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.
- The drug's manufacturer advises that you choose whether to stop breastfeeding or stop taking the medication.
- Due to the potential for serious adverse effects in breastfed infants, this is taking the treatment of the mother into mind.
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
- The labelling from the manufacturer does not list any contraindications.
Canadian labeling:
- Hypersensitivity to nimodipine and/or any formulation ingredient
- 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.
- The rate of blood pressure reduction must be suitable 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.
- Reduce the dosage and keep a close eye on your blood pressure and heart rate.
-
Hypertrophic cardiomyopathy and outflow tract obstruction
- When treating individuals with outflow tract blockage and hypertrophic cardiomyopathy, exercise caution.
Nimodipine: Drug Interaction
Risk Factor C (Monitor therapy) |
|
Alfuzosin |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
Alpha1-Blockers |
The hypotensive effects of calcium channel blockers may be strengthened. |
Amphetamines |
May lessen the effectiveness of antihypertensive agents. |
Antipsychotic Agents (Second Generation [Atypical]) |
Antipsychotic drugs' hypotensive effects may be enhanced by blood pressure-lowering medications (Second Generation [Atypical]). |
Aprepitant |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
Atosiban |
Calcium channel blockers may intensify Atosiban's harmful or hazardous effects. Particularly, pulmonary edoema and/or dyspnea may be at higher risk. |
Barbiturates |
Calcium Channel Blockers' metabolic rate might be increased. Management: Keep an eye out for any diminished therapeutic effects of barbiturate medication when concurrently using calcium channel blockers. There may need to be dose modifications with calcium channel blockers. The concurrent use of phenobarbital and nimodipine is not recommended. |
Barbiturates |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
Benperidol |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
Bosentan |
May lower CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
Brigatinib |
May lessen the effectiveness of antihypertensive agents. Antihypertensive Agents' bradycardic action may be strengthened by brutinib. |
Brimonidine (Topical) |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
Calcium Channel Blockers (Nondihydropyridine) |
Dihydropyridine, a calcium channel blocker, may increase the hypotensive effects of calcium channel blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may cause an increase in serum calcium channel blocker concentration (Dihydropyridine). |
Calcium Salts |
The hypotensive effects of calcium channel blockers may be strengthened. |
Clofazimine |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
Clopidogrel |
Calcium channel blockers may reduce Clopidogrel's therapeutic efficacy. |
CycloSPORINE (Systemic) |
The serum concentration of CycloSPORINE may rise when Calcium Channel Blockers (Dihydropyridine) are taken (Systemic). Calcium Channel Blockers' serum levels may rise when CycloSPORINE (Systemic) is used (Dihydropyridine). |
CYP3A4 Inducers (Moderate) |
NiMODipine serum concentration can drop. |
CYP3A4 Inducers (Weak) |
NiMODipine serum concentration can drop. |
CYP3A4 Inhibitors (Moderate) |
NiMODipine serum concentration can drop. |
CYP3A4 Inhibitors (Weak) |
NiMODipine serum concentration can drop. |
Dapoxetine |
The orthostatic hypotensive effects of calcium channel blockers may be strengthened. |
Deferasirox |
May lower CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
Diazoxide |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
DULoxetine |
The hypotensive impact of DULoxetine may be enhanced by blood pressure lowering medications. |
Duvelisib |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
Efavirenz |
Calcium Channel Blockers' serum concentration can drop. |
Erdafitinib |
May lower CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
Erdafitinib |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
Fluconazole |
The hypotensive effects of calcium channel blockers may be strengthened. |
FLUoxetine |
NiMODipine serum concentration can rise. |
Fosaprepitant |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
Fosnetupitant |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
Herbs (Hypertensive Properties) |
May lessen the effectiveness of antihypertensive agents. |
Herbs (Hypotensive Properties) |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
Ivosidenib |
May lower CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
Larotrectinib |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
Levodopa-Containing Products |
Levodopa-Containing Products' hypotensive effects may be strengthened by blood pressure-lowering medications. |
Lormetazepam |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
Magnesium Salts |
Calcium channel blockers might make magnesium salts more harmful or poisonous. Calcium Channel Blockers' hypotensive effects may be strengthened by magnesium salts. |
Melatonin |
May reduce the effectiveness of calcium channel blockers as an antihypertensive (Dihydropyridine). |
Methylphenidate |
May lessen the effectiveness of antihypertensive agents. |
Molsidomine |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
Naftopidil |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
Netupitant |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
Neuromuscular-Blocking Agents (Nondepolarizing) |
The neuromuscular-blocking impact of neuromuscular-blocking agents may be enhanced by calcium channel blockers (Nondepolarizing). |
Nicergoline |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
Nicorandil |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
Nitroprusside |
Nitroprusside's hypotensive impact may be strengthened by blood pressure-lowering medications. |
Palbociclib |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
Pentoxifylline |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
Pholcodine |
Pholcodine's hypotensive impact may be strengthened by blood pressure lowering medications. |
Phosphodiesterase 5 Inhibitors |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
Prostacyclin Analogues |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
Quinagolide |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
QuiNIDine |
The serum concentration of QuiNIDine may be lowered by calcium channel blockers (Dihydropyridine). The serum concentration of QuiNIDine may rise in response to calcium channel blockers (Dihydropyridine). Calcium Channel Blockers' serum levels may rise in response to quinine (Dihydropyridine). |
Sarilumab |
May lower CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
Siltuximab |
May lower CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
Simeprevir |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
Tacrolimus (Systemic) |
Tacrolimus serum levels may rise when Calcium Channel Blockers (Dihydropyridine) are used (Systemic). |
Tocilizumab |
May lower CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
Yohimbine |
May lessen the effectiveness of antihypertensive agents. |
Risk Factor D (Consider therapy modification) |
|
Amifostine |
Amifostine's hypotensive impact may be strengthened by blood pressure lowering medications. Treatment: Blood pressure-lowering drugs need to be avoided for 24 hours before amifostine is administered when used at chemotherapeutic doses. Amifostine should not be given if blood pressure lowering treatment cannot be stopped. |
Cimetidine |
Calcium Channel Blockers' serum levels can rise. Management: Take cimetidine substitutes into consideration. If there is no suitable substitute, watch for increased calcium channel blocker effects after starting or increasing the dosage of cimetidine and decreased effects after stopping or decreasing the dosage. |
Cladribine |
The serum content of Cladribine may rise in response to inhibitors of equilibrative nucleoside (ENT1) and concentrated nucleoside (CNT3) transport proteins. Management: Whenever possible, avoid using ENT1 or CNT3 inhibitors concurrently during the 4 to 5 day oral cladribine therapy cycles. |
Dabrafenib |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: When possible, look for substitutes for the CYP3A4 substrate. If concurrent therapy cannot be avoided, pay special attention to the substrate's clinical consequences (particularly therapeutic effects). |
Lorlatinib |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Avoid taking lorlatinib at the same time as any CYP3A4 substrates for which even a small drop in serum levels of the substrate could result in therapeutic failure and negative clinical outcomes. |
Macrolide Antibiotics |
Calcium Channel Blockers' metabolic rate might be decreased. Use a noninteracting macrolide as a possible management strategy. The Canadian labelling for felodipine expressly advises against using it in conjunction with clarithromycin. Azithromycin (Systemic), Fidaxomicin, Roxithromycin, and Spiramycin are exceptions. |
Obinutuzumab |
The hypotensive effects of blood pressure-lowering medications may be strengthened. Management: Take into account temporarily stopping blood pressure-lowering drugs 12 hours before the start of the obinutuzumab infusion and keeping them off until 1 hour after the infusion is finished. |
Rifamycin Derivatives |
Calcium Channel Blockers' serum concentration can drop. This predominantly affects calcium channel blockers used orally. Management: Using rifampin with certain calcium channel blockers is not advised according to the labelling in the US and Canada. Look up the relevant labelling. |
Sincalide |
The therapeutic benefit of Sincalide may be reduced by medications that affect gallbladder function. Prior to using sincalide to induce gallbladder contraction, you should think about stopping any medications that can impair gallbladder motility. |
Stiripentol |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). Management: Due to the increased potential for side effects and toxicity, stiripentol should not be used with CYP3A4 substrates that are thought to have a narrow therapeutic index. Use of stiripentol with any CYP3A4 substrate necessitates closer observation. |
Risk Factor X (Avoid combination) |
|
Bromperidol |
The hypotensive impact of bromperidol may be enhanced by blood pressure lowering medications. Blood Pressure Lowering Agents' hypotensive effects may be lessened by bromperidol. |
Conivaptan |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
CYP3A4 Inducers (Strong) |
NiMODipine serum concentration can drop. |
CYP3A4 Inhibitors (Strong) |
NiMODipine serum concentration can rise |
Fusidic Acid (Systemic) |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
Grapefruit Juice |
NiMODipine serum concentration can rise |
Idelalisib |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
St John's Wort |
NiMODipine serum concentration can drop. |
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 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 prevents calcium ions from entering the "slow channel" or particular voltage-sensitive regions of the heart and vascular smooth muscles 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 |