DOXY Powder for solution for injection Ref.[28060] Active ingredients: Doxycycline

Tetracyclines are readily absorbed and are bound to plasma proteins in varying degree. They are concentrated by the liver in the bile, and excreted in the urine and feces at high concentrations and in a biologically active form.

Following a single 100 mg dose administered in a concentration of 0.4 mg/mL in a one-hour infusion, normal adult volunteers averaged a peak of 2.5 mcg/mL, while 200 mg of a concentration of 0.4 mg/mL administered over two hours averaged a peak of 3.6 mcg/mL.

Excretion of doxycycline by the kidney is about 40 percent/72 hours in individuals with normal function (creatinine clearance about 75 mL/min). This percentage of excretion may fall as low as 1 to 5 percent/72 hours in individuals with severe renal insufficiency (creatinine clearance below 10 mL/min). Studies have shown no significant difference in serum half-life of doxycycline (range 18 to 22 hours) in individuals with normal and severely impaired renal function.

Hemodialysis does not alter this serum half-life of doxycycline.

Population pharmacokinetic analysis of sparse concentration-time data of doxycycline following standard of care intravenous and oral dosing in 44 pediatric patients (2-18 years of age) showed that allometrically-scaled clearance (CL) of doxycycline in pediatric patients ≥2 to ≤8 years of age (median [range] 3.58 [2.27-10.82] L/h/70 kg, N=11) did not differ significantly from pediatric patients >8 to 18 years of age (3.27 [1.11-8.12] L/h/70 kg, N=33).

For pediatric patients weighing ≤45 kg, body weight normalized doxycycline CL in those ≥2 to ≤8 years of age (median [range] 0.071 [0.041-0.202] L/kg/h, N=10) did not differ significantly from those >8 to 18 years of age (0.081 [0.035-0.126] L/kg/h, N=8) In pediatric patients weighing >45 kg, no clinically significant differences in body weight normalized doxycycline CL were observed between those ≥2 to ≤8 years of age (0.050 L/kg/h, N=1) and those >8 to 18 years of age (0.044 [0.014-0.121] L/kg/h, N=25). No clinically significant difference in CL between oral and IV dosing was observed in the small cohort of pediatric patients who received the oral (N=19) or IV (N=21) formulation alone.

Microbiology

Mechanism of Action

Doxycycline inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit. Doxycycline has bacteriostatic activity against a broad range of Gram-positive and Gram-negative bacteria.

Resistance

Cross resistance with other tetracyclines is common.

Antimicrobial Activity

Doxycycline has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections (see INDICATIONS AND USAGE).

Gram-Negative Bacteria

Acinetobacter species
Bartonella bacilliformis
Brucella species
Enterobacter aerogenes
Escherichia coli
Francisella tularensis
Haemophilus ducreyi
Haemophilus influenzae
Klebsiella granulomatis
Klebsiella species
Neisseria gonorrhoeae
Shigella species
Vibrio cholerae
Campylobacter fetus
Yersinia pestis

Gram-Positive Bacteria

Bacillus anthracis
Listeria monocytogenes
Streptococcus pneumoniae

Anaerobic Bacteria

Clostridium species
Fusobacterium fusiforme
Propionibacterium acnes

Other Bacteria

Nocardiae and other aerobic Actinomyces species
Borrelia recurrentis
Chlamydophila psittaci
Chlamydia trachomatis
Mycoplasma pneumoniae
Rickettsiae
Treponema pallidum
Treponema pallidum subspecies pertenue
Ureaplasma urealyticum

Parasites

Balantidium coli
Entamoeba species
Plasmodium falciparum*

^* Doxycycline has been found to be active against the asexual erythrocytic forms of Plasmodium falciparum but not against the gametocytes of P. falciparum. The precise mechanism of action of the drug is not known.

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.