Ergotism and factitious hypotension associated with interaction of ergotamine with CYP3A4 inhibitors.

Abstract

BACKGROUND:

Although uncommon, severe ergotism continues to occur. The purpose of this study is to describe causes and clinical effects of ergotism in recent years.

METHODS:

This is an observational case series with data obtained retrospectively from all patients with ergotism referred to Ramathibodi Poison Center in Bangkok, Thailand from January 2006 to August 2013.

RESULT:

Twelve cases of ergotism were identified. All cases involved ergotamine 1 mg/caffeine 100 mg combination tablets. Nine cases (75%) were precipitated by drug-drug interactions with CYP3A4 inhibitors. The other cases involved suicidal attempt (2 cases) and pediatric unsupervised ingestion (1 case). Ten patients (83%) had signs of peripheral vascular insufficiency. Five of these patients initially had factitiously low or unmeasurable blood pressure using non-invasive technique and had paradoxical increase following intravenous vasodilator administration. Two patients required partial foot amputations due to gangrene. Two patients, including a 15-month-old boy with an unsupervised ingestion, died.

DISCUSSION:

In this series, most cases of severe ergotism were associated with interaction with CYP3A4 inhibitors, which increase ergotamine bioavailability. Factitious low blood pressure in these cases was likely caused by severe vasospasm.

CONCLUSION:

Critical ergotism continues to occur in Thailand, most commonly associated with the drug-drug interactions.

• Authors: S Srisuma, E J Lavonas, W Wananukul
• Journal: Clinical toxicology (Philadelphia, Pa.) (Clin Toxicol (Phila)) Vol. 52 Issue 7 Pg. 674-7 (Aug 2014) ISSN: 1556-9519 [Electronic] England
• PMID: 24978905 (Publication Type: Case Reports, Journal Article, Observational Study)

Chemical References

• Cytochrome P-450 CYP3A Inhibitors
• Enzyme Inhibitors
• Vasoconstrictor Agents
• Cytochrome P-450 CYP3A
• CYP3A4 protein, human
• Ergotamine

Topics

• Adult
• Biological Availability
• Cytochrome P-450 CYP3A (metabolism)
• Cytochrome P-450 CYP3A Inhibitors
• Drug Interactions
• Enzyme Inhibitors (adverse effects)
• Ergotamine (pharmacokinetics, toxicity)
• Ergotism (physiopathology, therapy)
• Fatal Outcome
• Female
• Humans
• Hypotension (etiology)
• Infant
• Male
• Middle Aged
• Peripheral Vascular Diseases (etiology)
• Poison Control Centers
• Thailand
• Treatment Outcome
• Vasoconstrictor Agents (toxicity)