From the FDA Drug Label
Do not take Valproic Acid Oral Solution, USP if you: •have liver problems •have or think you have a genetic liver problem caused by a mitochondrial disorder (e. g. Alpers-Huttenlocher syndrome)
Mitochondrial cell disease medications to avoid:
- Valproic acid (PO) Why:
- Patients with mitochondrial disorders may be at risk of worsening their condition due to the potential hepatotoxic effects of valproic acid.
- The drug label explicitly states that valproic acid is contraindicated in patients with known or suspected mitochondrial disorders, such as Alpers-Huttenlocher syndrome 1.
From the Research
Patients with mitochondrial diseases should avoid several medications due to their potential to worsen mitochondrial function, including valproic acid, statins, metformin, propofol, and certain antipsychotics, as these can trigger liver failure, exacerbate muscle symptoms, inhibit complex I of the respiratory chain, or increase the risk of propofol infusion syndrome. These medications interfere with mitochondrial function through various mechanisms, including inhibition of the electron transport chain, disruption of mitochondrial DNA replication, increased oxidative stress, or depletion of essential cofactors 2. The treatment of mitochondrial diseases is still inadequate, and therapies that have been attempted include respiratory chain cofactors, other metabolites secondarily decreased in mitochondrial disorders, antioxidants, and agents acting on lactic acidosis 3. However, their role in the treatment of the majority of mitochondrial diseases is still unclear.
Some of the key medications to avoid in patients with mitochondrial diseases include:
- Certain antibiotics like aminoglycosides (gentamicin, tobramycin), chloramphenicol, and tetracyclines, which can impair mitochondrial protein synthesis
- Valproic acid, an antiepileptic medication, which should be strictly avoided as it can trigger liver failure and worsen metabolic decompensation in mitochondrial disorders, particularly those with POLG mutations
- Statins (simvastatin, atorvastatin) may exacerbate muscle symptoms in mitochondrial patients due to their effects on coenzyme Q10 production
- Metformin should be used cautiously as it can inhibit complex I of the respiratory chain
- Other medications to avoid include propofol (risk of propofol infusion syndrome), certain antipsychotics like haloperidol, and high-dose acetaminophen.
Randomized clinical trials are necessary to establish efficacy and safety of drugs, and multicenter collaboration is essential for the advancement of therapy for mitochondrial disorders 4, 5. Patients with mitochondrial disease should always consult with their specialist before starting new medications, and healthcare providers should carefully weigh risks versus benefits when prescribing, considering alternative medications with better safety profiles to avoid triggering metabolic crises or worsening of underlying mitochondrial dysfunction 6.