Valpros: Neoplasms Benign, Malignant and Unspecified (including cysts and polyps):
Blood and Lymphatic System Disorders:
Thrombocytopenia, anemia, aplastic anemia, leukopenia, pancytopenia with or without bone marrow depression, decreased blood fibrinogen,
red cell hypoplasia, neutropenia; bone marrow failure, including pure red cell aplasia, agranulocytosis; anemia including macrocytic with or without folate deficiency, anemia macrocytosis, ecchymosis, petechia, lymphocytosis, bone marrow suppression, acute intermittent porphyria.
Immune System Disorders:
Angioedema, anaphylaxis, allergic reaction, cutaneous vasculitis.
Hypothyroidism, hyperandrogenism (e.g., hirsutism, virilism, androgen increased), parotid gland swelling, hyperglycemia.
Nausea, upper abdominal pain, diarrhea, gingival disorder (mainly gingival hyperplasia), stomatitis, vomiting, abdominal cramp, upper abdominal pain, anorexia, increased appetite, pancreatitis, constipation, gastralgia, dyspepsia, flatulence, hematemesis, eructation, periodontal abscess, taste perversion, fetal incontinence, gastroenteritis, glossitis, dry mouth.
Hepatic dysfunction, including hepatic failure; liver injury, AST and ALT increased.
Metabolism and Nutrition Disorders:
Hyperammonemia, asymptomatic elevations of ammonia, hyponatremia, syndrome of inappropriate secretion of ADH (SIADH).
Depression, excitement, hyperactivity, behavioral disorders, confusional state, hallucinations, aggression, agitation, disturbance in attention, abnormal behavior, psychomotor hyperactivity, learning disorder, emotional lability, thinking abnormal, anxiety, abnormal gait, personality disorder, emotional upset, psychosis, hostility, behavioral deterioration, developmental delay.
Nervous System Disorders:
Drowsiness, sedation, tremor, stupor, somnolence, convulsion, memory impairment, headache, nystagmus, dizziness, ataxia, coma, encephalopathy, lethargy, paresthesia, reversible dementia associated with reversible cerebral atrophy and cognitive disorder; reversible parkinsonism, extrapyramidal disorder which may not be reversible; twitching, hypertonia, incoordination, abnormal dreams, catatonic reaction, hypokinesia, reflexes increased, tardive dyskinesia, vertigo.
Diplopia, amblyopia/blurred vision, abnormal vision, conjunctivitis, dry eyes, eye pain.
Ear and Labyrinth Disorders:
Deafness, either reversible or irreversible, tinnitus, otitis media, hearing loss.
Chest pain, tachycardia, hypertension, palpitation, hypotension, postural hypotension, bradycardia.
Hemorrhage, vasculitis, vasodilation.
Respiratory, Thoracic and Mediastinal Disorders:
Pleural effusion, flu syndrome, bronchitis, rhinitis, pharyngitis, dyspnea, sinusitis, cough increased, pneumonia, epistaxis.
Skin and Subcutaneous Tissue Disorders:
Hypersensitivity, transient and/or dose-related alopecia, hirsutism, acne, pruritus, urticaria, Stevens-Johnson Syndrome, angioedema, rash, hair disorder (e.g., hair texture abnormal, hair color changes, hair growth abnormal), toxic epidermal necrolysis, erythema multiforme, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome, dry skin, furunculosis, maculopapular rash, seborrhea, photosensitivity.
Musculoskeletal and Connective Tissue Disorders:
Decreased bone mineral density, osteopenia, osteoporosis, and fractures, systemic lupus erythematosus, rhabdomyolysis, back pain, neck pain, neck rigidity, myalgia, twitching, arthralgia, leg cramps, myasthenia, arthrosis, bone pain.
Renal and Urinary Disorders:
Enuresis, tubulointerstitial nephritis, Fanconi's syndrome, urinary incontinence, urinary frequency, dysuria, cystitis, enuresis, urinary tract infection.
Reproductive System and Breast Disorders:
Irregular menses, amenorrhea, breast enlargement, galactorrhea, dysmenorrhea, male infertility, polycystic ovaries, vaginitis, metrorrhagia, vaginal hemorrhage.
Coagulation factors decreased, abnormal coagulation tests (such as prolonged prothrombin time, activated partial thromboplastin time, thrombin time and INR) and biotin
deficiency/biotinidase deficiency; decreased carnitine concentrations.
General Disorders and Administration Site Conditions:
Edema, peripheral edema, face edema, hypothermia, increased weight, weight loss, pain, asthenia, fever, fatigue, malaise, chills,
(see Statement on Usage for High Risk Groups under Precautions): Body as a whole:
Very Common: Infection. Common: Fever, back pain, malaise, chills, neck pain, neck rigidity, facial edema. Rare: Myelodysplastic syndrome (may be reversible). Other Reported Effects: Hypothermia, fever with chills, sweating, cyst, accidental injury, fatigue.
Common: Chest pain, tachycardia, hypertension, palpitation, hypotension, postural hypotension, vasodilation. Other Reported Effects: Bradycardia, arrhythmia.
Very Common: Nausea. Common: Diarrhea, vomiting, indigestion, abdominal pain, abdominal cramps, dyspepsia, constipation, flatulence, hematemesis, eructation, acute pancreatitis (may be hemorrhagic with a rapid progression from initial symptoms to death), periodontal abscess, fecal incontinence, gastroenteritis, glossitis, stomatitis, dry mouth. Uncommon: Pancreatitis (sometimes lethal), dysphagia, gum hemorrhage, mouth ulceration.
Common: Anemia (including macrocytic with or without folate deficiency), thrombocytopenia, hemorrhage, ecchymosis, petechiae. Uncommon: Pancytopenia, leukopenia, vasculitis. Rare: Bone marrow failure (i.e., red cell aplasia, agranulocytosis, macrocytic anemia, macrocytosis). Other Reported Effects: Red cell hypoplasia, neutropenia, reduction in blood fibrinogen and/or increase in prothrombin time, bruising, bleeding, hematoma formation, epistaxis, frank hemorrhage, relative lymphocytosis, hypofibrinogenemia, eosinophilia, aplastic anemia, acute intermittent porphyria, bone marrow suppression, inhibition of platelet aggregation resulting in prolonged bleeding time.
Common: Liver injury, severe liver damage (including hepatic failure), minor elevations of transaminases (i.e., alanine aminotransferase, ALT; aspartate aminotransferase, AST) and lactate dehydrogenase (LDH). Other Reported Effects: Increased serum bilirubin, abnormal changes in other liver function tests, hepatitis.
Common: Myalgia, leg cramps, arthralgia, twitching, myasthenia, arthrosis. Uncommon: Decreased bone mass (potentially leading to osteoporosis and osteopenia), fractures. Rare: Systemic lupus erythematosus, muscular weakness, reversible skeletal muscle weakness. Other Reported Effects: Weakness, bone pain.
Common: Hyponatremia, weight gain, anorexia with some weight loss, increased appetite. Uncommon: Inappropriate antidiuretic hormone (ADH) secretion, peripheral edema, angioedema. Rare: Hyperammonemia, hypothyroidism, reversible Fanconi syndrome, galactorrhea. Other Reported Effects: Parotid gland swelling, decreased carnitine concentrations, hyperglycemia, abnormal thyroid test results, hypoglycemia.
Very Common: Tremor. Common: Extrapyramidal disorder, stupor, somnolence, convulsion, memory impairment, headache, confusion, aggression, euphoria, agitation, disturbance in attention, asthenia, dizziness, emotional lability, thinking abnormalities, amnesia, depression, anxiety, abnormal gait, hypertonia, incoordination, abnormal dreams, personality disorder, catatonic reaction, hypokinesia, increased reflexes, tardive dyskinesia, vertigo. Uncommon: Coma, encephalopathy (with or without fever or hyperammonemia), lethargy, reversible Parkinsonism, ataxia, paresthesia. Rare: Hallucinations, excitement, increased alertness, hyperactivity, reversible dementia associated with cerebral atrophy, cognitive disorder, sedation, abnormal behavior, psychomotor hyperactivity, learning disorder, encephalopathy with or without fever. Other Reported Effects: Dysarthria, asterixis, hypesthesia, incoordination, reversible and irreversible cerebral and cerebellar atrophy, emotional upset, psychosis/acute psychosis, hostility, behavioral deterioration, insomnia, nervousness, suicidal behavior, spasmodic dysphonia.
Common: Flu syndrome, infection, bronchitis, rhinitis, pharyngitis, dyspnea, sinusitis, increased cough, pneumonia, epistaxis. Uncommon: Pleural effusion, hiccups.
Dermatologic and Hypersensitivity:
Common: Hypersensitivity, transient alopecia (hair loss), pruritus, rash (including maculopapular), dry skin, furunculosis, seborrhea. Rare: Toxic epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome, multi-organ hypersensitivity. Very Rare: Hirsutism, acne. Other Reported Effects: Generalized pruritus, anaphylaxis, discoid lupus erythematosus, cutaneous vasculitis, photosensitivity, erythema nodosum.
Common: Hearing loss (either reversible or irreversible), diplopia, amblyopia/blurred vision, tinnitus, taste perversion, abnormal vision, nystagmus, otitis media, conjunctivitis, dry eyes, eye pain. Other Reported Effects: Ear pain, "spots before the eyes", otic disorder, ocular disorder, photophobia.
Common: Dysmenorrhea, urinary incontinence, urinary frequency, vaginitis, dysuria, metrorrhagia, cystitis, vaginal hemorrhage. Uncommon: Secondary amenorrhea. Rare: Male infertility, polycystic ovary disease, enuresis, gynecomastia, hyperandrogenism. Other Reported Effects: Irregular menses, urinary tract infection, developmental delay, autism and/or autism spectrum disorder in the offspring of women exposed to valproate during pregnancy, interstitial nephritis.
Valpros i-IV: Body as a Whole:
Pain (unspecified), peripheral edema.
Chest pain, vasodilation, vasculitis.
Weight gain, hyperammonemia, hyponatremia.
Headache, dizziness, nervousness, sedation, ataxia, paresthesia, hypesthesia, extrapyramidal symptoms including parkinsonism, tremor, reversible dementia, somnolence, hallucination, convulsion, encephalopathy, coma, euphoria, lethargy, confusion, abnormal gait, aggression, alertness increased, hyperactivity, behavioral deterioration.
Abdominal pain, diarrhea, nausea, vomiting, pancreatitis, gastralgia.
Thrombocytopenia; anemia; leukopenia; pancytopenia; bone marrow failure, including red cell aplasia; agranulocytosis; blood fibrinogen reduced; increased prothrombin time.
Hepatic dysfunction; severe liver damage, including hepatic failure; increased liver enzymes.
Skin and appendages:
Injection site inflammation, injection site pain, injection site reaction, sweating, transient hair loss, hirsutism, acne, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, angioedema, drug rash with eosinophilia systemic symptoms (DRESS) syndrome, allergic reactions.
Hearing loss, taste perversion.
Fanconi's syndrome, amenorrhea, irregular periods, gynecomastia.
Adverse events that have been reported with all dosage forms of valproate: Body as a Whole:
Asthenia, fever, hypothermia, chills, infection, malaise, fatigue, edema of the extremities, face edema.
Tachycardia, bradycardia, hypertension, hypotension, postural hypotension, vasodilation, palpitation.
Anorexia, weight loss, increased appetite, syndrome of inappropriate secretion of ADH (SIADH), parotid gland swelling, abnormal thyroid function tests, decreased carnitine concentrations, hyperglycinemia.
Drowsiness, hypertonia, incoordination, catatonic reaction, hypokinesia, reflexes increased, tardive dyskinesia, asterixis, insomnia, abnormal dreams, amnesia, dementia, dysarthria, vertigo, cerebral atrophy, emotional lability, thinking abnormal, emotional upset, depression, anxiety, stupor, personality disorder, excitement, psychosis, hostility, agitation.
Periodontal abscess, dry mouth, glossitis, stomatitis, abdominal cramps, dyspepsia, indigestion, constipation, gastroenteritis, flatulence, hematemesis, eructation, fecal incontinence.
Ecchymosis, petechia, neutropenia, altered bleeding time, bruising, hematoma formation, epistaxis, hemorrhage, lymphocytosis, macrocytosis, hypofibrinogenemia, eosinophilia, anemia including macrocytic anemia with or without folate deficiency, aplastic anemia, acute intermittent porphyria, bone marrow suppression, lupus erythematosus.
Serum bilirubin increased.
Back pain, neck pain, neck rigidity, myalgia, twitching, arthralgia, arthrosis, leg cramps, myasthenia, weakness, bone pain.
Flu syndrome, bronchitis, rhinitis, dyspnea, sinusitis, cough increased.
Skin and appendages:
Alopecia, rash, pruritus, dry skin, photosensitivity, furunculosis, maculopapular rash, seborrhea.
Diplopia, amblyopia/blurred vision, abnormal vision, spots before eyes, conjunctivitis, dry eyes, eye pain, nystagmus, deafness, otitis media, tinnitus.
Urinary incontinence, urinary frequency, enuresis, dysuria, cystitis, vaginitis, vaginal hemorrhage, dysmenorrhea, metrorrhagia, galactorrhea.