inhibitors (Weak) |
May increase the serum concentration of NiMODipine. |
|
Dapoxetine |
May enhance the orthostatic hypotensive effect of Calcium Channel Blockers. |
|
Deferasirox |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Dexmethylphenidate |
May diminish the therapeutic effect of Antihypertensive Agents. |
|
Diazoxide |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
DULoxetine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. |
|
Duvelisib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Efavirenz |
May decrease the serum concentration of Calcium Channel Blockers. |
|
Erdafitinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Erdafitinib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Fluconazole |
May increase the serum concentration of Calcium Channel Blockers. |
|
FLUoxetine |
May increase the serum concentration of NiMODipine. |
|
Fosaprepitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Fosnetupitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Herbs (Hypertensive Properties) |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Herbs (Hypotensive Properties) |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Hypotension-Associated Agents |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. |
|
Ivosidenib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Larotrectinib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Levodopa-Containing Products |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. |
|
Lormetazepam |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Magnesium Salts |
Calcium Channel Blockers may enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. |
|
Melatonin |
May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine). |
|
Methylphenidate |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Molsidomine |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Naftopidil |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Netupitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Neuromuscular-Blocking Agents (Nondepolarizing) |
Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). |
|
Nicergoline |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Nicorandil |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Nitroprusside |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. |
|
Palbociclib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Pentoxifylline |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Pholcodine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. |
|
Phosphodiesterase 5 Inhibitors |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Prostacyclin Analogues |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Quinagolide |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
QuiNIDine |
Calcium Channel Blockers (Dihydropyridine) may decrease the serum concentration of QuiNIDine. Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of QuiNIDine. QuiNIDine may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). |
|
Sarilumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Siltuximab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Simeprevir |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Tacrolimus (Systemic) |
Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic). |
|
Tocilizumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Yohimbine |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Risk Factor D (Consider therapy modification) |
|
|
Amifostine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. |
|
Cimetidine |
May increase the serum concentration of Calcium Channel Blockers. Management: Consider alternatives to cimetidine. If no suitable alternative exists, monitor for increased effects of calcium channel blockers following cimetidine initiation/dose increase, and decreased effects following cimetidine discontinuation/dose decrease. |
|
Cladribine |
Inhibitors of Equilibrative Nucleoside (ENT1) and Concentrative Nucleoside (CNT3) Transport Proteins may increase the serum concentration of Cladribine. Management: Avoid concomitant use of ENT1 or CNT3 inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider an ENT1 or CNT3 inhibitor dose reduction and separation in the timing of administration. |
|
Dabrafenib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). |
|
Lorlatinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. |
|
Macrolide Antibiotics |
May decrease the metabolism of Calcium Channel Blockers. Management: Consider using a noninteracting macrolide. Felodipine Canadian labeling specifically recommends avoiding its use in combination with clarithromycin. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin. |
|
Obinutuzumab |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. |
|
Rifamycin Derivatives |
May decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Management: The labeling for some US and Canadian calcium channel blockers contraindicate use with rifampin, however recommendations vary. Consult appropriate labeling. |
|
Sincalide |
Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. |
|
Stiripentol |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. |
|
Risk Factor X (Avoid combination) |
|
|
Bromperidol |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. |
|
Conivaptan |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
CYP3A4 Inducers (Strong) |
May decrease the serum concentration of NiMODipine. |
|
CYP3A4 Inhibitors (Strong) |
May increase the serum concentration of NiMODipine. |
|
Fusidic Acid (Systemic) |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Grapefruit Juice |
May increase the serum concentration of NiMODipine. |
|
Idelalisib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
St John's Wort |
May decrease the serum concentration of NiMODipine. |
Mnitoring parameters:
- None mentioned. Monitor blood pressure the response to treatment.
- When administered to patients with subarachnoid hemorrhage, monitor for the clinical features of raised intracranial pressure.
How to administer Nimodipine (Nimotop)?
- For enteral administration ONLY.
- When administered parenterally, life-threatening adverse events have occurred.
- Administer on an empty stomach at least 1 hour before or 2 hours after meals.
P/O:
- US labeling:
- Administer on an empty stomach at least 1 hour before or 2 hours after meals.
- Canadian labeling:
- Administer without regard to meals.
- But administer consistently with or without meals.
- With an adequate amount of fluid, the tablet should be swallowed whole (eg, a glass of water).
- Do not crush tablets.
- Before or after administration, avoid alkaline mixtures for 2 hours.
- During administration, the patient should not be lying down.
Nasogastric (NG) or gastric tube administration:
- Oral solution (Nymalize):
- Administer using the supplied oral syringe labeled "ORAL USE ONLY".
- Refill the oral syringe with 20 mL of NS and flush any remaining contents from NG or gastric tube into the stomach, following administration.
- Capsules:
- If the capsules cannot be swallowed, the liquid may be removed by making a hole in each end of the capsule with an 18-gauge needle & extracting the contents into a syringe.
- Transfer these contents into an oral syringe (amber-colored oral syringe preferred).
- It is strongly recommended that preparation should be done in the pharmacy.
- Label oral syringe with "WARNING: For ORAL use only” or “Not for IV use.”
- Follow with a flush of 30 mL NS.
Mechanism of action of Nimodipine (Nimotop):
- Nimodipine shares many of the same pharmacological characteristics as other calcium channel blocking drugs.
- Animal studies have shown that nimodipine exerts a greater effect on cerebral arterials then other arterials.
- The drug's higher lipophilicity and cerebral distribution may account for the enhanced specificity, as opposed to nifedipine.
- This inhibits calcium ion's entry into the "slow channel" or selected voltage sensitive areas in vascular smooth muscles and myocardium during depolarization
Protein binding:
- >95%
Metabolism:
- Extensively hepatic via CYP3A4.
- Undergoes first-pass metabolism
Bioavailability:
- Capsule:
- 13%.
- Tablet [Canadian product]:
- 16% (range: 3% to 30%)
Half-life elimination:
- 1-2 hours.
- Extended with renal impairment
Time to peak, serum:
- ~1 hour
Excretion:
- Urine (<1% as unchanged drug).
- Feces
International Brands of Nimodipine:
- Nimodipine
- Nimotop
- Amocure
- Brainal
- Eftipine
- Eugerial
- Grifonimod
- Irrigor
- Kenesil
- Kenzolol
- Modip
- Nidip
- Nimo
- Nimobal
- Nimocal
- Nimodi
- Nimodilat
- Nimodin
- Nimotask
- Nimotop
- Nisom
- Nymalize
- Oxigen
- Periplum
- Tropocer
- Vasoactin
- Vasoflex
- Vasotop
- Vexdipine
Nimodipine Brand Names in Pakistan:
Nimodipine Infusion 0.2 mg/ml |
|
| Bredin | Medisure Laboratories Pakistan (Pvt.) Ltd. |
| Nimotop | Bayer Health Care |
Nimodipine Tablets 30 mg |
|
| Bredin | Medisure Laboratories Pakistan (Pvt.) Ltd. |
| Duranim | Pearl Pharmaceuticals |
| Nidopin | Global Pharmaceuticals |
| Nimoden | High - Q International |
| Nimodex | Mass Pharma (Private) Limited |
| Nimopro | Pulse Pharmaceuticals |
| Nimotin | Mediate Pharmaceuticals (Pvt) Ltd |
| Nimotop | Bayer Health Care |
| Nimovas | Spencer Pharma |
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