Acute Porphyria Medication

Updated: Nov 22, 2019
  • Author: Richard E Frye, MD, PhD; Chief Editor: Lawrence C Wolfe, MD  more...
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Medication

Medication Summary

Conservative therapy includes IV fluid with a substantial carbohydrate supply (eg, dextrose 500 g/d), pain control with opiates, and relief of nausea and vomiting with phenothiazines. If conservative treatment proves unsatisfactory, an IV heme infusion is indicated. Seizure control using anticonvulsants is also indicated.

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Heme analogues

Class Summary

Iron-containing metalloporphyrins reduce hepatic and marrow synthesis of porphyrin by inhibiting aminolevulinic acid (ALA) synthetase, the rate-limiting enzyme in the porphyrin biosynthetic pathway. Clinical symptoms (eg, pain, hypertension, tachycardia, mental status changes, neuropathy) may be controlled.

Heme arginate (Normosang; Leiras Medica, Finland) is not approved for use in the United States. Heme arginate may have a lower frequency of thrombophlebitis than hemin (Panhematin) and improves drug metabolism mediated by the cytochrome P-450 system.

Hemin (Panhematin)

Heme analogue for treatment of acute episodes. Enzyme inhibitor derived from processed RBCs and iron-containing metalloporphyrin. Was known as hematin, term used to describe chemical reaction product of hemin and sodium carbonate solution.

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Anticonvulsants

Class Summary

Seizures, which can occur as a neurologic manifestation of acute porphyria, are best treated with a drug not metabolized by the liver.

Gabapentin (Neurontin)

Structurally related to GABA but does not interact with GABA receptors; not metabolically converted into GABA or a GABA agonist; does not inhibit GABA uptake or degradation. Among safest anticonvulsants, no significant interactions, and not metabolized by the liver. Usually used as adjunct anticonvulsant but can be first-line medication for long-term seizure control in some circumstances.

Magnesium sulfate

Depresses CNS, possibly by inhibiting acetylcholine release by motor nerve impulses. Blocks peripheral neuromuscular transmission. Used for acute seizure control. Elemental magnesium 49.3 mg (4.1 mEq) = 500 mg magnesium sulfate

Diazepam (Valium, Diastat)

Long-acting PO, parenteral, and PR benzodiazepine, with antianxiety properties useful for acute seizure control. PR diazepam particularly useful for outpatients in whom seizures may occur.

Lorazepam (Ativan)

A benzodiazepine with antianxiety properties used for acute seizure control. Minimal respiratory and circulation adverse effects. Primarily eliminated by kidneys and metabolized by liver but not cytochrome pathway.

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Analgesic agents

Class Summary

Opiates are first-line agents for pain control in porphyria because the pain is usually intense and because these medications are safe to use for this condition.

Morphine (Generic, Astramorph PF, Duramorph)

DOC for analgesia. Can be administered IV or IM. Wide spectrum of pharmacologic effects, including analgesia, dysphoria, euphoria, somnolence, respiratory depression, diminished GI motility, and physical dependence. Continuous infusion useful for extended use and minimizes tolerance. Hepatic glucuronidation to morphine-3-glucuronide pharmacologically inactivates morphine; major excretion pathway of conjugate is through kidneys. Half-life 1.5-4.5 h.

Meperidine (Demerol)

Analgesic with multiple actions similar to those of morphine; may produce less constipation, smooth muscle spasm, and depression of cough reflex than similar analgesic doses of morphine. Do not exceed administration >48 h because of risk of seizures secondary to accumulation of normeperidine metabolite.

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Antipsychotics/antiemetics

Class Summary

Phenothiazines have antiemetic and antipsychotic properties, making them the medication of choice for acute porphyria episodes.

Chlorpromazine (Thorazine, Ormazine)

Principally psychotropic but also exerts sedative and antiemetic activity. Acts at all levels of CNS but primarily subcortical levels. Strong antiadrenergic and weak anticholinergic, antihistaminic, and antiserotonergic activity.

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Beta-adrenergic blocking agents

Class Summary

These agents reduce sympathetic hyperactivity during acute episodes.

Propranolol (Inderal)

Competitive beta-adrenergic antagonist that blocks chronotropic, inotropic, and vasodilator responses to beta-adrenergic stimulation. Reduces increased sympathetic outflow due to acute neuropathy associated with porphyria, but insufficient to treat hypertensive emergencies associated with acute porphyria episodes.

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Hormones

Class Summary

Premenstrual episodes occur in some women. Inhibiting or controlling the menstrual cycle can control these episodes.

Leuprolide (Lupron)

Gonadotropin-releasing hormone agonist; potent inhibitor of gonadotropin secretion when given continuously. Long-term stimulation causes downregulation of gonadotropins and suppression of ovarian and testicular steroidogenesis, essentially inducing menopause. Effects reversible on discontinuation. Use under guidance of specialist in reproductive medicine.

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RNAi Agents

Class Summary

Small interfering RNA agents. Via RNA interference, they lead to degradation of aminolevulinate synthase 1 (ALAS1) mRNA in hepatocytes, which in turn lowers elevated liver ALAS1 mRNA levels. This decreases circulating levels of the neurotoxic intermediates aminolevulinic acid (ALA) and porphobilinogen (PBG), both of which are linked to attacks and other manifestations of the acute hepatic porphyrias (AHP).

Givosiran (Givlaari)

Indicated for adults with acute hepatic porphyria.

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