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| Product NDC Code | 71205-430 | ||||||
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| Drug Name | Azithromycin dihydrate |
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| Type | Generic | ||||||
| Pharm Class | Macrolide Antimicrobial [EPC], Macrolides [CS] |
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| Route | ORAL | ||||||
| Dosage Form | TABLET, FILM COATED | ||||||
| RxCUI drug identifier | 308460, 749783 |
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| Application Number | ANDA208250 | ||||||
| Labeler Name | Proficient Rx LP | ||||||
| Packages |
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| Check if available Online | Get Medication Prices online with Discount |
Overdosage of Azithromycin Dihydrate
Information about signs, symptoms, and laboratory findings of acute ovedosage and the general principles of overdose treatment.10 OVERDOSAGE Adverse reactions experienced at higher than recommended doses were similar to those seen at normal doses particularly nausea, diarrhea, and vomiting. In the event of overdosage, general symptomatic and supportive measures are indicated as required.
Adverse reactions
Information about undesirable effects, reasonably associated with use of the drug, that may occur as part of the pharmacological action of the drug or may be unpredictable in its occurrence. Adverse reactions include those that occur with the drug, and if applicable, with drugs in the same pharmacologically active and chemically related class. There is considerable variation in the listing of adverse reactions. They may be categorized by organ system, by severity of reaction, by frequency, by toxicological mechanism, or by a combination of these.6 ADVERSE REACTIONS Most common adverse reactions are diarrhea (5% to 14%), nausea (3% to 18%), abdominal pain (3% to 7%), or vomiting (2% to 7%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact TAGI Pharma, Inc. at 1-855-225-8244 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical trials, most of the reported side effects were mild to moderate in severity and were reversible upon discontinuation of the drug. Potentially serious adverse reactions of angioedema and cholestatic jaundice were reported. Approximately 0.7% of the patients (adults and pediatric patients) from the 5-day multiple-dose clinical trials discontinued azithromycin therapy because of treatment-related adverse reactions. In adults given 500 mg/day for 3 days, the discontinuation rate due to treatment-related adverse reactions was 0.6%. In clinical trials in pediatric patients given 30 mg/kg, either as a single dose or over 3 days, discontinuation from the trials due to treatment-related adverse reactions was approximately 1%. Most of the adverse reactions leading to discontinuation were related to the gastrointestinal tract, e.g., nausea, vomiting, diarrhea, or abdominal pain. [see Clinical Studies (14.2) ] Adults Multiple-dose regimens: Overall, the most common treatment-related adverse reactions in adult patients receiving multiple-dose regimens of azithromycin were related to the gastrointestinal system with diarrhea/loose stools (4% to 5%), nausea (3%), and abdominal pain (2% to 3%) being the most frequently reported. No other adverse reactions occurred in patients on the multiple-dose regimens of azithromycin with a frequency greater than 1%. Adverse reactions 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, pruritus, photosensitivity, and angioedema. Single 1-gram dose regimen: Overall, the most common adverse reactions in patients receiving a single-dose regimen of 1 gram of azithromycin were related to the gastrointestinal system and were more frequently reported than in patients receiving the multiple-dose regimen. Adverse reactions that occurred in patients on the single 1-gram dosing regimen of azithromycin with a frequency of 1% or greater included diarrhea/loose stools (7%), nausea (5%), abdominal pain (5%), vomiting (2%), dyspepsia (1%), and vaginitis (1%). Single 2-gram dose regimen: Overall, the most common adverse reactions in patients receiving a single 2-gram dose of azithromycin were related to the gastrointestinal system. Adverse reactions that occurred in patients in this study with a frequency of 1% or greater included nausea (18%), diarrhea/loose stools (14%), vomiting (7%), abdominal pain (7%), vaginitis (2%), dyspepsia (1%), and dizziness (1%). The majority of these complaints were mild in nature. Pediatric Patients Single and Multiple-dose regimens: The types of adverse reactions in pediatric patients were comparable to those seen in adults, with different incidence rates for the dosage regimens recommended in pediatric patients. Acute Otitis Media: For the recommended total dosage regimen of 30 mg/kg, the most frequent adverse reactions (≥ 1%) attributed to treatment were diarrhea, abdominal pain, vomiting, nausea, and rash. [see Dosage and Administration (2) and Clinical Studies (14.2) ] The incidence, based on dosing regimen, is described in the table below: Dosage Regimen Diarrhea % Abdominal Pain % Vomiting % Nausea % Rash % 1-day 4.3% 1.4% 4.9% 1.0% 1.0% 3-day 2.6% 1.7% 2.3% 0.4% 0.6% 5-day 1.8% 1.2% 1.1% 0.5% 0.4% Community-Acquired Pneumonia: For the recommended dosage regimen of 10 mg/kg on Day 1 followed by 5 mg/kg on Days 2 to 5, the most frequent adverse reactions attributed to treatment were diarrhea/loose stools, abdominal pain, vomiting, nausea, and rash. The incidence is described in the table below: Dosage Regimen Diarrhea/Loose stools % Abdominal Pain % Vomiting % Nausea % Rash % 5-day 5.8 % 1.9 % 1.9 % 1.9 % 1.6% Pharyngitis/Tonsillitis: For the recommended dosage regimen of 12 mg/kg on Days 1 to 5, the most frequent adverse reactions attributed to treatment were diarrhea, vomiting, abdominal pain, nausea, and headache. The incidence is described in the table below: Dosage Regimen Diarrhea % Abdominal Pain % Vomiting % Nausea % Rash % Headache % 5-day 5.4 % 3.4 % 5.6 % 1.8 % 0.7 % 1.1 % With any of the treatment regimens, no other adverse reactions occurred in pediatric patients treated with azithromycin with a frequency greater than 1%. Adverse reactions that occurred with a frequency of 1% or less included the following: Cardiovascular: Chest pain. Gastrointestinal: Dyspepsia, constipation, anorexia, enteritis, flatulence, gastritis, jaundice, loose stools, and oral moniliasis. Hematologic and Lymphatic: Anemia and leukopenia. Nervous System: Headache (otitis media dosage), hyperkinesia, dizziness, agitation, nervousness, and insomnia. General: Fever, face edema, fatigue, fungal infection, malaise, and pain. Allergic: Rash and allergic reaction. Respiratory: Cough, pharyngitis, pleural effusion, and rhinitis. Skin and Appendages: Eczema, fungal dermatitis, pruritus, sweating, urticaria, and vesiculobullous rash. Special Senses: Conjunctivitis. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of azithromycin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Adverse reactions 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, and angioedema. Cardiovascular: Arrhythmias including ventricular tachycardia and hypotension. There have been reports of QT prolongation and torsades de pointes . Gastrointestinal: Anorexia, constipation, dyspepsia, flatulence, vomiting/diarrhea, pseudomembranous colitis, pancreatitis, oral candidiasis, pyloric stenosis, and reports of tongue discoloration. General: Asthenia, paresthesia, fatigue, malaise, and anaphylaxis. Genitourinary: Interstitial nephritis, acute renal failure, and vaginitis. Hematopoietic: Thrombocytopenia. Liver/Biliary: Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure. [see Warnings and Precautions (5.2) ] Nervous System: Convulsions, dizziness/vertigo, headache, somnolence, hyperactivity, nervousness, agitation, and syncope. Psychiatric: Aggressive reaction and anxiety. Skin/Appendages: Pruritus serious skin reactions including erythema multiforme, AGEP, Stevens-Johnson Syndrome, toxic epidermal necrolysis, and DRESS. Special Senses: Hearing disturbances including hearing loss, deafness and/or tinnitus, and reports of taste/smell perversion and/or loss. 6.3 Laboratory Abnormalities Adults: Clinically significant abnormalities (irrespective of drug relationship) occurring during the clinical trials were reported as follows: with an incidence of greater than 1%: decreased hemoglobin, hematocrit, lymphocytes, neutrophils, and blood glucose; elevated serum creatine phosphokinase, potassium, ALT, GGT, AST, BUN, creatinine, blood glucose, platelet count, lymphocytes, neutrophils, and eosinophils; with an incidence of less than 1%: leukopenia, neutropenia, decreased sodium, potassium, platelet count, elevated monocytes, basophils, bicarbonate, serum alkaline phosphatase, bilirubin, LDH, and phosphate. The majority of subjects with elevated serum creatinine also had abnormal values at baseline. When follow-up was provided, changes in laboratory tests appeared to be reversible. In multiple-dose clinical trials involving more than 5,000 patients, four patients discontinued therapy because of treatment-related liver enzyme abnormalities and one because of a renal function abnormality. Pediatric Patients: One, Three, and Five Day Regimens Laboratory data collected from comparative clinical trials employing two 3-day regimens (30 mg/kg or 60 mg/kg in divided doses over 3 days), or two 5-day regimens (30 mg/kg or 60 mg/kg in divided doses over 5 days) were similar for regimens of azithromycin and all comparators combined, with most clinically significant laboratory abnormalities occurring at incidences of 1% to 5%. Laboratory data for patients receiving 30 mg/kg as a single dose were collected in one single center trial. In that trial, an absolute neutrophil count between 500 cells/mm 3 to 1,500 cells/mm 3 was observed in 10/64 patients receiving 30 mg/kg as a single dose, 9/62 patients receiving 30 mg/kg given over 3 days, and 8/63 comparator patients. No patient had an absolute neutrophil count < 500 cells/mm 3 . In multiple-dose clinical trials involving approximately 4,700 pediatric patients, no patients discontinued therapy because of treatment-related laboratory abnormalities.
Azithromycin Dihydrate Drug Interactions
Information about and practical guidance on preventing clinically significant drug/drug and drug/food interactions that may occur in people taking the drug.7 DRUG INTERACTIONS • Nelfinavir: Close monitoring for known adverse reactions of azithromycin, such as liver enzyme abnormalities and hearing impairment, is warranted. ( 7.1 ) • Warfarin: Use with azithromycin may increase coagulation times; monitor prothrombin time. ( 7.2 ) 7.1 Nelfinavir Co-administration of nelfinavir at steady-state with a single oral dose of azithromycin resulted in increased azithromycin serum concentrations. Although a dose adjustment of azithromycin is not recommended when administered in combination with nelfinavir, close monitoring for known adverse reactions of azithromycin, such as liver enzyme abnormalities and hearing impairment, is warranted. [see Adverse Reactions (6) ] 7.2 Warfarin Spontaneous postmarketing reports suggest that concomitant administration of azithromycin may potentiate the effects of oral anticoagulants such as warfarin, although the prothrombin time was not affected in the dedicated drug interaction study with azithromycin and warfarin. Prothrombin times should be carefully monitored while patients are receiving azithromycin and oral anticoagulants concomitantly. 7.3 Potential Drug-Drug Interactions with Macrolides Interactions with digoxin, colchicine or phenytoin have not been reported in clinical trials with azithromycin. No specific drug interaction studies have been performed to evaluate potential drug-drug interactions. However, drug interactions have been observed with other macrolide products. Until further data are developed regarding drug interactions when digoxin, colchicine or phenytoin are used with azithromycin careful monitoring of patients is advised.
Clinical pharmacology
Information about the clinical pharmacology and actions of the drug in humans.12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Azithromycin is a macrolide antibacterial drug . [see Microbiology (12.4) ] 12.2 Pharmacodynamics Based on animal models of infection, the antibacterial activity of azithromycin appears to correlate with the ratio of area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC) for certain pathogens ( S. pneumoniae and S. aureus ). The principal pharmacokinetic/pharmacodynamic parameter best associated with clinical and microbiological cure has not been elucidated in clinical trials with azithromycin. Cardiac Electrophysiology QTc interval prolongation was studied in a randomized, placebo-controlled parallel trial in 116 healthy subjects who received either chloroquine (1,000 mg) alone or in combination with oral azithromycin (500 mg, 1,000 mg, and 1,500 mg once daily). Co-administration of azithromycin increased the QTc interval in a dose- and concentration- dependent manner. In comparison to chloroquine alone, the maximum mean (95% upper confidence bound) increases in QTcF were 5 (10) ms, 7 (12) ms and 9 (14) ms with the co-administration of 500 mg, 1,000 mg and 1,500 mg azithromycin, respectively. 12.3 Pharmacokinetics Following oral administration of a single 500 mg dose (two 250 mg tablets) to 36 fasted healthy male volunteers, the mean (SD) pharmacokinetic parameters were AUC 0-72 = 4.3 (1.2) mcg∙hr/mL; C max = 0.5 (0.2) mcg/mL; T max = 2.2 (0.9) hours. Two azithromycin 250 mg tablets are bioequivalent to a single 500 mg tablet. In a two-way crossover study, 12 adult healthy volunteers (6 males, 6 females) received 1,500 mg of azithromycin administered in single daily doses over either 5 days (two 250 mg tablets on day 1, followed by one 250 mg tablet on days 2 to 5) or 3 days (500 mg per day for days 1 to 3). Due to limited serum samples on day 2 (3-day regimen) and days 2 to 4 (5-day regimen), the serum concentration-time profile of each subject was fit to a 3-compartment model and the AUC0–∞ for the fitted concentration profile was comparable between the 5-day and 3-day regimens. 3-Day Regimen 5-Day Regimen Pharmacokinetic Parameter [mean (SD)] Day 1 Day 3 Day 1 Day 5 C max (serum, mcg/mL) 0.44 (0.22) 0.54 (0.25) 0.43 (0.20) 0.24 (0.06) Serum AUC 0–∞ (mcg∙hr/mL) 17.4 (6.2) Total AUC for the entire 3-day and 5-day regimens. 14.9 (3.1) Serum T 1/2 71.8 hr 68.9 hr Absorption The absolute bioavailability of azithromycin 250 mg capsules is 38%. In a two-way crossover study in which 12 healthy subjects received a single 500 mg dose of azithromycin (two 250 mg tablets) with or without a high fat meal, food was shown to increase C max by 23% but had no effect on AUC. When azithromycin oral suspension was administered with food to 28 adult healthy male subjects, C max increased by 56% and AUC was unchanged. Distribution The serum protein binding of azithromycin is variable in the concentration range approximating human exposure, decreasing from 51% at 0.02 mcg/mL to 7% at 2 mcg/mL. The antibacterial activity of azithromycin is pH related and appears to be reduced with decreasing pH. However, the extensive distribution of drug to tissues may be relevant to clinical activity. Azithromycin has been shown to penetrate into human tissues, including skin, lung, tonsil, and cervix. Extensive tissue distribution was confirmed by examination of additional tissues and fluids (bone, ejaculum, prostate, ovary, uterus, salpinx, stomach, liver, and gallbladder). As there are no data from adequate and well-controlled studies of azithromycin treatment of infections in these additional body sites, the clinical significance of these tissue concentration data is unknown. Following a regimen of 500 mg on the first day and 250 mg daily for 4 days, very low concentrations were noted in cerebrospinal fluid (less than 0.01 mcg/mL) in the presence of noninflamed meninges. Metabolism In vitro and in vivo studies to assess the metabolism of azithromycin have not been performed. Elimination Plasma concentrations of azithromycin following single 500 mg oral and IV doses declined in a polyphasic pattern resulting in a mean apparent plasma clearance of 630 mL/min and terminal elimination half-life of 68 hr. The prolonged terminal half-life is thought to be due to extensive uptake and subsequent release of drug from tissues. Biliary excretion of azithromycin, predominantly as unchanged drug, is a major route of elimination. Over the course of a week, approximately 6% of the administered dose appears as unchanged drug in urine. Specific Populations Patients with Renal Impairment Azithromycin pharmacokinetics was investigated in 42 adults (21 to 85 years of age) with varying degrees of renal impairment. Following the oral administration of a single 1.0 g dose of azithromycin (4 × 250 mg capsules), mean C max and AUC 0-120 increased by 5.1% and 4.2%, respectively, in subjects with mild to moderate renal impairment (GFR 10 mL/min to 80 mL/min) compared to subjects with normal renal function (GFR > 80 mL/min). The mean C max and AUC 0-120 increased 61% and 35%, respectively, in subjects with severe renal impairment (GFR < 10 mL/min) compared to subjects with normal renal function (GFR > 80 mL/min). Patients with Hepatic Impairment The pharmacokinetics of azithromycin in subjects with hepatic impairment has not been established. Male and Female Patients There are no significant differences in the disposition of azithromycin between male and female subjects. No dosage adjustment is recommended based on gender. Geriatric Patients Pharmacokinetic parameters in older volunteers (65 to 85 years old) were similar to those in young adults (18 to 40 years old) for the 5-day therapeutic regimen. Dosage adjustment does not appear to be necessary for older patients with normal renal and hepatic function receiving treatment with this dosage regimen . [see Geriatric Use (8.5) ] Pediatric Patients In two clinical studies, azithromycin for oral suspension was dosed at 10 mg/kg on day 1, followed by 5 mg/kg on days 2 through 5 in two groups of pediatric patients (aged 1 to 5 years and 5 to 15 years, respectively). The mean pharmacokinetic parameters on day 5 were C max = 0.216 mcg/mL, T max = 1.9 hr, and AUC 0-24 = 1.822 mcg∙hr/mL for the 1- to 5-year-old group and were C max = 0.383 mcg/mL, T max = 2.4 hr, and AUC 0-24 = 3.109 mcg∙hr/mL for the 5- to 15-year-old group. In another study, 33 pediatric patients received doses of 12 mg/kg/day (maximum daily dose 500 mg) for 5 days, of whom 31 patients were evaluated for azithromycin pharmacokinetics following a low fat breakfast. In this study, azithromycin concentrations were determined over a 24 hr period following the last daily dose. Patients weighing above 41.7 kg received the maximum adult daily dose of 500 mg. Seventeen patients (weighing 41.7 kg or less) received a total dose of 60 mg/kg. The following table shows pharmacokinetic data in the subset of pediatric patients who received a total dose of 60 mg/kg. Pharmacokinetic Parameter [mean (SD)] 5-Day Regimen (12 mg/kg for 5 days ) N 17 C max (mcg/mL) 0.5 (0.4) T max (hr) 2.2 (0.8) AUC 0–24 (mcg∙hr/mL) 3.9 (1.9) Single dose pharmacokinetics of azithromycin in pediatric patients given doses of 30 mg/kg have not been studied. [see Dosage and Administration (2) ] Drug Interaction Studies Drug interaction studies were performed with azithromycin and other drugs likely to be co-administered. The effects of co-administration of azithromycin on the pharmacokinetics of other drugs are shown in Table 1 and the effects of other drugs on the pharmacokinetics of azithromycin are shown in Table 2. Co-administration of azithromycin at therapeutic doses had a modest effect on the pharmacokinetics of the drugs listed in Table 1. No dosage adjustment of drugs listed in Table 1 is recommended when co-administered with azithromycin. Co-administration of azithromycin with efavirenz or fluconazole had a modest effect on the pharmacokinetics of azithromycin. Nelfinavir significantly increased the C max and AUC of azithromycin. No dosage adjustment of azithromycin is recommended when administered with drugs listed in Table 2. [see Drug Interactions (7.3) ] Table 1. Drug Interactions: Pharmacokinetic Parameters for Co-administered Drugs in the Presence of Azithromycin Co-administered Drug Dose of Co-administered Drug Dose of Azithromycin n Ratio (with/without azithromycin) of Co-administered Drug Pharmacokinetic Parameters (90% CI); No Effect = 1.00 Mean C max Mean AUC Atorvastatin 10 mg/day for 8 days 500 mg/day orally on days 6 to 8 12 0.83 (0.63 to 1.08) 1.01 (0.81 to 1.25) Carbamazepine 200 mg/day for 2 days, then 200 mg twice a day for 18 days 500 mg/day orally for days 16 to 18 7 0.97 (0.88 to 1.06) 0.96 (0.88 to 1.06) Cetirizine 20 mg/day for 11 days 500 mg orally on day 7, then 250 mg/day on days 8 to 11 14 1.03 (0.93 to 1.14) 1.02 (0.92 to 1.13) Didanosine 200 mg orally twice a day for 21 days 1,200 mg/day orally on days 8 to 21 6 1.44 (0.85 to 2.43) 1.14 (0.83 to 1.57) Efavirenz 400 mg/day for 7 days 600 mg orally on day 7 14 1.04 - 90% Confidence interval not reported 0.95 Fluconazole 200 mg orally single dose 1,200 mg orally single dose 18 1.04 (0.98 to 1.11) 1.01 (0.97 to 1.05) Indinavir 800 mg three times a day for 5 days 1,200 mg orally on day 5 18 0.96 (0.86 to 1.08) 0.90 (0.81 to 1.00) Midazolam 15 mg orally on day 3 500 mg/day orally for 3 days 12 1.27 (0.89 to 1.81) 1.26 (1.01 to 1.56) Nelfinavir 750 mg three times a day for 11 days 1,200 mg orally on day 9 14 0.90 (0.81 to 1.01) 0.85 (0.78 to 0.93) Sildenafil 100 mg on days 1 and 4 500 mg/day orally for 3 days 12 1.16 (0.86 to 1.57) 0.92 (0.75 to 1.12) Theophylline 4 mg/kg IV on days 1, 11, 25 500 mg orally on day 7, 250 mg/day on days 8 to 11 10 1.19 (1.02 to 1.40) 1.02 (0.86 to 1.22) Theophylline 300 mg orally twice a day for 15 days 500 mg orally on day 6, then 250 mg/day on days 7 to 10 8 1.09 (0.92 to 1.29) 1.08 (0.89 to 1.31) Triazolam 0.125 mg on day 2 500 mg orally on day 1, then 250 mg/day on day 2 12 1.06 1.02 Trimethoprim/ Sulfamethoxazole 160 mg/800 mg/day orally for 7 days 1,200 mg orally on day 7 12 0.85 (0.75 to 0.97)/ 0.90 (0.78 to 1.03) 0.87 (0.80 to 0.95)/ 0.96 (0.88 to 1.03) Zidovudine 500 mg/day orally for 21 days 600 mg/day orally for 14 days 5 1.12 (0.42 to 3.02) 0.94 (0.52 to 1.70) Zidovudine 500 mg/day orally for 21 days 1,200 mg/day orally for 14 days 4 1.31 (0.43 to 3.97) 1.30 (0.69 to 2.43) Table 2. Drug Interactions: Pharmacokinetic Parameters for Azithromycin in the Presence of Co-administered Drugs. [see Drug Interactions (7) ] Co-administered Drug Dose of Co-administered Drug Dose of Azithromycin n Ratio (with/without co-administered drug) of Azithromycin Pharmacokinetic Parameters (90% CI); No Effect = 1.00 Mean C max Mean AUC Efavirenz 400 mg/day for 7 days 600 mg orally on day 7 14 1.22 (1.04 to 1.42) 0.92 - 90% Confidence interval not reported Fluconazole 200 mg orally single dose 1,200 mg orally single dose 18 0.82 (0.66 to 1.02) 1.07 (0.94 to 1.22) Nelfinavir 750 mg three times a day for 11 days 1,200 mg orally on day 9 14 2.36 (1.77 to 3.15) 2.12 (1.80 to 2.50) 12.4 Microbiology Mechanism of Action Azithromycin acts by binding to the 23S rRNA of the 50S ribosomal subunit of susceptible microorganisms inhibiting bacterial protein synthesis and impeding the assembly of the 50S ribosomal subunit. Resistance Azithromycin demonstrates cross resistance with erythromycin. The most frequently encountered mechanism of resistance to azithromycin is modification of the 23S rRNA target, most often by methylation. Ribosomal modifications can determine cross resistance to other macrolides, lincosamides, and streptogramin B (MLS B phenotype). Antimicrobial Activity Azithromycin has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections. [see Indications and Usage (1) ] Gram-Positive Bacteria Staphylococcus aureus Streptococcus agalactiae Streptococcus pneumoniae Streptococcus pyogenes Gram-Negative Bacteria Haemophilus ducreyi Haemophilus influenzae Moraxella catarrhalis Neisseria gonorrhoeae Other Bacteria Chlamydophila pneumoniae Chlamydia trachomatis Mycoplasma pneumoniae The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for azithromycin against isolates of similar genus or organism group. However, the efficacy of azithromycin in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials. Gram-Positive Bacteria Beta-hemolytic streptococci (Groups C, F, G) Viridans group streptococci Gram-Negative Bacteria Bordetella pertussis Legionella pneumophila Anaerobic Bacteria Prevotella bivia Peptostreptococcus species Other Bacteria Ureaplasma urealyticum Susceptibility Testing For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for azithromycin tablets, please see: https://www.fda.gov/STIC.
Mechanism of action
Information about the established mechanism(s) of the drugÕs action in humans at various levels (for example receptor, membrane, tissue, organ, whole body). If the mechanism of action is not known, this field contains a statement about the lack of information.12.1 Mechanism of Action Azithromycin is a macrolide antibacterial drug . [see Microbiology (12.4) ]
Pharmacodynamics
Information about any biochemical or physiologic pharmacologic effects of the drug or active metabolites related to the drugÕs clinical effect in preventing, diagnosing, mitigating, curing, or treating disease, or those related to adverse effects or toxicity.12.2 Pharmacodynamics Based on animal models of infection, the antibacterial activity of azithromycin appears to correlate with the ratio of area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC) for certain pathogens ( S. pneumoniae and S. aureus ). The principal pharmacokinetic/pharmacodynamic parameter best associated with clinical and microbiological cure has not been elucidated in clinical trials with azithromycin. Cardiac Electrophysiology QTc interval prolongation was studied in a randomized, placebo-controlled parallel trial in 116 healthy subjects who received either chloroquine (1,000 mg) alone or in combination with oral azithromycin (500 mg, 1,000 mg, and 1,500 mg once daily). Co-administration of azithromycin increased the QTc interval in a dose- and concentration- dependent manner. In comparison to chloroquine alone, the maximum mean (95% upper confidence bound) increases in QTcF were 5 (10) ms, 7 (12) ms and 9 (14) ms with the co-administration of 500 mg, 1,000 mg and 1,500 mg azithromycin, respectively.
Pharmacokinetics
Information about the clinically significant pharmacokinetics of a drug or active metabolites, for instance pertinent absorption, distribution, metabolism, and excretion parameters.12.3 Pharmacokinetics Following oral administration of a single 500 mg dose (two 250 mg tablets) to 36 fasted healthy male volunteers, the mean (SD) pharmacokinetic parameters were AUC 0-72 = 4.3 (1.2) mcg∙hr/mL; C max = 0.5 (0.2) mcg/mL; T max = 2.2 (0.9) hours. Two azithromycin 250 mg tablets are bioequivalent to a single 500 mg tablet. In a two-way crossover study, 12 adult healthy volunteers (6 males, 6 females) received 1,500 mg of azithromycin administered in single daily doses over either 5 days (two 250 mg tablets on day 1, followed by one 250 mg tablet on days 2 to 5) or 3 days (500 mg per day for days 1 to 3). Due to limited serum samples on day 2 (3-day regimen) and days 2 to 4 (5-day regimen), the serum concentration-time profile of each subject was fit to a 3-compartment model and the AUC0–∞ for the fitted concentration profile was comparable between the 5-day and 3-day regimens. 3-Day Regimen 5-Day Regimen Pharmacokinetic Parameter [mean (SD)] Day 1 Day 3 Day 1 Day 5 C max (serum, mcg/mL) 0.44 (0.22) 0.54 (0.25) 0.43 (0.20) 0.24 (0.06) Serum AUC 0–∞ (mcg∙hr/mL) 17.4 (6.2) Total AUC for the entire 3-day and 5-day regimens. 14.9 (3.1) Serum T 1/2 71.8 hr 68.9 hr Absorption The absolute bioavailability of azithromycin 250 mg capsules is 38%. In a two-way crossover study in which 12 healthy subjects received a single 500 mg dose of azithromycin (two 250 mg tablets) with or without a high fat meal, food was shown to increase C max by 23% but had no effect on AUC. When azithromycin oral suspension was administered with food to 28 adult healthy male subjects, C max increased by 56% and AUC was unchanged. Distribution The serum protein binding of azithromycin is variable in the concentration range approximating human exposure, decreasing from 51% at 0.02 mcg/mL to 7% at 2 mcg/mL. The antibacterial activity of azithromycin is pH related and appears to be reduced with decreasing pH. However, the extensive distribution of drug to tissues may be relevant to clinical activity. Azithromycin has been shown to penetrate into human tissues, including skin, lung, tonsil, and cervix. Extensive tissue distribution was confirmed by examination of additional tissues and fluids (bone, ejaculum, prostate, ovary, uterus, salpinx, stomach, liver, and gallbladder). As there are no data from adequate and well-controlled studies of azithromycin treatment of infections in these additional body sites, the clinical significance of these tissue concentration data is unknown. Following a regimen of 500 mg on the first day and 250 mg daily for 4 days, very low concentrations were noted in cerebrospinal fluid (less than 0.01 mcg/mL) in the presence of noninflamed meninges. Metabolism In vitro and in vivo studies to assess the metabolism of azithromycin have not been performed. Elimination Plasma concentrations of azithromycin following single 500 mg oral and IV doses declined in a polyphasic pattern resulting in a mean apparent plasma clearance of 630 mL/min and terminal elimination half-life of 68 hr. The prolonged terminal half-life is thought to be due to extensive uptake and subsequent release of drug from tissues. Biliary excretion of azithromycin, predominantly as unchanged drug, is a major route of elimination. Over the course of a week, approximately 6% of the administered dose appears as unchanged drug in urine. Specific Populations Patients with Renal Impairment Azithromycin pharmacokinetics was investigated in 42 adults (21 to 85 years of age) with varying degrees of renal impairment. Following the oral administration of a single 1.0 g dose of azithromycin (4 × 250 mg capsules), mean C max and AUC 0-120 increased by 5.1% and 4.2%, respectively, in subjects with mild to moderate renal impairment (GFR 10 mL/min to 80 mL/min) compared to subjects with normal renal function (GFR > 80 mL/min). The mean C max and AUC 0-120 increased 61% and 35%, respectively, in subjects with severe renal impairment (GFR < 10 mL/min) compared to subjects with normal renal function (GFR > 80 mL/min). Patients with Hepatic Impairment The pharmacokinetics of azithromycin in subjects with hepatic impairment has not been established. Male and Female Patients There are no significant differences in the disposition of azithromycin between male and female subjects. No dosage adjustment is recommended based on gender. Geriatric Patients Pharmacokinetic parameters in older volunteers (65 to 85 years old) were similar to those in young adults (18 to 40 years old) for the 5-day therapeutic regimen. Dosage adjustment does not appear to be necessary for older patients with normal renal and hepatic function receiving treatment with this dosage regimen . [see Geriatric Use (8.5) ] Pediatric Patients In two clinical studies, azithromycin for oral suspension was dosed at 10 mg/kg on day 1, followed by 5 mg/kg on days 2 through 5 in two groups of pediatric patients (aged 1 to 5 years and 5 to 15 years, respectively). The mean pharmacokinetic parameters on day 5 were C max = 0.216 mcg/mL, T max = 1.9 hr, and AUC 0-24 = 1.822 mcg∙hr/mL for the 1- to 5-year-old group and were C max = 0.383 mcg/mL, T max = 2.4 hr, and AUC 0-24 = 3.109 mcg∙hr/mL for the 5- to 15-year-old group. In another study, 33 pediatric patients received doses of 12 mg/kg/day (maximum daily dose 500 mg) for 5 days, of whom 31 patients were evaluated for azithromycin pharmacokinetics following a low fat breakfast. In this study, azithromycin concentrations were determined over a 24 hr period following the last daily dose. Patients weighing above 41.7 kg received the maximum adult daily dose of 500 mg. Seventeen patients (weighing 41.7 kg or less) received a total dose of 60 mg/kg. The following table shows pharmacokinetic data in the subset of pediatric patients who received a total dose of 60 mg/kg. Pharmacokinetic Parameter [mean (SD)] 5-Day Regimen (12 mg/kg for 5 days ) N 17 C max (mcg/mL) 0.5 (0.4) T max (hr) 2.2 (0.8) AUC 0–24 (mcg∙hr/mL) 3.9 (1.9) Single dose pharmacokinetics of azithromycin in pediatric patients given doses of 30 mg/kg have not been studied. [see Dosage and Administration (2) ] Drug Interaction Studies Drug interaction studies were performed with azithromycin and other drugs likely to be co-administered. The effects of co-administration of azithromycin on the pharmacokinetics of other drugs are shown in Table 1 and the effects of other drugs on the pharmacokinetics of azithromycin are shown in Table 2. Co-administration of azithromycin at therapeutic doses had a modest effect on the pharmacokinetics of the drugs listed in Table 1. No dosage adjustment of drugs listed in Table 1 is recommended when co-administered with azithromycin. Co-administration of azithromycin with efavirenz or fluconazole had a modest effect on the pharmacokinetics of azithromycin. Nelfinavir significantly increased the C max and AUC of azithromycin. No dosage adjustment of azithromycin is recommended when administered with drugs listed in Table 2. [see Drug Interactions (7.3) ] Table 1. Drug Interactions: Pharmacokinetic Parameters for Co-administered Drugs in the Presence of Azithromycin Co-administered Drug Dose of Co-administered Drug Dose of Azithromycin n Ratio (with/without azithromycin) of Co-administered Drug Pharmacokinetic Parameters (90% CI); No Effect = 1.00 Mean C max Mean AUC Atorvastatin 10 mg/day for 8 days 500 mg/day orally on days 6 to 8 12 0.83 (0.63 to 1.08) 1.01 (0.81 to 1.25) Carbamazepine 200 mg/day for 2 days, then 200 mg twice a day for 18 days 500 mg/day orally for days 16 to 18 7 0.97 (0.88 to 1.06) 0.96 (0.88 to 1.06) Cetirizine 20 mg/day for 11 days 500 mg orally on day 7, then 250 mg/day on days 8 to 11 14 1.03 (0.93 to 1.14) 1.02 (0.92 to 1.13) Didanosine 200 mg orally twice a day for 21 days 1,200 mg/day orally on days 8 to 21 6 1.44 (0.85 to 2.43) 1.14 (0.83 to 1.57) Efavirenz 400 mg/day for 7 days 600 mg orally on day 7 14 1.04 - 90% Confidence interval not reported 0.95 Fluconazole 200 mg orally single dose 1,200 mg orally single dose 18 1.04 (0.98 to 1.11) 1.01 (0.97 to 1.05) Indinavir 800 mg three times a day for 5 days 1,200 mg orally on day 5 18 0.96 (0.86 to 1.08) 0.90 (0.81 to 1.00) Midazolam 15 mg orally on day 3 500 mg/day orally for 3 days 12 1.27 (0.89 to 1.81) 1.26 (1.01 to 1.56) Nelfinavir 750 mg three times a day for 11 days 1,200 mg orally on day 9 14 0.90 (0.81 to 1.01) 0.85 (0.78 to 0.93) Sildenafil 100 mg on days 1 and 4 500 mg/day orally for 3 days 12 1.16 (0.86 to 1.57) 0.92 (0.75 to 1.12) Theophylline 4 mg/kg IV on days 1, 11, 25 500 mg orally on day 7, 250 mg/day on days 8 to 11 10 1.19 (1.02 to 1.40) 1.02 (0.86 to 1.22) Theophylline 300 mg orally twice a day for 15 days 500 mg orally on day 6, then 250 mg/day on days 7 to 10 8 1.09 (0.92 to 1.29) 1.08 (0.89 to 1.31) Triazolam 0.125 mg on day 2 500 mg orally on day 1, then 250 mg/day on day 2 12 1.06 1.02 Trimethoprim/ Sulfamethoxazole 160 mg/800 mg/day orally for 7 days 1,200 mg orally on day 7 12 0.85 (0.75 to 0.97)/ 0.90 (0.78 to 1.03) 0.87 (0.80 to 0.95)/ 0.96 (0.88 to 1.03) Zidovudine 500 mg/day orally for 21 days 600 mg/day orally for 14 days 5 1.12 (0.42 to 3.02) 0.94 (0.52 to 1.70) Zidovudine 500 mg/day orally for 21 days 1,200 mg/day orally for 14 days 4 1.31 (0.43 to 3.97) 1.30 (0.69 to 2.43) Table 2. Drug Interactions: Pharmacokinetic Parameters for Azithromycin in the Presence of Co-administered Drugs. [see Drug Interactions (7) ] Co-administered Drug Dose of Co-administered Drug Dose of Azithromycin n Ratio (with/without co-administered drug) of Azithromycin Pharmacokinetic Parameters (90% CI); No Effect = 1.00 Mean C max Mean AUC Efavirenz 400 mg/day for 7 days 600 mg orally on day 7 14 1.22 (1.04 to 1.42) 0.92 - 90% Confidence interval not reported Fluconazole 200 mg orally single dose 1,200 mg orally single dose 18 0.82 (0.66 to 1.02) 1.07 (0.94 to 1.22) Nelfinavir 750 mg three times a day for 11 days 1,200 mg orally on day 9 14 2.36 (1.77 to 3.15) 2.12 (1.80 to 2.50)
Contraindications
Information about situations in which the drug product is contraindicated or should not be used because the risk of use clearly outweighs any possible benefit, including the type and nature of reactions that have been reported.4 CONTRAINDICATIONS • Patients with known hypersensitivity to azithromycin, erythromycin, any macrolide, or ketolide drug. ( 4.1 ) • Patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin. ( 4.2 ) 4.1 Hypersensitivity Azithromycin is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, any macrolide, or ketolide drug. 4.2 Hepatic Dysfunction Azithromycin is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin.
Description
General information about the drug product, including the proprietary and established name of the drug, the type of dosage form and route of administration to which the label applies, qualitative and quantitative ingredient information, the pharmacologic or therapeutic class of the drug, and the chemical name and structural formula of the drug.11 DESCRIPTION Azithromycin Tablets, USP contain the active ingredient azithromycin, a macrolide antibacterial drug, for oral administration. Azithromycin has the chemical name (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)oxy]-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one. Azithromycin is derived from erythromycin; however, it differs chemically from erythromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring. Its molecular formula is C 38 H 72 N 2 O 12 , and its molecular weight is 749.00. Azithromycin has the following structural formula: Azithromycin, as the dihydrate, is a white crystalline powder with a molecular formula of C 38 H 72 N 2 O 12 ∙2H 2 O and a molecular weight of 785.0. Azithromycin is supplied as tablets containing azithromycin dihydrate equivalent to 250 mg azithromycin and the following inactive ingredients: croscarmellose sodium, dibasic calcium phosphate anhydrous, FD&C Blue #1 aluminum lake and lecithin, FD&C Red #40 aluminum Lake, FD&C Yellow #6 aluminum Lake, macrogol/PEG, magnesium stearate, polyvinyl alcohol, pregelatinized starch, talc, and titanium dioxide. Chemical Structure
Dosage and administration
Information about the drug product’s dosage and administration recommendations, including starting dose, dose range, titration regimens, and any other clinically sigificant information that affects dosing recommendations.2 DOSAGE AND ADMINISTRATION • Adult Patients ( 2.1 ) Infection Recommended Dose/Duration of Therapy Community-acquired pneumonia (mild severity) Pharyngitis/tonsillitis (second-line therapy) Skin/skin structure (uncomplicated) 500 mg as a single dose on Day 1, followed by 250 mg once daily on Days 2 through 5 Acute bacterial exacerbations of chronic bronchitis (mild to moderate) 500 mg as a single dose on Day 1, followed by 250 mg once daily on Days 2 through 5 or 500 mg once daily for 3 days Acute bacterial sinusitis 500 mg once daily for 3 days Genital ulcer disease (chancroid) Non-gonococcal urethritis and cervicitis One single 1 gram dose Gonococcal urethritis and cervicitis One single 2 gram dose • Pediatric Patients ( 2.2 ) Infection Recommended Dose/Duration of Therapy Acute otitis media (6 months of age and older) 30 mg/kg as a single dose or 10 mg/kg once daily for 3 days or 10 mg/kg as a single dose on Day 1 followed by 5 mg/kg/day on Days 2 through 5 Acute bacterial sinusitis (6 months of age and older) 10 mg/kg once daily for 3 days Community-acquired pneumonia (6 months of age and older) 10 mg/kg as a single dose on Day 1 followed by 5 mg/kg once daily on Days 2 through 5 Pharyngitis/tonsillitis (2 years of age and older) 12 mg/kg once daily for 5 days 2.1 Adult Patients [see Indications and Usage (1.1) and Clinical Pharmacology (12.3) ] Infection DUE TO THE INDICATED ORGANISMS [see Indications and Usage (1.1) ] Recommended Dose/Duration of Therapy Community-acquired pneumonia Pharyngitis/tonsillitis (second-line therapy) Skin/skin structure (uncomplicated) 500 mg as a single dose on Day 1, followed by 250 mg once daily on Days 2 through 5 Acute bacterial exacerbations of chronic obstructive pulmonary disease 500 mg once daily for 3 days OR 500 mg as a single dose on Day 1, followed by 250 mg once daily on Days 2 through 5 Acute bacterial sinusitis 500 mg once daily for 3 days Genital ulcer disease (chancroid) One single 1 gram dose Non-gonococcal urethritis and cervicitis One single 1 gram dose Gonococcal urethritis and cervicitis One single 2 gram dose Azithromycin tablets can be taken with or without food. 2.2 Pediatric Patients 1 Infection DUE TO THE INDICATED ORGANISMS [see Indications and Usage (1.2) ] Recommended Dose/Duration of Therapy 1 see dosing tables below for maximum doses evaluated by indication Acute otitis media 30 mg/kg as a single dose or 10 mg/kg once daily for 3 days or 10 mg/kg as a single dose on Day 1 followed by 5 mg/kg/day on Days 2 through 5 Acute bacterial sinusitis 10 mg/kg once daily for 3 days Community-acquired pneumonia 10 mg/kg as a single dose on Day 1 followed by 5 mg/kg once daily on Days 2 through 5 Pharyngitis/tonsillitis 12 mg/kg once daily for 5 days Azithromycin for oral suspension can be taken with or without food. PEDIATRIC DOSAGE GUIDELINES FOR OTITIS MEDIA, ACUTE BACTERIAL SINUSITIS, AND COMMUNITY-ACQUIRED PNEUMONIA (Age 6 months and above, [see Use in Specific Populations (8.4) ] ) Based on Body Weight OTITIS MEDIA AND COMMUNITY-ACQUIRED PNEUMONIA: (5-Day Regimen) Effectiveness of the 3-day or 1-day regimen in pediatric patients with community-acquired pneumonia has not been established. Dosing Calculated on 10 mg/kg/day Day 1 and 5 mg/kg/day Days 2 to 5. Weight 100 mg/5 mL 200 mg/5 mL Total mL per Treatment Course Total mg per Treatment Course Kg Day 1 Days 2 to 5 Day 1 Days 2 to 5 5 2.5 mL; (½ tsp) 1.25mL; (¼ tsp) 7.5 mL 150 mg 10 5 mL; (1 tsp) 2.5 mL; (½ tsp) 15 mL 300 mg 20 5 mL; (1 tsp) 2.5 mL; (½ tsp) 15 mL 600 mg 30 7.5 mL; (1½ tsp) 3.75 mL; (¾ tsp) 22.5 mL 900 mg 40 10 mL; (2 tsp) 5 mL; (1 tsp) 30 mL 1,200 mg 50 and above 12.5 mL; (2½ tsp) 6.25 mL; (1¼ tsp) 37.5 mL 1,500 mg OTITIS MEDIA AND ACUTE BACTERIAL SINUSITIS: (3-Day Regimen) Effectiveness of the 5-day or 1-day regimen in pediatric patients with acute bacterial sinusitis has not been established. Dosing Calculated on 10 mg/kg/day. Weight 100 mg/5 mL 200 mg/5 mL Total mL per Treatment Course Total mg per Treatment Course Kg Days 1 to 3 Days 1 to 3 5 2.5 mL; (½ tsp) 7.5 mL 150 mg 10 5 mL; (1 tsp) 15 mL 300 mg 20 5 mL; (1 tsp) 15 mL 600 mg 30 7.5 mL; (1½ tsp) 22.5 mL 900 mg 40 10 mL; (2 tsp) 30 mL 1,200 mg 50 and above 12.5 mL; (2½ tsp) 37.5 mL 1,500 mg OTITIS MEDIA: (1-Day Regimen) Dosing Calculated on 30 mg/kg as a single dose. Weight 200 mg/5 mL Total mL per Treatment Course Total mg per Treatment Course Kg 1-Day Regimen 5 3.75 mL; (3/4 tsp) 3.75 mL 150 mg 10 7.5 mL; (1½ tsp) 7.5 mL 300 mg 20 15 mL; (3 tsp) 15 mL 600 mg 30 22.5 mL; (4½ tsp) 22.5 mL 900 mg 40 30 mL; (6 tsp) 30 mL 1,200 mg 50 and above 37.5 mL; (7½ tsp) 37.5 mL 1,500 mg The safety of re-dosing azithromycin in pediatric patients who vomit after receiving 30 mg/kg as a single dose has not been established. In clinical studies involving 487 patients with acute otitis media given a single 30 mg/kg dose of azithromycin, 8 patients who vomited within 30 minutes of dosing were re-dosed at the same total dose. Pharyngitis/Tonsillitis: The recommended dose of azithromycin for children with pharyngitis/tonsillitis is 12 mg/kg once daily for 5 days. (See chart below.) PEDIATRIC DOSAGE GUIDELINES FOR PHARYNGITIS/TONSILLITIS (Age 2 years and above, [see Use in Specific Populations (8.4) ] ) Based on Body Weight PHARYNGITIS/TONSILLITIS: (5-Day Regimen) Dosing Calculated on 12 mg/kg/day for 5 days. Weight 200 mg/5 mL Total mL per Treatment Course Total mg per Treatment Course Kg Days 1 to 5 8 2.5 mL; (½ tsp) 12.5 mL 500 mg 17 5 mL; (1 tsp) 25 mL 1,000 mg 25 7.5 mL; (1½ tsp) 37.5 mL 1,500 mg 33 10 mL; (2 tsp) 50 mL 2,000 mg 40 12.5 mL; (2½ tsp) 62.5 mL 2,500 mg
Dosage forms and strengths
Information about all available dosage forms and strengths for the drug product to which the labeling applies. This field may contain descriptions of product appearance.3 DOSAGE FORMS AND STRENGTHS Azithromycin Tablets USP, 250 mg (debossed "OE" on one side and "250" on the other side) are supplied as red, oval, film coated tablets containing azithromycin dihydrate equivalent to 250 mg azithromycin. • Azithromycin tablets 250 mg ( 3 )
Indications and usage
A statement of each of the drug products indications for use, such as for the treatment, prevention, mitigation, cure, or diagnosis of a disease or condition, or of a manifestation of a recognized disease or condition, or for the relief of symptoms associated with a recognized disease or condition. This field may also describe any relevant limitations of use.1 INDICATIONS AND USAGE Azithromycin is a macrolide antibacterial drug indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the specific conditions listed below. Recommended dosages and durations of therapy in adult and pediatric patient populations vary in these indications. [see Dosage and Administration (2) ] Azithromycin is a macrolide antibacterial drug indicated for mild to moderate infections caused by designated, susceptible bacteria: • Acute bacterial exacerbations of chronic bronchitis in adults ( 1.1 ) • Acute bacterial sinusitis in adults ( 1.1 ) • Uncomplicated skin and skin structure infections in adults ( 1.1 ) • Urethritis and cervicitis in adults ( 1.1 ) • Genital ulcer disease in men ( 1.1 ) • Acute otitis media in pediatric patients (6 months of age and older) ( 1.2 ) • Community-acquired pneumonia in adults and pediatric patients (6 months of age and older) ( 1.1 , 1.2 ) • Pharyngitis/tonsillitis in adults and pediatric patients (2 years of age and older) ( 1.1 , 1.2 ) Limitation of Use: Azithromycin should not be used in patients with pneumonia who are judged to be inappropriate for oral therapy because of moderate to severe illness or risk factors. ( 1.3 ) To reduce the development of drug-resistant bacteria and maintain the effectiveness of azithromycin and other antibacterial drugs, azithromycin should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. ( 1.4 ) 1.1 Adult Patients • Acute bacterial exacerbations of chronic bronchitis due to Haemophilus influenzae , Moraxella catarrhalis, or Streptococcus pneumoniae . • Acute bacterial sinusitis due to Haemophilus influenzae , Moraxella catarrhalis. or Streptococcus pneumoniae . • Community-acquired pneumonia due to Chlamydophila pneumoniae , Haemophilus influenzae , Mycoplasma pneumoniae, or Streptococcus pneumoniae in patients appropriate for oral therapy. • Pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy in individuals who cannot use first-line therapy. • Uncomplicated skin and skin structure infections due to Staphylococcus aureus , Streptococcus pyogenes , or Streptococcus agalactiae . • Urethritis and cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae . • Genital ulcer disease in men due to Haemophilus ducreyi (chancroid). Due to the small number of women included in clinical trials, the efficacy of azithromycin in the treatment of chancroid in women has not been established. 1.2 Pediatric Patients [see Use in Specific Populations (8.4) and Clinical Studies (14.2) ] • Acute otitis media ( > 6 months of age ) caused by Haemophilus influenzae , Moraxella catarrhalis, or Streptococcus pneumoniae • Community-acquired pneumonia ( > 6 months of age ) due to Chlamydophila pneumoniae , Haemophilus influenzae , Mycoplasma pneumonia , or Streptococcus pneumoniae in patients appropriate for oral therapy. • Pharyngitis/tonsillitis ( > 2 years of age ) caused by Streptococcus pyogenes as an alternative to first-line therapy in individuals who cannot use first-line therapy. 1.3 Limitations of Use Azithromycin should not be used in patients with pneumonia who are judged to be inappropriate for oral therapy because of moderate to severe illness or risk factors such as any of the following: • patients with cystic fibrosis, • patients with nosocomial 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). 1.4 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of azithromycin and other antibacterial drugs, azithromycin should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Spl product data elements
Usually a list of ingredients in a drug product.Azithromycin Dihydrate Azithromycin Dihydrate Azithromycin Dihydrate Azithromycin anhydrous croscarmellose sodium ANHYDROUS DIBASIC CALCIUM PHOSPHATE FD&C BLUE NO. 1 Lecithin, soybean FD&C RED NO. 40 FD&C YELLOW NO. 6 polyethylene glycol 3350 magnesium stearate polyvinyl alcohol, unspecified STARCH, CORN talc titanium dioxide OE;250
Animal pharmacology and or toxicology
Information from studies of the drug in animals, if the data were not relevant to nor included in other parts of the labeling. Most labels do not contain this field.13.2 Animal Toxicology and/or Pharmacology Phospholipidosis (intracellular phospholipid accumulation) has been observed in some tissues of mice, rats, and dogs given multiple doses of azithromycin. It has been demonstrated in numerous organ systems (e.g., eye, dorsal root ganglia, liver, gallbladder, kidney, spleen, and/or pancreas) in dogs and rats treated with azithromycin at doses which, expressed on the basis of body surface area, are similar to or less than the highest recommended adult human dose. This effect has been shown to be reversible after cessation of azithromycin treatment. Based on the pharmacokinetic data, phospholipidosis has been seen in the rat (50 mg/kg/day dose) at the observed maximal plasma concentration of 1.3 mcg/mL (1.6 times the observed C max of 0.821 mcg/mL at the adult dose of 2 g). Similarly, it has been shown in the dog (10 mg/kg/day dose) at the observed maximal serum concentration of 1 mcg/mL (1.2 times the observed C max of 0.821 mcg/mL at the adult dose of 2 g). Phospholipidosis was also observed in neonatal rats dosed for 18 days at 30 mg/kg/day, which is less than the pediatric dose of 60 mg/kg based on the surface area. It was not observed in neonatal rats treated for 10 days at 40 mg/kg/day with mean maximal serum concentrations of 1.86 mcg/mL, approximately 1.5 times the C max of 1.27 mcg/mL at the pediatric dose. Phospholipidosis has been observed in neonatal dogs (10 mg/kg/day) at maximum mean whole blood concentrations of 3.54 mcg/mL, approximately 3 times the pediatric dose C max . The significance of these findings for animals and for humans is unknown.
Carcinogenesis and mutagenesis and impairment of fertility
Information about carcinogenic, mutagenic, or fertility impairment potential revealed by studies in animals. Information from human data about such potential is part of the warnings field.13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals have not been performed to evaluate carcinogenic potential. Azithromycin has shown no mutagenic potential in standard laboratory tests: mouse lymphoma assay, human lymphocyte clastogenic assay, and mouse bone marrow clastogenic assay. In fertility studies conducted in male and female rats, oral administration of azithromycin for 64 to 66 days (males) or 15 days (females) prior to and during cohabitation resulted in decreased pregnancy rate at 20 mg/kg/day and 30 mg/kg/day when both males and females were treated with azithromycin. This minimal effect on pregnancy rate (approximately 12% reduction compared to concurrent controls) did not become more pronounced when the dose was increased from 20 mg/kg/day to 30 mg/kg/day (approximately 0.4 to 0.6 times the adult daily dose of 500 mg based on body surface area) and it was not observed when only one animal in the mated pair was treated. There were no effects on any other reproductive parameters, and there were no effects on fertility at 10 mg/kg/day. The relevance of these findings to patients being treated with azithromycin at the doses and durations recommended in the prescribing information is uncertain.
Nonclinical toxicology
Information about toxicology in non-human subjects.13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals have not been performed to evaluate carcinogenic potential. Azithromycin has shown no mutagenic potential in standard laboratory tests: mouse lymphoma assay, human lymphocyte clastogenic assay, and mouse bone marrow clastogenic assay. In fertility studies conducted in male and female rats, oral administration of azithromycin for 64 to 66 days (males) or 15 days (females) prior to and during cohabitation resulted in decreased pregnancy rate at 20 mg/kg/day and 30 mg/kg/day when both males and females were treated with azithromycin. This minimal effect on pregnancy rate (approximately 12% reduction compared to concurrent controls) did not become more pronounced when the dose was increased from 20 mg/kg/day to 30 mg/kg/day (approximately 0.4 to 0.6 times the adult daily dose of 500 mg based on body surface area) and it was not observed when only one animal in the mated pair was treated. There were no effects on any other reproductive parameters, and there were no effects on fertility at 10 mg/kg/day. The relevance of these findings to patients being treated with azithromycin at the doses and durations recommended in the prescribing information is uncertain. 13.2 Animal Toxicology and/or Pharmacology Phospholipidosis (intracellular phospholipid accumulation) has been observed in some tissues of mice, rats, and dogs given multiple doses of azithromycin. It has been demonstrated in numerous organ systems (e.g., eye, dorsal root ganglia, liver, gallbladder, kidney, spleen, and/or pancreas) in dogs and rats treated with azithromycin at doses which, expressed on the basis of body surface area, are similar to or less than the highest recommended adult human dose. This effect has been shown to be reversible after cessation of azithromycin treatment. Based on the pharmacokinetic data, phospholipidosis has been seen in the rat (50 mg/kg/day dose) at the observed maximal plasma concentration of 1.3 mcg/mL (1.6 times the observed C max of 0.821 mcg/mL at the adult dose of 2 g). Similarly, it has been shown in the dog (10 mg/kg/day dose) at the observed maximal serum concentration of 1 mcg/mL (1.2 times the observed C max of 0.821 mcg/mL at the adult dose of 2 g). Phospholipidosis was also observed in neonatal rats dosed for 18 days at 30 mg/kg/day, which is less than the pediatric dose of 60 mg/kg based on the surface area. It was not observed in neonatal rats treated for 10 days at 40 mg/kg/day with mean maximal serum concentrations of 1.86 mcg/mL, approximately 1.5 times the C max of 1.27 mcg/mL at the pediatric dose. Phospholipidosis has been observed in neonatal dogs (10 mg/kg/day) at maximum mean whole blood concentrations of 3.54 mcg/mL, approximately 3 times the pediatric dose C max . The significance of these findings for animals and for humans is unknown.
Microbiology
Microbiology12.4 Microbiology Mechanism of Action Azithromycin acts by binding to the 23S rRNA of the 50S ribosomal subunit of susceptible microorganisms inhibiting bacterial protein synthesis and impeding the assembly of the 50S ribosomal subunit. Resistance Azithromycin demonstrates cross resistance with erythromycin. The most frequently encountered mechanism of resistance to azithromycin is modification of the 23S rRNA target, most often by methylation. Ribosomal modifications can determine cross resistance to other macrolides, lincosamides, and streptogramin B (MLS B phenotype). Antimicrobial Activity Azithromycin has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections. [see Indications and Usage (1) ] Gram-Positive Bacteria Staphylococcus aureus Streptococcus agalactiae Streptococcus pneumoniae Streptococcus pyogenes Gram-Negative Bacteria Haemophilus ducreyi Haemophilus influenzae Moraxella catarrhalis Neisseria gonorrhoeae Other Bacteria Chlamydophila pneumoniae Chlamydia trachomatis Mycoplasma pneumoniae The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for azithromycin against isolates of similar genus or organism group. However, the efficacy of azithromycin in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials. Gram-Positive Bacteria Beta-hemolytic streptococci (Groups C, F, G) Viridans group streptococci Gram-Negative Bacteria Bordetella pertussis Legionella pneumophila Anaerobic Bacteria Prevotella bivia Peptostreptococcus species Other Bacteria Ureaplasma urealyticum Susceptibility Testing For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for azithromycin tablets, please see: https://www.fda.gov/STIC.
Package label principal display panel
The content of the principal display panel of the product package, usually including the product’s name, dosage forms, and other key information about the drug product.PRINCIPAL DISPLAY PANEL - 250 mg Tablet Carton NDC 71205-430-06 1 Cartons × 6 Tablets Azithromycin Tablets, USP 250 mg A full course of antibiotic therapy in 5 daily doses Rx only 71205-430-06
Spl unclassified section
Information not classified as belonging to one of the other fields. Approximately 40% of labeling with effective_time between June 2009 and August 2014 have information in this field.Manufactured by: CSPC Ouyi Pharmaceutical Co., Ltd. Shijiazhuang, Hebei, China, 052160 Manufactured for: TAGI Pharma, Inc. South Beloit, IL 61080 Relabeled and Repackaged by: Proficient Rx LP Thousand Oaks, CA 91320
Azithromycin Dihydrate: Information for patients
Information necessary for patients to use the drug safely and effectively, such as precautions concerning driving or the concomitant use of other substances that may have harmful additive effects.17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). General Patient Counseling Azithromycin tablets can be taken with or without food. Patients should also be cautioned not to take aluminum- and magnesium-containing antacids and azithromycin simultaneously. The patient should be directed to discontinue azithromycin immediately and contact a physician if any signs of an allergic reaction occur. Direct parents or caregivers to contact their physician if vomiting and irritability with feeding occurs in the infant. Patients should be counseled that antibacterial drugs including azithromycin should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When azithromycin is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of the therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by azithromycin or other antibacterial drugs in the future. Diarrhea is a common problem caused by antibacterials which usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial drug. If this occurs, patients should contact their physician as soon as possible. See FDA-approved Patient Labeling
Spl patient package insert
Information necessary for patients to use the drug safely and effectively.Patient Information Azithromycin Tablets, USP [ay zith" roe mye' sin] Read this Patient Information leaflet before you start taking azithromycin tablets and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment. What are azithromycin tablets? Azithromycin tablets are a macrolide antibiotic prescription medicine used in adults 18 years or older to treat certain infections caused by certain germs called bacteria. These bacterial infections include: • acute worsening of chronic bronchitis • acute sinus infection • community-acquired pneumonia • infected throat or tonsils • skin infections • infections of the urethra or cervix • genital ulcers in men Azithromycin tablets are also used in children to treat: • ear infections • community-acquired pneumonia • infected throat or tonsils Azithromycin should not be taken by people who cannot tolerate oral medications because they are very ill or have certain other risk factors including: • have cystic fibrosis • have hospital acquired infections • have known or suspected bacteria in the blood • need to be in the hospital • are elderly • have any medical problems that can lower the ability of the immune system to fight infections Azithromycin tablets are not for viral infections such as the common cold. It is not known if azithromycin tablets are safe and effective for genital ulcers in women. It is not known if azithromycin tablets are safe and effective for children with ear infections, sinus infections, and community-acquired pneumonia under 6 months of age. It is not known if azithromycin tablets are safe and effective for infected throat or tonsils in children under 2 years of age. Who should not take azithromycin tablets? Do not take azithromycin tablets if you: • have had a severe allergic reaction to certain antibiotics known as macrolides or ketolides including azithromycin and erythromycin. • have a history of cholestatic jaundice or hepatic dysfunction that happened with the use of azithromycin. What should I tell my healthcare provider before taking azithromycin tablets? Before you take azithromycin tablets, tell your healthcare provider if you: • have pneumonia • have cystic fibrosis • have known or suspected bacteremia (bacterial infection in the blood) • have liver or kidney problems • have an irregular heartbeat, especially a problem called "QT prolongation" • have a problem that causes muscle weakness (myasthenia gravis) • have any other medical problems • are pregnant or plan to become pregnant. It is not known if azithromycin will harm your unborn baby. • are breastfeeding or plan to breastfeed. Azithromycin has been reported to pass into breast milk. Talk to your healthcare provider about the best way to feed your baby while you take azithromycin tablets. Contact your healthcare provider immediately if you are giving azihtromycin tablets to a young child (less than 6 weeks of age) and he or she vomits or becomes irritable when fed. Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Azithromycin tablets and other medicines may affect each other causing side effects. Azithromycin tablets may affect the way other medicines work, and other medicines may affect how azithromycin tablets work. Especially tell your healthcare provider if you take: • nelfinavir • a blood thinner (warfarin) • digoxin • colchicine • phenytoin • an antacid that contains aluminum or magnesium Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine. How should I take azithromycin tablets? • Take azithromycin tablets exactly as your healthcare provider tells you to take it. • Azithromycin tablets can be taken with or without food. • Do not skip any doses of azithromycin tablets or stop taking it, even if you begin to feel better, until you finish your prescribed treatment unless you have a serious allergic reaction or your healthcare provider tells you to stop taking azithromycin tablets. "See Error! Hyperlink reference not valid." If you skip doses, or do not complete the total course of azithromycin tablets your treatment may not work as well and your infection may be harder to treat. Taking all of your azithromycin tablets doses will help lower the chance that the bacteria will become resistant to azithromycin tablets. • If the bacteria becomes resistant to azithromycin tablets, azithromycin tablets and other antibiotic medicines may not work for you in the future. • If you take too much azithromycin tablets, call your healthcare provider or get medical help right away. What are the possible side effects of azithromycin tablets? Azithromycin tablets can cause serious side effects, including: • Serious allergic reactions. Allergic reactions can happen in people taking azithromcyin the active ingredient in azithromycin tablets, even after only 1 dose. Stop taking azithromycin tablets and get emergency medical help right away if you have any of the following symptoms of a severe allergic reaction:Stop taking azithromycin tablets at the first sign of a skin rash and call your healthcare provider. Skin rash may be a sign of a more serious reaction to azithromycin tablets. • trouble breathing or swallowing • swelling of the lips, tongue, face • throat tightness, hoarseness • rapid heartbeat • faintness • skin rash (hives) • new onset of fever and swollen lymph nodes • Liver damage (hepatotoxicity). Hepatotoxicity can happen in people who take azithromycin tablets. Call your healthcare provider right away if you have unexplained symptoms such as:Stop taking azithromycin tablets and tell your healthcare provider right away if you have yellowing of your skin or white part of your eyes, or if you have dark urine. These can be signs of a serious reaction to azithromycin tablets (a liver problem). • nausea or vomiting • stomach pain • fever • weakness • abdominal pain or tenderness • itching • unusual tiredness • loss of appetite • change in the color of your bowel movements • dark colored urine • yellowing of your skin or of the whites of your eyes • Serious heart rhythm changes (QT prolongation and torsades de pointes). Tell your healthcare provider right away if you have a change in your heartbeat (a fast or irregular heartbeat), or if you feel faint and dizzy. Azithromycin tablets may cause a rare heart problem known as prolongation of the QT interval. This condition can cause an abnormal heartbeat and can be very dangerous. The chances of this happening are higher in people: • who are elderly • with a family history of prolonged QT interval • with low blood potassium • who take certain medicines to control heart rhythm (antiarrhythmics) • Worsening of myasthenia gravis (a problem that causes muscle weakness). Certain antibiotics like azithromycin tablets may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Call your healthcare provider right away if you have any worsening muscle weakness or breathing problems. • Diarrhea. Tell your healthcare provider right away if you have watery diarrhea, diarrhea that does not go away, or bloody stools. You may experience cramping and a fever. This could happen after you have finished your azithromycin tablets. The most common side effects of azithromycin tablets include: • nausea • stomach pain • vomiting These are not all the possible side effects of azithromycin tablets. Tell your healthcare provider about any side effect that bothers you or that does not go away. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800- FDA-1088. How should I store azithromycin tablets? • Store azithromycin tablets at 59ºF to 86ºF (15ºC to 30ºC). • Azithromycin tablets come in a child-resistant package. • Safely throw away any medicine that is out of date or no longer needed. Keep azithromycin tablets and all medicines out of the reach of children. General information about the safe and effective use of azithromycin tablets. Medicines are sometimes prescribed for purposes other than those listed in the Patient Information leaflet. Do not use azithromycin tablets for a condition for which it was not prescribed. Do not give azithromycin tablets to other people, even if they have the same symptoms you have. It may harm them. This Patient Information leaflet summarizes the most important information about azithromycin tablets. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about azithromycin tablets that is written for health professionals. For more information, call 1-855-225-8244. What are the ingredients in azithromycin tablets? Active ingredient: azithromycin dihydrate Inactive ingredients: croscarmellose sodium, dibasic calcium phosphate anhydrous, FD&C Blue #1 aluminum lake and lecithin, FD&C Red #40 aluminum Lake, FD&C Yellow #6 aluminum Lake, macrogol/PEG, magnesium stearate, polyvinyl alcohol, pregelatinized starch, talc, and titanium dioxide. This Patient Information has been approved by the U.S. Food and Drug Administration. Manufactured by: CSPC Ouyi Pharmaceutical Co., Ltd. Shijiazhuang, Hebei, China, 052160 Manufactured for: TAGI Pharma, Inc. South Beloit, IL 61080 Relabeled and Repackaged by: Proficient Rx LP Thousand Oaks, CA 91320 Revised May 2019
Clinical studies
This field may contain references to clinical studies in place of detailed discussion in other sections of the labeling.14 CLINICAL STUDIES 14.1 Adult Patients Acute Bacterial Exacerbations of Chronic Bronchitis In a randomized, double-blind controlled clinical trial of acute exacerbation of chronic bronchitis (AECB), azithromycin (500 mg once daily for 3 days) was compared with clarithromycin (500 mg twice daily for 10 days). The primary endpoint of this trial was the clinical cure rate at Days 21 to 24. For the 304 patients analyzed in the modified intent-to-treat analysis at the Days 21 to 24 visit, the clinical cure rate for 3 days of azithromycin was 85% (125/147) compared to 82% (129/157) for 10 days of clarithromycin. The following outcomes were the clinical cure rates at the Days 21 to 24 visit for the bacteriologically evaluable patients by pathogen: Pathogen Azithromycin (3 Days ) Clarithromycin (10 Days ) S. pneumoniae 29/32 (91%) 21/27 (78%) H. influenzae 12/14 (86%) 14/16 (88%) M. catarrhalis 11/12 (92%) 12/15 (80%) Acute Bacterial Sinusitis In a randomized, double-blind, double-dummy controlled clinical trial of acute bacterial sinusitis, azithromycin (500 mg once daily for 3 days) was compared with amoxicillin/clavulanate (500/125 mg three times a day for 10 days). Clinical response assessments were made at Day 10 and Day 28. The primary endpoint of this trial was prospectively defined as the clinical cure rate at Day 28. For the 594 patients analyzed in the modified intent to treat analysis at the Day 10 visit, the clinical cure rate for 3 days of azithromycin was 88% (268/303) compared to 85% (248/291) for 10 days of amoxicillin/clavulanate. For the 586 patients analyzed in the modified intent to treat analysis at the Day 28 visit, the clinical cure rate for 3 days of azithromycin was 71.5% (213/298) compared to 71.5% (206/288), with a 97.5% confidence interval of -8.4 to 8.3, for 10 days of amoxicillin/clavulanate. In an open label, non-comparative study requiring baseline transantral sinus punctures, the following outcomes were the clinical success rates at the Day 7 and Day 28 visits for the modified intent to treat patients administered 500 mg of azithromycin once daily for 3 days with the following pathogens: Clinical Success Rates of Azithromycin (500 mg per day for 3 Days) Pathogen Day 7 Day 28 S. pneumoniae 23/26 (88%) 21/25 (84%) H. influenzae 28/32 (87%) 24/32 (75%) M. catarrhalis 14/15 (93%) 13/15 (87%) 14.2 Pediatric Patients From the perspective of evaluating pediatric clinical trials, Days 11 to 14 were considered on-therapy evaluations because of the extended half-life of azithromycin. Days 11 to 14 data are provided for clinical guidance. Days 24 to 32 evaluations were considered the primary test of cure endpoint. Pharyngitis/Tonsillitis In three double-blind controlled studies, conducted in the United States, azithromycin (12 mg/kg once a day for 5 days) was compared to penicillin V (250 mg three times a day for 10 days) in the treatment of pharyngitis due to documented Group A β-hemolytic streptococci (GABHS or S. pyogenes ). Azithromycin was clinically and microbiologically statistically superior to penicillin at Day 14 and Day 30 with the following clinical success (i.e., cure and improvement) and bacteriologic efficacy rates (for the combined evaluable patient with documented GABHS): Three U.S. Streptococcal Pharyngitis Studies Azithromycin vs. Penicillin V EFFICACY RESULTS Day 14 Day 30 Bacteriologic Eradication: Azithromycin 323/340 (95%) 255/330 (77%) Penicillin V 242/332 (73%) 206/325 (63%) Clinical Success (cure plus improvement): Azithromycin 336/343 (98%) 310/330 (94%) Penicillin V 284/338 (84%) 241/325 (74%) Approximately 1% of azithromycin-susceptible S. pyogenes isolates were resistant to azithromycin following therapy. Acute Otitis Media Efficacy using azithromycin given over 5 days (10 mg/kg on Day 1 followed by 5 mg/kg on Days 2 to 5). Trial 1 In a double-blind, controlled clinical study of acute otitis media performed in the United States, azithromycin (10 mg/kg on Day 1 followed by 5 mg/kg on Days 2 to 5) was compared to amoxicillin/clavulanate potassium (4:1). For the 553 patients who were evaluated for clinical efficacy, the clinical success rate (i.e., cure plus improvement) at the Day 11 visit was 88% for azithromycin and 88% for the control agent. For the 521 patients who were evaluated at the Day 30 visit, the clinical success rate was 73% for azithromycin and 71% for the control agent. Trial 2 In a non-comparative clinical and microbiologic trial performed in the United States, where significant rates of beta-lactamase producing organisms (35%) were found, 131 patients were evaluable for clinical efficacy. The combined clinical success rate (i.e., cure and improvement) at the Day 11 visit was 84% for azithromycin. For the 122 patients who were evaluated at the Day 30 visit, the clinical success rate was 70% for azithromycin. Microbiologic determinations were made at the pre-treatment visit. Microbiology was not reassessed at later visits. The following clinical success rates were obtained from the evaluable group: Pathogen Day 11 Day 30 Azithromycin Azithromycin S. pneumoniae 61/74 (82%) 40/56 (71%) H. influenzae 43/54 (80%) 30/47 (64%) M. catarrhalis 28/35 (80%) 19/26 (73%) S. pyogenes 11/11 (100%) 7/7 (100%) Overall 177/217 (82%) 97/137 (73%) Trial 3 In another controlled comparative clinical and microbiologic study of otitis media performed in the United States, azithromycin (10 mg/kg on Day 1 followed by 5 mg/kg on Days 2 to 5) was compared to amoxicillin/clavulanate potassium (4:1). This study utilized two of the same investigators as Protocol 2 (above), and these two investigators enrolled 90% of the patients in Protocol 3. For this reason, Protocol 3 was not considered to be an independent study. Significant rates of beta-lactamase producing organisms (20%) were found. Ninety-two (92) patients were evaluable for clinical and microbiologic efficacy. The combined clinical success rate (i.e., cure and improvement) of those patients with a baseline pathogen at the Day 11 visit was 88% for azithromycin vs. 100% for control; at the Day 30 visit, the clinical success rate was 82% for azithromycin vs. 80% for control. Microbiologic determinations were made at the pre-treatment visit. Microbiology was not reassessed at later visits. At the Day 11 and Day 30 visits, the following clinical success rates were obtained from the evaluable group: Day 11 Day 30 Pathogen Azithromycin Control Azithromycin Control S. pneumoniae 25/29 (86%) 26/26 (100%) 22/28 (79%) 18/22 (82%) H. influenzae 9/11 (82%) 9/9 (100%) 8/10 (80%) 6/8 (75%) M. catarrhalis 7/7 (100%) 5/5 (100%) 5/5 (100%) 2/3 (66%) S. pyogenes 2/2 (100%) 5/5 (100%) 2/2 (100%) 4/4 (100%) Overall 43/49 (88%) 45/45 (100%) 37/45 (82%) 30/37 (81%) Efficacy using azithromycin given over 3 days (10 mg/kg/day). Trial 4 In a double-blind, controlled, randomized clinical study of acute otitis media in pediatric patients from 6 months to 12 years of age, azithromycin (10 mg/kg per day for 3 days) was compared to amoxicillin/clavulanate potassium (7:1) in divided doses q12h for 10 days. Each patient received active drug and placebo matched for the comparator. For the 366 patients who were evaluated for clinical efficacy at the Day 12 visit, the clinical success rate (i.e., cure plus improvement) was 83% for azithromycin and 88% for the control agent. For the 362 patients who were evaluated at the Days 24 to 28 visit, the clinical success rate was 74% for azithromycin and 69% for the control agent. Efficacy using azithromycin 30 mg/kg given as a single dose Trial 5 A double-blind, controlled, randomized trial was performed at nine clinical centers. Pediatric patients from 6 months to 12 years of age were randomized 1:1 to treatment with either azithromycin (given at 30 mg/kg as a single dose on Day 1) or amoxicillin/clavulanate potassium (7:1), divided q12h for 10 days. Each child received active drug, and placebo matched for the comparator. Clinical response (Cure, Improvement, Failure) was evaluated at End of Therapy (Days 12 to 16) and Test of Cure (Days 28 to 32). Safety was evaluated throughout the trial for all treated subjects. For the 321 subjects who were evaluated at End of Treatment, the clinical success rate (cure plus improvement) was 87% for azithromycin, and 88% for the comparator. For the 305 subjects who were evaluated at Test of Cure, the clinical success rate was 75% for both azithromycin and the comparator. Trial 6 In a non-comparative clinical and microbiological trial, 248 patients from 6 months to 12 years of age with documented acute otitis media were dosed with a single oral dose of azithromycin (30 mg/kg on Day 1). For the 240 patients who were evaluable for clinical modified Intent-to-Treat (MITT) analysis, the clinical success rate (i.e., cure plus improvement) at Day 10 was 89% and for the 242 patients evaluable at Days 24 to 28, the clinical success rate (cure) was 85%. Presumed Bacteriologic Eradication Day 10 Days 24 to 28 S. pneumoniae 70/76 (92%) 67/76 (88%) H. influenzae 30/42 (71%) 28/44 (64%) M. catarrhalis 10/10 (100%) 10/10 (100%) Overall 110/128 (86%) 105/130 (81%)
Geriatric use
Information about any limitations on any geriatric indications, needs for specific monitoring, hazards associated with use of the drug in the geriatric population.8.5 Geriatric Use In multiple-dose clinical trials of oral azithromycin, 9% of patients were at least 65 years of age (458/4,949) and 3% of patients (144/4,949) were at least 75 years of age. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Elderly patients may be more susceptible to development of torsades de pointes arrhythmias than younger patients. [see Warnings and Precautions (5.4) ]
Pediatric use
Information about any limitations on any pediatric indications, needs for specific monitoring, hazards associated with use of the drug in any subsets of the pediatric population (such as neonates, infants, children, or adolescents), differences between pediatric and adult responses to the drug, and other information related to the safe and effective pediatric use of the drug.8.4 Pediatric Use [see Clinical Pharmacology (12.3) , Indications and Usage (1.2) , and Dosage and Administration (2.2) ] Safety and effectiveness in the treatment of pediatric patients with acute otitis media, acute bacterial sinusitis and community-acquired pneumonia under 6 months of age have not been established. Use of azithromycin for the treatment of acute bacterial sinusitis and community-acquired pneumonia in pediatric patients (6 months of age or greater) is supported by adequate and well-controlled trials in adults. Pharyngitis/Tonsillitis: Safety and effectiveness in the treatment of pediatric patients with pharyngitis/tonsillitis under 2 years of age have not been established.
Pregnancy
Information about effects the drug may have on pregnant women or on a fetus. This field may be ommitted if the drug is not absorbed systemically and the drug is not known to have a potential for indirect harm to the fetus. It may contain information about the established pregnancy category classification for the drug. (That information is nominally listed in the teratogenic_effects field, but may be listed here instead.)8.1 Pregnancy Risk Summary Available data from published literature and postmarketing experience over several decades with azithromycin use in pregnant women have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Error! Hyperlink reference not valid. ) . Developmental toxicity studies with azithromycin in rats, mice, and rabbits showed no drug-induced fetal malformations at doses up to 4, 2, and 2 times, respectively, an adult human daily dose of 500 mg based on body surface area. Decreased viability and delayed development were observed in the offspring of pregnant rats administered azithromycin from day 6 of pregnancy through weaning at a dose equivalent to 4 times an adult human daily dose of 500 mg based on body surface area (see Error! Hyperlink reference not valid. ) . The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data Available data from published observational studies, case series, and case reports over several decades do not suggest an increased risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes with azithromycin use in pregnant women. Limitations of these data include the lack of randomization and inability to control for confounders such as underlying maternal disease and maternal use of concomitant medications. Animal Data Azithromycin administered during the period of organogenesis did not cause fetal malformations in rats and mice at oral doses up to 200 mg/kg/day (moderately maternally toxic). Based on body surface area, this dose is approximately 4 (rats) and 2 (mice) times an adult human daily dose of 500 mg. In rabbits administered azithromycin at oral doses of 10 mg/kg/day, 20 mg/kg/day, and 40 mg/kg/day during organogenesis, reduced maternal body weight and food consumption were observed in all groups; no evidence of fetotoxicity or teratogenicity was observed at these doses, the highest of which is estimated to be 2 times an adult human daily dose of 500 mg based on body surface area. In a pre- and postnatal development study, azithromycin was administered orally to pregnant rats from day 6 of pregnancy until weaning at doses of 50 mg/kg/day or 200 mg/kg/day. Maternal toxicity (reduced food consumption and body weight gain; increased stress at parturition) was observed at the higher dose. Effects in the offspring were noted at 200 mg/kg/day during the postnatal development period (decreased viability, delayed developmental landmarks). These effects were not observed in a pre- and postnatal rat study when up to 200 mg/kg/day of azithromycin was given orally beginning on day 15 of pregnancy until weaning.
Use in specific populations
Information about use of the drug by patients in specific populations, including pregnant women and nursing mothers, pediatric patients, and geriatric patients.8 USE IN SPECIFIC POPULATIONS • Pediatric use: Safety and effectiveness in the treatment of patients under 6 months of age have not been established. ( 8.4 ) • Geriatric use: Elderly patients may be more susceptible to development of torsades de pointes arrhythmias. ( 8.5 ) 8.1 Pregnancy Risk Summary Available data from published literature and postmarketing experience over several decades with azithromycin use in pregnant women have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Error! Hyperlink reference not valid. ) . Developmental toxicity studies with azithromycin in rats, mice, and rabbits showed no drug-induced fetal malformations at doses up to 4, 2, and 2 times, respectively, an adult human daily dose of 500 mg based on body surface area. Decreased viability and delayed development were observed in the offspring of pregnant rats administered azithromycin from day 6 of pregnancy through weaning at a dose equivalent to 4 times an adult human daily dose of 500 mg based on body surface area (see Error! Hyperlink reference not valid. ) . The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data Available data from published observational studies, case series, and case reports over several decades do not suggest an increased risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes with azithromycin use in pregnant women. Limitations of these data include the lack of randomization and inability to control for confounders such as underlying maternal disease and maternal use of concomitant medications. Animal Data Azithromycin administered during the period of organogenesis did not cause fetal malformations in rats and mice at oral doses up to 200 mg/kg/day (moderately maternally toxic). Based on body surface area, this dose is approximately 4 (rats) and 2 (mice) times an adult human daily dose of 500 mg. In rabbits administered azithromycin at oral doses of 10 mg/kg/day, 20 mg/kg/day, and 40 mg/kg/day during organogenesis, reduced maternal body weight and food consumption were observed in all groups; no evidence of fetotoxicity or teratogenicity was observed at these doses, the highest of which is estimated to be 2 times an adult human daily dose of 500 mg based on body surface area. In a pre- and postnatal development study, azithromycin was administered orally to pregnant rats from day 6 of pregnancy until weaning at doses of 50 mg/kg/day or 200 mg/kg/day. Maternal toxicity (reduced food consumption and body weight gain; increased stress at parturition) was observed at the higher dose. Effects in the offspring were noted at 200 mg/kg/day during the postnatal development period (decreased viability, delayed developmental landmarks). These effects were not observed in a pre- and postnatal rat study when up to 200 mg/kg/day of azithromycin was given orally beginning on day 15 of pregnancy until weaning. 8.2 Lactation Risk Summary Azithromycin is present in human milk (see Error! Hyperlink reference not valid. ) . Non-serious adverse reactions have been reported in breastfed infants after maternal administration of azithromycin (see Error! Hyperlink reference not valid. ) . There are no available data on the effects of azithromycin on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for azithromycin and any potential adverse effects on the breastfed infant from azithromycin or from the underlying maternal condition. Clinical Considerations Advise women to monitor the breastfed infant for diarrhea, vomiting, or rash. Data Azithromycin breastmilk concentrations were measured in 20 women after receiving a single 2 g oral dose of azithromycin during labor. Breastmilk samples collected on days 3 and 6 postpartum as well as 2 and 4 weeks postpartum revealed the presence of azithromycin in breastmilk up to 4 weeks after dosing. In another study, a single dose of azithromycin 500 mg was administered intravenously to 8 women prior to incision for cesarean section. Breastmilk (colostrum) samples obtained between 12 and 48 hours after dosing revealed that azithromycin persisted in breastmilk up to 48 hours. 8.4 Pediatric Use [see Clinical Pharmacology (12.3) , Indications and Usage (1.2) , and Dosage and Administration (2.2) ] Safety and effectiveness in the treatment of pediatric patients with acute otitis media, acute bacterial sinusitis and community-acquired pneumonia under 6 months of age have not been established. Use of azithromycin for the treatment of acute bacterial sinusitis and community-acquired pneumonia in pediatric patients (6 months of age or greater) is supported by adequate and well-controlled trials in adults. Pharyngitis/Tonsillitis: Safety and effectiveness in the treatment of pediatric patients with pharyngitis/tonsillitis under 2 years of age have not been established. 8.5 Geriatric Use In multiple-dose clinical trials of oral azithromycin, 9% of patients were at least 65 years of age (458/4,949) and 3% of patients (144/4,949) were at least 75 years of age. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Elderly patients may be more susceptible to development of torsades de pointes arrhythmias than younger patients. [see Warnings and Precautions (5.4) ]
How supplied
Information about the available dosage forms to which the labeling applies, and for which the manufacturer or distributor is responsible. This field ordinarily includes the strength of the dosage form (in metric units), the units in which the dosage form is available for prescribing, appropriate information to facilitate identification of the dosage forms (such as shape, color, coating, scoring, and National Drug Code), and special handling and storage condition information.16 HOW SUPPLIED/STORAGE AND HANDLING Azithromycin Tablets USP, 250 mg are supplied as red, oval, film coated tablets containing azithromycin dihydrate equivalent to 250 mg of azithromycin. Azithromycin Tablets USP, 250 mg are debossed "OE" on one side and "250" on the other side. These are packaged in bottles of 4 tablets and blister cards of 6 tablets: Bottles of 4 tablets with child-resistant closure Cartons of 1 blister card with child-resistant package (6 tablets per blister card) NDC 71205-430-04 NDC 71205-430-06 Store at 20° to 25°C (68° to 77°F); excursions permitted from 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Dispense in tight containers (USP).
Storage and handling
Information about safe storage and handling of the drug product.Store at 20° to 25°C (68° to 77°F); excursions permitted from 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Dispense in tight containers (USP).
Disclaimer: Do not rely on openFDA or Phanrmacy Near Me to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated. Source: OpenFDA, Healthporta Drugs API