<p>There are various precautions to be undertaken while doxycyline is administered <sup class="text-reference-group"><a class="reference-popover-link" data-content="Doxycycline MedSafe NZ" href="#reference-F3052">15</a></sup>. A full list of adverse events is included in the "Adverse Effects" section of this drug entry.</p><p><strong>A note on tooth development and tetracycline use</strong></p><p>The use of tetracyclines, including doxycycline, during tooth development (i.e. the last half of pregnancy, throughout infancy, and in childhood up to 8 years of age) may lead to tooth enamel hypoplasia and yellow-gray discoloration of teeth. It is advisable not to administer doxycycline in this age group according to the FDA label, except for in cases of post-exposure cases of anthrax (including inhalational anthrax) <sup class="text-reference-group"><a class="reference-popover-link" data-content="Official drug label" href="#label-reference">Label</a></sup>. Other sources state that doxycycline should not be administered in children under 12 years <sup class="text-reference-group"><a class="reference-popover-link" data-content="Doxycycline MedSafe NZ" href="#reference-F3052">15</a></sup>.</p><p><strong>A note on Clostridium difficile</strong>
Clostridium difficile associated diarrhea (CDAD) and antibiotic associated pseudomembranous colitis may result from doxycycline use. Administering antibacterial agents changes the normal flora of the colon leading to an overgrowth of C. difficile. This bacteria produces toxins A and B, which contribute to the development of CDAD <sup class="text-reference-group"><a class="reference-popover-link" data-content="Doxycycline MedSafe NZ" href="#reference-F3052">15</a></sup>. in moderate to severe cases, therapy with a suitable oral antibacterial agent effective against Clostridium difficile should be considered. Fluids, electrolytes and protein replacement should be provided when warranted <sup class="text-reference-group"><a class="reference-popover-link" data-content="Doxycycline MedSafe NZ" href="#reference-F3052">15</a></sup>.</p><p><strong>A note on gastrointestinal irritation</strong>
Gastrointestinal irritation may also occur. Rarely, esophagitis and esophageal ulcers have been reported in patients receiving doxycycline. Most of these patients took medication immediately before going to bed. Administration of appropriate amounts of fluid with the tablets is recommended to reduce the risk of esophageal irritation and ulceration, and late evening ingestion of the dose should be avoided <sup class="text-reference-group"><a class="reference-popover-link" data-content="Doxycycline MedSafe NZ" href="#reference-F3052">15</a></sup>. To decrease the risk of gastric irritation, it is recommended that doxycycline is taken with food or milk. The absorption of doxycycline is not significantly influenced by simultaneous ingestion of food or milk <sup class="text-reference-group"><a class="reference-popover-link" data-content="Doxycycline MedSafe NZ" href="#reference-F3052">15</a></sup>.</p><p><strong>Pregnancy</strong>
Results of animal research indicate that tetracyclines cross the placenta, are found in fetal tissues and exert toxic effects on the developing fetus, manifested by retardation of skeletal development. The importance of this in humans is not known, however, doxycycline should not be used in pregnant women unless the benefit significantly outweighs the risk <sup class="text-reference-group"><a class="reference-popover-link" data-content="Doxycycline MedSafe NZ" href="#reference-F3052">15</a></sup>. </p><p><strong>Carcinogenicity</strong>
In vivo studies conducted in rats and mice have not provided conclusive evidence that tetracyclines may be carcinogenic or that they affect fertility. In two mammalian cell lines, positive tests for mutagenicity occurred at concentrations of 60 and 10 mcg/ml respectively. In humans, no association between tetracyclines and these effects have been established <sup class="text-reference-group"><a class="reference-popover-link" data-content="Doxycycline MedSafe NZ" href="#reference-F3052">15</a></sup>.</p>