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Acute symptomatic seizures occur in 10–20% of patients with acute intermittent porphyria in relapse. There are rarer reports of porphyria in people with chronic epilepsy who are mostly drug resistant. The association between epilepsy and porphyria is unclear. Porphyria might be the cause of chronic symptomatic epilepsy (if so, this would be rare or frequently undiagnosed) or there might be a chance association, given that epilepsy is common. Nevertheless, in drug-resistant epilepsy, clinicians should consider metabolic causes such as the porphyrias, especially when the seizure frequency increases on higher doses of certain antiepileptic drugs. Acute porphyric attacks can be potentially fatal and are usually precipitated, in susceptible individuals, by exposure to commonly used drugs, including certain antiepileptic drugs. It is, therefore, important to determine the correct dose and safety of use of certain drugs in people with porphyria. Having diagnosed porphyria-related seizures, the patient will also need treatment of the porphyria itself; its management includes appropriate selection of a non-porphyrinogenic antiepileptic drug. Enzyme-inducing medications induce hepatic heme synthesis, which can exacerbate porphyria symptoms, or provoke acute attacks.
Clinical experience and findings from experimental systems using whole animal or cell culture models have been used to determine porphyrogenicity (the potential of a drug to induce an acute porphyric attack) and to classify drugs as safe or unsafe in freely available drug lists (eg, http://www.drugs-porphyria.org; http://www.wmic.wales.nhs.uk/pdfs/porphyria/2015%20Porphyria%20safe%20list.pdf).
In acute porphyric attacks, seizures can be treated with intravenous diazepam, levetiracetam or propofol if status epilepticus develops; a single or few seizures may not require antiepileptic drug treatment in the long term, provided the porphyria itself is properly managed (box 1).
Antiepileptic drugs and porphyria
Antiepileptic drugs considered safe for use in the acute porphyrias (not porphyrinogenic or probably not porphyrinogenic)
▸ Pregabalin …
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