150 mg or 300 mg enteric tablet is
sodium valproate
| WARNING |
| Orfiril, sodium valproate can seriously harm an unborn baby when taken during pregnancy. If you are a pregnant woman, you must use an effective contraceptive without interruption throughout your treatment with Orfiril. Your doctor will discuss this with you, but you must also follow the instructions in section 2 of this leaflet. Tell your doctor immediately if you want to get pregnant or if you think you may be pregnant. Do not stop using Orfiril unless your doctor tells you to as your condition may get worse. |
What Orfiril is and what it is used for
Orfiril contains sodium valproate which is an antiepileptic drug.
The mechanism of action of Orfiril is not fully understood. One theory is that Orfiril normalizes disorders in the chemical processes that occur between the nerve cells in the brain and thus prevents the onset of epileptic seizures.
Orfiril enteric- tablet is used in different types of epilepsy .
Sodium valproate contained in Orfiril may also be approved for the treatment of other conditions not mentioned in this product information. Ask your doctor, pharmacist or other healthcare professional if you have any further questions and always follow their instructions.
What you need to know before you take Orfiril
Do not take Orfiril
- if you are allergic to sodium valproate or to any of the other ingredients of this medicine (listed in section 6).
- if you have impaired liver function.
- if you have acute intermittent porphyria (hereditary metabolic disease with disturbed production of blood pigments).
- if you have a hereditary problem that causes a disturbance in the cells’ energy supply (eg Alpers-Huttenlocher syndrome).
- if you suffer from urea cycle disorders (a specific metabolic disease).
- for epilepsy , do not use Orfiril if you are pregnant, unless otherwise indicated for you.
- For epilepsy , if you are a woman who may have children, do not take Orfiril unless you are using an effective contraceptive throughout treatment with Orfiril. Do not stop taking Orfiril or your contraceptive until you have discussed it with your doctor. Your doctor will give you further advice (see below under “Pregnancy, breast-feeding and fertility – Important advice for women”).
Warnings and cautions
Talk to your doctor before taking Orfiril.
Contact a doctor immediately if you experience symptoms such as weakness, loss of appetite, nausea, repeated vomiting, upper abdominal pain, swelling ( edema ), agitation, lack of interest or concern for emotional, social or physical life ( apathy ), confusion, movement disorders or if the seizures recur or increase in frequency. Orfiril can affect the liver (and in very rare cases the pancreas). This is especially true in infants and children under 3 years of age with severe form of epilepsy (especially children with brain damage, developmental disorders, genetic and / or metabolic diseases) and in combination therapy with other antiepileptic drugs .
Consult your doctor:
- if you have impaired kidney function.
- if you have a metabolic disorder (especially if you have a hereditary enzyme deficiency disease). If urea cycle disorders are suspected, metabolic studies should be performed before taking Orfiril, due to the risk of an increase in ammonia in the blood (hyperammonemia).
- if you have disorders of the blood’s ability to clot or other blood disease (eg bone marrow damage).
- if you have systemic lupus erythematosus ( SLE , autoimmune collagen disease, which can affect many organ systems).
- if you gain weight. Check your weight regularly, especially at the beginning of treatment.
- if you know that there is a hereditary problem in your family that is causing a disruption in the cells’ energy supply.
- if you are missing an enzyme called type II carnitine palmitoyltransferase (CPT) and have severe muscle pain, as this may be a sign of muscle damage.
Sodium valproate may affect certain urine tests ( ketone body tests ). Therefore, information that you are using Orfiril for urine sampling.
Before starting treatment with Orfiril, in connection with surgery, bruising, or bleeding, the blood’s ability to coagulate should be examined. Orfiril treatment may require close monitoring of blood counts, platelets , liver and pancreas functions.
A small number of people being treated with antiepileptic drugs such as sodium valproate have also had thoughts of harming themselves or committing suicide. If you ever get these thoughts, contact your doctor immediately.
As with other antiepileptic medicines, some patients may experience worsening attacks with Orfiril.
Other medicines and Orfiril
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The effect of the treatment can be affected if Orfiril and certain other medicines are taken at the same time:
- acetylsalicylic acid (medicine for fever and pain)
- cimetidine (medicine for stomach upset)
- antiepileptic drugs ( etosuximide , felbamate, phenytoin , phenobarbital, carbamazepine, lamotrigine, topiramate, rufinamide)
- diazepam , lorazepam (medicines used to treat anxiety)
- antidepressants (amitriptyline, nortriptyline, clomipramine, fluoxetine )
- nimodipine (drug for increased blood flow to the brain)
- haloperidol (drug for the treatment of mental illness)
- Cholestyramine (Cholesterol Lowering Drug)
- anti – infective drugs (erythromycin, aciclovir, valaciclovir, zidovudine), anti- HIV drugs ( protease inhibitors such as lopinavir and ritonavir)
- meflokine (anti- malarial drug )
- rifampicin ( antibiotic used to treat tuberculosis )
- certain so-called pivalic acid-containing antibiotics (pivmecillinam, pivampicillin)
- carbapenems ( antibiotics for bacterial infections). Orfiril in combination with carbapenems should be avoided as it may lead to a reduced effect of Orfiril
- acetazolamide (medicine used to treat increased pressure in the eye, ie glaucoma )
- drugs for the treatment of mental disorders (quetiapine, olanzapine)
- propofol (used for anesthesia and sedation in surgical and diagnostic procedures )
- drugs containing estrogen (including some birth control pills )
- metamizole, a medicine used to treat pain and fever
Co-administration of sodium valproate and anticoagulants (blood-thinning drugs, eg warfarin , salicylates) may increase the tendency to bleed.
In some cases, concomitant use of valproic acid and topiramate has been associated with an increase in ammonia in the blood (hyperammonemia) with and without organic brain diseases ( encephalopathy ).
If lithium is taken at the same time, the blood levels of both medicines may be affected.
Orfiril with alcohol
Alcohol should be avoided during treatment with Orfiril.
Pregnancy, breastfeeding and fertility
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before using this medicine.
If you are a woman of childbearing potential, you must use effective contraception during treatment.
Important advice for women
- For epilepsy , do not use Orfiril if you are pregnant unless otherwise indicated for you.
- For epilepsy , if you are a woman who may have children, do not take Orfiril unless you are using an effective contraceptive throughout treatment with Orfiril. Do not stop taking Orfiril or your contraceptive until you have discussed it with your doctor. Your doctor will give you further advice.
The risks of valproate when taken during pregnancy (regardless of the disease for which valproate is used):
- Tell your doctor immediately if you are planning to become pregnant or are pregnant.
- Valproate is a risk if taken during pregnancy. The higher the dose , the higher the risk, but all doses involve a risk.
- It can cause serious birth defects and can affect how the baby develops as it grows. Fetal injuries that have been reported include spina bifida (where the bones of the spine are not properly developed), malformations of the face and skull; heart, kidney, urinary tract and malformations of the genitals as well as malformations of the extremities er. Hearing problems or deafness have been reported in children exposed to valproate during pregnancy.
- If you take valproate during pregnancy, you are at greater risk than other women of having a child with birth defects that require medical treatment. Because valproate has been used for many years, we know that in women taking valproate , about 10 children out of 100 will have birth defects. This compares with 2 to 3 children in 100 born to women without epilepsy .
- It is estimated that up to 30-40% of preschool children, whose mothers took valproate during pregnancy, may have problems with early childhood development. Affected children may be late to walk and talk, have a lower intellectual ability than other children, and have difficulty with language and memory.
- Autism spectrum disorders are more commonly diagnosed in children exposed to valproate during pregnancy and there is some support that children who have been exposed to valproate during pregnancy have a higher risk of developing ADHD (Attention Deficit Hyperactivity Disorder).
- Before you are prescribed this medicine, your doctor will have explained what can happen to your baby if you become pregnant while taking valproate . If you later decide to have a child, do not stop taking your medicine or contraceptive until you have discussed it with your doctor.
- If you are the parent or caregiver of a girl treated with valproate , consult your doctor when your child using valproate gets his first period.
- Talk to your doctor about taking folic acid when trying to conceive. Folic acid can lower the overall risk of spina bifida and early miscarriage that is present with all pregnancies. However, it is unlikely that it will reduce the risk of birth defects in connection with valproate use.
Please select and read the situations that apply to you from the situations described below:
- I BEGIN TREATMENT WITH ORFIRIL
- I TAKE ORFIRIL BUT I DON’T PLAN TO HAVE CHILDREN
- I TAKE ORFIRIL AND PLAN TO HAVE CHILDREN
- I AM PREGNANT AND I TAKE ORFIRIL
I BEGIN TREATMENT WITH ORFIRIL
If this is the first time you have been prescribed Orfiril, your doctor will explain the risks to an unborn baby if you become pregnant. If you can have children, you must ensure that you use an effective method of contraception without interruption during your treatment with Orfiril. Talk to your doctor or midwife if you need contraceptive advice.
Main message:
- Pregnancy must be ruled out as a result of a pregnancy test, which has been confirmed by your doctor before starting treatment with Orfiril.
- You must use an effective contraceptive throughout the treatment with Orfiril.
- You must discuss appropriate methods of birth control (contraception) with your doctor. Your doctor will give you information on how to prevent pregnancy and can refer you to a specialist doctor for advice on birth control.
- Some birth control pills (estrogen -containing birth control pills ) can lower the valproate levels in your blood. Make sure you talk to your doctor about which contraceptive (birth control) is most suitable for you.
- You must have regular (at least annual) appointments with a specialist doctor who has experience in treating epilepsy . During this visit, your doctor should make sure that you are well aware of and have understood all the risks and advice related to the use of valproate during pregnancy.
- Tell your doctor if you want to get pregnant.
- Tell your doctor immediately if you are pregnant or think you may be pregnant.
I TAKE ORFIRIL BUT I DON’T PLAN TO HAVE CHILDREN
If you continue treatment with Orfiril but do not plan to have children, make sure you use an effective contraceptive without interruption throughout the treatment with Orfiril. Talk to your doctor or midwife if you need contraceptive advice.
Main message:
- You must use an effective contraceptive throughout the treatment with Orfiril.
- You must discuss contraception (birth control) with your doctor. Your doctor will give you information on how to prevent pregnancy and may refer you to a specialist for birth control advice.
- Some birth control pills (estrogen -containing birth control pills ) can lower the valproate levels in your blood. Make sure you talk to your doctor about which contraceptive (birth control) is most suitable for you.
- You must have regular (at least annual) appointments with a specialist doctor who has experience in treating epilepsy . During this visit, your doctor should make sure that you are well aware of and have understood all the risks and advice related to the use of valproate during pregnancy.
- Tell your doctor if you want to get pregnant.
- Tell your doctor immediately if you are pregnant or think you may be pregnant.
I TAKE ORFIRIL AND PLAN TO HAVE CHILDREN
If you are planning to have a baby, make an appointment with your doctor.
Do not stop taking Orfiril or your contraceptive until you have discussed it with your doctor. Your doctor will give you further advice.
Children born to mothers who have taken valproate have a serious risk of birth defects and developmental disorders that can be severely impaired. Your doctor will refer you to a specialist who has experience in treating epilepsy so that other treatment options can be evaluated early. Your specialist doctor can take several measures so that your pregnancy goes as smoothly as possible and any risks to you and your unborn child are reduced as much as possible.
Your specialist doctor may decide to change the dose of one of Orfiril or switch to another medicine, or stop treatment with Orfiril, in good time before you become pregnant – to ensure that your disease is stable. Consult your doctor about taking folic acid when planning to have children. Folic acid can lower the overall risk of spina bifida and early miscarriage that is present with all pregnancies. However, it is unlikely that it will reduce the risk of birth defects associated with valproate use.
Main message:
- Do not stop taking Orfiril unless your doctor tells you to.
- Do not stop using your contraceptive until you have talked to your doctor and worked out a plan together to ensure that your condition is stable and that the risks to your child are reduced.
- Book an appointment with your doctor. During this visit, your doctor should make sure that you are well aware of and have understood all the risks and advice related to the use of valproate during pregnancy.
- Your doctor will try to switch you to another medicine, or stop your treatment with Orfiril well before you become pregnant.
- Tell your doctor immediately if you are pregnant or think you may be pregnant.
I AM PREGNANT AND I TAKE ORFIRIL
Do not stop taking Orfiril unless your doctor tells you that your condition may be getting worse. Tell your doctor immediately if you are pregnant or think you may be pregnant. Your doctor will give you further advice. Children born to mothers who have taken valproate have a serious risk of birth defects and developmental disorders that can be severely impaired.
You will be referred to a specialist doctor who has experience in treating epilepsy so that other treatment options can be evaluated.
In the exceptional circumstances when Orfiril is the only available treatment option during pregnancy, you will be examined very carefully both in terms of your medical condition and to check how your unborn baby is developing. You and your partner can get advice and support regarding pregnancy that is exposed to valproate.
Ask your doctor for folic acid. Folic acid can lower the overall risk of spina bifida and early miscarriage that is present with all pregnancies. However, it is unlikely that it will reduce the risk of birth defects associated with valproate use.
Main message:
- Tell your doctor immediately if you are pregnant or think you may be pregnant.
- Do not stop taking Orfiril unless your doctor tells you to.
- Make sure you are referred to a specialist with experience in the treatment of epilepsy to evaluate the need for alternative treatment options.
- You must receive careful advice on the risks of Orfiril during pregnancy, including the risk of birth defects and developmental disorders in children.
- Be sure to refer to a specialist doctor for “prenatal monitoring” to detect possible incidences of malformations in the unborn baby.
Make sure you read the patient information brochure that you will receive from your doctor. Your doctor will discuss the annual risk confirmation form and will ask you to sign and keep it. You will also receive a patient card from your doctor to remind you of the risks of valproate during pregnancy.
Breast-feeding
Valproate passes into breast milk. Talk to your doctor before using Orfiril during breastfeeding.
Fertility
Orfiril may reduce fertility in both men and women. However, available information suggests that fertility will return to normal when Orfiril is discontinued.
Driving and using machines
Orfiril can impair the ability to react, which should be kept in mind at times when sharper attention is required, such as driving a car and precision work.
You are responsible for assessing whether you are fit to drive a motor vehicle or perform work that requires sharpened vigilance. One of the factors that can affect your ability in these respects is the use of drugs due to their effects and/or side effects. Descriptions of these effects and side effects can be found in other sections. Read all the information in this leaflet for guidance. If you are not sure, talk to your doctor or pharmacist.
Orfiril contains sodium
Orfiril 150 mg: This medicine contains 20.7 mg sodium (the main ingredient in table salt/table salt) per tablet. This corresponds to 1% of the maximum recommended daily sodium intake for adults.
Orfiril 300 mg: This medicine contains 41.4 mg of sodium (the main ingredient in table salt/table salt) per tablet. This corresponds to 2% of the maximum recommended daily sodium intake for adults.
How to take Orfiril
Always take this medicine exactly as your doctor has told you. Ask your doctor or pharmacist if you are unsure.
Orfiril treatment must be started and supervised by a doctor who specializes in the treatment of epilepsy.
The dose is determined by your doctor, who will tailor it for you. Dosage varies widely, depending on age, body weight, and severity of the disease. As a rule, treatment is started with a low dose, which is then gradually increased if necessary.
The tablets should preferably be taken with a meal and should be swallowed whole, together with water or other beverage, and should not be crushed or chewed.
If you take more Orfiril than you should
If you have ingested too much medicine or if e.g. a child ingested the medicine accidentally contact a doctor or hospital for risk assessment and advice.
If you forget to take Orfiril
If you forget to take your medicine, take a dose as soon as you remember. Do not take a double dose to make up for a forgotten dose.
If you stop taking Orfiril
You should not stop using Orfiril without talking to your doctor first. Quitting medication abruptly or simply reducing the dose may increase the risk of seizures.
If you have any further questions on the use of this product, ask your doctor, pharmacist, or nurse.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact a doctor immediately if you experience symptoms such as weakness, loss of appetite, nausea, repeated vomiting, upper abdominal pain, swelling ( edema ), apathy, confusion, movement disorders, or if seizures recur or increase in frequency. Orfiril can affect the liver (and in very rare cases the pancreas). This is especially true in infants and children under 3 years of age with the severe form of epilepsy (especially children with brain damage, developmental disorders, genetic and/or metabolic diseases) and combination therapy with other antiepileptic drugs.
The following side effects have been reported:
Very common side effects (may affect more than 1 user in 10):
- transient increase in ammonia in the blood
- mood and emotional disorders
- tremors
- nausea
Common side effects (may affect up to 1 in 10 people):
- anemia
- slightly reduced platelet count ( thrombocytopenia ), impaired platelet function
- allergic reactions
- increased appetite, loss of appetite, abnormal weight gain (risk of developing polycystic ovary disease), weight loss
- low levels of sodium in the blood
- confusion
- aggression, agitation , problems with attention
- extrapyramidal disorders, eg parkinsonism , conditions with impaired alertness ( stupor )
- dizziness, drowsiness, speech disorders
- impaired memory
- headache
- involuntary eye movements ( nystagmus )
- hearing loss (transient or permanent)
- bleeding
- stomach upset in the form of pain, sucking, vomiting and diarrhea
- gum disease (mainly gingival hyperplasia ), inflammation of the gums
- liver damage, changes in liver tests (elevated transaminases or phosphatases)
- transient hair loss, altered hair quality
- menstrual pain that interferes with your daily activities ( dysmenorrhea )
- prolonged bleeding time
- problems with nails and nail bed
- accidental urination (urinary incontinence)
Uncommon side effects (may affect up to 1 in 100 people):
- pancytopenia, severe leukopenia
- syndrome with fluid accumulation in the blood and decreased urine production (SIADH)
- increased male hormone ( androgen ), which can lead to masculinization and increased male hair growth in women ( hirsutism ), acne or hair loss with the typical male appearance (eg hair loss at the hairline)
- insomnia , transient coma (in some cases due to increased seizure frequency)
- impaired movement coordination ( ataxia )
- brain disease ( encephalopathy )
- a feeling in the skin, e.g. burning, stinging, itching or tingling, without obvious physical cause ( paresthesia )
- inflammation of blood vessels ( vasculitis )
- fluid around the lungs ( eosinophilic pleural effusion)
- increased salivation (hypersalivation)
- inflammation of the pancreas (pancreatitis)
- severe liver damage (sometimes fatal) in children under 3 years of age who received high doses in combination with other antiepileptic drugs
- swelling of the face, mouth, tongue or other parts of the body that may cause breathing or swallowing difficulties ( angioedema )
- rash
- changes in hair color
- There have been reports of skeletal diseases such as osteopenia and osteoporosis (decreased bone density and osteoporosis) and bone fractures. Check with your doctor or pharmacist if you are on long-term antiepileptic treatment, have a history of osteoporosis , or are taking steroids .
- frequent urination
- missed or irregular menstruation
- abnormal fatigue or exhaustion (fatigue)
- swelling of hands, feet and / or legs ( edema )
Rare side effects (may affect up to 1 in 1,000 people):
- condition in which normal blood formation is disturbed ( myelodysplastic syndrome )
- bone marrow damage, severe blood diseases with low white blood cell count , platelets and / or red blood cells (eg thrombocytopenia ), increased white blood cell count ( eosinophilia ), decreased blood coagulation protein (fibrinogen), inhibited red blood cell development , certain blood cells ( agranulocytosis ), anemia with enlargement of red blood cells (macrocytic anemia , macrocytosis), decreased concentration of at least one coagulation factorand abnormal coagulation tests (see sections “Warnings and precautions” and “Pregnancy, lactation and fertility”)
- impaired thyroid function
- increase in ammonia in the blood associated with brain disease ( encephalopathy ), confusion, nausea, vomiting and movement disorders ( ataxia )
- abnormal mental state with lack of perception of reality ( psychosis ), behavioral disorders, hyperactivity, learning difficulties
- dementia when the brain shrinks (the brain withers)
- cognitive impairment
- constipation
- severe liver damage in children under 3 years
- severe skin and mucosal changes ( Stevens-Johnson syndrome , toxic epidermal necrolysis )
- redness of the skin (erythema multiforme)
- syndrome with rash from drugs, enlarged lymph nodes , fever and possible involvement of other organs (DRESS syndrome)
- a disorder of the immune system that causes joint pain, rash and fever (systemic lupus erythematosus)
- severe muscle breakdown ( rhabdomyolysis )
- involuntary urination ( enuresis )
- renal impairment (Fanconi syndrome)
- male infertility
- polycystic disease of the ovaries
- low body temperature
- obesity
- biotin deficiency ( vitamin B )
- double vision
Very rare side effects (may affect up to 1 in 10,000 people):
- low number of the most important type of white blood cells in the blood ( neutropenia )
No known frequency (number of patients affected can not be calculated from the available data):
- abnormal thyroid function test
- aggravated seizures
- ringing in the ears ( tinnitus )
- increased hair growth on the face and body of women (so-called hirsutism , which can be a result of polycystic disease of the ovaries, a condition that leads to the formation of cysts of different sizes in the ovaries)
- kidney failure , inflammation of the kidney tissue, impaired renal function
- abnormal sperm production (with decreased number and / or activity of sperm)
Additional side effects are in children
Some side effects of valproate occur more frequently or are more severe in children compared to adults. These include liver damage, inflammation of the pancreas ( pancreatitis ), aggressive behavior, agitation , attention deficit disorder, deviant behavior, hyperactivity and learning difficulties.
How to store Orfiril
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton after “EXP”. The expiration date is the last day of the specified month.
The medicine should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
Contents of the pack and other information
Content declaration
- The active substance is sodium valproate. An enteric- containing tablet contains 150 mg or 300 mg of sodium valproate.
- The other ingredients are calcium behenate, microcrystalline cellulose, gelatin, macrogol, polymethacrylate, sodium lauryl sulphate, polysorbate 80, methylated colloidal anhydrous silica, talc, titanium dioxide (E171), glycerol triacetate.
What the medicine looks like and contents of the pack
White to pale yellow, round, cupped tablets.
Pack sizes of 100 or 200 enteric tablets.
Marketing Authorization Holder and Manufacturer
Desitin Arzneimittel GmbH
Weg beim Jäger 214
22335 Hamburg
Germany
Fax: +49 40 59101 433
Information
provider Desitin Pharma AB
Niels Leuchs Vei 99
1359 Eiksmarka
Norway