Panhematin

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.

• • Before administering PANHEMATIN, consider an appropriate period of carbohydrate loading (i.e., 400 g glucose/day for 1 to 2 days)
  [See Dosage and Administration (

  2.1 Dosing

  • •PANHEMATIN should only be used by or in consultation with physicians experienced in the management of porphyrias.
  • •Before PANHEMATIN therapy is begun, the presence of acute porphyria must be diagnosed using the following criteria:
  • 1.000000000000000e+00Presence of clinical symptoms suggestive of acute porphyric attack.
  • 2.000000000000000e+00Quantitative measurement of porphobilinogen (PBG) in urine. The single-void urine sample should be refrigerated or frozen without additives and shielded from light for subsequent quantitative δ-aminolevulinic acid (ALA), PBG, and total porphyrin determinations. (Note: the classical Watson-Schwartz or Hoesch tests are considered to be less reliable).
  • •Clinical benefit from PANHEMATIN depends on prompt administration. For mild porphyric attacks (mild pain, no vomiting, no paralysis, no hyponatremia, no seizures), a trial of glucose therapy is recommended while awaiting hemin treatment or if hemin is unavailable. For moderate to severe attacks, immediate hemin treatment is recommended. Symptoms of severe attacks are severe or prolonged pain, persistent vomiting, hyponatremia, convulsion, psychosis, and neuropathy. In addition to treatment with PANHEMATIN, consider other necessary measures such as the elimination of triggering factors.
  • •The dose of PANHEMATIN is 1 to 4 mg/kg/day of hematin for 3 to 14 days based on the clinical signs. The standard dose in clinical practice is 3 to 4 mg/kg/day. In more severe cases this dose may be repeated no earlier than every 12 hours. Do not exceed 6 mg/kg of hematin in any 24 hour period. After reconstitution each mL of PANHEMATIN contains the equivalent of approximately 7 mg of hematin (see dosage calculation tablebelow).

  Dosage Calculation Table

  1 mg hematin equivalent = 0.14 mL PANHEMATIN

  2 mg hematin equivalent = 0.28 mL PANHEMATIN

  3 mg hematin equivalent = 0.42 mL PANHEMATIN

  4 mg hematin equivalent = 0.56 mL PANHEMATIN

  • •Monitor urinary concentrations of the following compounds during PANHEMATIN therapy. Effectiveness is demonstrated by a decrease in one or more of the following compounds.
    
    ALA - δ-aminolevulinic acid
    
    PBG - porphobilinogen
    
    Uroporphyrin
    
    Coproporphyrin

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• • 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.

PANHEMATIN is available as a sterile, lyophilized black powder in single dose dispensing vials. Each vial contains the equivalent of 350 mg hemin, 240 mg sodium carbonate and 335 mg of sorbitol. When mixed as directed with Sterile Water for Injection, USP, each 48 mL provides the equivalent of approximately 336 mg hematin (7 mg/mL).

About 50% of the women with acute intermittent porphyria experience an acute attack of porphyria in pregnancy and/or the puerperium. It is most severe in early pregnancy and the puerperium, and can result in fatal outcome. Although anecdotal evidence suggests safe use of hematin during pregnancy, the available human data is not sufficient to establish the presence or absence of drug-associated risk. Animal reproduction studies have not been conducted with hematin. It is also not known whether hematin can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. PANHEMATIN should be given to a pregnant woman only if clearly needed.

Avoid administering hematin in severe pre-eclampsia because of a theoretical risk of potentiation of the coagulation disorder

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

• • Phlebitis is possible. Utilize a large arm vein or a central venous catheter for administration to minimize the risk of phlebitis. (
  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 ]
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• • Elevated iron and serum ferritin may occur. Monitor iron and serum ferritin in patients receiving multiple administrations of PANHEMATIN. (
  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 ]

  . In case of elevated iron or serum ferritin levels, consider iron chelation therapy.
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• • PANHEMATIN has transient and mild anticoagulant effect. Avoid concurrent anticoagulant 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.
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• • 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 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.
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• • PANHEMATIN may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. (
  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.
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