Metabolic Disorders

Acute porphyria - affects 1 in 75,000 people

What happens in acute porphyric crises - MOA and symptoms?

Acute porphyria = hereditary disorders of haem biosynthesis

A build up of porphyrins which leads to acute attacks of the torso, leg and arm causing pain, nausea, vomiting, constipations, confusion, tachycardia and increased BP.

Certain drugs induce acute porphyric crises.

What can be used to treat recurrent attacks in acute hepatic porphyria for patients aged 12+?

Givosiran - used to prevent attacks for those with severe, recurrent attacks i.e 4 or more within a 12 month period.

• SC monthly injection

What is used as haem replacement in an acute porphyria crisis?

Haem arginate

What drugs are unsafe in patients with acute porphyria?

• Anabolic steroids

• Antidepressants, MAOIs (contact UKPMIS for advice)

• Antidepressants, Tricyclic and related (contact UKPMIS for advice)

• Barbiturates (includes primidone and thiopental)

• Contraceptives, hormonal (for detailed advice contact UKPMIS or a porphyria specialist)

• Hormone replacement therapy (for detailed advice contact UKPMIS or a porphyria specialist)

• Imidazole antifungals (applies to oral and intravenous use; topical antifungals are thought to be safe due to low systemic exposure)

• Non-nucleoside reverse transcriptase inhibitors (contact UKPMIS for advice)

• Progestogens (for detailed advice contact UKPMIS or a porphyria specialist)

• Protease inhibitors (contact UKPMIS for advice)

• Sulfonamides (includes co-trimoxazole and sulfasalazine)

• Sulfonylureas (glipizide and glimepiride are thought to be safe)

• Taxanes (contact UKPMIS for advice)

• Triazole antifungals (applies to oral and intravenous use; topical antifungals are thought to be safe due to low systemic exposure)

The above are CYP substrates - inhibitors and inducers.