Rubilim CR Prolonged-Release Tablets

RUBILIM CR is a prolonged release tablet which means that the active ingredient sodium valproate, is slowly released from the tablets over a period of time.

RUBILIM CR is a medicine for the treatment of epilepsy and mania. RUBILIM CR is used in the treatment of:

• Epilepsy (fits) in adults and children
• Mania, where you may feel excited, elated, agitated, enthusiastic or hyperactive. Mania occurs in an illness called ‘‘bipolar disorder’’.

Do not take RUBILIM CR:

• If you are hypersensitive (allergic) to sodium valproate or any of the other ingredients of RUBILIM CR (listed in section 6).
• If you are breastfeeding your baby (see “Pregnancy and Breastfeeding”).
• if you are pregnant: For the treatment of epilepsy:
• if you or your female (girl) child are pregnant, unless there is no suitable alternative treatment.
• if you or your female (girl) child are able to have a baby, unless the conditions of the pregnancy prevention programme are met (see “Pregnancy – Important advice 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 advice for women”).
• If you have an active disease of the liver, including the following:
• if you have short or long-term (severe) hepatitis (inflammation of the liver)
• if you (or any of your close relatives) have a past history of severe hepatitis (Inflammation of the liver), especially when caused by medicines
• if you suffer from liver porphyria (a very rare metabolic disease)
• if you have been told you have a genetic problem caused by a mitochondrial disorder (e.g. Alpers-Huttenlocher syndrome)
• if you have a known metabolic disorder, i.e. a urea cycle disorder.

If you think you may have any of these problems, or if you are in any doubt at all, consult your doctor before taking RUBILIM CR.

Warnings and precautions

Take special care with RUBILIM CR:

• 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 RUBILIM CR if you are not pregnant and you fulfil the requirements of the pregnancy prevention programme. See “Pregnancy: Pregnancy: Important information for women”.
• If you are taking RUBILIM CR and you decide you want to start a family, talk to your doctor about this as soon as possible. Do not stop RUBILIM CR 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. You and your doctor should agree on what to do with your treatment before you start trying for a baby.
• If you are pregnant, talk to your doctor immediately.
• If you develop 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 or worsening of your epilepsy or a general feeling of being unwell, YOU SHOULD TELL YOUR DOCTOR IMMEDIATELY. RUBILIM CR can affect the liver (and sometimes the pancreas) in a very small number of patients.
• If you have (SLE) systemic lupus erythematosus (a rare disease of the immune system which affects skin, bones, joints and internal organs)
• If you have 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 have kidney problems. Your doctor may want to monitor the level of RUBILIM CR in your body or give you a lower dose.
• If you put on weight as your appetite may be increased. Talk to your doctor about how this will affect you.
• If you or your child have diabetes, RUBILIM CR may affect the results of urine tests.
• If at any time you have thoughts of harming or killing yourself, immediately contact your doctor.
• If you drink alcohol. Alcohol intake is not recommended during treatment with RUBILIM CR.
• If you have 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.

Your doctor or your child’s doctor may wish to do blood tests before you or your child start taking RUBILIM CR and during your treatment. RUBILIM CR should only be used in adult males who plan to father a child if alternative treatment options are not suitable. RUBILIM CR should not be used in children under the age of 18 years for the treatment of mania associated with bipolar disorders.

Taking with food and drink

Alcohol intake is not recommended during treatment.

Other medicines and RUBILIM CR

Always tell your health care provider if you are taking any other medicine. (This includes all complementary or traditional medicines.) This is because RUBILIM CR can affect the way some other medicines work. Also some medicines can affect the way RUBILIM CR works.

The following medicines can increase the chance of you getting side effects, when taken with RUBILIM CR:

• Some medicines used for pain and inflammation (salicylates) such as aspirin.
• Some other medicines used to treat fits (epilepsy) – phenobarbital, primidone, phenytoin, carbamazepine, topiramate, acetazolamide, lamotrigine, rufinamide and felbamate.
• Medicines which are used to treat schizophrenia or bipolar disorder containing quetiapine.

RUBILIM CR may increase the effect of the following medicines:

• Medicines used for thinning the blood (such as warfarin)
• Medicines used for HIV infection containing zidovudine
• Medicines for depression such as citalopram, escitalopram, fluoxetine, fluvoxamine, sertraline, venlafaxine, aripiprazole
• Monoamine oxidase inhibitors (MAOI) such as moclobemide, selegiline, linezolid
• Medicines used to calm emotional and mental conditions such as diazepam and olanzapine
• Propofol, an anaesthetic
• Nimodipine

The following medicines can affect the way RUBILIM CR works:

• Some medicines used for the prevention and treatment of malaria such as mefloquine and chloroquine
• Cimetidine - used for stomach ulcers
• Cholestyramine used to lower blood fat (cholesterol) levels
• Some medicines used for infections (antibiotics) such as rifampicin and erythromycin
• Lopinavir and ritonavir – used for HIV treatment
• Estrogen-containing products (including some birth control pills)

In particular, tell your doctor or nurse if you are taking any of the following medicines: Carbapenem medicines (antibiotics used to treat bacterial infections). The combination of valproic acid and carbapenems should be avoided because it may decrease the effect of sodium valproate.

Do not share medicines prescribed for you with any other person. Always take RUBILIM CR exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure. RUBILIM CR treatment must be started and supervised by a doctor specialised in the treatment of epilepsy or bipolar disorders.

Taking this medicine

• Your doctor will decide how much RUBILIM CR to give you or your child depending on your or your child’s body weight
• Take this medicine by mouth
• Take RUBILIM CR with or after food. This will help to stop the feelings of sickness that may happen after taking RUBILIM CR.
• Do not crush or chew the tablets
• If you feel the effect of your medicine is too weak or too strong, do not change the dose yourself but ask your doctor

How much to take:

The daily dosage should be established and controlled individually by your doctor. Initial dose: The recommended initial daily dose is 1000mg. Mean daily dose: The recommended daily doses usually range between 1000 mg and 2000 mg.

Adults (including the elderly)

• The starting dose is 600mg daily. Your doctor will gradually increase this dose by 200mg every 3 days depending on your condition
• The usual dose is generally between 1000mg and 2000mg (20-30mg per kilogram of body weight) each day
• This may be increased to 2500mg each day depending on your illness

Children over 20 kilograms

• The starting dose should be 400mg daily. Your doctor should increase this dose depending on your child’s illness
• The usual dose is then between 20mg and 30mg for each kilogram of body weight each day
• This may be further increased to 35mg for each kilogram of body weight each day depending on your child’s illness

Children under 20 kilograms

The usual dose of RUBILIM CR is based on the child's weight as an amount of RUBILIM CR for each kg of bodyweight. The usual dose ls 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.

RUBILIM CR can have side effects. Not all side effects reported for RUBILIM CR are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking this medicine, please consult your doctor, pharmacist or other healthcare professional for advice.

If you get any of the following side effects, stop taking RUBILIM CR and tell your doctor immediately, or go to the casualty department at your nearest hospital:

• Allergic reactions (including swelling of the face, eyelids, lips, tongue, throat; difficulty in breathing and swallowing). These are all very serious side effects. If you have them, you may have had a serious reaction to RUBILIM CR. You may need urgent medical attention or hospitalisation.

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

• changes in the amount of ammonia in the blood (symptoms are vomiting, problems with balance, feeling less alert);
• liver problems (being nauseous and vomiting many times, being very tired, sleepy and weak, stomach pain, yellowing of the skin or whites of the eye);
• inflammation of the pancreas (acute abdominal pain); chest pain; shortness of breath; see also Take special care with RUBILIM CR above.

These are all serious side effects. You may need urgent medical attention.

Tell your doctor if you notice any of the following:

The following side effects occur frequently: Headache; sleep disorders; clumsiness or unsteadiness; trembling of hands and arms; nervousness; changing moods; blurred vision; ringing in ears; deafness, dizziness; flu; abdominal or stomach pain; heartburn; nausea and vomiting; diarrhoea; skin rash; hair loss or thinning of hair; back pain; change in menstrual periods; lack or loss of strength, mental confusion, aggression, convulsion, memory problems, becoming unreactive, bedwetting.

The following side effects occur less frequently: Unusual bleeding or bruising; abnormal dreams; anxiety; feeling sad; irritability; pain in joints; cough; constipation; rolling of the eyes; dry eyes; spots before the eyes; ear infection; ear pain; runny nose; dental pain; bloated full feeling; muscle pains or stiffness; fatigue, weight gain or loss, learning disorder, coma, loss of muscle control, brittle bones and fractures, shortness of breath and chest pain, blood clotting problems.

Side effects occurring at unknown frequency: RUBILIM CR can change levels of liver enzymes, salts or sugars shown up on blood and urine tests. Various birth defects and developmental delays have been reported in babies born of women taking RUBILIM CR during pregnancy (see Pregnancy and breastfeeding for details and advice).

If you notice any side effects not mentioned in this leaflet please inform your doctor or pharmacist.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects to SAHPRA via the “6.04 Adverse Drug Reaction Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8. By reporting side effects, you can help provide more information on the safety of RUBILIM CR

Store all medicines out of reach of children.

Store at or below 25 °C

Store in the original package in order to protect from light and moisture.