Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous, as tosylate [preservative free]:
Nuzyra: 100 mg (1 ea)
Tablet, Oral, as tosylate:
Nuzyra: 150 mg [contains sodium bisulfite]
Pharmacology
Mechanism of Action
Omadacycline inhibits protein synthesis by binding with the 30S ribosomal subunit of susceptible bacteria.
Pharmacokinetics/Pharmacodynamics
Absorption
Food decreases rate and extent of absorption
Distribution
IV: Vdss: 190 L; tissue concentrations exceed plasma concentrations in alveolar cells and epithelial lining fluid
Metabolism
Not metabolized
Excretion
IV: Urine (27% as unchanged drug)
Oral: Feces: (77.5% to 84.0%); Urine: ~14.4 % (range 10.8% to 17.4%)
Time to Peak
IV: ~0.5 hours; Oral: 2.5 hours
Half-Life Elimination
IV: ~16 hours; Oral: 13.45 to 16.83 hours
Protein Binding
20%; not concentration dependent
Use: Labeled Indications
Pneumonia, community-acquired: Treatment of community-acquired bacterial pneumonia (CABP) in adult patients caused by susceptible Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates), Haemophilus influenzae, H. parainfluenzae, Klebsiella pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae.
Skin and skin structure infections: Treatment of acute bacterial skin and skin structure infections (ABSSSI) in adult patients caused by susceptible Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Staphylococcus lugdunensis, Streptococcus pyogenes, Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Enterococcus faecalis, Enterobacter cloacae, and Klebsiella pneumoniae.
Contraindications
Hypersensitivity to omadacycline, tetracycline-class antibacterial drugs, or any component of the formulation.
Dosage and Administration
Dosing: Adult
Pneumonia, community acquired:
Loading dose: IV: 200 mg as a single dose on day 1 or 100 mg twice daily on day 1
Maintenance dose:
IV: 100 mg once daily
Oral: 300 mg once daily
Duration of therapy: 7 to 14 days
Skin and skin structure infections:
Loading dose:
IV: 200 mg as a single dose on day 1 or 100 mg twice daily on day 1
Oral: 450 mg once daily on days 1 and 2
Maintenance dose:
IV: 100 mg once daily
Oral: 300 mg once daily
Duration of therapy: 7 to 14 days
Dosing: Geriatric
Refer to adult dosing.
Reconstitution
IV: Reconstitute 100 mg vial with 5 mL of SWFI, NS, or D5W. Gently swirl and let vial stand until cake dissolves and any foam disperses; do not shake vial. Reconstituted solution should be yellow to dark orange; if not, discard. Prior to further dilution, invert vial to dissolve any remaining powder and gently swirl to prevent foaming, if necessary. Immediately (within 1 hour) withdraw 5 or 10 mL of the reconstituted solution and further dilute to a 100 mL of NS or D5W for final infusion concentration of 1 mg/mL or 2 mg/mL, respectively.
Administration
IV: If stored under refrigeration, allow diluted infusion solution to reach room temperature prior to infusion. Infuse 200 mg dose over a total of 60 minutes and 100 mg dose over a total of 30 minutes through a dedicated line or Y-site; if no dedicated line available, flush line with NS or D5W before and after infusion of omadacycline.
Oral: Administer with water on an empty stomach (after fasting ≥4 hours); avoid food and drink (except water) for 2 hours after administration and avoid dairy and other products with multivalent cations (eg, antacids, multivitamins) for 4 hours after administration.
Dietary Considerations
Tablets: Take with water on an empty stomach (after ≥4 hours of fasting); avoid food and drink (except water) for 2 hours after taking and avoid dairy products for 4 hours after taking.
Storage
Store intact vials and tablets at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Diluted infusion solutions are stable for 12 hours at room temperature (≤25°C) or for 7 days when refrigerated (2°C to 8°C). Do not freeze.
Note: Prior to June 2019, the manufacturer's labeling stated diluted infusion solutions were stable for 24 hours at room temperature and for 48 hours when refrigerated.
Drug Interactions
Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Avoid combination
Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Monitor therapy
Antacids: May decrease the absorption of Tetracyclines. Management: Separate administration of antacids and oral tetracycline derivatives by several hours when possible to minimize the extent of this potential interaction. Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Tetracyclines. Consider therapy modification
Bismuth Subcitrate: May decrease the serum concentration of Tetracyclines. Management: Avoid administration of oral tetracyclines within 30 minutes of bismuth subcitrate administration. This is of questionable significance for at least some regimens intended to treat H. pylori infections. Consider therapy modification
Bismuth Subsalicylate: May decrease the serum concentration of Tetracyclines. Management: Consider dosing tetracyclines 2 hours before or 6 hours after bismuth. The need to separate doses during Helicobacter pylori eradication regimens is questionable. Consider therapy modification
Calcium Salts: May decrease the serum concentration of Tetracyclines. Management: If coadministration of oral calcium with oral tetracyclines can not be avoided, consider separating administration of each agent by several hours. Consider therapy modification
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination
Iron Preparations: Tetracyclines may decrease the absorption of Iron Preparations. Iron Preparations may decrease the serum concentration of Tetracyclines. Management: Avoid this combination if possible. Administer oral iron preparations at least 2 hours before, or 4 hours after, the dose of the oral tetracycline derivative. Monitor for decreased therapeutic effect of oral tetracycline derivatives. Exceptions: Ferric Carboxymaltose; Ferric Derisomaltose; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Consider therapy modification
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy
Lanthanum: May decrease the serum concentration of Tetracyclines. Management: Administer oral tetracycline antibiotics at least two hours before or after lanthanum. Consider therapy modification
Magnesium Dimecrotate: May interact via an unknown mechanism with Tetracyclines. Monitor therapy
Magnesium Salts: May decrease the absorption of Tetracyclines. Only applicable to oral preparations of each agent. Consider therapy modification
Mecamylamine: Tetracyclines may enhance the neuromuscular-blocking effect of Mecamylamine. Avoid combination
Methoxyflurane: Tetracyclines may enhance the nephrotoxic effect of Methoxyflurane. Avoid combination
Mipomersen: Tetracyclines may enhance the hepatotoxic effect of Mipomersen. Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Tetracyclines. Management: If coadministration of a polyvalent cation-containing multivitamin with oral tetracyclines can not be avoided, separate administration of each agent by several hours. Consider therapy modification
Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Tetracyclines. Management: If coadministration of a polyvalent cation-containing multivitamin with oral tetracyclines can not be avoided, separate administration of each agent by several hours. Consider therapy modification
Neuromuscular-Blocking Agents: Tetracyclines may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy
Penicillins: Tetracyclines may diminish the therapeutic effect of Penicillins. Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy
Quinapril: May decrease the serum concentration of Tetracyclines. Management: Separate doses of quinapril and oral tetracycline derivatives by at least 2 hours in order to reduce the risk of interaction. Monitor for reduced efficacy of the tetracycline if these products are used concomitantly. Consider therapy modification
Retinoic Acid Derivatives: Tetracyclines may enhance the adverse/toxic effect of Retinoic Acid Derivatives. The development of pseudotumor cerebri is of particular concern. Exceptions: Adapalene; Bexarotene (Topical); Tretinoin (Topical). Avoid combination
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification
Strontium Ranelate: May decrease the serum concentration of Tetracyclines. Management: In order to minimize any potential impact of strontium ranelate on tetracycline antibiotic concentrations, it is recommended that strontium ranelate treatment be interrupted during tetracycline therapy. Avoid combination
Sucralfate: May decrease the absorption of Tetracyclines. Management: Administer most tetracycline derivatives at least 2 hours prior to sucralfate in order to minimize the impact of this interaction. Administer oral omadacycline 4 hours prior to sucralfate. Consider therapy modification
Sucroferric Oxyhydroxide: May decrease the serum concentration of Tetracyclines. Management: Administer oral/enteral doxycycline at least 1 hour before sucroferric oxyhydroxide. Specific dose separation guidelines for other tetracyclines are not presently available. No interaction is anticipated with parenteral administration of tetracyclines. Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy
Vitamin K Antagonists (eg, warfarin): Tetracyclines may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy
Zinc Salts: May decrease the absorption of Tetracyclines. Only a concern when both products are administered orally. Management: Consider doxycycline as a noninteracting tetracycline derivative. Separate dose administration of oral tetracycline derivative and oral zinc salts by at least 2 hours to minimize interaction. Exceptions: Zinc Chloride. Consider therapy modification
Adverse Reactions
>10%: Gastrointestinal: Nausea (2% to 22%), vomiting (3% to 11%)
1% to 10%:
Cardiovascular: Hypertension (3%), insomnia (3%), atrial fibrillation (<2%), tachycardia (<2%)
Central nervous system: Headache (2% to 3%), fatigue (<2%), lethargy (<2%), vertigo (<2%)
Dermatologic: Erythema (<2%), hyperhidrosis (<2%), pruritus (<2%), urticaria (<2%)
Endocrine & metabolic: Increased gamma-glutamyl transferase (3%)
Gastrointestinal: Diarrhea (3%), constipation (2%), abdominal pain (<2%), dysgeusia (<2%), dyspepsia (<2%), increased serum lipase (<2%), oral candidiasis (<2%)
Genitourinary: Vulvovaginal candidiasis (<2%)
Hematologic & oncologic: Anemia (<2%), thrombocythemia (<2%)
Hepatic: Increased serum alanine aminotransferase (4%), increased serum aspartate aminotransferase (2% to 4%), increased serum alkaline phosphatase (<2%), increased serum bilirubin (<2%)
Hypersensitivity: Hypersensitivity reaction (<2%)
Local: Infusion site reaction (5%)
Neuromuscular & skeletal: Increased creatine phosphokinase (<2%)
Respiratory: Oropharyngeal pain (<2%)
Warnings/Precautions
Concerns related to adverse effects:
- Anaphylactic/Hypersensitivity reactions: Hypersensitivity reactions have been reported; life-threatening hypersensitivity (anaphylactic) reactions have been reported with other tetracyclines. Discontinue if an allergic reaction occurs. Avoid use in patients with known hypersensitivity to tetracyclines.
- Antianabolic effects: May be associated with antianabolic effects observed with the tetracycline class (including increased BUN, azotemia, acidosis, and hyperphosphatemia); discontinue use if suspected.
- Hepatotoxicity: May be associated with abnormal liver function tests due to structural similarities with tetracyclines; discontinue use when suspected.
- Pancreatitis: May be associated with pancreatitis due to structural similarities with tetracyclines; discontinue use if suspected.
- Photosensitivity: May be associated with photosensitivity due to structural similarities with tetracyclines. Use skin protection and avoid prolonged exposure to sunlight and ultraviolet light. Discontinue use if skin erythema occurs.
- Pseudotumor cerebri: May be associated with pseudotumor cerebri due to structural similarities with tetracyclines; discontinue use if suspected.
- Superinfection: Use may result in fungal or bacterial superinfection, including Clostridioides (formerly Clostridium) difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
- Community-acquired bacterial pneumonia: Mortality rate was higher in patients treated with omadacycline for community-acquired bacterial pneumonia (CABP) compared to patients treated with moxifloxacin. All deaths occurred in patients >65 years of age with multiple comorbidities. Monitor CABP patients, particularly those with higher mortality risk, closely for clinical response.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Elderly: Numerically lower clinical success rates at the early clinical response timepoint were observed in CABP patients ≥65 years of age compared to patients <65 years of age. In addition, all deaths in the CABP trial occurred in patients >65 years of age. Monitor closely for clinical response.
- Pediatric: May cause reversible inhibition of bone growth when used during the second and third trimesters of pregnancy, infancy, and childhood ≤8 years of age. May cause tooth enamel hypoplasia or permanent tooth discoloration (more common with long-term use, but observed with repeated, short courses) when used during tooth development (last half of pregnancy, infancy, and childhood ≤8 years of age). Avoid use in children <8 years of age.
Monitoring Parameters
Periodic renal and hepatic function tests
Pregnancy
Pregnancy Considerations
Tetracyclines accumulate in developing teeth and long tubular bones. Permanent discoloration of teeth (yellow, gray, brown) can occur following in utero exposure and is more likely to occur in the second or third trimesters and following long-term or repeated exposure. Reversible inhibition of bone growth may occur following maternal use of tetracyclines in the second and third trimesters.
Due to the potential for adverse pregnancy outcomes, the manufacturer recommends effective contraception for females of reproductive potential during omadacycline therapy.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience nausea, vomiting, or diarrhea. Have patient report immediately to prescriber signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin), signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), signs of acidosis (confusion, fast breathing, fast heartbeat, abnormal heartbeat, severe abdominal pain, nausea, vomiting, fatigue, shortness of breath, or loss of strength and energy), unable to pass urine, change in amount of urine passed, signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools), blindness, blurred vision, double vision, headache, or injection site pain or irritation (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
