Hematin (panhematin ®)

HEMATIN (PANHEMATIN ®)

Usual Diluents

Standard Dilutions [Amount of drug] [Infusion volume] [Infusion rate]

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.

Key points:
•Because PANHEMATIN contains no preservative and undergoes rapid chemical decomposition in solution, it must be reconstituted immediately before use.

•Reconstitute PANHEMATIN by aseptically adding 48 mL of Sterile Water for Injection, USP, to the dispensing vial. Shake the vial well for a period of 2 to 3 minutes to aid dissolution.

•PANHEMATIN may be administered directly from the vial. After the first withdrawal from the vial, discard any solution remaining.

•Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. 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.

•Do not add other drug or chemical agent to a PANHEMATIN fluid admixture.

•Infuse the dose over a period of at least 30 minutes via a separate line.

•After the infusion, flush the vein with 100 mL of 0.9% NaCl.

Additional information - Revision date 7/2017

INDICATIONS AND USAGE
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) [ See Dosage and Administration (2.1)].

•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.

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

DOSAGE AND ADMINISTRATION
For intravenous infusion only.

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. Presence of clinical symptoms suggestive of acute porphyric attack.
2. Quantitative 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 d-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 table below).

•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 - d-aminolevulinic acid
PBG - porphobilinogen
Uroporphyrin
Coproporphyrin

Preparation and Administration

•Because PANHEMATIN contains no preservative and undergoes rapid chemical decomposition in solution, it must be reconstituted immediately before use.

•Reconstitute PANHEMATIN by aseptically adding 48 mL of Sterile Water for Injection, USP, to the dispensing vial. Shake the vial well for a period of 2 to 3 minutes to aid dissolution.

•PANHEMATIN may be administered directly from the vial. After the first withdrawal from the vial, discard any solution remaining.

•Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. 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.

•Do not add other drug or chemical agent to a PANHEMATIN fluid admixture.

•Infuse the dose over a period of at least 30 minutes via a separate line.

•After the infusion, flush the vein with 100 mL of 0.9% NaCl.

DOSAGE FORMS AND STRENGTHS

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).

HOW SUPPLIED/STORAGE AND HANDLING
PANHEMATIN is supplied as a sterile, lyophilized black powder in single dose dispensing vials (NDC 55292-702-54) in a carton (NDC 55292-702-55).

The vial stopper contains natural rubber latex.

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

Manufactured by:
Xellia Pharmaceuticals USA, LLC
Raleigh, NC 27616

For:
Recordati Rare Diseases Inc.
Lebanon, NJ 08833, U.S.A.

U.S. Lic. No. 1899

RECORDATI RARE DISEASES GROUP

Panhematin® is a registered trademark of Recordati Rare Diseases Inc.

750-09241
Revised: 7/2017