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 Guide Editors
 Editor In Chief
    Joel E. Gallant, MD, MPH

Pharmacology Editor
    Paul Pham, PharmD, BCPS

Zambia Guideline Team
   Peter Mwaba MMed PhD FRCP
   Alywn Mwinga MMed
   Isaac Zulu MMed MPH
   Velepie Mtonga MMed
   Albert Mwango MBChB
   Jabbin Mulwanda MMed FCS
 

 

 

Drugs>Antimicrobial Agents>
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Doxycycline

Paul A. Pham Pharm.D. and John G. Bartlett M.D.
11-23-2010

Zambia Specific Information

  • Available formulation in Zambia: Capsule or tablet: 100 mg (hydrochloride).
  • High rates of V. cholerae resistance
  • Drug of choice for brucellosis, chlamydia, and tick-borne infections.
  • Brucellosis: doxycycline 100 mg PO q12h x 6 wks PLUS rifampicin 7.5 mg/kg q12h x 6 wks OR streptomycin 1gm IM q24h x 3 weeks (preferred regimen for osteo-articular or cardiac involvement)
  • Tick-borne infection due to R. conorii and R. africae: doxycycline 100 mg q12h x 7 days
  • P. falciparum malaria (2nd line): doxycycline 200 mg x 1, then 100-200 mg daily x 7 d PLUS quinine.
  • STDs in men and non-pregnant women: doxycycline 100 mg twice daily x 7 days for pt and female partner PLUS ciprofloxacin 500 mg x1. Metronidazole 2000 mg x1 should also be given to female partner.
  • Chlamydia: doxycycline 100 mg twice daily x 7 days (first line).
  • LVG: doxycycline 100 mg twice daily x 14 days (first line).
  • Tick-bite fever (rickettsial disease): doxycycline 200 mg x 1, then 100 mg twice daily x 7 d
  • Significant drug-drug interactions with PIs and NNRTIs are unlikely.

REFERENCES

Zambia Information Author: Paul A. Pham, Pharm. D.

INDICATIONS

FDA

  • Anthrax due to Bacillus anthracis, including inhalation anthrax (post-exposure). CDC recommends as first line agent + 1-2 additional agents with in vitro activity (for inhalation anthrax, see "biodefense-anthrax")
  • Granuloma inguinale caused by Calymmatobacterium granulomatis
  • If PCN: uncomplicated gonorrhea caused by  N. gonorrhoeae; syphilis caused by T. pallidum; yaws caused by Treponema pertenue; listeriosis due to L. monocytogenes; Vincentâ??s infection caused by Fusobacterium fusiforme; actinomycosis caused by A. israelli; Infections caused by Clostridium spp. 
  • Psittacosis caused by Chlamydia psitta
  • Relapsing fever caused by Borrelia recurrentis 
  • Pneumonia caused by Mycoplasma pneumoniae  
  • Rocky mountain spotted fever, typhus, Q fever, rickettsial pox, and tick fevers cased by Rickettsiae.
  • Uncomplicated urethral, endocervical or rectal infections caused by Chlamydia trachomatis; nongonococcal urethritis caused by Ureaplasma urealyticum; lymphogranuloma venereum caused by Chlamydia spp
  • Trachoma; inclusion conjunctivitis cause by C. trachomatis.
  • Gram-negative infections caused by: H. ducreyi, Y. pestis, F. tularensis, V. cholerae, C. fetus, Brucella spp., B. bacilliformis, C. granulomatis. . 

FORMS

brand 
name
 
generic 
Mfg 
brand 
forms
 
cost* 
Vibramycin DoxycyclinePfizeroral
suspension
25 mg/5 ml
 $308.89 per 16oz
      oral
capsule
100 mg
 $6.56
       oral
syrup
 50 mg/5 ml
 na
Doxycycline; Monodox; AdoxaDoxycyclineGeneric manufacturers (Imiren, Watson/Schein and others)oral
capsule
50 mg; 100 mg
$.73-- 50 mg; $1.94 -- 100 mg 
      IV
vial
100 mg
$18.55
      oral
tablet
50 mg; 75 mg; 100 mg
$1.15 --100 mg tab
Periostat   DoxycyclineCollagenex Pharmaceutical and generic manufacturer (Mutual pharmaceutical)Oral
20 mg
tablets 
$3.48
 Doryx DR    Doxycycline Warner Chilcott Labs. oral
delayed release pellet
75 mg, 100 mg, 150 mg
NA 

*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP). AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's information, and the McKesson database.

^Dosage is indicated in mg unless otherwise noted.

USUAL ADULT DOSING

RENAL DOSING

DOSING FOR GLOMERULAR FILTRATION OF 50-80

Usual dose

DOSING FOR GLOMERULAR FILTRATION OF 10-50

Usual dose

DOSING FOR GLOMERULAR FILTRATION OF <10 ML/MIN

Usual dose

DOSING IN HEMODIALYSIS

Usual dose

DOSING IN PERITONEAL DIALYSIS

Usual dose

DOSING IN HEMOFILTRATION

Usual dose

ADVERSE DRUG REACTIONS

OCCASIONAL

  • GI intolerance (dose related)
  • Stains and deforms teeth in children up to 8 yrs old
  • Photosensitivity
RARE

  • Candida overgrowth (vaginitis and esophagitis)
  • Worsening azotemia in pts with renal failure
  • Rash
  • "Black tongue" syndrome; benign fungus infection that is generally reversible upon drug discontinuation.
  • Esophageal ulceration
  • Elevated liver function tests
  • Jarisch-Herxheimer reaction
  •  C. difficile colitis (less likely compared to cephalosporins, carbapenems, and fluoroquinolones)
  • Pseudotumor cerebri
  • Pancreatitis

DRUG INTERACTIONS

Drug-to-Drug Interactions

Drug-to-Drug Interaction

DrugEffect of InteractionRecommendations/Comments
Rifampin Coadministration may decrease tetracyclines serum concentrations. Avoid rifampin co-administration. Monitor closely for tetracycline therapy failure.
Acitretin May increase intracranial pressure. Contraindicated
Bismuth salts (bismuth subsalicylate-pepto-bismol) Bismuth salts chelate tetracyclines resulting in a decreased absorption of tetracycline. Administer bismuth 2 hrs after tetracycline.
Carbamazepine Coadministration may decrease tetracyclines serum concentrationsAvoid carbamazepine co-administration. Monitor closely for tetracycline therapy failure.
Cholestyramine Coadminstration may significantly reduce tetracyclines absorption Avoid co-administration
Colestipol Coadminstration significantly reduce tetracyclines absorption Avoid co-administration
ddI (buffer in peds formulation) contains cations: Polyvalent metal cations form an insoluble chelate with tetracyclines resulting in decreased absorption and serum levels of tetracyclines Separate administration by 4 hrs.
Digoxin Coadministration may result in increased digoxin concentration (in about 10% of pts). Monitor serum level with sign and symptoms of digoxin toxicity.
MethoxyfluraneCase reports of renal failure with co-administration with tetracycline Avoid co-administration.
Non-depolarizing neuromuscular blocker (e.g vecuronium, pancuronium, rocuronium) May potentiate non-depolarizing neuromuscular blocker Use with close monitoring.
Oral contraceptives Tetracyclines may decrease the efficacy of oral contraceptives Consider an additional form of contraception.
Penicillins In vitro antagonism when co-administered. Bacteriocidal effect of penicillins may be diminished in vivo. Avoid co-administration.
Phenobarbital Coadministration may decrease tetracyclines serum concentrations. Avoid phenobarbital co-administration. Monitor closely tetracycline for therapy failure.
Phenytoin Coadministration may decrease tetracyclines serum concentrations. Avoid phenytoin co-administration. Monitor closely for tetracycline therapy failure.
Polyvalent metal cations (aluminum, zinc, magnesium, iron, calcium [milk]) Polyvalent metal cations form an insoluble chelate with tetracyclines resulting in decreased absorption. Separate administration by 4 hrs.
Quinapril Magnesium excipient may reduce tetracyclines absorption. Avoid co-administration.
Rifabutin Coadministration may decrease tetracyclines serum concentrations. Avoid rifabutin co-administration. Monitor closely for tetracycline therapy failure.
Urinary alkalinizers (sodium lactate, sodium bicarbonate) Coadministration results in increased urinary excretion of tetracyclines by 24-65% Avoid co-administration.
Warfarin Coadministration may increase INR. Monitor INR closely.

SPECTRUM

Detailed Spectrum of Activity

Doxycycline also has activity against Plasmodium (malaria), Rickettsia and Brucella spp.

RESISTANCE

  • S. pneumoniae: 12 and 27% resistance in bloodstream infection and pneumonia, respectively. Cross-resistance with PCN-resistant S. pneumoniae with only 60% susceptible.
  • Some strains of CA-MRSA are sensitive doxycycline, but minocycline should be used due to better in vitro activity and demonstrated efficacy in vivo.

PHARMACOLOGY

Pharmacology

COMMENTS

Preferred tetracycline derivative due to more convenient twice-daily dosing regimen and no food-drug interaction. Recommended tetracycline derivative in pts with renal failure. Agents of choice for Rickettsia and Vibrio infections. Minocycline preferred for mild to moderate soft tissue infections caused by CA-MRSA.

REFERENCES

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