Hematopoietic
PREGNANCY RECOMMENDATION: Limited Human Data—No Relevant Animal Data
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
Animal reproduction studies have not been conducted with hemin and there is only one report on its use in human pregnancy. The citations below, however, suggest that hemin has been used more frequently in pregnant women. The primary embryo or fetal risk from hemin appears to be from the transmission of viruses or other agents from a hemin-induced maternal infection or from a hemin-induced maternal adverse reaction (e.g., thrombocytopenia or coagulopathy). Therefore, the drug should not be withheld because of pregnancy.
FETAL RISK SUMMARY
The enzyme inhibitor hemin (previously known as hematin) limits the hepatic and/or marrow synthesis of porphyrin. It is indicated for the amelioration of recurrent attacks of acute intermittent porphyria that are temporally related to the menstrual cycle (1). Hemin is an iron molecule derived from human red blood cells. Although multiple steps have been taken to lessen the chance of blood-borne infection, a risk still exists for the transmission of infectious agents, such as viruses, and for the agent that causes Creutzfeldt-Jacob disease (1).
Reproduction studies in animals have not been conducted. It is not known if hemin can cross the human placenta to the fetus. As a natural constituent of human blood, it is unlikely that clinically significant amounts would cross to the fetal compartment.
A 1989 review summarized the prevalence, genetics, biochemistry, classification, and the treatment of acute intermittent porphyria (2). The authors also cited evidence that female hormones affect the onset and expression of the disease. Before an understanding of the disease and improved prenatal care were achieved, porphyria was associated with significant maternal mortality and poor pregnancy outcome (2). Although the authors did not specifically state that hemin treatment was indicated during pregnancy, they did state that patients with acute attacks should be hospitalized for symptomatic treatment. They also noted that treatment with hemin could shorten the duration of the attack and reduce its severity (2).
Earlier, a brief response to a question concerning porphyria and pregnancy hinted at the potential severity of this disease. The author, although noting the lack of information relating to the potential to cause adverse pregnancy outcomes, still recommended hematin therapy for an acute porphyric attack before considering termination of pregnancy (3). Responding to this recommendation, another author suggested that glucose infusions were safer and expressed concern that the anticoagulant effect of hemin could jeopardize a pregnancy (4). However, hemin was not thought to have a clinically significant anticoagulant effect at low doses and was indicated in pregnancy if glucose infusions were not effective in reversing the disease process (5).
A 34-year-old woman, in the 1st or 2nd month of pregnancy, was treated with hematin, 3 mg/kg/day administered as an IV infusion for 5 days, for an exacerbation of acute intermittent porphyria (6). A second IV infusion course, 1.5 mg/kg/day for 2 weeks, was started 41 days after the first course. No adverse fetal effects of the exposure were noted and the woman eventually delivered a healthy, 2570-g male infant at 39 weeks’ gestation. At follow-up, no evidence of porphyria was noted in the 5-year-old child (6).
A 1984 study investigated the effect of hematin on bilirubin binding (7). Cord blood of newborn infants with ABO hemolytic disease was thought to contain endogenous hematin, which could increase the risk of kernicterus. In an in vitro experiment, hematin was added to bilirubin-enriched cord blood and was found to have a significant adverse effect on bilirubin binding. However, the high concentrations required were not physiologic and, thus, were not thought to have clinical significance for infants with ABO-isoimmune hemolysis (7).
A 2010 review of the treatment of acute intermittent porphyria in pregnancy concluded that although the available information was limited, hemin could be safely given in pregnancy (8).
BREASTFEEDING SUMMARY
No reports describing the use of hemin during lactation have been located. Hemin is an enzyme inhibitor that is derived from human red blood cells. It is doubtful if hemin is excreted in milk but even if small amounts were excreted, they would be digested in the infant’s gut.
References
1.Product information. Panhematin. Ovation Pharmaceuticals, 2004.
2.Kanaan C, Veille JC, Lakin M. Pregnancy and acute intermittent porphyria. Obstet Gynecol Surv 1989;44:244–9.
3.Bissell DM. Acute intermittent porphyria and pregnancy. JAMA 1985; 252:1457.
4.Loftin EB III. Hematin therapy in acute porphyria. JAMA 1985;254:613.
5.Bissell DM. In reply: hematin therapy in acute porphyria. JAMA 1985;254:1457.
6.Wenger S, Meisinger V, Brücke T, Deecke L. Acute porphyric neuropathy during pregnancy—effect of haematin therapy. Eur Neurol 1998;39:187–8.
7.Kirk JJ, Ritter DA, Kenny JD. The effect of hematin on bilirubin binding in bilirubin-enriched neonatal cord serum. Biol Neonate 1984;45:53–7.
8.Farfaras A, Zagouri F, Zografos G, Kostopoulou A, Sergentanis N, Antoniou S. Acute intermittent porphyria in pregnancy: a common misdiagnosis. Clin Exp Obstet Gynecol 2010;37:256–60.