___________________________________________________________________________ Antibiotics Review
(SIADH) [6; 141]. However, studies have suggested that there is limited high-quality evidence to suggest that demeclocycline is effective in managing this condition, and European clinical practice guidelines recommend against the use of demeclocy- cline for the management of hyponatremia in patients with SIADH [6; 142]. Long-Acting Tetracyclines The long-acting tetracycline agents include doxycycline and minocycline. The main difference between these and the short-acting agents is that these may be dosed less frequently (once or twice daily), which is an advantage in ensuring compli- ance [6]. The spectrum of bacterial coverage is essentially the same and the indications are the same, with the additional indication for the treatment of inhalation anthrax as part of a multidrug regimen. ABSORPTION/ELIMINATION Tetracycline is well absorbed after an oral dose taken in the fasting state. Doxycycline and minocycline are well absorbed after an oral dose and may be given with or without food. The tetracyclines are well distributed throughout body tissues and fluids; distribution in the CSF is adequate for the treat- ment of some infections [6; 143; 144]. The excellent tissue penetration results in the ability of the drug to cross into the dentin, where the tetracycline permanently chelates with the calcium [145]. Most of the tetracycline dose is excreted unchanged into the urine by glomerular filtration, although there is some biliary excretion as well. Nonrenal, possibly hepatic, mechanisms account in large part for excretion of doxycycline and mino- cycline. Approximately 23% to 40% of doxycycline and 5% to 12% of minocycline is excreted in the urine [6]. Tetracycline should be used with caution in the presence of renal insufficiency, because it accumulates rapidly in the serum in the presence of decreased renal function [6]. Doxycycline may be used in renal failure, as it will be excreted into the bile [6; 146]. Hepatotoxicity has been rarely reported [6]. SIDE EFFECTS/TOXICITY Tetracyclines commonly cause GI upset, including nausea, vomiting, and diarrhea. There is conflicting evidence of stain- ing and deformity of the teeth in children younger than 8 years of age. Photosensitivity, idiopathic intracranial hypertension, esophageal ulceration, and hepatotoxicity occur rarely [6]. Minocycline is often associated with vertigo, nausea, and vomiting, and it may increase azotemia in renal failure. In addition, prolonged use of minocycline may cause reversible discoloration of the fingernails, the sclera, and the skin [6]. Minocycline has been associated with a lupus-like reaction [6].
Allergic reactions to tetracyclines are not common but may range from mild rashes to anaphylaxis. Tetracyclines are con- traindicated in patients who have shown hypersensitivity to any tetracyclines. DRUG INTERACTIONS Several types of drug interactions result in alterations in serum levels of tetracyclines. Agents that alkalinize the urine will increase excretion of the tetracyclines. Polyvalent metal cations (calcium, aluminum, zinc, magnesium, and iron) and bismuth decrease absorption [6; 147]. Drugs that induce hepatic enzymes may decrease the half-life of doxycycline. Interactions that affect the efficacy of other drugs also occur. The bactericidal effect of penicillins may be decreased by co-administration with tetracyclines. Concurrent use of oral contraceptives may make the contraceptive less effective [6; 148; 149]. The effects of warfarin are increased, probably because tetracyclines depress warfarin metabolism and plasma prothrombin activity, resulting in a synergistic effect [6; 150]. Digoxin effects may be increased because of changes in the bowel flora that are responsible for digoxin metabolism [151]. SPECIAL POPULATIONS Tetracycline is pregnancy category D because of impaired bone development in the fetus. Hypoplasia of the enamel and discoloration of fetal teeth may occur, and maternal hepatic toxicity has been reported as well [6; 152; 153]. Tetracyclines are excreted into the breast milk in small amounts. Most exposed infants have very low blood levels of the drug and probably are not at risk [6]. In the past, tet- racyclines were contraindicated in children younger than 8 years of age because of the risk for tooth deformity. However, doxycycline is the current first-line therapy for Rocky Mountain spotted fever in children of all ages, including those younger than 8 years of age [154]. Limited studies indicate that short courses of the medication were not associated with dental side effects in this population [155].
The Infectious Diseases Society of America asserts that tetracyclines should not be used in children younger than 8 years of age. (https://academic.oup.com/cid/article/ 52/3/e18/306145. Last accessed January 11, 2024.)
Level of Evidence : A-II (Good evidence from >1 well- designed clinical trial, without randomization; cohort or case-controlled analytic studies; multiple time-series; or dramatic results from uncontrolled experiments)
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