AZITHROMYCIN powder, for suspension

United States - English - NLM (National Library of Medicine)

Buy It Now

Active ingredient:
AZITHROMYCIN MONOHYDRATE (UNII: JTE4MNN1MD) (AZITHROMYCIN ANHYDROUS - UNII:J2KLZ20U1M)
Available from:
RPK Pharmaceuticals, Inc.
Administration route:
PARENTERAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Azithromycin for oral suspension USP is a macrolide antibacterial drug indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the specific conditions listed below. Recommended dosages and durations of therapy in adult and pediatric patient populations vary in these indications. [see Dosage and Administration (2) ] Azithromycin for oral suspension is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide drug. Azithromycin for oral suspension is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin. Risk Summary Available data from published literature and postmarketing experience over several decades with azithromycin use in pregnant women have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data) . Developmental toxicity s
Product summary:
Product: 53002-2231 NDC: 53002-2231-1 15 mL in a BOTTLE, PLASTIC NDC: 53002-2231-2 30 mL in a BOTTLE, PLASTIC
Authorization status:
Abbreviated New Drug Application
Authorization number:
53002-2231-1, 53002-2231-2

Read the complete document

AZITHROMYCIN- azithromycin powder, for suspension

RPK Pharmaceuticals, Inc.

----------

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use AZITHROMYCIN FOR ORAL SUSPENSION

safely and effectively. See full prescribing information for AZITHROMYCIN FOR ORAL SUSPENSION.

AZITHROMYCIN for oral suspension

Initial U.S. Approval: 1991

INDICATIONS AND USAGE

Azithromycin for oral suspension USP is a macrolide antibacterial drug indicated for mild to moderate infections caused by

designated, susceptible bacteria:

Limitation of Use:

Azithromycin should not be used in patients with pneumonia who are judged to be inappropriate for oral therapy because

of moderate to severe illness or risk factors. (1.3)

To reduce the development of drug-resistant bacteria and maintain the effectiveness of azithromycin for oral suspension

USP and other antibacterial drugs, azithromycin for oral suspension USP should be used only to treat infections that are

proven or strongly suspected to be caused by susceptible bacteria. (1.4)

DOSAGE AND ADMINISTRATION

Acute bacterial exacerbations of chronic bronchitis in adults (1.1)

Acute bacterial sinusitis in adults (1.1)

Uncomplicated skin and skin structure infections in adults (1.1)

Urethritis and cervicitis in adults (1.1)

Genital ulcer disease in men (1.1)

Acute otitis media in pediatric patients (1.2)

Community-acquired pneumonia in adults and pediatric patients (1.1, 1.2)

Pharyngitis/tonsillitis in adults and pediatric patients (1.1, 1.2)

Adult Patients (2.1)

Infe c tio n

Recommended Dose/Duration of Therapy

Community-acquired pneumonia (mild severity)

Pharyngitis/tonsillitis (second-line therapy)

Skin/skin structure (uncomplicated)

500 mg as a single dose on Day 1, followed by 250 mg

once daily on Days 2 through 5.

Acute bacterial exacerbations of chronic bronchitis

(mild to moderate)

500 mg as a single dose on Day 1, followed by 250 mg

once daily on Days 2 through 5 or 500 mg once daily

for 3 days.

Acute bacterial sinusitis

500 mg once daily for 3 days.

Genital ulcer disease (chancroid)

Non-gonococcal urethritis and cervicitis

One single 1 gram dose.

Gonococcal urethritis and cervicitis

One single 2 gram dose.

Pediatric Patient(2.2)

Infe c tio n

Recommended Dose/Duration of Therapy

Acute otitis media (6 months of age and older)

30 mg/kg as a single dose or 10 mg/kg once daily for 3

days or 10 mg/kg as a single dose on Day 1 followed by

5 mg/kg/day on Days 2 through 5.

Acute bacterial sinusitis (6 months of age and older)

10 mg/kg once daily for 3 days.

Community-acquired pneumonia (6 months of age and

10 mg/kg as a single dose on Day 1 followed by 5

DOSAGE FORMS AND STRENGTHS

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS

ADVERSE REACTIONS

Most common adverse reactions are diarrhea (5 to 14%), nausea (3 to 18%), abdominal pain (3 to 7 %), or vomiting (2 to 7

%). (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Epic Pharma, LLC at 1-888-374-2791 or FDA at 1-800-

FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

USE IN SPECIFIC POPULATIONS

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

Revised: 12/2020

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

2.1 Adult Patients

2.2 Pediatric Patients

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

4.1 Hypersensitivity

olde r)

mg/kg once daily on Days 2 through 5.

Pharyngitis/tonsillitis (2 years of age and older)

12 mg/kg once daily for 5 days.

Azithromycin for oral suspension 100 mg/5 mL and 200 mg/5 mL (3)

Patients with known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide drug. (4.1)

Patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin. (4.2)

Serious (including fatal) allergic and skin reactions: Discontinue azithromycin if reaction occurs. (5.1)

Hepatotoxicity: Severe, and sometimes fatal, hepatotoxicity has been reported. Discontinue azithromycin

immediately if signs and symptoms of hepatitis occur. (5.2)

Infantile Hypertrophic Pyloric Stenosis (IHPS): Following the use of azithromycin in neonates (treatment up to 42

days of life), IHPS has been reported. Direct parents and caregivers to contact their physician if vomiting or irritability

with feeding occurs. (5.3)

Prolongation of QT interval and cases of torsades de pointes have been reported. This risk which can be fatal should

be considered in patients with certain cardiovascular disorders including known QT prolongation or history torsades

de pointes, those with proarrhythmic conditions, and with other drugs that prolong the QT interval. (5.4)

Clostridium difficile-associated diarrhea: Evaluate patients if diarrhea occurs. (5.5)

Azithromycin may exacerbate muscle weakness in persons with myasthenia gravis. (5.6)

Nelfinavir: Close monitoring for known adverse reactions of azithromycin, such as liver enzyme abnormalities and

hearing impairment, is warranted. (7.1)

Warfarin: Use with azithromycin may increase coagulation times; monitor prothrombin time. (7.2)

Pediatric use: Safety and effectiveness in the treatment of patients under 6 months of age have not been established.

(8.4)

Geriatric use: Elderly patients may be more susceptible to development of torsades de pointes arrhythmias. (8.5)

4.2 Hepatic Dysfunction

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity

5.2 Hepatotoxicity

5.3 Infantile Hypertrophic Pyloric Stenosis(IHPS)

5.4 QT Prolongation

5.5 Clostridium difficile-Associated Diarrhea (CDAD)

5.6 Exacerbation of Myasthenia Gravis

5.7 Use in Sexually Transmitted Infections

5.8 Development of Drug-Resistant Bacteria

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

6.3 Laboratory Abnormalities

7 DRUG INTERACTIONS

7.1 Nelfinavir

7.2 Warfarin

7.3 Potential Drug-Drug Interaction with Macrolides

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

8.5 Geriatric Use

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

12.4 Microbiology

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

13.2 Animal Toxicology and/or Pharmacology

14 CLINICAL STUDIES

14.1 Adult Patients

14.2 Pediatric Patients

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

Azithromycin for oral suspension USP is a macrolide antibacterial drug indicated for the treatment of

patients with mild to moderate infections caused by susceptible strains of the designated

microorganisms in the specific conditions listed below. Recommended dosages and durations of

therapy in adult and pediatric patient populations vary in these indications. [see Dosage and

Administration (2)]

Sections or subsections omitted from the full prescribing information are not listed.

2 DOSAGE AND ADMINISTRATION

2.1 Adult Patients

[see Indications and Usage (1.1) and Clinical Pharmacology (12.3)]

Infection*

Recommended Dose/Duration of Therapy

Community-acquired pneumonia

Pharyngitis/tonsillitis (second-line therapy)

Skin/skin structure (uncomplicated)

500 mg as a single dose on Day 1, followed by 250

mg once daily on Days 2 through 5

Acute bacterial exacerbations of chronic

obstructive pulmonary disease

500 mg once daily for 3 days

500 mg as a single dose on Day 1, followed by 250

mg once daily on Days 2 through 5

Acute bacterial sinusitis

500 mg-once daily for 3 days

Genital ulcer disease (chancroid)

One single 1 gram dose

Non-gonococcal urethritis and cervicitis

One single 1 gram dose

Gonococcal urethritis and cervicitis

One single 2 gram dose

*DUE TO THE INDICATED ORGANISMS [see Indications and Usage (1.1)]

Azithromycin tablets can be taken with or without food.

2.2 Pediatric Patients

Infection*

Recommended Dose/Duration of Therapy

Acute otitis media

30 mg/kg as a single dose or 10 mg/kg once daily

for 3 days or 10 mg/kg as a single dose on Day 1

followed by 5 mg/kg/day on Days 2 through 5.

Acute bacterial sinusitis

10 mg/kg once daily for 3 days.

Community-acquired pneumonia

10 mg/kg as a single dose on Day 1 followed by 5

mg/kg once daily on Days 2 through 5.

Pharyngitis/tonsillitis

12 mg/kg once daily for 5 days.

*DUE TO THE INDICATED ORGANISMS [see Indications and Usage (1.2)]

see dosing tables below for maximum doses evaluated by indication

Azithromycin for oral suspension can be taken with or without food.

PEDIATRIC DOSAGE GUIDELINES FOR OTITIS MEDIA, ACUTE BACTERIAL

SINUSITIS, AND COMMUNITY-ACQUIRED PNEUMONIA

(Age 6 months and above, [see Use in Specific Populations (8.4)])

Based on Body Weight

OTITIS MEDIA AND COMMUNITY-ACQUIRED PNEUMONIA: (5-Day Regimen)*

Dosing Calculated on 10 mg/kg/day Day 1 and 5 mg/kg/day Days 2 to 5.

Weight

100 mg/5 mL

200 mg/5 mL

Total mL per

Treatment

Cours e

Total mg

per

Treatment

Cours e

Kg

Day 1

Days 2-5

Day 1

Days 2-5

2.5 mL; (½ tsp)

1.25 mL; (¼ tsp)

7.5 mL

150 mg

5 mL; (1 tsp)

2.5 mL; (½ tsp)

15 mL

300 mg

1

1

5 mL;

(1 tsp)

2.5 mL;

(½ tsp)

15 mL

600 mg

7.5 mL;

(1½ tsp)

3.75 mL;

(¾ tsp)

22.5 mL

900 mg

10 mL;

(2 tsp)

5 mL;

(1 tsp)

30 mL

1200 mg

50 and above

12.5 mL; (2½

tsp)

6.25 mL;

(1¼ tsp)

37.5 mL

1500 mg

*Effectiveness of the 3-day or 1-day regimen in pediatric patients with community-acquired pneumonia

has not been established.

OTITIS MEDIA AND ACUTE BACTERIAL SINUSITIS: (3-Day Regimen)*

Dosing Calculated on 10 mg/kg/day.

Weight

100 mg/5 mL

200 mg/5 mL

Total mL per

Treatment

Cours e

Total mg per

Treatment

Cours e

Kg

Days 1-3

Days 1-3

2.5 mL; (½ tsp)

7.5 mL

150 mg

5 mL; (1 tsp)

15 mL

300 mg

5 mL

(1 tsp)

15 mL

600 mg

7.5 mL

(1½ tsp)

22.5 mL

900 mg

10 mL

(2 tsp)

30 mL

1200 mg

50 and above

12.5 mL

(2½ tsp)

37.5 mL

1500 mg

*Effectiveness of the 5-day or 1-day regimen in pediatric patients with acute bacterial sinusitis has not

been established.

OTITIS MEDIA: (1-Day Regimen)

Dosing Calculated on 30mg/kg as a single dose.

Weight

200 mg/5 mL

Total mL per

Treatment Course

Total mg per

Treatment Course

Kg

1-Day Regimen

3.75 mL; (¾ tsp)

3.75 mL

150 mg

7.5 mL; (1½ tsp)

7.5 mL

300 mg

15 mL; (3 tsp)

15 mL

600 mg

22.5 mL; ( 4½ tsp)

22.5 mL

900 mg

30 mL;(6 tsp)

30 mL

1200 mg

50 and above

37.5 mL; (7½ tsp)

37.5 mL

1500 mg

The safety of re-dosing azithromycin in pediatric patients who vomit after receiving 30 mg/kg as a

single dose has not been established. In clinical studies involving 487 patients with acute otitis media

given a single 30 mg/kg dose of azithromycin, 8 patients who vomited within 30 minutes of dosing were

re-dosed at the same total dose.

Pharyngitis/Tonsillitis: The recommended dose of azithromycin for children with pharyngitis/tonsillitis

is 12 mg/kg once daily for 5 days. (See chart below.)

PEDIATRIC DOSAGE GUIDELINES FOR PHARYNGITIS/TONSILLITIS

(Age 2 years and above, [see Use in Specific Populations (8.4)])

Based on Body Weight

PHARYNGITIS/TONSILLITIS: (5-Day Regimen)

Dosing Calculated on 12 mg/kg/day for 5 days.

Weight

200 mg/5 mL

Total mL per

Treatment Course

Total mg per

Treatment Course

Kg

Day 1-5

2.5 mL; (½ tsp)

12.5 mL

500 mg

5 mL; (1 tsp)

25 mL

1000 mg

7.5 mL; (1½ tsp)

37.5 mL

1500 mg

10 mL; (2 tsp)

50 mL

2000 mg

12.5 mL; (2½ tsp)

62.5 mL

2500 mg

Constituting instructions for Azithromycin Oral Suspension 300, 600, 900, 1200 mg bottles. The table

below indicates the volume of water to be used for constitution:

Amount of water to be added

Total volume after constitution

(azithromycin content)

Azithromycin concentration

after constitution

9 mL (300 mg)

15 mL (300 mg)

100 mg/5 mL

9 mL (600 mg)

15 mL (600 mg)

200 mg/5 mL

12 mL (900 mg)

22.5 mL (900 mg)

200 mg/5 mL

15 mL (1200 mg)

30 mL (1200 mg)

200 mg/5 mL

Shake well before each use. Oversized bottle provides shake space. Keep tightly closed.

After mixing, store suspension at 5° to 30°C (41° to 86°F) and use within 10 days. Discard after full

dosing is completed.

3 DOSAGE FORMS AND STRENGTHS

Azithromycin for oral suspension USP after constitution contains a banana-cherry flavored suspension.

Azithromycin for oral suspension USP is supplied to provide 100 mg/5 mL or 200 mg/5 mL suspension

in bottles.

4 CONTRAINDICATIONS

4.1 Hypersensitivity

Azithromycin for oral suspension is contraindicated in patients with known hypersensitivity to

azithromycin, erythromycin, any macrolide or ketolide drug.

4.2 Hepatic Dysfunction

Azithromycin for oral suspension is contraindicated in patients with a history of cholestatic

jaundice/hepatic dysfunction associated with prior use of azithromycin.

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity

Serious allergic reactions, including angioedema, anaphylaxis, and dermatologic reactions including

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 presently unknown.

If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be

instituted. Physicians should be aware that allergic symptoms may reappear when symptomatic therapy

has been discontinued.

5.2 Hepatotoxicity

Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure have been

reported, some of which have resulted in death. Discontinue azithromycin immediately if signs and

symptoms of hepatitis occur.

5.3 Infantile Hypertrophic Pyloric Stenosis(IHPS)

Following the use of azithromycin in neonates (treatment up to 42 days of life), IHPS has been reported.

Direct parents and caregivers to contact their physician if vomiting or irritability with feeding occurs.

5.4 QT Prolongation

Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and

torsades de pointes, have been seen with treatment with macrolides, including azithromycin. Cases of

torsades de pointes have been spontaneously reported during postmarketing surveillance in patients

receiving azithromycin. Providers should consider the risk of QT prolongation which can be fatal when

weighing the risks and benefits of azithromycin for at-risk groups including:

Elderly patients may be more susceptible to drug-associated effects on the QT interval.

5.5 Clostridium difficile-Associated Diarrhea (CDAD)

Clostridium difficile-associated diarrhea has been reported with use of nearly all antibacterial agents,

including azithromycin, and may range in severity from mild diarrhea to fatal colitis. Treatment with

antibacterial agents alters the normal flora of the colon, leading to overgrowth of C. difficile.

C. difficileproduces toxins A and B which contribute to the development of CDAD. Hypertoxin

producing strains of C. 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 antibiotic 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 antibiotic use not directed against C. difficile may need to

be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic

treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

5.6 Exacerbation of Myasthenia Gravis

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.

Exacerbation of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been

reported in patients receiving azithromycin therapy.

5.7 Use in Sexually Transmitted Infections

Azithromycin, at the recommended dose, should not be relied upon to treat syphilis. Antibacterial agents

used to treat non-gonococcal urethritis may mask or delay the symptoms of incubating syphilis. All

patients with sexually transmitted urethritis or cervicitis should have a serologic test for syphilis and

appropriate testing for gonorrhea performed at the time of diagnosis. Appropriate antibacterial therapy

and follow-up tests for these diseases should be initiated if infection is confirmed.

5.8 Development of Drug-Resistant Bacteria

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.

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed

in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug

and may not reflect the rates observed in practice.

In clinical trials, most of the reported side effects were mild to moderate in severity and were

reversible upon discontinuation of the drug. Potentially serious adverse reactions of angioedema and

cholestatic jaundice were reported. Approximately 0.7% of the patients (adults and pediatric patients)

from the 5-day multiple-dose clinical trials discontinued azithromycin therapy because of treatment-

related adverse reactions. In adults given 500 mg/day for 3 days, the discontinuation rate due to

treatment-related adverse reactions was 0.6%. In clinical trials in pediatric patients given 30 mg/kg,

either as a single dose or over 3 days, discontinuation from the trials due to treatment-related adverse

reactions was approximately 1%. Most of the adverse reactions leading to discontinuation were related

to the gastrointestinal tract, e.g., nausea, vomiting, diarrhea, or abdominal pain. [see Clinical Studies

(14.2)]

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of azithromycin.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always

possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse reactions reported with azithromycin during the postmarketing period in adult and/or pediatric

patients for which a causal relationship may not be established include:

Allergic: Arthralgia, edema, urticaria, and angioedema.

Cardiovascular: Arrhythmias including ventricular tachycardia and hypotension. There have been

reports of QT prolongation and torsades de pointes.

Gastrointestinal: Anorexia, constipation, dyspepsia, flatulence, vomiting/diarrhea, pseudomembranous

colitis, pancreatitis, oral candidiasis, pyloric stenosis, and reports of tongue discoloration.

General: Asthenia, paresthesia, fatigue, malaise, and anaphylaxis

Genitourinary: Interstitial nephritis 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, Stevens-Johnson

Syndrome, toxic epidermal necrolysis, and DRESS.

Special Senses: Hearing disturbances including hearing loss, deafness and/or tinnitus, and reports of

taste/smell perversion and/or loss.

6.3 Laboratory Abnormalities

Adults:

Clinically significant abnormalities (irrespective of drug relationship) occurring during the clinical

trials were reported as follows: with an incidence of greater than 1%: decreased hemoglobin,

hematocrit, lymphocytes, neutrophils, and blood glucose; elevated serum creatine phosphokinase,

potassium, ALT, GGT, AST, BUN, creatinine, blood glucose, platelet count, lymphocytes, neutrophils,

and eosinophils; with an incidence of less than 1%: leukopenia, neutropenia, decreased sodium,

potassium, platelet count, elevated monocytes, basophils, bicarbonate, serum alkaline phosphatase,

bilirubin, LDH, and phosphate. The majority of subjects with elevated serum creatinine also had

abnormal values at baseline. When follow-up was provided, changes in laboratory tests appeared to be

reversible.

In multiple-dose clinical trials involving more than 5000 patients, four patients discontinued therapy

because of treatment-related liver enzyme abnormalities and one because of a renal function

abnormality.

Pediatric Patients:

One, Three, and Five-Day Regimens

Laboratory data collected from comparative clinical trials employing two 3-day regimens (30 mg/kg or

60 mg/kg in divided doses over 3 days), or two 5-day regimens (30 mg/kg or 60 mg/kg in divided doses

over 5 days) were similar for regimens of azithromycin and all comparators combined, with most

clinically significant laboratory abnormalities occurring at incidences of 1-5%. Laboratory data for

patients receiving 30 mg/kg as a single dose were collected in one single center trial. In that trial, an

absolute neutrophil count between 500-1500 cells/mm was observed in 10/64 patients receiving 30

mg/kg as a single dose, 9/62 patients receiving 30 mg/kg given over 3 days, and 8/63 comparator

patients. No patient had an absolute neutrophil count <500 cells/mm .

In multiple-dose clinical trials involving approximately 4700 pediatric patients, no patients discontinued

therapy because of treatment-related laboratory abnormalities.

7 DRUG INTERACTIONS

7.1 Nelfinavir

Co-administration of nelfinavir at steady-state with a single oral dose of azithromycin resulted in

increased azithromycin serum concentrations. Although a dose adjustment of azithromycin is not

recommended when administered in combination with nelfinavir, close monitoring for known adverse

reactions of azithromycin, such as liver enzyme abnormalities and hearing impairment, is warranted. [see

Adverse Reactions (6)]

7.2 Warfarin

Spontaneous postmarketing reports suggest that concomitant administration of azithromycin may

potentiate the effects of oral anticoagulants such as warfarin, although the prothrombin time was not

potentiate the effects of oral anticoagulants such as warfarin, although the prothrombin time was not

affected in the dedicated drug interaction study with azithromycin and warfarin. Prothrombin times

should be carefully monitored while patients are receiving azithromycin and oral anticoagulants

concomitantly.

7.3 Potential Drug-Drug Interaction with Macrolides

Interactions with digoxin, colchicine or phenytoin have not been reported in clinical trials with

azithromycin. No specific drug interaction studies have been performed to evaluate potential drug-drug

interaction. However, drug interactions have been observed with other macrolide products. Until

further data are developed regarding drug interactions when digoxin or phenytoin are used with

azithromycin careful monitoring of patients is advised.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Available data from published literature and postmarketing experience over several decades with

azithromycin use in pregnant women have not identified any drug-associated risks for major birth

defects, miscarriage, or adverse maternal or fetal outcomes (see Data). Developmental toxicity studies

with azithromycin in rats, mice, and rabbits showed no drug-induced fetal malformations at doses up to

4, 2, and 2 times, respectively, an adult human daily dose of 500 mg based on body surface area.

Decreased viability and delayed development were observed in the offspring of pregnant rats

administered azithromycin from day 6 of pregnancy through weaning at a dose equivalent to 4 times an

adult human daily dose of 500 mg based on body surface area (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated populations is

unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In

the U.S. general population, the estimated background risk of major birth defects and miscarriage in

clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Human Data

Available data from published observational studies, case series, and case reports over several decades

do not suggest an increased risk for major birth defects, miscarriage, or adverse maternal or fetal

outcomes with azithromycin use in pregnant women. Limitations of these data include the lack of

randomization and inability to control for confounders such as underlying maternal disease and maternal

use of concomitant medications.

Animal Data

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

Similar products

Search alerts related to this product

View documents history

Share this information