Azithromycin monohydrate

Injection, Powder, Lyophilized, For Solution · Intravenous

Prescription (Rx) Macrolide Antimicrobial

Uses

Azithromycin for injection is a macrolide antibacterial drug indicated for the treatment of the following infections caused by designated susceptible microorganisms:
• Community-acquired pneumonia in adults ( 1.1 )
• Pelvic inflammatory disease in adults ( 1.2 ) 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 or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. ( 1.3 ) 1.1 Community-Acquired Pneumonia Azithromycin for injection is indicated for the treatment of adult patients with community-acquired pneumonia due to the following susceptible microorganisms: Chlamydophila pneumoniae , Haemophilus influenzae , Legionella pneumophila , Moraxella catarrhalis , Mycoplasma pneumoniae , Staphylococcus aureus , or Streptococcus pneumoniae in patients who require initial intravenous therapy. 1.2 Pelvic Inflammatory Disease Azithromycin for injection is indicated for the treatment of adult patients with pelvic inflammatory disease due to the following susceptible microorganisms: Chlamydia trachomatis , Neisseria gonorrhoeae , or Mycoplasma hominis in patients who require initial intravenous therapy. If anaerobic microorganisms are suspected of contributing to the infection, an antimicrobial agent with anaerobic activity should be administered in combination with azithromycin for injection. 1.3 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 or prevent 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.

Dosage and administration

• Recommended Dosage for Community-acquired pneumonia: 500 mg as a single daily dose by the intravenous route for at least two days. ( 2.1 )
• Recommended Dosage for Pelvic inflammatory disease in adults: 500 mg as a single daily dose by the intravenous route for one or two days. ( 2.2 ) 2.1 Recommended Dosage for Community-Acquired Pneumonia The recommended dosage of azithromycin for injection for the treatment of adult patients with community-acquired pneumonia due to the indicated organisms is 500 mg as a single daily dose by the intravenous route for at least two days. Intravenous therapy should be followed by azithromycin by the oral route at a single, daily dose of 500 mg, administered as two 250 mg tablets to complete a 7- to 10-day course of therapy. The timing of the switch to oral therapy should be done at the discretion of the physician and in accordance with clinical response. [see Indications and Usage ( 1.1 ) and Clinical Pharmacology ( 12.3 )]. 2.2 Recommended Dosage for Pelvic Inflammatory Disease The recommended dosage of azithromycin for injection for the treatment of adult patients with pelvic inflammatory disease due to the indicated organisms is 500 mg as a single daily dose by the intravenous route for one or two days. Intravenous therapy should be followed by azithromycin by the oral route at a single, daily dose of 250 mg to complete a 7-day course of therapy. The timing of the switch to oral therapy should be done at the discretion of the physician and in accordance with clinical response. [see Indications and Usage ( 1.2 ) and Clinical Pharmacology ( 12.3 )]. 2.3 Preparation of the Solution for Intravenous Administration The infusate concentration and rate of infusion for azithromycin for injection should be either 1 mg/mL over 3 hr or 2 mg/mL over 1 hr. Azithromycin for injection should not be given as a bolus or as an intramuscular injection. Azithromycin for injection should be followed by azithromycin by the oral route as required. [see Dosage and Administration ( 2.1 ) and ( 2.2 )]. Reconstitution Prepare the initial solution of azithromycin for injection by adding 4.8 mL of Sterile Water for Injection to the 500 mg vial, and shaking the vial until all of the drug is dissolved. Since azithromycin for injection is supplied under vacuum, it is recommended that a standard 5 mL (non-automated) syringe be used to ensure that the exact amount of 4.8 mL of Sterile Water is dispensed. Each mL of reconstituted solution contains 100 mg azithromycin. Reconstituted solution is stable for 24 hr when stored below 30°C (86°F). Parenteral drug products should be inspected visually for particulate matter prior to administration. If particulate matter is evident in reconstituted fluids, the drug solution should be discarded. Dilute this solution further prior to administration as instructed below. Dilution To provide azithromycin over a concentration range of 1 to 2 mg/mL, transfer 5 mL of the 100 mg/mL azithromycin solution into the appropriate amount of any of the diluents listed below: Normal Saline (0.9% sodium chloride) 1/2 Normal Saline (0.45% sodium chloride) 5% Dextrose in Water Lactated Ringer’s Solution 5% Dextrose in 1/2 Normal Saline (0.45% sodium chloride) with 20 mEq KCl 5% Dextrose in Lactated Ringer’s Solution 5% Dextrose in 1/3 Normal Saline (0.3% sodium chloride) 5% Dextrose in 1/2 Normal Saline (0.45% sodium chloride) Normosol ® -M in 5% Dextrose Normosol ® -R in 5% Dextrose Final Infusion Solution Concentration (mg/mL) Amount of Diluent (mL) 1 mg/mL 2 mg/mL 500 mL 250 mL Other intravenous substances, additives, or medications should not be added to azithromycin for injection, or infused simultaneously through the same intravenous line. Storage When diluted according to the instructions (1 mg/mL to 2 mg/mL), azithromycin for injection is stable for 24 hr at or below room temperature 30°C (86°F), or for 7 days if stored under refrigeration 5°C (41°F).

Dosage forms and strengths

Azithromycin for Injection, USP is supplied as white to off-white lyophilized powder in a single-dose vial equivalent to 500 mg of azithromycin for intravenous administration. Azithromycin for Injection, USP is supplied as white to off-white lyophilized powder in a single-dose vial equivalent to 500 mg of azithromycin for intravenous administration. ( 3 )

Contraindications

• Patients with known hypersensitivity to azithromycin, erythromycin, any macrolide, or ketolide antibacterial 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 drugs. 4.2 Hepatic Dysfunction Azithromycin is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin.

Warnings and precautions

• Serious (including fatal) allergic and skin reactions. Discontinue azithromycin and initiate appropriate therapy if reaction occurs. ( 5.1 )
• Hepatotoxicity: Severe and sometimes fatal, hepatoxicity has been reported. Discontinue azithromycin immediately if signs and symptoms of hepatitis occur. ( 5.2 )
• Infantile Hypertrophic Pyloric Stenosis (IHPS): Following the use of azithromycin in neonates (treatment up to 42 days of life), IHPS has been reported. Direct parents and caregivers to contact their physician if vomiting or irritability with feeding occurs. ( 5.3 )
• Prolongation of QT interval and cases of torsades de pointes have been reported. This risk which can be fatal should be considered in patients with certain cardiovascular disorders including known QT prolongation or history torsades de pointes, those with proarrhythmic conditions, and with other drugs that prolong the QT interval. ( 5.4 )
• Cardiovascular Death: Some observational studies have shown an approximately two-fold increased short-term potential risk of acute cardiovascular death in adults exposed to azithromycin relative to other antibacterial drugs, including amoxicillin. Consider balancing this potential risk with treatment benefits when prescribing azithromycin. ( 5.5 )
• Clostridioides difficile -Associated Diarrhea: Evaluate patients if diarrhea occurs. ( 5.6 )
• Azithromycin may exacerbate muscle weakness in persons with myasthenia gravis. ( 5.7 ) 5.1 Hypersensitivity Serious allergic reactions, including angioedema, anaphylaxis, and dermatologic reactions including Acute Generalized Exanthematous Pustulosis (AGEP), Stevens-Johnson Syndrome, and toxic epidermal necrolysis have been reported in patients on azithromycin therapy. [see Contraindications (4.1) ] Fatalities have been reported. Cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have also been reported. Despite initially successful symptomatic treatment of the allergic symptoms, when symptomatic therapy was discontinued, the allergic symptoms recurred soon thereafter in some patients without further azithromycin exposure. These patients required prolonged periods of observation and symptomatic treatment. The relationship of these episodes to the long tissue half-life of azithromycin and subsequent prolonged exposure to antigen is unknown at present. If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Physicians should be aware that the allergic symptoms may reappear after symptomatic therapy has been discontinued. 5.2 Hepatotoxicity Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure have been reported, some of which have resulted in death. Discontinue azithromycin immediately if signs and symptoms of hepatitis occur. 5.3 Infantile Hypertrophic Pyloric Stenosis (IHPS) Following the use of azithromycin in neonates (treatment up to 42 days of life), IHPS has been reported. Direct parents and caregivers to contact their physician if vomiting or irritability with feeding occurs. 5.4 QT Prolongation Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen with treatment with macrolides, including azithromycin. Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving azithromycin. Providers should consider the risk of QT prolongation, which can be fatal when weighing the risks and benefits of azithromycin for at-risk groups including:
• patients with known prolongation of the QT interval, a history of torsades de pointes, congenital long QT syndrome, bradyarrhythmias or uncompensated heart failure
• patients on drugs known to prolong the QT interval
• patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, and in patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents. Elderly patients may be more susceptible to drug-associated effects on the QT interval. 5.5 Cardiovascular Death Some observational studies have shown an approximately two-fold increased short-term potential risk of acute cardiovascular death in adults exposed to azithromycin relative to other antibacterial drugs, including amoxicillin. The five-day cardiovascular mortality observed in these studies ranged from 20 to 400 per million azithromycin treatment courses. This potential risk was noted to be greater during the first five days of azithromycin use and does not appear to be limited to those patients with preexisting cardiovascular diseases. The data in these observational studies are insufficient to establish or exclude a causal relationship between acute cardiovascular death and azithromycin use. Consider balancing this potential risk with treatment benefits when prescribing azithromycin. 5.6 Clostridioides difficile -Associated Diarrhea Clostridioides difficile -Associated Diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including azithromycin for injection, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antibacterial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued.

Side effects

The following clinically significant adverse reactions are described elsewhere in labeling: Hypersensitivity [see Warnings and Precautions (5.1) ] Hepatotoxicity [see Warnings and Precautions (5.2) ] Infantile Hypertrophic Pyloric Stenosis (IHPS) [see Warnings and Precautions (5.3) ] QT Prolongation [see Warnings and Precautions (5.4) ] Cardiovascular Death [see Warnings and Precautions (5.5) ] Clostridioides difficile- Associated Diarrhea (CDAD) [see Warnings and Precautions (5.6) ] Exacerbation of Myasthenia Gravis [see Warnings and Precautions (5.7) ] Most common adverse reactions are nausea (4%), diarrhea (4%), abdominal pain (3%), or vomiting (1%). ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Gland Pharma Limited at 866-770-7144 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 of intravenous azithromycin for community-acquired pneumonia, in which 2 to 5 IV doses were given, the reported adverse reactions were mild to moderate in severity and were reversible upon discontinuation of the drug. The majority of patients in these trials had one or more co-morbid diseases and were receiving concomitant medications. Approximately 1.2% of the patients discontinued intravenous azithromycin therapy, and a total of 2.4% discontinued azithromycin therapy by either the intravenous or oral route because of clinical or laboratory side effects. In clinical trials conducted in patients with pelvic inflammatory disease, in which 1 to 2 IV doses were given, 2% of women who received monotherapy with azithromycin and 4% who received azithromycin plus metronidazole discontinued therapy due to clinical side effects. Clinical adverse reactions leading to discontinuations from these studies were gastrointestinal (abdominal pain, nausea, vomiting, diarrhea), and rashes; laboratory side effects leading to discontinuation were increases in transaminase levels and/or alkaline phosphatase levels. Overall, the most common adverse reactions associated with treatment in adult patients who received IV/Oral azithromycin in studies of community-acquired pneumonia were related to the gastrointestinal system with diarrhea/loose stools (4.3%), nausea (3.9%), abdominal pain (2.7%), and vomiting (1.4%) being the most frequently reported. Approximately 12% of patients experienced a side effect related to the intravenous infusion; most common were pain at the injection site (6.5%) and local inflammation (3.1%). The most common adverse reactions associated with treatment in adult women who received IV/Oral azithromycin in trials of pelvic inflammatory disease were related to the gastrointestinal system. Diarrhea (8.5%) and nausea (6.6%) were most commonly reported, followed by vaginitis (2.8%), abdominal pain (1.9%), anorexia (1.9%), rash and pruritus (1.9%). When azithromycin was co-administered with metronidazole in these trials, a higher proportion of women experienced adverse reactions of nausea (10.3%), abdominal pain (3.7%), vomiting (2.8%), infusion site reaction, stomatitis, dizziness, or dyspnea (all at 1.9%). Adverse reactions that occurred with a frequency of 1% or less included the following: Gastrointestinal: Dyspepsia, flatulence, mucositis, oral moniliasis, and gastritis. Nervous system: Headache, somnolence. Allergic: Bronchospasm. Special senses: Taste perversion. 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, torsades de pointes, and cardiovascular death. 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 (including fatalities). Genitourinary: Interstitial nephritis and 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 Significant abnormalities (irrespective of drug relationship) occurring during the clinical trials were reported as follows:
• elevated ALT (SGPT), AST (SGOT), creatinine (4 to 6%)
• elevated LDH, bilirubin (1 to 3%)
• leukopenia, neutropenia, decreased platelet count, and elevated serum alkaline phosphatase (less than 1%) When follow-up was provided, changes in laboratory tests appeared to be reversible.

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 Interaction 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 interaction. 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.

Use in specific populations

• 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 Data) . 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 Data) . 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 Reproductive and developmental toxicology studies have not been conducted using IV administration of azithromycin to animals. 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, 20, 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 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 Data) . Non-serious adverse reactions have been reported in breastfed infants after maternal administration of azithromycin (see Clinical Considerations) . 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 Safety and effectiveness of azithromycin for injection in pediatric patients have not been established. 8.5 Geriatric Use Pharmacokinetic studies with intravenous azithromycin have not been performed in older volunteers. Pharmacokinetics of azithromycin following oral administration in older volunteers (65 to 85 years old) were similar to those in younger volunteers (18 to 40 years old) for the 5-day therapeutic regimen. In multiple-dose clinical trials of intravenous azithromycin in the treatment of community-acquired pneumonia, 45% of patients (188/414) were at least 65 years of age and 22% of patients (91/414) were at least 75 years of age. No overall differences in safety were observed between these subjects and younger subjects in terms of adverse reactions, laboratory abnormalities, and discontinuations. Similar decreases in clinical response were noted in azithromycin- and comparator-treated patients with increasing age. Azithromycin for injection contains 114 mg (4.96 mEq) of sodium per vial. At the usual recommended doses, patients would receive 114 mg (4.96 mEq) of sodium. The geriatric population may respond with a blunted natriuresis to salt loading. The total sodium content from dietary and non-dietary sources may be clinically important with regard to such diseases as congestive heart failure. Elderly patients may be more susceptible to development of torsades de pointes arrhythmias than younger patients. [see Warnings and Precautions (5.4) ]

Pregnancy

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 Data) . 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 Data) . 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 Reproductive and developmental toxicology studies have not been conducted using IV administration of azithromycin to animals. 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, 20, 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 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.

Pediatric use

8.4 Pediatric Use Safety and effectiveness of azithromycin for injection in pediatric patients have not been established.

Geriatric use

8.5 Geriatric Use Pharmacokinetic studies with intravenous azithromycin have not been performed in older volunteers. Pharmacokinetics of azithromycin following oral administration in older volunteers (65 to 85 years old) were similar to those in younger volunteers (18 to 40 years old) for the 5-day therapeutic regimen. In multiple-dose clinical trials of intravenous azithromycin in the treatment of community-acquired pneumonia, 45% of patients (188/414) were at least 65 years of age and 22% of patients (91/414) were at least 75 years of age. No overall differences in safety were observed between these subjects and younger subjects in terms of adverse reactions, laboratory abnormalities, and discontinuations. Similar decreases in clinical response were noted in azithromycin- and comparator-treated patients with increasing age. Azithromycin for injection contains 114 mg (4.96 mEq) of sodium per vial. At the usual recommended doses, patients would receive 114 mg (4.96 mEq) of sodium. The geriatric population may respond with a blunted natriuresis to salt loading. The total sodium content from dietary and non-dietary sources may be clinically important with regard to such diseases as congestive heart failure. Elderly patients may be more susceptible to development of torsades de pointes arrhythmias than younger patients. [see Warnings and Precautions (5.4) ]

Overdosage

Adverse reactions experienced in 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.

Description

Azithromycin for Injection, USP contains the active ingredient azithromycin, an azalide, a subclass of macrolide antibacterial drug, for intravenous injection. 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-hepta-methyl-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. Azithromycin has the following structural formula: Azithromycin, as the monohydrate, is a white crystalline powder with a molecular formula of C 38 H 72 N 2 O 12 ·H 2 O and a molecular weight of 767. Azithromycin for Injection, USP consists of azithromycin monohydrate USP and the following inactive ingredients: citric acid and sodium hydroxide. Sodium hydroxide is added to adjust the pH. Azithromycin for Injection, USP is supplied as white to off-white lyophilized powder in a single-dose vial for intravenous administration. Each vial contains azithromycin monohydrate USP equivalent to 500 mg of azithromycin, 384.5 mg citric acid, and sodium hydroxide. Reconstitution, according to label directions, results in approximately 5 mL of azithromycin for intravenous injection with each mL containing azithromycin monohydrate USP equivalent to 100 mg of azithromycin, 76.9 mg citric acid, and sodium hydroxide. azithromycin-spl-structure

Mechanism of action

12.1 Mechanism of Action Azithromycin is a macrolide antibacterial drug [see Microbiology (12.4) ]

How supplied

Azithromycin for Injection, USP is supplied as white to off-white lyophilized powder under a vacuum in a single-dose vial equivalent to 500 mg of azithromycin for intravenous administration. These are packaged as follows: NDC Azithromycin for Injection, USP, 500 mg/vial Package Factor 68083-199-10 500 mg Single-Dose Vial 10 vials per carton Storage Conditions Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Sterile, Nonpyrogenic, Preservative-free. The container closure is not made with natural rubber latex.

Patient information

Allergic Reactions Instruct patients to immediately contact a physician if any signs of an allergic reaction occur. [see Warnings and Precautions ( 5.1 )]. Vomiting, Irritability, Diarrhea or Rash with Feeding in Infants Direct parents or caregivers to contact their physician if vomiting, irritability, diarrhea or rash with feeding occurs in the infant. [see Warnings and Precautions ( 5.3 ) and Use in Specific Population ( 8.2 )]. Diarrhea Inform patients that diarrhea is a common problem caused by antibacterial drugs 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. If this occurs, patients should notify their physician as soon as possible. Antibacterial Resistance Patients should be counseled that antibacterial drugs including azithromycin for injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When azithromycin for injection is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of 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 for injection or other antibacterial drugs in the future. All brands listed are the trademarks of their respective owners and are not trademarks of Gland Pharma Limited. Manufactured by: Gland Pharma Limited D.P. Pally, Dundigal post, Hyderabad-500 043, India. Revised: 08/2026

Label text from the FDA structured product label by Gland Pharma Limited (revised Aug 12, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Azithromycin Monohydrate in 2 products

Azithromycin monohydrate NDC products (2)

NDC	Strength & form	Labeler	Type
68083-199	Azithromycin Monohydrate 500 mg/10mL Injection, Powder, Lyophilized, For Solution	Gland Pharma Limited	ANDA
70095-025	Azithromycin Monohydrate 500 mg/10mL Injection, Powder, Lyophilized, For Solution	Sun Pharmaceutical Industries Limited	ANDA

Frequently asked questions

What is Azithromycin monohydrate used for?

What are the side effects of Azithromycin monohydrate?

Who makes Azithromycin monohydrate?

Azithromycin monohydrate is listed by 2 labelers in the FDA NDC directory, including Gland Pharma Limited, Sun Pharmaceutical Industries Limited.