Over 50 medications may trigger porphyria attacks, study finds
Work drew on database collecting reports of problems with treatments
By combing through a database from the U.S. Food and Drug Administration (FDA), scientists in China have compiled a list of more than 50 medications that can trigger porphyria attacks.
Their findings were reported in the study, “Drug-associated porphyria: a pharmacovigilance study,” published in the Orphanet Journal of Rare Diseases.
A group of genetic disorders, porphyrias are due to the body not being able to efficiently produce heme, a molecule needed for oxygen transport. With disruptions in heme production, intermediary molecules known as porphyrins build to toxic levels and ultimately drive porphyria symptoms.
Medications are a known trigger of porphyria attacks
Porphyrinogenic drugs are medications that can trigger porphyria attacks or flares, because they either directly or indirectly affect the biological pathways involved in porphyrin production. Giving a porphyrinogenic drug to someone with porphyria can result in life-threatening complications, so it’s crucial to be aware of which medications are porphyrinogenic to avoid their use in porphyria patients.
“Patients who experience drug-induced porphyria generally have bad outcomes. Hence, considerable care must be taken to ensure that carriers of acute porphyria genetic mutations are not prescribed porphyrinogenic drugs,” the researchers wrote.
To some degree, the porphyrinogenic capacity of a particular medication can be predicted based on its pharmacological properties. However, this only tells part of the story. To fully assess the porphyrinogenic capacity of different medications, it’s necessary to consider clinical data from people.
The FDA’s Adverse Event Reporting System, known as FAERS, is a database where clinicians and patients can report adverse reactions and side effects they come across or experience, and which they believe are related to the use of specific medications. More than half of all reports, 52.8%, originated in the U.S., France, and Spain.
Researchers, all with the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, combed through hundreds of porphyria-related reports in FAERS concerning more than 400 drugs, using multiple algorithms to assess the porphyrinogenic potential of these medications.
They ultimately came up with a list of 52 medications found to have porphyrinogenic capacity based on the four algorithms that were used.
Medications to treat or prevent infections often were noted
Medications taken to prevent or treat infections accounted for the majority of the reports (27.7%), followed by cancer or immune therapies (15.8%). Medications that affect the digestive and nervous systems each accounted for more than 10% of the cases.
Five medications that were associated with the highest number of porphyria-related reports included givosiran (sold as Givlaari), which is used to treat acute hepatic porphyria attacks; the antiviral agent ribavirin (sold as Virazole); the cancer therapy imatinib (sold as Gleevec); the nonsteroidal anti-inflammatory drug diclofenac (sold as Zipsor and others); and the diuretic furosemide (sold as Lasix and others), which is used to treat swelling associated with heart disease and to control blood pressure.
“The analysis of FAERS reports provides critical information on drug porphyrogenicity, allowing rational and evidence-based drug prescription and improving the accuracy of predicted porphyrogenicity by model algorithms,” the researchers wrote.
They noted, however, that the database has limitations, such as the potential for false or incomplete reporting, so the findings should be interpreted with appropriate caution.
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