Declomycin

Generic Name: Demeclocycline Hydrochloride
Class: Tetracyclines
VA Class: AM250
CAS Number: 64-73-3  

Introduction

Antibacterial; tetracycline antibiotic derived from Streptomyces aureofaciens.100

Uses for Declomycin

Respiratory Tract Infections

Treatment of respiratory tract infections caused by Mycoplasma pneumoniae.100

Treatment of respiratory tract infections caused by Haemophilus influenzae, Streptococcus pneumoniae, or Klebsiella.100 Should only be used for treatment of infections caused by these bacteria when in vitro susceptibility tests indicate the organism is susceptible.100 a

Acinetobacter Infections

Treatment of infections caused by Acinetobacter;100 minocycline may be the preferred tetracycline for use as an alternative to imipenem or meropenem.e

Acne

Adjunctive treatment of moderate to severe inflammatory acne.100 Not indicated for treatment of noninflammatory acne.a

Actinomycosis

Treatment of actinomycosis caused by Actinomyces israelii;100 oral tetracyclines used as follow-up after initial parenteral treatment with penicillin G.d

Amebiasis

Adjunct to amebicides for treatment of acute intestinal amebiasis.100 Tetracyclines generally not recommended for treatment of amebiasis caused by Entamoeba.d

Anthrax

Alternative to doxycycline for treatment of inhalational anthrax when a parenteral regimen is not available (e.g., when there are supply or logistic problems because large numbers of individuals require treatment in a mass casualty setting).100 A multiple-drug parenteral regimen (ciprofloxacin or doxycycline and 1 or 2 other anti-infectives predicted to be effective) is preferred for treatment of inhalational anthrax that occurs as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism.f

Bartonella Infections

Treatment of infections caused by Bartonella bacilliformis.100

Brucellosis

Treatment of brucellosis;100 tetracyclines considered drugs of choice.d e Used in conjunction with other anti-infectives (e.g., streptomycin or gentamicin and/or rifampin),100 d e especially for severe infections or when there are complications (e.g., endocarditis, meningitis, osteomyelitis).d

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Campylobacter Infections

Treatment of infections caused by Campylobacter.100 Tetracyclines are alternatives, not drugs of choice.d e

Chancroid

Treatment of chancroid caused by Haemophilus ducreyi.100 Not included in CDC recommendations for treatment of chancroid.101

Chlamydial Infections

Treatment of uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia trachomatis.100 Doxycycline is the preferred tetracycline for treatment of these infections, including presumptive treatment of chlamydial infections in patients with gonorrhea.101

Treatment of trachoma and inclusion conjunctivitis caused by C. trachomatis.100 Consider that anti-infectives may not eliminate C. trachomatis in all cases of chronic trachoma.100

Treatment of lymphogranuloma venereum (genital, inguinal, or anorectal infections) caused by C. trachomatis.100 Doxycycline is the preferred tetracycline for these infections.101 d

Treatment of psittacosis (ornithosis) caused by C. psittaci.100 Doxycycline and tetracycline are drugs of choice.a d For initial treatment of severely ill patients, use IV doxycycline.a

Clostridium Infections

Alternative for treatment of infections caused by Clostridium.100 Tetracyclines are alternatives to metronidazole or penicillin G for adjunctive treatment of C. tetani infections.e

Enterobacteriaceae Infections

Treatment of infections caused by susceptible Escherichia coli, Enterobacter aerogenes, Klebsiella, or Shigella.100 Should only be used for treatment of infections caused by these common gram-negative bacteria when other appropriate anti-infectives are contraindicated or ineffectivea and when in vitro susceptibility tests indicate the organism is susceptible.100 a

Fusobacterium Infections

Alternative to penicillin G for the treatment of infections caused by Fusobacterium fusiforme (Vincent’s infection).100

Gonorrhea and Associated Infections

Alternative for treatment of uncomplicated gonorrhea (including urethritis) caused by susceptible Neisseria gonorrhoeae.100 However, tetracyclines are considered inadequate therapy and are not recommended by CDC for treatment of gonorrhea.101 a

Granuloma Inguinale (Donovanosis)

Treatment of granuloma inguinale (donovanosis) caused by Calymmatobacterium granulomatis.100 Doxycycline is the tetracycline recommended as drug of choice by CDC.101

Listeria Infections

Alternative for treatment of listeriosis caused by Listeria monocytogenes.100 Not usually considered a drug of choice or alternative for these infections.d e

Nongonococcal Urethritis

Treatment of nongonococcal urethritis (NGU) caused by Ureaplasma urealyticum, C. trachomatis, or Mycoplasma.100 Doxycycline usually is the tetracycline of choice for NGU.101

Consider that some cases of recurrent urethritis following treatment may be caused by tetracycline-resistant U. urealyticum.101

Plague

Treatment of plague caused by Yersinia pestis.100 Regimen of choice is streptomycin or gentamicin (with or without doxycycline).d e

Relapsing Fever

Treatment of relapsing fever caused by Borrelia recurrentis.100 Tetracyclines are drugs of choice.e

Rickettsial Infections

Treatment of rickettsial infections including Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, and tick fevers caused by Rickettsiae.100 Tetracyclines are drugs of choice for treatment of most rickettsial infections; doxycycline usually is the preferred tetracycline.a d

Syndrome of Inappropriate Antidiuretic Hormone Secretion

Treatment of syndrome of inappropriate antidiuretic hormone secretion (SIADH).a Only limited value in patients with acute water intoxication caused by excess ADH secretion, but may be effective in inhibiting the action of ADH in patients with chronic form of the disease.a

Also has been used to treat hyponatremia and water retention in patients with congestive heart failure or cirrhosis, but a high incidence of renal failure has been reported and the drug probably should not be used in these patients.a

Syphilis

Alternative to penicillin G for treatment of primary, secondary, latent, or tertiary syphilis (not neurosyphilis) in nonpregnant adults and adolescents hypersensitive to penicillins.100 Doxycycline and tetracycline are the preferred tetracyclines in patients hypersensitive to penicillins.101 Use tetracyclines only if compliance and follow-up can be ensured since efficacy not well documented.101

Tularemia

Treatment of tularemia caused by Francisella tularensis.100 Tetracyclines considered alternatives to streptomycin (or gentamicin);d e g risk of relapse and primary treatment failure may be higher than with aminoglycosides.g

Vibrio Infections

Treatment of cholera caused by Vibrio cholerae.100 Doxycycline and tetracycline are drugs of choice; used as an adjunct to fluid and electrolyte replacement in moderate to severe disease.d e

Yaws

Alternative to penicillin G for treatment of yaws caused by Treponema pertenue.100

Declomycin Dosage and Administration

Administration

Oral Administration

Administer orally 1 hour before or 2 hours after meals and/or milk.100

Administer with adequate amounts of fluid to reduce the risk of esophageal irritation and ulceration.100

Dosage

Pediatric Patients

General Pediatric Dosage
Oral

Children >8 years of age: 7–13 mg/kg daily given in 2–4 divided doses.c

Adults

General Adult Dosage
Oral

150 mg 4 times daily or 300 mg 2 times daily.c

Gonorrhea and Associated Infections
Oral

600 mg initially followed by 300 mg every 12 hours for 4 days for a total of 3 g.100

No longer recommended for gonorrhea by CDC or other experts.101

Syndrome of Inappropriate Antidiuretic Hormone Secretion
Oral

600 mg to 1.2 g daily in 3 or 4 divided doses.b Diuresis usually occurs within 5 days after initiation of therapy and reverses within 2–6 days after drug discontinued.b

Prescribing Limits

Pediatric Patients

Maximum 600 mg daily.c

Special Populations

Hepatic Impairment

Adjust dosage by decreasing doses or increasing dosing interval.100

Use with caution.100

Renal Impairment

Adjust dosage by decreasing doses or increasing dosing interval.100

Use with caution.100

Cautions for Declomycin

Contraindications

  • Known hypersensitivity to demeclocycline, other tetracyclines, or any ingredient in the formulation.100

Warnings/Precautions

Warnings

Adverse Dental and Bone Effects

Use during tooth development (e.g., pregnancy, children <8 years of age) may cause permanent yellow-gray to brown discoloration of teeth and enamel hypoplasia100 Effects are most common following long-term use, but may occur following repeated short-term use.100

Tetracyclines form a stable calcium complex in any bone-forming tissue.100 Reversible decrease in fibula growth rate has occurred in prematures receiving tetracycline.100

Use not recommended in children <8 years of age unless other appropriate drugs are ineffective or are contraindicated or unless the benefits in certain indications (e.g., anthrax) outweigh the risks.100 (See Pediatric Use under Cautions.)

Fetal/Neonatal Morbidity

Animal studies indicate possible fetal toxicity (e.g., retardation of skeletal development) and embryotoxicity.100 If used during pregnancy or if patient becomes pregnant while receiving demeclocycline, patient should be apprised of the potential hazard to the fetus.100 (See Pregnancy under Cautions.)

Nervous System Effects

Possibility of adverse CNS effects (light-headedness, dizziness, vertigo) that may impair ability to drive vehicles or operate hazardous machinery.100

Benign intracranial hypertension (pseudotumor cerebri) in adults reported with tetracyclines; usually manifested as headache and blurred vision.100 Bulging fontanels reported in infants.100 Effects usually resolve when drug discontinued, but possibility for permanent sequelae exists.100

Renal Effects

Tetracyclines have antianabolic effects and may increase BUN.100

In patients with impaired renal function, high serum demeclocycline concentrations may result in azotemia, hyperphosphatemia, and acidosis.100 Excessive drug accumulation and possible liver toxicity may occur if usual dosage is used patients with renal impairment.100 (See Renal Impairment under Dosage and Administration.)

Diabetes Insipidus Syndrome

Diabetes insipidus syndrome (polyuria, polydipsia and weakness) reported with long-term demeclocycline therapy.100 Syndrome is nephrogenic, dose-dependent, and reversible when drug discontinued.100

Laboratory Monitoring

Periodically assess organ system function, including renal, hepatic and hematopoietic, during long-term therapy.100

Sensitivity Reactions

Photosensitivity Reactions

Photosensitivity, manifested by an exaggerated sunburn reaction, reported with tetracyclines.100

Photosensitivity reactions may develop within a few minutes to several hours after sun exposure and usually persist 1–2 days after discontinuance of the drug.a Most reactions result from accumulation of tetracyclines in skin and are phototoxic in nature; photoallergic reactions may also occur.a

Discontinue drug at first evidence of skin erythema.100

General Precautions

Superinfection

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.100 Discontinue drug and institute appropriate therapy if superinfection occurs.100

Selection and Use of Anti-infectives

Because many strains of Acinetobacter, Bacteroides, Enterobacter, E. coli, Klebsiella, Shigella, S. pyogenes (group A β-hemolytic streptococci), S. pneumoniae, enterococci, and α-hemolytic streptococci are resistant to tetracyclines (including demeclocycline), in vitro susceptibility tests should be performed if the drug is used for treatment of infections caused by these bacteria.100

Incision and drainage or other surgical procedures should be performed in conjunction with demeclocycline therapy when indicated.100

Specific Populations

Pregnancy

Category D.100 (See Fetal/Neonatal Morbidity under Cautions.)

Lactation

Distributed into milk;100 discontinue nursing or the drug.100

AAP states maternal use of tetracyclines usually is compatible with breast-feeding since absorption of the drugs by nursing infants is negligible.d

Pediatric Use

Should not be used in children <8 years of age unless benefits outweigh the risks.100 (See Adverse Dental and Bone Effects under Cautions.)

Hepatic Impairment

Use with caution.100 Reduce dosage.100

Renal Impairment

Use with caution.100 Reduce dosage.100

Because usual dosage of doxycycline can be used in patients with impaired renal function, it may preferred when a tetracycline is indicated in a patient with impaired renal function.b

Common Adverse Effects

GI effects (anorexia, nausea, vomiting, diarrhea); maculopapular and erythematous rash; dose-related BUN increase; hypersensitivity reactions.100

Interactions for Declomycin

Specific Drugs

Drug

Interaction

Comments

Antacids (aluminum-, calcium-, or magnesium-containing)

Decreased demeclocycline absorption100

Administer antacids containing aluminum, calcium, or magnesium 1–2 hours before or after demeclocyclinea

Anticoagulants, oral

Possible increased anticoagulant effect;100 tetracyclines may impair utilization of prothrombin or decrease vitamin K production by intestinal bacteriaa

Monitor PT carefully; adjust anticoagulant dosage as neededa 100

Hormonal contraceptives

Possible decreased effectiveness of oral contraceptives100

Use alternative nonhormonal contraceptivesa

Iron-containing preparations

Possible decreased absorption of demeclocycline100

Administer demeclocycline 2 hours before or 3 hours after an oral iron preparationa

Methoxyflurane

Possible fatal nephrotoxicity100

Concomitant use not recommendeda

Penicillins

Possible antagonism100

Concomitant use not recommendeda

Declomycin Pharmacokinetics

Absorption

Bioavailability

Approximately 60–80% of a dose absorbed from the GI tract in fasting adults.b Peak serum concentrations attained within 2–4 hours.b c

Food

Food and/or milk decrease GI absorption by ≥50%.b c

Distribution

Extent

Well distributed into body tissues and fluids.c

Plasma Protein Binding

36–91%.a c

Elimination

Metabolism

Does not appear to be metabolized.a

Elimination Route

Excreted into the GI tract via bile and by nonbiliary routes.a Excreted in urine by glomerular filtration.a c

44% of a 150-mg oral dose excreted in urine and 13–46% excreted in feces as unchanged drug.b c

Half-life

Adults with normal renal function: 10–17 hours.b c

Special Populations

Patients with severe renal impairment: half-life 42–68 hours.b

Stability

Storage

Oral

Tablets

20–25°C.100

Actions and Spectrum

  • Usually bacteriostatic,100 a but may be bactericidal in high concentrations or against highly susceptible organisms.a

  • Inhibits protein synthesis100 in susceptible organisms by reversibly binding to 30S and 50S ribosomal subunits.a

  • The complete mechanisms by which tetracyclines reduce acne lesions have not been fully elucidated.a The effects appear to result in part from the antibacterial activity of the drugs, but other mechanisms also are involved.a

  • Spectrum of activity includes many gram-positive and -negative bacteria and various other organisms (e.g., Rickettsia, Chlamydia, Mycoplasma, spirochetes).a c Inactive against fungi and viruses.a

  • Gram-positive aerobes and anaerobes: active against Actinomyces israelii, Bacillus anthracis, Clostridium, Propionibacterium acnes, and some staphylococci and streptococci.a c Many strains of S. pyogenes and Enterococci are resistant.a

  • Gram-negative aerobes and anaerobes: active against Bartonella bacilliformis, Brucella, Calymmatobacterium granulomatis, Francisella tularensis, Haemophilus ducreyi, H. influenzae, Neisseria gonorrhoeae, Vibrio cholerae, and Y. pestis.100 Many strains of Acinetobacter, E. aerogenes, E. coli, Klebsiella, and Shigella and nearly all strains of Proteus and Pseudomonas are resistant.a c

  • Other organisms: active against Rickettsia, Coxiella burnetii, Chlamydia psittaci, C. trachomatis, Mycoplasma hominis, M. pneumoniae, Ureoplasma urealyticum, B. recurrentis, Leptospira, Treponema pallidum, and T. pertenue.a c

  • Complete cross-resistance usually occurs between demeclocycline and other tetracyclines (doxycycline, minocycline, oxytetracycline, tetracycline).a c

Advice to Patients

  • Importance of drinking sufficient quantities of fluids when taking tablets to reduce the risk of esophageal irritation and ulceration.100

  • Advise patients that absorption of demeclocycline may be reduced when taken with foods, especially those containing calcium, and that tablets should be taken at least 1 hour before or 2 hours after meals and/or milk.100

  • Advise patients that adverse CNS effects (light-headedness, dizziness, vertigo) may occur and caution should be used when driving vehicles or operating hazardous machinery.100

  • Advise patients to avoid excessive sunlight or artificial UV light and to discontinue the drug at the first sign of skin erythema;100 consider use of sunscreen or sunblock.a

  • Advise patients that demeclocycline may decrease effectiveness of oral contraceptives and that alternative nonhormonal contraceptive measures should be used.100

  • Advise patients that unused supplies of demeclocycline should be discarded by the expiration date.100

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.100 (See Fetal/Neonatal Morbidity under Cautions.)

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs.100

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Demeclocycline Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder*

Oral

Tablets, film-coated

150 mg*

Declomycin

Glades

Demeclocycline Tablets

Barr, Impax

300 mg*

Declomycin

Glades

Demeclocycline Tablets

Barr, Impax

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

100. Lederle Pharmaceuticals. Declomycin (demeclocycline hydrochloride) for oral use prescribing information. Pearl River, NY. 2002 Mar 14.

101. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2002. MMWR Morb Mortal Wkly Rep. 2002; 51(No. RR-6):1-78.

a. AHFS Drug Information 2004. McEvoy GK, ed. Tetracyclines General Statement. American Society of Health-System Pharmacists; 2004:433-49.

b. AHFS Drug Information 2004. McEvoy GK, ed. Demeclocycline hydrochloride. Bethesda, MD: American Society of Health-System Pharmacists; 2004:449.

c. Lederle Pharmaceuticals. Declomycin (demeclocycline hydrochloride) tablets prescribing information. Pearl River, NY. 2003 Jun.

d. Committee on Infectious Diseases, American Academy of Pediatrics. 2000 Red book: report of the Committee on Infectious Diseases. 25th ed. Elk Grove Village, IL: American Academy of Pediatrics: 2000:187-8,192-3,374-9,547-59.

e. Anon. The choice of antibacterial drugs. Med Lett Drugs Ther. 2001; 43:69-78. [PubMed 11518876]

f. Inglesby TV, O’Toole T, Henderson DA et al for the Working Group on Civilian Biodefense. Anthrax as a biological weapon, 2002. Updated recommendations for management. JAMA. 2002; 287:2236-52. [IDIS 480001] [PubMed 11980524]

g. Dennis DT, Inglesby TV, Henderson DA et al for the Working Group on Civilian Biodefense. Tularemia as a biological weapon: medical and public health management. JAMA. 2001; 285:2763-73. [IDIS 465175] [PubMed 11386933]

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