Nimotop 0.02% w/v Concentrate for Solution for Infusion.

BP22036, REC30610

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Text in blue = added text

Text in red with strikethrough = deleted text

6. Contents of the pack and other information

[…]

Marketing Authorisation Holder:

Bayer Limited, 1st Floor, The Grange Offices, The Grange, Brewery Road, Stillorgan, Co. Dublin, A94 H2K7, The Atrium, Blackthorn road, Dublin 18, Ireland

[…]

This leaflet was last revised in September 2022January 2021

BP22036, REC30610

Note:

Text in blue = added text

Text in red with strikethrough = deleted text

7. MARKETING AUTHORISATION HOLDER

 Bayer Limited

1^st Floor

The Grange Offices

The Grange

Brewery Road

Stillorgan

Co. Dublin

A94 H2K7

The Atrium

Blackthorn Road

Dublin 18

Ireland

10. DATE OF REVISION OF THE TEXT

 JanuarySeptember 20222021

Correction to Section 8 - Marketing Authorisation numbers.

The Maltese MA number was included in Section 8 along with the HPRA PA number in error in the previous version. The Maltese MA has now been deleted. There have been no other changes made to the text.

In Section 7, "Ireland" has been added to the MAH address.

In Section 8, the HPRA PA number has been reformatted, as follows: PA1410/030/002. Note: Removal of space between "PA" and "1410" and additional zeros added. A Maltese licence number has also been added: MA639/02401

In section 4.2 the following was inserted

“Special populations

Paediatric population

Safety and efficacy of nimodipine in patients under 18 years of age have not been established.”

In section 4.8 information on Reporting of suspected adverse reactions was introduced.

The date of revision was updated

(Inserted text; Deleted text)

4.3       Contraindications

            Nimodipine solution for infusion must not be used in cases of hypersensitivity to nimodipine or to any of the excipients. Known hypersensitivity to Nimodipine or any of the excipients.

Nimodipine should not be administered to patients during or within one month of a myocardial infarction of an episode of unstable angina.

4.4       Special warnings and precautions for use

            Nimotop solution should be used with care when cerebral oedema or severely raised intracranial pressure are present. Although treatment with Nimotop 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 (generalised cerebral oedema).

Caution is required in patients with hypotension (systolic blood pressure lower than 100mg Hg). Nimotop solution must be used with caution in hypotensive patients.

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).

Patients with known renal disease and/or receiving nephrotoxic drugs should have renal function monitored closely during intravenous treatment with Nimotop solution.

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The amount of alcohol in this medicine may alter the effects of other medicines (See Section 4.5 Interaction with other medicinal products and other forms of interactions).

This medicinal product contains 1 mmol (23mg) sodium per 50ml bottle. To be taken into consideration by patients on a controlled sodium diet.

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 (see “Interaction with other medicinal products and other forms of interaction”). This medicinal product contains 2 mmol sodium per daily dose. This should be taken into consideration for patients on a controlled sodium diet.

4.5       Interaction with other medicinal products and other forms of interaction

Fluoxetine

Concomitant administration of nimodipine with the antidepressant fluoxetine, once steady state has been achieved has led to approximately 50% higher plasma nimodipine levels.  Fluoxetine plasma levels were exposure was markedly decreased, however the while its active metabolite, norfluoxetine was not affected.

Nortryptyline

The steady-state concomitant administration of nimodipine and nortriptyline led to a slight decrease in nimodipine plasma concentrations exposure with unaffected nortriptyline plasma concentrations.

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Blood pressure lowering drugs:

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However, iIf a combination of this type proves unavoidable particularly careful monitoring of the patient is necessary.

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Renal function must be monitored carefully in such cases and if deterioration is found discontinuation of the treatment should be considered (See Section 4.4 Special warnings and precautions for use).

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.

Animal studies have shown that when nimodipine and zidovudine are administered concomitantly, the AUC for zidovudine was increased, and the volume of distribution and clearance rate decreased.

Other forms of interaction:

Since Nimotop nimodipine solution for infusion contains 23.7 vol % ethanol (alcohol), patients should be monitored for any possible interactions with alcohol-incompatible drugs should be taken into consideration (see Section 4.4 Special warnings and precautions for use).

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4.6       Pregnancy and lactation

Pregnancy:

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Reproductive toxicology studies in animals after oral administration showed no teratogenic effect.  Therefore, if Nimotop solution nimodipine solution for infusion is to be administered during pregnancy, the benefits and the potential risks must be carefully weighed according to the severity of the clinical picture.

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In vitro fertilisationFertility:

            In single cases of in-vitro fertilisation calcium antagonists have been associated with reversible biochemical changes in the spermatozoa’s head section that may result in impaired sperm function. The relevance of this finding in short-term treatment is unknown.

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4.8       Undesirable effects

The frequencies of ADRs reported with nimodipine summarized in the tables below are 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). 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).

Table 01: ADR

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 below:

4.9       Overdose

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In the event of acute overdosage, treatment with Nimotop nimodipine must be discontinued immediately. Emergency measures should be governed by the symptoms. Gastric If the substance was ingested orally, gastric lavage with addition of charcoal should be considered as an emergency therapeutic measure. If there is a marked fall in blood pressure, dopamine or noradrenaline can be administered intravenously. As Since no specific antidote is known, subsequent treatment for other side effects should be aimed at governed by the most prominent symptoms.

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10.       DATE OF REVISION OF THE TEXT

June 2010 April 2013

Please note where new text has been inserted into a sentence the text has been highlighted  in red:

1.         NAME OF THE MEDICINAL PRODUCT

Nimotop 0.02% w/v Concentrate for Solution for Infusion.

2.         QUALITATIVE AND QUANTITATIVE COMPOSITION

Addition of:

“Each 50ml vial also contains 10g of ethanol (0.2g/ml) and 2.3mg of sodium (as sodium citrate dihydrate).”

For a full list of excipients, see 6.1.

3.         PHARMACEUTICAL FORM

            Concentrate for solution for infusion (Sterile concentrate).

            A clear, yellow solution.

4.2       Posology and method of administration

Therapeutic administration

Subsection: Route of administration

“Nimotop solution must not be added to an infusion bag or bottle and msut not be moixed with other drugs.”  has been changed to:

“Nimotop must not be mixed with other drugs so it should not be added to an infusion bag or bottle which contains other drugs.” 

4.4       Special warnings and precautions for use

At the end of this section addition of “Nimotop should not be used in concentrated form.”

6.2              Incompatibilities

Addition of “Nimotop must not be mixed with other drugs so it should not be added to an infusion bag or bottle which contains other drugs.”

6.4       Special precautions for storage

            Do not store above 25°C.  Keep the vial in the outer carton to protect from light.

9.         DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION

Date of first authorisation:          15 February 1994

Date of last renewal:     15 Feburary 2009

10.       DATE OF REVISION OF THE TEXT

Changed to “June 2010”

Sections 4.2, 5.1, 5.2, 5.3 and 6.6 where updated following internal review.