indication

Used primarily to treat Lyme disease, acne, and bronchitis. Also indicated (but rarely used) to treat urinary tract infections, gum disease, malaria, and other bacterial infections such as gonorrhea and chlamydia. One of its other registered uses is the treatment of hyponatremia (low blood sodium concentration) due to the syndrome of inappropriate antidiuretic hormone (SIADH) where fluid restriction alone has been ineffective.

pharmacology

Demeclocycline is a tetracycline antibiotic active against the following microorganisms: Rickettsiae (Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsial pox, tick fevers), Mycoplasma pneumoniae (PPLO, Eaton agent), agents of psittacosis and ornithosis, agents of lymphogranulomavenereum and granuloma inguinale, the spirochetal agent of relapsing fever (Borrelia recurrentis), Haemophilus ducreyi (chancroid), Yersinia pestis, Pasteurella pestis and Pasteurella tularensis, Bartonella bacilliformis, Bacteroides species, Vibrio comma and Vibrio fetus, and Brucella species (in conjunction with streptomycin). Demeclocycline inhibits cell growth by inhibiting translation. Demeclocycline is lipophilic and can easily pass through the cell membrane or passively diffuses through porin channels in the bacterial membrane. Demeclocycline is bacteriostatic (it impairs bacterial growth but does not kill bacteria directly). Because it is excreted more slowly than tetracycline, it maintains effective blood levels for longer periods of time.

mechanism of action

Demeclocycline inhibits cell growth by inhibiting translation. It binds (reversibly) to the 30S and 50S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome, which impairs protein synthesis by bacteria. The binding is reversible in nature. The use in SIADH actually relies on a side-effect of tetracycline antibiotics; many may cause diabetes insipidus (dehydration due to the inability to concentrate urine). It is not completely understood why demeclocycline impairs the action of antidiuretic hormone, but it is thought that it blocks the binding of the hormone to its receptor.

toxicity

Oral, rat: LD₅₀ = 2372 mg/kg

biotransformation

Hepatic

absorption

Tetracyclines are readily absorbed.

half life

10-17 hours

route of elimination

Demeclocycline hydrochloride, like other tetracyclines, is concentrated in the liver and excreted into the bile where it is found in much higher concentrations than in the blood. Following a single 150 mg dose of demeclocycline hydrochloride in normal volunteers, 44% (n = 8) was excreted in urine and 13% and 46%, respectively, were excreted in feces in two patients within 96 hours as active drug.

drug interactions

Acenocoumarol: The tetracycline, demeclocycline, 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: The tetracycline, demeclocycline, may increase the anticoagulant effect of anisindione.

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 demeclocycline 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).

Calcium: Formation of non-absorbable complexes

Calcium Acetate: Calcium salts such as calcium acetate may decrease the serum concentration of tetracycline derivatives such as demeoclocycline. 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 demeclocycline. 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: The tetracycline, demeclocycline, may increase the anticoagulant effect of dicumarol.

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 oxide: Formation of non-absorbable complexes

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

Methoxyflurane: The tetracycline, demeclocycline, may increase the renal toxicity of methoxyflurane.

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

Piperacillin: Possible antagonism of action

Pivampicillin: Possible antagonism of action

Pivmecillinam: Possible antagonism of action

Tazobactam: Possible antagonism of action

Ticarcillin: Demeclocycline 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 Demeclocycline.

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

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

Zinc: Formation of non-absorbable complexes