Acute porphyrias result from deficiency of certain enzymes in the heme biosynthetic pathway, resulting in accumulation of heme precursors that cause intermittent attacks of abdominal pain and neurologic symptoms. Attacks are precipitated by certain drugs and other factors. Patients with variegate porphyria and hereditary coproporphyria may develop bullous eruptions especially on the hands, forearms, face, neck, or other areas of the skin exposed to sunlight. Diagnosis is based on elevated levels of δ-aminolevulinic acid and porphyrin precursor porphobilinogen in the urine during attacks. Attacks are treated with glucose or, if more severe, IV heme. Symptomatic treatment, including analgesia, is given as necessary.

Acute porphyrias (see also Porphyrias: Overview of Porphyrias) include, in order of prevalence, acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), and the exceedingly rare δ-aminolevulinic acid dehydratase (ALAD)–deficiency porphyria.

Among heterozygotes, acute porphyrias are rarely expressed clinically before puberty; after puberty, they are expressed in only about 20 to 30%. Among homozygotes and compound heterozygotes, onset typically is in childhood, and symptoms are often severe.

Precipitating Factors

Many precipitating factors exist, typically accelerating heme biosynthesis above the catalytic capacity of the defective enzyme. Accumulation of the porphyrin precursors porphobilinogen (PBG) and δ-aminolevulinic acid (ALA), or in the case of ALAD-deficiency porphyria, ALA alone, results.

Hormonal factors are important. Women are more prone to attacks than men, particularly during periods of hormonal change (eg, luteal phase of the menstrual cycle, during oral contraceptive use, during early weeks of gestation, in the immediate postpartum period). Nevertheless, pregnancy is not contraindicated.

Other factors include drugs (including barbiturates, hydantoins, other antiepileptic drugs, and sulfonamide antibiotics—see Table 4: Porphyrias: Drugs and Porphyria*) and reproductive hormones (progesterone and related steroids), particularly those that induce hepatic ALA synthase and cytochrome P-450 enzymes. Attacks usually occur within 24 h after exposure to a precipitating drug. Low-calorie and low-carbohydrate diets, alcohol ingestion, and exposure to organic solvents can also precipitate symptoms. Infection or other illness, surgery, and mental problems are sometimes implicated. Attacks probably result from several, sometimes unidentifiable, factors.

Exposure to sunlight precipitates cutaneous symptoms in VP and HCP.

Table 4
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Drugs and Porphyria* Category/Disorder Treated Unsafe Safe Probably Safe Analgesic Dextropropoxyphene DiclofenacSome Trade Names CATAFLAM VOLTAREN Click for Drug Monograph MeprobamateSome Trade Names EQUANIL MILTOWN Click for Drug Monograph PropoxypheneSome Trade Names DARVON DOLENE TramadolSome Trade Names ULTRAM Click for Drug Monograph AspirinSome Trade Names BUFFERIN ECOTRIN GENACOTE Click for Drug Monograph BuprenorphineSome Trade Names BUPRENEX SUBUTEX Click for Drug Monograph Caffeine CodeineSome Trade Names No US trade name Click for Drug Monograph MorphineSome Trade Names DURAMORPH MS CONTIN MSIR ROXANOL Click for Drug Monograph PropofolSome Trade Names DIPRIVAN Click for Drug Monograph AtropineSome Trade Names ATROPEN ATROPINE-CARE SAL-TROPINE Click for Drug Monograph Dexibuprofen FentanylSome Trade Names ACTIQ DURAGESIC SUBLIMAZE Click for Drug Monograph HydromorphoneSome Trade Names DILAUDID Click for Drug Monograph Ketobemidone KetoprofenSome Trade Names ORUDIS ORUVAIL Click for Drug Monograph NaproxenSome Trade Names ALEVE NAPROSYN Click for Drug Monograph Anesthetic (local) LidocaineSome Trade Names XYLOCAINE Click for Drug Monograph BupivacaineSome Trade Names MARCAINE SENSORCAINE Click for Drug Monograph Articaine Anesthetic (premedication, induction, or maintenance) Barbiturates AtropineSome Trade Names ATROPEN ATROPINE-CARE SAL-TROPINE Click for Drug Monograph MorphineSome Trade Names DURAMORPH MS CONTIN MSIR ROXANOL Click for Drug Monograph PropofolSome Trade Names DIPRIVAN Click for Drug Monograph AlfentanilSome Trade Names ALFENTA Click for Drug Monograph Desflurane DroperidolSome Trade Names INAPSINE Click for Drug Monograph Enflurane FentanylSome Trade Names ACTIQ DURAGESIC SUBLIMAZE Click for Drug Monograph Isoflurane RemifentanilSome Trade Names ULTIVA Click for Drug Monograph ScopolamineSome Trade Names TRANSDERM SCOP Click for Drug Monograph SufentanilSome Trade Names SUFENTA Click for Drug Monograph Antidepressant — LithiumSome Trade Names ESKALITH LITHOBID LITHONATE Click for Drug Monograph FluoxetineSome Trade Names PROZAC SARAFEM Click for Drug Monograph Antidiarrheal — Active carbon LoperamideSome Trade Names IMODIUM Click for Drug Monograph — Antiemetic — ChlorpromazineSome Trade Names THORAZINE Click for Drug Monograph GranisetronSome Trade Names KYTRIL Click for Drug Monograph OndansetronSome Trade Names ZOFRAN Click for Drug Monograph ScopolamineSome Trade Names TRANSDERM SCOP Click for Drug Monograph Tropisetron Anticonvulsant Barbiturates CarbamazepineSome Trade Names TEGRETOL Click for Drug Monograph Diones (paramethadione, trimethadioneSome Trade Names TRIDIONE ) FelbamateSome Trade Names FELBATOL Click for Drug Monograph LamotrigineSome Trade Names LAMICTAL Click for Drug Monograph Mephenytoin PhenytoinSome Trade Names DILANTIN Click for Drug Monograph PrimidoneSome Trade Names MYSOLINE Click for Drug Monograph Succinimides (ethosuximideSome Trade Names ZARONTIN Click for Drug Monograph , methsuximideSome Trade Names CELONTIN Click for Drug Monograph ) ValproateSome Trade Names DEPAKENE Click for Drug Monograph — ClonazepamSome Trade Names KLONOPIN Click for Drug Monograph DiazepamSome Trade Names VALIUM Click for Drug Monograph (active seizure) GabapentinSome Trade Names NEURONTIN Click for Drug Monograph LevetiracetamSome Trade Names KEPPRA Click for Drug Monograph TopiramateSome Trade Names TOPAMAX Click for Drug Monograph Vigabatrin Antihyperglycemic Sulfonylureas AcarboseSome Trade Names PRECOSE Click for Drug Monograph InsulinSome Trade Names HUMULIN NOVOLIN Click for Drug Monograph MetforminSome Trade Names GLUCOPHAGE Click for Drug Monograph — Anti-infective ChloramphenicolSome Trade Names CHLOROMYCETIN Click for Drug Monograph ClindamycinSome Trade Names CLEOCIN Click for Drug Monograph ErythromycinSome Trade Names ERY-TAB ERYTHROCIN Click for Drug Monograph IndinavirSome Trade Names CRIXIVAN Click for Drug Monograph KetoconazoleSome Trade Names NIZORAL Click for Drug Monograph Mecillinam NitrofurantoinSome Trade Names FURADANTIN MACROBID MACRODANTIN Click for Drug Monograph PivampicillinSome Trade Names No US trade name Pivmecillinam RifampinSome Trade Names RIFADIN RIMACTANE Click for Drug Monograph RitonavirSome Trade Names NORVIR Click for Drug Monograph Sulfonamides TrimethoprimSome Trade Names PROLOPRIM TRIMPEX Click for Drug Monograph AcyclovirSome Trade Names ZOVIRAX Click for Drug Monograph AmikacinSome Trade Names AMIKIN Click for Drug Monograph AmoxicillinSome Trade Names AMOXIL TRIMOX Click for Drug Monograph AmoxicillinSome Trade Names AMOXIL TRIMOX Click for Drug Monograph with a β-lactamase inhibitor AmpicillinSome Trade Names OMNIPEN PRINCIPEN Click for Drug Monograph CloxacillinSome Trade Names No US trade name Click for Drug Monograph DicloxacillinSome Trade Names DYCILL DYNAPEN PATHOCIL Click for Drug Monograph Fusidic acidSome Trade Names No US trade name Click for Drug Monograph GanciclovirSome Trade Names CYTOVENE Click for Drug Monograph GentamicinSome Trade Names GARAMYCIN Click for Drug Monograph Immune globulin Immune sera MethenamineSome Trade Names HIPREX MANDELAMINE UREX Click for Drug Monograph hippurate Netilmicin OseltamivirSome Trade Names TAMIFLU Click for Drug Monograph Penicillin GSome Trade Names BICILLIN WYCILLIN Click for Drug Monograph Penicillin V PiperacillinSome Trade Names PIPRACIL Click for Drug Monograph Teicoplanin TobramycinSome Trade Names NEBCIN TOBI TOBREX Click for Drug Monograph Vaccines ValacyclovirSome Trade Names VALTREX Click for Drug Monograph VancomycinSome Trade Names VANCOCIN Click for Drug Monograph Zanamivir Amphotericin BSome Trade Names ABELCET AMBISOME AMPHOCIN AMPHOTEC Click for Drug Monograph AzithromycinSome Trade Names ZITHROMAX Click for Drug Monograph Bacampicillin Cephalosporins CiprofloxacinSome Trade Names CILOXAN CIPRO Click for Drug Monograph DidanosineSome Trade Names VIDEX Click for Drug Monograph EthambutolSome Trade Names MYAMBUTOL Click for Drug Monograph ErtapenemSome Trade Names INVANZ Click for Drug Monograph FamciclovirSome Trade Names FAMVIR Click for Drug Monograph FlucytosineSome Trade Names ANCOBON Click for Drug Monograph FoscarnetSome Trade Names FOSCAVIR Click for Drug Monograph with cilastatin Imipenem LevofloxacinSome Trade Names IQUIX LEVAQUIN QUIXIN Click for Drug Monograph MeropenemSome Trade Names MERREM Click for Drug Monograph MoxifloxacinSome Trade Names AVELOX Click for Drug Monograph NorfloxacinSome Trade Names NOROXIN Click for Drug Monograph OfloxacinSome Trade Names FLOXIN Click for Drug Monograph PiperacillinSome Trade Names PIPRACIL Click for Drug Monograph with tazobactam Phosphomycin RibavirinSome Trade Names VIRAZOLE Click for Drug Monograph Anti-inflammatory or antirheumatic — Hyaluronic acid PenicillamineSome Trade Names CUPRIMINE Click for Drug Monograph Salicylates AbacavirSome Trade Names ZIAGEN Click for Drug Monograph Dexibuprofen IbuprofenSome Trade Names ADVIL MOTRIN NUPRIN Click for Drug Monograph KetoprofenSome Trade Names ORUDIS ORUVAIL Click for Drug Monograph LamivudineSome Trade Names EPIVIR Click for Drug Monograph Lornoxicam NaproxenSome Trade Names ALEVE NAPROSYN Click for Drug Monograph PiroxicamSome Trade Names FELDENE Click for Drug Monograph TenofovirSome Trade Names VIREAD Click for Drug Monograph Tenoxicam ZalcitabineSome Trade Names HIVID Anxiolytic, sedative-hypnotic, or antipsychotic Ethchlorvynol Glutethimide HydroxyzineSome Trade Names ATARAX VISTARIL Click for Drug Monograph MeprobamateSome Trade Names EQUANIL MILTOWN Click for Drug Monograph ChlorpromazineSome Trade Names THORAZINE Click for Drug Monograph DroperidolSome Trade Names INAPSINE Click for Drug Monograph FluoxetineSome Trade Names PROZAC SARAFEM Click for Drug Monograph FluphenazineSome Trade Names PROLIXIN DECANOATE PROLIXIN Click for Drug Monograph HaloperidolSome Trade Names HALDOL Click for Drug Monograph Levomepromazine ProchlorperazineSome Trade Names COMPAZINE Click for Drug Monograph Propiomazine AlprazolamSome Trade Names XANAX Click for Drug Monograph ClozapineSome Trade Names CLOZARIL Click for Drug Monograph Dixyrazine LorazepamSome Trade Names ATIVAN Click for Drug Monograph OlanzapineSome Trade Names ZYPREXA Click for Drug Monograph OxazepamSome Trade Names SERAX Click for Drug Monograph PerphenazineSome Trade Names TRILAFON Click for Drug Monograph TriazolamSome Trade Names HALCION Click for Drug Monograph Zopiclone Cardiovascular disorders Dihydralazine Ergoloid mesylate HydralazineSome Trade Names APRESOLINE Click for Drug Monograph LidocaineSome Trade Names XYLOCAINE Click for Drug Monograph MethyldopaSome Trade Names ALDOMET Click for Drug Monograph NifedipineSome Trade Names ADALAT PROCARDIA Click for Drug Monograph SpironolactoneSome Trade Names ALDACTONE Click for Drug Monograph AmilorideSome Trade Names MIDAMOR Click for Drug Monograph β-Blockers CholestyramineSome Trade Names QUESTRAN Click for Drug Monograph ColestipolSome Trade Names COLESTID Click for Drug Monograph Digitalis glycosides DiltiazemSome Trade Names CARDIZEM CARTIA DILACOR Click for Drug Monograph EnalaprilSome Trade Names VASOTEC Click for Drug Monograph EpinephrineSome Trade Names ADRENALIN PRIMATENE MIST Click for Drug Monograph Heparins LisinoprilSome Trade Names PRINIVIL ZESTRIL Click for Drug Monograph LosartanSome Trade Names COZAAR Click for Drug Monograph Nicotinic acid Organic nitrates AdenosineSome Trade Names ADENOCARD Click for Drug Monograph AmrinoneSome Trade Names INOCOR Bendroflumethiazide BezafibrateSome Trade Names No US trade name Click for Drug Monograph BumetanideSome Trade Names BUMEX Click for Drug Monograph DigoxinSome Trade Names DIGITEK LANOXIN Click for Drug Monograph DobutamineSome Trade Names DOBUTREX Click for Drug Monograph DopamineSome Trade Names INTROPIN Click for Drug Monograph Dopexamine DoxazosinSome Trade Names CARDURA Click for Drug Monograph Ethacrynic acidSome Trade Names EDECRIN Click for Drug Monograph Etilefrine FenofibrateSome Trade Names ANTARA LIPOFEN TRICOR TRIGLIDE Click for Drug Monograph FurosemideSome Trade Names LASIX Click for Drug Monograph HydrochlorothiazideSome Trade Names ESIDRIX HYDRODIURIL Click for Drug Monograph MilrinoneSome Trade Names PRIMACOR Click for Drug Monograph PhenylephrineSome Trade Names NEO-SYNEPHRINE Click for Drug Monograph Prostaglandins QuinidineSome Trade Names CARDIOQUIN QUINAGLUTE Click for Drug Monograph Hormones DanazolSome Trade Names DANOCRINE Click for Drug Monograph Progesterone Synthetic progestins Nonreproductive hormones, including glucocorticoids Natural estrogens Laxatives — BisacodylSome Trade Names DULCOLAX Click for Drug Monograph Dietary fiber Lactitol LactuloseSome Trade Names CEPHULAC CHRONULAC KRISTALOSE Click for Drug Monograph Lauryl sulfate Psyllium seed Sagrada SennaSome Trade Names EX-LAX SENOKOT Click for Drug Monograph glycosides Sodium docusateSome Trade Names COLACE SURFAK Click for Drug Monograph Sodium picosulfate Sorbitol — Migraines Ergots — — Muscle relaxants CarisoprodolSome Trade Names SOMA Click for Drug Monograph OrphenadrineSome Trade Names NORFLEX Click for Drug Monograph AtracuriumSome Trade Names TRACRIUM Click for Drug Monograph CisatracuriumSome Trade Names NIMBEX Click for Drug Monograph MivacuriumSome Trade Names MIVACRON PancuroniumSome Trade Names PAVULON Click for Drug Monograph RocuroniumSome Trade Names ZEMURON Click for Drug Monograph Suxethonium Vecuronium BaclofenSome Trade Names LIORESAL Click for Drug Monograph Osteoporosis — Bisphosphonates Ca supplements — Peptic ulcers — Alginic acid Ca-containing antacids CimetidineSome Trade Names TAGAMET Click for Drug Monograph Mg-containing antacids SucralfateSome Trade Names CARAFATE Click for Drug Monograph FamotidineSome Trade Names PEPCID Click for Drug Monograph MisoprostolSome Trade Names CYTOTEC Click for Drug Monograph NizatidineSome Trade Names AXID Click for Drug Monograph RanitidineSome Trade Names ZANTAC Click for Drug Monograph Respiratory disorders ClemastineSome Trade Names TAVIST Click for Drug Monograph DimenhydrinateSome Trade Names DRAMAMINE TRIPTONE Click for Drug Monograph Alimemazine CodeineSome Trade Names No US trade name Click for Drug Monograph Corticosteroids Dipalmitoyl phosphatidylcholine Dornase alfaSome Trade Names PULMOZYME Click for Drug Monograph EphedrineSome Trade Names PRETZ-D Click for Drug Monograph Ethylmorphine IpratropiumSome Trade Names ATROVENT Click for Drug Monograph Phenylpropanolamine Phospholipid surfactant Salbutamol Bambuterol Cromoglycic acid CromolynSome Trade Names CROLOM INTAL NASALCROM Click for Drug Monograph Declorahidine DesloratadineSome Trade Names CLARINEX Click for Drug Monograph FexofenadineSome Trade Names ALLEGRA Click for Drug Monograph FormoterolSome Trade Names FORADIL AEROLIZER PERFOROMIST Click for Drug Monograph LevocabastineSome Trade Names LIVOSTIN Click for Drug Monograph LidocaineSome Trade Names XYLOCAINE Click for Drug Monograph (solution for gargling) LoratadineSome Trade Names ALAVERT CLARITIN Click for Drug Monograph Mizolastine OxymetazolineSome Trade Names AFRIN DURATION Click for Drug Monograph Phenoterol SalmeterolSome Trade Names SEREVENT Click for Drug Monograph TerbutalineSome Trade Names BRETHINE BRICANYL Click for Drug Monograph TiotropiumSome Trade Names SPIRIVA Click for Drug Monograph *The classification of the drugs in the list is based on a combination of clinical observations, case reports in the literature, and theoretical considerations derived from the structure and metabolism of the substances. However, clinical observations may in many cases be unreliable. Also, the biochemical and molecular-biologic models for the activation of the disease are incomplete. This list is meant as guidance only and is neither complete nor applicable to all patients. Drugs must always be used cautiously in people who carry genes for acute porphyria. For questions about specific drugs, physicians can consult www.drugs-porphyria.org. Drugs and Porphyria* Category/Disorder Treated Unsafe Safe Probably Safe Analgesic Dextropropoxyphene DiclofenacSome Trade Names CATAFLAM VOLTAREN Click for Drug Monograph MeprobamateSome Trade Names EQUANIL MILTOWN Click for Drug Monograph PropoxypheneSome Trade Names DARVON DOLENE TramadolSome Trade Names ULTRAM Click for Drug Monograph AspirinSome Trade Names BUFFERIN ECOTRIN GENACOTE Click for Drug Monograph BuprenorphineSome Trade Names BUPRENEX SUBUTEX Click for Drug Monograph Caffeine CodeineSome Trade Names No US trade name Click for Drug Monograph MorphineSome Trade Names DURAMORPH MS CONTIN MSIR ROXANOL Click for Drug Monograph PropofolSome Trade Names DIPRIVAN Click for Drug Monograph AtropineSome Trade Names ATROPEN ATROPINE-CARE SAL-TROPINE Click for Drug Monograph Dexibuprofen FentanylSome Trade Names ACTIQ DURAGESIC SUBLIMAZE Click for Drug Monograph HydromorphoneSome Trade Names DILAUDID Click for Drug Monograph Ketobemidone KetoprofenSome Trade Names ORUDIS ORUVAIL Click for Drug Monograph NaproxenSome Trade Names ALEVE NAPROSYN Click for Drug Monograph Anesthetic (local) LidocaineSome Trade Names XYLOCAINE Click for Drug Monograph BupivacaineSome Trade Names MARCAINE SENSORCAINE Click for Drug Monograph Articaine Anesthetic (premedication, induction, or maintenance) Barbiturates AtropineSome Trade Names ATROPEN ATROPINE-CARE SAL-TROPINE Click for Drug Monograph MorphineSome Trade Names DURAMORPH MS CONTIN MSIR ROXANOL Click for Drug Monograph PropofolSome Trade Names DIPRIVAN Click for Drug Monograph AlfentanilSome Trade Names ALFENTA Click for Drug Monograph Desflurane DroperidolSome Trade Names INAPSINE Click for Drug Monograph Enflurane FentanylSome Trade Names ACTIQ DURAGESIC SUBLIMAZE Click for Drug Monograph Isoflurane RemifentanilSome Trade Names ULTIVA Click for Drug Monograph ScopolamineSome Trade Names TRANSDERM SCOP Click for Drug Monograph SufentanilSome Trade Names SUFENTA Click for Drug Monograph Antidepressant — LithiumSome Trade Names ESKALITH LITHOBID LITHONATE Click for Drug Monograph FluoxetineSome Trade Names PROZAC SARAFEM Click for Drug Monograph Antidiarrheal — Active carbon LoperamideSome Trade Names IMODIUM Click for Drug Monograph — Antiemetic — ChlorpromazineSome Trade Names THORAZINE Click for Drug Monograph GranisetronSome Trade Names KYTRIL Click for Drug Monograph OndansetronSome Trade Names ZOFRAN Click for Drug Monograph ScopolamineSome Trade Names TRANSDERM SCOP Click for Drug Monograph Tropisetron Anticonvulsant Barbiturates CarbamazepineSome Trade Names TEGRETOL Click for Drug Monograph Diones (paramethadione, trimethadioneSome Trade Names TRIDIONE ) FelbamateSome Trade Names FELBATOL Click for Drug Monograph LamotrigineSome Trade Names LAMICTAL Click for Drug Monograph Mephenytoin PhenytoinSome Trade Names DILANTIN Click for Drug Monograph PrimidoneSome Trade Names MYSOLINE Click for Drug Monograph Succinimides (ethosuximideSome Trade Names ZARONTIN Click for Drug Monograph , methsuximideSome Trade Names CELONTIN Click for Drug Monograph ) ValproateSome Trade Names DEPAKENE Click for Drug Monograph — ClonazepamSome Trade Names KLONOPIN Click for Drug Monograph DiazepamSome Trade Names VALIUM Click for Drug Monograph (active seizure) GabapentinSome Trade Names NEURONTIN Click for Drug Monograph LevetiracetamSome Trade Names KEPPRA Click for Drug Monograph TopiramateSome Trade Names TOPAMAX Click for Drug Monograph Vigabatrin Antihyperglycemic Sulfonylureas AcarboseSome Trade Names PRECOSE Click for Drug Monograph InsulinSome Trade Names HUMULIN NOVOLIN Click for Drug Monograph MetforminSome Trade Names GLUCOPHAGE Click for Drug Monograph — Anti-infective ChloramphenicolSome Trade Names CHLOROMYCETIN Click for Drug Monograph ClindamycinSome Trade Names CLEOCIN Click for Drug Monograph ErythromycinSome Trade Names ERY-TAB ERYTHROCIN Click for Drug Monograph IndinavirSome Trade Names CRIXIVAN Click for Drug Monograph KetoconazoleSome Trade Names NIZORAL Click for Drug Monograph Mecillinam NitrofurantoinSome Trade Names FURADANTIN MACROBID MACRODANTIN Click for Drug Monograph PivampicillinSome Trade Names No US trade name Pivmecillinam RifampinSome Trade Names RIFADIN RIMACTANE Click for Drug Monograph RitonavirSome Trade Names NORVIR Click for Drug Monograph Sulfonamides TrimethoprimSome Trade Names PROLOPRIM TRIMPEX Click for Drug Monograph AcyclovirSome Trade Names ZOVIRAX Click for Drug Monograph AmikacinSome Trade Names AMIKIN Click for Drug Monograph AmoxicillinSome Trade Names AMOXIL TRIMOX Click for Drug Monograph AmoxicillinSome Trade Names AMOXIL TRIMOX Click for Drug Monograph with a β-lactamase inhibitor AmpicillinSome Trade Names OMNIPEN PRINCIPEN Click for Drug Monograph CloxacillinSome Trade Names No US trade name Click for Drug Monograph DicloxacillinSome Trade Names DYCILL DYNAPEN PATHOCIL Click for Drug Monograph Fusidic acidSome Trade Names No US trade name Click for Drug Monograph GanciclovirSome Trade Names CYTOVENE Click for Drug Monograph GentamicinSome Trade Names GARAMYCIN Click for Drug Monograph Immune globulin Immune sera MethenamineSome Trade Names HIPREX MANDELAMINE UREX Click for Drug Monograph hippurate Netilmicin OseltamivirSome Trade Names TAMIFLU Click for Drug Monograph Penicillin GSome Trade Names BICILLIN WYCILLIN Click for Drug Monograph Penicillin V PiperacillinSome Trade Names PIPRACIL Click for Drug Monograph Teicoplanin TobramycinSome Trade Names NEBCIN TOBI TOBREX Click for Drug Monograph Vaccines ValacyclovirSome Trade Names VALTREX Click for Drug Monograph VancomycinSome Trade Names VANCOCIN Click for Drug Monograph Zanamivir Amphotericin BSome Trade Names ABELCET AMBISOME AMPHOCIN AMPHOTEC Click for Drug Monograph AzithromycinSome Trade Names ZITHROMAX Click for Drug Monograph Bacampicillin Cephalosporins CiprofloxacinSome Trade Names CILOXAN CIPRO Click for Drug Monograph DidanosineSome Trade Names VIDEX Click for Drug Monograph EthambutolSome Trade Names MYAMBUTOL Click for Drug Monograph ErtapenemSome Trade Names INVANZ Click for Drug Monograph FamciclovirSome Trade Names FAMVIR Click for Drug Monograph FlucytosineSome Trade Names ANCOBON Click for Drug Monograph FoscarnetSome Trade Names FOSCAVIR Click for Drug Monograph with cilastatin Imipenem LevofloxacinSome Trade Names IQUIX LEVAQUIN QUIXIN Click for Drug Monograph MeropenemSome Trade Names MERREM Click for Drug Monograph MoxifloxacinSome Trade Names AVELOX Click for Drug Monograph NorfloxacinSome Trade Names NOROXIN Click for Drug Monograph OfloxacinSome Trade Names FLOXIN Click for Drug Monograph PiperacillinSome Trade Names PIPRACIL Click for Drug Monograph with tazobactam Phosphomycin RibavirinSome Trade Names VIRAZOLE Click for Drug Monograph Anti-inflammatory or antirheumatic — Hyaluronic acid PenicillamineSome Trade Names CUPRIMINE Click for Drug Monograph Salicylates AbacavirSome Trade Names ZIAGEN Click for Drug Monograph Dexibuprofen IbuprofenSome Trade Names ADVIL MOTRIN NUPRIN Click for Drug Monograph KetoprofenSome Trade Names ORUDIS ORUVAIL Click for Drug Monograph LamivudineSome Trade Names EPIVIR Click for Drug Monograph Lornoxicam NaproxenSome Trade Names ALEVE NAPROSYN Click for Drug Monograph PiroxicamSome Trade Names FELDENE Click for Drug Monograph TenofovirSome Trade Names VIREAD Click for Drug Monograph Tenoxicam ZalcitabineSome Trade Names HIVID Anxiolytic, sedative-hypnotic, or antipsychotic Ethchlorvynol Glutethimide HydroxyzineSome Trade Names ATARAX VISTARIL Click for Drug Monograph MeprobamateSome Trade Names EQUANIL MILTOWN Click for Drug Monograph ChlorpromazineSome Trade Names THORAZINE Click for Drug Monograph DroperidolSome Trade Names INAPSINE Click for Drug Monograph FluoxetineSome Trade Names PROZAC SARAFEM Click for Drug Monograph FluphenazineSome Trade Names PROLIXIN DECANOATE PROLIXIN Click for Drug Monograph HaloperidolSome Trade Names HALDOL Click for Drug Monograph Levomepromazine ProchlorperazineSome Trade Names COMPAZINE Click for Drug Monograph Propiomazine AlprazolamSome Trade Names XANAX Click for Drug Monograph ClozapineSome Trade Names CLOZARIL Click for Drug Monograph Dixyrazine LorazepamSome Trade Names ATIVAN Click for Drug Monograph OlanzapineSome Trade Names ZYPREXA Click for Drug Monograph OxazepamSome Trade Names SERAX Click for Drug Monograph PerphenazineSome Trade Names TRILAFON Click for Drug Monograph TriazolamSome Trade Names HALCION Click for Drug Monograph Zopiclone Cardiovascular disorders Dihydralazine Ergoloid mesylate HydralazineSome Trade Names APRESOLINE Click for Drug Monograph LidocaineSome Trade Names XYLOCAINE Click for Drug Monograph MethyldopaSome Trade Names ALDOMET Click for Drug Monograph NifedipineSome Trade Names ADALAT PROCARDIA Click for Drug Monograph SpironolactoneSome Trade Names ALDACTONE Click for Drug Monograph AmilorideSome Trade Names MIDAMOR Click for Drug Monograph β-Blockers CholestyramineSome Trade Names QUESTRAN Click for Drug Monograph ColestipolSome Trade Names COLESTID Click for Drug Monograph Digitalis glycosides DiltiazemSome Trade Names CARDIZEM CARTIA DILACOR Click for Drug Monograph EnalaprilSome Trade Names VASOTEC Click for Drug Monograph EpinephrineSome Trade Names ADRENALIN PRIMATENE MIST Click for Drug Monograph Heparins LisinoprilSome Trade Names PRINIVIL ZESTRIL Click for Drug Monograph LosartanSome Trade Names COZAAR Click for Drug Monograph Nicotinic acid Organic nitrates AdenosineSome Trade Names ADENOCARD Click for Drug Monograph AmrinoneSome Trade Names INOCOR Bendroflumethiazide BezafibrateSome Trade Names No US trade name Click for Drug Monograph BumetanideSome Trade Names BUMEX Click for Drug Monograph DigoxinSome Trade Names DIGITEK LANOXIN Click for Drug Monograph DobutamineSome Trade Names DOBUTREX Click for Drug Monograph DopamineSome Trade Names INTROPIN Click for Drug Monograph Dopexamine DoxazosinSome Trade Names CARDURA Click for Drug Monograph Ethacrynic acidSome Trade Names EDECRIN Click for Drug Monograph Etilefrine FenofibrateSome Trade Names ANTARA LIPOFEN TRICOR TRIGLIDE Click for Drug Monograph FurosemideSome Trade Names LASIX Click for Drug Monograph HydrochlorothiazideSome Trade Names ESIDRIX HYDRODIURIL Click for Drug Monograph MilrinoneSome Trade Names PRIMACOR Click for Drug Monograph PhenylephrineSome Trade Names NEO-SYNEPHRINE Click for Drug Monograph Prostaglandins QuinidineSome Trade Names CARDIOQUIN QUINAGLUTE Click for Drug Monograph Hormones DanazolSome Trade Names DANOCRINE Click for Drug Monograph Progesterone Synthetic progestins Nonreproductive hormones, including glucocorticoids Natural estrogens Laxatives — BisacodylSome Trade Names DULCOLAX Click for Drug Monograph Dietary fiber Lactitol LactuloseSome Trade Names CEPHULAC CHRONULAC KRISTALOSE Click for Drug Monograph Lauryl sulfate Psyllium seed Sagrada SennaSome Trade Names EX-LAX SENOKOT Click for Drug Monograph glycosides Sodium docusateSome Trade Names COLACE SURFAK Click for Drug Monograph Sodium picosulfate Sorbitol — Migraines Ergots — — Muscle relaxants CarisoprodolSome Trade Names SOMA Click for Drug Monograph OrphenadrineSome Trade Names NORFLEX Click for Drug Monograph AtracuriumSome Trade Names TRACRIUM Click for Drug Monograph CisatracuriumSome Trade Names NIMBEX Click for Drug Monograph MivacuriumSome Trade Names MIVACRON PancuroniumSome Trade Names PAVULON Click for Drug Monograph RocuroniumSome Trade Names ZEMURON Click for Drug Monograph Suxethonium Vecuronium BaclofenSome Trade Names LIORESAL Click for Drug Monograph Osteoporosis — Bisphosphonates Ca supplements — Peptic ulcers — Alginic acid Ca-containing antacids CimetidineSome Trade Names TAGAMET Click for Drug Monograph Mg-containing antacids SucralfateSome Trade Names CARAFATE Click for Drug Monograph FamotidineSome Trade Names PEPCID Click for Drug Monograph MisoprostolSome Trade Names CYTOTEC Click for Drug Monograph NizatidineSome Trade Names AXID Click for Drug Monograph RanitidineSome Trade Names ZANTAC Click for Drug Monograph Respiratory disorders ClemastineSome Trade Names TAVIST Click for Drug Monograph DimenhydrinateSome Trade Names DRAMAMINE TRIPTONE Click for Drug Monograph Alimemazine CodeineSome Trade Names No US trade name Click for Drug Monograph Corticosteroids Dipalmitoyl phosphatidylcholine Dornase alfaSome Trade Names PULMOZYME Click for Drug Monograph EphedrineSome Trade Names PRETZ-D Click for Drug Monograph Ethylmorphine IpratropiumSome Trade Names ATROVENT Click for Drug Monograph Phenylpropanolamine Phospholipid surfactant Salbutamol Bambuterol Cromoglycic acid CromolynSome Trade Names CROLOM INTAL NASALCROM Click for Drug Monograph Declorahidine DesloratadineSome Trade Names CLARINEX Click for Drug Monograph FexofenadineSome Trade Names ALLEGRA Click for Drug Monograph FormoterolSome Trade Names FORADIL AEROLIZER PERFOROMIST Click for Drug Monograph LevocabastineSome Trade Names LIVOSTIN Click for Drug Monograph LidocaineSome Trade Names XYLOCAINE Click for Drug Monograph (solution for gargling) LoratadineSome Trade Names ALAVERT CLARITIN Click for Drug Monograph Mizolastine OxymetazolineSome Trade Names AFRIN DURATION Click for Drug Monograph Phenoterol SalmeterolSome Trade Names SEREVENT Click for Drug Monograph TerbutalineSome Trade Names BRETHINE BRICANYL Click for Drug Monograph TiotropiumSome Trade Names SPIRIVA Click for Drug Monograph *The classification of the drugs in the list is based on a combination of clinical observations, case reports in the literature, and theoretical considerations derived from the structure and metabolism of the substances. However, clinical observations may in many cases be unreliable. Also, the biochemical and molecular-biologic models for the activation of the disease are incomplete. This list is meant as guidance only and is neither complete nor applicable to all patients. Drugs must always be used cautiously in people who carry genes for acute porphyria. For questions about specific drugs, physicians can consult www.drugs-porphyria.org.

Symptoms and Signs

Symptoms and signs involve the nervous system, abdomen, or both (neurovisceral). Attacks develop over hours or days and can last up to several weeks. Most gene carriers experience no, or only a few, attacks in their lifetime. Others experience recurrent symptoms. In women, recurrent attacks often coincide with the luteal phase of the menstrual cycle.

The acute porphyric attack: Constipation, fatigue, irritability, and insomnia typically precede an acute attack. The most common symptoms of an attack are abdominal pain and vomiting. The pain may be excruciating and is disproportionate to abdominal tenderness or other physical signs. Abdominal manifestations may result from effects on visceral nerves or from local vasoconstrictive ischemia. Because there is no inflammation, the abdomen is not tender and there are no peritoneal signs. Temperature and WBC count are normal or only slightly increased. Bowel distention may develop as a result of paralytic ileus. The urine is red or reddish brown and positive for PBG during an attack.

All components of the peripheral nervous system and the CNS may be involved. Motor neuropathy is common with severe and prolonged attacks. Muscle weakness usually begins in the extremities but can involve any motor neuron or cranial nerve and proceed to tetraplegia. Bulbar involvement can cause respiratory failure.

CNS involvement may cause seizures or mental disturbances (eg, apathy, depression, agitation, frank psychosis, hallucinations). Seizures, psychotic behavior, and hallucinations may be due to or exacerbated by hyponatremia or hypomagnesemia, which can also contribute to cardiac arrhythmias. Hyponatremia may occur during an acute attack due to excessive antidiuretic hormone (ADH) release and/or administration of hypotonic IV solutions (5% or 10% dextrose in water), a standard therapy for acute attacks.

Excess catecholamines generally cause restlessness and tachycardia. Rarely, catecholamine-induced arrhythmias cause sudden death. Labile hypertension with transiently high BP may cause vascular changes progressing to irreversible hypertension if untreated. Renal failure in acute porphyria is multifactorial; acute hypertension (possibly leading to chronic hypertension) is likely a main precipitating factor.

Subacute or subchronic symptoms: Some patients have prolonged symptoms of lesser intensity (eg, obstipation, fatigue, headache, back or thigh pain, paresthesia, tachycardia, dyspnea, insomnia, depression, anxiety or other disturbances of mood, seizures).

Skin symptoms in VP and HCP: Fragile skin and bullous eruptions may develop on sun-exposed areas, even in the absence of neurovisceral symptoms. Often patients are not aware of the connection to sun exposure. Cutaneous manifestations are identical to those of porphyria cutanea tarda (see Porphyrias: Porphyria Cutanea Tarda); lesions typically occur on the dorsal aspects of the hands and forearms, the face, ears, and neck.

Late manifestations: Motor involvement during acute attacks may lead to persistent muscle weakness and muscle atrophy between attacks. Cirrhosis, hepatocellular carcinoma, systemic arterial hypertension, and renal impairment become more common after middle age in AIP and possibly also in VP and HCP, especially in patients with previous porphyric attacks.

Diagnosis

• Urine screen for PBG
• If urine results are positive, quantitative ALA and PBG determination
• For confirmation of AIP, measurement of PBG deaminase activity in erythrocytes
• Genetic analysis if type is to be identified

Acute attack: Misdiagnosis is common because the acute attack is confused with other causes of acute abdomen (sometimes leading to unnecessary surgery) or with a primary neurologic or mental disorder. However, in patients previously diagnosed as gene carriers or who have a positive family history, porphyria should be suspected. Still, even in known gene carriers, other causes must be considered.

Red or reddish brown urine, not present before onset of symptoms, is a cardinal sign and is present during full-blown attacks. A urine specimen should be examined in patients with abdominal pain of unknown cause, especially if severe constipation, vomiting, tachycardia, muscle weakness, bulbar involvement, or mental symptoms occur.

If porphyria is suspected, the urine is analyzed for PBG using a rapid qualitative or semiquantitative determination. A positive result or high clinical suspicion necessitates quantitative ALA and PBG measurements preferentially obtained from the same specimen. PBG and ALA levels > 5 times normal indicate an acute porphyric attack unless patients are gene carriers in whom porphyrin precursor excretion occurs at similar levels even during the latent phase of the disorder.

If urinary PBG and ALA levels are normal, an alternative diagnosis must be considered. Measurement of urinary total porphyrins and high-performance liquid chromatography profiles of these porphyrins are helpful. Elevated urinary ALA and coproporphyrin with normal or slightly increased PBG suggests lead poisoning, ALAD-deficiency porphyria, or hereditary tyrosinemia type 1. Analysis of a 24-h urine specimen is not necessary. Instead, a random urine specimen is used, and PBG and ALA levels are corrected for dilution by relating to the creatinine level of the sample. Electrolytes and Mg should be measured. Hyponatremia may be present because of excessive vomiting or diarrhea after hypotonic fluid replacement or because of the syndrome of inappropriate ADH secretion (SIADH).

Determination of type: Because treatment does not depend on the type of acute porphyria, identification of the specific type is valuable mainly for finding gene carriers among relatives. When the type and mutation are already known from previous testing of relatives, the diagnosis is clear but may be confirmed by gene analysis. Activity of the enzymes ALAD and PBGD in the red blood cells is readily measurable and can be helpful for establishing the diagnosis in ALAD-deficiency porphyria and acute intermittent porphyria, respectively. RBC PBG deaminase levels that are about 50% of normal suggest AIP. If there is no family history to guide the diagnosis, the different forms of acute porphyria are distinguished by characteristic patterns of porphyrin (and precursor) accumulation and excretion in plasma, urine, and stool. When urinalysis reveals increased levels of ALA and PBG, fecal porphyrins may be measured. Fecal porphyrins are usually normal or minimally increased in AIP but elevated in HCP and VP. Often, these markers are not present in the quiescent phase of the disorder. Plasma fluorescence emission after excitation with Soret band of light (~410 nm) can be used to differentiate HCP and VP, which have different peak emissions.

Family studies: Children of a gene carrier for an autosomal dominant form of acute porphyria (AIP, HCP, VP) have a 50% risk of inheriting the disorder. In contrast, children of patients with ALAD-deficiency porphyria (autosomal recessive inheritance) are obligate carriers but are very unlikely to develop clinical disease. Because early diagnosis followed by counseling reduces the risk of morbidity, children in affected families should be tested before the onset of puberty. Genetic testing is used if the mutation has been identified in the index case. If not, pertinent RBC or WBC enzyme levels are measured. Gene analysis can be used for in utero diagnosis (using amniocentesis or chorionic villus sampling) but is seldom indicated because of the favorable outlook for most gene carriers.

Prognosis

Advances in medical care and self-care have improved the prognosis for symptomatic patients. Still, some patients develop recurrent crises or progressive disease with permanent paralysis or renal failure. Also, frequent need for opioids analgesics may give rise to opioid dependence.

Treatment

• Triggers eliminated if possible
• Dextrose (oral or IV)
• IV heme

Treatment of the acute attack is identical for all the acute porphyrias. Possible triggers (eg, excessive alcohol use, drugs) are identified and eliminated. Unless the attack is mild, patients are hospitalized in a darkened, quiet, private room. Heart rate, BP, and fluid and electrolyte balance are monitored. Neurologic status, bladder function, muscle and tendon function, respiratory function, and pulse oximetry are continuously monitored. Symptoms (eg, pain, vomiting) are treated with nonporphyrinogenic drugs as needed (see Table 4: Porphyrias: Drugs and Porphyria*).

Dextrose 300 to 500 g daily down-regulates hepatic ALA synthase (ALAS 1) and relieves symptoms. Dextrose can be given by mouth if patients are not vomiting; otherwise, it is given IV. The usual regimen is 3 L of 10% dextrose solution, given by a central venous catheter over 24 h (125 mL/h). However, to avoid overhydration with consequent hyponatremia, 1 L of 50% dextrose solution can be used instead.

IV heme is more effective than dextrose and should be given immediately in severe attacks, electrolyte imbalance, or muscle weakness. Heme usually resolves symptoms in 3 to 4 days. If heme therapy is delayed, nerve damage is more severe and recovery is slower and possibly incomplete. Heme is available in the US as lyophilized hematin to be reconstituted in a glass vial with sterile water. The dose is 3 to 4 mg/kg IV once/day for 4 days. An alternative is heme arginate, which is given at the same dose, except that it is diluted in 5% dextrose or half-normal or quarter-normal saline. Hematin and heme arginate may cause venous thrombosis and/or thrombophlebitis. Risk of these adverse events appears to be lower if the heme is administered bound to human serum albumin. Such binding also decreases the rate of development of hematin aggregates. Thus, most authorities recommend administration of hematin or heme arginate with human serum albumin.

In patients with severe recurrent attacks, who are at risk of renal damage or permanent neurologic damage, liver transplantation is an option. Successful liver transplantation leads to permanent cure of all acute porphyrias other than ALAD-deficiency porphyria. Patients with acute porphyrias should not serve as liver donors even though their liver may appear structurally normal (ie, no cirrhosis) because recipients have developed acute porphyric syndromes; such an outcome helped establish that the acute porphyrias are hepatic disorders. Renal transplantation, with or without simultaneous liver exchange, should be considered in patients with active disease and terminal renal failure, because there is considerable risk that nerve damage will progress at the start of dialysis.

Prevention

Carriers of acute porphyria should avoid the following:

• Potentially harmful drugs (see Table 4: Porphyrias: Drugs and Porphyria*)
• Heavy alcohol use
• Physical or emotional stress or exhaustion
• Exposure to organic solvents (eg, in painting or dry cleaning)
• Crash diets
• Periods of starvation

Diets for obesity should provide gradual weight loss and be adopted only during periods of remission. Carriers of VP or HCP should minimize sun exposure; sunscreens that block only ultraviolet B light are ineffective, but opaque zinc oxide or titanium dioxide preparations are beneficial. Support associations such as the American Porphyria Foundation and the European Porphyria Network, for porphyria patients can provide written information and direct counseling.

Patients should be identified prominently in the medical record as carriers and should carry a card verifying the carrier state and precautions to be observed.

A high-carbohydrate diet may decrease the risk of acute attacks. A high-carbohydrate diet or a lump of sugar every hour may help relieve symptoms of an acute attack. Prolonged use should be avoided in order to decrease risk of obesity and dental caries.

Patients who experience recurrent and predictable attacks (typically women with attacks related to the menstrual cycle) may benefit from prophylactic heme therapy given shortly before the expected onset. There is no standardized regimen; a specialist should be consulted. Frequent premenstrual attacks in some women are aborted by administration of a gonadotropin-releasing hormone analog plus low-dose estrogen. Low-dose oral contraceptives are sometimes used successfully, but the progestin component is likely to exacerbate the porphyria.

To prevent renal damage, chronic hypertension should be treated aggressively (using safe drugs). Patients with evidence of impaired renal function are referred to a nephrologist. Recent anecdotal experience indicates that tolvaptan, an ADH blocker, is helpful in the management of hyponatremia during acute attacks.

The incidence of hepatocellular cancer is high among carriers of acute porphyria, especially in patients with active disease. Patients who are > 50 should undergo yearly or twice yearly surveillance, including liver screening with ultrasonography. Early intervention can be curative and increases life expectancy.

Key Points

• Acute porphyrias cause intermittent attacks of abdominal pain and neurologic symptoms; some types also have cutaneous manifestations that are triggered by sun exposure.
• Attacks have many triggers, including hormones, drugs, low-calorie and low-carbohydrate diets, and alcohol ingestion.
• Attacks typically involve severe abdominal pain (with a non-tender abdomen) and vomiting; any component of the peripheral and central nervous system may be affected but muscle weakness is common.
• Urine is often reddish-brown during an attack.
• Do a qualitative urine test for PBG and confirm a positive result with quantitative ALA and PBG measurements
• Treat acute attacks with oral or IV dextrose and, for severe attacks, IV heme.

Last full review/revision March 2013 by Herbert L. Bonkovsky; Vinaya Maddukuri, MD

Content last modified March 2013