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Friday, February 5, 2010

Drug Interaction: Cyclophosphamide and Allopurinol

*Interaction detected between allopurinol and cyclophosphamide, MAJOR increased toxicity (increase myelosuppression, nausea and vomiting) as per Micromedex Online
(Micromedex® Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Reuters (Healthcare) Inc. Updated periodically).

Onset: Delayed

Severity: Major

Documentation: Good

Summary: There may be an increase in cyclophosphamide levels and prolongation in half-life of cyclophosphamide (Anon, 1974; Stolbach et al, 1982).

Literature:


The Boston Collaborative Drug Surveillance Program examined the incidence of bone marrow depression in a series of 160 patients, 95 of whom were controls, during combined allopurinol use with either cyclophosphamide or other cytotoxic drugs (Anon, 1974). Their results indicated that the frequency of bone marrow depression in those patients who received allopurinol and cyclophosphamide was 57.7% as compared to 18.8% in those who did not receive allopurinol. In addition they noted that mortality may be somewhat higher in allopurinol recipient patients.

One study has reported that concomitant allopurinol and cyclophosphamide therapy results in significant elevations of cyclophosphamide cytotoxic metabolites, which may contribute to the increased bone marrow depression observed during concomitant therapy (Witten et al, 1980).

*At our centre and in this individual case, patient was on allopurinol 100 mg daily continuously for management of gout. The patient was to start FEC. After discussing with treating physician, there was insufficient time to temporarily discontinue allopurinol without delaying treatment. Therefore, it was decided to monitor CBCs carefully - that is, weekly (at least for the first cycle). It will then be decided if allopurinol will be held at all next cycle.

One possible recommendation would be to hold allopurinol for 5 days before and 2 days after chemotherapy treatment. This is based on half-life of active metabolite of allopurinol, oxypurinol, being 18-30 hours and cyclophosphamide's 3-12 hours.

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Pharmacy History

"The earliest known compilation of medicinal substances was ARIANA the Sushruta Samhita, an Indian Ayurvedic treatise attributed to Sushruta in the 6th century BC. However, the earliest text as preserved dates to the 3rd or 4th century AD.
Many Sumerian (late 6th millennium BC - early 2nd millennium BC) cuneiform clay tablets record prescriptions for medicine.[3]

Ancient Egyptian pharmacological knowledge was recorded in various papyri such as the Ebers Papyrus of 1550 BC, and the Edwin Smith Papyrus of the 16th century BC.

The earliest known Chinese manual on materia medica is the Shennong Bencao Jing (The Divine Farmer's Herb-Root Classic), dating back to the 1st century AD. It was compiled during the Han dynasty and was attributed to the mythical Shennong. Earlier literature included lists of prescriptions for specific ailments, exemplified by a manuscript "Recipes for 52 Ailments", found in the Mawangdui tomb, sealed in 168 BC. Further details on Chinese pharmacy can be found in the Pharmacy in China article."

From Wikipedia: http://en.wikipedia.org/wiki/Pharmacy#History_of_pharmacy

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