Doxycycline

Generic name
Doxycycline
Brand name
ATC Code
J01AA02
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Doxycycline

Dosages
Side effects in children
Warnings & precautions in children
Contra-indications in children

Interactions
PK
Renal impairment
References

Pharmacokinetics in children

Absorption is almost complete after oral administration, Cmax is reached after approximately 2 hours, steady state plasma concentration is reached after 4 days. The elimination half-life is approximately 20 hours. Due to the relatively long half-life, a loading dose of doxycycline is recommended. The exact metabolic pathway is unknown, but doxycycline concentrations are decreased by potent CYP3A4 inducers. It undergoes enterohepatic circulation. After oral administration, doxycycline is primarily unchanged excreted (approximately 40%) in urine. The remainder (20-50%) is excreted in the feces as an inactive complex after diffusion into the intestinal lumen [SmPC].  

In adults, the Vd is 0.7-1.4 l/kg and the half-life is 12 to 25 hours. In one study of 10 children aged >24 months old, who received respectively one dose of doxycycline 4 mg/kg (N=5 children) or 2 mg/kg (N=5 children), the apparent Vd was respectively 0.859 to 1.841 l/kg of the actual body weight (wt) and the half-life was respectively 11.18 to 8.89 hours [Ceccarelli 1971]. 

In a population pharmacokinetic study, children (N=47 in total of which N=14 ≤8 years) receiving doxycycline treatment as antimicrobial treatment (all indications) with a median dose of 1.69 (0.88-2.94) mg/kg, the following individual empirical Bayesian post hoc parameter estimates were found [Thompson 2019]:

Parameter N= CL (liter/kg/h)* V (liter/kg)* Half-life (h)*
Age        
<2 years 3 0.059 (0.050-0.077) 1.50 (1.41-1.91) 17.7 (12.6-26.5)
Weight        
≥2 to ≤8 years 11 0.068 (0.041-0.202) 1.43 (1.02-2.56) 17.2 (5.8-24.0)
    ≤45 kg 10 0.071 (0.041-0.202) (p=0.86) 1.51 (1.02-2.56) (p=0.29) 16.9 (5.8-24.0) (p=0.79)
    >45 kg 1 0.050 1.43 19.9
>8 years 33 0.047 (0.014-0.126) 1.25 (0.38-3.18) 20.4 (4.8-41.3)
    ≤45 kg 8 0.081 (0.035-0.126) 1.16 (0.87-3.18) 15.2 (4.8-30.5)
    >45 kg 25 0.044 (0.014-0.121) 1.26 (0.38-2.93) 20.4 (6.3-41.3)
Overall 47 0.051 (0.014-0.202) 1.36 (0.38-3.18) 18.8 (4.8-41.3)

*Median value(s) range or p value

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

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Bacterial infections
  • Oral
    • ≥ 8 years and < 45 kg
      [2]
      • Initial dose: 4.4 mg/kg/day in 1 dose
      • Maintenance dose: 2.2 mg/kg/day in 1 dose
  • Intravenous
    • ≥ 8 years and < 45 kg
      [2]
      • Initial dose: 4.4 mg/kg/day in 1 dose
      • Maintenance dose: 2.2 mg/kg/day in 1 dose
Severe bacterial infections
  • Oral
    • ≥ 8 years and < 45 kg
      [2]
      • Initial dose: 4.4 mg/kg/day in 1 dose
      • Maintenance dose: 4.4 mg/kg/day in 2 doses.
  • Intravenous
    • ≥ 8 years and < 45 kg
      [2]
      • Initial dose: 4.4 mg/kg/day in 1 dose
      • Maintenance dose: 4.4 mg/kg/day in 2 doses.
    • ≥ 45 kg
      [2]
      • Initial dose: 200 mg/day in 1 dose
      • Maintenance dose: 200 mg/day in 2 doses.
Infection in cystic fibrosis
  • Oral
    • 8 years up to 18 years
      • Initial dose: 5 mg/kg/day, once only.
      • Maintenance dose: 5 mg/kg/day in 1 - 2 doses. Max: 200 mg/day.
Early localized, disseminated and late Lyme disease
  • Oral
    • ≥ 8 years and < 45 kg
      [2] [3]
      • 4.4 mg/kg/day in 2 doses.
      • Duration of treatment:
        • Early localized Lyme disease: 10 days
        • Lyme meningitis, facial paresis without cell reaction in the CSF: 14 days
        • Early disseminated lyme disease other than meningitis and lyme arthritis: 21 days
        • Late Lyme disease and Lyme arthritis: 30 days
        • Chronic neuroborreliosis with pleiocytosis in the CSF: 30 days
    • ≥ 45 kg
      [2] [3]
      • 200 mg/day in 2 doses.
      • Duration of treatment:
        • Early localised lyme disease: 10 days
        • Lyme meningitis, facial paresis without cell reaction in the liquor: 14 days
        • Early disseminated lyme disease other than meningitis and lyme arthritis: 21 days
        • Late lyme disease and lyme arthritis: 30 days
        • Chronic neuroborreliosis without pleiocytosis in the liquor: 30 days

        (duration of treatment based on Dutch guideline; adjust to local guidelines if needed)
Prophylaxis for malaria
  • Oral
    • 1 month up to 18 years
      • 2.2 mg/kg/day in 1 dose. Max: 100 mg/day.
      • Duration of treatment:

        Commence on the day of arrival in a region where malaria is endemic; take while staying there and continue until 4 weeks after leaving the endemic area

    • ≥ 8 years
      [5]
      • 2.2 mg/kg/day in 1 dose Max single dose: 100 mg/dose.
      • Duration of treatment:

        Commence on the day of arrival in a region where malaria is endemic; take while staying there and continue until 4 weeks after leaving the endemic area
Prophylaxis after a tick bite
  • Oral
    • ≥ 8 years
      • 200 mg/dose, once only.

      • < 8 Jahre: Azithromycin

    • < 8 years
      [3]

      • In dieser Altersgruppe sollte Azithromycin verwendet werden.

    • ≥ 8 years and < 45 kg
      [3] [4] [6]
      • 4.4 mg/kg/day in 1 dose once only.
Treatment of uncomplicated malaria
  • Oral
    • ≥ 8 years
      [4]
      • 4.4 mg/kg/day in 2 doses. Max: 200 mg/day.
      • Duration of treatment:

        At least 7 days

      • Always give in combination with a schizonticide.

Renal impaiment in children > 3 months

GFR ≥10 ml/min/1.73m2: Dose adjustment not required.

GFR <10 ml/min/1.73m2: A general recommendation on dose adjustment cannot be provided.

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

(Irreversible) tooth discoloration in children (1%), disturbances in tooth development, hypoplasia of tooth enamel [Rajan 2025][Ma 2025].

Chelation of tetracycline in tooth enamel can cause enamel hypoplasia and permanent tooth discoloration [Stultz 2019]. 
In literature, incidence rates of tooth discoloration after tetracycline exposure ranged from 23 to 92%, with increasing incidence related to the dose, duration (eg, >21 days of exposure), and number of courses [Todd 2015].
In a recent review one premature infant (1/162) developed tooth discoloration and two children (2/162) developed enamel hypoplasia after being exposed to doxycycline [Dou 2024]. In addition, a recent meta-analysis found a pooled incidence of tooth discoloration of 0.92% (95% 0.34%-1.50%) with no significant heterogeneity (I2 < 0%) [Ma 2025].

The top six positive signals with the highest proportional reporting ratio (PRR) in the FEARS database for adverse drug reactions of doxycycline in children aged ≤8 years were laryngeal injury, Horner’s syndrome, nerve injury, gastritis erosive, vanishing bile duct syndrome and methaemoglobinaemia [Dou 2024]. None of these adverse drug reactions are mentioned in the Summary of Product Characteristics of doxycycline. It is therefore important that clinical practitioners are aware of these potential adverse drug reactions

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications in children

with facial rosacea <12 years

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

The risk of enamel hypoplasia and permanent tooth discoloration is greatest when drug exposure occurs during odontogenesis before complete formation of permanent teeth enamel with calcification. This process usually ends by 8 years of age and is the reason for use restriction in children <8 years of age [Stultz 2019]. Yet, unlike tetracycline, doxycycline binds to calcium to a lesser extent (respectively 39.5% versus 19%) [Todd 2015]. Recent observational studies show that treating young children with doxycycline may not lead to permanent tooth discoloration [Biggs 2016][Volovitz 2007][Poyhonen 2017][Todd 2015][Ravindra 2023][Boast 2016][Stultz 2019]. The risk of tooth discoloration and enamel hypoplasia is low, which led to the withdrawal of the former contraindication in children aged < 8 years old. In 2018, the Infectious Disease Committee of the American Academy of Pediatrics stated that short courses (up to 21 days) of oral doxycycline are safe in patients of all ages The total recommended duration of doxycycline treatment should not exceed 21 days and repeated courses should be avoided because of cumulative exposure [Red Book 2024].  

Based on pharmacokinetic data, the doxycycline dose in children aged 1 month to 8 years is similar on a mg/kg basis to that used in children older than 8 years [Thompson 2019]. However, due to limited data in children under 2 years of age, doxycycline should be used with caution in this group. Furthermore, in children aged 1 month to 8 years, doxycycline should only be considered when no alternative treatment options are available, the duration of therapy should be kept as short as possible, and repeated courses should be avoided.

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

TETRACYCLINES

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

Tetracyclines
J01AA08
J01AA07
J01AA12

References

  1. Hartwig NC, et al, Vademecum pediatrische antimicrobiële therapie, 2005
  2. Teva, SPC Doxycycline (RVG 09519) 06-11-2018, www.cbg-meb.nl
  3. CBO, Richlijn Lymeziekte, www.cbo.nl, 2013
  4. Aurobindo, SmPC Doxycycline (RVG12871) 12-11-2018, www.cbg-meb.nl
  5. Landelijk Coordinatiecentrum Reizigers Advisering, Malariaprofylaxe bulletin, 2015, Feb
  6. Wichers IM et al, NHG Behandelrichtlijn tekenbeet, 2017
  7. Biggs HM, et al., Diagnosis and management of tickborne rickettsial diseases: Rocky mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis - United States, MMWR Recomm Rep, 2016, 65(2), 1-44
  8. Volovitz B, et al., Absence of tooth staining with doxycycline treatment in young children, Clin Pediatr, 2007, 46(2), 121-6
  9. Poyhonen H, et al., Dental staining after doxycycline use in children, J Antimicrob Chemoth, 2017, 72(10), 2887-90
  10. Todd SR, et al., No visible dental staining in children treated with doxycycline for suspected Rocky Mountain Spotted Fever, J Pediatr, 2015, 166(5), 1246-51
  11. Dermapharm, SmPC Doxyderma 50 mg (11619.00.00), 06/2016
  12. Ratiopharm, SmPC Doxy-M-ratiopharm Tabletten (16390.00.00/ 16390.01.00), 11/2017
  13. Lalloo, D.G., et al., UK malaria treatment guidelines 2016, J Infect, 2016, 72(6), 635-649
  14. Hexal, SmPC DoxyHEXAL SF (14975.00.00), 04/2017
  15. Aliud Pharma, SmPC Doxycyclin AL (10543.00.00/ 10543.01.00/ 8552.00.00/ 8184.00.00), 12/2017
  16. Hexal, SmPC DoxyHEXAL® tabs 100 mg Tabletten/ DoxyHEXAL® 200 mg tabs Tabletten (7481.00.00/ 7481.01.00), 10/2016
  17. GALENpharma, SmPC Doxakne tabs (1230.02.00), 05/2015
  18. Ratiopharm, SmPC Doxycyclin-ratiopharm SF (576.00.01), 11/2017
  19. Galderma Laboratorium, SmPC Oraycea 40 mg Hartkapseln mit veränderter Wirkstofffreisetzung (65881.00.00), 09/2017
  20. Robert Koch Institut, "Ratgeber für Ärzte - Malaria", abgerufen: 20.03.2018
  21. Ratiopharm, SmPC Doxycyclin-ratiopharm 100 mg Weichkapseln (576.00.00), 11/2017
  22. Dermapharm, SmPC Doxyderma 100 mg (16637.00.00), 03/2016
  23. Deutsche Dermatologische Gesellschaft (DDG), Kutane Lyme Borreliose, S2k Leitlinie, 2016
  24. Ceccarelli G, et al., Pharmacokinetic Study of Doxycycline in Children. Chemotherapy., Chemotherapy., 1971, 1-10
  25. Ma K, et al., Incidence and influencing factors of tooth discoloration in children using doxycycline: a meta-analysis., Front Pediatr., 2025
  26. Dou W, et al., Real-world safety profile of tetracyclines in children younger thand 8 years old: an analysis of FEARS database and review of case report., Expert Opin Drug Saf., 2024, 23(7), 885-892
  27. Red Book: Report of the Committee on Infectious Diseases, Tetracyclines, 2024, 975-976
  28. Aurobindo, SmPC Doxycycline (RVG 12871), www.cbg-meb.nl, 23-7-2024
  29. Thompson E.J, et al., Population pharmacokinetcs of doxycycline in Children., Antimicrobial Agents and Chemotherapy., 2019, 63(12)
  30. Rajan A.S, et al., Dental safety of short-term doxycycline use in children under 8 years: a systematic review and meta-analysis., Front Pharmacol., 2025
  31. Stultz J.S, et al., Doxycycline and Tooth Discolaration in Children: Changing of Recommendations Based on Evidence of Safety., Annals of Pharmacotherapy., 2019, 53(11), 1162-1166
  32. Ravindra D, et al., Antibiotic Exposure and Dental Health: A Systematic Review. Pediatrics., 2023, 152(1)
  33. Boast A, et al., QUESTION 1 : teething issues : can doxycycline be safely used in young children?, Arch Dis Child., 2016, 63(12)
  34. Teva, SmPC Doxycycline (RVG 15344), www.cbg-meb.nl, 2-4-2024

Changes

Therapeutic Drug Monitoring


Overdose