Azithromycin Injection

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: digoxin, live bacterial vaccines, lovastatin, nelfinavir, warfarin.Although most antibiotics probably do not affect hormonal birth control such as pills, patch, or ring, some antibiotics may decrease their effectiveness. This could cause pregnancy. Examples include rifamycins such as rifampin or rifabutin. Be sure to ask your doctor or pharmacist if you should use additional reliable birth control methods while using this antibiotic.Many drugs besides azithromycin may affect the heart rhythm (QT prolongation), including amiodarone, disopyramide, dofetilide, dronedarone, ibutilide, pimozide, procainamide, quinidine, sotalol, among others.

For all patients taking azithromycin injection:

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Do not use longer than you have been told. A second infection may happen.
• If you are taking warfarin, talk with your doctor. You may need to have your blood work checked more closely while you are taking it with azithromycin injection.
• A very bad and sometimes deadly reaction has happened with this medicine. Most of the time, this reaction has signs like fever, rash, or swollen glands with problems in body organs like the liver, kidney, blood, heart, muscles and joints, or lungs. Talk with the doctor.
• This medicine may cause a type of abnormal heartbeat (prolonged QT interval). If this happens, the chance of other unsafe and sometimes deadly abnormal heartbeats may be raised. Talk with the doctor.
• If you have myasthenia gravis, talk with your doctor. Call your doctor if your signs get worse. Signs of myasthenia gravis have also happened in people who do not have it. Call your doctor right away if you have new or worse muscle weakness, trouble chewing or swallowing, trouble breathing, droopy eyelids, or change in eyesight like blurred eyesight or seeing double.
• If you are 65 or older, use azithromycin injection with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Newborns:

• A very bad stomach problem has happened in newborns taking azithromycin injection. Call the doctor right away if your child throws up or gets irritable with feeding.

Azithromycin for Injection is a macrolide antibacterial drug indicated for the treatment of patients with infections caused by susceptible strains of the designated microorganisms in the conditions listed below.

Community-Acquired Pneumonia

due to Chlamydophila pneumoniae, Haemophilus influenzae, Legionella pneumophila, Moraxella catarrhalis, Mycoplasma pneumoniae, Staphylococcus aureus, or Streptococcus pneumoniae in patients who require initial intravenous therapy.

Pelvic Inflammatory Disease

due to 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.

Azithromycin for injection should be followed by azithromycin by the oral route as required [see Dosage and Administration (2)].

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.

Hypersensitivity

Azithromycin is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide drugs.

Hepatic Dysfunction

Azithromycin is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin.

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.

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 post-marketing 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 (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.

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.

In multiple-dose clinical trials involving more than 750 patients treated with azithromycin (IV/Oral), less than 2% of patients discontinued azithromycin therapy because of treatment-related liver enzyme abnormalities.

1.     Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard - Tenth Edition. CLSI document M07-A10, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.

2.     Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-sixth Informational Supplement. CLSI document M100-S26. CLSI document M100-S26, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2016.

3.     Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard – Twelfth Edition CLSI document M02-A12, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.

4.     Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Dilution and Disk Susceptibility Testing for Infrequently Isolated or Fastidious Bacteria; Approved Guidelines - Third Edition CLSI document M45-A3, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2016.

Patients should be informed of the following serious and potentially serious adverse reactions that have been associated with azithromycin for injection.

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.

Manufactured by:
Gland Pharma Limited
D.P. Pally, Dundigal post,
Hyderabad-500 043, INDIA.

PRINCIPAL DISPLAY PANEL - 500 mg*/vial
Gland Pharma Limited, NDC 68083-199-10
AZITHROMYCIN for Injection, USP 
Equivalent to 500 mg*/vial
Sterile, Rx only
10 Single Dose Vials
For Intravenous Infusion Only
Carton Label

PRINCIPAL DISPLAY PANEL - 500 mg*/vial
Gland Pharma Limited, NDC 68083-199-01
AZITHROMYCIN for Injection, USP 
Equivalent to 500 mg*/vial
Sterile, Rx only
Single Dose Vial
For Intravenous Infusion Only
Vial Label

AZITHROMYCIN MONOHYDRATE  azithromycin monohydrate injection, powder, lyophilized, for solution

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:68083-199 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength AZITHROMYCIN MONOHYDRATE (AZITHROMYCIN ANHYDROUS) AZITHROMYCIN ANHYDROUS 500 mg  in 10 mL

Inactive Ingredients Ingredient Name Strength CITRIC ACID MONOHYDRATE   SODIUM HYDROXIDE

Packaging # Item Code Package Description 1 NDC:68083-199-10 10 VIAL in 1 CARTON 1 10 mL in 1 VIAL

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA065501 11/09/2009

Labeler - Gland Pharma Limited (918601238)

Establishment
Name	Address	ID/FEI	Operations
Gland Pharma Limited		918601238	ANALYSIS(68083-199), MANUFACTURE(68083-199), PACK(68083-199)

Revised: 08/2017   Gland Pharma Limited