Source: Health Products and Food Branch (CA) Revision Year: 2018
PANHEMATIN is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see Dosage Forms, Strengths, Composition and Packaging.
There are insufficient data available for a long term use of PANHEMATIN for prevention.
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).
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 Canada Inc. at 905-827-1300.
See Part II: Scientific Information – Non-Clinical Toxicology.
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.
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.
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.
The available human data is not sufficient to assess the risks of PANHEMATIN during pregnancy. 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 (see Warnings and Precautions).
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for PANHEMATIN and any potential adverse effects on the breastfed child from PANHEMATIN or from the underlying maternal condition.
Pediatrics (<16 years of age): Safety and effectiveness in pediatric patients under 16 years of age have not been established.
Geriatrics (≥65 years of age): Clinical data for subjects aged 65 and over was not sufficient to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
The most common adverse reactions (occurring in >1% of patients) are: headache, pyrexia, infusion site reactions, and phlebitis.
Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.
The safety of PANHEMATIN use was evaluated in a compassionate use study. A total of 130 patients were treated with hemin for acute attacks, prophylaxis or both. Of those, 111 patients were administered hemin for treatment of 305 acute porphyria attacks and to 40 patients for prophylaxis. The majority (92%) of patients were Caucasian. Most (72%) were female; all adult patients had a mean age ± SD of 40.3 ± 12.3 years. Proportionally more females (15 out of 19) received prophylaxis or a combination of acute treatment and prophylaxis (19 out of 21). For the treatment of acute attacks, patients received 2 to 4 mg/kg/day PANHEMATIN intravenously for 1 to 9 doses. For prophylaxis patients, the most common doses were weekly or biweekly infusions. Table 3 summarizes adverse reactions occurring in >1% of patients treated with PANHEMATIN, categorized by body system and order of decreasing frequency.
Table 3. Adverse Reactions in >1% of Patients Treated with PANHEMATIN:
| System Organ Class Preferred Term | Adverse Events N (% of Total Adverse Events) | |
|---|---|---|
| Description | Total | Possibly or Probably Related to Treatment |
| Infections and infestations | ||
| Cellulitis | 3 (1.5%) | 2 (1.0%) |
| Nervous System Disorders | ||
| Headache | 18 (9.2%) | 5 (2.6%) |
| Vascular Disorders | ||
| Phlebitis/Injection site phlebitis | 7 (3.6%) | 6 (3.1%) |
| Skin and subcutaneous tissue disorders | ||
| Rash | 3 (1.5%) | 3 (1.5%) |
| General Disorders and Administration Site Conditions | ||
| Pyrexia | 9 (4.6%) | 6 (3.1%) |
| Catheter-related Complication | 7 (3.6%) | 3 (1.5%) |
Note: In this study, the actual content of drug in the supplied vials ranged from 64.4% to 88.2% of the labelled content. Therefore, the actual amount of drug given to the patients was less than the calculated dose.
The following adverse reactions associated with the use of PANHEMATIN were identified in open-label clinical trials or postmarketing reports. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure.
Blood and Lymphatic System Disorders: thrombocytopenia, coagulopathy (including prolonged prothrombin time and prolonged partial thromboplastin time), and hemolysis
Immune System Disorders: hypersensitivity reactions including a report of infusion-related anaphylactoid reaction presenting as circulatory collapse
Vascular Disorders: injection site venous thrombosis including some that occurred in large veins such as venae cavae.
General Disorders and Administration Site Conditions: infusion site reactions (such as erythema, pain, bleeding and extravasation)
Metabolism and Nutrition Disorders: iron overload and serum ferritin increased (see Warnings and Precautions).
PANHEMATIN therapy is intended to limit the rate of porphyria/heme biosynthesis possibly by inhibiting the enzyme δ-aminolevulinic acid synthase 1 (ALAS1) (see Action and Clinical Pharmacology). 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.
Interactions with other drugs have not been established.
Interactions with food have not been established.
Interactions with herbal products have not been established.
Interactions with laboratory tests have not been established.
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