What are the recommended adult dosing regimens, durations, contraindications, adverse effects, drug interactions, and alternatives for doxycycline for infections and malaria prophylaxis?

Doxycycline: Comprehensive Clinical Guide

Adult Dosing Regimens

For Infections

For most bacterial infections, start with 200 mg on day 1 (given as 100 mg every 12 hours), then continue 100 mg daily thereafter. 1

• For severe infections, particularly chronic urinary tract infections, maintain 100 mg every 12 hours throughout treatment 1
• For uncomplicated gonococcal infections (except anorectal infections in men): 100 mg twice daily for 7 days 1
• For chlamydial infections (urethral, endocervical, or rectal): 100 mg twice daily for 7 days 1
• For nongonococcal urethritis caused by C. trachomatis or U. urealyticum: 100 mg twice daily for 7 days 1
• For early syphilis in penicillin-allergic patients: 100 mg twice daily for 2 weeks 1
• For late syphilis (>1 year duration) in penicillin-allergic patients: 100 mg twice daily for 4 weeks 1
• For acute epididymo-orchitis: 100 mg twice daily for at least 10 days 1
• For inhalational anthrax post-exposure: 100 mg twice daily for 60 days 1

For Malaria Prophylaxis

For malaria prevention in chloroquine-resistant areas, take 100 mg daily starting 1-2 days before travel, continuing daily during travel, and for 4 weeks after leaving the malarious area. 2, 1

• This regimen is necessary because doxycycline has an unacceptably high failure rate (33% in some studies) as a causal prophylactic agent, requiring the full 4-week post-travel continuation 3
• Doxycycline serves as an alternative for travelers who cannot tolerate mefloquine or for whom mefloquine is contraindicated 2

For STI Post-Exposure Prophylaxis (Doxy PEP)

For men who have sex with men (MSM) and transgender women (TGW) with a bacterial STI diagnosis in the past 12 months, take 200 mg within 72 hours after oral, vaginal, or anal sex, with a maximum of 200 mg per 24-hour period. 2

• This represents a novel prevention strategy with demonstrated efficacy in reducing syphilis, chlamydia, and gonorrhea 2
• Patients using doxy PEP require bacterial STI testing at baseline and every 3-6 months, with ongoing need assessment at the same intervals 2

Contraindications

Absolute Contraindications

Doxycycline is absolutely contraindicated in pregnancy at any trimester and in children under 8 years of age due to teeth discoloration and bone growth inhibition. 2, 4

• Tetracyclines cause permanent tooth discoloration, dental enamel dysplasia, and inhibition of bone growth in developing children 2
• During pregnancy, these effects extend to the developing fetus 2
• Note: Recent evidence suggests this dogma may be overstated for doxycycline specifically, but current guidelines maintain this restriction 5

Relative Contraindications

• Known hypersensitivity to tetracyclines 2
• Severe hepatic impairment (though doxycycline is safer than other tetracyclines in renal impairment) 2

Adverse Effects

Common Adverse Effects

The most frequent adverse effects are photosensitivity and gastrointestinal symptoms, both of which are manageable with proper precautions. 2

• Photosensitivity: Manifests as exaggerated sunburn reaction; minimize by avoiding prolonged sun exposure, using UVA-absorbing sunscreens, and taking the drug in the evening 2
• Gastrointestinal effects: Nausea and vomiting can be minimized by taking doxycycline with food or milk, which does not significantly affect absorption 2, 1
• Esophageal irritation and ulceration: Administer with adequate fluid to wash down the medication 1
• Monilial vaginitis: Increased frequency reported, particularly with daily use 2

Serious Adverse Effects

• In doxy PEP trials, serious adverse events attributed to doxycycline were rare, with discontinuation rates of 0.9% due to gastrointestinal symptoms or fear of adverse events 2
• A meta-analysis of long-term daily doxycycline use (≥8 weeks) found increased risk of gastrointestinal and dermatological adverse events compared to placebo, but no significant differences in severe or neurologic adverse events 2

Drug Interactions

Significant Interactions

Phenytoin, carbamazepine, and barbiturates shorten doxycycline's half-life, theoretically requiring dose increases, though clinical experience with increased dosing for malaria prophylaxis is limited. 2

• The clinical significance of this interaction for malaria prophylaxis remains unclear 2
• Food and milk do not markedly influence doxycycline absorption, unlike other tetracyclines 1

Antimicrobial Resistance Concerns

• In the DoxyPEP study, tetracycline-resistant S. aureus carriage increased from 5% to 13% at 12 months in the doxy PEP arm, though overall S. aureus carriage decreased 2
• Among gonococcal isolates, 30% showed tetracycline resistance in the doxy PEP arm versus 11% in standard care 2
• Despite these concerns, doxycycline remains effective against many N. gonorrhoeae strains in the United States 2

Alternatives

For Malaria Prophylaxis

In chloroquine-resistant areas, mefloquine is the first-line alternative, with atovaquone-proguanil as another option. 6

• Mefloquine: Contraindicated in patients with seizure history, epilepsy, serious psychiatric disorders, cardiac conduction abnormalities, or those requiring fine motor coordination 2, 6
• Atovaquone-proguanil: First-line option alongside mefloquine for chloroquine-resistant areas 6
• Chloroquine alone: For pregnant women and children <15 kg who cannot use other agents, though this provides suboptimal protection in resistant areas 2

For Infections

• For chlamydial infections: Azithromycin 1 g single dose is an alternative
• For syphilis: Penicillin remains the gold standard when not contraindicated 1
• For gonorrhea: Ceftriaxone-based regimens are preferred, as doxycycline is not recommended as monotherapy due to resistance 2

Special Populations

Renal Impairment

Doxycycline is safe in renal impairment and does not require dose adjustment, even in patients on dialysis, because it is primarily metabolized and excreted through the liver. 2, 6

Pregnancy and Lactation

• Absolutely contraindicated throughout pregnancy 2
• Chloroquine and proguanil are the preferred malaria prophylaxis options for pregnant women 6
• Small amounts are secreted in breast milk but are not thought harmful to nursing infants; however, infants requiring malaria prophylaxis need their own appropriate dosing 7

Pediatric Considerations

• Contraindicated in children <8 years of age 2, 4
• For children ≥8 years and ≤100 lbs: 2 mg/lb divided into two doses on day 1, then 1 mg/lb daily (or divided twice daily) thereafter 1
• For malaria prophylaxis in children >8 years: 2 mg/kg daily up to adult dose 1
• For children >100 lbs: Use adult dosing 1

Critical Clinical Pitfalls

Compliance and Timing

Most malaria deaths in travelers occur due to incomplete compliance with prophylaxis regimens, particularly failing to continue for 4 weeks after leaving endemic areas. 6

• Starting 1-2 weeks before travel (1-2 days for doxycycline) allows assessment of tolerability and ensures adequate drug levels 2
• The 4-week post-travel continuation is essential because doxycycline is not reliably causal prophylactic 3

Overdose Risk

Antimalarial drug overdose can be fatal; medication must be stored in child-proof containers out of children's reach. 2

• Pediatric doses must be calculated carefully by body weight 2, 4

Breakthrough Malaria

Any fever or flu-like illness within one year of travel to a malarious area requires emergency evaluation for malaria, even with appropriate prophylaxis, as no regimen provides 100% protection. 6

• Chemoprophylaxis must be combined with mosquito avoidance measures including DEET-containing repellents, long-sleeved clothing after sunset, and permethrin-treated bed nets 6