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  • CLASSES

    Other Hematological Agents

    DEA CLASS

    Rx

    DESCRIPTION

    Also known as hematin; parenteral enzyme inhibitor used for acute intermittent porphyria (AIP); made from processed red blood cells.

    COMMON BRAND NAMES

    Panhematin

    HOW SUPPLIED

    Panhematin Intravenous Inj Pwd F/Sol: 313mg, 350mg

    DOSAGE & INDICATIONS

    For the treatment of recurrent attacks of acute intermittent porphyria related to the menstrual cycle or other patients† with acute intermittent porphyria, porphyria variegata†, or hereditary coproporphyria†.
    NOTE: Clinical benefits from hemin depend on prompt administration. Control of pain, hypertension, tachycardia, abnormal mental status, and mild to progressive neurologic signs may be achieved in patients with acute intermittent porphyria, porphyria variegata, or hereditary coproporphyria. Attacks of porphyria may progress to a point where irreversible neuronal damage has occurred. Hemin therapy is intended to prevent an attack from reaching the critical stage of neuronal degeneration; it does not repair neuronal damage.
    NOTE: Recommended dosage guidelines should be strictly followed.
    Intravenous infusion dosage
    Adults

    1 to 4 mg/kg/day IV over 10 to 15 minutes. Treatment usually continues for 3 to 14 days based on clinical signs. In more severe cases, the dose may be repeated no earlier than every 12 hours. Do not exceed 6 mg/kg/day. May consider hemin after an appropriate period of alternate therapy (i.e., 400 g glucose/day for 1 to 2 days). Monitor hemin therapy by a decrease in urinary concentrations of 1 or more of the following compounds: (delta)-aminolevulinic acid (ALA), uroporphyrinogen (UPG), porphobilinogen (PBG), or coproporphyrin.

    Adolescents 16 years and older

    1 to 4 mg/kg/day IV over 10 to 15 minutes. Treatment usually continues for 3 to 14 days based on clinical signs. In more severe cases, the dose may be repeated no earlier than every 12 hours. Do not exceed 6 mg/kg/day. May consider hemin after an appropriate period of alternate therapy (i.e., 400 g glucose/day for 1 to 2 days). Monitor hemin therapy by a decrease in urinary concentrations of 1 or more of the following compounds: (delta)-aminolevulinic acid (ALA), uroporphyrinogen (UPG), porphobilinogen (PBG), or coproporphyrin.

    MAXIMUM DOSAGE

    Adults

    6 mg/kg/day IV.

    Elderly

    6 mg/kg/day IV.

    Adolescents

     >= 16 years: 6 mg/kg/day IV.
     < 16 years: Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Reconstitution:
    Because hemin products contain no preservatives and undergo rapid chemical decomposition in solution, reconstitute immediately before use.
    Add 48 mL of Sterile Water for Injection to the dispensing vial.
    Shake well for 2 to 3 minutes to aid dissolution.
    After reconstitution, the concentration is approximately 7 mg/mL.
    Storage: After the first withdrawal from the vial, any remaining solution must be discarded.
     
    Intravenous infusion:
    The reconstituted drug may be administered directly from the vial.
    Inspection of reconstituted hemin injection solutions for undissolved particulate matter prior to administration is difficult since the solutions are not transparent. Terminal filtration through a sterile 0.45 micron or smaller filter is recommended.
    Do not add other drug or chemical agent to a hemin fluid admixture.
    A large arm vein or a central venous catheter should be utilized for administration to minimize the risk of phlebitis.
    Infuse over at least 30 minutes via a separate line.
    After infusion, flush the vein with 100 mL of 0.9% Sodium Chloride Injection.

    STORAGE

    Panhematin:
    - Discard unused portion. Do not store for later use.
    - Reconstituted product should be used immediately. Discard unused portion
    - Store unreconstituted product at 68 to 77 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Hemin is contraindicated in patients with known hemin hypersensitivity.

    Intramuscular administration, subcutaneous administration

    Hemin for injection is for intravenous administration via intravenous infusion only; do not give via intramuscular administration or subcutaneous administration.

    Infection, requires an experienced clinician, viral infection

    Because hemin is derived from human blood, it may carry a risk of transmitting infectious agents such as viruses, and theoretically, the Creutzfeldt-Jakob disease (CJB) agent. The risk that such products will transmit an infectious agent or cause infection has been reduced by screening blood donors for prior exposure to certain viruses, by testing for the presence of certain current viruses, and by inactivating certain viruses. Despite these measures, such products can still potentially transmit disease (e.g., viral infection). There is also the possibility that unknown infectious agents may be present in such products. All infections thought by a clinician possibly to have been transmitted by hemin should be reported by the physician or other healthcare provider to Recordati Rare Diseases at 888-575-8344. The clinician should discuss the risks and benefits of this product with the patient. Hemin therapy requires an experienced clinician knowledgeable in the management of porphyrias.

    Anticoagulant therapy

    Avoid anticoagulant therapy during the use of hemin. Mild, transient anticoagulant effects have occurred during clinical studies of hemin. The extent and duration of the hypocoagulable state induced by hemin have not been established.

    Pregnancy

    It is not known whether hemin can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Although anecdotal evidence suggests safe use of hemin 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 hemin. Use hemin during pregnancy only if clearly needed.

    Breast-feeding

    It is not known if hemin is excreted in human breast milk. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for hemin and any potential adverse effects on the breast-fed child from hemin or the underlying maternal condition.

    Latex hypersensitivity

    Administration of hemin to a patient with latex hypersensitivity may be inappropriate, as the vial stopper contains natural rubber latex.

    Preeclampsia

    Avoid hemin use in women with severe preeclampsia. Hemin has exhibited transient, mild anticoagulant effects during clinical trials. The extent and duration of the hypocoagulable state induced by hemin has not been established. There is a theoretical risk of potentiation of the coagulation disorder if used during severe preeclampsia.

    ADVERSE REACTIONS

    Severe

    coagulopathy / Delayed / Incidence not known
    oliguria / Early / Incidence not known
    azotemia / Delayed / Incidence not known

    Moderate

    phlebitis / Rapid / Incidence not known
    thrombocytopenia / Delayed / Incidence not known

    Mild

    leukocytosis / Delayed / Incidence not known
    fever / Early / Incidence not known
    infection / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Butalbital: (Major) Hemin works by inhibiting the enzyme (delta)-aminolevulinic acid synthetase. Drugs which increase the activity of this enzyme, such as barbiturates should not be used with hemin.
    Acetaminophen; Butalbital; Caffeine: (Major) Hemin works by inhibiting the enzyme (delta)-aminolevulinic acid synthetase. Drugs which increase the activity of this enzyme, such as barbiturates should not be used with hemin.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Major) Hemin works by inhibiting the enzyme (delta)-aminolevulinic acid synthetase. Drugs which increase the activity of this enzyme, such as barbiturates should not be used with hemin.
    Amobarbital: (Major) Hemin works by inhibiting the enzyme (delta)-aminolevulinic acid synthetase. Drugs which increase the activity of this enzyme, such as barbiturates should not be used with hemin.
    Anticoagulants: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.
    Antithrombin III: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.
    Apixaban: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.
    Argatroban: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.
    Aspirin, ASA; Butalbital; Caffeine: (Major) Hemin works by inhibiting the enzyme (delta)-aminolevulinic acid synthetase. Drugs which increase the activity of this enzyme, such as barbiturates should not be used with hemin.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Hemin works by inhibiting the enzyme (delta)-aminolevulinic acid synthetase. Drugs which increase the activity of this enzyme, such as barbiturates should not be used with hemin.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Major) Hemin works by inhibiting the enzyme (delta)-aminolevulinic acid synthetase. Drugs which increase the activity of this enzyme, such as barbiturates should not be used with hemin.
    Barbiturates: (Major) Hemin works by inhibiting the enzyme (delta)-aminolevulinic acid synthetase. Drugs which increase the activity of this enzyme, such as barbiturates should not be used with hemin.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Hemin works by inhibiting the enzyme (delta)-aminolevulinic acid synthetase. Drugs which increase the activity of this enzyme, such as barbiturates should not be used with hemin.
    Betrixaban: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.
    Bivalirudin: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.
    Butabarbital: (Major) Hemin works by inhibiting the enzyme (delta)-aminolevulinic acid synthetase. Drugs which increase the activity of this enzyme, such as barbiturates should not be used with hemin.
    Conjugated Estrogens: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Conjugated Estrogens; Bazedoxifene: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Conjugated Estrogens; Medroxyprogesterone: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Corticosteroids: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Corticosteroids increase the activity of this enzyme should not be used with hemin.
    Dabigatran: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.
    Dalteparin: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.
    Danaparoid: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.
    Desirudin: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.
    Dienogest; Estradiol valerate: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Diethylstilbestrol, DES: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Drospirenone; Estradiol: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Drospirenone; Ethinyl Estradiol: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Edoxaban: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.
    Enoxaparin: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.
    Esterified Estrogens: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Esterified Estrogens; Methyltestosterone: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Estradiol Cypionate; Medroxyprogesterone: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Estradiol: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Estradiol; Levonorgestrel: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Estradiol; Norethindrone: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Estradiol; Norgestimate: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Estrogens: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Estropipate: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Ethinyl Estradiol: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Ethinyl Estradiol; Desogestrel: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Ethinyl Estradiol; Etonogestrel: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Ethinyl Estradiol; Levonorgestrel: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Ethinyl Estradiol; Norelgestromin: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Ethinyl Estradiol; Norethindrone: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Ethinyl Estradiol; Norgestimate: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Ethinyl Estradiol; Norgestrel: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Fondaparinux: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.
    Heparin: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.
    Lepirudin: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.
    Mephobarbital: (Major) Hemin works by inhibiting the enzyme (delta)-aminolevulinic acid synthetase. Drugs which increase the activity of this enzyme, such as barbiturates should not be used with hemin.
    Mestranol; Norethindrone: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Estrogens increase the activity of this enzyme should not be used with hemin.
    Methohexital: (Major) Hemin works by inhibiting the enzyme (delta)-aminolevulinic acid synthetase. Drugs which increase the activity of this enzyme, such as barbiturates should not be used with hemin.
    Pentobarbital: (Major) Hemin works by inhibiting the enzyme (delta)-aminolevulinic acid synthetase. Drugs which increase the activity of this enzyme, such as barbiturates should not be used with hemin.
    Pentosan: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.
    Phenobarbital: (Major) Hemin works by inhibiting the enzyme (delta)-aminolevulinic acid synthetase. Drugs which increase the activity of this enzyme, such as barbiturates should not be used with hemin.
    Primidone: (Major) Hemin works by inhibiting the enzyme (delta)-aminolevulinic acid synthetase. Drugs which increase the activity of this enzyme, such as barbiturates should not be used with hemin.
    Rivaroxaban: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.
    Secobarbital: (Major) Hemin works by inhibiting the enzyme (delta)-aminolevulinic acid synthetase. Drugs which increase the activity of this enzyme, such as barbiturates should not be used with hemin.
    Thiopental: (Major) Hemin works by inhibiting the enzyme (delta)-aminolevulinic acid synthetase. Drugs which increase the activity of this enzyme, such as barbiturates should not be used with hemin.
    Tinzaparin: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.
    Warfarin: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.

    PREGNANCY AND LACTATION

    Pregnancy

    It is not known whether hemin can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Although anecdotal evidence suggests safe use of hemin 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 hemin. Use hemin during pregnancy only if clearly needed.

    It is not known if hemin is excreted in human breast milk. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for hemin and any potential adverse effects on the breast-fed child from hemin or the underlying maternal condition.

    MECHANISM OF ACTION

    Hemin inhibits the enzyme (delta)-aminolevulinic acid synthetase. In normal patients, heme inhibits this enzyme and limits the rate of the porphyrin/heme biosynthetic pathway. Administration of hemin results in effects similar to heme and limits the hepatic and/or marrow synthesis of porphyrin. The exact mechanism by which hemin improves symptoms in patients with acute episodes of the hepatic porphyrias has not been determined. Hemin therapy is intended to prevent an attack from reaching the critical stage of neuronal degeneration; it is not effective in repairing neuronal damage nor is hemin therapy curative. After stopping therapy, 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.

    PHARMACOKINETICS

    Hemin is administered by intravenous infusion. Data on the pharmacokinetics of hemin in humans are limited. After intravenous infusion of hemin in non-jaundiced patients, an increase in fecal urobilinogen can be observed which is roughly proportional to the amount of hemin administered. Therefore, an enterohepatic pathway is considered to be a route of elimination. Bilirubin metabolites are also excreted in the urine. Other aspects of human pharmacokinetics have not been defined.