PANHEMATIN Powder for reconstitution for injection Ref.[50408] Active ingredients: Hemin

3.1 Dosing Considerations

• 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 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.
• 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

3.2 Recommended Dose and Dosage Adjustment

The dose of PANHEMATIN is 0.8 to 3.1 mg/kg/day of hematin for 3 to 14 days based on the clinical signs. The standard dose in clinical practice is 2.3 to 3.1 mg/kg/day. In more severe cases this dose may be repeated no earlier than every 12 hours. Do not exceed 4.6 mg/kg of hematin in any 24 hour period. After reconstitution each mL of PANHEMATIN contains the equivalent of approximately 5.4 mg of hematin (see dosage calculation table below).

Health Canada has not authorized an indication for pediatric use.

3.3 Administration

• For intravenous infusion only.
• 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.
• 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.

3.4 Reconstitution

Parenteral Products: 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.

Table 1. Reconstitution:

• Because PANHEMATIN contains no preservative and undergoes rapid chemical decomposition in solution, it must be reconstituted immediately before use.
• Do not add other drug or chemical agent to a PANHEMATIN fluid admixture.

Reversible renal shutdown has been observed in a case where an excessive hematin dose (12.2 mg/kg) was administered in a single infusion (see Warnings and Precautions). Treatment of this case consisted of ethacrynic acid and mannitol.

For management of a suspected drug overdose, contact your regional poison control centre.

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