Patient Medication Information: uses, side effects, how to take - Apo-Divalproex
Serious warnings and precautions box
Pregnancy, Birth Defects and Development Disorders: APO-DIVALPROEX may cause birth defects and/or physical or mental development problems in your unborn baby if taken during pregnancy. This can include:
These can seriously affect your child and result in disabilities, which can be severe.
If you are a parent of, or are caring for a female child taking APO-DIVALPROEX, tell your healthcare professional as soon as your child has her first period. Pregnancy Prevention Program: Information on the Pregnancy Prevention Program including educational resources, as well as to report suspected embryo-fetal exposure to valproate, can be provided by contacting Apotex at 1-800-667-4708. Do not take APO-DIVALPROEX during pregnancy, unless you suffer from epilepsy and you and your healthcare professional have discussed the risks and have decided that you should. It should only be taken if alternative treatments do not work. If you become pregnant while taking APO-DIVALPROEX, talk to your healthcare professional right away. Do not stop taking APO-DIVALPROEX unless your healthcare professional has told you to do so. Pregnancy Registry: If you become pregnant while taking APO-DIVALPROEX, talk to your healthcare professional about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect information about the safety of antiepileptic medicines during pregnancy. Information on the registry can also be found at the following website: http://www.aedpregnancyregistry.org/.
(See the Serious side effects and what to do about them table below for symptoms of liver failure and pancreatitis). |
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What APO-DIVALPROEX is used for:
APO-DIVALPROEX is used to:
- control epilepsy in adults and children on its own or with other medicines.
- treat symptoms of mania associated with bipolar disorder in adults, such as aggressiveness, agitation, impulsive behaviour or excessively elevated mood.
How APO-DIVALPROEX works:
APO-DIVALPROEX is thought to work by increasing the amount of an amino acid in the brain called “gamma-aminobutyric acid" (GABA). By changing the amount of GABA in the brain, APO-DIVALPROEX is able to help control epilepsy and stabilize mood.
The ingredients in APO-DIVALPROEX are:
Medicinal ingredients: Divalproex sodium
Non-medicinal ingredients:
APO-DIVALPROEX 125 mg delayed-release tablets also contain D & C red No. 30, FD & C yellow No. 6, guar gum, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methacrylic acid, microcrystalline cellulose, polyethylene glycol, talc, titanium dioxide and triethyl citrate.
APO-DIVALPROEX 250 mg delayed-release tablets also contain FD & C yellow No. 6, guar gum, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methacrylic acid, microcrystalline cellulose, polyethylene glycol, talc, titanium dioxide and triethyl citrate.
APO-DIVALPROEX 500 mg delayed-release tablets also contain D & C red No. 33, ferric oxide red, guar gum, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methacrylic acid, microcrystalline cellulose, polyethylene glycol, talc, titanium dioxide and triethyl citrate.
APO-DIVALPROEX comes in the following dosage form(s):
Delayed-release tablets: 125 mg, 250 mg and 500 mg valproic acid (as divalproex sodium).
Do not use APO-DIVALPROEX if:
- you are allergic to divalproex sodium or to any other ingredient in APO-DIVALPROEX.
- you are pregnant or think you are pregnant, unless your healthcare professional determines that no other treatment options work to treat your epilepsy. You and your healthcare professional must discuss the risks and decide that you should take APO-DIVALPROEX. You should not use APO-DIVALPROEX to treat your bipolar disorder if you are pregnant.
- you are a girl or woman of childbearing potential, unless you meet all conditions of the Pregnancy Prevention Program, your healthcare professional will talk to you about this.
- you have liver disease or severe liver problems.
you have a mitochondrial disorder, such as Alpers-Huttenlocher Syndrome. Children under 2 years of age who may have a mitochondrial disorder should not take APO-DIVALPROEX
- you have or have a family history of a urea cycle disorder (a condition that affects how your body removes waste).
- you have an inborn deficiency in carnitine that is untreated.
- you have porphyria (a condition that affects the nervous system and skin).
- you or any of your close relatives have a history of severe hepatitis, especially when caused by medicines.
To help avoid side effects and ensure proper use, talk to your healthcare professional before you take APO-DIVALPROEX. Talk about any health conditions or problems you may have, including if you:
- have or have a history of liver disease or liver problems;
- are planning to become pregnant;
- are planning to father a child;
- are breastfeeding or planning to breastfeed. You must discuss with your healthcare professional whether to breastfeed or take APO-DIVALPROEX, you cannot do both. Do not breastfeed for one month after stopping APO-DIVALPROEX;
- have kidney disease or kidney problems;
- have Human Immunodeficiency Virus (HIV) or Cytomegalovirus (CMV);
- have a history of muscular disorders (including carnitine palmitoyl transferase type II deficiency);
- are on a diet with low carnitine (found in meat and dairy products), especially in children; • have an inborn deficiency in carnitine and are taking carnitine supplement for this condition;
- have other medical conditions including a history of unexplained coma, intellectual disability or any type of brain dysfunction;
- drink alcohol on a regular basis;
- are elderly (65 years of age or older).
Other warnings you should know about:
If you are a female of childbearing potential when you are prescribed APO-DIVALPROEX:
- your healthcare professional will give you a patient guide;
- you should receive a patient card every time you get APO-DIVALPROEX from the pharmacy.
Make sure you understand these documents.
Fertility:
Use in Women: If you are female and taking APO-DIVALPROEX you may no longer get your period. You may also develop cysts (fluid filled sacs) on the ovaries and your testosterone levels may increase.
Use in Men: APO-DIVALPROEX may affect male fertility during treatment. APO-DIVALPROEX can make you less fertile or infertile. This may or may not be reversible if your dose is decreased or if you stop taking APO-DIVALPROEX.
If you have interest in starting a family, talk to your healthcare professional. Do not stop taking APO-DIVALPROEX unless your healthcare professional has told you to do so.
Monitoring and Blood Tests: Your healthcare professional should do blood tests before starting treatment with APO-DIVALPROEX and while you are taking it. These tests may monitor:
- platelet (a type of blood cell) count and your blood’s ability to clot;
- liver function;
- the amount of valproate (the active ingredient in APO-DIVALPROEX) in the body;
- the amount of any other medications you are taking in your body;
- sugar (glucose) levels in your blood;
- ammonia levels in your blood.
Your healthcare professional will monitor your response to APO-DIVALPROEX on a regular basis. If you start to have more seizures or your seizures get worse, tell your healthcare professional immediately.
Suicidal Thoughts and Behaviour Changes: If you have thoughts of harming or killing yourself at any time, contact your healthcare professional or go to a hospital right away.
APO-DIVALPROEX may also cause behavioural changes in you such as aggression, agitation, change in attention span and learning disorders.
Driving and Using Machines: APO-DIVALPROEX may cause you to become drowsy or light-headed. Avoid driving, using machinery, or doing dangerous activities until you know how APO-DIVALPROEX affects you.
Tell your healthcare professional about all the medicines you take, including any drugs, vitamins, minerals, natural supplements or alternative medicines.
The following may interact with APO-DIVALPROEX:
- phenobarbital and lamotrigine, which are anticonvulsants (drugs used to treat seizures). These might cause serious life-threatening effects when mixed with APO-DIVALPROEX;
- other anticonvulsants such as carbamazepine, primidone, topiramate, felbamate, phenytoin, ethosuximide, rufinamide;
- anticoagulants (drugs used to thin blood) such as warfarin, dicumarol;
- acetylsalicylic acid (aspirin); especially if your child is under 3 years of age, APO-DIVALPROEX should not be administered together with acetylsalicylic acid;
- benzodiazepines such as diazepam, lorazepam, clonazepam;
- some medicines used to treat infections such as rifampin;
- some medicines used to treat diabetes such as tolbutamide;
- some HIV-antiviral medicines such as zidovudine, ritonavir, lopinavir, lamivudine;
- antibiotics in the carbapenem class such as doripenem, ertapenem, imipenem, meropenem;
- some medicines used to treat heartburn and peptic ulcers such as cimetidine;
- medicines used to treat depression such as Selective Serotonin Re-Uptake Inhibitors (SSRIs), Monoamine Oxidase Inhibitors (MAOIs), Tricyclic antidepressants such as amitriptyline, nortriptyline;
- acetazolamide, a drug used to treat glaucoma and epilepsy;
- cholestyramine, a drug used to lower cholesterol;
- propofol, a drug used to relax you before and after surgery;
- nimodipine, a drug used to prevent brain damage;
- metamizole (used to treat pain and fever; not approved in Canada for human use);
- methotrexate (used to treat cancer and inflammatory diseases);
- some medicines that contain pivalate (e.g. adefovir dipivoxil);
- antipsychotics (drugs used to manage psychosis) such as olanzapine, chlorpromazine, quetiapine;
- estrogen-containing products (including contraceptives that contain estrogen);
- alcohol;
- cannabidiol (CBD).
How to take APO-DIVALPROEX:
- APO-DIVALPROEX treatment must only be started and supervised by a healthcare professional specialised in the treatment of epilepsy or mania (bipolar disorders).
- It is important to keep your appointments for medical checkups.
- Take APO-DIVALPROEX exactly as your healthcare professional prescribes, do not change your dose unless your healthcare professional tells you to.
- Do not stop taking APO-DIVALPROEX without talking to your healthcare professional as this can increase the number of seizures you have and their severity.
APO-DIVALPROEX can be taken with or without food.
- Swallow tablets whole, do not chew.
Usual dose:
Your healthcare professional will decide the dose of APO-DIVALPROEX for you. The dose is based on your weight, your seizures, or manic episodes and the other medicines you take. Your healthcare professional may slowly increase the dosage until your condition is well controlled, without side effects.
APO-DIVALPROEX is not for the treatment of the symptoms of mania in patients under 18 years of age.
Overdose:
| If you think you, or a person you are caring for, have taken too much APO-DIVALPROEX, contact a healthcare professional, hospital emergency department, regional poison control centre or Health Canada’s toll-free number, 1-844 POISON-X (1-844-764-7669) immediately, even if there are no signs or symptoms. |
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Missed dose:
If you miss a dose, do not try to make up for it by doubling the next dose. Take the next regularly scheduled dose and try not to miss any more doses.
Possible side effects from using APO-DIVALPROEX:
These are not all the possible side effects you may have when taking APO-DIVALPROEX. If you experience any side effects not listed here, tell your healthcare professional.
- headache;
- nausea or vomiting;
- indigestion;
- diarrhea;
- tremors (involuntary shaking);
- feeling tired;
- feeling weak or dizzy;
- hair loss or hair growth on the face, chest or back;
- increased appetite that may lead to weight gain.
Additional side effects in children:
Compared to adults, some side effects of APO-DIVALPROEX occur more frequently and/or are more severe in children. These include liver damage, inflammation of the pancreas (pancreatitis), aggression, agitation, disturbance in attention, abnormal behavior, hyperactivity and learning disorder.
Serious side effects and what to do about them
| Frequency/Side Effect/Symptom | Talk to your healthcare professional | Get immediate medical help | |
|---|---|---|---|
| Only if severe | In all cases | ||
| and genitals and spread to other areas of the body, pink/red ring on the skin, itchy skin, redness, scaly skin, spots on the skin, yellow skin or eyes, shortness of breath, dry cough, chest pain or discomfort, feeling thirsty, urinating less often, less urine, chills, aching muscle, joint pain | |||
| Thoughts of suicide or hurting yourself | X | ||
| Thrombocytopenia (low blood platelets): bruising or bleeding for longer than usual if you hurt yourself, fatigue and weakness | X | ||
| Rare | |||
| Brain atrophy (loss of brain cells): memory loss, seizures, loss of motor skills, difficulty speaking, reading or understanding | X | ||
| Coagulation abnormalities (problems with how your blood clots): abnormal bleeding, bruising easily, won’t stop bleeding when you are injured, sudden nosebleeds, fatigue, headache | X | ||
| Fanconi syndrome (kidney does not function properly leading to certain essential substances to exit through urine): passing a lot of urine, feeling thirsty, bone pain, weakness | X | ||
| Rhabdomyolysis (breakdown of damaged muscle): muscle tenderness, weakness, red-brown (tea-coloured) urine | X | ||
| Unknown | |||
| Frequency/Side Effect/Symptom | Talk to your healthcare professional | Get immediate medical help | |
| Only if severe | In all cases | ||
| Hyperammonemia (high ammonia levels in the blood): tiredness, vomiting, abnormal walking, extreme irritability, combative/bizarre behaviour, not wanting to eat meat or high protein products | X | ||
| Hypothermia (low body temperature): shivering, slurred speech or mumbling, slow, shallow breathing, weak pulse, very low energy, confusion or memory loss | X | ||
Kidney problems: nausea, vomiting, fever, swelling of extremities, fatigue, thirst, dry skin, irritability, dark urine, increased or decreased urine output, blood in the urine, rash, weight gain (from retaining fluid), loss of appetite, abnormal blood test results, mental status changes (drowsiness, confusion, coma) | X | ||
| Liver injury: yellowing of the skin or eyes, itchy skin, dark urine and pale stools, abdominal pain, nausea, vomiting, loss of appetite | X | ||
| Pancreatitis (inflammation of the pancreas): upper abdominal pain, fever, rapid heart beat, nausea, vomiting, tenderness when touching the abdomen | X | ||
| Serious skin reactions: fever, rash, swollen lymph nodes, flu-like feeling, blisters and peeling skin that may start in and around the mouth, nose, eyes | X | ||
| Frequency/Side Effect/Symptom | Talk to your healthcare professional | Get immediate medical help | |
| Only if severe | In all cases | ||
| Angioedema (swelling of tissue under the skin): swollen face, hands, feet, genitals tongue, or throat, difficulty breathing, swelling of the digestive tract causing diarrhea, nausea or vomiting | X | ||
| Hypocarnitinemia (low carnitine levels in the blood and/or tissues): fatigue, muscle weakness and pain | X | ||
| Frequency/Side Effect/Symptom | Talk to your healthcare professional | Get immediate medical help | |
| Only if severe | In all cases | ||
| Common | |||
| Allergic reaction: difficulty swallowing or breathing, wheezing; drop in blood pressure; feeling sick to your stomach and throwing up; hives or rash; swelling of the face, lips, tongue or throat | X | ||
| Hallucinations (seeing or hearing things that are not there) | X | ||
| Urinary incontinence (involuntary loss of urine) | X | ||
| Uncommon | |||
| Aggravated convulsions (an increase in the number of seizures you have or having new types of seizures) | X | ||
| Depression (sad mood that won’t go away): difficulty sleeping or sleeping too much, changes in appetite or weight, feelings of worthlessness, guilt, regret, helplessness or hopelessness, withdrawal from social situations, family, gatherings and activities with friends, reduced libido (sex drive) and thoughts of death. If you have a history of depression, your depression may become worse | X | ||
If you have a troublesome symptom or side effect that is not listed here or becomes bad enough to interfere with your daily activities, tell your healthcare professional.
Reporting side effects
You can report any suspected side effects associated with the use of health products to Health Canada by:
NOTE: Contact your healthcare professional if you need information about how to manage your side effects. The Canada Vigilance Program does not provide medical advice. |
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Storage:
Store at controlled room temperature 15°C to 30°C, in tight, light-resistant containers.
Keep out of reach and sight of children.
If you want more information about APO-DIVALPROEX:
- Talk to your healthcare professional.
- Find the full product monograph that is prepared for healthcare professionals and includes the Patient Medication Information by visiting the Health Canada Drug Product Database website (https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database.html); the manufacturer’s website