What are the potential side effects of valproic acid (valproate)?

From the Guidelines

Valproic acid (valproate) can cause several potential side effects, including weight gain, menstrual irregularities, polycystic ovaries, and hyperandrogenism, which are particularly concerning in women of childbearing age 1.

Common Side Effects

• Nausea, vomiting, indigestion, diarrhea, and tremors, which often improve with continued use or dose adjustment
• Weight gain, with some patients gaining 5-10 pounds or more
• Drowsiness, dizziness, and hair loss

Serious Side Effects

• Liver damage (indicated by yellowing skin/eyes, dark urine, abdominal pain)
• Pancreatitis (severe abdominal pain, nausea, vomiting)
• Blood disorders (unusual bleeding, bruising, fever, sore throat)
• Hyperammonemia (confusion, vomiting, lethargy)

Reproductive Side Effects

• Menstrual irregularities, such as amenorrhoea, oligomenorrhoea, prolonged cycles, and irregular menstruation
• Polycystic ovaries and hyperandrogenism, which can be associated with weight gain and insulin resistance 1

Monitoring and Precautions

• Regular blood tests to monitor liver function, blood counts, and drug levels are essential during treatment
• Women of childbearing age should use effective contraception to prevent birth defects and developmental problems
• Long-term use may lead to decreased bone density, and patients should be monitored for this potential side effect 1

Recent Guidelines

• A recent study found that valproic acid may be associated with higher hematologic toxicities in brain tumor patients on chemotherapy 1
• Another study suggested that levetiracetam may be a better option than valproic acid in terms of side effect profile 1

From the FDA Drug Label

The common side effects of Valproic Acid Oral Solution, USP include:

• nausea
• headache
• sleepiness
• vomiting
• weakness
• tremor
• dizziness
• stomach pain
• blurry vision
• double vision
• diarrhea
• increased appetite
• weight gain
• hair loss
• loss of appetite
• problems with walking or coordination Valproic Acid Oral Solution, USP can cause other serious side effects including:
• Bleeding problems: red or purple spots on your skin, bruising, pain and swelling into your joints due to bleeding or bleeding from your mouth or nose.
• High ammonia levels in your blood: feeling tired, vomiting, changes in mental status.
• Low body temperature (hypothermia): drop in your body temperature to less than 95°F, feeling tired, confusion, coma.
• Allergic (hypersensitivity) reactions: fever, skin rash, hives, sores in your mouth, skin blistering and peeling of your skin, swelling of your lymph nodes, swelling of your face, eyes, lips, tongue, or throat, trouble swallowing or breathing. The potential side effects of valproic acid (valproate) are nausea, headache, sleepiness, vomiting, weakness, tremor, dizziness, stomach pain, blurry vision, double vision, diarrhea, increased appetite, weight gain, hair loss, loss of appetite, and problems with walking or coordination. Additionally, valproic acid can cause serious side effects such as bleeding problems, high ammonia levels in the blood, low body temperature (hypothermia), and allergic (hypersensitivity) reactions 2.

From the Research

Potential Side Effects of Valproic Acid

The potential side effects of valproic acid (valproate) are numerous and can be severe. Some of the possible side effects include:

• Hepatotoxicity, which can range from reversible hepatic dysfunction to irreversible hepatic failure 3, 4
• Hyperammonemic encephalopathy, a condition characterized by elevated levels of ammonia in the blood, which can cause symptoms such as mental confusion, nausea, and apathy 5, 6
• Mitochondrial toxicity, which can lead to a range of symptoms including fatigue, muscle weakness, and neurological problems 7
• Hypersensitivity syndrome reactions, which can cause symptoms such as fever, rash, and lymphadenopathy 7
• Neurological toxicity, which can cause symptoms such as tremors, ataxia, and seizures 7
• Metabolic and endocrine adverse events, such as weight gain, hair loss, and menstrual irregularities 7
• Teratogenicity, which can increase the risk of birth defects in pregnant women taking valproic acid 7

Specific Studies

Several studies have investigated the side effects of valproic acid. For example, a study published in 1978 found that altered hepatic function tests occurred in four of 25 patients treated with valproic acid 3. Another study published in 2013 found that valproic acid can cause a range of adverse drug reactions, including hepatotoxicity, mitochondrial toxicity, and hyperammonemic encephalopathy 7. A study published in 1988 found that valproic acid can cause biochemical abnormalities in the liver, including inhibition of beta-oxidation and synthesis of fatty acids 4. A case report published in 2008 described a patient who developed hyperammonemic encephalopathy due to valproic acid 5. A study published in 2019 found that valproic acid can cause adverse effects in newborns, including disturbances in consciousness, hyperammoniemia, and hematological alterations 6.