HEMIN Drug Interactions: What You Need to Know

INTERACTIONS PANHEMATIN therapy is intended to limit the rate of porphyria/heme biosynthesis possibly by inhibiting the enzyme δ-aminolevulinic acid synthetase 1 (ALAS1) [See Clinical Pharmacology ( 12.1 )] . Most of the heme synthesized in liver is used for the production of cytochrome P450 (CYP) enzymes. Therefore, avoid CYP inducing drugs (such as estrogens, barbituric acid derivatives and steroid metabolites) while on PANHEMATIN therapy, because these drugs increase the activity of ALAS leading to induction of ALAS1 through a feedback mechanism. Avoid CYP inducing drugs such as estrogens, barbituric acid derivatives and steroid metabolites which induce δ-aminolevulinic acid synthetase 1 (ALAS1) through a feedback mechanism. ( 7 )

PANHEMATIN is contraindicated in patients with known hypersensitivity to this drug. Do not use in patients with known hypersensitivity to PANHEMATIN. ( 4 )

AND PRECAUTIONS

• Phlebitis is possible. Utilize a large arm vein or a central venous catheter for administration to minimize the risk of phlebitis. ( 5.1 )
• Elevated iron and serum ferritin may occur. Monitor iron and serum ferritin in patients receiving multiple administrations of PANHEMATIN. ( 5.2 )
• PANHEMATIN has transient and mild anticoagulant effect. Avoid concurrent anticoagulant therapy. ( 5.3 )
• Reversible renal shutdown has been observed with an excessive hematin dose (12.2 mg/kg in a single infusion). Strictly follow recommended dosage guidelines. ( 5.4 )
• PANHEMATIN may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. ( 5.5 )

5.1 Risk of Phlebitis A large arm vein or a central venous catheter should be utilized for the administration of PANHEMATIN to minimize the risk of phlebitis. Since reconstituted PANHEMATIN is not transparent, any undissolved particulate matter is difficult to see when inspected visually. Therefore, terminal filtration through a sterile 0.45 micron or smaller filter is recommended. [See Dosage and Administration ( 2.2 )]

5.2 Iron and Serum Ferritin Because increased levels of iron and serum ferritin have been reported in post-marketing experience, physicians must monitor iron and serum ferritin in patients receiving multiple administrations of PANHEMATIN [See Adverse Reactions ( 6.2 )] . In case of elevated iron or serum ferritin levels, consider iron chelation therapy.

5.3 Anticoagulant Effects Because PANHEMATIN has exhibited transient, mild anticoagulant effects during clinical studies, avoid concurrent anticoagulant therapy. The extent and duration of the hypocoagulable state induced by PANHEMATIN has not been established.

5.4 Renal Effects Recommended dosage guidelines should be strictly followed. Reversible renal shutdown has been observed in a case where an excessive hematin dose (12.2 mg/kg) was administered in a single infusion. Oliguria and increased nitrogen retention occurred although the patient remained asymptomatic. No worsening of renal function has been seen with administration of recommended dosages of hematin.

5.5 Transmissible Infectious Agents Because PANHEMATIN is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jacob disease (vCJD) agent, and theoretically the Creutzfeldt-Jacob disease (CJD) agent. The risk that this product may transmit an infectious agent has been reduced by screening blood donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating certain viruses. Despite these measures, this product can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in the product. All infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Recordati Rare Diseases at 1-888-575-8344.