Is Lurasidone (Lurasidone) safe to use in patients with Hereditary Coproporphyria?

Lurasidone Safety in Hereditary Coproporphyria

Lurasidone should be avoided in patients with Hereditary Coproporphyria (HCP) as it may potentially trigger acute porphyric attacks by inducing cytochrome P450 enzymes. 1

Understanding Hereditary Coproporphyria

Hereditary Coproporphyria (HCP) is one of the acute hepatic porphyrias (AHPs), characterized by:

• Autosomal dominant inheritance with deficiency in coproporphyrinogen oxidase enzyme 1
• Biochemical pattern of excessive coproporphyrin excretion in feces and urine 2
• Clinical presentation similar to other acute porphyrias with neurovisceral symptoms 1
• Potential for acute attacks triggered by certain medications, including those that induce cytochrome P450 enzymes 1, 3

Medication Management in HCP

Risk Assessment for Lurasidone

Lurasidone is an atypical antipsychotic that is metabolized by cytochrome P450 enzymes, particularly CYP3A4. For patients with HCP:

• Medications that induce cytochrome P450 enzymes are known precipitants of acute attacks in acute hepatic porphyrias 1
• The American Gastroenterological Association (AGA) specifically advises avoiding medications that induce cytochrome P450s as they can directly up-regulate ALAS1 messenger RNA, which is central to the pathophysiology of acute porphyric attacks 1
• Drug safety databases should always be checked before prescribing new medications to patients with porphyria 3

Alternative Psychiatric Medications

When psychiatric treatment is needed for patients with HCP:

• Benzodiazepines are generally considered safer options for patients with acute hepatic porphyrias 1
• Levetiracetam is considered safe for seizure management in the context of AHP 1
• Gabapentin may be used safely for both seizure control and anxiety management 3

Management Approach for HCP Patients

Prevention of Acute Attacks

1. Medication screening:

   • All medications should be verified through porphyria drug safety databases (available at https://www.porphyria.org/patient-resources/drug-safety-database-for-ahp/ and http://www.drugs-porphyria.org/) 1
   • Avoid medications that induce cytochrome P450 enzymes 1

2. Additional preventive measures:

   • Avoid alcohol consumption 1
   • Avoid fasting or severe caloric restriction 3
   • Minimize physical and psychological stress 1

3. Monitoring:

   • Regular neurological assessment for chronic neuropathic pain, motor and sensory deficits 3
   • Renal function monitoring with eGFR and blood pressure checks 3
   • Hepatic screening with liver function tests 3

Management During Acute Attacks

If an acute attack occurs:

1. Immediate interventions:

   • Discontinue any potentially triggering medications 1
   • Administer carbohydrate loading (300g/day) orally or as 10% glucose intravenously 1, 3
   • Treat pain aggressively with safe analgesics 1
   • Monitor and correct electrolyte abnormalities, particularly hyponatremia and hypomagnesemia 1

2. Advanced treatments:

   • Intravenous hemin therapy for severe attacks 1
   • Consider givosiran for patients with recurrent attacks (4 or more per year) 1, 4

Clinical Pearls and Pitfalls

• Diagnostic challenge: HCP is often misdiagnosed due to nonspecific symptoms, with diagnosis delays exceeding 15 years from initial presentation 1
• Medication errors: Prescribing unsafe medications is a common pitfall that can precipitate potentially life-threatening attacks 3
• Chronic manifestations: HCP is associated with long-term risks including hypertension, chronic kidney disease, and hepatocellular carcinoma 1
• Treatment response: Some patients may experience prolonged improvement in symptoms even after discontinuation of treatments like givosiran 4

Conclusion

When managing patients with Hereditary Coproporphyria who require psychiatric treatment, lurasidone should be avoided due to its potential to trigger acute porphyric attacks through cytochrome P450 induction. Alternative psychiatric medications with established safety profiles in porphyria should be selected instead, and all medication decisions should be verified through porphyria-specific drug safety databases.