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Variegate Porphyria Medication

  • Author: Maureen B Poh-Fitzpatrick, MD; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Apr 15, 2016
 

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications. Acute attack episodes often require use of many medications in intensive care settings, too numerous to list exhaustively here. Consultation with experts in the management of acute porphyrias is strongly recommended to obtain up-to-date guidance, especially in crisis situations. Judicious selection of agents, dosages, and routes of administration should take into account not only avoiding drugs known or suspected to be unsafe in acute porphyrias, but also best practices and continuously evolving guidelines for optimal use of agents generally considered safe.

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Heme analogues

Class Summary

Infusion of hemelike agents rapidly restores the free-heme pool in hepatocytes, thereby exerting negative feedback repression on the rate-limiting enzyme of heme synthesis. Prompt use may prevent an attack from causing neuronal degeneration.

Hemin (Panhematin)

 

This agent is an enzyme inhibitor derived from processed red blood cells that 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]) and infuse it into large vein to reduce the risk of thrombophlebitis.

Heme arginate (Normosang)

 

Heme arginate is not currently available in the United States. It has fewer adverse effects than hemin.

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Luteinizing hormone-releasing hormone analogues

Class Summary

These agents decrease endogenous estrogen and progesterone production. The infrequency of menses-related attacks in variegate porphyria would make this therapy infrequently considered.

Leuprolide (Lupron)

 

Leuprolide suppresses ovarian and testicular steroidogenesis by decreasing luteinizing hormone and follicle-stimulating hormone levels.

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Beta-adrenergic blocking agents

Class Summary

These agents reduce sympathetic hyperactivity.

Propranolol (Inderal)

 

Propranolol has membrane-stabilizing activity and decreases the automaticity of contractions. It is not suitable for emergency treatment of hypertension. Do not give intravenously in hypertensive emergencies.

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Opiate analgesics

Class Summary

These agents provide relief of severe abdominal and/or other pain. Very large doses may be required over the course of a day.

Morphine sulfate (Duramorph, Astramorph, MS Contin)

 

Morphine sulfate is the drug of choice for analgesia, owing to its reliable and predictable effects, safety profile, and ease of reversibility with naloxone. Various intravenous doses are used; it is commonly titrated until the desired effect is obtained.

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Antiemetics/sedatives

Class Summary

These drugs reduce nausea and vomiting, control anxiety and agitation, and potentiate analgesia.

Chlorpromazine (Thorazine)

 

Chlorpromazine’s mechanisms responsible for relieving nausea and vomiting include blocking postsynaptic mesolimbic dopamine receptors, anticholinergic effects, and depression of RAS. It blocks alpha-adrenergic receptors and depresses the release of hypophyseal and hypothalamic hormones. Use a slow intravenous infusion (patient lying flat) when symptoms persist (25-50 mg with 500-1000 mL of normal saline); monitor blood pressure.

Ondansetron (Zofran, Zofran ODT, Zuplenz)

 

Ondansetron is one of a class of agents termed serotonin 5-HT3 receptor antagonists. It blocks the action of serotonin, a neurotransmitter manufactured in the brain that may cause nausea and vomiting.

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Anticonvulsants

Class Summary

These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.

Gabapentin (Neurontin)

 

Gabapentin is structurally related to GABA but does not interact with GABA receptors; it is not converted metabolically into GABA or a GABA agonist and is not an inhibitor of GABA uptake or degradation. Gabapentin does not exhibit an affinity for other common receptor sites.

Diazepam (Valium)

 

Diazepam is for acute seizure control by intravenous infusion. It depresses all levels of the CNS (eg, limbic and reticular formation), possibly by increasing the activity of GABA. Individualize the dose and increase cautiously to avoid adverse effects.

Clonazepam (Klonopin)

 

Clonazepam is a long-acting benzodiazepine that increases presynaptic GABA inhibition and reduces monosynaptic and polysynaptic reflexes. It suppresses muscle contractions by facilitating inhibitory GABA neurotransmission and other inhibitory transmitters. It has multiple indications, including suppression of myoclonic, akinetic, or petit mal seizure activity and focal or generalized dystonias (eg, tardive dystonia). It reaches peak plasma concentrations 2-4 hours after oral or rectal administration. It is not often used intravenously in the United States.

Levetiracetam (Keppra, Keppra XR, Spritam)

 

Levetiracetam is most often used in combination with other medications to treat partial (focal), myoclonic, and tonic-clonic seizures in people with epilepsy.

Magnesium sulfate

 

Magnesium sulphate corrects hypomagnesemia and helps control seizures. It is a nutritional supplement in hyperalimentation; it is a cofactor in enzyme systems involved in neurochemical transmission and muscular excitability.

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Oral photoprotectants

Class Summary

These agents may reduce cutaneous photosensitivity.

Beta carotene (Lumitene)

 

The effectiveness of beta carotene is uncertain in variegate porphyria, but a trial may be warranted in view of its low-risk profile. The mechanism of action is not completely elucidated. The patient must become carotenemic before effects are observed. This agent may provide a limited level of photoprotection. It causes yellowing of the skin (carotenoderma). Any photoprotection afforded increases slowly after the drug is commenced over a 4- to 6-week period. When it is discontinued, skin color and benefit fade over several weeks.

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Contributor Information and Disclosures
Author

Maureen B Poh-Fitzpatrick, MD Professor Emerita of Dermatology and Special Lecturer, Columbia University College of Physicians and Surgeons

Maureen B Poh-Fitzpatrick, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, New York Dermatological Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Julia R Nunley, MD Professor, Program Director, Dermatology Residency, Department of Dermatology, Virginia Commonwealth University Medical Center

Julia R Nunley, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, American Society of Nephrology, International Society of Nephrology, Medical Dermatology Society, Medical Society of Virginia, National Kidney Foundation, Phi Beta Kappa, Women's Dermatologic Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Board of Dermatology<br/>Co-Editor for the text Dermatological Manifestations of Kidney Disease .

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

David Timothy Woodley, MD Professor and Chair, Department of Dermatology, Keck School of Medicine of the University of Southern California

David Timothy Woodley, MD is a member of the following medical societies: American Academy of Dermatology, American Association for the Advancement of Science, American College of Emergency Physicians, American College of Physicians, American Federation for Medical Research, American Society for Clinical Investigation, New York Academy of Medicine, Society for Investigative Dermatology, Southern Medical Association

Disclosure: Received consulting fee from Shire Pharmaceuticals for consulting.

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