About AHP

Acute hepatic porphyria (AHP) is a rare, genetic disease characterized by debilitating, potentially life-threatening attacks1-3

There are 4 types of AHP2,4

Most common
Extremely rare
Chart showing the 4 types of AHP ranging from most to least common
  • Acute Intermittent Porphyria (AIP)
    • ~80% of all AHP cases are AIP
  • Variegate Porphyria (VP)
  • Hereditary Coproporphyria (HCP)
  • ALAD-Deficiency Porphyria (ADP)

ALAD, delta-aminolevulinic acid dehydratase.

AHP attacks can be severe, unpredictable, and progressive

  • AHP can affect anyone, but is most commonly seen in women of childbearing age5
  • Attacks generally last 3 to 7 days, but recovery can take longer4
  • Severe attacks can progress to respiratory failure or paralysis, leading to temporary or permanent disability3,4
  • Some patients with recurrent attacks report chronic symptoms and can develop long-term complications4,6

Common signs and symptoms of an AHP attack2,4

Cardinal symptom

SEVERE, DIFFUSE ABDOMINAL PAIN2,4

The cardinal symptom severe, diffuse abdominal pain plus 1 or more additional findings
1 or more additional findings2

AUTONOMIC
Nervous System2,6

  • Nausea/Vomiting
  • Constipation
  • Tachycardia

CENTRAL
Nervous System2,6

  • Seizures
  • Anxiety
  • Mental status changes

PERIPHERAL
Nervous System2,6

  • Limb weakness or pain

CUTANEOUS2✱

  • Skin lesions
    on sun-exposed areas

*Cutaneous symptoms only occur in HCP and VP.2

>90% of patients report abdominal pain during AHP attacks.2

AHP can go undiagnosed for many years7

Patients with AHP are often diagnosed with other diseases with overlapping symptoms2,8,9

Icon of intestines

  • Acute gastroenteritis with vomiting
  • Cholecystitis
  • Crohn's disease
  • Intestinal occlusion
  • Irritable bowel syndrome (IBS)

Icon of a person

  • Appendicitis
  • Chronic hepatitis
  • Endometriosis
  • Pancreatitis
  • Peritonitis

Icon of a brain

  • Anxiety/depression
  • Fibromyalgia
  • Guillain-Barré syndrome
  • Polyneuropathy
  • Psychosis
  • Seizure disorders

References: 1. Balwani M et al; the Porphyrias Consortium of the Rare Diseases Clinical Research Network. Acute hepatic porphyrias: recommendations for evaluation and long-term management. Hepatology. 2017;66(4):1314-1322. 2. Ventura P et al; Gruppo Italiano Porfiria (GrIP). A challenging diagnosis for potential fatal diseases: recommendations for diagnosing acute porphyrias. Eur J Intern Med. 2014;25(6):497-505. 3. Neeleman RA et al. Medical and financial burden of acute intermittent porphyria. J Inherit Metab Dis. 2018;41(5):809-817. 4. Simon A et al. Patient perspective on acute intermittent porphyria with frequent attacks: a disease with intermittent and chronic manifestations. Patient. 2018;11(5):527-537. 5. Bissell DM et al. Porphyria. N Engl J Med. 2017;377(9):862-872. 6. Puy H et al. Porphyrias. Lancet. 2010;375(9718):924-937. 7. Anderson KE. Acute hepatic porphyrias: current diagnosis & management. Mol Genet Metab. doi: 10.1016/j.ymgme.2019.07.002. 8. Alfadhel M et al. Acute intermittent porphyria caused by novel mutation in HBMS gene, misdiagnosed as cholecystitis. Neuropsychiatr Dis Treat. 2014;10:2135-2137. 9. Ko JJ et al. Real-world analysis of symptoms, diagnostic patterns, and provider perspective on acute hepatic porphyrias. Poster presented at: American College of Gastroenterology Annual Scientific Meeting; October 5-10, 2018; Philadelphia, PA. 

 

IMPORTANT SAFETY INFORMATION

Contraindications

GIVLAARI® (givosiran) is contraindicated in patients with known severe hypersensitivity to givosiran. Reactions have included anaphylaxis.

Anaphylactic Reaction

Anaphylaxis has occurred with GIVLAARI treatment (<1% of patients in clinical trials). Ensure that medical support is available to appropriately manage anaphylactic reactions when administering GIVLAARI. Monitor for signs and symptoms of anaphylaxis. If anaphylaxis occurs, immediately discontinue administration of GIVLAARI and institute appropriate medical treatment.

Hepatic Toxicity

Transaminase elevations (ALT) of at least 3 times the upper limit of normal (ULN) were observed in 15% of patients receiving GIVLAARI in the placebo-controlled trial. Transaminase elevations primarily occurred between 3 to 5 months following initiation of treatment.

Measure liver function tests prior to initiating treatment with GIVLAARI, repeat every month during the first 6 months of treatment, and as clinically indicated thereafter. Interrupt or discontinue treatment with GIVLAARI for severe or clinically significant transaminase elevations. In patients who have dose interruption and subsequent improvement, reduce the dose to 1.25 mg/kg once monthly. The dose may be increased to the recommended dose of 2.5 mg/kg once monthly if there is no recurrence of severe or clinically significant transaminase elevations at the 1.25 mg/kg dose.

Renal Toxicity

Increases in serum creatinine levels and decreases in estimated glomerular filtration rate (eGFR) have been reported during treatment with GIVLAARI. In the placebo-controlled study, 15% of patients receiving GIVLAARI experienced a renally-related adverse reaction. The median increase in creatinine at Month 3 was 0.07 mg/dL. Monitor renal function during treatment with GIVLAARI as clinically indicated.

Injection Site Reactions

Injection site reactions were reported in 25% of patients receiving GIVLAARI in the placebo-controlled trial. Symptoms included erythema, pain, pruritus, rash, discoloration, or swelling around the injection site. One (2%) patient experienced a single, transient, recall reaction of erythema at a prior injection site with a subsequent dose administration.

Drug Interactions

Concomitant use of GIVLAARI increases the concentration of CYP1A2 or CYP2D6 substrates, which may increase adverse reactions of these substrates. Avoid concomitant use of GIVLAARI with CYP1A2 or CYP2D6 substrates for which minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, decrease the CYP1A2 or CYP2D6 substrate dosage in accordance with approved product labeling.

Adverse Reactions

The most common adverse reactions that occurred in patients receiving GIVLAARI were nausea (27%) and injection site reactions (25%).

INDICATION

GIVLAARI is indicated for the treatment of adults with acute hepatic porphyria (AHP).

For additional information about GIVLAARI, please see full Prescribing Information.