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. 2009 Jan 23;106(4):56. doi: 10.3238/arztebl.2009.0056

Correspondence (reply): In Reply

Boris Zernikow *, Tanja Hechler *
PMCID: PMC2695308

The risk of agranulocytosis in childhood owing to treatment with metamizole seems negligible—to date only one such case has been reported. We wish to mention the most important data on nonchemotherapy associated agranylocytosis in adults from the recent review by Andersohn et al (1):

  • Over a time span of 40 years (1966–2006), only 980 cases were identified

  • 56 cases were definitely and 436 probably associated with the administration of one of the 125 identified medications

  • For 11 medications, more than 10 case reports existed: these included penicillin G and metamizole, with 11 cases each classified as certainly or probably associated with agranulocytosis

  • Mortality due to agranulocytosis was less than 5% when modern therapeutic options were available.

For adults, Neumann’s statement that the use of metamizole should be strongly advised against is not supported by science and is even potentially harmful if the gastrointestinal side effects of therapy with non-steroidal anti-rheumatic or anti-inflammatory drugs (NSARs or NSAIDs) are taken into account:

  • The annual death rate is 0.08%

  • The chance of dying as a result of gastrointestinal complications is 1 in 1200 after two months’ therapy with NSARs (2)

  • In the US, 41 000 patients are hospitalized for this reason every year, and 3300 die (3).

Migraine can be distinguished phenomenologically from headache in the context of impaired eyesight. Still, for the child, impaired eyesight may be an additional stress factor and thus affect the frequency of headaches. It therefore certainly makes sense to actively investigate eye problems in children with headaches. The statements made by Razeghi are correct and do not contradict what we said our article.

We thank Hack and Mader and wish to use this opportunity to specify our dosage recommendations for intravenous paracetamol.

The manufacturers recommend for mature neonates, infants, toddlers, and children weighing <10 kg up to 4 x 7.5 mg/kg i.v. per diem. Allegaert recommends for premature babies and neonates a load dose of 20 mg/kg. Subsequent doses for premature babies <31 weeks of gestation are 20 mg up to every 12 hours, for neonates of 31 to 36 weeks’ gestation 10 mg/kg up to every 8 hours, and for older premature babies and neonates 10 mg/kg up to every 6 hours (maximum dosis <36 weeks’ gestation: 40 mg/kg/d i.v., >36 weeks’ gestation 50 mg/kg/d i.v.) (4).

Footnotes

Conflict of interest statement

Dr Zernikow has reported associations with Astra Zeneca, Aventis, Boots Healthcare, Bristol Meyer-Squibb, Cephalen, Grünenthal, Janssen-Cilag, Mundipharma, Pfizer, and Reckitt-Benckiser.

References

  • 1.Andersohn F, Konzen C, Garbe E. Systematic review: agranulocytosis induced by nonchemotherapy drugs. Ann Intern Med. 2007;146:657–665. doi: 10.7326/0003-4819-146-9-200705010-00009. [DOI] [PubMed] [Google Scholar]
  • 2.Moore RA. The hidden costs of arthritis treatment and the cost of new therapy—the burden of non-steroidal anti-inflammatory drug gastropathy. Rheumatology (Oxford) 2002;41(Suppl 1):7–15. doi: 10.1093/rheumatology/41.suppl_1.7. [DOI] [PubMed] [Google Scholar]
  • 3.Griffin MR. Epidemiology of nonsteroidal anti-inflammatory drug-associated gastrointestinal injury. Am J Med. 1998;104:23–29. doi: 10.1016/s0002-9343(97)00207-6. [DOI] [PubMed] [Google Scholar]
  • 4.Allegaert K, Murat I. Not all intravenous paracetamol formulations are created equal. Paediatr Anaesth. 2007;17 doi: 10.1111/j.1460-9592.2007.02227.x. [DOI] [PubMed] [Google Scholar]
  • 5.Zernikow B, Hechler T. Pain Therapy in Children and Adolescents. Dtsch Arztebl Int. 2008;105(28-29):511–522. doi: 10.3238/arztebl.2008.0511. [DOI] [PMC free article] [PubMed] [Google Scholar]

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