indication

Doxycycline is indicated for use in respiratory tract infections caused by Mycoplasma pneumoniae, Haemophilus influenzae, Streptococcus pneumoniae, Legionella spp., or Klebsiella spp. It is also used for prophylaxis of malaria. Doxycycline is indicated for a variety of bacterial infections, from Mycobacterium fortuitum and M. marinum, to susceptible E. coli and Brucella spp. It can be used as an alternative to treating plague, tetanus, Campylobacter fetus

pharmacology

Doxycycline, a long-acting tetracycline derived from oxytetracycline, is used to inhibit bacterial protein synthesis and treat non-gonococcal urethritis and cervicitis, exacerbations of bronchitis in patients with COPD, and adult periodontitis.

mechanism of action

Doxycycline, like minocycline, is lipophilic and can pass through the lipid bilayer of bacteria. Doxycycline reversibly binds to the 30 S ribosomal subunits and possibly the 50S ribosomal subunit(s), blocking the binding of aminoacyl tRNA to the mRNA and inhibiting bacterial protein synthesis. Doxycycline prevents the normal function of the apicoplast of Plasmodium falciparum, a malaria causing organism.

toxicity

Symptoms of overdose include anorexia, nausea, diarrhoea, glossitis, dysphagia, enterocolitis and inflammatory lesions (with monilial overgrowth) in the anogenital region, skin reactions such as maculopapular and erythematous rashes, exfoliative dermatitis, photosensitivity, hypersensitivity reactions such as urticaria, angioneurotic oedema, anaphylaxis, anaphyl-actoid purpura, pericarditis, and exacerbation of systemic lupus erythematosus, benign intracranial hypertension in adults disappearing on discontinuation of the medicine, haematologic abnormalities such as haemolytic anaemia, thrombocytopenia, neutropenia, and eosinophilia. LD₅₀=262 mg/kg (I.P. in rat).

biotransformation

Hepatic

absorption

Completely absorbed following oral administration.

half life

18-22 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: The tetracycline, doxycycline, may increase the anticoagulant effect of acenocoumarol.

Acitretin: Increased risk of intracranial hypertension

Aluminium: Formation of non-absorbable complexes

Amobarbital: The anticonvulsant, amobarbital, decreases the effect of doxycycline.

Amoxicillin: Possible antagonism of action

Ampicillin: Possible antagonism of action

Anisindione: The tetracycline, doxycycline, may increase the anticoagulant effect of anisindione.

Aprobarbital: The anticonvulsant, aprobarbital, decreases the effect of doxycycline.

Attapulgite: Formation of non-absorbable complexes

Azlocillin: Possible antagonism of action

Aztreonam: Possible antagonism of action

Bacampicillin: Possible antagonism of action

Bexarotene: Tetracycline derivatives like doxycycline 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).

Butabarbital: The anticonvulsant, butabarbital, decreases the effect of doxycycline.

Butalbital: The anticonvulsant, butalbital, decreases the effect of doxycycline.

Butethal: The anticonvulsant, butethal, decreases the effect of doxycycline.

Calcium: Formation of non-absorbable complexes

Calcium Acetate: Calcium salts such as calcium acetate may decrease the serum concentration of tetracycline derivatives such as doxycycline. 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 doxycycline. 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.

Carbamazepine: The anticonvulsant, carbamazepine, may decrease the therapeutic effect of doxycycline.

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: The tetracycline, doxycycline, may increase the anticoagulant effect of dicumarol.

Dihydroquinidine barbiturate: The anticonvulsant, dihydroquinidine barbiturate, decreases the effect of doxycycline.

Ethinyl Estradiol: Doxycycline may decrease the contraceptive effect of ethinyl estradiol.

Ethotoin: The anticonvulsant, ethotoin, decreases the effect of doxycycline.

Etretinate: Increased risk of intracranial hypertension

Flucloxacillin: Possible antagonism of action

Fosphenytoin: The anticonvulsant, fosphenytoin, decreases the effect of doxycycline.

Heptabarbital: The anticonvulsant, heptabarbital, decreases the effect of doxycycline.

Hetacillin: Possible antagonism of action

Hexobarbital: The anticonvulsant, hexobarbital, decreases the effect of doxycycline.

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 oxide: Formation of non-absorbable complexes

Mephenytoin: The anticonvulsant, mephenytoin, decreases the effect of doxycycline.

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

Methohexital: The anticonvulsant, methohexital, decreases the effect of doxycycline.

Methotrexate: The tetracycline, doxycycline, may increase methotrexate toxicity.

Methylphenobarbital: The anticonvulsant, methylphenobarbital, decreases the effect of doxycycline.

Meticillin: Possible antagonism of action

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

Pentobarbital: The anticonvulsant, pentobarbital, decreases the effect of doxycycline.

Phenobarbital: The anticonvulsant, phenobarbital, may decrease the therapeutic effect of doxycycline.

Phenytoin: The anticonvulsant, phenytoin, may decrease the effect of doxycycline.

Piperacillin: Possible antagonism of action

Pivampicillin: Possible antagonism of action

Pivmecillinam: Possible antagonism of action

Primidone: The anticonvulsant, primidone, decreases the effect of doxycycline.

Quinidine barbiturate: The anticonvulsant, quinidine barbiturate, decreases the effect of doxycycline.

Rifabutin: The rifamycin decreases the effect of doxycycline

Rifampin: The rifamycin decreases the effect of doxycycline

Secobarbital: The anticonvulsant , secobarbital, decreases the effect of doxycycline.

Talbutal: The anticonvulsant, talbutal, decreases the effect of doxycycline.

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

Tazobactam: Possible antagonism of action

Thiopental: Thiopental may decrease the serum levels of Doxycycline. A reduction in antimicrobial effects may occur. An alternative antibiotic may be considered.

Ticarcillin: Doxycycline 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 Doxycycline.

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

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

Warfarin: The tetracycline, doxycycline, may increase the anticoagulant effect of warfarin.

Zinc: Formation of non-absorbable complexes