Primidone and Hydrocortisone Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Primidone
Hydrocortisone Injection
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Reduced hydrocortisone exposure and reduced efficacy of hydrocortisone
Interaction Deep Dive
Concomitant use of PHENobarbital (a CYP3A inducer) with hydrocortisone (a CYP3A substrate) may decrease hydrocortisone exposure, which may reduce the efficacy of hydrocortisone. If concomitant use cannot be avoided, closely monitor neonates and consider increasing the hydrocortisone dosage accordingly3. Concomitant use of PHENobarbital and a corticosteroid may result in decreased plasma levels and therapeutic effects of the corticosteroid 24516. Primidone, as a result of its metabolite PHENobarbital, has been demonstrated to increase the hepatic metabolism of corticosteroids 748.
Why it happens (mechanism)
Induction of CYP3A-mediated metabolism of hydrocortisone by PHENobarbital
Literature reports
2 reports — tap to read
a) The half-life of dexamethasone was significantly decreased with concurrent PHENobarbital administration in one study. In the same study, 2 steroid-resistant asthmatics receiving high doses of prednisone were reported to exhibit worsening of asthma, pulmonary function deterioration, and eosinophilia with the addition of PHENobarbital. Upon discontinuation of PHENobarbital in these patients, the effects reversed, which permitted a reduction of prednisone dosage 4.
b) Concomitant methylprednisolone and PHENobarbital therapy has been reported to enhance the metabolism of the corticosteroid, probably as a result of microsomal liver enzyme induction by PHENobarbital. In one study, the base-line half-life was decreased by 53% 1.
Common questions
Can I take Primidone and Hydrocortisone Injection together?
Reduced hydrocortisone exposure and reduced efficacy of hydrocortisone Always confirm with your pharmacist or prescriber before making any change.
How serious is the Primidone and Hydrocortisone Injection interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Primidone or Hydrocortisone Injection need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (8)
- Stjernholm MR & Katz FH: Effects of diphenylhydantoin, phenobarbital, and diazepam on the metabolism of methylprednisolone and its sodium succinate. J Clin Endocrinol Metab 1975; 41:887-893. PubMed
- Gambertoglio JG, Holford NH, Kapusnik JE, et al: Disposition of total and unbound prednisolone in renal transplant patients receiving anticonvulsants. Kidney Int 1984; 25:119-123. PubMed
- Product Information: SEZABY(TM) intravenous injection, phenobarbital sodium intravenous injection. Sun Pharmaceutical Industries Inc (per manufacturer), Cranbury, NJ, 2022. DailyMed
- Brooks SM, Werk EE, Ackerman SJ, et al: Adverse effects of phenobarbital on corticosteroid metabolism in patients with bronchial asthma. N Engl J Med 1972; 286:1125-1128. PubMed
- Brooks PM, Buchanan WW, Grove M, et al: Effects of enzyme induction on metabolism of prednisolone. Clinical and laboratory study. Ann Rheum Dis 1976; 35:339-343. PubMed
- Product Information: Luminal(R), phenobarbital sodium injection. Sanofi Winthrop Pharmaceuticals, New York, NY, 1993. DailyMed
- Hancock KW & Levell MJ: Primidone/dexamethasone interaction (letter). Lancet 1978; 2:97-98. PubMed
- Young MC & Hughes IA: Loss of therapeutic control in congenital adrenal hyperplasia due to interaction between dexamethasone and primidone. Acta Paediatr Scand 1991; 80:120-124. PubMed
Keep reading about Primidone
Keep reading about Hydrocortisone Injection
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist