Demeclocycline Hydrochloride

(BANM, rINNM)
Synonyms: Déméclocycline, chlorhydrate de; Demeclocyclini hydrochloridum; Demeklociklin-hidroklorid; Demeklociklino hidrochloridas; Demeklocyklin-hydrochlorid; Demeklocyklinhydroklorid; Demeklocykliny chlorowodorek; Demeklosiklin Hidroklorür; Demeklosykliinihydrokloridi; Demethylchlortetracycline Hydrochloride; Hidrocloruro de demeclociclina.
Cyrillic synonym: Демеклоциклина Гидрохлорид.

💊 Chemical information

Chemical formula: C21H21ClN2O8,HCl = 501.3.
CAS — 64-73-3.
ATC — D06AA01; J01AA01.
ATC Vet — QD06AA01; QJ01AA01.

Pharmacopoeias.

In Eur., Jpn, and US.

Ph. Eur. 6.2

(Demeclocycline Hydrochloride). The hydrochloride of a substance produced by certain strains of Streptomyces aureofaciens or by any other means. A yellow powder. Soluble or sparingly soluble in water; slightly soluble in alcohol; very slightly soluble in acetone. It dissolves in solutions of alkali hydroxides and carbonates. A 1% solution in water has a pH of 2.0 to 3.0. Protect from light.

USP 31

(Demeclocycline Hydrochloride). A yellow, odourless, crystalline powder. Soluble 1 in 60 of water and 1 in 50 of methyl alcohol; slightly soluble in alcohol; practically insoluble in acetone and in chloroform; sparingly soluble in solutions of alkali hydroxides and carbonates. pH of a 1% solution in water is between 2.0 and 3.0. Store in airtight containers. Protect from light.

💊 Adverse Effects and Precautions

As for Tetracycline. Phototoxic reactions occur more frequently with demeclocycline than with other tetracyclines and patients should avoid direct exposure to sunlight or artificial ultraviolet light. Reversible nephrogenic diabetes insipidus with polyuria, polydipsia, and weakness may occur in patients treated with demeclocycline, particularly with prolonged treatment and/or high doses. Plasma creatinine should be monitored in patients receiving demeclocycline for long periods for the treatment of inappropriate secretion of antidiuretic hormone, since tetracyclineinduced renal impairment may not otherwise be apparent in the absence of oliguria. For a comment that the usefulness of demeclocycline for this indication may be limited by nephrotoxicity in patients with cardiac or hepatic disease, see Syndrome of Inappropriate ADH Secretion under Uses and Administration, below.

💊 Interactions

As for Tetracycline.

💊 Antimicrobial Action

As for Tetracycline. Demeclocycline is stated to be somewhat more active against certain strains of some organisms including Neisseria gonorrhoeae and Haemophilus influenzae, as well as to being the most active of the tetracyclines
in vitro against Brucella spp.

💊 Pharmacokinetics

For the general pharmacokinetics of the tetracyclines, see Tetracycline. About 60 to 80% of a dose of demeclocycline is absorbed from the gastrointestinal tract. Peak plasma concentrations of about 1.5 to 1.7 micrograms/mL have been reported 3 to 4 hours after a single oral dose of 300 mg, but higher plasma concentrations may be achieved with repeated dosage. Its plasma elimination half-life is about 12 hours, although this may be prolonged in patients with renal impairment; values of 42 to 68 hours have been reported in severe impairment. The renal clearance of demeclocycline is about half that of tetracycline.

💊 Uses and Administration

Demeclocycline is a tetracycline derivative with uses similar to those of tetracycline. It is excreted more slowly and effective blood concentrations are maintained for a longer period. Demeclocycline is given orally as the hydrochloride; the usual adult dose is 600 mg daily in 2 or 4 divided doses, preferably 1 hour before or 2 hours after meals. For atypical pneumonia, 900 mg daily in 3 divided doses may be given. It is also sometimes given orally with other tetracycline derivatives. For details of doses in children and adolescents, see below. Demeclocycline may also be given to adults in the treatment of chronic hyponatraemia associated with the syndrome of inappropriate antidiuretic hormone secretion, when water restriction has proved ineffective. Initially 900 to 1200 mg is given daily in divided doses, reducing to maintenance doses of 600 to 900 mg daily. For dosage recommendations in patients with hepatic impairment, see below. The calcium and magnesium salts of demeclocycline have also been used.

Administration in children.

In children, the effects on teeth should be considered and tetracyclines only used when absolutely essential; demeclocycline may be used for the treatment of susceptible infections. In the UK, it is licensed for use in children aged 12 years and over; the usual adult dose (see above) may be given orally. However, in the USA, it may be given to those over 8 years old in usual doses of 7 to 13 mg/kg daily by mouth in 2 or 4 divided doses.

Administration in hepatic impairment.

UK licensed product information states that the dosage of demeclocycline should not exceed 1 g daily in patients with known liver disease.

Syndrome of inappropriate ADH secretion.

Demeclocycline may be given in the treatment of the syndrome of inappropriate ADH (antidiuretic hormone) secretion to antagonise the effect of ADH on the renal tubules; lithium has been given as an alternative. Both lithium and demeclocycline act by interfering with the cellular action of ADH to produce nephrogenic diabetes insipidus. Demeclocycline was reported to be superior to lithium1 and became the preferred treatment for chronic SIADH if water restriction was unsuccessful,2 although fluid restriction is probably still the treatment of choice. However, since nephrotoxicity has been reported in patients with cardiac or hepatic disease, the usefulness of demeclocycline in the treatment of hyponatraemic states might be limited; this view was supported by studies in patients with heart failure3 and cirrhosis.4
1. Forrest JN, et al. Superiority of demeclocycline over lithium in the treatment of chronic syndrome of inappropriate secretion of antidiuretic hormone. N Engl J Med 1978; 298: 173–7
2. Schrier RW. Treatment of hyponatremia. N Engl J Med 1985; 312: 1121–2
3. Zegers de Beyl D, et al. Demeclocycline treatment of water retention in congestive heart failure. BMJ 1978; 1: 760
4. Miller PD, et al. Plasma demeclocycline levels and nephrotoxicity: correlation in hyponatremic cirrhotic patients. JAMA 1980; 243: 2513–15.

💊 Preparations

BP 2008: Demeclocycline Capsules; USP 31: Demeclocycline Hydrochloride Capsules; Demeclocycline Hydrochloride Tablets; Demeclocycline Oral Suspension.

Proprietary Preparations

Austral.: Ledermycin†; Canad.: Declomycin; Fr.: Ledermycine; India: Ledermycin; Neth.: Ledermycin; UK: Ledermycin; USA: Declomycin. Multi-ingredient: Austria: Ledermix; Denm.: Ledermix†; Ger.: Ledermix; Israel: Ledermix; Ital.: Rubrociclina†; S.Afr.: Tr itet ; Switz.: Ledermix; UK: Deteclo†; Ledermix.
Published February 01, 2019.