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

For clinicians managing patients with acute hepatic porphyria (AHP), Givlaari (givosiran) represents the most significant therapeutic advance in decades. Yet prescribing it and getting it to patients remains an operationally demanding process. Insurance denials, step therapy requirements, mandatory monitoring, and the limited distribution network create barriers that delay treatment — sometimes for months.

This guide is written for prescribers: hematologists, hepatologists, gastroenterologists, metabolic disease specialists, and other clinicians involved in AHP management. It covers what's driving access challenges in 2026 and what you can do to get your patients the treatment they need.

Is There a Givlaari Supply Shortage?

Givlaari is not listed on the FDA's official Drug Shortages Database. Alnylam Pharmaceuticals continues to manufacture and distribute givosiran through its limited distribution network (McKesson as specialty distributor; CVS Specialty and Accredo as specialty pharmacies). The manufacturing supply appears stable.

The access challenges your patients face are systemic — driven by cost (list price ~$575,000/year), mandatory prior authorization, step therapy requirements, and the rarity of AHP expertise. Resolving these requires clinical advocacy from prescribers, not calls to manufacturing.

What Payer Criteria Do Your Patients Need to Meet?

Across major payers (Aetna, UnitedHealthcare, Cigna, Humana, BCBS), the criteria for Givlaari approval are largely consistent:

• Patient is ≥ 18 years of age
• Confirmed diagnosis of AHP (AIP, VP, HCP, or ADP) via biochemical testing (elevated urine ALA and/or PBG) and/or molecular confirmation
• Active disease: ≥ 2 documented porphyria attacks in the prior 6 months requiring hospitalization, urgent healthcare visit, or IV hemin administration (some payers require ≥ 4/year)
• Prescribed by or in consultation with a specialist (hematologist, hepatologist, gastroenterologist, or geneticist)
• Patient agreement to avoid known AHP triggers (alcohol, fasting, certain medications including barbiturates, sulfa antibiotics, and most anti-epileptics)

Step Therapy: What You Need to Document

Many payers (particularly Humana, UnitedHealthcare, and some BCBS plans) require documented prior hemin therapy before approving Givlaari. Your prior authorization letter should address this explicitly:

• Document prior hemin use including dates, doses, frequency, and clinical response
• Document reasons hemin is inadequate for your patient (ongoing attacks despite prophylactic hemin, vein access issues, coagulopathy, or quality-of-life burden)
• If hemin prophylaxis was never tried: document clinical reasons (e.g., vein access complications, patient preference for subcutaneous route, risk of repeated IV access)

Monitoring Requirements: Clinical and Regulatory

Prescribers must monitor patients closely on Givlaari. The FDA label requires:

• Liver function tests (ALT/AST) at baseline and monthly for the first 6 months; then as clinically indicated. ALT elevations ≥ 3x ULN occurred in 15% of patients in clinical trials.
• Kidney function monitoring (serum creatinine and eGFR). Renal toxicity has been observed.
• Homocysteine levels — Givlaari can elevate homocysteine; supplementation with B6 or a multivitamin may be indicated.
• If ALT is ≥ 3x-5x ULN: consider withholding dose and rechecking in 2 weeks. If ≥ 5x ULN or clinical evidence of liver injury: discontinue.

Payers also require these labs for annual renewal — maintaining monitoring is critical not just clinically but to preserve coverage.

Drug Interactions: The CYP1A2 and CYP2D6 Problem

Givlaari's mechanism — reducing hepatic ALAS1 — also depletes hepatic cytochrome P450 (CYP) enzymes. This creates clinically important drug interactions. Givlaari significantly increases plasma concentrations of:

• CYP1A2 substrates: caffeine AUC increased 3.1-fold, Cmax 1.3-fold. Avoid sensitive CYP1A2 substrates including theophylline, clozapine, olanzapine, alosetron, tizanidine.
• CYP2D6 substrates: dextromethorphan AUC increased 2.4-fold, Cmax 2-fold. Avoid sensitive CYP2D6 substrates including aripiprazole, brexpiprazole, atomoxetine, amitriptyline. Givosiran has serious interactions with at least 87 other drugs.

Before initiating Givlaari, conduct a comprehensive medication reconciliation. Dose adjustments or substitutions may be necessary for CYP1A2 and CYP2D6 substrates currently in your patient's regimen.

Alnylam Assist®: A Key Resource for Prescribers

Alnylam Assist® offers prescriber-focused support including prior authorization guidance, site of care identification, and patient financial assistance. Key resources include:

• Fax the completed Givlaari Start Form to 1-833-256-2747 to initiate the access process
• Patient Education Liaisons (PELs) available for patient/caregiver education
• Bridge Program: free Givlaari while PA is pending for eligible patients
• Patient Assistance Program: free drug for eligible uninsured patients meeting financial criteria

medfinder: Supporting Your Patients Between Appointments

Consider directing your AHP patients to medfinder for providers. medfinder contacts specialty pharmacies and clinical sites on behalf of your patients to locate where their Givlaari can be ordered and administered — reducing the logistical burden on your office staff and ensuring patients don't miss doses due to site-of-care availability issues.

Clinical Bottom Line

Givlaari is not in a supply shortage, but the access landscape remains challenging for prescribers and patients alike. The most successful strategies involve robust PA documentation, early specialist referral, proactive renewal management, and close coordination with Alnylam Assist®. See our companion provider guide: How to help your patients find Givlaari in stock.