Epifri Adverse Reactions

Epilepsy: Complex Partial Seizures (CPS): Divalproex sodium was generally well tolerated with most adverse events rated as mild to moderate in severity.
Adverse events that listed as follows are reported for patients receiving divalproex sodium as adjunctive therapy for complex partial seizures. Since patients were also treated with other antiepilepsy drugs, it is not possible, in most cases, to determine whether the following adverse events can be ascribed to divalproex sodium alone or the combination of divalproex sodium and other antiepilepsy drugs.
Body as a whole: Headache, asthenia, fever.
Gastrointestinal system: Nausea, vomiting, abdominal pain, diarrhea, anorexia, dyspepsia, constipation.
Nervous system: Somnolence, tremor, dizziness, diplopia, amblyopia/blurred vision, ataxia, nystagmus, emotional lability, thinking abnormal, amnesia.
Respiratory system: Flu syndrome, infection, bronchitis, rhinitis.
Other: Alopecia, weight loss.
Adverse events listed as follows are reported for patients who received high dose divalproex sodium for complex partial seizures. Since patients were being titrated off another antiepilepsy drug, it is not possible, in many cases, to determine whether the following adverse events can be ascribed to divalproex sodium alone or the combination of divalproex sodium and other antiepilepsy drugs.
Body as whole: Asthenia, headache.
Digestive System: Nausea, diarrhea, vomiting, abdominal pain, anorexia, dyspepsia.
Hemic/lymphatic system: Thrombocytopenia, ecchymosis.
Metabolic/Nutritional: Weight gain, peripheral edema.
Nervous system: Tremor, somnolence, dizziness, insomnia, nervousness, amnesia, nystagmus, depression.
Respiratory system: Infection, pharyngitis, dyspnea.
Skin and appendages: Alopecia.
Special senses: Amblyopia/blurred vision, tinnitus.
The following adverse events were reported by patients treated with divalproex sodium for complex partial seizures.
Body as a Whole: Back pain, chest pain, malaise.
Cardiovascular System: Tachycardia, hypertension, palpitation.
Digestive System: Increased appetite, flatulence, hematemesis, eructation, pancreatitis, periodontal abscess.
Hemic/lymphatic System: Petechia.
Metabolic/Nutritional Disorders: SGOT increased, SGPT increased.
Musculoskeletal System: Myalgia, twitching, arthralgia, leg cramps, myasthenia.
Nervous system: Anxiety, confusion, abnormal gait, paresthesia, hypertonia, incoordination, abnormal dreams, personality disorder.
Respiratory system: Sinusitis, cough increased, pneumonia, epistaxis.
Skin and Appendages: Rash, pruritis, dry skin.
Special Senses: Taste perversion, abnormal vision, deafness, otitis media.
Urogenital System: Urinary incontinence, vaginitis, dysmenorrhea, amenorrhea, urinary frequency.
Other Patient Populations: The following are adverse events with all dosage form of valproate that have been reported as epilepsy therapy and other reports.
Gastrointestinal: The most commonly reported side effects at the initiation of therapy are nausea, vomiting and indigestion. These effects are usually transient and rarely require discontinuation of therapy. Diarrhea, abdominal cramps and constipation have been reported. Both anorexia with some weight loss and increased appetite with weight gain have also been reported. The administration of delayed-release divalproex sodium may result in reduction of gastrointestinal side effect in some patients.
CNS Effects: Sedative effects have been noted in patients receiving valproate alone but occur most often in patients receiving combination therapy. Sedation usually abates upon reduction of other antiepileptic medication. Tremor (may be dose-related), hallucinations, ataxia, headache, nystagmus, diplopia, asterixis, "spots before eyes", dysarthria, dizziness, confusion, hypesthesia, vertigo, incoordination and parkinsonism have been reported with the use of valproate. Rare cases of coma have been noted in patients receiving valproate alone or in conjunction with phenobarbital. In rare instances encephalopathy with or without fever has developed shortly after the introduction of valproate monotherapy without evidence of hepatic dysfunction or inappropriately high plasma valproate levels. Although recovery has been described following drug withdrawal, there have been fatalities in patients with hyperammonemic encephalopathy, particularly in patients with underlying urea cycle disorders (see Urea Cycle Disorders under Warnings and Precautions). Several reports have been noted reversible dementia and reversible pseudoatrophy in association with valproate therapy.
Dermatologic: Transient hair loss, skin rash, photo sensitivity, generalized pruritus, erythema multiforme and Stevens-Johnson syndrome. Rare cases of toxic epidermal necrolysis have been reported including a fatal case in a six-month-old infant taking valproate and several other concomitant medications. An additional case of toxic epidermal necrosis resulting in death was reported in 35-year-old patient with AIDS taking several concomitant medications and with a history of multiple cutaneous drug reactions. Serious skin reactions have been reported with concomitant administration of lamotrigine and valproate (see Interactions).
Psychiatric: Emotional upset, depression, psychosis, aggression, hyperactivity, hostility and behavioral deterioration.
Musculoskeletal Weakness: Reports have been received of decreased bone mass, potentially leading to osteoporosis and osteopenia, during long-term therapy with anticonvulsant medications, including valproate. Some studies have indicated that supplemental calcium and vitamin D may be of benefit to patients who are on chronic valproate therapy.
Hematologic: Thrombocytopenia and inhibition of the secondary phase of platelet aggregation may be reflected in altered bleeding time, petechiae, bruising, hematoma formation, epistaxis, and frank hemorrhage (see General under Precautions and Interactions). Relative lymphocytosis, macrocytosis, hypofibrinogenemia, leukopenia, eosinophilia, anemia including macrocytic with or without folate deficiency, bone marrow suppression, pancytopenia, aplastic anemia agranulocytosis, and acute intermittent porphyria.
Hepatic: Minor elevations of transaminases (e.g., SGOT and SGPT) and LDH are frequent and appear to be dose-related. Occasionally, laboratory test result include increases in serum bilirubin and abnormal changes in other liver function tests. These results may reflect potentially serious hepatotoxicity (see Warnings).
Endocrine: Irregular menses, secondary amenorrhea, breast enlargement, galactorrhea and parotid grand swelling. Abnormal thyroid function tests (see Precautions). There have been rare spontaneous reports of polycystic ovary disease. A cause and effect relationship has not been established.
Pancreatic: Acute pancreatitis including fatalities (see Warnings).
Metabolic: Hyperammonemia (see General under Precautions), hyponatremia, and inappropriate ADH secretion.
There have been rare reports of Fanconi's syndrome occurring chiefly in children. Decreased carnitine concentrations have been reported although the clinical relevance is unknown.
Hyperglycinemia (elevated plasma glycine concentration) has occurred and was associated with a fatal outcome in a patient with preexistent nonketotic hyperglycinemia.
Genitourinary: Enuresis and urinary tract infection.
Special Senses: Hearing loss, either reversible or irreversible, has been reported; however, a cause and effect relationship has not been established. Ear pain has also been reported.
Others: Allergic reaction, anaphylaxis, edema of the extremities, lupus erythematosus, bone pain, cough increased, pneumonia, otitis media, bradycardia, cutaneous vasculitis, fever and hypothermia.
Mania: Although valproic acid has not been evaluated for safety and efficacy in the treatment of manic episodes associated with bipolar disorder, the following adverse events not listed previously were reported by patients of divalproex sodium tablets.
Body as Whole: Chills, neck pain, neck rigidity.
Cardiovascular system: Hypotension, postural hypotension, vasodilatation.
Digestive system: Fecal incontinence, gastroenteritis, glossitis.
Musculoskeletal: Arthrosis.
Nervous system: Agitation, catatonic reaction, hypokinesia, reflexes increased, tardive dyskinesia, vertigo.
Skin and Appendages: Furunculosis, maculopapular rash, seborrhea.
Special senses: Conjunctivitis, dry eyes, eye pain.
Urogenital system: Dysuria.
Migraine: Although valproic acid has not been evaluated for safety and efficacy in the treatment of prophylaxis of migraine headaches, the following adverse events not listed previously were reported by patients of divalproex sodium tablets.
Body as whole: Face edema.
Digestive system: Dry mouth, stomatitis.
Urogenital system: Cystitis, menorrhagia, vaginal hemorrhage.