Epilepsan ECC Adverse Reactions

Epilepsy: Complex Partial Seizure (CPS): Divalproex sodium was generally well tolerated with most adverse events rated as mild to moderate in severity.
The following are adverse events in patients treated with Divalproex sodium: Body as a whole: Back pain, chest pain, malaise.
Cardiovascular: Tachycardia, hypertension, palpitation.
Digestive System: Increased appetite, flatulence, hematemesis, eructation, pancreatitis, periodontal abscess.
Hemic and Lymphatic System: Petechia.
Metabolic and 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, pruritus, dry skin.
Special Senses: Taste perversion, abnormal vision, deafness, otitis media.
Urogenital System: Urinary incontinence, vaginitis, dysmenorrhea, amenorrhea, urinary frequency.
Other Patient Populations: 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. Obesity is rare. Diarrhea, abdominal cramps, constipation and gingival disorder (mainly gingival hyperplasia) have been reported. Both anorexia with some weight loss and increased appetite wait weight gain have also been reported. The administration of delayed-release divalproex sodium may result in reduction of gastrointestinal side effects in some patients.
Central Nerve System (CNS) Effects: Sedative effects have occurred 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, memory impairment, cognitive disorder, and extrapyramidal disorders including parkinsonism have been reported with the use of Valproate. Rare cases of coma have occurred 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, Hyperammonemia and Encephalopathy Associated with Concomitant Topiramate Use, and Hyperammonemia under PRECAUTIONS]. Additionally, there have been reports of encephalopathy in the absence of elevated ammonia levels.
Reversible and irreversible cerebral and cerebellar atrophy temporally associated with the use of Valproate products. In some cases the patients recovered with permanent sequelae [see Brain Atrophy under PRECAUTIONS]. Cerebral atrophy seen in children exposed to Valproate in utero led to various forms of neurological events, including developmental delays and psychomotor impairment. Congenital malformations and developmental disorders have been as well reported [see USE IN PREGNANCY & LACTATION].
Dermatologic: Transient hair loss, hair disorders (such as hair texture abnormal, hair colour changes, hair growth abnormal) skin rash, photosensitivity, generalized pruritus, erythema multiforme, and Stevens-Johnson syndrome. Rare cases of toxic epidermal necrolysis have been discovered including a fatal case in a six-month-old infant taking Valproate and several other concomitant medications. Toxic epidermal necrosis resulting in death occurs in a patient with AIDS taking several concomitant medications and with a history of multiple cutaneous drug reactions. Serious skin reactions have been discovered with concomitant administration of Lamotrigine and Valproate [see INTERACTIONS]. Nail and nail bed disorders.
Psychiatric: Emotional upset, depression, psychosis, aggression, psychomotor hyperactivity, hostility, agitation, disturbance in attention, abnormal behavior, learning disorders, and behavioral deterioration.
Musculoskeletal: Weakness: There are 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 hemorrhage [see General under PRECAUTIONS and Warfarin under 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 transaminase (e.g., SGOT and SGPT) and LDH are frequent and appear to be dose-related. Occasionally, laboratory test results include increases in serum bilirubin and abnormal changes in other liver function tests. These results may reflect potentially serious hepatotoxicity [see Hepatotoxicity under PRECAUTIONS].
Endocrine: Irregular menses, secondary amenorrhea, breast enlargement, galactorrhea, and parotid gland swelling. Hyperandrogenism (hirsutism, virilism, acnea, male pattern alopecia, and/or androgen increased). Abnormal thyroid function tests including hypothyroidism [see General under PRECAUTIONS]. There have been rare spontaneous reports of polycystic ovary disease, but a cause and effect relationship has not been established.
Pancreatic: Acute pancreatitis including fatalities [see Pancreatitis under PRECAUTIONS].
Metabolic: Hyperammonemia [see Hyperammonemia 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.
Insulin resistance and dyslipidemia also may occur.
Genitourinary: Enuresis, renal failure, tubulointerstitial nephritis and urinary tract infection.
Reproductive: Male infertility including azoospermia, abnormal semen analysis, decrease sperm count, spermatozoa morphology abnormal, aspermia, and decrease spermatozoa motility have been reported.
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.
Neoplasms benign, malignant and unspecified (including cysts and polyps): Myelodysplastic syndrome.
Respiratory, thoracic and mediastinal disorders: Pleura effusion.
Other: Allergic reaction, anaphylaxis, edema of the extremities, lupus erythematosus, rhabdomyolysis, biotin deficiency/biotinidase deficiency, bone pain, cough increased, pneumonia, otitis media, bradycardia, cutaneous vasculitis, fever, and hypothermia.
Other patient population: Extrapyramidal disorders and encephalopathy in the absence of elevated ammonia levels.