NUZYRA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NUZYRA (NUZYRA).
Omadacycline is a aminomethylcycline antibiotic that inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit, blocking aminoacyl-tRNA binding to the A site.
| Metabolism | Minimal hepatic metabolism; not significantly metabolized by CYP enzymes. Excreted primarily unchanged in urine and feces. |
| Excretion | Fecal (approximately 76%) as unchanged drug; renal (approximately 14%) as unchanged drug; biliary excretion is minimal. |
| Half-life | Terminal elimination half-life is approximately 17-21 hours; supports once-daily dosing. |
| Protein binding | 80-90% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Approximately 7-10 L/kg; indicates extensive tissue distribution, exceeding total body water. |
| Bioavailability | Oral: approximately 34% (fasting) to 62% (with high-fat meal); food significantly increases absorption. |
| Onset of Action | Intravenous: clinical effect observed within 24-48 hours; Oral: similar onset after IV to oral transition. |
| Duration of Action | Sustained for 24 hours with once-daily dosing; clinical duration extends beyond half-life due to prolonged post-antibiotic effect. |
| Molecular Weight | 496.9 |
200 mg intravenously once on day 1, then 100 mg IV once daily; or 200 mg orally once on day 1, then 100 mg orally once daily.
| Dosage form | POWDER |
| Renal impairment | For CrCl 30-49 mL/min: 200 mg IV/PO once on day 1, then 100 mg IV/PO once every 48 hours. For CrCl <30 mL/min (including dialysis): 200 mg IV/PO once on day 1, then 100 mg IV/PO once every 48 hours. For hemodialysis: administer after dialysis. |
| Liver impairment | Child-Pugh Class B or C: no dose adjustment recommended; use with caution. No specific dose adjustment provided in labeling. |
| Pediatric use | Safety and efficacy not established in pediatric patients below 18 years of age. |
| Geriatric use | No specific dose adjustment required; monitor renal function and consider age-related decline in CrCl for dosing adjustments. |
| 1st trimester | Avoid use in first trimester due to potential for fetal harm based on animal studies showing skeletal abnormalities. |
| 2nd trimester | Use only if benefit outweighs risk; limited human data, but animal studies suggest risk of skeletal and tooth discoloration in fetus. |
| 3rd trimester | Use only if benefit outweighs risk; may cause dental discoloration and bone growth impairment in the fetus. |
Clinical note
Comprehensive clinical and safety monograph for NUZYRA (NUZYRA).
| Placental transfer | Expected to cross placenta based on animal studies; molecular weight and lipophilicity suggest significant transfer. |
| Breastfeeding | Not recommended during breastfeeding as no data available on excretion in human milk; potential for adverse effects in nursing infant (e.g., tooth discoloration, bone growth inhibition). |
■ FDA Black Box Warning
No boxed warning.
| Serious Effects |
Hypersensitivity to omadacycline or any tetracycline-class antibiotic
| Precautions | Tooth discoloration and enamel hypoplasia with use during tooth development, Inhibition of bone growth in premature infants and children under 8 years, Clostridioides difficile-associated diarrhea, Photosensitivity reactions, Potential for microbial overgrowth, Tetracycline class effects (e.g., antianabolic action leading to increased BUN, azotemia, hyperphosphatemia, and acidosis) |
| Food/Dietary | Oral omadacycline should be taken with food to enhance absorption and tolerability. Avoid concomitant intake of dairy products (milk, cheese, yogurt), antacids, iron supplements, calcium supplements, magnesium supplements, and multivitamins containing these cations within 4 hours of dosing, as they chelate and reduce absorption. |
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| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | NUZYRA (omadacycline) is a tetracycline-class antibiotic. Tetracyclines can cause fetal harm when administered to a pregnant woman. Use during the second and third trimesters may cause reversible inhibition of bone growth and permanent discoloration of teeth (yellow-gray-brown). Use during the first trimester is associated with an increased risk of neural tube defects and other malformations. Omadacycline is contraindicated in pregnant women. |
| Fetal Monitoring | Monitor maternal liver function tests and renal function periodically. For fetal monitoring, ultrasound assessment may be considered if exposure occurs during the first trimester. No specific fetal monitoring is required but assess for potential tetracycline-associated effects in neonates. |
| Fertility Effects | In animal studies, omadacycline did not impair fertility in rats. However, tetracyclines may affect spermatogenesis in males at high doses. Clinical data on human fertility are lacking. |
| Clinical Pearls | NUZYRA (omadacycline) is a once-daily aminomethylcycline antibiotic effective against community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI). It is available in both IV and oral formulations with high oral bioavailability. Avoid use in patients with hypersensitivity to tetracyclines. Monitor for photosensitivity and tooth discoloration in children under 8. Dose adjustment required in severe hepatic impairment (Child-Pugh C). IV formulation contains sulfobutylether-β-cyclodextrin, use with caution in renal impairment. |
| Patient Advice | Take oral omadacycline with food to reduce nausea; avoid dairy products, antacids, iron, calcium, magnesium, and multivitamins within 4 hours of dosing. · Report diarrhea, especially if watery or bloody, as it may indicate Clostridioides difficile infection. · Avoid excessive sun exposure and use sunscreen; photosensitivity can occur. · Complete the full course of therapy even if you feel better. · If pregnant or breastfeeding, inform your healthcare provider before use. |