Primidone Side Effects
Primidone commonly causes ataxia and vertigo as the most frequent early side effects, along with serious risks including behavioral disturbances, blood disorders, and severe sedation that can impair daily functioning. 1
Most Common Side Effects
The most frequently occurring side effects include:
- Ataxia (problems with walking and moving) and vertigo (dizziness, spinning, or swaying sensations) are the most common early adverse effects, though these tend to diminish with continued therapy or dose reduction 1
- Severe sleepiness and sedation, particularly when first starting primidone, which can significantly impair daily activities 1
- Nausea, anorexia, and vomiting 1
- Fatigue and drowsiness 1
- Diplopia (double vision) and nystagmus (involuntary eye movements) 1
In a pediatric study, primidone had a 29% overall side effect rate, with 8% requiring drug withdrawal—notably lower than phenytoin (71% side effects, 10% withdrawal) but behavioral disorders involving excitement occurred most commonly at low plasma levels 2
Serious Neuropsychiatric Effects
Behavioral and cognitive impairment can be significant:
- Hyperirritability and emotional disturbances 1
- Behavioral disorders, particularly excitement-type reactions that paradoxically occur at low plasma levels 2
- Depression-type behavioral disorders at high plasma levels 2
- Rare but documented catatonic schizophrenia with supratherapeutic levels 3
- Slowed thinking and impaired motor skills that affect driving and operating machinery 1
Hematologic Complications
Rare but serious blood disorders require vigilance:
- Granulocytopenia and agranulocytosis (severe reduction in white blood cells) 1
- Red-cell hypoplasia and aplasia 1
- Megaloblastic anemia as a rare idiosyncratic reaction, which responds to folic acid without necessarily discontinuing the medication 1
Warning signs include: fever, swollen glands, persistent sore throat, frequent infections, tiredness, and shortness of breath 1
Allergic and Dermatologic Reactions
Primidone may rarely cause allergic reactions including:
- Morbilliform (measles-like) skin eruptions 1
- Skin rash and hives 1
- Sores in the mouth 1
- Blistering or peeling skin 1
Other Notable Side Effects
- Sexual impotency 1
- Central nervous system depression, particularly in overdose situations where toxic effects are primarily due to primidone itself rather than its phenobarbital metabolite 4
Long-Term Considerations
In a prospective study of essential tremor patients, sedative effects were common at 4 weeks and 3 months but tended to subside thereafter, though three patients discontinued the drug because sedation outweighed therapeutic benefit 5. Some loss of efficacy during long-term administration was also noted 5.
Critical Safety Warnings
Abrupt discontinuation poses serious risks:
- Stopping primidone suddenly can cause withdrawal seizures, some of which may be severe 6
- Patients must taper gradually under medical supervision 1
Avoid alcohol and CNS depressants as primidone's sedative effects are potentiated, worsening sleepiness and dizziness 1
Monitoring Recommendations
While the FDA label does not specify routine laboratory monitoring intervals, clinicians should maintain vigilance for signs of blood disorders and consider baseline and periodic monitoring given the hematologic risks 1. Patients should be counseled to report fever, infections, unusual bleeding, or bruising immediately 1.