FDA label 7cdd3fbf-2e15-39b2-e053-2991aa0ae758

WARNINGS Rare serious allergic reactions, including angioedema and anaphylaxis, have been reported rarely in patients on azithromycin therapy. (See CONTRAINDICATIONS .) Despite initially successful symptomatic treatment of the allergic symptoms, when symptomatic therapy was discontinued, the allergic symptoms recurred soon thereafter in some patients without further azithromycin exposure . These patients required prolonged periods of observation and symptomatic treatment. The relationship of these episodes to the long tissue half-life of azithromycin and subsequent prolonged exposure to antigen is unknown at present. If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Physicians should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued. In the treatment of pneumonia, azithromycin has only been shown to be safe and effective in the treatment of community-acquired pneumonia of mild severity due to Streptococcus pneumoniae or Haemophilus influenzae in patients appropriate for outpatient oral therapy. Azithromycin should not be used in patients with pneumonia who are judged to be inappropriate for outpatient oral therapy because of moderate to severe illness or risk factors such as any of the following: patients with nosocomially acquired infections, patients with known or suspected bacteremia, patients requiring hospitalization, elderly or debilitated patients, or patients with significant underlying health problems that may compromise their ability to respond to their illness (including immunodeficiency or functional asplenia). Pseudomembranous colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of “antibiotic-associated colitis.” After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to discontinuation of the drug alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridium difficile colitis.

ADVERSE REACTIONS In clinical trials, most of the reported side effects were mild to moderate in severity and were reversible upon discontinuation of the drug. Approximately 0.7% of the patients from the multiple-dose clinical trials discontinued azithromycin therapy because of treatment-related side effects. Most of the side effects leading to discontinuation were related to the gastrointestinal tract, e.g., nausea, vomiting, diarrhea, or abdominal pain. Rarely but potentially serious side effects were angioedema and cholestatic jaundice. Clinical Multiple-dose Regimen Overall, the most common side effects in adult patients receiving a multiple-dose regimen of azithromycin were related to the gastrointestinal system with diarrhea/loose stools (5%), nausea (3%), and abdominal pain (3%) being the most frequently reported. No other side effects occurred in patients on the multiple-dose regimen of azithromycin with a frequency greater than 1%. Side effects that occurred with a frequency of 1% or less included the following: Cardiovascular: Palpitations, chest pain. Gastrointestinal: Dyspepsia, flatulence, vomiting, melena, and cholestatic jaundice. Genitourinary: Monilia, vaginitis, and nephritis. Nervous System: Dizziness, headache, vertigo, and somnolence. General: Fatigue. Allergic: Rash, photosensitivity, and angioedema. Chronic Therapy with 1200 mg Weekly Regimen The nature of side effects seen with the 1200 mg weekly dosing regimen for the prevention of Mycobacterium avium infection in severely immunocompromised HIV-infected patients were similar to those seen with short term dosing regimens. (See CLINICAL STUDIES .) Chronic Therapy with 600 mg Daily Regimen Combined with Ethambutol The nature of side effects seen with the 600 mg daily dosing regimen for the treatment of Mycobacterium avium complex infection in severely immunocompromised HIV-infected patients were similar to those seen with short term dosing regimens. Five percent of patients experienced reversible hearing impairment in the pivotal clinical trial for the treatment of disseminated MAC in patients with AIDS. Hearing impairment has been reported with macrolide antibiotics, especially at higher doses. Other treatment related side effects occurring in > 5% of subjects and seen at any time during a median of 87.5 days of therapy include: abdominal pain (14%), nausea (14%), vomiting (13%), diarrhea (12%), flatulence (5%), headache (5%) and abnormal vision (5%). Discontinuations from treatment due to laboratory abnormalities or side effects considered related to study drug occurred in 8/88 (9.1%) of subjects. Postmarketing Experience Adverse events reported with azithromycin during the postmarketing period in adult and/or pediatric patients for which a causal relationship may not be established include: Allergic: Arthralgia, edema, urticaria, angioedema. Cardiovascular: Arrhythmias including ventricular tachycardia, hypotension. There have been rare reports of QT prolongation and torsades de pointes . Gastrointestinal: Anorexia, constipation, dyspepsia, flatulence, vomiting/diarrhea rarely resulting in dehydration, pseudomembranous colitis, pancreatitis, oral candidiasis and rare reports of tongue discoloration. General: Asthenia, paresthesia, fatigue, malaise and anaphylaxis (rarely fatal). Genitourinary: Interstitial nephritis and acute renal failure, vaginitis. Hematopoietic: Thrombocytopenia. Liver/Biliary: Abnormal liver function including hepatitis and cholestatic jaundice, as well as rare cases of hepatic necrosis and hepatic failure, some of which have resulted in death. Nervous System: Convulsions, dizziness/vertigo, headache, somnolence, hyperactivity, nervousness, agitation and syncope. Psychiatric: Aggressive reaction and anxiety. Skin/Appendages: Pruritus, rarely serious skin reactions including erythema multiforme, Stevens Johnson Syndrome, and toxic epidermal necrolysis. Special Senses: Hearing disturbances including hearing loss, deafness, and/or tinnitus, rare reports of taste perversion. Laboratory Abnormalities Significant abnormalities (irrespective of drug relationship) occurring during the clinical trials were reported as follows: With an incidence of 1 to 2%, elevated serum creatine phosphokinase, potassium, ALT (SGPT), GGT, and AST (SGOT). With an incidence of less than 1%, leukopenia, neutropenia, decreased platelet count, elevated serum alkaline phosphatase, bilirubin, BUN, creatinine, blood glucose, LDH, and phosphate. When follow-up was provided, changes in laboratory tests appeared to be reversible. In multiple-dose clinical trials involving more than 3000 patients, 3 patients discontinued therapy because of treatment-related liver enzyme abnormalities and 1 because of a renal function abnormality. In a phase I drug interaction study performed in normal volunteers, 1 of 6 subjects given the combination of azithromycin and rifabutin, 1 of 7 given rifabutin alone and 0 of 6 given azithromycin alone developed a clinically significant neutropenia (less than 500 cells/mm 3 ). Laboratory abnormalities seen in clinical trials for the prevention of disseminated Mycobacterium avium disease in severely immunocompromised HIV-infected patients are presented in the CLINICAL STUDIES section. Chronic therapy (median duration: 87.5 days, range: 1 to 229 days) that resulted in laboratory abnormalities in greater than 5% subjects with normal baseline values in the pivotal trial for treatment of disseminated MAC in severely immunocompromised HIV infected patients treated with azithromycin 600 mg daily in combination with ethambutol include: a reduction in absolute neutrophils to less than 50% of the lower limit of normal (10/52, 19%) and an increase to five times the upper limit of normal in alkaline phosphatase (3/35, 9%). These findings in subjects with normal baseline values are similar when compared to all subjects for analyses of neutrophil reductions (22/75 [29%]) and elevated alkaline phosphatase (16/80 [20%]). Causality of these laboratory abnormalities due to the use of study drug has not been established.