Evalex Tm 300 mg/400 mg/1 g

EVALEX IV contains sodium valproate, which belongs to a group of medicines called antiepileptics. These are used to control epileptic seizures. EVALEX IV solution for injection is used to treat various types of epileptic seizures (fits) when it is not possible to take sodium valproate tablets. EVALEX IV is also used in mania: where you may feel excited, elated, agitated, enthusiastic or hyperactive. Mania occurs in an illness called ‘bipolar disorder’.

EVALEX IV should not be administered to you:

• if you are hypersensitive (allergic) to sodium valproate or any of the ingredients of EVALEX IV (listed in Section 6)
• if you have liver problems, or have a family history of liver problems
• if you suffer from porphyria (a rare condition that affects the breakdown of components of red blood cells)
• if you have a genetic problem causing a mitochondrial disorder (e.g. Alpers-Huttenlocher syndrome)
• if you suffer from urea cycle disorder (a certain metabolic disorder)
• if you are pregnant or breastfeeding your baby. See “Warnings and precautions” and “Pregnancy, breastfeeding and fertility”.

Warnings and precautions

Talk to your doctor or healthcare provider before you are given EVALEX IV, if you:

• have diabetes. EVALEX IV may affect the results of urine tests
• have a carnitine palmitoyltransferase type II deficiency, which prevents the body from using certain fats for energy, as you may be more prone to serious side effects
• have kidney problems. Your doctor may give you a lower dose
• have a brain disease or a metabolic condition affecting your brain
• have a ‘urea cycle disorder’ where too much ammonia builds up in the body
• have an illness called ‘systemic lupus erythematosus (SLE)’ – a disease of the immune system which affects skin, bones, joints and internal organs
• know that there is a genetic problem caused by a mitochondrial disorder in your family. If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking EVALEX IV
• are having surgery, including dental surgery, tell the doctor or dentist that you are receiving EVALEX IV. You will need to take extra care in cleaning your teeth to prevent infection, as side effects of EVALEX IV include bleeding and swelling of the gums (see section 4).

Liver damage

EVALEX IV may cause severe and life-threatening damage to your liver. Signs that you may notice include seizures that are becoming more severe or happen more often, or excessive tiredness, lack of energy, weakness, stomach pain, loss of appetite, nausea, vomiting, yellow skin and eye whites) or swelling of the face. Tell your doctor immediately if you notice these symptoms.

Pancreas damage

EVALEX IV may cause serious or life-threatening damage to the pancreas. This may occur at any time during your treatment. If you experience any of the following symptoms, tell your doctor immediately: stomach pain, nausea, vomiting, or loss of appetite.

You will not be expected to give yourself EVALEX IV. It will be given to you by a person who is qualified to do so. EVALEX IV treatment must be started and supervised by a doctor specialised in the treatment of epilepsy.

Dosage

Your doctor will decide on the amount of EVALEX IV you will be given. This will depend on your age and weight and will be adjusted to achieve adequate control of your seizures. If you have been taking sodium valproate by mouth, the dose given to you will be the same by injection. Your doctor will tell you when you are ready to switch over to an oral dosage form of valproate. If you have been receiving other medicines for epilepsy the dose of EVALEX IV will be increased gradually over about 2 weeks. The total daily dose will normally be given by three or four slow injections, lasting 3-5 minutes, into your veins during the day, or by a continuous infusion (drip).

Patients with kidney problems

Your doctor may decide to adjust your or your child’s dose.

Patients taking other medicines for fits (epilepsy)

You or your child may be taking other medicines for epilepsy at the same time as EVALEX IV. If so, your doctor should gradually initiate treatment depending on your or your child’s condition. If you have any concerns tell your doctor or nurse. It is important for you to keep having your EVALEX IV treatment until your doctor decides to stop. If you stop, your seizures may return.

Tests

Make sure you or your child keep your regular appointments for a check-up. They are very important as your or your child’s dose may need to be changed. EVALEX IV can change the levels of liver enzymes shown up in blood tests. This can mean that your or your child’s liver is not working properly.

If you receive more EVALEX IV than you should

Since a healthcare provider will administer EVALEX IV, he/she will control the dosage. However, in the event of overdosage your doctor will manage the overdosage.

If you miss a dose of EVALEX IV

Since a healthcare provider will administer EVALEX IV, it is unlikely that the dose will be missed.

EVALEX IV can have side effects. Not all side effects reported for EVALEX IV are included in this leaflet. Should your general health worsen or if you experience any untoward effects while using EVALEX IV, please consult your doctor healthcare provider for advice.

If any of the following happens, tell your doctor immediately:

• You have an allergic reaction. The signs include: a rash, joint pain, fever (systemic lupus erythematosus), swallowing or breathing problems, swelling of your lips, face, throat or tongue. Hands, feet or genitals may also be affected. More severe allergic reactions can lead to lymph node enlargement and possible impairment of other organs (also known as DRESS syndrome).
• Liver problems and problems of the pancreas: A sudden illness which may happen in the first six months of treatment. It includes feeling and being sick many times; being very tired, sleepy and weak; stomach pain including very bad upper stomach pain; jaundice (yellowing of the skin or whites of the eyes); loss of appetite; swelling (especially of the legs and feet but may include other parts of the body); worsening of your fits or a general feeling of being unwell. It may sometimes even lead to death.

These are all very serious side effects. If you have them, you may have had a serious reaction to EVALEX IV. You may need urgent medical attention or further hospitalisation.

Tell your doctor immediately if you notice any of the following:

• You have a skin rash or skin lesions with a pink/red ring and a pale centre which may be itchy, scaly or filled with fluid. The rash may appear especially on the palms or soles of your feet. These could be signs of a serious allergy to the medicine called ‘erythema multiforme’.
• Blistering or bleeding of the skin around the lips, eyes, mouth, nose and genitals. Also, flu-like symptoms and fever. This may be something called ‘Stevens-Johnson syndrome’.
• Severe blistering rash where layers of the skin may peel off to leave large areas of raw exposed skin over the body. Also, a feeling of being generally unwell, fever, chills, and aching muscles. This may be something called ‘Toxic epidermal necrolysis’.
• Bruising more easily and getting more infections than usual. This could be a blood problem called ‘thrombocytopenia’. It can also be due to a fall in the number of white blood cells, bone marrow depression or another condition that affects red blood cells, white blood cells and platelets (pancytopenia) or how the blood clots.
• Blood clotting problems (bleeding for longer than normal), bruising or bleeding for no reason.
• Changes in mood, loss of memory, lack of concentration and deep loss of consciousness (coma).

These are all serious side effects. You may need urgent medical attention. Tell your doctor if you notice any of the following:

• Frequent side effects:
• Anaemia (the number of red blood cells in your body is too low), causing weakness, fatigue, pale skin)
• Too low blood sodium concentration (signs may be mental changes, headache, nausea, vomiting, tiredness, muscle spasms)
• Weight gain (see “Warnings and precautions”)
• State of confusion, hallucinations (seeing and hearing things that do not exist)
• Aggression, agitation
• Attention disturbances
• Sleepiness
• Convulsions
• Trembling of hands and arms, clumsiness or unsteadiness
• Headache
• Involuntary eye movements (nystagmus)
• Dizziness
• Hearing loss (which may be irreversible)
• Diarrhoea
• Nausea, vomiting
• Indigestion
• Gum disease (swollen gums)
• Stomach or abdominal pain.
• Sore mouth
• Hair loss or thinning of hair
• Nail and nail bed disorders
• Losing bladder control (incontinence)
• Painful menstrual periods.

Less frequent side effects:

• Hyperandrogenism (excessive presence of male hormones in females including symptoms like excessive hair growth, acne, male pattern hair loss)
• Double vision (diplopia)
• Encephalopathy (an altered mental state – declining ability to reason and concentrate, memory loss, personality change, seizures and twitching may be experienced)
• Lethargy (a lack of energy)
• Parkinsonism (which is reversible), lack of muscle control, affected movement, speech (ataxia)
• Pins and needles sensation in arms, hands, legs and feet (paraesthesia)
• Dementia (which is reversible)
• Trouble understanding things (cognitive disorder)
• Sedation
• Vasculitis (inflammation of the blood vessels – you may experience fever, fatigue, weight loss and muscle and joint pain)
• Build-up of fluid in the area between the layers of tissue that line the lungs causing chest pain, cough, difficulty breathing
• Skin rash
• Change in hair texture, colour, growth
• Decreased bone mineral density (brittle bones and fractures)
• Osteoporosis (brittle bones), osteopenia (reduced bone mass)
• Frequent urination at night
• Inflammation of the kidneys (back pain, fever)
• Fanconi syndrome: a rare disorder of kidney tubule function that causes increased urination, increased thirst, pain and weakness in muscle and bones
• Absent menstrual periods or abnormal bleeding from uterus
• Male infertility
• Polycystic ovaries (symptoms may be weight gain, irregular periods, heavy bleeding)
• Swollen breasts in males
• Feeling very cold, shivering (hypothermia)
• Swelling of the hands, ankles and feet
• Myelodysplastic syndrome (symptoms may include fatigue, shortness of breath and unusual paleness). This is a condition where immature blood cells in the bone marrow do not mature and therefore do not become healthy blood cells.
• Frequency unknown
• Malformation of the foetus and developmental disorders (see “Pregnancy, breastfeeding and fertility” and “Warnings and precautions”).

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

Reporting of side effects

If you get side effects, talk to your doctor, pharmacist or nurse. You can also report side effects to SAHPRA via the “Adverse drug reaction and quality problem 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 EVALEX IV can help provide more information on the safety of this medicine.

Store all medicines out of reach of children. Store at or below 25 °C. Keep ampoules in their original package until required for use. The contents of the ampoule are for single use only. Do not use EVALEX IV after the expiry date printed on the label, container or blister. Return any expired or unused medicine to your pharmacist for safe disposal. Do not dispose of unused medicine in drains or sewerage systems (e.g. toilets).