Important Safety Information | Prescribing Information | Indications and Usage | Medical Information | Report An Adverse Event
Important Safety Information
Prescribing Information | Indications & Usage
Medical Information | Report An Adverse Event
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About Acute Intermittent Porphyria (AIP)

Acute intermittent porphyria (AIP) - one of the hepatic porphyrias - is a rare, inherited genetic condition caused by a partial deficiency of the enzyme porphobilinogen (PBG) deaminase,1 which can disrupt normal heme production in the body.2

What causes an acute AIP attack?

Exposure to one or more precipitating factors, such as endogenous steroid hormones or certain prescription drugs, may increase the body's need for heme.3 The partial deficiency of PBG deaminase, the third enzyme in the multi-step heme biosynthetic pathway, can become rate-limiting in the production of heme.4 This can cause neurotoxic porphyrin precursors to accumulate as the body continues to signal for additional heme.4

Prompt recognition and treatment of an acute AIP attack are critical

If unrecognized and untreated, an AIP attack can progress to neurologic damage or death due to cardiac arrhythmia or paralysis.3

Common Signs & Symptoms of an AIP Attack

The most common symptom is severe abdominal pain, which is neuropathic in origin.3 Other symptoms that can increase suspicion of an AIP attack are urine that turns dark or reddish when exposed to light or air and hyponatremia.1 Untreated attacks can cause serious consequences both during and after attacks.3

Clinical features of an AIP attack can include3:

GASTROINTESTINAL
  • Severe, unremitting, diffuse abdominal pain
  • Nausea/vomiting
  • Constipation
URINARY
  • Dark or reddish urine
NEUROLOGIC
  • Pain in extremities, back, chest, neck, or head
  • Paresis
  • Hyponatremia, leading to seizures or other complications5
  • Psychiatric symptoms such as agitation, confusion, or hallucinations
CARDIOVASCULAR
  • Tachycardia
  • Systemic arterial hypertension

MOST COMMON SYMPTOM:
Severe abdominal pain occurs in 85%-95% of attacks3

Serious consequences of not treating an AIP attack include3:

  • Peripheral neuropathy
  • Paresis
  • Respiratory and bulbar paralysis
  • Chronic neuropathic pain
  • Death resulting from cardiac arrhythmia or paralysis during an attack

Recurring and untreated attacks increase the risk of irreversible neuronal damage3

AIP attacks can be triggered by internal or external precipitating factors

Symptoms of an AIP attack can be general and nonspecific3. However, symptoms can occur after certain triggering events,3 such as:

  • Luteal phase of a woman's menstrual cycle from changes in estrogen and progesterone levels3,7
  • Use of certain prescription drugs that are metabolized by the heme-based cytochrome P450 (CYP) enzyme system3,8
  • Use of alcohol or illicit drugs such as amphetamines, cocaine, and derivatives6
  • Fasting7 or crash dieting3
  • Cigarette smoking3
  • Metabolic stress induced by infections or surgery3
  • Psychological stress3

American Porphyria Foundation – Safe/Unsafe Drug Database

Search the American Porphyria Foundation's safe/unsafe drug database for prescription and over-the-counter drugs that may trigger AIP attacks

Diagnostic testing is available for AIP

INITIAL TESTING:

A PBG urine test should be done at or near the time of AIP symptoms. Urinary PBG levels are substantially increased (20–200 mg/L) in patients with acute attacks of AIP.3



SECOND LINE TESTING:

If PBG levels are elevated, second-line testing should be done to determine the precise type of acute porphyria. These tests may include δ-aminolevulinic acid (ALA) and porphyrin testing on the same urine sample, as well as testing for plasma and fecal porphyrins and erythrocyte PBG deaminase. Treatment should not be delayed pending these results.3



DNA STUDIES

can be done to determine the disease-causing mutation(s) in the defective gene. Family members can then be tested to determine if they may be at risk of AIP attacks.3

LABORATORY FINDINGS THAT DIFFERENTIATE AIP FROM OTHER ACUTE PORPHYRIAS

AN INCREASE IN:

Urine porphyrin levels (mostly uroporphyrin)
markedly increased

Fecal porphyrin levels
normal or slightly increased

Plasma porphyrin levels
normal or slightly increased

A DECREASE IN:

Erythrocyte PBG deaminase levels
decreased by ~50%

Diagnostic tests are available through major clinical laboratories

DISCUSSING ACUTE INTERMITTENT PORPHYRIA WITH YOUR FAMILY
A GUIDE FOR PATIENTS

Download here to help your patients discuss AIP with their families

DOWNLOAD an AIP ATTACK PLAN

template for your patients to fill out with key action steps and contact information

DOWNLOAD an EMERGENCY PROTOCOL LETTER

template for your patients to have on hand if they need to seek emergency care

Indications And Usage

PANHEMATIN® is a hemin for injection indicated for the amelioration of recurrent attacks of acute intermittent porphyria temporally related to the menstrual cycle in susceptible women, after initial carbohydrate therapy is known or suspected to be inadequate.

Limitations of Use

  • Before administering PANHEMATIN, consider an appropriate period of carbohydrate loading (i.e., 400 g glucose/day for 1 to 2 days).
  • Attacks of porphyria may progress to a point where irreversible neuronal damage has occurred. PANHEMATIN therapy is intended to prevent an attack from reaching the critical stage of neuronal degeneration. PANHEMATIN is not effective in repairing neuronal damage.

Indications and Important
Safety Information

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Indications And Usage

PANHEMATIN® is a hemin for injection indicated for the amelioration of recurrent attacks of acute intermittent porphyria temporally related to the menstrual cycle in susceptible women, after initial carbohydrate therapy is known or suspected to be inadequate.

Important Safety Information

  • Do not use in patients with known hypersensitivity to PANHEMATIN.
  • Phlebitis is possible. Utilize a large arm vein or a central venous catheter for administration to minimize the risk of phlebitis.
  • Elevated iron and serum ferritin may occur. Monitor iron and serum ferritin in patients receiving multiple administrations of PANHEMATIN.
  • PANHEMATIN has transient and mild anticoagulant effect. Avoid concurrent anticoagulant therapy.
  • Reversible renal shutdown has been observed with an excessive hematin dose (12.2 mg/kg in a single infusion). Strictly follow recommended dosage guidelines.
  • PANHEMATIN may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent.
  • Most common adverse reactions in >1% of patients are headache, pyrexia, infusion site reactions, and phlebitis.
  • To report SUSPECTED ADVERSE EFFECTS, contact Recordati Rare Diseases Inc. at 1-888-575-8344, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
  • Avoid CYP inducing drugs such as estrogens, barbituric acid derivatives and steroid metabolites which induce δ‑aminolevulinic acid synthetase 1 (ALAS1) through a feedback mechanism.
For more information, please see PANHEMATIN Full Prescribing Information at www.recordatirarediseases.com.

References

  1. Whatley SD, Badminton MN. Acute Intermittent Porphyria. 2005 Sep 27 [Updated 2013 Feb 7]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
  2. Gonzalez-Arriaza HL, Bostwick JM. Acute porphyrias: A case report and review. Am J Psych. 2003;160(3);450-458.
  3. Anderson KE, Bloomer JR, Bonkovsky HL, Kushner JP, Pierach CA, Pimstone NR, Desnick RJ. Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med. 2005;142:439-450.
  4. Balwani M, Wang B, Anderson KE, Bloomer JR, Bissell DM, Bonkovsky HL, Phillips JD, Desnick RJ; for the Porphyrias Consortium of the Rare Diseases Clinical Research Network. Acute hepatic porphyrias: Recommendations for evaluation and long-term management. Hepatol. 2017;66(4):1314-1322.
  5. Wang B, Rudnick S, Cengia B, Bonkovsky HL. Acute hepatic porphyrias: Review and recent progress. Hepatol Commun. 2019;3(2):193-206.
  6. Ventura P, Cappellini MD, Rocchi E. The acute porphyrias: a diagnostic and therapeutic challenge in internal and emergency medicine. Intern Emerg Med. 2009;4:297-308.
  7. Besur S, Hou W, Schmeltzer P, Bonkovsky HL. Clinically important features of porphyrin and heme metabolism and the porphyrias. Metabolites. 2014;4:977-1006.

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