Zinc Salts
Tetracycline Interactions
Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain aluminum salts, calcium salts, iron salts, magnesium salts, and/or zinc salts, particularly if the time of administration is within 60 minutes of each other. Examples of compounds that may interfere with the bioavailability of tetracycline antibiotics include antacids; sucralfate; magnesium salicylate; magnesium citrate; Moban® brand of molindone (contains calcium ions) ; polysaccharide-iron complex; quinapril (tablets contain magnesium); and multivitamins that contain iron, calcium, manganese, or zinc. Laxative preparations containing magnesium are also contraindicated. Didanosine, ddI, may also decrease tetracycline antibiotic bioavailability due to the buffering agents in didanosine tablets or powder. Delayed-release didanosine capsules do not contain a buffering agent and would not be expected to interact with tetracycline antibiotics. Some antidiarrheals also contain cations that will form chelated compounds. Tetracycline should not be administered with or within 4 hours of any of the above drugs. Calcium salts and magnesium salts that are present in food and dairy products can form chelates with tetracycline and impair absorption. Clinicians should warn patients about all dairy products and other high calcium- and iron-containing foods while taking tetracycline. To reduce this effect, administer tetracycline at least one hour prior to or two hours after a meal and/or milk. Patients should be monitored aggressively for continued antibiotic effectiveness because staggered administration may not be totally reliable.
In a study of 15 healthy subjects, the bioavailability of ciprofloxacin was decreased by approximately 50 percent when coadministered with sevelamer. While not specifically studied, it is possible that sevelamer will affect the absorption of other antibiotics, including the tetracyclines. To minimize this interaction, patients should be advised to separate the administration of tetracyclines by at least 1 hour before or 3 hours after sevelamer. In addition, patients should be monitored for changes in efficacy of the antibiotic when these drugs are coadministered.
Many texts warn not to use bacteriostatic and bactericidal antibiotics together since the bactericidal actions of, for example, penicillins may be inhibited by the bacteriostatic agent. The clinical significance of these interactions is debatable. The classic explanation of this antagonism is that the bacteriostatic antimicrobial agent inhibits the growth of the target organism, and interferes with the action of the bactericidal agent, which is dependent on cell growth/replication for proper activity. However, despite reports of pharmacologic antagonism in vitro with such combinations, few clinical data to substantiate in vivo antagonism exist. Combination antimicrobial therapy has been a useful strategy for treating clinical infections. For example, the concomitant clinical use of cephalosporins and tetracyclines (e.g., doxycycline) is common in some mixed bacterial infections without loss of clinical efficacy of either agent. Similarly, many mixed bacterial infections are treated safely and efficaciously with the concomitant administration of cephalosporins and macrolides (e.g., azithromycin, clarithromycin, erythromycin). Although the potential for antagonism should be considered when prescribing antibiotics, in general it is safe to administer combinations, refining treatment based on the nature of the clinical infection and individual parameters such as susceptibility data.
Tetracycline exhibits a clinically significant interaction with warfarin; although the mechanism is not well described. Tetracycline may increase the action of warfarin and other oral anticoagulants by either impairing prothrombin utilization or, possibly, decreasing production of vitamin K because of its antiinfective action on gut bacteria.
Digoxin is partially metabolized by bacteria in the large intestine. For digoxin-stabilized patients, an alteration in the enteric bacterial flora by an antiinfective agent, such as tetracycline, can result in an increase in the bioavailability of digoxin. Patients should be monitored carefully for digoxin toxicity and the dose of digoxin reduced, if necessary.
Colestipol has been shown to reduce tetracycline absorption by roughly 40% . It is likely this is enough to cause a clinically significant effect. Although no data are available for other tetracyclines, or for cholestyramine, it should be assumed that any tetracycline antibiotic may be affected similarly by either cholestyramine or colestipol. Staggering oral doses of each agent is recommended to minimize this pharmacokinetic interaction.
It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Methoxyflurane can increase the potential for nephrotoxicity (sometimes fatal) from tetracycline.
Tetracyclines may interact with retinoids in several different ways. The concomitant use of acitretin (a retinoids class drug) and tetracyclines is contraindicated, due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). There have been reports of benign intracranial hypertension during concurrent use of vitamin A and tetracycline. Pseudotumor cerebri has been reported with acitretin use alone, and has been reported with other systemic retinoids including isotretinoin. Early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances. In addition to the potential additive effect on intracranial pressure, tetracyclines are known to cause photosensitivity and may enhance the photosensitizing effects of retinoids.
Tetracyclines cause photosensitivity and may increase the photosensitizing effects of griseofulvin, phenothiazines, retinoids , sulfonamides, sulfonylureas , thiazide diuretics, and photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.
Tetracycline may potentiate the neuromuscular effects of nondepolarizing neuromuscular blockers.
Tetracycline can reduce the plasma concentrations of atovaquone by approximately 40%. Avoid concomitant use of tetracycline with atovaquone when possible. Parasitemia should be closely monitored in patients receiving atovaquone and tetracycline when co-use is not avoidable.
Chloramphenicol, rifampin, and tetracycline have been reported to inhibit the bactericidal action of norfloxacin.
Bacteria in the intestine produce enzymes which hydrolyze the soy isoflavones to the active isoflavonoids genistein and daidzein; alterations in gut microflora have been correlated with effects on soy isoflavone bioavailability. Selected antibiotics (e.g., clindamycin, lincomycin, macrolides, neomycin, tetracyclines) significantly reduce the GI microflora and could theoretically prevent the formation of the active components of the soy isoflavones.
Concomitant administration of quinine and tetracycline may result in higher quinine plasma concentrations. In 8 patients with acute uncomplicated Plasmodium falciparum malaria being treated with oral quinine sulfate in combination with oral tetracycline, the mean plasma quinine concentrations were about 2-fold higher than in 8 patients receiving quinine alone. It is recommended that patients be monitored closely for quinine-associated adverse reactions if tetracycline is given with quinine.
[ Last revised: 8/26/2005 10:56:00 AM ]
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