ALLOPURINOL
Drugs in Pregnancy and Lactation.
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Name: ALLOPURINOL
Class: Miscellaneous
Risk Factor: CM
Fetal Risk Summary
Allopurinol, a xanthine oxidase inhibitor, is used for the treatment of primary or secondary hyperuricemias, such as those occurring in gout or during cancer chemotherapy. Because these conditions are relatively rare in women of childbearing age, there are few reports describing the use of allopurinol during pregnancy. No adverse fetal outcomes attributable to allopurinol have been reported in humans. The manufacturer is aware of two unpublished reports of women receiving the drug during pregnancy who gave birth to normal infants (1). In a 1972 study, allopurinol produced cleft palate and skeletal defects in mice (2). However, in studies involving other animal species, no fetal harm was observed (1,3).
Allopurinol, in daily doses of 300–400 mg, was combined with cancer chemotherapeutic agents in four patients for the treatment of leukemia occurring during pregnancy (4,5 and 6). Treatment in each of these cases was begun in the 2nd or 3rd trimester. The outcomes of these pregnancies were as follows: two normal healthy infants (4); one intrauterine fetal death probably a result of severe preeclampsia (5); and one growth-retarded infant with absence of the right kidney, hydronephrosis of the left kidney, and hepatic subcapsular calcifications (6). The cause of the defects in the latter infant was unknown but, because drug therapy was not started until the 20th week of gestation, any relationship to allopurinol can be excluded. The intrauterine growth retardation was thought to be caused by the chemotherapeutic agent, busulfan, that the mother received (6).
A 1976 case report described the use of allopurinol in a woman with type I glycogen storage disease (von Gierke's disease) (7). One of the characteristics of this inherited disease is hyperuricemia as a result of decreased renal excretion and increased production of uric acid (7). The woman was receiving allopurinol, 300 mg/day, at the time of conception and during the early portion of the 1st trimester (exact dates were not specified). The drug was stopped at that time. A term female infant was delivered by cesarean section for failed labor. Phenylketonuria, an autosomal recessive disorder, was subsequently diagnosed in the infant.
A woman with primary gout and gouty nephropathy was treated with 300 mg/day of allopurinol throughout gestation (8). She was delivered of an appropriate-for-gestational-age 2510-g healthy female infant at 35 weeks' gestation. The infant's weight gain was normal at 10 weeks of age, but other developmental milestones were not provided.
Breast Feeding Summary
Allopurinol and the metabolite, oxypurinol, are excreted into human milk (9,10). A woman with hyperuricemia was taking allopurinol 300 mg/day for 4 weeks while breast-feeding her 5-week-old infant (9,10). Maternal plasma and milk samples were drawn 2 and 4 hours after a 300-mg dose. Her plasma levels of allopurinol and the metabolite, oxypurinol, at these times were 1.0 and 13.8 µg/mL, and 1.0 and 19.9 µg/mL, respectively. Milk levels of the drug and metabolite at 2 and 4 hours were 0.9 and 53.7 µg/mL, and 1.4 and 48.0 µg/mL, respectively, representing milk:plasma ratios of the active drug of 0.9 and 1.4, respectively. The mother breast-fed her infant 2 hours after her dose and a single infant plasma sample was taken 2 hours later. Allopurinol was not detected (detection limit 0.5 µg/mL) in the infantís plasma but the concentration of oxypurinol was 6.6 µg/mL. The average daily dose of allopurinol ingested by the infant from the milk was 0.14–0.20 mg/kg (10). No adverse effects in the nursing infant were observed. The American Academy of Pediatrics considers allopurinol to be compatible with breast feeding (11).
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References
- Product information. Zyloprim. Burroughs Wellcome, 1990.
- Fujii T, Nishimura H. Comparison of teratogenic action of substances related to purine metabolism in mouse embryos. Jpn J Pharmacol 1972;22:201–6.
- Chaube S, Murphy ML. The teratogenic effects of the recent drugs active in cancer chemotherapy. In Woollam DHM, ed. Advances in Teratology. New York, NY:Academic Press, 1968;3:181-237. As cited in Shepard TH. Catalog of Teratogenic Agents. 6th ed. Baltimore, MD:Johns Hopkins University Press, 1989:58.
- Awidi AS, Tarawneh MS, Shubair KS, Issa AA, Dajani YF. Acute leukemia in pregnancy: report of five cases treated with a combination which included a low dose of Adriamycin. Eur J Cancer Clin Oncol 1983;19:881–4.
- O'Donnell R, Costigan C, O'Connell LG. Two cases of acute leukaemia in pregnancy. Acta Haematol 1979;61:298–300.
- Boros SJ, Reynolds JW. Intrauterine growth retardation following third-trimester exposure to busulfan. Am J Obstet Gynecol 1977;129:111–2.
- Farber M, Knuppel RA, Binkiewicz A, Kennison RD. Pregnancy and von Gierke's disease. Obstet Gynecol 1976;47:226–8.
- Coddington CC, Albrecht RC, Cefalo RC. Gouty nephropathy and pregnancy. Am J Obstet Gynecol 1979;133:107–8.
- Kamilli I, Gresser U, Schaefer C, Zollner N. Allopurinol in breast milk. Adv Exp Med Biol 1991;309A:143–5.
- Kamilli I, Gresser U. Allopurinol and oxypurinol in human breast milk. Clin Invest 1993;71:161–4.
- Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.
Q&A about Allopurinol
My son who is 29 yrs old has gout from 2 yrs.He started taking allopurinol 100 mgs on oct 19th 06 increasing the dose to 200mgs on 13thnov.He saw dryness at first and later rash on his face for the last 3 weeks.In the past he tried to control the gout attacks with colchicine and indocin but was still getting frequent attacks in all big joints.My question is the skin rash a serious reaction to stop the drug and is it a precursor to other side effects.Please advise.
Please read the excerpts from Wikipedia on allopurinal -
The side effects of high levels of precursors are usually minor. A small percentage of people develop a rash and must discontinue this drug. The most serious adverse event is a hypersensitivity syndrome consisting of fever, skin rash, eosinophilia, hepatitis, and worsening renal function. In some cases, allopurinol hypersensitivity syndrome.-
Accordingly you should stop giving allopurinol immediately and consult your doctor for alternative drug to be given. With out doctors advise do not give any medicine. This is very important-.
As a gout sufferer, I take 300mg daily, usually before bed. My doctor doesn't seem to think time of day matters, however, I'd like a second, third, fourth (etc...) opinion.
i was having pain in my testicles.doctor diagnosed maybe due to bacteril infection and prescribed doxycycline-100m.g for 14 days with pain killer .also i was taking zyloric for reducing my uric acid levels in blood.does this cause any fungal infection of skin asi experienced a small rash on my thigh and neck,chest which the doctor identified as sebbahoric dermatitis.
Seborrheic dermatitis doesn't affect the chest as often (except right down the center sometimes). Does the rash itch? Seborrheic dermatitis usually doesn't itch very much, while exfoliative dermatitis does. Also, do you have any systemic symptoms? Exfoliative dermatitis often is associated with fevers, chills, and/or generalized weakness.
The distinction is important because the treatments for the two conditions are different (although, as I mentioned earlier, it is possible to have both). If your rash is minor, you may not require any treatment at all (just discontinue the doxycycline or wait out the 14-day course).
what reactions am i going to use?
what could be the synthesis?
Its for Gout prevention or treatment.
It lowers uric acid build up.
I am a 50 years old male good health. Since my first gout attack, I have been taking colchicine 500 gm daily for the last 10 months, and have not had a second gout attack, except for some minor pains in the knee caps. which usually happens after a night of alcohol drinking. I drink up to half a bottle of whisky and red wine each week. My uric acid is high. I was treated for kidney stones several years back.
This interaction is poorly documented and is considered major in severity.
good? bad? side effects? How long gout? How long on either gout. I just developed gout and was perscribed however I am having stomach reactions to both.
thanks for your answers
2) Your doctor should be the one telling you the dose, not the
random person on here (who may not be who/what they claim).
