Protoporphyria Medication

Updated: Dec 18, 2019
  • Author: Jose A Plaza, MD; Chief Editor: William D James, MD  more...
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Medication

Medication Summary

Synthetic beta-carotene (Lumitene), an oral photoprotective agent, is available as a nonprescription product. Cysteine showed benefit in clinical trials, but is rarely used. Pyridoxine was reported effective in two cases. H1-receptor blockade may reduce symptoms due to mast cell histamine release during acute phototoxic reactions if established prior to exposure. Whether H2-receptor antagonists reproducibly slow porphyrin production in various porphyrias remains unproven.

Afamelanotide is a synthetic alpha-melanocyte–stimulating hormone analogue that increases the production of eumelanin in skin, thus producing a tan. Afamelanotide binds to the melanocortin-1 receptor (MC1R). MC1R signaling up-regulates the synthesis of eumelanin and pheomelanin, induces antioxidant activity, enhances DNA repair processes, and modulates inflammation. It is administered as a subcutaneous implant containing 16 mg of afamelanotide. It is approved in the European Union and the United States for use in adults with erythropoietic protoporphyria (EPP).

Liver dysfunction warrants individualized design of therapeutic regimens that may include the administration of enteric sorbents to promote protoporphyrin excretion, bile acids to enhance porphyrin clearance from the liver, and hematin to repress porphyrin production. Combinations of these and other adjunctive agents and modalities may moderate the urgency presented by a failing organ, allowing orderly preparation for an optimal transplantation.

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Alpha-Melanocyte Stimulating Hormone Analog

Class Summary

Alpha melanocyte stimulating hormone analogs increase production of eumelanin (the most common type of melanin) in the skin independent of exposure to sunlight or artificial light sources. 

Afamelanotide (Scenesse)

Erythropoietic protoporphyria is a rare disorder caused by mutations leading to impaired activity of ferrochelatase, an enzyme involved in heme production; decreased ferrochelatase activity leads to protoporphyrin IX (PPIX) accumulation in the body; light reaching the skin can react with PPIX causing intense skin pain and skin changes (eg, redness, thickening). Afamelanotide, a melanocortin-1 receptor (MC1-R) agonist, increases production of eumelanin (the most common type of melanin) in the skin independent of exposure to sunlight or artificial light sources. It is indicated to increase pain-free light exposure in adults with history of phototoxic reactions from erythropoietic protoporphyria (EPP).

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Photoprotectants

Class Summary

Beta-carotene is a scavenger of singlet-exited oxygen and is believed to interfere with the efficiency of porphyrin-sensitized photoxidative damage in the skin. Ingestion of beta-carotene at recommended doses produces carotenodermia after several weeks. Increasing tolerance of sunlight develops during this loading period. Tolerance diminishes over several weeks when treatment is stopped. Only some individuals with EPP reported that beta-carotene provided photoprotection; others reported no noticeable benefit.

Beta carotene (Lumitene)

The exact mechanism of action is not completely elucidated. The patient must become carotenemic before effects are observed. More than one internal light screen may be responsible for effects. This agent may provide a limited level of photoprotection. It causes yellowing of skin (carotenoderma). Any photoprotection afforded increases slowly over a 4- to 6-week period after drug therapy is commenced. When discontinued, skin color and benefit diminish over several weeks.

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Antihistamines

Class Summary

H1-receptor antagonists modulate effects of histamine in skin. If taken prior to anticipated strong sunlight exposure that cannot be avoided, acute reactions may be attenuated to some extent; minimal benefit is expected if taken afterward.

Fexofenadine (Allegra)

Fexofenadine is a nonsedating second-generation medication with fewer adverse effects than first-generation medications. It competes with histamine for H1 receptors in the GI tract, blood vessels, and respiratory tract, reducing hypersensitivity reactions. Fexofenadine does not sedate. It is available in daily and twice-daily preparations.

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Antihistamines, H2 blocker

Class Summary

These agents produce blockade of H2 receptors.

Cimetidine (Tagamet)

Cimetidine is an H2 antagonist, which, when combined with an H1-type, may be useful in treating itching and flushing in urticaria. Porphyria-specific usage for inhibiting overproduction of porphyrins is experimental.

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Enteric adsorbents

Class Summary

Agents that bind protoporphyrin in the intestinal lumen promote its excretion by interrupting enterohepatic recirculation, thereby reducing the porphyrin load presented to the liver for clearance.

Cholestyramine (Questran)

Cholestyramine is a polymeric resin that binds bile acids, porphyrins, and other molecules to form nonabsorbable complexes that are excreted unchanged in feces. It adsorbs many drugs and nutrients; long-term use requires proper timing of oral drugs and may warrant supplementation of vitamins D, E, A, and K.

Activated charcoal (Actidose)

Activated charcoal prevents absorption by adsorbing porphyrin in the intestine. Multidose charcoal may interrupt enterohepatic recirculation and enhance elimination by enterocapillary exsorption. It does not dissolve in water. It adsorbs many medications and nutrients; long-term use requires proper timing of oral drugs and may warrant supplementation of vitamins D, E, A, and K.

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Gallstone dissolution agents

Class Summary

Increasing bile flow enhances secretion of protoporphyrin by the liver into the enteric tract and clearance from the body.

Ursodiol (Actigall)

Ursodiol has been shown to promote bile flow in cholestatic conditions associated with a patent extrahepatic biliary system. It decreases the cholesterol content of bile and therefore reduces bile stone and sludge formation.

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Heme analogues

Class Summary

Intravenous infusion of a heme analogue may repress heme synthesis in liver and bone marrow cells, thereby reducing rate of protoporphyrin overproduction.

Hemin (Panhematin)

Hemin in an enzyme inhibitor derived from processed red blood cells and is an iron-containing metalloporphyrin. It was previously known as hematin, a term used to describe the chemical reaction product of hemin and sodium carbonate solution.

It has an anticoagulant effect and may cause thrombophlebitis at the infusion site. It must be reconstituted from lyophilized powder. Reconstitute it with human serum albumin 25% (132 mL of 25% human serum albumin to 1 vial of hemin [301 mg heme]).

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