Section 4.2
Amended information has now been included for aneurysmal subarachnoid haemorrhage, qualifying the details of increasing the dosage, to include the wording, ‘If it is well tolerated…’. The information relating to ‘route of administration’ has been expanded and updated to include additional detail, and the description of potential clinical scenarios for the usage of Nimotop Solution now also includes angiography.
Section 4.3
Addition of a new contraindication, regarding known hypersensitivity to nimodipine or to any of the tablet excipients.
Section 4.4
Expanded information content has now been included, describing a recommendation to closely monitor intracranial pressure in patients suffering from (generalised) cerebral oedema or raised intracranial pressure, after treatment with Nimotop. A cautionary statement has been added regarding cytochrome P450-mediated metabolism of nimodipine, and the influence on nimodipine metabolism of other drugs known to inhibit (e.g., certain antidepressants, antibiotics, amongst other types of drug) the cytochrome P450 system, and possible increases in nimodipine plasma levels. A statement has been added describing the necessity for monitoring of blood pressure upon co-administration of such drugs and for consideration of a dose reduction in such cases. Warning statements have also been added regarding the significant alcohol content of Nimotop Solution and related possible harmful effects in certain patient groups, and possible alterations to the effects of other drugs.
Section 4.5
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Substantial modifications have been made to this section, such that it has now been re-phrased/re-ordered. Overall, the current information content, describing possible drug interactions and their likely effects on nimodipine metabolism, the necessity for patient monitoring, dose adjustment, etc., has been either maintained or expanded. More specifically, information describing cytochrome P450 3A4-mediated metabolism of nimodipine and the influence thereon of drugs that inhibit/induce this enzyme system has been updated, and similar information relating to the effect of nimodipine on the potency of co-administered anti-hypertensive drugs has also been amended. Warning statements have also been added regarding the possible effects of the intravenous co-administration of beta-blockers, and the possible deterioration of renal functioning and the necessity for monitoring.
The current warning information regarding the alcohol content of Nimotop Solution has been updated and an additional statement has been added detailing certain drugs (e.g., diazepam, warfarin, etc.) that show no apparent interaction with oral nimodipine upon co-administration.
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Section 4.6
Further information has been provided detailing the absence of well-controlled clinical studies in pregnant women and the occurrence of reproductive toxicity in animal studies. Additional cautionary information has also been supplied regarding treatment with Nimotop and lactation and breast-feeding.
Section 4.8
The information content has now been expanded to include more specific information on possible side effects and an indication of the observed frequency of occurrence has been assigned for each. Overall, these details have now been sub-divided and listed by affected body system (e.g., cardiac disorders). Various side-effects not listed previously are now shown, including: certain immune system disorders; unspecific cerebrovascular symptoms; unspecific cardiac arrhythmias; unspecific cardiovascular symptoms, including uncommon vasodilatation; and, unspecific gastrointestinal and abdominal symptoms. Furthermore, the frequency of occurrence of thrombocytopenia has been amended from ‘very rare’ to ‘uncommon’, and that of ileus from ‘very rare’ to ‘rare’; in addition, ‘dizziness’ has been deleted from the amended list of side-effects. Information describing the alcohol content of Nimotop Solution and co-infusion products has now been deleted.
Section 4.9 -
The level of information has now been significantly expanded to detail: anticipated symptoms of acute overdosage (e.g., marked lowering of blood pressure, etc.); immediate treatment discontinuation in the event of acute overdosage; a description of emergency therapeutic measures to be used (as governed by symptoms), such as gastric lavage with charcoal, etc.; and, further direction regarding the treatment of side effects.
Section 5.1
This section has been updated by the addition of the ATC code and a statement quantifying the ability of nimodipine to prevent/reduce vasoconstrictions provoked in vitro by certain vasoactive substances/blood (products), by up to 75 %.
Section 5.2
The information content of this section has been expanded. Further details have now been added describing absorption, peak plasma concentration, first pass metabolism, and bioavailability after oral administration. Further to this, extra information has been included detailing the distribution volume and the total systemic clearance after i.v. administration of nimodipine. A statement describing the significant role of the cytochrome P450 3A4 system in the metabolic elimination of nimodipine is also included in line with current knowledge.
Section 5.3
The information in this section has been expanded overall, to include a statement detailing the absence of special hazards for humans, based on the results of conventional pre-clinical dosing studies of (geno)toxicity, carcinogenicity and fertility. Further specific information is provided, describing possible dose-related negative effects on foetal growth/weight, and of embryolethality at a higher dose, in pregnant rats. Other information describes single-case equivocal evidence of dose-related teratogenicity in rabbits that was not subsequently reproduced and unconfirmed delayed physical development/mortality in a single rat study.
Section 6.2
An additional statement has been included describing the possibility of crystallization during co-infusion with certain products.
Section 6.6
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An additional statement has been included describing the recommended needle type for use with the coated injection stoppers.
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Section 9
Dates amended from, ’21 January 1988/24 November 1998’, to,’ 21 January 1988/23 November 2003’.
Section 10
Date amended from, ’August 2005’, to, ‘November 2007’.
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