Patient Medication Information: uses, side effects, how to take - Mylan-Divalproex

Serious warnings and precautions box

Pregnancy, Birth Defects and Developmental Disorders: Mylan-Divalproex may cause your baby to develop birth defects and/or physical or mental development problems if taken during pregnancy. These can include:

spina-bifida (a condition where the bones of the spine are not properly developed);
problems with the development of the bones of the face and skull;
heart, kidney, urinary and sexual organ malformations; limb defects;
multiple associated malformations affecting several organs and parts of the body (including eye malformations. These eye malformations may affect vision);
hearing problems or deafness;
problems with early childhood development (e.g., slow to walk and talk, lower IQ, or problems with brain development);
autism or autism spectrum disorders;
Attention Deficit Hyperactivity Disorder (ADHD);
your baby being born at a much lower birthweight than normal for the number of weeks of pregnancy.

These can seriously affect your child and result in disabilities, which can be severe.

If you are a female of childbearing potential: Do not use Mylan-Divalproex if 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. Your healthcare professional may require you to do a pregnancy test before you start treatment with Mylan-Divalproex to make sure you are not pregnant. You must use an effective method of birth control if you are taking Mylan-Divalproex. It is recommended that you use a form of birth control that does not rely on you to remember to use or take it such as an intrauterine device (IUD), or 2 forms of birth control, such as the pill and a condom. Use birth control:
- For at least one month before starting Mylan-Divalproex;
- While you are taking Mylan-Divalproex;
- For at least one month after stopping Mylan-Divalproex.

If you are a parent of, or are caring for a female child taking Mylan-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 found at the following website: https://www.viatris.ca/en-ca/products/branded-specialty.

Do not take Mylan-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 Mylan-Divalproex, talk to your healthcare professional right away. Do not stop taking Mylan-Divalproex unless your healthcare professional has told you to do so.

Pregnancy Registry: If you become pregnant while taking Mylan-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/.

If you are a male able to father a child: You and your partner must use an effective method of birth control if you are taking Mylan-Divalproex. As soon as you are planning to father a child and before you stop birth control, talk to your healthcare professional to discuss alternative treatment options to Mylan-Divalproex. Your healthcare professional will discuss how to stop your treatment with Mylan-Divalproex and that you must wait at least 3 months after stopping treatment to father a child. Do NOT donate sperm during treatment with Mylan-Divalproex and for at least 3 months after stopping treatment. If you are taking or have taken Mylan-Divalproex within the last 3 months and your partner becomes pregnant, talk to your healthcare professional right away.

Liver Failure: cases of fatal liver failure have occurred in patients receiving Mylan-Divalproex. If liver failure occurs, it usually happens during the first 6 months of treatment. You are more at risk for liver failure if you:

take other drugs used to treat seizures;
are a child (especially a child under 2 years of age taking multiple drugs to treat seizures);
have a history of liver disease;
were born with a metabolic disorder (including mitochondrial disorders);
have seizures with an intellectual disability;
have brain disease.

Mitochondrial Disorders: if you have a mitochondrial disorder such as Alpers Huttenlocher Syndrome, do not take Mylan-Divalproex. If your child is under 2 years of age and you think they may have a mitochondrial disorder, they should not be given Mylan-Divalproex unless all other medications have failed.

Pancreatitis (inflammation of the pancreas): cases of life-threatening pancreatitis have occurred in both children and adults taking Mylan-Divalproex. Some instances happen shortly after the first use of Mylan-Divalproex, while others after several years of use. Talk to your healthcare professional right away if you start to have any symptoms of pancreatitis.

What Mylan-Divalproex is used for:

Mylan-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 Mylan-Divalproex works:

Mylan-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, Mylan-Divalproex is able to help control epilepsy and stabilize mood.

The ingredients in Mylan-Divalproex are:

Medicinal ingredient(s): valproic acid (as divalproex sodium).

Non-medicinal ingredients: D&C Red No. 30 (500 mg tablet only), diacetylated monoglycerides, FD&C Blue No. 2 (500 mg tablet only), FD&C Red No. 40 (125 mg tablet only), FD&C Yellow No. 6 (250 mg tablet only), hydroxypropylmethyl cellulose phthalate, povidone, pregelatinized starch (contains corn starch), silicon dioxide, talc, titanium dioxide, and vanillin.

Mylan-Divalproex comes in the following dosage form(s):

Delayed-release tablets; 125 mg, 250 mg, and 500 mg of valproic acid (as divalproex sodium).

Do not use Mylan-Divalproex if:

you are allergic to divalproex sodium or to any other ingredient in Mylan-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 Mylan-Divalproex. You should not use Mylan-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 Mylan-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.

(See the Serious side effects and what to do about them table below for symptoms of liver failure and pancreatitis).

To help avoid side effects and ensure proper use, talk to your healthcare professional before you take Mylan-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 Mylan-Divalproex, you cannot do both. Do not breastfeed for one month after stopping Mylan-Divalproex;
have kidney disease or kidney problems;
have Human Immunodeficiency Virus (HIV) or Cytomegalovirus (CMV);
have a history of muscular disorders (including carnitine palmitoyltransferase 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 Mylan-Divalproex:

your healthcare professional will give you a patient guide;
you should receive a patient card every time you get Mylan-Divalproex from the pharmacy

Make sure you understand these documents.

Fertility:

Use in Women: If you are female and taking Mylan-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: Mylan-Divalproex may affect male fertility during treatment. Mylan-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 Mylan-Divalproex.

If you have interest in starting a family, talk to your healthcare professional. Do not stop taking Mylan-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 Mylan-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 Mylan-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 Mylan-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. Mylan-Divalproex may also cause behavioural changes in you such as aggression, agitation, change in attention span and learning disorders.

Driving and Using Machines: Mylan-Divalproex may cause you to become drowsy or light-headed. Avoid driving, using machinery, or doing dangerous activities until you know how Mylan-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 also interact with Mylan-Divalproex:

phenobarbital and lamotrigine, which are anticonvulsants (drugs used to treat seizures). These might cause serious life-threatening effects when mixed with Mylan-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, Mylan-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, clozapine;
estrogen-containing products (including contraceptives that contain estrogen);
alcohol;
cannabidiol (CBD).

If you think you, or a person you are caring for, have taken too much Mylan-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.

How to take Mylan-Divalproex:

Mylan-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 Mylan-Divalproex exactly as your healthcare professional prescribes, do not change your dose unless your healthcare professional tells you to.
Do not stop taking Mylan-Divalproex without talking to your healthcare professional as this can increase the number of seizures you have and their severity.
Mylan-Divalproex can be taken with or without food.
Swallow tablets whole, do not chew.

Usual dose:

Your healthcare professional will decide the dose of Mylan-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.

Mylan-Divalproex is not for the treatment of the symptoms of mania in patients under 18 years of age.

Overdose:

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 Mylan-Divalproex:

These are not all the possible side effects you may have when taking Mylan-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 Mylan-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
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
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

Frequency/Side Effect/Symptom	Talk to your healthcare professional	Get immediate medical help
Only if severe	In all cases
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 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			X
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

Frequency/Side Effect/Symptom	Talk to your healthcare professional	Get immediate medical help
Only if severe	In all cases
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
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

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.

Storage:

Mylan-Divalproex tablets should be stored between 15°C and 25°C. Tablets should be protected from light.

Keep out of reach and sight of children.

If you want more information about Mylan-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 (Drug Product Database: Access the database); the manufacturer’s website www.mylan.ca; or by calling
1-844-596-9526.

Reporting side effects

You can report any suspected side effects associated with the use of health products to Health Canada by:

Visiting the Web page on Adverse Reaction Reporting (canada.ca/drug-device-reporting) for information on how to report online, by mail or by fax; or
Calling toll-free at 1-866-234-2345.

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.

Mylan-Divalproex: Uses, Side Effects and Dosage