indication

Used to treat bacterial infections such as Rocky Mountain spotted fever, typhus fever, tick fevers, Q fever, rickettsialpox and Brill-Zinsser disease. May be used to treat infections caused by Chlamydiae spp., B. burgdorferi (Lyme disease), and upper respiratory infections caused by typical (S. pneumoniae, H. influenzae, and M. catarrhalis) and atypical organisms (C. pneumoniae, M. pneumoniae, L. pneumophila). May also be used to treat acne. Tetracycline may be an alternative drug for people who are allergic to penicillin.

pharmacology

Tetracycline is a short-acting antibiotic that inhibits bacterial growth by inhibiting translation. It binds to the 30S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome. It also binds to some extent to the 50S ribosomal subunit. This binding is reversible in nature. Additionally tetracycline may alter the cytoplasmic membrane of bacteria causing leakage of intracellular contents, such as nucleotides, from the cell.

mechanism of action

Tetracycline passively diffuses through porin channels in the bacterial membrane and reversibly binds to the 30S ribosomal subunit, preventing binding of tRNA to the mRNA-ribosome complex, and thus interfering with protein synthesis.

toxicity

LD₅₀=808mg/kg (orally in mice)

biotransformation

Not metabolized

absorption

Bioavailability is less than 40% when administered via intramuscular injection, 100% intravenously, and 60-80% orally (fasting adults). Food and/or milk reduce GI absorption of oral preparations of tetracycline by 50% or more.

half life

6-12 hours

route of elimination

They are concentrated by the liver in the bile and excreted in the urine and feces at high concentrations in a biologically active form.

drug interactions

Acenocoumarol: Tetracycline may increase the anticoagulant effect of acenocoumarol.

Acitretin: Increased risk of intracranial hypertension

Aluminium: Formation of non-absorbable complexes

Amoxicillin: Possible antagonism of action

Ampicillin: Possible antagonism of action

Anisindione: Tetracycline may increase the anticoagulant effect of anisindione.

Atovaquone: Tetracycline may decrease the effect of atovaquone.

Attapulgite: Formation of non-absorbable complexes

Azlocillin: Possible antagonism of action

Aztreonam: Possible antagonism of action

Bacampicillin: Possible antagonism of action

Bexarotene: Tetracycline may enhance the adverse/toxic effect of Retinoic Acid Derivatives. Due to the risk of developing pseudotumor cerebri (also known as intracranial hypertension), avoid this combination of drugs if possible. If used concomitantly, monitor for evidence of this interaction (eg, dizziness, diplopia, headache).

Bismuth Subsalicylate: Formation of non-absorbable complexes

Calcium: Formation of non-absorbable complexes

Calcium Acetate: Calcium salts such as calcium acetate may decrease the serum concentration of tetracycline derivatives such as tetracycline. In general, the coadministration of oral calcium salts and oral tetracycline derivatives should be avoided. Interactions may be able to be minimized by administering oral calcium preparations several hours before or after the dose of the oral tetracycline derivatives. Even with dose separation, therapy may still be compromised. Monitor for decreased therapeutic effect of oral tetracycline derivatives.

Calcium Chloride: Calcium salts such as calcium chloride may decrease the serum concentration of tetracycline derivatives such as tetracycline. In general, the coadministration of oral calcium salts and oral tetracycline derivatives should be avoided. Interactions may be able to be minimized by administering oral calcium preparations several hours before or after the dose of the oral tetracycline derivatives. Even with dose separation, therapy may still be compromised. Monitor for decreased therapeutic effect of oral tetracycline derivatives.

Carbenicillin: Possible antagonism of action

Clavulanate: Possible antagonism of action

Cloxacillin: Possible antagonism of action

Colesevelam: Bile acid sequestrants such as colesevelam may decrease the absorption of Tetracycline Derivatives. Monitor for decreased therapeutic effects of tetracycline derivatives if coadministered with a bile acid sequestrant. If these agents are used concomitantly, separate doses 2 or more hours to minimize the interaction. The manufacturer of colesevelam suggests that drugs should be administered at least 1 hour before or 4 hours after colesevelam.

Cyclacillin: Possible antagonism of action

Dicloxacillin: Possible antagonism of action

Dicumarol: Tetracycline may increase the anticoagulant effect of dicumarol.

Dihydroxyaluminium: Formation of non-absorbable complexes

Ethinyl Estradiol: This anti-infectious agent could decrease the effect of the oral contraceptive

Etretinate: Increased risk of intracranial hypertension

Flucloxacillin: Possible antagonism of action

Hetacillin: Possible antagonism of action

Iron: Formation of non-absorbable complexes

Iron Dextran: Formation of non-absorbable complexes

Isotretinoin: Increased risk of intracranial hypertension

Magnesium: Formation of non-absorbable complexes

Magnesium salicylate: Formation of non-absorbable complexes

Mestranol: This anti-infectious agent could decrease the effect of the oral contraceptive

Methicillin Acyl-Serine: Possible antagonism of action

Methotrexate: Tetracycline may increase methotrexate toxicity.

Methoxyflurane: Tetracycline may increase the renal toxicity of methoxyflurane.

Mezlocillin: Possible antagonism of action

Nafcillin: Possible antagonism of action

Oxacillin: Possible antagonism of action

Penicillin G: Possible antagonism of action

Penicillin V: Possible antagonism of action

Piperacillin: Possible antagonism of action

Pivampicillin: Possible antagonism of action

Pivmecillinam: Possible antagonism of action

Quinapril: Quinapril may decrease the absorption of tetracycline.

Tamsulosin: Tetracycline, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Tetracycline is initiated, discontinued, or dose changed.

Tazobactam: Possible antagonism of action

Ticarcillin: Tetracycline may reduce the effect of Ticarcillin by inhibiting bacterial growth. Ticarcillin exerts its effects on actively growing bacteria. To achieve synergism, Ticarcillin should be administered at least 2 hours prior to using Tetracycline.

Tolterodine: Tetracycline may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.

Tramadol: Tetracycline may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.

Trazodone: The CYP3A4 inhibitor, Tetracycline, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Tetracycline is initiated, discontinued or dose changed.

Tretinoin: Demeclocycline may increase the adverse effects of oral Tretinoin. Increase risk of pseudotumour cerebri. Concurrent therapy should be avoided.

Trisalicylate-choline: Formation of non-absorbable complexes

Warfarin: Tetracycline may increase the anticoagulant effect of warfarin.

Zinc: Formation of non-absorbable complexes