Phenobarbital Shortage: What Providers and Prescribers Need to Know in 2026

Phenobarbital remains a cornerstone anticonvulsant for specific patient populations, yet ongoing supply chain vulnerabilities continue to challenge prescribers and healthcare systems. This guide provides clinicians with an evidence-based overview of the current Phenobarbital supply landscape, therapeutic considerations for alternative agents, and practical strategies for patient management during periods of limited availability.

Current Supply Status

As of February 2026, Phenobarbital oral formulations are not listed on the FDA's active drug shortage database. However, clinicians should be aware that:

• Spot shortages persist at the pharmacy level, particularly for higher-strength tablets (60 mg, 97.2 mg, 100 mg) and the oral elixir formulation
• Injectable Phenobarbital (65 mg/mL, 130 mg/mL) has experienced intermittent shortages over the past several years, affecting acute care settings
• Geographic variability is significant — availability can differ substantially between regions and between chain and independent pharmacies
• The limited number of generic manufacturers (fewer than five active US manufacturers) creates systemic fragility in the supply chain

Factors Contributing to Supply Vulnerability

Regulatory Constraints

Phenobarbital is classified as a DEA Schedule IV controlled substance, subjecting it to annual aggregate production quotas. These quotas, while necessary for controlled substance oversight, can limit manufacturers' ability to rapidly scale production in response to demand fluctuations. The quota allocation process typically occurs on an annual cycle, creating delays when supply-demand mismatches emerge.

Manufacturing Concentration

The generic Phenobarbital market has consolidated significantly. With limited manufacturers, any production disruption — whether from facility maintenance, FDA inspection findings, or raw material sourcing issues — can create outsized market impact. The active pharmaceutical ingredient (API) supply chain for Phenobarbital relies on a limited number of global suppliers, adding an additional layer of vulnerability.

Dual Human-Veterinary Demand

Phenobarbital occupies a unique position as a high-volume veterinary medication, particularly for canine epilepsy management. Human and veterinary formulations share API supply chains and, in some cases, finished product manufacturers. Demand spikes in the veterinary market can directly impact availability for human patients.

Clinical Implications for Patient Management

Risk of Abrupt Discontinuation

The most critical clinical concern during supply disruptions is the risk of abrupt Phenobarbital discontinuation. Given Phenobarbital's long half-life (53-118 hours in adults) and significant physiological dependence potential, abrupt cessation can precipitate:

• Breakthrough seizures, including status epilepticus
• Barbiturate withdrawal syndrome (anxiety, tremor, diaphoresis, tachycardia, seizures, delirium)
• Potentially life-threatening autonomic instability

Proactive identification of patients at risk of supply gaps is essential. Consider contacting patients on chronic Phenobarbital therapy to assess their medication supply and develop contingency plans.

Therapeutic Alternatives

When Phenobarbital is unavailable, alternative agent selection should consider the patient's seizure type, comorbidities, concurrent medications, and the anticipated duration of unavailability.

For Seizure Prophylaxis

• Levetiracetam (Keppra): Broad-spectrum efficacy, minimal drug interactions, no hepatic enzyme induction. Consider as first-line alternative for most patients. Monitor for behavioral side effects.
• Valproic Acid/Divalproex (Depakote): Broad-spectrum efficacy. Caution in women of childbearing potential (teratogenicity), hepatic disease, and thrombocytopenia. Inhibits CYP2C9 — review drug interactions.
• Lamotrigine (Lamictal): Broad-spectrum with favorable side effect profile. Requires slow titration (risk of Stevens-Johnson syndrome). Significant interaction with Valproic Acid.
• Carbamazepine (Tegretol): Effective for focal seizures. CYP3A4 inducer — similar interaction profile to Phenobarbital. HLA-B*1502 screening recommended in appropriate populations.

For Neonatal Seizures

Phenobarbital remains the standard first-line agent for neonatal seizures. When unavailable, Levetiracetam has emerging evidence supporting its use in this population, though data are more limited. Consult neonatology and pediatric neurology for individualized management.

For Alcohol/Benzodiazepine Withdrawal

If using Phenobarbital-based protocols for withdrawal management, alternative benzodiazepine-based protocols (e.g., symptom-triggered Diazepam or Chlordiazepoxide) are well-established alternatives with robust evidence.

Cross-Tapering Considerations

When transitioning patients from Phenobarbital to an alternative anticonvulsant:

1. Initiate the replacement agent at therapeutic doses while maintaining current Phenobarbital dosing
2. Once the replacement agent reaches steady state, begin gradual Phenobarbital taper (typically 10-25% reduction every 1-2 weeks)
3. Monitor seizure frequency and withdrawal symptoms throughout the taper
4. Obtain drug levels as clinically indicated (Phenobarbital therapeutic range: 15-40 mcg/mL)
5. Increase monitoring frequency during the transition period

Strategies for Maintaining Patient Access

Prescribing Flexibility

• Consider prescribing alternative strengths when a patient's usual strength is unavailable (e.g., two 30 mg tablets instead of one 60 mg tablet)
• The oral elixir (20 mg/5 mL) may serve as an alternative when tablets are unavailable, though palatability and dosing precision should be discussed
• Prescribe 90-day supplies when clinically appropriate and permitted by payer and state regulations

Pharmacy Coordination

• Direct patients to MedFinder for Providers to assist with real-time pharmacy availability searches
• Develop relationships with specialty pharmacies and compounding pharmacies that may have more reliable Phenobarbital supply
• Hospital outpatient pharmacies may stock Phenobarbital when community pharmacies do not

Patient Communication

Proactive communication is critical. Consider:

• Identifying all patients in your panel on chronic Phenobarbital therapy
• Providing written guidance on what to do if they cannot fill their prescription
• Establishing clear protocols for after-hours supply emergencies
• Directing patients to educational resources: Phenobarbital Shortage Update for Patients and How to Find Phenobarbital in Stock

Reporting and Advocacy

Clinicians can play an active role in shortage mitigation:

• Report shortages to the FDA: Use the FDA Drug Shortage Reporting system to document supply gaps you observe
• Contact the DEA: If quotas appear to be limiting supply, clinician advocacy to the DEA regarding quota adequacy can influence allocation decisions
• Engage with professional societies: AES, AAN, and ASHP regularly advocate for shortage mitigation policies

Additional Resources for Your Practice

• How to Help Your Patients Find Phenobarbital in Stock: A Provider's Guide
• How to Help Patients Save Money on Phenobarbital
• Alternatives to Phenobarbital (patient-facing — share with patients)
• MedFinder for Providers

Summary

Phenobarbital supply vulnerabilities require prescribers to maintain heightened vigilance and proactive patient management strategies. The key priorities are: (1) preventing abrupt discontinuation, (2) having individualized contingency plans for chronic Phenobarbital patients, (3) leveraging tools like MedFinder to locate available supply, and (4) facilitating safe transitions to alternative agents when necessary. By staying informed and planning ahead, clinicians can minimize the clinical impact of Phenobarbital supply disruptions on their patients.