Doxycycline - Drug Monograph

Introduction

Doxycycline is a broad-spectrum tetracycline-class antibiotic that has been widely used in clinical practice since the 1960s. It is a semi-synthetic derivative of oxytetracycline with improved pharmacokinetic properties, including better oral absorption and longer half-life compared to earlier tetracyclines. Doxycycline remains a cornerstone therapy for numerous bacterial infections and certain parasitic infections due to its favorable safety profile and wide spectrum of activity.

Mechanism of Action

Doxycycline exerts its antibacterial effects primarily through inhibition of protein synthesis. It binds reversibly to the 30S ribosomal subunit, preventing the attachment of aminoacyl-tRNA to the ribosomal acceptor site. This inhibition ultimately disrupts bacterial protein synthesis and leads to bacteriostatic activity against susceptible organisms. Doxycycline demonstrates concentration-dependent killing and exhibits post-antibiotic effects against many pathogens.

Indications

FDA-approved indications include:

• Treatment of Rocky Mountain spotted fever, typhus fever, and Q fever
• Respiratory tract infections caused by susceptible strains of Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae
• Genitourinary infections including uncomplicated gonorrhea, chlamydia, and syphilis (as alternative therapy)
• Skin and soft tissue infections
• Anthrax (including inhalational anthrax)
• Malaria prophylaxis and treatment (in combination with other agents)
• Acne vulgaris
• Ocular infections (topical formulation)

Off-label uses include:

• Lyme disease
• Pelvic inflammatory disease
• Periodontal disease
• Community-acquired pneumonia
• Various rickettsial infections

Dosage and Administration

• Most infections: 100 mg every 12 hours on first day, then 100 mg daily or 50 mg every 12 hours
• Severe infections: 100 mg every 12 hours
• Gonorrhea: 100 mg BID for 7 days
• Syphilis: 100 mg BID for 14 days
• Malaria prophylaxis: 100 mg daily starting 1-2 days before travel and continuing for 4 weeks after return
• Anthrax: 100 mg BID for 60 days

• Renal impairment: No dosage adjustment required
• Hepatic impairment: Use with caution; monitor for toxicity
• Elderly: Standard dosing unless significant hepatic impairment
• Pediatrics (>8 years): 2-4 mg/kg/day divided BID (maximum 200 mg/day)

• Take with food or milk to minimize GI upset
• Maintain adequate fluid intake to prevent esophageal irritation
• Avoid concurrent administration with antacids, iron preparations, or dairy products (separate by 2-3 hours)

Pharmacokinetics

Contraindications

• Hypersensitivity to doxycycline, other tetracyclines, or any component of the formulation
• Pregnancy (category D) due to risk of tooth discoloration and inhibition of bone growth in fetus
• Breastfeeding infants due to risk of tooth discoloration
• Children under 8 years (except for anthrax or Rocky Mountain spotted fever when benefits outweigh risks)

Warnings and Precautions

• Photosensitivity: Severe sunburn may occur; advise patients to avoid sun exposure and use protective measures
• Pseudotumor cerebri: Benign intracranial hypertension has been reported; monitor for headache, blurred vision, diplopia
• Esophageal irritation/ulceration: Administer with adequate fluid and avoid bedtime administration
• Hepatotoxicity: Rare cases of hepatic toxicity reported; monitor liver function in prolonged therapy
• Tooth discoloration: Permanent tooth discoloration may occur if used during tooth development (last half of pregnancy, infancy, childhood to age 8)
• Clostridium difficile-associated diarrhea: May range from mild to life-threatening
• Antianabolic action: May increase BUN and cause azotemia in patients with renal impairment
• Superinfection: May result in bacterial or fungal overgrowth

Drug Interactions

• Antacids containing aluminum, calcium, or magnesium: Decreased absorption (separate administration by 2-3 hours)
• Iron preparations: Decreased absorption (separate administration by 2-3 hours)
• Warfarin: Potentiation of anticoagulant effect; monitor INR closely
• Oral contraceptives: Possible reduced efficacy of oral contraceptives
• Penicillin: May interfere with bactericidal activity of penicillin
• Barbiturates, carbamazepine, phenytoin: Decreased doxycycline half-life
• Methoxyflurane: May cause fatal renal toxicity
• Isotretinoin: Increased risk of pseudotumor cerebri

Adverse Effects

• Nausea, vomiting, diarrhea
• Photosensitivity reactions
• Esophageal irritation
• Vaginal candidiasis

• Hepatotoxicity
• Pseudotumor cerebri
• Blood dyscrasias (neutropenia, thrombocytopenia)
• Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)
• Anaphylaxis
• Esophageal ulceration
• Pancreatitis
• Antibiotic-associated colitis

Monitoring Parameters

• Clinical response: Signs and symptoms of infection
• Adverse effects: GI symptoms, skin reactions, visual changes
• Renal function: BUN and creatinine in patients with pre-existing renal impairment
• Liver function: Periodic monitoring with prolonged therapy
• CBC: With long-term therapy
• For warfarin users: INR monitoring
• For pediatric patients: Growth and development monitoring

Patient Education

• Complete full course of therapy even if feeling better
• Take with food or milk to reduce stomach upset
• Do not take with antacids, calcium supplements, or dairy products (separate by 2-3 hours)
• Avoid excessive sun exposure; use sunscreen and protective clothing
• Report severe diarrhea, skin rash, or visual changes immediately
• Notify all healthcare providers of doxycycline use
• Use alternative contraception methods if taking oral contraceptives
• Do not use in pregnancy or while breastfeeding without medical advice
• Store at room temperature away from moisture and heat

References

1. FDA Prescribing Information: Doxycycline. U.S. Food and Drug Administration. 2. Zhanel GG, et al. The tetracyclines: a comprehensive review. Drugs. 2004;64(1):63-88. 3. Smilack JD. The tetracyclines. Mayo Clin Proc. 1999;74(7):727-729. 4. Lexicomp Online. Doxycycline monograph. Wolters Kluwer Clinical Drug Information. 5. Clinical Pharmacology [database online]. Tampa, FL: Elsevier. 6. Gilbert DN, et al. The Sanford Guide to Antimicrobial Therapy. 52nd ed.; 2022. 7. CDC Guidelines for Sexually Transmitted Diseases. MMWR Recomm Rep. 2021;70(4):1-187. 8. Nelson ML, Levy SB. The history of the tetracyclines. Ann N Y Acad Sci. 2011;1241:17-32.