Hemin

PANHEMATIN is a hemin for injection indicated for the amelioration of recurrent attacks of acute intermittent porphyria temporally related to the menstrual cycle in susceptible women, after initial carbohydrate therapy is known or suspected to be inadequate. Limitations of Use • Before administering PANHEMATIN, consider an appropriate period of carbohydrate loading (i.e., 400 g glucose/day for 1 to 2 days). • Attacks of porphyria may progress to a point where irreversible neuronal damage has occurred. PANHEMATIN therapy is intended to prevent an attack from reaching the critical stage of neuronal degeneration. PANHEMATIN is not effective in repairing neuronal damage.

Heme acts to limit the hepatic and/or marrow synthesis of porphyrin. This action is likely due to the inhibition of δ-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. PANHEMATIN 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.

For intravenous infusion only. Dose 1 to 4 mg/kg/day for 3 to 14 days based on the clinical signs. The standard dose in clinical practice is 3 to 4 mg/kg/day. Repeat dose in more severe cases no earlier than every 12 hours. Do not exceed 6 mg/kg in any 24 hour period. Administration. Use sterile 0.45 micron or smaller filter to remove any undissolved particulate matter. The dose may be administered directly from the vial over a period of at least 30 minutes. After the infusion, flush the vein with 100 mL of 0.9% NaCl.

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

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

The most common adverse reactions (occurring in >1% of patients) are: headache, pyrexia, infusion site reactions, and phlebitis. Most common adverse reactions in >1% of patients are headache, pyrexia, infusion site reactions, and phlebitis.

PANHEMATIN therapy is intended to limit the rate of porphyria/heme biosynthesis possibly by inhibiting the enzyme δ-aminolevulinic acid synthetase 1 (ALAS1). 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.

Store lyophilized powder at 20-25°C (68-77°F).