Complete adverse effect profile including incidence rates and management
Important Safety Information
This is not a complete list of all possible side effects. Contact your healthcare provider if you experience any unexpected symptoms. For serious or life-threatening side effects, seek emergency medical attention immediately.
6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: • Hepatic Failure [see Warnings and Precautions (5.1) ] • Birth Defects [see Warnings and Precautions (5.2) ] • Decreased IQ and Neurodevelopmental Disorders following in utero exposure [see Warnings and Precautions (5.3) ] • Pancreatitis [see Warnings and Precautions (5.5) ] • Hyperammonemic Encephalopathy [see Warnings and Precautions (5.6 , 5.9 , 5.10) ] • Suicidal Behavior and Ideation [see Warnings and Precautions (5.7) ] • Bleeding and Other Hematopoietic Disorders [see Warnings and Precautions (5.8) ] • Hypothermia [see Warnings and Precautions (5.11) ] • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Reactions [see Warnings and Precautions (5.12) ] • Serious Dermatologic Reactions [see Warnings and Precautions (5.13) ] • Angioedema [see Warnings and Precautions (5.14) ] • Somnolence in the Elderly [see Warnings and Precautions (5.16) ] Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
Information on pediatric adverse reactions is presented in section
• Most common adverse reactions (reported ≥ 15% for any indication) are abdominal pain, alopecia, asthenia, diarrhea, diplopia, dizziness, dyspepsia, headache, infection, insomnia, nausea, somnolence, thrombocytopenia, tremor, vomiting ( 6.1 , 6.2 , 6.3 ).
• The safety and tolerability of valproate in pediatric patients were shown to be comparable to those in adults ( 8.4 ).
To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Mania The incidence of treatment-emergent events has been ascertained based on combined data from two three week placebo-controlled clinical trials of divalproex sodium extended-release tablets in the treatment of manic episodes associated with bipolar disorder.
Table 3 summarizes those adverse reactions reported for patients in these trials where the incidence rate in the divalproex sodium extended-release tablets-treated group was greater than 5% and greater than the placebo incidence.
Adverse Reactions Reported by > 5% of Divalproex Sodium Extended-Release Tablets-Treated Patients During Placebo-Controlled Trials of Acute Mania The following adverse reactions/event occurred at an equal or greater incidence for placebo than for divalproex sodium extended-release tablets: headache Adverse Event Divalproex Sodium Extended-Release Tablets (n = 338) % Placebo (n = 263) % Somnolence 26 14 Dyspepsia 23 11 Nausea 19 13 Vomiting 13 5 Diarrhea 12 8 Dizziness 12 7 Pain 11 10 Abdominal Pain 10 5 Accidental Injury 6 5 Asthenia 6 5 Pharyngitis 6 5 The following additional adverse reactions were reported by greater than 1% of the divalproex sodium extended-release tablets-treated patients in controlled clinical trials: Body as a Whole: Back Pain, Chills, Chills and Fever, Drug Level Increased, Flu Syndrome, Infection, Infection Fungal, Neck Rigidity.
Cardiovascular System: Arrhythmia, Hypertension, Hypotension, Postural Hypotension.
Digestive System: Constipation, Dry Mouth, Dysphagia, Fecal Incontinence, Flatulence, Gastroenteritis, Glossitis, Gum Hemorrhage, Mouth Ulceration.
5 WARNINGS AND PRECAUTIONS • Birth defects, decreased IQ, and neurodevelopmental disorders following in utero exposure: Should not be used to treat women with epilepsy or bipolar disorder who are pregnant or who plan to become pregnant or to treat a woman of childbearing potential unless other medications have failed to provide adequate symptom control or are otherwise unacceptable ( 5.2 , 5.3 , 5.4 ) • Pancreatitis: Divalproex sodium extended-release tablets should ordinarily be discontinued ( 5.5 ) • Suicidal behavior or ideation: Antiepileptic drugs, including divalproex sodium extended-release tablets, increase the risk of suicidal thoughts or behavior ( 5.7 ) • Bleeding and other hematopoietic disorders: Monitor platelet counts and coagulation tests ( 5.8 ) • Hyperammonemia and hyperammonemic encephalopathy: Measure ammonia level if unexplained lethargy and vomiting or changes in mental status, and also with concomitant topiramate use;
consider discontinuation of valproate therapy ( 5.6 , 5.9 , 5.10 ) • Hypothermia: Hypothermia has been reported during valproate therapy with or without associated hyperammonemia.
This adverse reaction can also occur in patients using concomitant topiramate ( 5.11 ) • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan hypersensitivity reactions, serious dermatologic reactions, and angioedema: Discontinue divalproex sodium extended-release tablets unless an alternate etiology is established ( 5.12 , 5.13 , 5.14 ) 5.1 Hepatotoxicity General Information on Hepatotoxicity Hepatic failure resulting in fatalities has occurred in patients receiving valproate.
These incidents usually have occurred during the first six months of treatment.
Serious or fatal hepatotoxicity may be preceded by non-specific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, and vomiting.
Like all medications, Divalproex Sodium can cause side effects. However, not everyone who takes this medication will experience them. Many side effects are dose-dependent and may improve as your body adjusts to the medication. Others may require dose adjustment or medical attention.
Contact your healthcare provider promptly if you experience:
Seek immediate emergency medical care if you experience signs of: