Doxycycline

1. Drug Name

• Generic Name: Doxycycline

• Brand Names: Vibramycin, Doryx, Monodox, Adoxa, and others.

2. Drug Classification

• Class: Antibiotic, Tetracycline

• Subclass: None (Tetracycline class)

3. Mechanism of Action

• Primary Action: Doxycycline works by inhibiting bacterial protein synthesis. It does so by binding to the 30S ribosomal subunit, preventing the attachment of the aminoacyl-tRNA to the ribosome. This interferes with the elongation of the polypeptide chain, effectively preventing bacterial protein synthesis, which leads to the inhibition of bacterial growth.

• Spectrum of Activity: Doxycycline is a broad-spectrum antibiotic with activity against both gram-positive and gram-negative bacteria, as well as certain atypical pathogens. Its spectrum includes:

  • Gram-negative organisms: Escherichia coli, Haemophilus influenzae, Neisseria gonorrhoeae, Chlamydia species, Legionella species, Bartonella species.

  • Gram-positive organisms: Streptococcus pneumoniae, Staphylococcus aureus (including some MRSA strains), Enterococcus species.

  • Atypical pathogens: Mycoplasma pneumoniae, Chlamydia trachomatis, Rickettsia species, Borrelia burgdorferi (Lyme disease), Brucella species.

• Resistance Mechanisms: Bacterial resistance to doxycycline can occur through several mechanisms, including efflux pump overexpression and ribosomal protection proteins, which reduce the drug's binding to the ribosome. The development of resistance is less common compared to other antibiotics, but it can occur with improper or overuse.

4. Pharmacokinetics

• Absorption: Doxycycline is well absorbed after oral administration, with bioavailability ranging from 90-100%. It is less affected by food compared to other tetracyclines, though absorption can be slightly reduced by dairy products and antacids.

• Distribution: Doxycycline is widely distributed in body tissues and fluids, including lung tissue, prostatic fluid, and bone. It achieves therapeutic concentrations in many tissues and is effective in treating infections in these areas.

• Metabolism: Doxycycline undergoes partial metabolism in the liver but remains largely unchanged in the body. It does not rely heavily on the cytochrome P450 enzyme system for metabolism.

• Excretion: The half-life of doxycycline is approximately 18-22 hours. It is primarily excreted unchanged in the feces (about 40-60%) and to a lesser extent in urine (10-20%).

• Special Considerations: Doxycycline is excreted in both urine and feces. In patients with renal impairment, no significant dose adjustments are required, though close monitoring is recommended for severe renal dysfunction.

5. Indications

• Primary Indications:

  • Respiratory Infections: Community-acquired pneumonia, acute exacerbations of chronic bronchitis, and sinusitis.

  • Sexually Transmitted Infections (STIs): Gonorrhea, chlamydia, syphilis (as part of combination therapy), and non-gonococcal urethritis.

  • Rickettsial Infections: Treatment of Rickettsia species causing diseases such as Rocky Mountain spotted fever and typhus.

  • Tick-borne Diseases: Lyme disease caused by Borrelia burgdorferi.

  • Acne: Effective in treating moderate-to-severe acne vulgaris.

  • Periodontal Disease: Adjunctive treatment in periodontal infections.

  • Malaria Prophylaxis: Doxycycline is used in travelers for the prevention of malaria in endemic areas.

• Off-label Uses:

  • Brucellosis: Used as part of combination therapy for brucellosis.

  • Prostatitis: Treatment of chronic prostatitis due to susceptible organisms.

• Specific Populations: Doxycycline is generally well tolerated in adults and older children. Its use in children under 8 years is contraindicated due to the risk of permanent tooth discoloration and enamel hypoplasia.

6. Dosage and Administration

• Adult Dosing:

  • Infections (e.g., respiratory, urinary tract, STIs): 100 mg orally every 12 hours for 7-14 days, depending on the severity of the infection.

  • Acne: 50-100 mg orally once or twice daily, typically for several weeks.

  • Malaria Prophylaxis: 100 mg daily, starting 1-2 days before travel, continuing during travel, and for 4 weeks after leaving the endemic area.

  • Lyme Disease (Early Stage): 100 mg orally every 12 hours for 10-21 days.

  • Rickettsial Infections: 100 mg orally every 12 hours for 7-14 days.

• Pediatric Dosing:

  • For children ≥8 years: 2.2 mg/kg orally every 12 hours for moderate to severe infections. The maximum dose should not exceed 100 mg per dose.

• Renal Adjustments: No significant dose adjustment is required in renal impairment.

• Route of Administration: Doxycycline is available in oral tablets, oral suspension, and intravenous formulations.

7. Contraindications

• Absolute Contraindications:

  • Hypersensitivity to doxycycline or any other tetracycline antibiotic.

  • Children under 8 years of age due to the risk of permanent tooth discoloration and enamel hypoplasia.

  • Pregnancy (especially during the second and third trimesters) due to potential effects on fetal bone and teeth development.

• Relative Contraindications:

  • Pregnancy (First Trimester): Doxycycline is a Category D drug in pregnancy and should only be used when clearly needed.

  • Lactation: Doxycycline is excreted in breast milk and should be used cautiously in nursing mothers, as it can affect the infant's teeth development.

8. Warnings and Precautions

• Teeth Discoloration: Doxycycline can cause permanent discoloration of teeth in children under 8 years and may also affect fetal teeth development during pregnancy.

• Photosensitivity: Doxycycline can increase sensitivity to sunlight, leading to an increased risk of sunburn. Patients should be advised to avoid prolonged exposure to sunlight or tanning beds.

• Liver Toxicity: Hepatotoxicity, including elevated liver enzymes, is rare but possible. Patients with pre-existing liver conditions should be monitored closely.

• Esophageal Irritation: Doxycycline can cause esophageal irritation or ulcers. It is recommended to take doxycycline with a full glass of water and remain upright for 30 minutes after taking the medication.

• Superinfection: Prolonged use of doxycycline may lead to superinfection, including fungal or bacterial overgrowth (e.g., Candida species).

• Intracranial Hypertension: Rarely, doxycycline may cause intracranial hypertension, leading to symptoms such as headache, vision changes, and papilledema.

9. Adverse Effects

• Common Adverse Effects (≥10%):

  • Gastrointestinal: Nausea, vomiting, diarrhea, abdominal discomfort.

• Less Common but Clinically Significant:

  • Hepatotoxicity: Elevations in liver enzymes.

  • Photosensitivity: Increased risk of sunburn.

  • Esophageal Irritation/Ulcers: Particularly if the drug is taken without adequate water or while lying down.

  • CNS Effects: Headache, dizziness, lightheadedness, and rare cases of increased intracranial pressure (pseudotumor cerebri).

• Serious Adverse Reactions:

  • Stevens-Johnson Syndrome (SJS): A rare but serious reaction causing skin peeling, fever, and mucosal lesions.

  • Severe Allergic Reactions: Including anaphylaxis, angioedema, and anaphylactic shock.

  • Clostridium difficile-associated Diarrhea (CDAD): Diarrhea caused by Clostridium difficile can be severe and life-threatening.

10. Drug Interactions

• Major Drug Interactions:

  • Antacids and Supplements (calcium, magnesium, iron): These can reduce the absorption of doxycycline. They should be taken 2 hours before or 4 hours after doxycycline.

  • Rifampin: Rifampin may decrease the effectiveness of doxycycline due to induction of liver enzymes.

  • Warfarin: Doxycycline may enhance the anticoagulant effects of warfarin, increasing the risk of bleeding.

  • Oral Contraceptives: Doxycycline may reduce the effectiveness of oral contraceptives, leading to breakthrough bleeding and potential pregnancy. Additional contraceptive methods should be considered.

  • CYP3A4 Inhibitors: Doxycycline metabolism may be affected by strong CYP3A4 inhibitors, though this is a less significant interaction compared to other drugs.

11. Clinical Pharmacology

• Pharmacodynamics: Doxycycline exhibits bacteriostatic activity by inhibiting bacterial protein synthesis, and its effect is time-dependent. The therapeutic drug levels are primarily based on AUC/MIC (area under the curve/minimum inhibitory concentration) ratio.

• Additional Effects: Doxycycline has anti-inflammatory properties, which contribute to its use in treating conditions like acne and periodontitis.

12. Special Populations

• Pregnancy: Category D (may cause harm to the fetus). Use only if no alternative therapy is available, particularly after the first trimester.

• Lactation: Doxycycline is excreted into breast milk in small amounts. Caution is advised, and alternative therapies should be considered.

• Geriatrics: No specific adjustments are needed for elderly patients, but they may be more susceptible to adverse effects, particularly photosensitivity and hepatotoxicity.

• Pediatrics: Contraindicated in children under 8 years due to risk of permanent tooth discoloration and enamel hypoplasia.

13. Therapeutic Uses

• First-Line Therapy: For respiratory infections, chlamydia, and Lyme disease.

• Second-Line Therapy: For malaria prophylaxis, brucellosis, and chronic acne.

• Combination Therapy: Used in combination with other antibiotics for infections like pelvic inflammatory disease (PID) or resistant tuberculosis.

14. Monitoring and Follow-Up

• Lab Tests: Liver function tests (AST, ALT), renal function (BUN, creatinine), and a complete blood count (CBC) during long-term therapy.

• Sun Exposure: Advise patients to avoid direct sunlight or tanning beds due to increased risk of photosensitivity.

• Signs of Superinfection: Monitor for symptoms of a new infection, especially oral or vaginal candidiasis.

15. Overdose Management

• Symptoms of Overdose: Nausea, vomiting, dizziness, and possible hypoglycemia.

• Treatment Protocols: There is no specific antidote for doxycycline overdose. Symptomatic treatment with fluids and supportive care should be given.

• Supportive Measures: Activated charcoal may be considered if the overdose occurred within a short time after ingestion.

16. Patient Counseling Information

• Key Points to Discuss with Patients:

  • Take doxycycline with a full glass of water and remain upright for 30 minutes after taking to prevent esophageal irritation.

  • Avoid taking doxycycline with dairy products, antacids, or supplements that contain calcium, magnesium, or iron.

  • Use sunscreen and avoid excessive sun exposure due to the risk of photosensitivity.

  • Inform your healthcare provider if you have a history of liver disease or gastrointestinal issues.

• Signs/Symptoms to Watch For:

  • Severe diarrhea or abdominal cramps.

  • Yellowing of the skin or eyes (jaundice), which may indicate liver problems.

  • Painful or swollen joints, muscle aches, or tendon inflammation.