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March 4, 1974, Vol 227, No. 9 >
ARTICLE | March 4, 1974

Allopurinol and Cytotoxic Drugs: Title and subTitle BreakInteraction in Relation to Bone Marrow Depression FREE

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For a complete list of participants in the program, see page 1040.

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JAMA. 1974;227(9):1036-1040. doi:10.1001/jama.1974.03230220026008
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In 160 patients with neoplastic diseases (other than leukemia) that were treated with cytotoxic drugs, bone marrow depression (BMD) was more common in 65 patients who also received allopurinol than in 95 who did not (P<.005). In 58 patients who received cyclophosphamide, the frequencies of BMD in allopurinol recipients and nonrecipients were 57.7% and 18.8%, respectively. A similar but less pronounced trend occurring with other cytotoxic drugs involved too few patients with any one drug to allow firm conclusions. Interaction between allopurinol and cytotoxic drugs is a possible explanation of these findings.

REFERENCES

1 +
Elion GB, et al:  Potentiation by inhibition of drug degradation: 6-substituted purines and xanthine oxidase . Biochem Pharmacol 12:85-93, 1963;.
2 +
DeConti RC, Calabresi P:  Use of allopurinol for prevention and control of hyperuricemia in patients neoplastic disease . N Engl J Med 274:481-486, 1966;.
3 +
Rundles RW, et al:  Effects of a xanthine oxidase inhibitor on thiopurine metabolism, hyperuricemia and gout . Trans Assoc Am Physicians 76:126-140, 1963;.
4 +
Rundles RW, Metz EN, Silberman HR:  Allopurinol in the treatment of gout . Ann Intern Med 64:229-258, 1966;.
5 +
Fox IH, Wyngaarden JB, Kelley WN:  Depletion of erythrocyte phosphoribosylpyrophosphate in man: A newly observed effect of allopurinol . N Engl J Med 283:1177-1182, 1970;.
6 +
Fox RM, Royse-Smith D, O'Sullivan WJ:  Orotidinuria induced by allopurinol . Science 168:861-862, 1970;.
7 +
Kelley WN, Beardmore TD:  Allopurinol: Alteration in pyrimidine metabolism in man . Science 169:388-390, 1970;.
8 +
Borda IT, Slone D, Jick H:  Assessment of adverse reactions within a drug surveillance program . JAMA 205:645-647, 1968;.
9 +
Jick H, et al:  Comprehensive drug surveillance . JAMA 213:1455-1460, 1970;.
10 +
Slone D, et al:  Computer analysis of epidemiologic data on effect of drugs on hospital patients . Public Health Rep 84:39-52, 1969;.
11 +
Mantel N, Haenszel W:  Statistical aspects of the analysis of data from retrospective studies of disease . J Natl Cancer Inst 22:719-748, 1959;.
12 +
Calabresi P, Parks JR:  Alkylating agents, antimetabolites, and other antiproliferative agents , in LS Goodman, A Gilman (eds): The Pharmacological Basis of Therapeutics , ed 4. New York, Macmillan Co, 1970;, p 1379.
13 +
Kann HE, et al:  The development of an intravenous preparation of allopurinol . Am J Med Sci 256:53-59, 1968;.
14 +
Prescott LF:  Antipyretic analgesics and drugs used in rheumatic diseases and gout in H Meyer , A Herxheimer (eds): Side Effects of Drugs . Amsterdam, Excerpta Medica, 1972;, p 173.
15 +
Greenberg MS, Zambrano SS:  Aplastic agranulocytosis after allopurinol therapy . Arthritis Rheum 15:413-416, 1972;.

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1 +
Elion GB, et al:  Potentiation by inhibition of drug degradation: 6-substituted purines and xanthine oxidase . Biochem Pharmacol 12:85-93, 1963;.
2 +
DeConti RC, Calabresi P:  Use of allopurinol for prevention and control of hyperuricemia in patients neoplastic disease . N Engl J Med 274:481-486, 1966;.
3 +
Rundles RW, et al:  Effects of a xanthine oxidase inhibitor on thiopurine metabolism, hyperuricemia and gout . Trans Assoc Am Physicians 76:126-140, 1963;.
4 +
Rundles RW, Metz EN, Silberman HR:  Allopurinol in the treatment of gout . Ann Intern Med 64:229-258, 1966;.
5 +
Fox IH, Wyngaarden JB, Kelley WN:  Depletion of erythrocyte phosphoribosylpyrophosphate in man: A newly observed effect of allopurinol . N Engl J Med 283:1177-1182, 1970;.
6 +
Fox RM, Royse-Smith D, O'Sullivan WJ:  Orotidinuria induced by allopurinol . Science 168:861-862, 1970;.
7 +
Kelley WN, Beardmore TD:  Allopurinol: Alteration in pyrimidine metabolism in man . Science 169:388-390, 1970;.
8 +
Borda IT, Slone D, Jick H:  Assessment of adverse reactions within a drug surveillance program . JAMA 205:645-647, 1968;.
9 +
Jick H, et al:  Comprehensive drug surveillance . JAMA 213:1455-1460, 1970;.
10 +
Slone D, et al:  Computer analysis of epidemiologic data on effect of drugs on hospital patients . Public Health Rep 84:39-52, 1969;.
11 +
Mantel N, Haenszel W:  Statistical aspects of the analysis of data from retrospective studies of disease . J Natl Cancer Inst 22:719-748, 1959;.
12 +
Calabresi P, Parks JR:  Alkylating agents, antimetabolites, and other antiproliferative agents , in LS Goodman, A Gilman (eds): The Pharmacological Basis of Therapeutics , ed 4. New York, Macmillan Co, 1970;, p 1379.
13 +
Kann HE, et al:  The development of an intravenous preparation of allopurinol . Am J Med Sci 256:53-59, 1968;.
14 +
Prescott LF:  Antipyretic analgesics and drugs used in rheumatic diseases and gout in H Meyer , A Herxheimer (eds): Side Effects of Drugs . Amsterdam, Excerpta Medica, 1972;, p 173.
15 +
Greenberg MS, Zambrano SS:  Aplastic agranulocytosis after allopurinol therapy . Arthritis Rheum 15:413-416, 1972;.

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