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.
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 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.
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 delayed-release tablets in the treatment of manic episodes associated with bipolar disorder.
The adverse reactions were usually mild or moderate in intensity, but sometimes were serious enough to interrupt treatment.
In clinical trials, the rates of premature termination due to intolerance were not statistically different between placebo, divalproex sodium delayed-release tablets and lithium carbonate.
A total of 4%, 8% and 11% of patients discontinued therapy due to intolerance in the placebo, divalproex sodium delayed-release tablets and lithium carbonate groups, respectively.
Table 2 summarizes those adverse reactions reported for patients in these trials where the incidence rate in the divalproex sodium delayed-release tablets-treated group was greater than 5% and greater than the placebo incidence, or where the incidence in the divalproex sodium delayed-release tablets-treated group was statistically significantly greater than the placebo group.
Vomiting was the only reaction that was reported by significantly (p ≤ 0.05) more patients receiving divalproex sodium delayed-release tablets compared to placebo.
Adverse Reactions Reported by > 5% of Divalproex Sodium Delayed-Release Tablets-Treated Patients During Placebo-Controlled Trials of Acute Mania* Adverse Reaction Divalproex Sodium Delayed-Release Tablets (n=89) % Placebo (n=97) % * The following adverse reactions occurred at an equal or greater incidence for placebo than for divalproex sodium delayed-release tablets: back pain, headache, constipation, diarrhea, tremor, and pharyngitis.
Nausea 22 15 Somnolence 19 12 Dizziness 12 4 Vomiting 12 3 Accidental Injury 11 5 Asthenia 10 7 Abdominal Pain 9 8 Dyspepsia 9 8 Rash 6 3 The following additional adverse reactions were reported by greater than 1% but not more than 5% of the 89 divalproex sodium delayed-release tablets-treated patients in controlled clinical trials: Body as a Whole: Chest pain, chills, chills and fever, fever, neck pain, neck rigidity.
Cardiovascular System: Hypertension, hypotension, palpitations, postural hypotension, tachycardia, vasodilation.
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.
In patients with epilepsy, a loss of seizure control may also occur.
Patients should be monitored closely for appearance of these symptoms.
Like all medications, Divalproex Sodium D/r 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: