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Chris HutchinsonPetra LoweJane Vella-BrincatMei Zhang SAFETY OF DOXYCYCLINE IN BREASTFEEDING
Question:A patient has received a 10 day course of doxycycline while breastfeeding a 14 month old. What isthe safety of this? Answer:It can be estimated that a breastfeeding infant would ingest approximately 3-7% of the maternaldoxycyline dose, after adjusting for the difference in body weight[1]. For most drugs, an infant dose(mg/kg) that is less than 10% of the maternal dose (mg/kg), is considered compatible withbreastfeeding. For drugs with greater inherent toxicity such as cytotoxic therapy, this cut-off is toohigh and breastfeeding is usually considered contraindicated.
It is usually recommended that tetracyclines are avoided during pregnancy, breastfeeding and inchildren prior to pubesence because of concern regarding the potential for adverse effects ondeveloping bone and teeth[1-6]:- Bone: tetracyclines chelate with newly formed bone producing a complex which may temporarilyinhibit bone growth. However, this effect is reported to be reversible upon cessation of drugtherapy[5,7].
Teeth: tetracycline exposure during pregnancy, or in children up to 4-6 months of age may resultin staining of deciduous teeth while permanent teeth may be affected until seven to eight yearsof age[2,8]. In general, the degree of tetracycline tooth staining and/or hypoplasia is considered tobe dose-dependent and the risk of staining increases with total dose and duration of therapy[9].
The limited information available suggests that doxycycline has a lower potential for toothdiscolouration compared with other tetracyclines. This may relate to the lower potential fordoxycycline to bind to calcium in enamel and dentine[10-12].
In this case, there are several factors which may reduce infant exposure to doxycycline:- Reduced absorption of doxycycline from the infant's gastrointestinal tract may occur secondaryto complex formation. Doxycycline binds to divalent cations including calcium in maternal milk.
Ingestion with milk is suggested to reduce the oral availability of doxycycline by 20%[14].
The advanced age of this infant will also serve to reduce doxycycline exposure since the infantwill have enhanced ability to eliminate drugs due to the physiological maturity of the kidneys andliver.
The use of non breast-milk foods in this 14 month old will further reduce the magnitude ofdoxycycline ingestion via breast milk.
The American Academy of Pediatrics considers that short courses of tetracycline are not overlyproblematical [1]. Specific comments on doxycycline were not available[1].
Conclusions :An infant is likely to receive 3-7% of a maternal doxycycline dose, after adjusting for the difference inbody weight. For most drugs, a weight adjusted maternal dose of less than 10% is consideredcompatible with breastfeeding. In this case, infant exposure will be reduced by a) chelation in milk,b) reduced exposure to breast milk, and c) increased hepatic and renal function.
CHRISTCHURCH HOSPITAL • PRIVATE BAG 4710, CHRISTCHURCH, NEW ZEALAND PHONE (03) 364 0900 • FAX (03) 364 0902 • E-MAIL It is generally recommended that tetracyclines are avoided during lactation due to the potential foradverse effects on developing teeth and bone, although some suggest short courses may not beproblematical. In this case, we cannot exclude the possibility that doxycycline exposure via breastmilk may affect developing bone and teeth. However, the risk would appear to be very low.
References :1. Briggs GG et al. Drugs in pregnancy and lactation (5th ed), 19992. Drugdex, Micromedex database3. Bennett PN. Drugs and Human Lactation (2nd ed), 1996.
4. British National Formulary (BNF) No 41 March 20015. AHFS Drug Information 20016. Parfitt K (ed) Martindale (32nd ed), 19997. Davies DM et al. Davies Textbook of Adverse Drug Reactions (5th ed), 19988. Dukes MNG. Meyler’s Side Effects of Drugs (13th ed), 19969. Witkop C et al. JAMA 1963; 1008-11.
10. Grossman E et al. Pediatrics 1971; 47: 567-7011. Echman M. J Infectious Dis 1975; 131: 30712. Toaff et al. Drug Induced Diseases Vol 3 1968 cited in [13]13. Anon (editorial). Med J Aust 1972; 954-5.
14. Lacy CF et al. Drug Information Handbook (7th ed), 1999-2000 The information contained within this document is provided on the understanding that although it may
be used to assist in your final clinical decision, the Drug Information Service at Christchurch Hospital
does not accept any responsibility for such decisions.


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CAS 2011/A/2403 World Anti-Doping Agency (WADA) v. Fédération Internationale de Gymnastique (FIG) & Anastasiya Melnychenko ARBITRAL AWARD delivered by THE COURT OF ARBITRATION FOR SPORT Mr Ercus Stewart, Senior Counsel in Dublin, Ireland Mr Patrick Lafranchi, attorney-at-law in Bern, Switzerland Mr Denis Oswald, attorney-at-law in Colombier, Switzerland World Anti-

Appendix xii

TABLE XII-1 SIGNIFICANT INTERACTIONS BETWEEN ANTIRETROVIRAL THERAPY AND PSYCHOTROPIC MEDICATIONS: CONTRAINDICATED COMBINATIONS AND AGENTS TO BE USED WITH CAUTION Medication Contraindicated Use With Caution Comments levels may be significantly increased with • Monitor tricyclic antidepressant therapy closely for toxicity. concentrations due to induction of the CYP45

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