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NIMOTOP 0.02% SOLUTION FOR INFUSION

Active substance(s): NIMODIPINE

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Package leaflet: Information for the user

Tell your doctor, if you are taking, have recently
August
taken or might take any other medicines. It’s
especially important to tell your doctor about these
medicines:
REVISED
• high blood pressure tablets (including
nifedipine, diltiazem, verapamil, methyldopa,
alpha-blockers or beta-blockers, such as atenolol,
propanolol). Nimotop solution may increase the effect of these
medicines.
an anti-ulcer drug called cimetidine or an anti-epilepsy drug
• called sodium valproate. These medicines may increase the
effect of Nimotop solution.

Nimotop
0 0.02%
Solution

2015

®

for Infusion
Nimodipine

Read all of this leaflet carefully before you
start taking this medicine because it contains
important information for you.
Keep this leaflet. You may need to read it again.




If you have any further questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only.
If you get any side effects, talk to your doctor or pharmacist. This
includes any possible side effects not listed in this leaflet. See section
4.

What is in this leaflet
1 What Nimotop solution is and what it is used for
2 What you need to know before you are given Nimotop solution
3 How you are given Nimotop solution
4 Possible side effects
5 How to store Nimotop solution
6 Contents of the pack and other information







the antidepressant drugs fluoxetine or nefazodone.
medicines causing harm to the kidney (nephrotoxic
medicines) such as aminoglycosides, cephalosporins,
furosemide. Your doctor will monitor your kidney function during
treatment.
the anti-HIV drug zidovudine (AZT).
the HIV protease inhibitor drugs indinavir, ritonavir, nelfinavir
or saquinavir.
the antibiotic erythromycin or the anti-fungal drug ketoconazole.
the antibiotic drug combination quinupristin / dalfopristin.
any other medicines you are on whose effects may be
changed by the amount of alcohol in Nimotop solution.
Your doctor should know which these are (for example,
metronidazole or tinidazole).

Nimotop solution with food and drink

1

Do not drink grapefruit juice or eat grapefruit while taking
Nimotop solution.

What Nimotop solution is and what
it is used for

Do not start treatment with Nimotop solution within 4 days of drinking
grapefruit juice or eating grapefruit. Tell your doctor if you have had
grapefruit or grapefruit juice in this time. Also, do not drink grapefruit
juice or eat grapefruit whilst being treated with Nimotop solution.
Grapefruit juice is known to increase the blood levels of the active
ingredient, nimodipine. This effect can last for at least four days.

Nimotop solution contains nimodipine, which belongs to a group of
medicines called calcium antagonists.
Nimotop solution is used to prevent changes in brain function
after bleeding around the brain (subarachnoid haemorrhage).

2

Pregnancy, breast-feeding and fertility

What you need to know before you
are given Nimotop solution

If you are pregnant or breast-feeding, think you may be pregnant
or are planning to have a baby, ask your doctor for advice before
receiving this medicine.
Do not breast-feed while you are being treated with Nimotop
solution.

Do not take Nimotop solution
You should not be given Nimotop solution:
• If you have had a heart attack within the last month.
• If you suffer from angina and notice an increase in the
frequency and severity of attacks.
• If you are allergic to nimodipine or any of the ingredients of
this medicine (listed in section 6).

If you are trying to father a child talk to your doctor. Medicines like
Nimotop solution can sometimes affect male fertility.

Driving and using machines

Tell your doctor and do not take Nimotop solution if any of these
apply to you.

Warnings and precautions
Talk to your doctor before receiving Nimotop solution
• If you had a head injury which caused bleeding around the
brain (traumatic subarachnoid haemorrhage).
• If you have fluid in the brain or severely raised pressure in
your skull. Your doctor will be able to advise you about this.
If
you have low blood pressure.

• If you have liver disease. You will probably need to have your
blood pressure measured regularly.
• If you have kidney problems. Your doctor may want to
monitor your kidney function during treatment.
• If you are susceptible to alcohol.
• If you are on a controlled salt (sodium) diet.

Tell your doctor before you take Nimotop Solution, if any of these
apply to you.

Nimotop solution may make you feel less alert, or dizzy. Do not drive
or operate machinery if you are affected in this way. The amount of
alcohol in the solution may also make you feel less alert.
If you continue your treatment with Nimotop (for example if your
doctor prescribes tablets), do not drive or operate machinery if you
think you might be affected.

Nimotop Solution contains ethanol
This medicinal product contains 23.7 vol % ethanol (alcohol), i.e. up
to 50 g per daily dose (250 ml), equivalent to 1200 ml beer or 500 ml
wine per dose.
Harmful for those suffering from alcoholism.
To be taken into account in pregnant or breast-feeding women,
children and high-risk groups such as patients with liver disease or
epilepsy. The amount of alcohol in this medicinal product may alter
the effects of other medicines.
The amount of alcohol in this medicinal product may impair your
ability to drive or use machines.

Nimotop Solution contains sodium citrate

Children and adolescents

This medicinal product contains 1 mmol (23 mg) sodium per 50ml
bottle or 5.1 mmol (115 mg) sodium per 250 ml bottle. To be taken
into consideration by patients on a controlled sodium diet.

Do not give Nimotop solution to children under the age of 18 as the
safety and efficacy of Nimotop have not been established.

Other medicines and Nimotop solution
You will not be given Nimotop solution if you are taking Nimotop
tablets.
You are not to be given injectable beta-blockers if you are given
Nimotop solution.

TEAR HERE

0

The following information is intended for healthcare professionals only:
SEPARATE PATIENT INFORMATION LEAFLET ABOVE BEFORE DISPENSING
ENSURE LEAFLET IS DISPENSED WITH PRODUCT
PACKAGE INSERT

Nimotop

®

0.02% Solution for Infusion
Nimodipine

1. NAME OF THE MEDICINAL PRODUCT
Nimotop 0.02% Solution for Infusion

2. QUALITATIVE AND QUANTITATIVE
COMPOSITION
A sterile solution containing 10 mg nimodipine in 50 ml vials of
aqueous alcoholic solvent (0.02%). Excipient with known effect:
ethanol and sodium citrate. For the full list of excipients see
section 6.1.

3. PHARMACEUTICAL FORM
Clear yellow sterile solution for intravenous use.

4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Nimodipine is indicated for the treatment of ischaemic
neurological deficits following aneurysmal subarachnoid
haemorrhage.
4.2 Posology and method of administration
Posology
Recommended dose - Aneurysmal Subarachnoid Haemorrhage
For the first two hours of treatment 1 mg of nimodipine, i.e. 5 ml
Nimotop solution, (about 15 µg/kg bw/h), should be infused
each hour via a central catheter. If it is well tolerated, the
dose should be increased after two hours to 2 mg nimodipine,
i.e. 10 ml Nimotop solution per hour (about 30 µg/kg bw/h),
providing no severe decrease in blood pressure is observed.
Patients of body weight less than 70 kg or with unstable blood
pressure should be started on a dose of 0.5 mg nimodipine per
hour (2.5 ml of Nimotop solution), or less if necessary.
Duration of treatment
Aneurysmal subarachnoid haemorrhage
Intravenous treatment should begin as early as possible
after neurological deficit occurs due to arterial spasm, post
subarachnoid haemorrhage. This should continue for at least
five days up to a maximum of 14 days.
In the event of surgical intervention during treatment,
administration of nimodipine should be continued (dose as
above) for at least five days.
Nimotop solution may be used with or without pre-treatment with
Nimotop tablets. In the event of Nimotop tablets and Nimotop
solution being administered sequentially the total duration of
treatment should not exceed 21 days. Nimotop solution should
not be administered for longer than 14 days. Nimotop solution
and tablets should not be used concomitantly.
Traumatic subarachnoid haemorrhage
Not recommended as a positive benefit to risk ratio has not
been established (see section 4.4).
Paediatric Population
The safety and efficacy of Nimotop in patients under 18 years of
age have not been established.
Method of administration
Nimotop solution is administered as a continuous I.V. infusion via
a central catheter using an infusion pump. It should be connected
to a three-way stopcock using the infusion line provided. The
three-way stopcock should be used to connect the Nimotop
polyethylene tube with the co-infusion line and the central catheter.
(The stopcock must allow for concomitant flow of the Nimotop
solution and a co-infusion solution.) Nimotop solution must be
administered with a co-infusion running at a rate of 40 ml/hr of
either sodium chloride 0.9%, glucose 5%, Ringer’s lactate solution,
lactated Ringer’s solution with magnesium, dextran 40, HAES®
(poly[O-2-hydroxyethyl]) starch 6%, human albumin 5%, blood or
mannitol 10% in a ratio of about 1:4 (Nimotop:co-infusion), which is
connected to the second port of the three-way stopcock prior to its
connection with the central line catheter.
Nimotop solution must not be added to an infusion bag or bottle
and must not be mixed with other drugs.
Nimotop solution may be used during anaesthesia, angiography
or surgical procedures.
4.3 Contraindications
Nimodipine solution for infusion must not be used in cases
of hypersensitivity to the active substance or to any of the
excipients listed in section 6.1.
Nimodipine should not be administered to patients during or
within one month of a myocardial infarction or an episode of
unstable angina.
4.4 Special warnings and precautions for use
Nimotop should not be used in patients with traumatic
subarachnoid haemorrhage as a positive benefit to risk ratio
has not been established and the specific patient groups that
might benefit cannot be identified for this indication.
Nimotop solution should be used with care when cerebral oedema
or severely raised intracranial pressure are present. Although
treatment with Nimotop 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).
Nimotop solution must be used with caution in hypotensive
patients (systolic blood pressure lower than 100 mm Hg).
Decreased drug clearance may occur in cirrhotic patients
receiving Nimotop and, therefore, close monitoring of blood
pressure is recommended in these patients.
This medicinal product contains 1 mmol (23 mg) sodium per 50 ml
bottle or 5.1 mmol (115 mg) sodium per 250 ml bottle. To be taken
into consideration by patients on a controlled sodium diet.
Patients with known renal disease and/or receiving nephrotoxic
drugs should have renal function monitored closely during
intravenous treatment with Nimotop solution (see section 4.5).

4.5






4.6

Nimodipine is metabolised via the cytochrome P450 3A4
system. Drugs which are known inhibitors of the cytochrome
P450 3A4 system and, therefore, may lead to increased plasma
concentrations of nimodipine are 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
and valproic acid (see section 4.5).
Upon co-administration with these drugs, the blood pressure
should be monitored and, if necessary, a reduction in the
nimodipine dose should be considered.
This medicinal product contains 23.7 vol % ethanol (alcohol),
i.e. up to 50 g per daily dose (250 ml). This may be harmful for
those suffering from alcoholism or impaired alcohol metabolism
and should be taken into account in pregnant or breast-feeding
women, children and high-risk groups such as patients with liver
disease or epilepsy. The amount of alcohol in this medicinal
product may alter the effects of other medicines (see section 4.5).
Interaction with other medicinal products and other forms
of interaction
Nimotop tablets should not be administered concomitantly with
Nimotop solution.
Drugs that affect nimodipine
Concurrent twice daily administration of 30mg nimodipine and
daily administration of 20mg of the antidepressant fluoxetine to
elderly patients resulted in about 50% higher nimodipine plasma
levels, a marked reduction in fluoxetine levels, whilst its active
metabolite norfluoxetine was not affected.
Concurrent three times daily administration of 30mg nimodipine
and three times daily administration of 10mg of the antidepressant
nortriptyline to elderly patients resulted in a slight decrease in
nimodipine plasma levels with no effect on nortriptyline plasma
levels. The daily dose used in patients with subarachnoid
haemorrhage is four times the daily dose used in this trial, thus
the clinical significance of this interaction in the treatment of
aneurysmal subarachnoid haemorrhage (aSAH) is uncertain.
Nimodipine is metabolised via the cytochrome P450 3A4
system, located both in the intestinal mucosa and in the liver.
Although no formal interaction studies have been performed
to investigate the potential interaction between nimodipine
and inhibitors of cytochrome P450 3A4, the potential for drug
interaction and increased nimodipine plasma concentrations
cannot be excluded. (See section 4.4).
Upon co-administration with the following inhibitors of the
cytochrome P450 3A4 system the blood pressure should be
monitored and, if necessary, an adaption in the nimodipine dose
should be considered (see section 4.2):
macrolide antibiotics (e.g. erythromycin)
anti-HIV protease inhibitors (e.g. ritonavir)
azole anti-mycotics (e.g. ketoconazole)
nefazodone.
Effects of nimodipine on other drugs
Blood pressure lowering drugs
Nimodipine may increase the blood pressure lowering effect of
concomitant antihypertensives, such as diuretics, beta-blockers,
ACE inhibitors, A1-antagonists, other calcium antagonists,
alpha-adrenergic blocking agents, PDE5 inhibitors and alphamethyldopa.
However, if a combination of this type proves unavoidable,
particularly careful monitoring of the patient is necessary.
Simultaneous intravenous administration of beta-blockers may
lead to mutual potentiation of negative inotropic 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 deterioration is found discontinuation of the
treatment should be considered (see section 4.4).
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. The clinical relevance of this interaction is unknown,
but since the side-effect profile of zidovudine is known to be dose
related, this interaction should be considered in patients receiving
nimodipine and zidovudine concomitantly.
Other forms of interaction
Since Nimotop solution contains 23.7 vol % ethanol (alcohol),
patients should be monitored for any possible interactions with
alcohol-incompatible drugs (see section 4.4).
The simultaneous administration of cimetidine or sodium valproate
may lead to an increase in the plasma nimodipine concentration.
The intake of grapefruit juice is not recommended in
combination with nimodipine as it can result in increased
plasma nimodipine concentrations due to the inhibition of the
oxidative metabolism of dihydropyridines.
Interactions shown not to exist
A study examining the effects of 90mg nimodipine (in divided
doses) on elderly patients receiving haloperidol did not show
evidence of potential interactions. It is unclear whether this
study is relevant to use in subarachnoid haemorrhage because
of the higher dose of nimodipine used.
Concomitant administration of oral nimodipine and diazepam,
digoxin, glibenclamide, indometacin, ranitidine and warfarin did
not reveal any potential for mutual interaction.
Fertility, pregnancy and lactation
Pregnancy
There are no adequate and well controlled studies in pregnant
women. No reproductive toxicology studies following parenteral
administration are available. Reproductive toxicology studies in
animals after oral administration showed no teratogenic effect,
although studies in animals have shown reproductive toxicity
(see section 5.3). If Nimotop solution is to be administered during
pregnancy, the benefits and the potential risks must, therefore, be
carefully weighed according to the severity of the clinical picture.
Breast-feeding
84691135

PMR 84691135 (93/04/MU-0201503086) Pantone: ORANGE 021, Schwarz

200x810-16443_11523

3

How you are given Nimotop
solution
Nimotop solution is given by a doctor or nurse, as a slow injection
through a vein into the bloodstream.
The recommended dose is 5 ml per hour in the first two hours of
treatment. This will be increased to 10 ml per hour, if there is no sign
of a drop in blood pressure.
Treatment will last for at least 5 days, up to a maximum of 14 days.
After the intravenous therapy you may be given Nimotop tablets for a
further period of time, but the total length of treatment with nimodipine
(Nimotop solution followed by Nimotop tablets) will not exceed 21
days.
If you weigh less than 70 kg or have unstable blood pressure, your
doctor will calculate the dose of Nimotop solution required.

If you are given more Nimotop solution than you
should
The amount of Nimotop solution you receive is carefully controlled by
your doctor. It is highly unlikely that you will be given too much medicine.
Tell your doctor if you feel faint or if your heartbeats are slower
or faster than normal.

If you have any further questions on the use of this medicine, ask your
doctor.

4

Possible side effects

Like all medicines, this medicine can cause side effects, although not
everybody gets them.

Potentially serious side effects
If you experience:
• signs of allergic reaction such as swelling of the face, lips, tongue or
throat, difficulty breathing, rash, itching, nausea or vomiting
• low blood pressure (may cause dizziness)
• slow heart beat
• easier bruising and bleeding caused by a reduced number of
blood platelets
Contact your doctor immediately as these side effects can
sometimes be serious.

Less serious side effects
In addition to the serious side effects listed above, these are the other
less serious side effects of Nimotop solution:

5

How to store Nimotop solution

Keep this medicine out of the sight and reach of children.
Store below 25°C and protect from light.
Store in the outer carton until just before use. Your doctor or hospital
pharmacist will store Nimotop solution appropriately before it is used.
This medicine should not be used after the expiry date which is stated
on both the outer carton and on each vial after EXP. The expiry date
refers to the last day of that month.
Do not throw away any medicines via wastewater or household
waste. Ask your pharmacist how to throw away medicines you no
longer use. These measures will help protect the environment.

6

Contents of the pack and other
information

What Nimotop solution contains
The active substance is nimodipine.
The other ingredients are ethanol, macrogol, sodium citrate, citric acid
and water for injection.

What Nimotop solution looks like and contents
of the pack
Each glass vial contains 10 mg of nimodipine in 50 ml of solution
(0.02% solution).
Each pack contains
1 x 50 ml vial with 1 polyethylene infusion line or
5 x 50 ml vials with 5 polyethylene infusion lines.

Marketing Authorisation Holder and
Manufacturer
Marketing Authorisation holder:
Bayer plc, Bayer House, Strawberry Hill, Newbury, Berkshire RG14
1JA
Manufacturer: Bayer Pharma AG, Leverkusen, Germany
This leaflet was last revised in August 2015.
Marketing authorisation number:
PL 00010/0138

Uncommon side effects
(These may affect up to 1 in 100 people)
• rash
• headache
• fast heart beat
• flushing, sweating, feeling of warmth
• feeling sick (nausea)

Rare side effects
(These may affect up to 1 in 1,000 people)
• constipation (lack of bowel movement)
• a slight rise in liver enzymes (this will show up in blood tests)
• pain and/or swelling in a vein (possibly caused by a blood clot)
where the needle was inserted
Reporting of side effects
If you get any side effects, talk to your doctor. This includes any
possible side effects not listed in this leaflet. You can also report side
effects directly (see details below). By reporting side effects you can
help provide more information on the safety of this medicine.
United Kingdom
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard
Malta
ADR Reporting
Website: www.medicinesauthority.gov.mt/adrportal

U

84691135

Nimodipine and its metabolites have been shown to be present
in human milk at concentrations of the same order of magnitude
as corresponding maternal plasma concentrations. Nursing
mothers should be advised not to breast-feed when taking this
drug.
Fertility
In single cases of in-vitro fertilization 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.
4.7 Effects on ability to drive and use machines
In theory, the possibility of the occurrence of the side-effect
dizziness may impair the patient’s ability to drive or operate
machinery. However, this is unlikely to be of clinical relevance
in patients receiving Nimotop Solution.
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)
System Organ Class
(MedDRA)
Blood and the
lymphatic system
disorders
Immune system
disorders
Nervous system
disorders
Cardiac disorders
Vascular disorders
Gastrointestinal
disorders
Hepatobiliary
disorders
General disorders
and administration
site conditions

Uncommon

Rare

Thrombocytopenia

6. PHARMACEUTICAL PARTICULARS

Allergic reaction
Rash
Headache
Tachycardia
Hypotension
Vasodilatation
Nausea

Elimination
Effects on liver enzymes by induction or inhibition are unknown.
In humans the metabolites are excreted about 50 % renally and
30 % in the bile.
Linearity/non-linearity
For oral administration, the peak plasma concentration and the
area under the curve increase proportionally to the dose up to
the highest dose under test (90 mg). The elimination kinetics
are linear. The half-life for nimodipine is between 1.1 and 1.7
hours. The terminal half-life is 5-10 hours, and is not relevant for
establishing the recommended dosing interval for the medicinal
product.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based
on conventional studies of safety pharmacology, single and
repeated dose toxicity, genotoxicity, carcinogenic potential,
toxicity to reproduction. However, several preclinical findings
may be of relevance to the prescribing physician. In chronic
repeat dose toxicity studies in dogs, doses of 1 and 2.5 mg/
kg/day were shown to be tolerated without adverse effect.
However, at the higher dose of 6.25 mg/kg/day significant
changes in ECGs were noted due to disturbances in myocardial
blood flow, but there was no indication of histopathological
damage to the heart. In pregnant rats, doses of 30 mg/kg/
day and higher inhibited fetal growth and resulted in reduced
fetal weights. At 100 mg/kg/day embryolethality occurred. No
evidence of teratogenicity was observed. In rabbits, equivocal
evidence of teratogenicity was seen in one study at doses up
to 10 mg/kg/day. In two subsequent studies (one at 30 mg/kg/
day), these findings were not reproduced. In one peri-postnatal
study in rats, mortality and delayed physical development were
observed at doses of 10 mg/kg/day and higher. The findings
were not confirmed in subsequent studies.

Bradycardia
Ileus
Transient increase in
liver enzymes
Injection and infusion
site reactions
Infusion site
(thrombo-) phlebitis

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation
of the medicinal product is important. It allows continued
monitoring of the benefit/risk balance of the medicinal product.
Healthcare professionals are asked to report any suspected
adverse reactions via the Yellow Card Scheme at: www.mhra.
gov.uk/yellowcard.
4.9 Overdose
Symptoms of intoxication
Symptoms of acute overdosage to be anticipated are marked
lowering of the blood pressure, tachycardia, bradycardia and
(after oral administration) gastro-intestinal complaints and
nausea.
Treatment of intoxication
In the event of acute overdosage, treatment with Nimotop must
be discontinued immediately. Emergency measures should
be governed by the symptoms. 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 no specific antidote is known,
subsequent treatment for other side effects should be aimed at
the most prominent symptoms.

5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: dihydropyridine derivatives,
ATC code: C08CA06. Nimodipine is a dihydropyridine
calcium channel blocker with particular cerebrovascular
effect. Nimodipine increases cerebral perfusion, particularly in
poorly perfused areas, by arterial dilatation, an effect which is
proportionately greater in smaller than in larger vessels.
Vasoconstrictions provoked in vitro by various vasoactive
substances (e.g., serotonin, prostaglandins and histamine) or
by blood and blood degradation products can be prevented or
reduced by up to 75 % by nimodipine.
5.2 Pharmacokinetic properties
The intravenous Nimotop solution is 100% available to the
tissues as the peripheral venous blood takes the drug to the
lungs and heart and from there to all organs.
Absorption
After oral ingestion, absorption is rapid. Peak plasma
concentrations are observed 30 to 60 minutes following oral
administration. Despite high gastrointestinal absorption of
nimodipine, the absolute bioavailability is 5 – 15 %, which is
attributed to extensive first pass metabolism (about 85 – 95 %).
Distribution
The distribution volume (Vss, 2 compartment model) for i.v.
administration is calculated to be 0.9 – 2.3 l/kg body weight.
The total (systemic) clearance is 0.8 – 1.6 l/h/kg. Nimodipine is
97 – 99 % bound to plasma proteins.
Biotransformation
The cytochrome P450 3A4 system plays a major role in the
metabolic elimination of nimodipine. Nimodipine is eliminated as
metabolites, mainly by dehydrogenation of the dihydropyridine
ring and oxidative O-demethylation. Oxidative ester
cleavage, hydroxylation of the 2- and 6-methyl groups, and
glucuronidation as a conjugation reaction are other important
metabolic steps. The three primary metabolites occurring in
plasma show no or only therapeutically negligible residual
activity.

6.1 List of excipients
Nimodipine 0.02% solution contains the following excipients:
Ethanol 96%, Macrogol 400, sodium citrate, citric acid, Water
for Injections Ph. Eur.
6.2 Incompatibilities
Nimotop solution reacts with polyvinylchloride (PVC) and should
not be allowed to come in contact with PVC. Nimotop solution
must not be added to an infusion bag or bottle and must not
be mixed with other drugs. Crystallization was observed during
co-infusion of Nimotop solution with 2.5% xylite in 0.4% sodium
chloride solution (Summafusin), Aminosteril (Fresenius) and
Ringer’s solution DAB7.
6.3 Shelf life
Shelf life of the product as packaged for sale:
Shelf life Pack size
Primary packaging material
A
B
(ml)
Brown glass type II infusion vials
4 years N/A
50
A = Unopened
B = After reconstitution or when the container is opened for
the first time, if appropriate.
6.4 Special precautions for storage
Nimotop solution is light sensitive and therefore should be
stored in the manufacturer’s light-protective container within the
cardboard carton at a temperature not above 25°C.
6.5 Nature and contents of container
Brown glass type II infusion vials containing 50 ml of solution;
with grey chlorobutyl stopper laminated with fluoropolymer.
6.6 Special precautions for disposal and other handling
The only plastic materials suitable for use are polyethylene
or polypropylene. Nimotop solution is compatible with glass
infusion bottles and infusion packs made of polyethylene (e.g.,
Polyfusor, Boots).
The solution when in the syringe must be protected from
direct sunlight during administration, but it is stable in diffuse
daylight and artificial light for up to 10 hours. Nimotop solution
should be infused using a glass or rigid plastic (polyethylene or
polypropylene) syringe and giving set (Gillette Sabre syringe;
BD plastipak syringe; Monoject disposable syringe, Sherwood
Medical Ltd; Combidyn tubes, Braun; Nitrocassette giving
set, Imed Ltd.). Nimotop solution is incompatible with infusion
bags and any giving sets made of PVC (e.g., Viaflex, Travenol;
Steriflex, Boots).
To penetrate the coated injection stoppers correctly, fine acute
injection needles are recommended. DO NOT use large-core
infusion needles, since this may result in cracked or bruised
stoppers and the stoppers may be forced into the vial.

7. MARKETING AUTHORISATION HOLDER
Bayer plc
Bayer House; Strawberry Hill, Newbury, Berkshire, RG14 1JA

8. MARKETING AUTHORISATION NUMBER
PL 00010/0138

9. DATE OF FIRST AUTHORISATION/RENEWAL
OF AUTHORISATION
21 January 1988/ 23 November 2003

10.DATE OF (PARTIAL) REVISION OF THE TEXT
August 2015

U
84691135

PMR 84691135 (93/04/MU-0201503086) Pantone: ORANGE 021, Schwarz

200x810-16443_11523

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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