From the Guidelines
Valproic acid toxicity symptoms can range from mild to severe, including nausea, vomiting, drowsiness, tremors, confusion, lethargy, slurred speech, ataxia, and nystagmus, with severe cases leading to coma, cerebral edema, respiratory depression, and death. The symptoms of valproic acid toxicity can be categorized into several key areas, including:
- Neurological symptoms: dizziness, tremors, confusion, lethargy, slurred speech, ataxia, and nystagmus 1
- Metabolic abnormalities: hyperammonemia, which can cause altered mental status without liver dysfunction 1
- Hematological symptoms: thrombocytopenia, pancytopenia 1
- Hepatic symptoms: hepatotoxicity with jaundice and elevated liver enzymes 1
- Gastrointestinal symptoms: nausea, vomiting, acute pancreatitis 1 It is essential to monitor therapeutic drug levels, with normal ranges between 50-100 μg/mL, and to discontinue the medication immediately if toxicity is suspected, providing supportive care as needed 1. In patients with valproic acid toxicity, it is crucial to consider the potential for severe complications, such as respiratory depression, cerebral edema, and death, and to manage these complications promptly and effectively 1.
From the FDA Drug Label
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 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
The symptoms of valproic acid toxicity include:
- Bleeding problems: red or purple spots on the skin, bruising, pain and swelling in the joints, bleeding from the mouth or nose
- High ammonia levels in the blood: feeling tired, vomiting, changes in mental status
- Low body temperature (hypothermia): drop in body temperature to less than 95°F, feeling tired, confusion, coma
- Allergic (hypersensitivity) reactions: fever, skin rash, hives, sores in the mouth, skin blistering and peeling, swelling of the lymph nodes, face, eyes, lips, tongue, or throat, trouble swallowing or breathing
- Common side effects: 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 2
From the Research
Valproic Acid Toxicity Symptoms
The symptoms of valproic acid toxicity can be numerous and varied, reflecting both exaggerated therapeutic effects and impaired intermediary metabolism 3. Some of the common symptoms include:
- Central nervous system depression, which can progress to coma and respiratory depression
- Cerebral edema
- Hepatotoxicity, although rare in acute overdose settings
- Pancreatitis
- Hyperammonemia
- Metabolic and hematologic derangements
Clinical Manifestations
Clinical manifestations of valproic acid toxicity can range from mild confusion and drowsiness to serious encephalopathy, leading to depressed sensorium and even coma and death 4. In some cases, valproic acid-induced hyperammonemic encephalopathy can occur, which is a rare yet serious sequela that can lead to grave outcomes.
Specific Cases
Specific cases of valproic acid toxicity have been reported, including:
- A 15-year-old girl who ingested approximately 100 drug tablets and presented with shock, altered laboratorial parameters, and suspect aspiration pneumonia 5
- A toddler who accidentally ingested valproic acid and developed hyperammonemic encephalopathy with preserved liver function 4
- A 3-year-old boy who accidentally poisoned himself with valproic acid and presented with profound coma, depressed respiration, and miosis 6
- A case of valproic acid toxicity that did not respond to carnitine treatment but was successfully treated with meropenem 7
Treatment and Management
Treatment and management of valproic acid toxicity require supportive care and close attention to the airway 3. The use of adjunctive therapies, such as extracorporeal drug elimination, L-carnitine supplementation, and carbapenems, may be considered in certain cases 3, 7. Prompt recognition and treatment of valproic acid toxicity are crucial to prevent serious complications and improve patient outcomes.