INTERACTIONS Patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage while taking NUZYRA. ( 7.1 ) Absorption of tetracyclines, including NUZYRA, is impaired by antacids containing aluminum, calcium, or magnesium, bismuth subsalicylate and iron containing preparations. ( 2.1 , 7.2 )
7.1 Anticoagulant Drugs Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage while also taking NUZYRA.
7.2 Antacids and Iron Preparations Absorption of oral tetracyclines, including NUZYRA, is impaired by antacids containing aluminum, calcium, or magnesium, bismuth subsalicylate, and iron containing preparations <span class="opacity-50 text-xs">[see Dosage and Administration (2.1) ]</span>.
NUZYRA is contraindicated in patients with known hypersensitivity to omadacycline or tetracycline class antibacterial drugs, or to any of the excipients [see Warnings and Precautions (5.3) and Adverse Reactions (6.1) ]. Known hypersensitivity to omadacycline, tetracycline class antibacterial drugs or any of the excipients in NUZYRA ( 4 )
AND PRECAUTIONS Mortality Imbalance in Patients with CABP : In the CABP trial, mortality rate of 2% was observed in NUZYRA-treated patients compared to 1% in moxifloxacin-treated patients. The cause of the mortality imbalance has not been established. Closely monitor clinical response to therapy in CABP patients, particularly in those at higher risk for mortality. ( 5.1 , 6.1 )
Tooth
Discoloration and Enamel Hypoplasia : The use of NUZYRA during tooth development (last half of pregnancy, infancy and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown) and enamel hypoplasia. ( 5.2 , 8.1 , 8.4 ) Inhibition of Bone Growth: The use of NUZYRA during the second and third trimester of pregnancy, infancy and childhood up to the age of 8 years may cause reversible inhibition of bone growth. ( 5.3 , 8.1 , 8.4 ) Clostridioides difficile -associated diarrhea : Evaluate if diarrhea occurs. ( 5.5 )
5.1 Mortality Imbalance in Patients with Community-Acquired Bacterial Pneumonia Mortality imbalance was observed in the CABP clinical trial with eight deaths (2%) occurring in patients treated with NUZYRA compared to four deaths (1%) in patients treated with moxifloxacin. The cause of the mortality imbalance has not been established. All deaths, in both treatment arms, occurred in patients >65 years of age; most patients had multiple comorbidities <span class="opacity-50 text-xs">[see Use in Specific Populations (8.5) ]</span> . The causes of death varied and included worsening and/or complications of infection and underlying conditions. Closely monitor clinical response to therapy in CABP patients, particularly in those at higher risk for mortality <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span>.
5.2 Tooth Discoloration and Enamel Hypoplasia The use of NUZYRA during tooth development (last half of pregnancy, infancy, and childhood up to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). This adverse reaction is more common during long-term use of the tetracycline class drugs, but it has been observed following repeated short-term courses. Enamel hypoplasia has also been reported with tetracycline class drugs. Advise the patient of the potential risk to the fetus if NUZYRA is used during the second or third trimester of pregnancy <span class="opacity-50 text-xs">[see Use in Specific Populations (8.1 , 8.4) ]</span>.
5.3 Inhibition of Bone Growth The use of NUZYRA during the second and third trimester of pregnancy, infancy and childhood up to the age of 8 years may cause reversible inhibition of bone growth. All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in premature infants given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued. Advise the patient of the potential risk to the fetus if NUZYRA is used during the second or third trimester of pregnancy <span class="opacity-50 text-xs">[see Use in Specific Populations (8.1 , 8.4) ]</span> .
5.4 Hypersensitivity Reactions Hypersensitivity reactions have been reported with NUZYRA <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span>. Life-threatening hypersensitivity (anaphylactic) reactions have been reported with other tetracycline class antibacterial drugs. NUZYRA is structurally similar to other tetracycline class antibacterial drugs and is contraindicated in patients with known hypersensitivity to tetracycline class antibacterial drugs <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> . Discontinue NUZYRA if an allergic reaction occurs.
5.5 Clostridioides difficile- Associated Diarrhea Clostridioides difficile- associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated.
5.6 Tetracycline Class Effects NUZYRA is structurally similar to tetracycline class of antibacterial drugs and may have similar adverse reactions. Adverse reactions including photosensitivity, fixed drug eruption, pseudotumor cerebri, and anti-anabolic action which has led to increased BUN, azotemia, acidosis, hyperphosphatemia, pancreatitis, and abnormal liver function tests, have been reported for other tetracycline class antibacterial drugs, and may occur with NUZYRA. Discontinue NUZYRA if any of these adverse reactions are suspected.
5.7 Development of Drug-Resistant Bacteria Prescribing NUZYRA in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria <span class="opacity-50 text-xs">[see Indications and Usage (1.3) ]</span>.