Known hypersensitivity to valproate or any of the ingredients used in the preparation
Urea cycle disorders
Hepatic porphyria
Hepatotoxicity
Mitochondrial disease
Pancreatitis
Porphyria

Adverse effects
Valproic acid has a black box warning for hepatotoxicity, pancreatitis, and fetal abnormalities.It is worthy of mentioning that some adverse effects related to valproic acid may be dose-dependent such as pancytopenia.There is evidence that valproic acid may cause premature growth plate ossification in children and adolescents, resulting in decreased height. Valproic acid can also cause mydriasis, a dilation of the pupils. There is evidence that shows valproic acid may increase the chance of polycystic ovary syndrome (PCOS) in women with epilepsy or bipolar disorder. Studies have shown this risk of PCOS is higher in women with epilepsy compared to those with bipolar disorder. Weight gain is also possible. Pregnancy
Valproate causes birth defects; exposure during pregnancy is associated with about three times as many major abnormalities as usual, mainly spina bifida with the risks being related to the strength of medication used and use of more than one drug. More rarely, with several other defects, including a "valproate syndrome". Characteristics of this valproate syndrome include facial features that tend to evolve with age, including a triangle-shaped forehead, tall forehead with bifrontal narrowing, epicanthic folds, medial deficiency of eyebrows, flat nasal bridge, broad nasal root, anteverted nares, shallow philtrum, long upper lip and thin vermillion borders, thick lower lip and small downturned mouth.
Pharmacokinetics
Taken by mouth, valproate is rapidly and virtually completely absorbed from the gut. When in the bloodstream, 80–90% of the substance are bound to plasma proteins, mainly albumin. Protein binding is saturable: it decreases with increasing valproate concentration, low albumin concentrations, the patients age, additional use of other drugs such as aspirin, as well as liver and kidney impairment. Concentrations in the cerebrospinal fluid and in breast milk are 1 to 10% of blood plasma concentrations.The vast majority of valproate metabolism occurs in the liver. Valproate is known to be metabolized by the cytochrome P450 enzymes CYP2A6, CYP2B6, CYP2C9, and CYP3A5. It is also known to be metabolized by the UDP-glucuronosyltransferase enzymes UGT1A3, UGT1A4, UGT1A6, UGT1A8, UGT1A9, UGT1A10, UGT2B7, and UGT2B15. Some of the known metabolites of valproate by these enzymes and uncharacterized enzymes include (see image):
via glucuronidation (30–50%): valproic acid β-O-glucuronide
via beta oxidation (>40%): 2E-ene-valproic acid, 2Z-ene-valproic acid, 3-hydroxyvalproic acid, 3-oxovalproic acid
via omega oxidation: 5-hydroxyvalproic acid, 2-propyl-glutaric acid
some others: 3E-ene-valproic acid, 3Z-ene-valproic acid, 4-ene-valproic acid, 4-hydroxyvalproic acidAll in all, over 20 metabolites are known.In adult patients taking valproate alone, 30–50% of an administered dose is excreted in urine as the glucuronide conjugate. The other major pathway in the metabolism of valproate is mitochondrial beta oxidation, which typically accounts for over 40% of an administered dose. Typically, less than 20% of an administered dose is eliminated by other oxidative mechanisms. Less than 3% of an administered dose of valproate is excreted unchanged (i.e., as valproate) in urine. Only a small amount is excreted via the faeces.