PACKAGE LEAFLET: INFORMATION FOR THE USER
Valproate chrono 300 mg/- 500 mg prolonged-release tablets
Sodium valproate/valproic acid
Read all of this leaflet carefully before you start taking this medicine.
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. Do not pass it on to others. It may harm them, even
if their symptoms are the same as yours.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet:
1.
What Valproate chrono is and what it is used for
2.
Before you take Valproate chrono
3.
How to take Valproate chrono
4.
Possible side effects
5.
How to store Valproate chrono
6.
Further information
1.
WHAT VALPROATE CHRONO IS AND WHAT IT IS USED FOR
Valproate chrono belongs to the medicinal product group of antiepileptics. These agents suppress attacks
in seizure disorders (epilepsy).
Valproate chrono is used in certain forms of epilepsy such as:
• certain forms of short-term unconsciousness as a result of a disorder in the brain (petit mal)
• sudden contraction of muscles (myoclonia)
• rhythmically contracting seizures in association with (muscular) tension (grand mal)
• combined forms of the above-named disorders.
Valproate chrono may also be used in epilepsy which does not sufficiently respond to other antiepileptics,
such as:
• epilepsy not associated with movements or (muscular) tension
• epilepsy with symptoms affecting perception as well as symptoms with regard to deliberate
movements.
Valproate chrono may be used alone and in combination with other antiepileptics.
2.
BEFORE YOU USE VALPROATE CHRONO
Do not use Valproate chrono
• if you are hypersensitive to sodium valproate and/or valproic acid or to any of the other
ingredients of the tablets
• if you suffer from an impaired function of your liver or pancreas
• if you or any of your dependants have a history of severe liver damage especially drug related
• if you suffer from a disease due to a disorder in the formation of red blood pigment (porphyria)
• if you are susceptible to bleeding.
Take special care with Valproate chrono
• if you must undergo surgery or a dental intervention and in case of spontaneous bruises or
bleeding (see “Possible side effects”), the doctor should monitor your blood count
• if Valproate chrono is given to infants and children aged less than 3 years with a severe form of
epilepsy (particularly those with anomalies regarding cerebrum, mental retardation, certain
disorders caused by genes and/or known metabolic disorders); there is a higher risk of liver
intoxication in the first 6 months of treatment, particularly in very young children. The risk of
liver intoxication is higher particularly in combined treatment with other antiepileptics.
• if you develop complaints during treatment with Valproate chrono, such as weakness, physical or
mental weakness, loss of appetite (anorexia), apathy, sleepiness, repeated vomiting, abdominal
pain, recurrence or worsening of seizures/convulsions and/or prolonged bleeding time, consult the
attending doctor immediately. Inflammation of the liver or pancreas, or an increased level of
ammonia in the blood may be the reason. Patients with suspected metabolic disturbances,
especially enzyme disturbances of the urea cycle should therefore undergo metabolic investigation
by the attending doctor before treatment is started.
• if you suffer from a reduced renal function; it may be necessary that your doctor reduces the dose
in order to decrease the content of valproic acid in blood (see “How to take Valproate chrono”)
• if you suffer from inflammation-like diseases of the skin and/or internals (SLE; systemic lupus
erythematosus); this disorder can be made worse or be induced due to Valproate chrono.
• If you notice that you gain weight, particularly at the beginning of treatment. This can be
attributed to an increased appetite (see “Possible side effects”). You should monitor your weight
and limit a possible weight gain to a minimum.
• If you have a history of bone marrow damage
Note:
It is possible that the matrix tablets are recovered in the stool.
Consult your doctor if one of the above-named warnings is relevant for you or was relevant once
before.
Taking other medicines
Valproate chrono and other medicinal products can reciprocally influence the effects and side effects.
This applies among others to:
• antipsychotics, MAO inhibitors, antidepressants and benzodiazepines (agents in psychiatric
disorders); the effect of these agents can be potentiated if Valproate chrono is used. Possible dose
adjustment can be necessary.
• phenobarbital (agent in case of epilepsy); the concentration of phenobarbital in the blood can increase
(particularly in children). Possible dose adjustment can be necessary.
• primidone (agent in case of epilepsy); the concentration of primidone can increase with an increase in
the side effects (such as dementia). This disappears in longer-term use.
• carbamazepine (agent in case of epilepsy and psychiatric disorders); the toxic effects of
carbamazepine can be potentiated if Valproate chrono is used concurrently. Possible dose adjustment
can be necessary.
• lamotrigine (agent in case of epilepsy); this combination involves an increased risk of (severe) skin
reactions, particularly in children. Valproic acid can reduce the metabolism of lamotrigine in the
body. Possible dose adjustment can be necessary.
• zidovudine (agent in HIV infections); valproic acid can increase the concentration of zidovudine in
blood. Dose reduction of zidovudine can be necessary.
• other agents in seizure disorders (antiepileptics, such as phenytoin, phenobarbital and carbamazepine); the concentration of valproic acid in blood can be reduced. Possible dose adjustment can
be necessary.
• felbamate (agent in case of epilepsy); the concentrations of valproic acid and felbamate in blood can
be increased. Possible dose adjustment of Valproate chrono and felbamate can be necessary.
• mefloquine (agent for the treatment and prophylaxis of malaria); epileptic seizures can occur during
concurrent use of Valproate chrono
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medicinal products inhibiting certain liver enzymes (such as cimetidine or erythromycin); the
concentration of valproic acid in blood can be increased
Carbapenem antibiotics e.g. panipenem, meropenem and imipenem (antibiotics; agents in
inflammation-like disorders); the concentration of valproic acid in blood can be reduced. Possible
dose adjustment of Valproate chrono can be necessary.
acetylsalicylic acid (blood thinning or pain relieving agent) ); valproic acid can potentiate the effect of
this agent. Concomitant use of these agents in children aged less than 3 years is not recommended
because of the risk of liver intoxication.
valproate and agents such as acetylsalicylic acid; the concentration of valproate in blood can be
increased.
Cholestyramine (cholesterol-lowering agent); the absorption of valproate may be decreased
Alcohol; Valproate may potentiate the effects of alcohol.
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
Taking Valproate chrono with food and drink
Food: The tablets may be taken 1 hour before or during meals but always in the same mode, together
with water (no carbonated beverages such as refreshments). Food appears not to change the extent of
absorption to a relevant extent.Alcohol: The combination of Valproate chrono and alcohol is not
recommended since seizures may be provoked and the effect of alcohol may be potentiated.
Pregnancy and breast-feeding
Women of childbearing potential should have been given specialist advice, before taking Valproate
chrono. The substance has shown to be harmful to the unborn child especially when given in the first
three month of pregnancy. As most other agents against epilepsy, this preparation has also shown to be
harmful in animal trials. Pregnant women using medicinal products against epilepsy are at increased
risk of giving birth to a child with congenital anomalies. After use of sodium valproate by the mother
during pregnancy, children with an open back or with anomalies affecting the face were born. In
women with epilepsy who want to become pregnant, the risks of continued or discontinued treatment
with medicinal products should be carefully weighed up. If pregnancy is desired, it is necessary to
discuss this with your doctor in advance.
Some malformations, such as spina bifida (open back) can be detected in the first months of pregnancy
by means of amniocentesis.
In exceptional cases children of mothers who used sodium valproate during pregnancy have a disorder
of blood coagulation. It is therefore necessary to monitor the blood coagulation in newborns (by means
of withdrawing some blood).
Sodium valproate is partially excreted via mother’s milk. If you want to breastfeed, the benefits should
carefully be weighed against the risk that side effects occur in your child. You may breastfeed your
child provided that your child will be monitored for side effects (such as sleepiness, difficulties when
drinking, vomiting, spot-like bleeding of the skin).
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
Valproate chrono can cause side effects such as dizziness, drowsiness and sleepiness which adversely
affects your reactivity. You should consider this when driving or using machines.
Epilepsy itself is also a reason to be careful in these activities, particularly if you have not had a
longer-term period without symptoms.
Important information about some of the ingredients of Valproate chrono
Valproate chrono 300 mg prolonged-release tablet
This medicinal product contains 28 mg sodium per dose. This has to be taken
into consideration if you follow a controlled sodium diet.
Valproate chrono 500 mg prolonged-release tablet
This medicinal product contains 47 mg sodium per dose. This has to be taken into consideration if you
follow a controlled sodium diet.
3.
HOW TO TAKE VALPROATE CHRONO
Always take Valproate chrono exactly as your doctor has told you.
You should check with your doctor or pharmacist if you are not sure.
Take the tablets or tablet parts without chewing, together with water 1 hour before or during meals, but
always in the same mode (no carbonated beverages such as refreshments). Intake during meals
reduces the risk of adverse events related to the gastro-intestinal tract.
Valproate chrono prolonged-release tablets can be halved.
Your doctor has prescribed how much Valproate chrono you must use. In general, the usual dose is:
Adults and children
Starting dose: 10-15 mg sodium valproate/kg bodyweight per day. To be taken in 2 or more doses.
(For example: A person weighing 75 kg who has been prescribed a dose of 10 mg [milligrams] per kg
[kilogram] body weight per day would have to take 2 ½ prolonged-release tablets Valproate chrono
300 mg per day.)
If necessary, the doctor can weekly increase the dosage by 5-10 mg sodium valproate /kg bodyweight
per day until the desired effect is achieved.
Maintenance dose: usually 20-30 mg sodium valproate/kg bodyweight per day.
Adults: 9-35 mg sodium valproate/kg bodyweight per day.
Children: 15-60 mg sodium valproate/kg bodyweight per day.
The optimal daily maintenance dose is usually divided into 1 to 2 doses during meals.
A maximum daily dose of 60 mg sodium valproate/kg bodyweight per day should not be exceeded.
Children under 20 kg bodyweight
An alternative formulation of valproate should be used in this group of patients, due to the need for
dose titration.
Elderly
The metabolism of valproate may be altered in the elderly. Dosage should be determined by seizure
control by your doctor.
The following daily doses for sodium valproate are recommended (table for orientation purposes):
Age
3 - 6 months
6 - 12 months
1 - 3 years
3 - 6 years
7 - 11 years
12 - 17 years
Adults and elderly
Reduced renal function
Body weight (kg)
≈ 5.5 - 7.5
≈ 7.5 - 10
≈ 10 - 15
≈ 15 - 20
≈ 20 - 40
≈ 40 - 60
≥ 60
Average dose (mg/day)
150
150 - 300
300 - 450
450 - 600
600 - 1200
1000 - 1500
1200 - 2100
The doctor can decide to reduce the above dosage if you suffer from reduced renal function (see “Take
special care with Valproate chrono”).
If you have the impression that the effect of Valproate chrono is too strong or too weak, consult your
doctor or pharmacist.
Duration of treatment
Your doctor should tell you how long you must use Valproate chrono. Do not stop treatment
prematurely, since the complaints can recur in this case.
If you use more Valproate chrono than you should
If you have used too much Valproate chrono, immediately contact your doctor or pharmacist.
Symptoms of overdose can be: coma with elevated muscular tension, reduced reflexes, contracted
pupils (miosis), confusion, sleepiness, metabolic acidosis, increased sodium in the blood and impaired
respiratory or heart function.
Furthermore in both, adults and children, high dosages caused abnormal neurological disturbances,
such as an increased tendency to seizures and behavioural changes
If you forget to take Valproate chrono
Do not take a double dose to make up for a forgotten dose.
If you have forgotten to take a dose, you can do this afterwards unless it is almost time to take your
following dose. In this case, follow the normal dosage scheme.
If you stop taking Valproate chrono
Do not discontinue treatment with Valproate chrono without the doctor’s advice under any
cicumstances.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Valproate chrono can cause side effects although not everybody gets them.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
Adverse drug reactions are listed below with frequencies defined as:
Very Common (>1/10)
Common
(>1/100, <1/10)
Uncommon
(>1/1000, <1/100)
Rare
(>1/10000, <1/1000)
Very rare
(<1/10000) including isolated reports
Blood and lymphatic system disorders
• Blood count alterations due to temporary suppression of bone marrow
- common: blood count alteration (deficiency of blood platelets) accompanied by bruises and
bleeding tendency (thrombocytopenia).Bleeding.
The suppression of bone marrow can uncommonly lead to severe count alterations, such as:
- very rare: very severe blood count alteration (deficiency of white blood cells) accompanied by
sudden high fever, severe sore throat and pustules in the mouth (agranulocytosis)
- very rare: anaemia
- very rare: reduction in all cells in the blood (pancytopenia)
• too many white blood cells in the blood (lymphocytosis)
• very rare: prolonged bleeding time due to impaired formation of blood clots and/or of a certain
disease of the blood platelets (deficiency of factor VIII/von Willebrand factor)
rare:
• reduction in the protein concentration (fibrinogen) in the blood
Hormone (endocrine) disorders
common:
• irregular menstruation
rare:
• missing menstruation, polycystic ovaries, raised testosterone levels
Nervous system disorders
common:
• trembling of hands
• headache
• drowsiness
• sleepiness
• apathy
• impaired coordination (ataxia), e.g. walking like a drunk
• paraesthesias
uncommon:
• hyperactivity
• irritability
• events associated with the occurrence of convulsions:
• confusion
• reduced consciousness (stupor) or hypersomnia (lethargy) leading to temporary coma
(encephalopathy)
rare:
• trembling of eyes, uncontrolled rapid movement of eyes (nystagmus)
• dizziness
very rarely reported:
• temporary mental decline which is associated with temporary shrinkage of the cerebrum
• temporary Parkinson’s disease (trembling muscles, impaired movements, so-called mask-like face,
etc.) is reported
• hallucinations
Gastrointestinal disorders
uncommon:
• nausea, vomiting, hypersalivation, gastrointestinal disorders (of temporary nature, at the beginning
of treatment)
rare:
• inflammation of the pancreas (pancreatitis)
Liver/bile (hepatobiliary) disorders
uncommon:
Hepatic dysfunctions, sometimes accompanied by too much ammonia in blood (smell of ammonia
identifiable in the urine) and sleepiness can occur in exceptional cases in the first 6 months of
treatment. Particularly in children, these can be very severe with possibly fatal course (see also section
“Take special care with Valproate chrono”).
Skin and subcutaneous tissue disorders
• temporary hair loss (common)
rare
• hair colour becoming fairer
• inflammation of a blood vessel of the skin
• skin reactions such as skin rash (exanthematous skin rash)
• skin rash with red (sweaty) irregular spots (erythema (exudativum) multiforme)
very rarely reported:
• severe, acute (hypersensitivity) reactions accompanied by fever and blisters on the skin/peeling of
the skin (toxic epidermal necrolysis)
• severe hypersensitivity reaction with (high) fever, red spots on the skin, joint pain and/or
inflammation of the eyes (Stevens-Johnson syndrome)
Others
common:
• weight gain (see also section “How to take Valproate chrono?”) or weight loss, increased or lack
of appetite
uncomon:
• accumulation of liquid in arms and legs (peripheral oedema)
rare:
• inflammation of the mucous membranes of the mouth (stomatitis)
• disease caused by a disorder in the formation of red blood pigment (porphyria)
• inflammation-like disease of the skin and/or internals (SLE; systemic lupus erythematosus)
• hearing loss (temporary or persistent)
• dwarfism (Fanconi’s syndrome)
very rare:
• bedwetting during the night.
• tinnitus
5.
HOW TO STORE VALPROATE CHRONO
Keep out of the reach and sight of children.
Do not use Valproate chrono after the expiry date which is stated on the carton.
The expiry date refers to the last day of that month.
This medicinal product does not require any special storage conditions.
Medicines should not be disposed on via waste water or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
6.
FURTHER INFORMATION
What Valproate chrono contains
The active substance is sodium valproate and valproic acid.
Valproate chrono 300 mg prolonged-release tablets
One prolonged-release tablet contains 200 mg sodium valproate and 87 mg valproic acid, together
equivalent to 300 mg sodium valproate
Valproate chrono 500 mg prolonged-release tablets
One prolonged-release tablet contains 333 mg sodium valproate and 145 mg valproic acid, together
equivalent to 500 mg sodium valproate
The other ingredients are
Tablet core
colloidal anhydrous silica , colloidal hydrated silica, ethyl cellulose , hypromellose
sodium (954)
Tablet coating
saccharin
hypromellose, macrogol 6000, methacrylic acid ethyl acrylate co-polymer (1:1) dispersion 30%, talc,
titanium dioxide (E 171)
What Valproate chrono looks like and contents of the pack
Valproate chrono prolonged-release tablets are white, oval tablets with a score.
The prolonged-release tablets are packed in blisters in a carton containing 20, 30, 50, 60, 90, 100 and 200
tablets.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
To be completed nationally.
Manufacturer
Salutas Pharma GmbH
Otto-von-Guericke-Allee 1
39179 Barleben
Germany
HEXAL A/S
Kanalholmen 8-12
2650 Hvidovre
Denmark
LEK S.A.
Ul. Podlipie 16
95-010 Stryków
Poland
manufacturing site
LEK S.A.
Ul. Domaniewska 50C
02-672 Warsaw
Poland
HEXAL B.V.
Pastoorslaan 28
2182 Hillegom
The Netherlands
Sandoz Pharmaceuticals GmbH
Carl-Zeiss-Ring 3
85737 Ismaning
manufacturing site:
Dieselstraße 5
70839 Gerlingen
Lek Pharmaceuticals d.d.
Verovškova 57,
1526 Ljubljana
Slovenia
This medicinal product is authorised in the Member States of the EEA under the following names:
NL/H/678/01
CZ: Valproat IA Pharma 300 mg
DK: Valproat 1A Farma
EE: Valproate sodium 1A Pharma 300 mg
LT: Valproate sodium 1A Pharma 300 mg prolonged release tablets
LV: Valproate sodium 1A Pharma 300 mg prolonged release tablets
NL: Natriumvalproaat chrono Sandoz 300 mg
NL/H/678/02
CZ: Valproat IA Pharma 500 mg
DK: Valproat 1A Farma
EE: Valproate sodium 1A Pharma 500 mg
LT: Valproate sodium 1A Pharma 500 mg prolonged release tablets
LV: Valproate sodium 1A Pharma 500 mg prolonged release tablets
NL: Natriumvalproaat chrono Sandoz 500 mg
NL/H/736/01
AT: Natriumvalproat Sandoz 300 mg – Retardtabletten
BE: Valproate Sandoz 300 mg tabletten met verlengde afgifte
CZ: Valproat Sandoz 300 mg
DE: Valproat-Sandoz 300 mg Retardtabletten
DK: Valproat Sandoz
EE: Valproate sodium Sandoz 300 mg
FI: Valproat SANDOZ
LT: Valproate sodium Sandoz 300 mg prolonged release tablets
LV: Valproate sodium Sandoz 300 mg prolonged release tablets
NL: Natriumvalproaat chrono Sandoz 300 mg
PL: ValproLEK 300
SK: Valproát chrono Sandoz 300 mg tablety s predĺženým uvoľňovaním
NL/H/736/02
AT: Natriumvalproat Sandoz 500 mg – Retardtabletten
BE: Valproate Sandoz 500 mg tabletten met verlengde afgifte
CZ: Valproat Sandoz 500 mg
DE: Valproat-Sandoz 500 mg Retardtabletten
DK: Valproat Sandoz
EE: Valproate sodium Sandoz 500 mg
FI: Valproat SANDOZ
LT: Valproate sodium Sandoz 500 mg prolonged release tablets
LV: Valproate sodium Sandoz 500 mg prolonged release tablets
NL: Natriumvalproaat chrono Sandoz 500 mg
PL: ValproLEK 500
SK: Valproát chrono Sandoz 500 mg tablety s predĺženým uvoľňovaním
NL/H/737/01
DK: Valproat HEXAL
DE: Valproat HEXAL chrono 300 mg Retardtabletten
IE: Valproat 300 mg Prolonged Release Tablets
LU: Valproat HEXAL chrono 300 mg Retardtabletten
NL: Natriumvalproaat chrono Sandoz 300 mg
PL: Valproate – 1 A Pharma
NL/H/737/02
DK: Valproat HEXAL
DE: Valproat HEXAL chrono 500 mg Retardtabletten
IE: Valproat 500 mg Prolonged Release Tablets
LU: Valproat HEXAL chrono 500 mg Retardtabletten
NL: Natriumvalproaat chrono Sandoz 500 mg
PL: Valproate – 1 A Pharma
This leaflet was last approved in July 2008.