What is the management and treatment for acute intermittent porphyria?

Management and Treatment of Acute Intermittent Porphyria

The management of acute intermittent porphyria (AIP) requires both acute attack treatment with intravenous hemin (3-4 mg/kg/day) and long-term preventive strategies focused on avoiding known triggers such as porphyrinogenic medications, alcohol, and fasting. 1

Acute Attack Management

First-line Treatment

• Intravenous hemin (3-4 mg/kg/day) administered once or twice daily for 3-5 days 2
  • Should be given into a high-flow central vein via PICC or central port
  • Heme bound to human serum albumin is preferred due to heme stabilization and less vein irritation
  • Collect urine for ALA and PBG levels before starting hemin

Supportive Care During Attacks

• Pain management: Aggressive treatment with safe analgesics (avoid porphyrinogenic medications)
• Intravenous carbohydrate loading: Approximately 300 g/day in adults 1
• Antiemetics for nausea and vomiting
• Electrolyte monitoring and correction:
  • Monitor for hyponatremia and hypomagnesemia
  • Correct hyponatremia slowly to prevent osmotic demyelination syndrome 3
  • Use 0.9% saline for hypovolemic hyponatremia; fluid restriction for SIADH

Seizure Management

• Use magnesium sulfate, benzodiazepines, or levetiracetam for seizure control 1
• AVOID barbiturates, hydantoins, carbamazepine, and valproic acid as they are contraindicated in AIP 1

Long-term Management Based on Patient Subgroups

1. For Patients with Recurrent Attacks (≥4 per year)

• Prophylactic therapy options:
  • Givosiran: FDA-approved subcutaneous therapy that targets ALAS1 mRNA 1
    • Monthly administration
    • Monitor for elevations in liver enzymes, BUN, creatinine, homocysteine, amylase, and lipase
  • Prophylactic hemin infusions: Consider for patients who cannot use givosiran 1
    • Monitor for iron overload, catheter-related complications

2. For Patients with Sporadic Attacks (<4 per year)

• Focus on trigger avoidance and prompt treatment of acute attacks
• Regular monitoring of biochemical markers

3. For Asymptomatic Carriers and High Excretors

• Patient education on trigger avoidance
• Regular follow-up based on biochemical activity

Preventive Strategies for All Patients

Trigger Avoidance

• Medications: Use only safe medications from porphyria drug databases 1
  • Resources: https://www.porphyria.org/patient-resources/drug-safety-database-for-ahp/ and http://www.drugs-porphyria.org/
• Lifestyle modifications:
  • Avoid alcohol and smoking
  • Prevent fasting and caloric deprivation
  • Manage physical and psychological stress
  • Avoid hormonal fluctuations (particularly progesterone) 1

Hormonal Management

• For women with menstrual cycle-associated attacks, consider GnRH agonists (though success may be limited) 1

Special Considerations

Liver Transplantation

• Reserved for patients with intractable symptoms and significantly decreased quality of life who are refractory to pharmacotherapy 1
• Has been shown to be curative in severe cases by normalizing ALA and PBG levels

Common Pitfalls to Avoid

1. Delayed diagnosis due to nonspecific symptoms
2. Use of contraindicated medications during attacks
3. Inadequate pain control
4. Overly rapid correction of hyponatremia
5. Failure to recognize and remove triggering factors

Monitoring

• Regular assessment of urinary ALA and PBG levels
• Monitor for long-term complications including chronic liver disease, chronic kidney disease, and hypertension
• Screen for iron overload in patients receiving chronic hemin therapy

AIP management requires prompt recognition and aggressive treatment of acute attacks while implementing comprehensive preventive strategies to minimize future attacks and improve quality of life.