Can Patients with Acute Intermittent Porphyria Receive Ajovy (Fremanezumab)?
Yes, patients with acute intermittent porphyria can receive Ajovy (fremanezumab) injection, as this monoclonal antibody targeting CGRP is not metabolized through hepatic cytochrome P450 pathways and does not induce heme synthesis, making it safe for porphyria patients.
Rationale for Safety
The critical concern in acute intermittent porphyria is avoiding medications that induce hepatic ALAS1 (aminolevulinic acid synthase-1), which increases production of neurotoxic porphyrin precursors ALA and PBG 1. Drugs that precipitate attacks typically do so by:
- Inducing hepatic cytochrome P450 enzymes, which increases heme demand 1
- Directly inducing ALAS1 through various mechanisms 2
- Depleting hepatic free heme pools 1
Fremanezumab is a fully humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP). As a large protein molecule (approximately 148 kDa), it is not hepatically metabolized through cytochrome P450 pathways and does not interact with heme biosynthesis 1, 2.
Key Safety Principles in AIP
When evaluating any medication for AIP patients, the primary considerations are 1, 3:
- Avoid drugs that induce hepatic enzymes (barbiturates, sulfonamides, certain anticonvulsants like phenytoin and carbamazepine)
- Avoid drugs that increase heme demand through hepatic metabolism
- Prefer drugs with minimal hepatic metabolism or those metabolized through non-P450 pathways
Monoclonal Antibodies in Porphyria
Monoclonal antibodies as a drug class have several characteristics that make them inherently safe in porphyria 4:
- They are catabolized into amino acids through proteolytic degradation, not hepatic metabolism
- They do not induce cytochrome P450 enzymes
- They do not affect heme biosynthesis pathways
- They do not deplete hepatic heme pools
Cyclosporine, another immunosuppressive agent, has been successfully used in AIP patients despite initial concerns, demonstrating that immunomodulatory therapies can be safe when they don't affect heme synthesis 4.
Clinical Considerations
While fremanezumab is safe from a porphyria standpoint, clinicians should still 1, 3:
- Ensure proper AIP diagnosis with elevated urinary PBG (>10 times upper limit of normal during attacks) 1
- Counsel patients on avoiding known triggers (fasting, alcohol, smoking, hormonal changes) 1, 5
- Monitor for chronic complications including hypertension and renal dysfunction, which occur in AIP patients 3
- Maintain baseline monitoring with CBC, ferritin, metabolic panel, and liver function tests 6, 3
Important Caveats
If the patient is experiencing an acute porphyric attack, the priority is immediate treatment with intravenous hemin and dextrose, not initiating preventive migraine therapy 3, 2. Fremanezumab should be administered during remission periods when the patient is biochemically stable 1, 3.
For women with AIP and migraines, hormonal fluctuations may trigger both conditions, so fremanezumab may provide dual benefit by preventing migraines without risking porphyric attacks 5, 3.