Jose Halabe Cherem, MD; Jose Malagon, MD; Haiko Nellen, MD
Potential Financial Conflict of Interest: None disclosed.
Cherem J., Malagon J., Nellen H.; Cimetidine and Acute Intermittent Porphyria. Ann Intern Med. 2005;143:694-695. doi: 10.7326/0003-4819-143-9-200511010-00023
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Published: Ann Intern Med. 2005;143(9):694-695.
TO THE EDITOR:
Background: Management of acute porphyric crisis involves withdrawal of offending drugs, treatment of symptoms with appropriate medications, and attempts to reverse factors that increase aminolevulinic acid synthetase activity. Hematin, the standard therapy for porphyria, is not always immediately available. Cimetidine may have a role in the treatment of acute intermittent porphyria by inhibiting heme oxidase activity, decreasing heme consumption, and inhibiting aminolevulinic acid synthetase through a negative feedback mechanism (1-4). We successfully treated 4 patients with acute intermittent porphyria with cimetidine; the drug also appeared to be effective for secondary prevention of subsequent episodes.
University of Pavia, 27100 Pavia, Italy
November 4, 2005
Cimetidine and acute intermittent porphyria
In the interesting report "Cimetidine and Acute Intermittent Porphyria", Cherem and colleagues, demonstrating the effectiveness of cimetidine for the treatment of acute porphyric crisis and for the long- term prophylaxis, point out the need to conduct larger studies to confirm these encouraging results. (1) However, attention should be paid for those patients suffering from an acute neurological porphyric attack (50-55% of the total attacks) characterized by the presence of psychiatric symptoms, such as anxiety, insomnia, agitation, hallucinations, delirium, confusion and psychosis. (2) Indeed, it is known that histamine-2 receptor (H2) blockers, and in particular cimetidine, may be associated with the development of the same neurological side effects (3), and, therefore, can possibly contribute to exacerbate and worsen the clinical situation. Moreover, several reports have documented an association between the chronic use of cimetidine and the rising of a depressive syndrome (4), which can represent a long-term complication of acute intermittent porphyria and a major risk factor for suicide, one of the most important and frequent cause of death seen in this disease. (2,5)
1) Cherem JH, Malagon J, Nellen H. Cimetidine and acute intermittent Porphyria [Letter]. Ann Intern Med. 2005;143:694-5. [PMID:16263899]
2) Anderson KE, Bloomer JR, Bonkovsky HL, Kushner JP, Pierach CA, Pimstone NR, et al. Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med. 2005;142:439-50. [PMID: 15767622]
3) Cantu TG, Korek JS. Central nervous system reactions to histamine- 2 receptor blockers. Ann Intern Med. 1991;114:1027-34. [PMID: 1674198]
4) Petite JP, Bloch F. Depressive syndrome during cimetidine treatment [Letter]. Nouv Presse Med. 1979;8:1260. [PMID: 440948]
5) Jeans JB, Savik K, Gross CR, Weimer MK, Bossenmaier IC, Pierach CA, et al. Mortality in patients with acute intermittent porphyria requiring hospitalization: a United States case series. Am J Med Genet. 1996;65:269- 73. [PMID: 8923933]
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