Epilim ® CR Tablets

EPILIM is used to treat epilepsy (fits) or used to treat bipolar disorders (severe mental illness) in adults.

Do not take EPILIM or give EPILIM to your child:

• If you or your child is hypersensitive (allergic) to sodium valproate (the active ingredient) or any of the other ingredients of EPILIM (see section 6).
• If you are breastfeeding your baby (see Pregnancy, breastfeeding and fertility).
• If you are pregnant or able to have a baby:
• For the treatment of epilepsy:
• If you or your female (girl) child is pregnant, unless there is no suitable alternative treatment (see Pregnancy, breastfeeding and fertility: Pregnancy – Important information for women).
• If you or your female (girl) child is able to have a baby, unless the conditions of the Pregnancy Prevention Programme are met (see Pregnancy, breastfeeding and fertility: Pregnancy – Important information for women).
• For the treatment of bipolar disorder:
• If you are pregnant.
• If you are a woman able to have a baby, unless the conditions of the Pregnancy Prevention Programme are met (see Pregnancy – Important information for women).
• If you or your child has an active disease of the liver, including the following:
• If you or your child has short- or long-term (severe) hepatitis (inflammation of the liver).
• If you or your child (or any of your close relatives) has a past history of severe hepatitis (inflammation of the liver), especially when caused by medicines.
• If you or your child suffers from liver porphyria (a very rare metabolic disease).
• If you or your child has been told you have a genetic problem caused by a mitochondrial disorder (e.g. Alpers-Huttenlocher syndrome).
• If you or your child has a known metabolic disorder, i.e. a urea cycle disorder.
• If you have an inborn carnitine deficiency (a very rare metabolic disease) that is untreated.

If you think you or your child may have any of these problems, or if you have any doubt at all, consult your doctor before taking EPILIM or giving EPILIM to your child.

Warnings and precautions

Take special care with EPILIM:

• If you are a woman or female adolescent able to have a baby:
• If you are a woman or female adolescent that is old enough to become pregnant, your doctor should only treat you with EPILIM if you are not pregnant and you fulfil the requirements of the Pregnancy Prevention Programme (see Pregnancy, breastfeeding and fertility: Pregnancy – Important information for women).
• If you are taking EPILIM and you decide you want to start a family, talk to your doctor about this as soon as possible. Do not stop EPILIM or using birth control (contraception) until you have been able to discuss this with your doctor. You need to talk to your doctor about the risks for your baby’s health while keeping your illness under control. Your doctor and you should agree on what to do with your treatment before you start trying for a baby (see Pregnancy, breastfeeding and fertility: Pregnancy – Important information for women).
• If you have a female (girl) child using EPILIM: Parents or caregivers of a female (girl) child treated for epilepsy with EPILIM, must contact the doctor once the female child using EPILIM experiences her first menstrual period.
• If you are pregnant: If you are pregnant, talk to your doctor immediately (see Do not take EPILIM or give EPILIM to your child and Pregnancy, breastfeeding and fertility).
• If you or your child develops a sudden illness, especially if it is within the first six months of treatment, and particularly if it includes repeated vomiting, extreme tiredness, abdominal pain, drowsiness, weakness, loss of appetite, upper stomach pain, nausea, jaundice (yellowing of the skin or whites of the eyes), swelling of the legs, worsening of your epilepsy or a general feeling of being unwell, YOU SHOULD TELL YOUR DOCTOR IMMEDIATELY. EPILIM can affect the liver (and sometimes the pancreas) in a very small number of patients.
• The risk of liver damage is increased if EPILIM is taken by your child who is less than 3 years of age, and who is taking other anti-epileptic medicines at the same time or has other neurological or metabolic diseases and severe forms of epilepsy.
• Especially if your child is below 3 years of age, EPILIM should not be administered together with acetylsalicylic acid (aspirin).
• If you or your child taking EPILIM develops problems with balance and co-ordination, vomiting, feeling lethargic or less alert, tell your doctor immediately. This may be due to an increased amount of ammonia in your blood.
• Convulsions may become worse or happen more frequently whilst taking EPILIM. If this happens contact your doctor immediately.
• If you or your child has systemic lupus erythematosus (SLE – a rare disease of the immune system which affects skin, bones, joints and internal organs).
• If you or your child has been told that you have any metabolic disorders, particularly hereditary enzyme deficiency disorders, such as a urea cycle disorder where too much ammonia builds up in the body.
• If you or your child has kidney problems. Your doctor may want to monitor the level of EPILIM in your body or give you a lower dose.
• If you or your child puts on weight, as your appetite may be increased. Talk to your doctor about how this will affect you or your child.
• If you or your child has diabetes, EPILIM may affect the results of urine tests.
• If at any time you or your child has thoughts of harming or killing yourselves, immediately contact your doctor.
• If you or your child drinks alcohol. Alcohol intake is not recommended during treatment with EPILIM (see Taking EPILIM with food, drink and alcohol).
• If you or your child has been told that you have carnitine palmitoyl transferase type II deficiency.
• If you have been told that there is a genetic problem caused by a mitochondrial disorder in your family.
• If you or your child experiences worsening of epilepsy control in terms of frequency or severity whilst taking EPILIM, contact your doctor immediately.
• Your doctor or your child’s doctor may wish to do blood tests before you or your child starts taking EPILIM and during your treatment.
• EPILIM should be used with caution in male and female children less than 18 years of age, for the treatment of epilepsy.
• EPILIM should only be used in adult males who plan to father a child if alternative treatment options are not suitable.
• EPILIM should not be used in children and adolescents under the age of 18 years for the treatment of mania associated with bipolar disorders.

Do not share medicines prescribed for you or your child with any other person. Always take or give your child EPILIM exactly as your doctor has instructed you. You should check with your doctor or pharmacist if you are unsure. EPILIM treatment must be started and supervised by a doctor experienced in the treatment of epilepsy.

EPILIM CR tablets: Swallow the EPILIM CR tablets whole (do not crush or chew them), with a drink of water (not with aerated mineral water), usually with or after meals. EPILIM CR is a controlled-release formulation and can be taken once or twice daily.

EPILIM 100 CRUSHABLE: The EPILIM 100 CRUSHABLE tablets may be crushed if necessary. Take with or after meals. EPILIM 100 CRUSHABLE should be taken in 2 separate doses.

EPILIM LIQUID SUGAR-FREE: Shake the bottle before each use. EPILIM LIQUID SUGAR-FREE should not be diluted and should be taken in divided doses. Take EPILIM LIQUID SUGAR-FREE using a measuring cup. After each dose, rinse the remaining liquid in the measuring cup with water and swallow the contents to make sure you take the complete dose. The measuring cup should be washed and dried after each use.

Epilepsy

Adults

The usual dose of EPILIM is between 1 000 mg and 2 000 mg per day but may be increased to 2 500 mg per day. This quantity may be given in one dose or can be divided and given in 2 separate doses, e.g. half in the morning and half in the evening.

Children

The oral solution and crushable tablets are more suitable to give to children less than 11 years of age. Children 20 kg and over: The usual dose of EPILIM is based on the child’s weight as an amount of EPILIM for each kg of body weight. The usual dose is between 20 mg and 30 mg for each kg of body weight but may be increased to 35 mg for each kg of body weight per day. This quantity may be given in one dose or can be divided and given in 2 separate doses, e.g. half in the morning and half in the evening. Children below 20 kg: The usual dose of EPILIM is based on the child’s weight as an amount of EPILIM for each kg of body weight. The usual dose is 20 mg for each kg of body weight. This quantity should be divided and given in 2 separate doses, e.g. half in the morning and half in the evening.

EPILIM CR for the treatment of mania associated with bipolar disorders in adults The usual initial dose is 1 000 mg/day.

Elderly patients Your dosage will be determined by the seizure control it gives you and be recommended by your doctor.

Patients with kidney problems Your doctor may decide to adjust your or your child’s dose.

Female children, women of childbearing potential and pregnant women Pregnant women as well as female children and women that are able to have a baby must not use EPILIM unless their doctor determined that there is no suitable alternative or the conditions for the Pregnancy Prevention Programme are met (see section 2).

EPILIM does not reduce the effectiveness of hormonal contraceptives. Estrogen-containing contraceptives may however increase the clearance of valproate, which may result in potentially decreased EPILIM effectiveness (see Other medicines and EPILIM).

If you have the impression that the effect of EPILIM is too strong or too weak, tell your doctor or pharmacist. Make sure you keep your regular check-up appointments. They are very important, as your dosage may need to be changed.

When treatment is first started, you may be prescribed a lower dose. This is because some patients need less EPILIM than others to control their fits. Your doctor will increase the dosage until your condition is controlled. Because of this, it is very important that you follow the instructions your doctor has given you about how much to take. Blood tests may be needed.

Combined therapy

If you are taking other medicines to control your epilepsy at the same time as EPILIM CR your doctor may increase the dose of EPILIM CR by 5 mg to 10 mg for each kg of body weight per day.

If you take or your child receives more EPILIM than required An overdose of EPILIM is dangerous. In the event of overdosage, consult your doctor or pharmacist. If neither is available, contact the nearest hospital or poison centre. Signs of overdosage or taking too much of EPILIM include:

• Coma, poor muscle tone resulting in limpness of the body.
• Inability to breathe properly.
• Having little or no reflexes when tested using a reflex hammer.
• Constriction of the pupils – pupils become smaller.
• Metabolic acidosis – which occurs when the body produces excessive quantities of acid or the kidneys are unable to remove enough acid from the body.
• Decrease in blood pressure and subsequent shutdown of the body due to shortage of blood flow.
• Death may occur in case of a large overdose.

Symptoms in cases of overdose:

This may vary but might include seizures, very high pressures within the skull.

The content of sodium in EPILIM may cause hypernatraemia (excessive sodium content in the body) when taken in excess.

EPILIM can have side effects. Not all side effects reported for EPILIM are included in this leaflet. Should your or your child’s general health worsen or if you experience any untoward effects while taking this medicine, please consult your doctor, pharmacist or other health care provider for advice.

Tell your doctor immediately or go to the casualty department at your nearest hospital if you notice any of the following serious side effects:

• allergic reactions, which cause joint pain, skin rashes and fever (systemic lupus erythematosus)
• an allergy-triggered swelling with painful itchy welts (most often around the eyes, lips, tongue and throat with difficulty in breathing or swallowing, and sometimes the hands and feet) (angioedema)
• syndrome with medicine rash, fever, lymph node enlargement and possible impairment of other organs (DRESS syndrome)
• repeated vomiting, extreme tiredness, abdominal pain, drowsiness, weakness, loss of appetite, severe upper stomach pain, nausea, jaundice (yellowing of the skin or whites of the eyes), swelling of the legs, worsening of your epilepsy or a general feeling of being unwell
• severe decrease in white blood cells or bone marrow failure, sometimes revealed by fever and breathing difficulty or recurring infection
• blood clotting problems (bleeding for longer than normal)
• bruising or bleeding for no reason
• EPILIM may also cause decreased platelet or red blood cell count (pancytopenia)
• memory impairment and cognitive disorders (changes in mood, loss of memory, lack of concentration)
• loss of consciousness (coma)
• underactive thyroid gland, which causes tiredness or weight gain (hypothyroidism)
• breathing difficulty and pain due to inflammation of the lungs (pleural effusion)
• changes in consciousness level, bizarre behaviour associated or not with more frequent or more severe fits, loss of drive, particularly if phenobarbital (phenobarbitone) and topiramate are taken at the same time or if the EPILIM dose has been increased suddenly
• changes in the amount of ammonia in the blood. Symptoms of this condition are feeling and being sick, problems with balance and co-ordination, feeling lethargic or less alert.
• confusion that may be due to decreased levels of sodium in your blood.
• extrapyramidal disorder (feeling shaky, [tremor], sleepy or unsteady when walking, or jerky muscle movements)
• blisters with skin detachment (skin flaking away)
• rapid, uncontrollable movements of the eyes
• muscle pain and muscle weakness (rhabdomyolysis)
• an increase in the number and severity of convulsions. These are all serious side effects. You may need urgent medical attention.

Other side effects are:

Frequent:

• vomiting, nausea (feeling sick) or stomach ache, diarrhoea
• dizziness
• hearing problems
• headache
• hair loss; when it grows back it may be curlier than before
• hair, including body and facial hair, grows more than normally in women (polycystic ovarian syndrome)
• menstrual changes (changes in a woman’s period)
• weight gain (as your appetite may be increased)
• decrease in carnitine levels (shown in blood or muscular tests)
• allergic reactions
• aggression, agitation, disturbance in attention
• tingling or numbness of the hands or feet
• gingival (gum) problems, especially overgrowth
• sore mouth, swollen mouth, mouth ulcers and burning feeling of your mouth (stomatitis).

Less frequent:

• fainting, hallucinations (seeing, feeling or hearing things that are not there)
• skin reactions such as rashes
• acne, lowered voice
• hair colour changes, nail and nail bed disorders
• swelling of the feet and legs (oedema)
• kidney problems, bedwetting or increased need to pass urine
• passing a lot of urine and feeling thirsty (Fanconi syndrome)
• abnormal behaviour, restlessness/hyperactivity and learning disorder
• impairment of fertility
• decrease in body temperature
• there have been reports of bone disorders including osteopenia and osteoporosis (thinning of the bone) and fractures. Check with your doctor or pharmacist if you are on long-term anti-epileptic medication, have a history of osteoporosis, or take steroids.
• double vision.

Frequency not known:

• Pelger-Huet anomaly (an inherited blood condition, where white blood cell cores have an unusual shape and structure), which your doctor will determine with a blood test.

Children: The safety profile of EPILIM in children is comparable to adults, but some adverse reactions are more severe or more often observed in children. There is a particular risk of severe liver damage in infants and young children, especially under the age of 3 years. Young children are also at particular risk of pancreatitis. These risks decrease with increasing age (see Warnings and precautions). Psychiatric disorders such as aggression, agitation, disturbance in attention, abnormal behaviour, psychomotor hyperactivity and learning disorder are mainly observed in children.

If you notice any side effects not mentioned in this leaflet, please inform your doctor, pharmacist or other health care provider.

Reporting of side effects

If you get side effects, talk to your doctor, pharmacist or nurse. You can report side effects directly to Sanofi’s Pharmacovigilance Unit at [email protected] (email) or 011 256 3700 (tel). You can also report side effects to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. By reporting side effects, you can help provide more information on the safety of EPILIM.

STORE ALL MEDICINES OUT OF REACH OF CHILDREN.

Store EPILIM in the original package at or below 25 °C. Protect from light and moisture. EPILIM may spoil if not stored properly. It is very important to keep the tablets in their protective foil until just before you take them. Do not take or use EPILIM after the expiry date stated on the pack. Return unused or expired medicines to your pharmacist for safe disposal. Do not dispose of unused medicine in drains or sewerage systems (e.g. toilets).