NIMOTOP Nimodipine 30mg Film-Coated Tablet 50's

Prophylaxis and treatment of ischemic neurological deficits caused by cerebral vasospasms following subarachnoid hemorrhage of aneurysmal origin. Nimodipine (Nimotop) tablets are indicated subsequently to Nimodipine (Nimotop) infusion solution.

 

Tab: Administration of Nimodipine (Nimotop) tablets is recommended for about 7 days after the end of the 5-14 days infusion therapy with Nimodipine (Nimotop) infusion solution.
In general, the tablets should be swallowed whole with a little liquid, independent of meal time.
Grapefruit juice is to be avoided (see Interactions). The interval between successive doses must not be less than 4 hours.
Dosage regimen: The recommended procedure is administration of Nimodipine (Nimotop) infusion solution for 5 - 14 days, followed by a daily dose of 6 x 2 Nimodipine (Nimotop) tablets (6 x 60 mg nimodipine).
In patients who develop adverse reactions the dose should be reduced as necessary or the treatment discontinued.
Upon co-administration with CYP 3A4 inhibitors or CYP 3A4 inducers a dose-adaptation may be necessary (see Interactions). Prophylactic Use: After the end of the infusion therapy, it is advisable to continue with oral administration of 6 x 60 mg Nimodipine (Nimotop) tablets daily at four-hourly intervals for about further 7 days.
Therapeutic Use: After intravenous application, oral administration of 6 x 60 mg Nimodipine (Nimotop) tablet per day at four-hourly intervals for 7 days is recommended.
Patients with hepatic impairment: Severely disturbed liver function, particularly liver cirrhosis, may result in an increased bioavailability of Nimodipine (Nimotop) due to a decreased first pass capacity and a reduced metabolic clearance. The effects and side-effects, e.g. reduction in blood-pressure, may be more pronounced in these patients. In such cases the dose should be reduced or, if necessary, discontinuation of the treatment should be considered.
Soln for IV infusion: Method of administration: Nimodipine (Nimotop) solution for infusion is administered as a continuous i.v. infusion via a central catheter using an infusion pump. It should be given via a three-way stopcock together with either glucose 5%, sodium chloride 0.9%, lactated Ringer's solution, lactated Ringer's solution with magnesium, dextran 40 solution or HAES (poly(O-2-hydroxyethyl) starch 6% in a ratio of about 1:4 (nimodipine: co-infusion). Also mannitol, human albumin or blood are suitable for co-infusion.
The three-way stopcock should be used to connect the nimodipine polyethylene tube with the co-infusion line and the central catheter.
Nimodipine (Nimotop) solution for infusion must not added to an infusion bag or bottle and must not be mixed with other drugs.
Administration of nimodipine (Nimotop) solution for infusion should be continued during anesthesia, surgery and angiography.
Dosage regimen: Intravenous infusion: At the beginning of treatment 1 mg/h nimodipine (=5 ml nimodipine (Nimotop) solution for infusion/h) for 2 h (about 15 µg/kg body weight/h). If this is well tolerated, and particularly if there is no marked reduction in blood pressure, the dose is increased after 2 h to 2 mg/h nimodipine (= 10 ml nimodipine (Nimotop) solution for infusion/h) (about 30 µg/kg body weight/h).
Patients whose body weight is appreciably below 70 kg or who have labile blood pressure should be started with a dose of 0.5 mg/h nimodipine (= 2.5 ml nimodipine (Nimotop) solution for infusion/h).
Intracisternal Installation: During surgery a freshly prepared dilute solution of nimodipine (1 ml nimodipine (Nimotop) solution for infusion and 19 ml Ringer's solution) warmed up to blood temperature may be instilled intracisternally.
This dilute solution of nimodipine (Nimotop) solution for infusionmust be used immediately after preparation.
Duration of use: Prophylactic Use: Intravenous therapy should be started no later than 4 days after the hemorrhage, and be continued during the period of maximum risk of vasospasm, i.e. up to 10-14 days after the hemorrhage.
If during prophylactic administration of nimodipine (Nimotop) solution for infusion, the source of the hemorrhage is treated surgically, intravenous treatment with nimodipine (Nimotop) solution for infusion should be continued post-operatively for at least 5 days.
After the end of the infusion therapy, it is advisable to continue with oral administration of 6 x 60 mg nimodipine daily at four-hourly intervals for about a further 7 days.
Therapeutic Use: If ischemic neurological disturbances caused by vasospasm after aneurysmal subarachnoid hemorrhage are already present, treatment should be started as early as possible and be continued for at least 5 days up to a maximum of 14 days. Thereafter, oral administration of 6 x 60 mg nimodipine per day at four-hourly intervals for 7 days is recommended.
If during therapeutic administration of nimodipine (Nimotop) solution for infusion, the source of the hemorrhage is treated surgically, intravenous treatment with nimodipine (Nimotop) solution for infusion should be continued post-operatively for at least 5 days.

 

Overdosage

May be taken with or without food: Swallow whole w/ a little liqd.

Nimodipine (Nimotop) tablets must not be used in cases of hypersensitivity to nimodipine or to any of the excipients.
Tab: The use of nimodipine in combination with rifampicin is contraindicated as efficacy of Nimodipine (Nimotop) tablets could be significantly reduced when concomitantly administered with rifampicin. (see Interactions).
The concomitant use of oral nimodipine and the antiepileptic drugs phenobarbital, phenytoin or carbamazepine is contraindicated as efficacy of Nimodipine (Nimotop) tablets could be significantly reduced (see Interactions).

Although treatment with nimodipine has not been shown to be associated with increases in intracranial pressure, close monitoring is recommended in these cases or when the water content of the brain tissue is elevated (generalized cerebral edema).
Caution is required in patients with hypotension (systolic blood pressure lower than 100 mm Hg). In patients with unstable angina or within the first 4 weeks after acute myocardial infarction, physicians should consider the potential risk (e.g. reduced coronary artery perfusion and myocardial ischemia) versus the benefit (e.g. improvement of brain perfusion).
Nimodipine is metabolized via the cytochrome P450 3A4 system. Drugs that are known to either inhibit or to induce this enzyme system may therefore alter the first pass or the clearance of nimodipine (see Interactions).
Tab: Drugs, which are known inhibitors of the cytochrome P450 3A4 system and therefore may lead to increased plasma concentrations of nimodipine are, e.g.: macrolide antibiotics (e.g., erythromycin), anti-HIV protease inhibitors (e.g., ritonavir), azole antimycotics (e.g., ketoconazole), the antidepressants nefazodone and fluoxetine, quinupristin/dalfopristin, cimetidine, valproic acid.
Upon co-administration with these drugs, the blood pressure should be monitored and, if necessary, a reduction of the nimodipine dose should be considered.

 

Use In Pregnancy & Lactation

Tabulated list of adverse reactions: Adverse drug reactions (ADRs) based on clinical trials with nimodipine in the indication aSAH sorted by CIOMS III categories of frequency (placebo-controlled studies: nimodipine N = 703; placebo N = 692; uncontrolled studies: nimodipine N = 2496; status: 31 Aug 2005) are listed as follows: The frequencies of ADRs reported with nimodipine are summarized in the table as follows. (See table.) Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000).

 

Tab: 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.
The extent as well the duration of interactions should be taken into account when administering nimodipine together with the following drugs: Rifampicin: From the experience with other calcium antagonists it has to be expected that rifampicin accelerates the metabolism of nimodipine due to enzyme induction. Thus, efficacy of nimodipine could be significantly reduced when concomitantly administered with rifampicin. The use of nimodipine in combination with rifampicin is therefore contraindicated (see Contraindications).
Cytochrome P450 3A4 system-inducing anti-epileptic drugs, such as phenobarbital, phenytoin or carbamazepine: Previous chronic administration of the antiepileptic drugs phenobarbital, phenytoin or carbamazepine markedly reduces the bioavailability of orally administered nimodipine. Therefore, the concomitant use of oral nimodipine and these antiepileptic drugs is contraindicated. (see Contraindications).
Upon co-administration with the following inhibitors of the cytochrome P450 3A4 system the blood pressure should be monitored and, if necessary, an adaptation in the nimodipine dose should be considered (see Dosage & Administration).
Macrolide antibiotics (e.g., erythromycin): No interaction studies have been carried out between nimodipine and macrolide antibiotics. Certain macrolide antibiotics are known to inhibit the cytochrome P450 3A4 system and the potential for drug interaction cannot be ruled out at this stage. Therefore, macrolide antibiotics should not be used in combination with nimodipine (see Precautions).
Azithromycin, although structurally related to the class of macrolide antibiotic is void of CYP3A4 inhibition.
Anti-HIV protease inhibitors (e.g., ritonavir): No formal studies have been performed to investigate the potential interaction between nimodipine and anti-HIV protease inhibitors. Drugs of this class have been reported to be potent inhibitors of the cytochrome P450 3A4 system. Therefore, the potential for a marked and clinically relevant increase in nimodipine plasma concentrations upon coadministration with these protease inhibitors cannot be excluded (see Precautions).
Azole anti-mycotics (e.g., ketoconazole): A formal interaction study investigating the potential of drug interaction between nimodipine and ketoconazole has not been performed. Azole anti-mycotics are known to inhibit the cytochrome P450 3A4 system, and various interactions have been reported for other dihydropyridine calcium antagonists. Therefore, when administered together with oral nimodipine, a substantial increase in systemic bioavailability of nimodipine due to a decreased first-pass metabolism cannot be excluded (see Precautions).
Nefazodone: No formal studies have been performed to investigate the potential interaction between nimodipine and nefazodone. This antidepressant drug has been reported to be a potent inhibitor of the cytochrome P450 3A4. Therefore, the potential for an increase in nimodipine plasma concentrations upon co-administration with nefazodone cannot be excluded (see Precautions).
Fluoxetine: The steady-state concomitant administration of nimodipine with the antidepressant fluoxetine led to about 50% higher nimodipine plasma concentrations. Fluoxetine exposure was markedly decreased, while its active metabolite norfluoxetine was not affected.
Quinupristin/dalfopristin: Based on experience with the calcium-antagonist nifedipine, co-administration of quinupristin/dalfopristin may lead to increased plasma concentrations of nimodipine (see Precautions).
Cimetidine: The simultaneous administration of the H2-antagonist cimetidine can lead to an increase in the plasma nimodipine concentration (see Precautions).
Valproic acid: The simultaneous administration of the anticonvulsant valproic acid can lead to an increase in the plasma nimodipine concentration (see Precautions).
Further drug interaction: Nortryptyline: The steady-state concomitant administration of nimodipine and nortryptyline led to a slight decrease in nimodipine exposure with unaffected nortryptyline plasma concentrations.
Effects of nimodipine on other drugs: Blood pressure lowering drugs: Nimodipine may increase the blood pressure lowering effect of concomitantly applied antihypertensives, such as: diuretics, β-blockers, ACE inhibitors, A1-antagonists, other calcium antagonists, α-adrenergic blocking agents, PDE5 inhibitors, α-methyldopa.
However, if a combination of this type proves unavoidable particularly careful monitoring of the patient is necessary.
Zidovudine: In a monkey study simultaneous administration of anti-HIV drug zidovudine i.v. and nimodipine bolus i.v. resulted for zidovudine in significantly higher AUC, whereas the distribution volume and clearance were significantly reduced.
Drug-food interactions: Grapefruit juice: Grapefruit juice inhibits the cytochrome P450 3A4 system. Administration of dyhydropyridine calcium antagonists together with grapefruit juice thus results in elevated plasma concentrations and prolonged action of nimodipine due to a decreased first pass metabolism or reduced clearance.
As a consequence, the blood pressure lowering effect may be increased. After intake of grapefruit juice this effect may last for at least 4 days after the last ingestion of grapefruit juice.
Ingestion of grapefruit/grapefruit juice is therefore to be avoided while taking nimodipine (see Dosage & Administration).
Soln for IV infusion: Drugs that affect nimodipine: Fluoxetine: The steady-state concomitant administration of nimodipine with the antidepressant fluoxetine led to about 50% higher nimodipine plasma concentrations. Fluoxetine exposure was markedly decreased, while its active metabolite norfluoxetine was not affected.
Nortryptyline: The steady-state concomitant administrationof nimodipine and nortryptyline led to a slight decrease in nimodipine exposure with unaffected nortryptyilne plasma concentrations. Effects of nimodipine on other drugs: Blood pressure lowering drugs: Nimodipine may increase the blood pressure lowering effect of concomitant applied anti-hypertensives, such as: diuretics, β-blockers, ACE inhibitors, A1-antagonists, other calcium antagonists, α-adrenergic blocking agents, PDE5 inhibitors, α-methyldopa.
However, if a combination of this type proves unavoidable particularly careful monitoring of the patient is necessary.
Simultaneous intravenous administration of β-blockers may lead to mutual potentiation of negative ionotropic action going as far as decompensated heart failure.
Renal function can deteriorate if potentially nephrotoxic drugs (e.g. aminoglycosides, cephalosporins, furosemide) are given simultaneously, and also in patients whose renal function is already impaired. Renal function must be monitored carefully in such cases, and if a deterioration is found discontinuation of the treatment should be considered.
Zidovudine: In a monkey study simultaneous administration of anti-HIV drug zidovudine i.v. and nimodipine bolus i.v. resulted for zidovudine in significantly higher AUC, whereas the distribution volume and clearance were significantly reduced.
Other forms of interaction: Since nimodipine (Nimotop) solution for infusion contain 23.7% vol-% of alcohol, interactions with alcohol-incompatible drugs should be taken into consideration (see Precautions).

 

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Nootropics & Neurotonics/Neurotrophics / Peripheral Vasodilators & Cerebral Activators