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Three Part Question

In [patients presenting to the emergency department with an acute porphyric attack] are [phenothiazines and cyclizine] safe and effective at [reducing nausea and vomiting]?

Clinical Scenario

A 51 year old patient present to the emergency department with abdominal pain and vomiting. She tells you she has acute intermittent porphyria and has vomited 7 times in the past hour. You wonder if cyclizine or a phenothiazine would be safe to use to stop her vomiting.

Search Strategy

Medline 1966-06/06, Embase 1980-06/06, CINAHL 1983- 06/06 via Ovid.
Medline: [Prochlorperazine.mp. or exp Prochlorperazine/ or chlorpromazine.mp. or exp chlorpromazine/ or compazine.mp. or thorazine.mp. or phenothiazine.mp. or exp Phenothiazines/ or cyclizine.mp. or valoid.mp.] AND [ exp porphyrias/ or porphyrias.mp. or porphyria.mp. or AIP.mp.] LIMIT humans and english.
Embase and Cinahl:[Prochlorperazine.mp. or exp Prochlorperazine/ or chlorpromazine.mp. or exp chlorpromazine/ or compazine.mp. or thorazine.mp. or phenothiazine.mp. or exp Phenothiazines/ or cyclizine.mp. or valoid.mp.]AND [exp porphyria or porphyrias.mp. or porphyria.mp. or AIP.mp.] LIMIT humans and english.
The Cochrane Library: porphyria

Search Outcome

Medline:22 results-1 relevant
Embase:59 results-0 relevant
Cinahl:1 result-0 relevant
Cochrane-32 results-0 relevant
A manual search of the results of other BETs on acute porphyria resulted in 2 more results.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Campos JH, Stein DK, Michel MK, Moyers JR. 1991 USA	68 year old female with acute intermittent porphyria undergoing aortic valve replacement. Chlorpromazine 25mg/d noted as a regular medication for abdominal pain.	Case study. Level 3 evidence.	Symptoms of acute attack related to chlorpromazine	None noted	Case study
Evans PR, Graham S, Kumar CM 2001 UK	Two patients with acute intermittent porphyria undergoing surgery. Post-operatively cyclizine and prochorperazine were given.	Case study. Level 3 evidence.	Symptoms suggestive of an acute attack	None occured	Case study No PBG measurements
Dean G 1967 South Africa	Double blinded study in which 30 patients with variegate porphyria were given chlorpromazine 10 mg three times daily.(20 patients given mefenamic acid).	The study design is a randomnised control trial but for the purpose of this BETs which was only looking at the safety ofchlorpromazine, it is a case series therefore level 3 evidence.	Number of patients with symptoms suggestive of an acute attack after administration of propofol	No acute attacks	Case series
			Urinary PBG levels	None detected

Comment(s)

The safe use of chlorpromazine has been reported in 31 patients and the safe use of cyclizine and prochorperazine in 1 patient. There were no acute attacks or increase in urinary PBG. Prochorperazine and chlorpramazine have been classified as safe to use in drug databases (Level 4 evidence) produced by the Norweigan Porphyria Centre, University of Cape Town Porphyria Service, The Welsh Medicines Information Centre and the European Porphyria Initiative . Cyclizine is not listed in two of these database and classed as safe in one and unsafe in the another.

Clinical Bottom Line

Chlorpromazine is safe to use as an anti-emetic in acute intermittent porphyria. There is insufficient evidence of insufficient quality as to whether other phenothiazines and cyclizine are safe therefore more research is needed.

References

1. Campos JH, Stein DK, Michel MK, Moyers JR. Anesthesia for aortic valve replacement in a patient with acute intermittent porphyria. Journal of cardiothoracic and vascular anesthesia 1991:5;258-261
2. Evans PR, Graham S, Kumar CM The use of sevoflurane in acute intermittent porphyria Anaesthesia 2001;56:388-389
3. Dean G. Mefanamic acid and chlorpromazine in porphyria variegata South African medical journal 1967:41;925-7
4. The norweigan porphyria centre The drug database for acute porphyria
5. University of Cape Town porphyria service Drug safety;alphabetical listing
6. The welsh medicines information centre Drugs that are considered safe for use in the acute porphyrias
7. European Porphyria Initative. Drugs and porphyria