Introduction
Omadacycline (marketed as Nuzyra®) is a novel aminomethylcycline antibiotic belonging to the tetracycline class. It is a semi-synthetic derivative of minocycline specifically designed to overcome common tetracycline resistance mechanisms. Approved by the FDA in 2018, omadacycline represents an important advancement in the treatment of community-acquired bacterial infections, particularly in the era of increasing antimicrobial resistance.
Mechanism of Action
Omadacycline exerts its antibacterial effects by binding to the 30S ribosomal subunit, thereby inhibiting bacterial protein synthesis. Its unique aminomethyl group modification allows it to evade common tetracycline resistance mechanisms, including efflux pumps (Tet(A-E), Tet(K), and Tet(L)) and ribosomal protection proteins (Tet(M) and Tet(O)). This structural modification provides activity against a broad spectrum of gram-positive, gram-negative, atypical, and anaerobic pathogens, including many drug-resistant strains.
Indications
Omadacycline is FDA-approved for the treatment of:
- Community-acquired bacterial pneumonia (CABP) caused by susceptible microorganisms including Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae
- Acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible microorganisms including Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Staphylococcus lugdunensis, Streptococcus pyogenes, Streptococcus anginosus group, Enterococcus faecalis, Enterobacter cloacae, and Klebsiella pneumoniae
Dosage and Administration
Loading Dose (Day 1):- Intravenous: 200 mg IV over 60 minutes OR
- Oral: 450 mg orally (as two 150 mg tablets in the morning and three 150 mg tablets in the evening)
- Intravenous: 100 mg IV over 30 minutes once daily OR
- Oral: 300 mg orally once daily (as two 150 mg tablets)
- Hepatic impairment: No dosage adjustment required
- Renal impairment: No dosage adjustment required
- Elderly patients: No dosage adjustment required
- Pediatric patients: Safety and effectiveness not established
- Oral administration should occur at least 4 hours before or after dairy products, antacids, or multivitamins containing cations
- IV formulation should not be administered with other medications through the same IV line
Pharmacokinetics
Absorption: Oral bioavailability is approximately 34.5% under fasting conditions. Food significantly reduces absorption (by approximately 50%). Distribution: Extensive tissue distribution with volume of distribution of approximately 190 L. Protein binding is approximately 21%. Metabolism: Minimal hepatic metabolism. Not a substrate, inhibitor, or inducer of major CYP450 enzymes. Elimination: Primarily excreted unchanged in feces (81%) with minor renal excretion (14%). Terminal elimination half-life is approximately 16 hours.Contraindications
- Known hypersensitivity to omadacycline or other tetracycline-class antibiotics
- Use in children under 8 years due to risk of permanent tooth discoloration and enamel hypoplasia
Warnings and Precautions
Tooth Discoloration and Enamel Hypoplasia: Omadacycline may cause permanent tooth discoloration (yellow-gray-brown) and enamel hypoplasia when used during tooth development (last half of pregnancy, infancy, childhood up to 8 years). Inhibition of Bone Growth: May cause reversible inhibition of bone growth when used during tooth development. Clostridium difficile-Associated Diarrhea: May cause antibiotic-associated colitis, including pseudomembranous colitis. Photosensitivity: Photosensitivity manifested by exaggerated sunburn reaction has been observed with tetracycline drugs. Intracranial Hypertension: Benign intracranial hypertension has been associated with tetracycline use. Hepatotoxicity: Hepatic adverse reactions have been reported with tetracycline-class antibiotics.Drug Interactions
Cation-Containing Products: Dairy products, antacids containing aluminum, calcium, or magnesium, and multivitamins containing iron, zinc, or other cations can significantly reduce omadacycline absorption. Administer omadacycline at least 4 hours before or after these products. Warfarin: Tetracyclines have been shown to depress plasma prothrombin activity. Monitor INR closely in patients on anticoagulant therapy. Oral Contraceptives: Tetracyclines may decrease the effectiveness of oral contraceptives. Recommend alternative or additional contraceptive methods.Adverse Effects
Common Adverse Reactions (≥2%):- Nausea (9.8%)
- Vomiting (6.0%)
- Infusion site reactions (4.3%)
- Hypertension (3.1%)
- Headache (2.8%)
- Diarrhea (2.7%)
- Insomnia (2.6%)
- Constipation (2.3%)
- Alanine aminotransferase increased (2.2%)
- Clostridium difficile-associated diarrhea
- Hypersensitivity reactions
- Hepatic toxicity
- Intracranial hypertension
- Severe skin reactions
Monitoring Parameters
- Clinical response to therapy (fever, WBC count, symptoms)
- Signs of superinfection or C. difficile-associated diarrhea
- Liver function tests (baseline and during prolonged therapy)
- INR in patients receiving warfarin
- Signs of intracranial hypertension (headache, blurred vision, diplopia)
- Photosensitivity reactions
- Complete blood count with differential
Patient Education
- Complete the full course of therapy even if feeling better
- Take oral tablets on an empty stomach (at least 4 hours before or after food)
- Avoid dairy products, antacids, and multivitamins within 4 hours of dosing
- Report any severe diarrhea, abdominal pain, or blood/mucus in stool
- Use sun protection measures (protective clothing, sunscreen) while taking this medication
- Report any visual changes, severe headaches, or skin reactions
- Inform healthcare providers of all medications being taken
- Oral contraceptives may be less effective; use alternative contraception
- Do not use in pregnancy or breastfeeding without medical advice
References
1. FDA Prescribing Information: Nuzyra (omadacycline) [Package Insert]. Paratek Pharmaceuticals, Inc.; 2021. 2. Stets R, Popescu M, Gonong JR, et al. Omadacycline for Community-Acquired Bacterial Pneumonia. N Engl J Med. 2019;380(6):517-527. 3. O'Riordan W, Green S, Overcash JS, et al. Omadacycline for Acute Bacterial Skin and Skin-Structure Infections. N Engl J Med. 2019;380(6):528-538. 4. Macone AB, Caruso BK, Leahy RG, et al. In vitro and in vivo antibacterial activities of omadacycline, a novel aminomethylcycline. Antimicrob Agents Chemother. 2014;58(2):1129-1135. 5. Villano S, Steenbergen J, Loh E. Omadacycline: development and therapeutic potential of a novel aminomethylcycline antibiotic. J Med Chem. 2016;59(6):2523-2535. 6. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing. 32nd ed. CLSI supplement M100. Wayne, PA: CLSI; 2022.