AZITHROMYCIN (azithromycin)

azithromycin

January 22, 2026

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Antibiotic medicine

Quick Facts

Used For

This medicine treats lung infections caused by certain germs. It works against germs like pneumonia...

Common Side Effects

**Side Effects from Studies** When doctors test medicines, the results can be...

What You Should Know

You should know about these serious side effects that can happen with azithromycin injection. Diarrhea:...

Prescription

Not Required

Generic Available

Indications and Usage

This medicine treats lung infections caused by certain germs. It works against germs like pneumonia bacteria, staph, and strep. You get this medicine through an IV first.

This medicine also treats pelvic infections in women. It works against germs that cause these infections. If other germs might be involved, your doctor may give you another antibiotic too.

After the IV medicine, you will take pills by mouth to finish treatment.

This medicine should only be used for infections caused by germs it can kill. Your doctor may test your germs first to make sure this medicine will work. If testing is not done, your doctor will use local germ patterns to choose treatment.

This medicine is an antibiotic that treats infections caused by certain germs that it can kill.

Community-acquired pneumonia due toChlamydophila pneumoniae,Haemophilus influenzae,Legionella pneumophila,Moraxella catarrhalis,Mycoplasma pneumoniae,Staphylococcus aureus, orStreptococcus pneumoniaein patients who require initial intravenous therapy.

Pelvic inflammatory disease due toChlamydia trachomatis,Neisseria gonorrhoeae, orMycoplasma hominisin 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)].

To reduce the development of drug-resistant bacteria and maintain the effectiveness of azithromycin for injection and other antibacterial drugs, Azithromycin for Injection 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.

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.

Dosage and Administration

**For Pneumonia (lung infection):**

You will get 500 mg once a day through an IV for at least 2 days. After that, you will take pills by mouth – two 250 mg tablets once a day. The total treatment is 7 to 10 days. Your doctor will decide when to switch from IV to pills.

**For Pelvic Inflammatory Disease:**

You will get 500 mg once a day through an IV for 1 or 2 days. After that, you will take 250 mg pills by mouth once a day. The total treatment is 7 days. Your doctor will decide when to switch from IV to pills.

**How the IV is given:**

The medicine goes into your vein slowly. It takes either 3 hours or 1 hour depending on how strong the mixture is. This medicine cannot be given as a shot in your muscle or pushed in quickly.

**How nurses prepare your IV:**

Nurses mix the powder with 4.8 mL of sterile water. This makes a solution that stays good for 24 hours if kept below 86°F. They check to make sure there are no particles floating in it. If there are particles, they throw it away and make a new batch.

Then they mix this solution with more fluid before giving it to you.

**What fluids can be mixed with this medicine:**

• Normal saline
• Half-strength saline
• Sugar water (5% dextrose)
• Lactated Ringer’s solution
• Sugar water with half-strength saline and potassium
• Sugar water with Lactated Ringer’s solution
• Sugar water with different strengths of saline
• Normosol-M with sugar water
• Normosol-R with sugar water

**Mixing amounts:**

• For weaker solution (1.0 mg/mL): Mix with 500 mL of fluid
• For stronger solution (2.0 mg/mL): Mix with 250 mL of fluid

No other medicines should be mixed with this medicine or given through the same IV line at the same time.

**Storage:**

Once mixed, the medicine stays good for 24 hours at room temperature (86°F or below) or 7 days in the refrigerator (41°F).

The recommended dose 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.

The recommended dose 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.

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.

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 1.0-2.0 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)1.0 mg/mL500 mL2.0 mg/mL250 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 (1.0 mg/mL to 2.0 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).

[see Indications and Usage (1) and Clinical Pharmacology (12.3)]

================================================================================
TABLE: Table
================================================================================

+——————————————+————————–+
| Final Infusion Solution Concentration (mg/mL) | Amount of Diluent (mL) |
+——————————————+————————–+
| 1.0 mg/mL | 500 mL |
| 2.0 mg/mL | 250 mL |
+——————————————+————————–+

Dosage Forms and Strengths

This medicine comes as a powder in a small bottle. Each bottle contains 500 mg of azithromycin. The powder is mixed with liquid and given through an IV.

Azithromycin for Injection, USP is supplied in lyophilized form in a 10-mL single-dose vial equivalent to 500 mg of azithromycin for intravenous administration.

Contraindications

Do not use azithromycin injection if you are allergic to azithromycin, erythromycin, or similar antibiotics called macrolides or ketolides.

Do not use azithromycin injection if you have had liver problems or yellowing of skin and eyes from using azithromycin before.

4.1 Allergic Reactions

Do not use azithromycin injection if you are allergic to azithromycin, erythromycin, or similar antibiotics called macrolides or ketolides.

4.2 Liver Problems

Do not use azithromycin injection if you have had liver problems or yellowing of skin and eyes from using azithromycin before.

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

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

4.1 Hypersensitivity

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

4.2 Hepatic Dysfunction

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

Warnings and Precautions

**Important Safety Warnings**

**Serious Allergic Reactions**

This medicine can cause very serious allergic reactions. Some people have died from these reactions. You might get swelling of your face or throat, trouble breathing, or serious skin problems.

Even after treatment for allergic reactions, the symptoms may come back. This can happen even if you don’t take more of this medicine. You may need to be watched by doctors for a long time.

If you have an allergic reaction, stop taking this medicine right away and get medical help. Your doctor should know that allergic symptoms might come back even after treatment.

**Liver Problems**

This medicine can cause serious liver problems that may lead to death. Stop taking this medicine right away if you have signs of liver problems like yellowing of skin or eyes, dark urine, or stomach pain.

**Problems in Newborns**

In babies up to 42 days old, this medicine can cause stomach problems that block food from passing through. Parents should call the doctor if the baby vomits or gets fussy during feeding.

**Heart Problems**

This medicine can cause dangerous heart rhythm problems that may be deadly. Your risk is higher if you:

• Have heart rhythm problems or heart failure
• Take other medicines that affect heart rhythm
• Have low potassium or magnesium levels
• Take certain heart medicines

Older adults may have higher risk of heart problems.

**Heart-Related Death**

Some studies show this medicine may double the risk of sudden heart-related death in the first 5 days of treatment. This risk may happen even if you don’t have heart disease. The risk is about 20 to 400 deaths per million people who take this medicine.

**Serious Diarrhea**

This medicine can cause serious diarrhea from harmful bacteria called C. diff. This can be mild or deadly. Antibiotics kill good bacteria in your gut, letting bad bacteria grow.

You can get this serious diarrhea up to 2 months after taking antibiotics. If you get diarrhea after taking antibiotics, tell your doctor right away.

If you have C. diff infection, you may need to stop other antibiotics and get special treatment.

**Muscle Weakness**

This medicine can make muscle weakness worse in people with myasthenia gravis. It can also cause new muscle weakness problems.

**IV Site Problems**

When given through an IV, this medicine must be given slowly over at least 60 minutes. It can cause pain, redness, or swelling where the IV goes into your arm.

Higher concentrations of the medicine cause more IV site problems and should not be used.

**Drug-Resistant Bacteria**

Taking this medicine when you don’t have a bacterial infection won’t help you. It can make bacteria stronger and harder to treat with antibiotics later.

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.

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.

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.

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 failurepatients on drugs known to prolong the QT intervalpatients 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.

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 for injection.

Clostridioides difficileassociated 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 ofC. difficile.

C. difficileproduces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains ofC. difficilecause 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 againstC. difficilemay need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment ofC. difficile, and surgical evaluation should be instituted as clinically indicated.

Exacerbations of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been reported in patients receiving azithromycin therapy.

Azithromycin for injection should be reconstituted and diluted as directed and administered as an intravenous infusion over not less than 60 minutes[see Dosage and Administration (2)].

Local IV site reactions have been reported with the intravenous administration of azithromycin. The incidence and severity of these reactions were the same when 500 mg azithromycin was given over 1 hour (2 mg/mL as 250 mL infusion) or over 3 hours (1 mg/mL as 500 mL infusion)[see Adverse Reactions (6)]. All volunteers who received infusate concentrations above 2.0 mg/mL experienced local IV site reactions and, therefore, higher concentrations should be avoided.

Prescribing azithromycin in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug‑resistant bacteria.

5.1 Hypersensitivity

[see Contraindications (

4.1

)].

5.2 Hepatotoxicity

5.3 Infantile Hypertrophic Pyloric Stenosis (IHPS)

5.4 QT Prolongation

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

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

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. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of

C. difficile

, and surgical evaluation should be instituted as clinically indicated.

5.7 Exacerbation of Myasthenia Gravis

Exacerbations of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been reported in patients receiving azithromycin therapy.

5.8 Infusion Site Reactions

Azithromycin for injection should be reconstituted and diluted as directed and administered as an intravenous infusion over not less than 60 minutes

[see Dosage and Administration (

)]

[see Adverse Reactions (

)]

. All volunteers who received infusate concentrations above 2.0 mg/mL experienced local IV site reactions and, therefore, higher concentrations should be avoided.

5.9 Development of Drug-Resistant Bacteria

Adverse Reactions

**Side Effects from Studies**

When doctors test medicines, the results can be different from one study to another. The side effects you get might be different from what happened in the studies.

**Studies for Pneumonia**

In studies where people got azithromycin through an IV for pneumonia, most side effects were mild to moderate. They went away when people stopped taking the medicine. Most people in these studies had other health problems and were taking other medicines too.

About 1 out of 100 people stopped the IV medicine because of side effects. About 2 out of 100 people stopped taking azithromycin completely because of side effects.

**Studies for Pelvic Infections**

In studies for pelvic infections, 2 out of 100 women stopped taking azithromycin alone because of side effects. When azithromycin was given with another medicine called metronidazole, 4 out of 100 women stopped because of side effects.

People stopped taking the medicine because of stomach problems (belly pain, feeling sick, throwing up, loose stools), skin rashes, or blood test changes showing liver problems.

**Most Common Side Effects in Pneumonia Studies**

The most common side effects were stomach problems:

• Loose stools or diarrhea (4 out of 100 people)
• Feeling sick to your stomach (4 out of 100 people)
• Belly pain (3 out of 100 people)
• Throwing up (1 out of 100 people)

About 12 out of 100 people had problems with the IV:

• Pain where the needle went in (7 out of 100 people)
• Swelling where the needle went in (3 out of 100 people)

**Most Common Side Effects in Pelvic Infection Studies**

The most common side effects were:

• Diarrhea (9 out of 100 women)
• Feeling sick to your stomach (7 out of 100 women)
• Vaginal infection (3 out of 100 women)
• Belly pain (2 out of 100 women)
• Not feeling hungry (2 out of 100 women)
• Skin rash and itching (2 out of 100 women)

When azithromycin was given with metronidazole, more women had these side effects:

• Feeling sick to your stomach (10 out of 100 women)
• Belly pain (4 out of 100 women)
• Throwing up (3 out of 100 women)
• Problems at the IV site, mouth sores, dizziness, or trouble breathing (2 out of 100 women each)

**Less Common Side Effects (1 out of 100 people or less)**

Stomach problems: Upset stomach, gas, mouth sores, yeast infections in the mouth, stomach irritation

Brain and nerves: Headache, feeling sleepy

Allergic reactions: Trouble breathing

Senses: Food tasting different

**Side Effects Reported After the Medicine Was Approved**

These side effects have been reported since the medicine started being sold, but we don’t know exactly how often they happen:

Allergic reactions: Joint pain, swelling, hives, severe swelling

Heart problems: Irregular heartbeat, fast heartbeat, low blood pressure, heart rhythm problems that can be deadly

Stomach problems: Not feeling hungry, constipation, upset stomach, gas, throwing up, diarrhea, serious bowel infection, pancreas inflammation, yeast infections in the mouth, stomach blockage, tongue color changes

General problems: Weakness, tingling, tiredness, feeling unwell, severe allergic reactions that can be deadly

Kidney and genital problems: Kidney inflammation, kidney failure, vaginal infections

Blood problems: Low platelet count

Liver problems: Abnormal liver tests, liver inflammation, liver damage, liver failure

Brain and nerve problems: Seizures, dizziness, headache, sleepiness, hyperactivity, nervousness, agitation, fainting

Mental problems: Aggressive behavior, anxiety

Skin problems: Itching, serious skin reactions including severe rashes that can be life-threatening

Senses: Hearing problems including hearing loss, deafness, ringing in ears, problems with taste or smell

**Blood Test Changes During Studies**

Some people had changes in their blood tests:

• Liver enzyme increases (4 to 6 out of 100 people)
• Other liver test increases (1 to 3 out of 100 people)
• Low white blood cell count, low platelet count, liver enzyme increases (less than 1 out of 100 people)

When doctors checked later, most blood test changes went back to normal.

In studies with more than 750 people, less than 2 out of 100 people stopped taking azithromycin because of liver test changes.

**Other Important Side Effects**

These serious side effects are explained in other parts of this information:

• Severe allergic reactions
• Liver damage
• Stomach blockage in babies
• Heart rhythm problems
• Heart-related death
• Serious bowel infections
• Muscle weakness getting worse

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.

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, 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.

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.

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)]

Drug Interactions

**Drug Interactions**

Taking this medicine with certain other drugs can cause problems. Tell your doctor about all medicines you take.

**Nelfinavir**

Taking nelfinavir with this medicine can increase the amount of this medicine in your blood. You don’t need to change your dose, but your doctor should watch you closely for side effects like liver problems or hearing loss.

**Warfarin (Blood Thinner)**

This medicine might make warfarin work stronger, which could cause more bleeding. Your doctor will need to check your blood more often to make sure it’s clotting normally.

**Other Medicines to Watch**

We don’t have complete information about how this medicine works with digoxin, colchicine, or phenytoin. But similar medicines can cause problems with these drugs. Your doctor should watch you closely if you take any of these medicines together.

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)].

Spontaneous post-marketing 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.

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.

7.1 Nelfinavir

[see Adverse Reactions (

)]

7.2 Warfarin

7.3 Potential Drug-Drug Interaction with Macrolides

Pregnancy

**Risk Summary**

Studies over many decades show that azithromycin is safe to use during pregnancy. The research has not found increased risks for birth defects, miscarriage, or problems for mothers or babies.

Animal studies tested azithromycin in rats, mice, and rabbits. The medicine did not cause birth defects when given at doses up to 2-4 times higher than what humans normally take. However, in one rat study, baby rats had some problems with survival and growth when their mothers got very high doses during pregnancy and nursing.

All pregnancies have some natural risk of problems. In the U.S., about 2-4% of babies are born with major birth defects. About 15-20% of known pregnancies end in miscarriage.

**Data**

**Human Data**

Many studies over several decades show azithromycin does not increase the risk of birth defects, miscarriage, or other pregnancy problems. These studies have some limits because they could not control for other factors like the mother’s illness or other medicines she was taking.

**Animal Data**

Scientists have not tested azithromycin given through an IV in pregnant animals. When given by mouth during the time when organs form, azithromycin did not cause birth defects in rats and mice at doses up to 200 mg per kg of body weight. This is about 2-4 times higher than what humans normally take.

In rabbits given azithromycin during organ formation, the mothers ate less food and lost weight, but their babies were normal. The highest dose tested was about 2 times what humans normally take.

In one study, pregnant rats got azithromycin from day 6 of pregnancy until their babies stopped nursing. At the highest dose, mothers had problems eating and gaining weight. Some baby rats had trouble surviving and growing normally. However, when the same dose was given starting later in pregnancy (day 15), these problems did not happen.

Risk SummaryAvailable 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[seeData]. 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[seeData].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.

DataHuman DataAvailable 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 DataReproductive 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.

Lactation

**What You Need to Know**

This medicine passes into breast milk. Some babies may have mild side effects when their mothers take this medicine while breastfeeding. We don’t know if this medicine affects how much breast milk you make.

Your doctor will think about the benefits of breastfeeding and your need for this medicine. They will also consider any possible effects on your baby.

**What to Watch For**

Watch your baby for diarrhea, throwing up, or skin rash while you are taking this medicine.

**Research Information**

Studies looked at breast milk from women who took this medicine. In one study, 20 women took a large dose during labor. The medicine was found in their breast milk for up to 4 weeks after taking it.

In another study, 8 women got this medicine through an IV before surgery. The medicine was found in their first breast milk for up to 48 hours.

Risk SummaryAzithromycin is present in human milk[seeData]. Non-serious adverse reactions have been reported in breastfed infants after maternal administration of azithromycin[seeClinical 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 for injection and any potential adverse effects on the breastfed infant from azithromycin for injection or from the underlying maternal condition.

Clinical ConsiderationsAdvise women to monitor the breastfed infant for diarrhea, vomiting, or rash.

DataAzithromycin 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.

Pediatric Use

We don’t know if azithromycin shots are safe or work well for children under 16 years old. In studies, doctors have given azithromycin pills and liquid to children from 6 months to 16 years old. For information about using azithromycin liquid in children, see the sections about uses and dosing in the medicine information for azithromycin liquid bottles.

Safety and effectiveness of azithromycin for injection in children or adolescents under 16 years have not been established. In controlled clinical studies, azithromycin has been administered to pediatric patients (age 6 months to 16 years) by the oral route. For information regarding the use of azithromycin for oral suspension in the treatment of pediatric patients, [see Indications and Usage (1), and Dosage and Administration (2)]of the prescribing information for azithromycin for oral suspension 100 mg/5 mL and 200 mg/5 mL bottles.

Geriatric Use

Studies have not been done with IV azithromycin in older adults. When taken by mouth, azithromycin works the same way in older adults (65 to 85 years old) as it does in younger adults (18 to 40 years old) for the 5-day treatment.

In studies of IV azithromycin for pneumonia, 45% of patients (188 out of 414) were at least 65 years old and 22% of patients (91 out of 414) were at least 75 years old. Older and younger patients had similar side effects, lab test changes, and rates of stopping the medicine. Both azithromycin and other comparison medicines worked less well as patients got older.

Each vial of azithromycin injection contains 114 mg of sodium (salt). At normal doses, patients get 114 mg of sodium. Older adults may not get rid of extra salt from their bodies as well as younger people. The total amount of salt from food and medicines may be important for people with heart failure.

Older patients may be more likely to develop a dangerous heart rhythm problem called torsades de pointes than younger patients.

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 oftorsades de pointesarrhythmias than younger patients[see Warnings and Precautions (5.4)].

Description

Azithromycin for Injection contains the active ingredient azithromycin. This is a type of antibiotic medicine that is given through an IV (into your vein).

Azithromycin is made from another antibiotic called erythromycin, but it has been changed to work better. It comes as a white powder.

This injection also contains citric acid and sodium hydroxide as inactive ingredients. The medicine comes in a small bottle that contains 500 mg of azithromycin.

When your nurse or doctor mixes the powder with liquid, it makes about 5 mL of medicine. Each mL contains 100 mg of azithromycin that can be given through your IV.

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 C38H72N2O12, 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 C38H72N2O12· 2H2O and a molecular weight of 785.0.

Azithromycin for Injection, USP consists of azithromycin dihydrate and the following inactive ingredients: citric acid and sodium hydroxide. Azithromycin for Injection, USP, is supplied in lyophilized form in a 10-mL single-dose vial equivalent to 500 mg of azithromycin for intravenous administration. Reconstitution, according to label directions, results in approximately 5 mL of azithromycin for intravenous injection with each mL containing azithromycin dihydrate equivalent to 100 mg of azithromycin.

Mechanism of Action

**How Azithromycin Works**

Azithromycin is a type of antibiotic called a macrolide.

Azithromycin works by sticking to a part of germs called ribosomes. This stops the germs from making proteins they need to survive and grow.

**Heart Effects**

Studies show that azithromycin can affect your heart rhythm. When taken with another medicine called chloroquine, it can make your heart beat differently. Higher doses cause bigger changes to your heart rhythm.

Getting azithromycin through an IV may cause more heart rhythm changes than taking pills.

**How the Body Handles Azithromycin**

When patients get azithromycin through an IV for pneumonia, the medicine reaches its highest level in the blood quickly. Then it slowly goes down over 24 hours.

A 1-hour IV gives higher blood levels than a 3-hour IV. Taking pills by mouth gives lower blood levels than getting an IV.

After taking azithromycin for several days, more medicine builds up in your body.

**Where the Medicine Goes in Your Body**

Azithromycin spreads throughout your body tissues like skin, lungs, and other organs. It doesn’t go into the brain fluid very well.

The medicine sticks to blood proteins differently depending on how much is in your blood.

**How the Body Gets Rid of Azithromycin**

Your body removes azithromycin slowly. It takes about 68 hours for half the medicine to leave your body. This happens because the medicine gets stored in your tissues and then slowly released.

Most of the medicine leaves through bile. Some leaves through urine. More leaves through urine when you get an IV compared to taking pills.

**Special Patient Groups**

People with mild to moderate kidney problems don’t need dose changes. People with severe kidney problems may have higher medicine levels in their blood.

Men and women process the medicine the same way. Older adults process it similarly to younger adults.

**Drug Interactions**

Azithromycin can interact with other medicines, but most interactions are small. Usually you don’t need to change doses when taking other medicines with azithromycin.

Some medicines like nelfinavir can increase azithromycin levels in your blood, but dose changes usually aren’t needed.

**How Azithromycin Kills Germs**

Azithromycin kills germs by stopping them from making proteins. It sticks to a specific part of the germ called 23S rRNA.

**Germ Resistance**

Some germs can become resistant to azithromycin. This usually happens when germs change their ribosomes so the medicine can’t stick to them.

**What Germs Azithromycin Fights**

Azithromycin works against many types of germs:

• Staph and strep bacteria
• Bacteria that cause pneumonia and ear infections
• Bacteria that cause sexually transmitted infections
• Other special bacteria like chlamydia and mycoplasma

Some other germs may be killed by azithromycin, but doctors need more studies to be sure it works for infections caused by these germs.

Azithromycin is a macrolide antibacterial drug[see Microbiology (12.4)].

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. pneumoniaeandS. 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 (1000 mg) alone or in combination with oral azithromycin (500 mg, 1000 mg, and 1500 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, 1000 mg and 1500 mg azithromycin, respectively.

Since the mean Cmaxof azithromycin following a 500 mg IV dose given over 1 hr is higher than the mean Cmaxof azithromycin following the administration of a 1500 mg oral dose, it is possible that QTc may be prolonged to a greater extent with IV azithromycin at close proximity to a one hour infusion of 500 mg.

In patients hospitalized with community-acquired pneumonia receiving single daily one-hour intravenous infusions for 2 to 5 days of 500 mg azithromycin at a concentration of 2 mg/mL, the mean Cmax± S.D. achieved was 3.63 ± 1.60 mcg/mL, while the 24-hour trough level was 0.20 ± 0.15 mcg/mL, and the AUC24was 9.60 ± 4.80 mcg·hour/mL.

The mean Cmax, 24-hour trough and AUC24values were 1.14 ± 0.14 mcg/mL, 0.18 ± 0.02 mcg/mL, and 8.03 ± 0.86 mcg·hour/mL, respectively, in normal volunteers receiving a 3‑hour intravenous infusion of 500 mg azithromycin at a concentration of 1 mg/mL. Similar pharmacokinetic values were obtained in patients hospitalized with community-acquired pneumonia who received the same 3‑hour dosage regimen for 2-5 days.

a500 mg (2 mg/mL) for 2-5 days in community-acquired pneumonia patients.b500 mg (1 mg/mL) for 5 days in healthy subjects.Infusion Concentration, DurationTime after starting the infusion (hr)0.512346812242 mg/mL, 1 hra2.98 ± 1.123.63 ± 1.730.60 ± 0.310.40 ± 0.230.33 ± 0.160.26 ± 0.140.27 ± 0.150.20 ± 0.120.20 ± 0.151 mg/mL, 3 hrb0.91 ± 0.131.02 ± 0.111.14 ± 0.131.13 ± 0.160.32 ± 0.050.28 ± 0.040.27 ± 0.030.22 ± 0.020.18 ± 0.02

Comparison of the plasma pharmacokinetic parameters following the 1st and 5th daily doses of 500 mg intravenous azithromycin showed only an 8% increase in Cmaxbut a 61% increase in AUC24reflecting a threefold rise in C24trough levels.

Following single-oral doses of 500 mg azithromycin (two 250 mg capsules) to 12 healthy volunteers, Cmax, trough level, and AUC24were reported to be 0.41 mcg/mL, 0.05 mcg/mL, and 2.6 mcg·hour/mL, respectively. These oral values are approximately 38%, 83%, and 52% of the values observed following a single 500-mg I.V. 3-hour infusion (Cmax: 1.08 mcg/mL, trough: 0.06 mcg/mL, and AUC24: 5.0 mcg·hour/mL). Thus, plasma concentrations are higher following the intravenous regimen throughout the 24-hour interval.

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.

Tissue concentrations have not been obtained following intravenous infusions of azithromycin, but following oral administration in humans azithromycin has been shown to penetrate into tissues, including skin, lung, tonsil, and cervix.

Tissue levels were determined following a single oral dose of 500 mg azithromycin in 7 gynecological patients. Approximately 17 hr after dosing, azithromycin concentrations were 2.7 mcg/g in ovarian tissue, 3.5 mcg/g in uterine tissue, and 3.3 mcg/g in salpinx. Following a regimen of 500 mg on the first day followed by 250 mg daily for 4 days, concentrations in the cerebrospinal fluid were less than 0.01 mcg/mL in the presence of non‑inflamed meninges.

Metabolism

In vitroandin vivostudies 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 with 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.

In a multiple-dose study in 12 normal volunteers utilizing a 500 mg (1 mg/mL) one-hour intravenous-dosage regimen for five days, the amount of administered azithromycin dose excreted in urine in 24 hr was about 11% after the 1st dose and 14% after the 5th dose. These values are greater than the reported 6% excreted unchanged in urine after oral administration of azithromycin. Biliary excretion is a major route of elimination for unchanged drug, following oral administration.

Specific Populations

Patients with Renal Impairment

Azithromycin pharmacokinetics were investigated in 42 adults (21 to 85 years of age) with varying degrees of renal impairment. Following the oral administration of a single 1,000 mg dose of azithromycin, mean Cmaxand AUC0-120increased by 5.1% and 4.2%, respectively in subjects with mild to moderate renal impairment (GFR 10 to 80 mL/min) compared to subjects with normal renal function (GFR >80 mL/min). The mean Cmaxand AUC0-120increased 61% and 35%, respectively in subjects with severe renal impairment (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 studies with intravenous azithromycin have not been performed in older volunteers. Pharmacokinetics of azithromycin following oral administration in older volunteers (65 – 85 years old) were similar to those in younger volunteers (18 – 40 years old) for the 5-day therapeutic regimen[see Geriatric Use (8.5)].

Pediatric Patients

Pharmacokinetic studies with intravenous azithromycin have not been performed in children.

Drug Interaction Studies

Drug interaction studies were performed with oral 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 Cmaxand 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 AzithromycinCo-administered DrugDose of Co‑administered DrugDose of AzithromycinnRatio (with/without azithromycin) ofCo-administered Drug Pharmacokinetic Parameters (90% CI); No Effect = 1.00Mean CmaxMean AUC* – 90% Confidence interval not reportedAtorvastatin10 mg/day for 8 days500 mg/day orally on days 6 to 8120.83(0.63 to 1.08)1.01(0.81 to 1.25)Carbamazepine200 mg/day for 2 days, then 200 mg twice a day for 18 days500 mg/day orally for days 16 to 1870.97(0.88 to 1.06)0.96(0.88 to 1.06)Cetirizine20 mg/day for 11 days500 mg orally on day 7,then 250 mg/day on days 8 to 11141.03(0.93 to 1.14)1.02(0.92 to 1.13)Didanosine200 mg orally twice a day for 21 days1,200 mg/day orally on days 8 to 2161.44(0.85 to 2.43)1.14(0.83 to 1.57)Efavirenz400 mg/day for 7 days600 mg orally on day 7141.04*0.95*Fluconazole200 mg orally single dose1,200 mg orally single dose181.04(0.98 to 1.11)1.01(0.97 to 1.05)Indinavir800 mg three times a day for 5 days1,200 mg orally on day 5180.96(0.86 to 1.08)0.90(0.81 to 1.00)Midazolam15 mg orally on day 3500 mg/day orally for 3 days121.27(0.89 to 1.81)1.26(1.01 to 1.56)Nelfinavir750 mg three times a day for 11 days1,200 mg orally on day 9140.90(0.81 to 1.01)0.85(0.78 to 0.93)Sildenafil100 mg on days 1 and 4500 mg/day orally for 3 days121.16(0.86 to 1.57)0.92(0.75 to 1.12)Theophylline4 mg/kg IV on days 1, 11, 25500 mg orally on day 7,250 mg/day on days 8 to 11101.19(1.02 to 1.40)1.02(0.86 to 1.22)Theophylline300 mg orally BID × 15 days500 mg orally on day 6,then 250 mg/day on days 7 to 1081.09(0.92 to 1.29)1.08(0.89 to 1.31)Triazolam0.125 mg on day 2500 mg orally on day 1,then 250 mg/day on day 2121.06*1.02*Trimethoprim/ Sulfamethoxazole160 mg/800 mg/day orally for 7 days1,200 mg orally on day 7120.85(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)Zidovudine500 mg/day orally for 21 days600 mg/day orally for 14 days51.12(0.42 to 3.02)0.94(0.52 to 1.70)Zidovudine500 mg/day orally for 21 days1,200 mg/day orally for 14 days41.31(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 (7.3)]Co-administered DrugDose of Co‑administered DrugDose of AzithromycinnRatio (with/withoutco‑administered drug) ofAzithromycin PharmacokineticParameters (90% CI);No Effect = 1.00Mean CmaxMean AUC* – 90% Confidence interval not reported]Efavirenz400 mg/day for 7 days600 mg orally on day 7141.22(1.04 to 1.42)0.92*Fluconazole200 mg orally single dose1,200 mg orally single dose180.82(0.66 to 1.02)1.07(0.94 to 1.22)Nelfinavir750 mg three times a dayfor 11 days1,200 mg orally on day 9142.36(1.77 to 3.15)2.12(1.80 to 2.50)

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 (MLSBphenotype).

Antimicrobial Activity

Azithromycin has been shown to be active against the following microorganisms, bothin vitroand in clinical infections[see Indications and Usage (1)].

Gram-positive Bacteria

Staphylococcus aureus

Streptococcus pneumoniae

Gram-negative Bacteria

Haemophilus influenzae

Moraxella catarrhalis

Neisseria gonorrhoeae

Legionella pneumophila

Other Bacteria

Chlamydophila pneumoniae

Chlamydia trachomatis

Mycoplasma hominis

Mycoplasma pneumoniae

The followingin vitrodata are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit anin vitrominimum 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.

Aerobic Gram-Positive Bacteria

Streptococci (Groups C, F, G)

Viridans group streptococci

Gram-Negative Bacteria

Bordetella pertussis

Anaerobic Bacteria

Peptostreptococcusspecies

Prevotella bivia

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 this drug, please see: https://www.fda.gov/STIC.

12.1 Mechanism of Action

Azithromycin is a macrolide antibacterial drug

[see Microbiology (

12.4

)].

12.2 Pharmacodynamics

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

Since the mean C

max

of azithromycin following a 500 mg IV dose given over 1 hr is higher than the mean C

max

of azithromycin following the administration of a 1500 mg oral dose, it is possible that QTc may be prolonged to a greater extent with IV azithromycin at close proximity to a one hour infusion of 500 mg.

12.3 Pharmacokinetics

In patients hospitalized with community-acquired pneumonia receiving single daily one-hour intravenous infusions for 2 to 5 days of 500 mg azithromycin at a concentration of 2 mg/mL, the mean C

max

± S.D. achieved was 3.63 ± 1.60 mcg/mL, while the 24-hour trough level was 0.20 ± 0.15 mcg/mL, and the AUC

was 9.60 ± 4.80 mcg·hour/mL.

The mean C

max

, 24-hour trough and AUC

values were 1.14 ± 0.14 mcg/mL, 0.18 ± 0.02 mcg/mL, and 8.03 ± 0.86 mcg·hour/mL, respectively, in normal volunteers receiving a 3‑hour intravenous infusion of 500 mg azithromycin at a concentration of 1 mg/mL. Similar pharmacokinetic values were obtained in patients hospitalized with community-acquired pneumonia who received the same 3‑hour dosage regimen for 2-5 days.

500 mg (2 mg/mL) for 2-5 days in community-acquired pneumonia patients.

500 mg (1 mg/mL) for 5 days in healthy subjects.

Infusion Concentration, Duration

Time after starting the infusion (hr)

0.5

2 mg/mL, 1 hr

2.98 ± 1.12

3.63 ± 1.73

0.60 ± 0.31

0.40 ± 0.23

0.33 ± 0.16

0.26 ± 0.14

0.27 ± 0.15

0.20 ± 0.12

0.20 ± 0.15

1 mg/mL, 3 hr

0.91 ± 0.13

1.02 ± 0.11

1.14 ± 0.13

1.13 ± 0.16

0.32 ± 0.05

0.28 ± 0.04

0.27 ± 0.03

0.22 ± 0.02

0.18 ± 0.02

Comparison of the plasma pharmacokinetic parameters following the 1st and 5th daily doses of 500 mg intravenous azithromycin showed only an 8% increase in C

max

but a 61% increase in AUC

reflecting a threefold rise in C

trough levels.

Following single-oral doses of 500 mg azithromycin (two 250 mg capsules) to 12 healthy volunteers, C

max

, trough level, and AUC

were reported to be 0.41 mcg/mL, 0.05 mcg/mL, and 2.6 mcg·hour/mL, respectively. These oral values are approximately 38%, 83%, and 52% of the values observed following a single 500-mg I.V. 3-hour infusion (C

max

: 1.08 mcg/mL, trough: 0.06 mcg/mL, and AUC

: 5.0 mcg·hour/mL). Thus, plasma concentrations are higher following the intravenous regimen throughout the 24-hour interval.

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.

Metabolism

In vitro

and

in vivo

studies to assess the metabolism of azithromycin have not been performed.

Elimination

Specific Populations

Patients with Renal Impairment

max

and AUC

0-120

increased by 5.1% and 4.2%, respectively in subjects with mild to moderate renal impairment (GFR 10 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 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 studies with intravenous azithromycin have not been performed in older volunteers. Pharmacokinetics of azithromycin following oral administration in older volunteers (65 – 85 years old) were similar to those in younger volunteers (18 – 40 years old) for the 5-day therapeutic regimen

[see Geriatric Use (

8.5

)].

Pediatric Patients

Pharmacokinetic studies with intravenous azithromycin have not been performed in children.

Drug Interaction Studies

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

Ratio (with/without azithromycin) of

Co-administered Drug Pharmacokinetic Parameters (90% CI); No Effect = 1.00

Mean C

max

Mean AUC

* – 90% Confidence interval not reported

Atorvastatin

10 mg/day for 8 days

500 mg/day orally on days 6 to 8

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

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

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

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

1.04*

0.95*

Fluconazole

200 mg orally single dose

1,200 mg orally single dose

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

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

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

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

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

1.19

(1.02 to 1.40)

1.02

(0.86 to 1.22)

Theophylline

300 mg orally BID × 15 days

500 mg orally on day 6,

then 250 mg/day on days 7 to 10

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

1.06*

1.02*

Trimethoprim/ Sulfamethoxazole

160 mg/800 mg/day orally for 7 days

1,200 mg orally on day 7

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

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

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 (

7.3

)]

Co-administered Drug

Dose of Co

‑

administered Drug

Dose of Azithromycin

Ratio (with/without

‑

administered drug) of

Azithromycin Pharmacokinetic

Parameters (90% CI);

No Effect = 1.00

Mean C

max

Mean AUC

* – 90% Confidence interval not reported]

Efavirenz

400 mg/day for 7 days

600 mg orally on day 7

1.22

(1.04 to 1.42)

0.92*

Fluconazole

200 mg orally single dose

1,200 mg orally single dose

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

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

phenotype).

Antimicrobial Activity

Azithromycin has been shown to be active against the following microorganisms, both

in vitro

and in clinical infections

[see Indications and Usage (

)].

Gram-positive Bacteria

Staphylococcus aureus

Streptococcus pneumoniae

Gram-negative Bacteria

Haemophilus influenzae

Moraxella catarrhalis

Neisseria gonorrhoeae

Legionella pneumophila

Other Bacteria

Chlamydophila pneumoniae

Chlamydia trachomatis

Mycoplasma hominis

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.

Aerobic Gram-Positive Bacteria

Streptococci (Groups C, F, G)

Viridans group streptococci

Gram-Negative Bacteria

Bordetella pertussis

Anaerobic Bacteria

Peptostreptococcus

species

Prevotella bivia

Other Bacteria

Ureaplasma urealyticum

Susceptibility Testing

================================================================================
TABLE: Table
================================================================================

================================================================================
TABLE: Table 1. Drug Interactions: Pharmacokinetic Parameters for Co-Administered Drugs in the Presence of Azithromycin
================================================================================

================================================================================
TABLE: Table 2. Drug Interactions: Pharmacokinetic Parameters for Azithromycin in the Presence of Co-Administered Drugs [see Drug Interactions (7.3)]
================================================================================

Pharmacodynamics

Studies in animals show that azithromycin works better against some germs when there is more medicine in the blood for a longer time. Doctors are still learning which blood levels work best in people.

Heart Rhythm Effects

Doctors studied how azithromycin affects heart rhythm in 116 healthy people. They gave some people chloroquine alone and others got chloroquine plus different amounts of azithromycin (500 mg, 1000 mg, or 1500 mg once daily). Taking azithromycin with chloroquine changed the heart rhythm slightly. Higher doses of azithromycin caused bigger changes. Compared to chloroquine alone, the heart rhythm changes were 5 ms with 500 mg azithromycin, 7 ms with 1000 mg, and 9 ms with 1500 mg.

When azithromycin is given through an IV, blood levels get higher than when taking pills by mouth. This means IV azithromycin might cause bigger heart rhythm changes, especially right after the one-hour IV treatment.

Cardiac Electrophysiology

Pharmacokinetics

**How Azithromycin Works in Your Body**

When patients with pneumonia got azithromycin through an IV for 2 to 5 days, doctors measured how much medicine was in their blood. The highest amount was 3.63 mcg/mL. After 24 hours, only 0.20 mcg/mL was left.

When healthy people got the same dose over 3 hours instead of 1 hour, the highest amount in their blood was lower at 1.14 mcg/mL. After 24 hours, 0.18 mcg/mL was left.

Here’s how the medicine levels changed over time in two different groups:

**1-hour IV (pneumonia patients):**
• At 1 hour: 3.63 mcg/mL
• At 6 hours: 0.33 mcg/mL
• At 24 hours: 0.20 mcg/mL

**3-hour IV (healthy people):**
• At 3 hours: 1.14 mcg/mL
• At 6 hours: 0.32 mcg/mL
• At 24 hours: 0.18 mcg/mL

After 5 days of treatment, the medicine built up more in the body. The highest blood level only went up 8%, but the total amount over 24 hours went up 61%.

**Pills vs IV**

When people took azithromycin pills instead of IV, the blood levels were much lower. Pills gave about half the amount compared to IV medicine.

**Where the Medicine Goes**

The medicine sticks to blood proteins differently depending on how much is in your blood. At low levels, 51% sticks to proteins. At higher levels, only 7% sticks to proteins.

The medicine goes into body tissues well. In women having surgery, doctors found the medicine in ovaries, uterus, and fallopian tubes about 17 hours after taking a pill. However, very little gets into the fluid around the brain and spinal cord.

**How Your Body Removes the Medicine**

Your body doesn’t change azithromycin much before getting rid of it.

The medicine stays in your body for a long time. It takes about 68 hours for half of it to leave your blood. This happens because tissues hold onto the medicine and then slowly release it back into the blood.

Your kidneys remove about 11-14% of IV azithromycin in urine within 24 hours. This is more than the 6% removed when you take pills. Your liver removes most of the medicine through bile.

**Special Patient Groups**

**Kidney Problems:**
People with mild to moderate kidney problems had almost the same blood levels as people with normal kidneys. People with severe kidney problems had 61% higher peak levels and 35% higher total amounts.

**Liver Problems:**
No studies have been done in people with liver problems.

**Men vs Women:**
The medicine works the same in men and women. No dose changes are needed.

**Older Adults:**
Studies with IV azithromycin haven’t been done in older people. When older people took pills, the medicine worked the same as in younger people.

**Children:**
No studies with IV azithromycin have been done in children.

**Drug Interactions**

Studies were done to see how azithromycin affects other medicines and how other medicines affect azithromycin.

**Other Medicines with Azithromycin:**

• Atorvastatin: Small decrease in blood levels
• Carbamazepine: No significant change
• Cetirizine: No significant change
• Didanosine: Small increase in blood levels
• Efavirenz: Small changes in both medicines
• Fluconazole: No significant change
• Indinavir: Small decrease in blood levels
• Midazolam: Small increase in blood levels
• Nelfinavir: Small decrease, but nelfinavir greatly increased azithromycin levels
• Sildenafil: No significant change
• Theophylline: Small increase in blood levels
• Triazolam: No significant change
• Trimethoprim/Sulfamethoxazole: Small decrease in blood levels
• Zidovudine: No significant change

Most of these changes were small and don’t require dose adjustments.

**Medicines That Affect Azithromycin:**

• Efavirenz: Increased peak levels but decreased total amount
• Fluconazole: Small decrease in peak levels
• Nelfinavir: Large increases in azithromycin levels (more than double)

No dose changes are recommended even with these interactions.

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.

Metabolism

In vitroandin vivostudies to assess the metabolism of azithromycin have not been performed.

Elimination

Specific Populations

Patients with Renal Impairment

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 studies with intravenous azithromycin have not been performed in older volunteers. Pharmacokinetics of azithromycin following oral administration in older volunteers (65 – 85 years old) were similar to those in younger volunteers (18 – 40 years old) for the 5-day therapeutic regimen[see Geriatric Use (8.5)].

Pediatric Patients

Pharmacokinetic studies with intravenous azithromycin have not been performed in children.

Drug Interaction Studies

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

Antimicrobial Activity

Azithromycin has been shown to be active against the following microorganisms, bothin vitroand in clinical infections[see Indications and Usage (1)].

Gram-positive Bacteria

Staphylococcus aureus

Streptococcus pneumoniae

Gram-negative Bacteria

Haemophilus influenzae

Moraxella catarrhalis

Neisseria gonorrhoeae

Legionella pneumophila

Other Bacteria

Chlamydophila pneumoniae

Chlamydia trachomatis

Mycoplasma hominis

Mycoplasma pneumoniae

Aerobic Gram-Positive Bacteria

Streptococci (Groups C, F, G)

Viridans group streptococci

Gram-Negative Bacteria

Bordetella pertussis

Anaerobic Bacteria

Peptostreptococcusspecies

Prevotella bivia

Other Bacteria

Ureaplasma urealyticum

Susceptibility Testing

Nonclinical Toxicology

**Cancer and Gene Changes**

Long-term studies have not been done to see if azithromycin causes cancer in animals. Tests show that azithromycin does not cause harmful changes to genes.

**Effects on Getting Pregnant**

Studies in rats showed that azithromycin made it slightly harder to get pregnant when both male and female rats were given the medicine. The pregnancy rate went down by about 12%. This only happened when both animals were treated. When only one animal got the medicine, there was no problem.

Lower doses did not affect pregnancy at all. It is not clear if this would happen in people taking normal doses of azithromycin.

**Fat Buildup in Body Tissues**

When animals were given azithromycin for many days, fat-like substances built up in their body tissues. This happened in the eyes, nerves, liver, gallbladder, kidneys, spleen, and pancreas of dogs and rats.

This fat buildup happened even at doses similar to what people normally take. The good news is that this effect went away after the animals stopped taking azithromycin.

The same fat buildup was seen in young rats and dogs given the medicine. It is not known if this fat buildup would happen in people or if it would cause problems.

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 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 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.

Phospholipidosis (intracellular phospholipid accumulation) has been observed in some tissues of mice, rats, and dogs given multiple oral 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 Cmaxof 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 Cmaxof 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 body 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 Cmaxof 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 Cmax. The significance of the findings for animals and for humans is unknown.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

13.2 Animal Toxicology and/or Pharmacology

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).

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 the findings for animals and for humans is unknown.

Clinical Studies

**Studies on Pneumonia Treatment**

Doctors tested azithromycin (an antibiotic) to see how well it works for pneumonia. They compared it to other antibiotics.

**First Study**

291 patients with pneumonia got either azithromycin or another antibiotic called cefuroxime. Doctors checked how patients were doing 10-14 days after treatment:

• Azithromycin: 78% of patients were cured or got better
• Other antibiotic: 74% of patients were cured or got better

**Second Study**

94 patients with pneumonia got azithromycin. After 10-14 days:

• 89% of patients were cured or got better

**How Well the Medicine Killed Germs**

Azithromycin got rid of different types of germs that cause pneumonia:

• S. pneumoniae germs: killed in 96% of patients
• H. influenzae germs: killed in 95% of patients
• M. catarrhalis germs: killed in 90% of patients
• S. aureus germs: killed in 90% of patients

**Special Types of Pneumonia Germs**

Some patients had harder-to-treat germs. Azithromycin helped most of these patients too:

• Mycoplasma pneumoniae: 89% got better or were cured
• Chlamydia pneumoniae: 82% got better or were cured
• Legionella pneumophila: 81% got better or were cured

In a controlled trial of community-acquired pneumonia performed in the U.S., azithromycin (500 mg as a single daily dose by the intravenous route for 2 to 5 days, followed by 500 mg/day by the oral route to complete 7 to 10 days therapy) was compared to cefuroxime (2250 mg/day in three divided doses by the intravenous route for 2 to 5 days followed by 1000 mg/day in two divided doses by the oral route to complete 7 to 10 days therapy), with or without erythromycin. For the 291 patients who were evaluable for clinical efficacy, the clinical outcome rates, i.e., cure, improved, and success (cure + improved) among the 277 patients seen at 10 to 14 days post-therapy were as follows:

Clinical OutcomeAzithromycinComparatorCure46%44%Improved32%30%Success (Cure + Improved)78%74%

In a separate, uncontrolled clinical and microbiological trial performed in the U.S., 94 patients with community-acquired pneumonia who received azithromycin in the same regimen were evaluable for clinical efficacy. The clinical outcome rates, i.e., cure, improved, and success (cure + improved) among the 84 patients seen at 10 to 14 days post-therapy were as follows:

Clinical OutcomeAzithromycinCure60%Improved29%Success (Cure + Improved)89%

Microbiological determinations in both trials were made at the pre-treatment visit and, where applicable, were reassessed at later visits. Serological testing was done on baseline and final visit specimens. The following combined presumptive bacteriological eradication rates were obtained from the evaluable groups:

Combined Bacteriological Eradication Rates for Azithromycin:

aNineteen of twenty-four patients (79%) with positive blood cultures forS. pneumoniaewere cured (intent-to-treat analysis) with eradication of the pathogen.(at last completed visit)AzithromycinS. pneumoniae64/67 (96%)aH. influenzae41/43 (95%)M. catarrhalis9/10 (90%)S. aureus9/10 (90%)

The presumed bacteriological outcomes at 10 to 14 days post-therapy for patients treated with azithromycin with evidence (serology and/or culture) of atypical pathogens for both trials were as follows:

Evidence of InfectionTotalCureImprovedCure + ImprovedMycoplasma pneumoniae1811 (61%)5 (28%)16 (89%)Chlamydia pneumoniae3415 (44%)13 (38%)28 (82%)Legionella pneumophila165 (31%)8 (50%)13 (81%)

14.1 Community-Acquired Pneumonia

Clinical Outcome

Azithromycin

Comparator

Cure

46%

44%

Improved

32%

30%

Success (Cure + Improved)

78%

74%

Clinical Outcome

Azithromycin

Cure

60%

Improved

29%

Success (Cure + Improved)

89%

Combined Bacteriological Eradication Rates for Azithromycin:

Nineteen of twenty-four patients (79%) with positive blood cultures for

S. pneumoniae

were cured (intent-to-treat analysis) with eradication of the pathogen.

(at last completed visit)

Azithromycin

S. pneumoniae

64/67 (96%)

H. influenzae

41/43 (95%)

M. catarrhalis

9/10 (90%)

S. aureus

9/10 (90%)

Evidence of Infection

Total

Cure

Improved

Cure + Improved

Mycoplasma pneumoniae

11 (61%)

5 (28%)

16 (89%)

Chlamydia pneumoniae

15 (44%)

13 (38%)

28 (82%)

Legionella pneumophila

5 (31%)

8 (50%)

13 (81%)

================================================================================
TABLE: Table
================================================================================

+—————————–+—————-+————–+
| Clinical Outcome | Azithromycin | Comparator |
+—————————–+—————-+————–+
| Cure | 46% | 44% |
| Improved | 32% | 30% |
| Success (Cure + Improved) | 78% | 74% |
+—————————–+—————-+————–+

================================================================================
TABLE: Table
================================================================================

+—————————–+—————-+
| Clinical Outcome | Azithromycin |
+—————————–+—————-+
| Cure | 60% |
| Improved | 29% |
| Success (Cure + Improved) | 89% |
+—————————–+—————-+

================================================================================
TABLE: Table
================================================================================

+————————–+———+————+————+——————-+
| Evidence of Infection | Total | Cure | Improved | Cure + Improved |
+————————–+———+————+————+——————-+
| Mycoplasma pneumoniae | 18 | 11 (61%) | 5 (28%) | 16 (89%) |
| Chlamydia pneumoniae | 34 | 15 (44%) | 13 (38%) | 28 (82%) |
| Legionella pneumophila | 16 | 5 (31%) | 8 (50%) | 13 (81%) |
+————————–+———+————+————+——————-+

Patient Counseling Information

You should know about these serious side effects that can happen with azithromycin injection.

Diarrhea: Diarrhea is a common problem caused by antibiotic medicines. It usually stops when you stop taking the antibiotic. Sometimes after starting treatment with antibiotics, you can get watery and bloody stools. You might also have stomach cramps and fever. This can happen even 2 or more months after your last dose of the antibiotic. If this happens, call your doctor right away.

This product’s label may have been updated. For current full prescribing information, please visit www.slaterunpharma.com/products.

Rx only

Made by: Hainan Poly Pharm Co., Ltd., China, Guilinyang Economic Development Zone, Haikou, Hainan Province, China 571127

Distributed by: Slate Run Pharmaceuticals, LLC, Columbus, Ohio 43215

10000142/05

Revised March 2022

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.

This product’s label may have been updated. For current full prescribing information, please visit www.slaterunpharma.com/products.

Rx only

Manufactured by:Hainan Poly Pharm Co., Ltd., ChinaGuilinyang Economic Development Zone, Haikou, Hainan Province, China 571127

Distributed by:Slate Run Pharmaceuticals, LLC, Columbus, Ohio 43215

10000142/05

Revised March 2022

AZITHROMYCIN (azithromycin)

azithromycin

Quick Facts

Indications and Usage

Dosage and Administration

Dosage Forms and Strengths

Contraindications

Warnings and Precautions

Adverse Reactions

Drug Interactions

Pregnancy

Lactation

Pediatric Use

Geriatric Use

Description

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Pharmacodynamics

Pharmacokinetics

Microbiology

Nonclinical Toxicology

Clinical Studies

Patient Counseling Information

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