Recommendations for Hemin Preparation and Infusion

What's UP Doc?
Written By Dr. Herbert Bonkovsky

What's UP Doc? Is a regular column where we feature a patient question along with a response from a member of the UPA Scientific Advisory Board.

Is there any way to make hemin infusions more comfortable? 

Today’s answer comes from Dr. Karl Anderson of University of Texas Medical Branch in Galveston, TX and Dr. Herbert Bonkovsky at Atrium Health Wake Forest Baptist in North Carolina.

Hemin is used to treat or prevent acute attacks of the hepatic porphyrias, AIP, HCP, VP and ADP. Administration of hemin can cause inflammation and pain where it is being infused and increase the risk of blood clots. The way that hemin is prepared and delivered can reduce the risk of side effects like clotting and inflammation. 

Hemin is available in the US and some other countries as heme hydroxide, also known as hematin (Panhematin™, Recordati Rare Diseases), and is provided in a vial as a lyophilized (freeze-dried) powder that needs to be reconstituted into a liquid solution before infusion.  

The FDA-approved method for reconstituting Panhematin, as described in the package insert that comes with the treatment, is to add sterile water to the vial before it is infused by vein.  Experience has found that hematin is unstable after dilution with water, and degrades relatively quickly into products that bind to veins and clotting factors, causing inflammation- especially if the infusion is into a small vein.  It has been found that reconstitution with albumin stabilizes hematin and helps prevent these complications.  Detailed instructions for using albumin by Anderson et al (see resources below) are based on limited published experience.  This method has been adopted by many centers, but is considered “off-label” because approval by the FDA has not been obtained. 

In a number of other countries hemin is available as heme arginate (Normosang™), which is supplied as a concentrated solution to be diluted with normal saline prior to infusion.  Although Normosang is more stable, varying amounts of albumin are sometimes added prior to infusion.

Experienced porphyria centers also recommend that hemin be infused into a central or large peripheral vein with a high blood flow rate to further reduce the chance of infusion site phlebitis (vein inflammation).  Central vein access is through a port or PICC line.  

After reconstitution with albumin using the instructions included in this response, the hemin dose should be infused over one hour.  It is likely that hemin is stable for longer than one hour after reconstitution with albumin, but this has not been studied.    

Resources for your medical team

  • Detailed guidance for your medical team on reconstitution of hematin with albumin
    Reconstitution of Hematin for Intravenous Infusion | Annals of Internal Medicine (acpjournals.org) 

    Anderson KE, Bonkovsky HL, Bloomer JR, Shedlofsky SI. Reconstitution of hematin for intravenous infusion. Ann Int Med 144: 537-538, 2006. 

  • Detailed FDA-approved information on Panhematin: www.Panhematin.com

Disclaimer

What’s UP Doc? is not intended as medical guidance for individual patients. Any individual care decisions should be made in consultation with your healthcare team. Please contact United Porphyrias to locate a physician in your area, to provide information about porphyria to a current physician, to advise about referral to a specialized porphyria center, or to arrange a peer-to-peer consult between your physician and a porphyria specialist, contact UPA at 800-868-1292 or info@porphyria.org. 

Thank you to Dr. Anderson and Dr. Bonkovsky for this What's UP Doc? answer! Do you have a question for a porphyria expert? Send it to info@porphyria.org.

 

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Dr. Herbert Bonkovsky

Dr. Bonkovsky’s interest in the porphyrias began in medical school and was strengthened during his time studying under porphyria researcher D.P. Tschudy at the National Institutes of Health. Dr. Bonkovsky was among the first to show that hepatic porphyrin and heme synthesis is under the negative feedback regulatory control of heme itself, acting chiefly to down-regulate delta-aminolevulinic acid (ALA) synthase-1, the rate controlling enzyme for heme synthesis. This discovery was the basis for developing heme therapy for acute porphyria attacks, which is still today the treatment of choice for these life-threatening attacks. Dr. Bonkovsky was the first physician-investigator to purify heme and to administer it to a patient with severe acute intermittent porphyria.

Since that time, Dr. Bonkovsky has continued the search for new treatments for the porphyrias, administering clinical trials for potential new therapies at hospitals and medical centers in Massachusetts, Connecticut, and now at the Atrium Health--Wake Forest Baptist Medical Center in Winston-Salem, North Carolina. He is principal investigator of the Porphyria Center of Excellence at Wake Forest/NC Baptist Medical Center, which is a part of the Porphyrias Consortium of the USA, sponsored by the National Institute of Diabetes, digestive and Kidney Diseases and the National Center of Rare Diseases Research.

Dr. Bonkovsky also identified deficiency of ferrochelatase, the final enzyme in the heme synthetic pathway as the fundamental metabolic defect in EPP. Studies on the regulation of hepatic heme metabolism, especially the mechanisms and factors that regulate ALA synthase and heme oxygenase, have been the subject of a large number of studies, both in the basic research laboratory and the clinical research center during the past 50 years.

Dr. Bonkovsky has trained many medical students, residents, and sub-specialty fellows, especially in the fields of internal medicine, gastroenterology, and hepatology, as well as graduate students and junior faculty working on laboratory research.

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