PANHEMATIN (hemin for injection) is an enzyme inhibitor derived from processed red blood cells. Hemin for injection was known previously as hematin. The term hematin has been used to describe the chemical reaction product of hemin and sodium carbonate solution. Hemin is an iron containing metalloporphyrin. Chemically hemin is represented as chloro [7,12-diethenyl-3,8,13,17-tetramethyl-21H,23H-porphine-2,18-dipropanoato(2-)-N21,N22,N23,N24 ] iron. The structural formula for hemin is:
PANHEMATIN is a sterile, lyophilized powder suitable for intravenous administration after reconstitution. Each dispensing vial of PANHEMATIN contains the equivalent of 313 mg hemin, 215 mg sodium carbonate and 300 mg of sorbitol. The pH may have been adjusted with hydrochloric acid; the product contains no preservatives. When mixed as directed with Sterile Water for Injection, USP, each 43 mL provides the equivalent of approximately 301 mg hematin (7 mg/mL).
Heme acts to limit the hepatic and/or marrow synthesis of porphyrin. This action is likely due to the inhibition of [dgr ]-aminolevulinic acid synthetase, the enzyme which limits the rate of the porphyrin/heme biosynthetic pathway. The exact mechanism by which hematin produces symptomatic improvement in patients with acute episodes of the hepatic porphyrias has not been elucidated. 1,9
Following intravenous administration of hematin in non-jaundiced human patients, an increase in fecal urobilinogen can be observed which is roughly proportional to the amount of hematin administered. This suggests an enterohepatic pathway as at least one route of elimination. Bilirubin metabolites are also excreted in the urine following hematin injections. 2
PANHEMATIN (hemin for injection) therapy for the acute porphyrias is not curative. After discontinuation of PANHEMATIN treatment, symptoms generally return although in some cases remission is prolonged. Some neurological symptoms have improved weeks to months after therapy although little or no response was noted at the time of treatment.
Other aspects of human pharmacokinetics have not been defined.