Does Phenobarbitone Cause Myositis?
No, phenobarbitone (phenobarbital) does not cause myositis. The FDA-approved drug label for phenobarbital lists myalgic pain as a rare adverse effect, but myositis is not documented as a known complication 1.
Evidence from FDA Drug Labeling
The official phenobarbital prescribing information describes musculoskeletal adverse effects as follows:
- Myalgic pain (muscle pain) may rarely occur, particularly in psychoneurotic patients with insomnia 1
- This pain appears in paroxysms, is most intense in early morning hours, and typically affects the neck, shoulder girdle, and upper limbs 1
- Symptoms may persist for days after drug discontinuation 1
- Critically, myositis (muscle inflammation) is not listed among the adverse reactions 1
Distinction Between Myalgia and Myositis
This distinction is clinically important:
- Myalgia = muscle pain without inflammation or weakness, with normal creatine kinase (CK) levels 2, 3
- Myositis = inflammatory muscle disease characterized by proximal muscle weakness, markedly elevated CK levels (often >10x normal), abnormal EMG findings, and muscle edema on MRI 2, 3
Phenobarbital causes the former (pain), not the latter (inflammatory disease) 1.
Other Documented Phenobarbital Toxicities
Long-term phenobarbital use is associated with:
- CNS effects: sedation, behavioral problems, hyperactivity, and rarely dementia 1, 4
- Hypersensitivity syndrome: fever, rash, lymphadenopathy, and hematologic abnormalities including thrombocytopenia 5
- Megaloblastic anemia with chronic use 1
- Respiratory depression and circulatory collapse in overdose 1, 6
Muscle twitching can paradoxically occur with phenobarbital toxicity (not myositis), representing a manifestation of drug toxicity rather than seizure recurrence 7.
Clinical Pitfall to Avoid
If a patient on phenobarbital develops true proximal muscle weakness with elevated CK, do not attribute this to phenobarbital. Instead, investigate alternative causes:
- Statin-induced necrotizing myopathy (if on concurrent statins) 2
- Autoimmune inflammatory myositis (polymyositis, dermatomyositis) 2, 3, 8
- Proton pump inhibitor-associated myopathy (if on concurrent PPIs) 9
- Paraneoplastic myositis 2
The diagnostic workup should include CK measurement, myositis-specific autoantibodies, EMG, and MRI imaging to establish the correct diagnosis 2, 3, 8.