(azithromycin dihydrate TABLET, SUSPENSION)
14 CLINICAL STUDIES
14 CLINICAL STUDIES
14.1 Adult Patients
Acute Bacterial Exacerbations of Chronic Bronchitis
In a randomized, double-blind controlled clinical trial of acute exacerbation of chronic bronchitis (AECB), azithromycin (500 mg once daily for 3 days) was compared with clarithromycin (500 mg twice daily for 10 days). The primary endpoint of this trial was the clinical cure rate at Days 21– 24. For the 304 patients analyzed in the modified intent-to-treat analysis at the Days 21–24 visit, the clinical cure rate for 3 days of azithromycin was 85% (125/147) compared to 82% (129/157) for 10 days of clarithromycin.
The following outcomes were the clinical cure rates at the Days 21–24 visit for the bacteriologically evaluable patients by pathogen:
| Pathogen | Azithromycin (3 Days) | Clarithromycin (10 Days) |
|---|---|---|
S. pneumoniae | 29/32 (91%) | 21/27 (78%) |
H. influenzae | 12/14 (86%) | 14/16 (88%) |
M. catarrhalis | 11/12 (92%) | 12/15 (80%) |
Acute Bacterial Sinusitis
In a randomized, double-blind, double-dummy controlled clinical trial of acute bacterial sinusitis, azithromycin (500 mg once daily for 3 days) was compared with amoxicillin/clavulanate (500/125 mg three times a day for 10 days). Clinical response assessments were made at Day 10 and Day 28. The primary endpoint of this trial was prospectively defined as the clinical cure rate at Day 28. For the 594 patients analyzed in the modified intent to treat analysis at the Day 10 visit, the clinical cure rate for 3 days of azithromycin was 88% (268/303) compared to 85% (248/291) for 10 days of amoxicillin/clavulanate. For the 586 patients analyzed in the modified intent to treat analysis at the Day 28 visit, the clinical cure rate for 3 days of azithromycin was 71.5% (213/298) compared to 71.5% (206/288), with a 97.5% confidence interval of –8.4 to 8.3, for 10 days of amoxicillin/clavulanate.
In an open label, non-comparative study requiring baseline transantral sinus punctures, the following outcomes were the clinical success rates at the Day 7 and Day 28 visits for the modified intent to treat patients administered 500 mg of azithromycin once daily for 3 days with the following pathogens:
| Pathogen | Day 7 | Day28 |
|---|---|---|
S. pneumoniae | 23/26 (88%) | 21/25 (84%) |
H. influenzae | 28/32 (87%) | 24/32 (75%) |
M. catarrhalis | 14/15 (93%) | 13/15 (87%) |
14.2 Pediatric Patients
From the perspective of evaluating pediatric clinical trials, Days 11–14 were considered on-therapy evaluations because of the extended half-life of azithromycin. Days 11–14 data are provided for clinical guidance. Days 24–32 evaluations were considered the primary test of cure endpoint.
Pharyngitis/Tonsillitis
In three double-blind controlled studies, conducted in the United States, azithromycin (12 mg/kg once a day for 5 days) was compared to penicillin V (250 mg three times a day for 10 days) in the treatment of pharyngitis due to documented Group A β-hemolytic streptococci (GABHS or S. pyogenes). Azithromycin was clinically and microbiologically statistically superior to penicillin at Day 14 and Day 30 with the following clinical success (i.e., cure and improvement) and bacteriologic efficacy rates (for the combined evaluable patient with documented GABHS):
| Day 14 | Day 30 | |
|---|---|---|
Bacteriologic Eradication: | ||
Azithromycin | 323/340 (95%) | 255/330 (77%) |
Penicillin V | 242/332 (73%) | 206/325 (63%) |
Clinical Success (cure plus improvement): | ||
Azithromycin | 336/343 (98%) | 310/330 (94%) |
Penicillin V | 284/338 (84%) | 241/325 (74%) |
Approximately 1% of azithromycin-susceptible S. pyogenes isolates were resistant to azithromycin following therapy.
Acute Otitis Media
Efficacy using azithromycin given over 5 days (10 mg/kg on Day 1 followed by 5 mg/kg on Days 2–5).
Trial 1
In a double-blind, controlled clinical study of acute otitis media performed in the United States, azithromycin (10 mg/kg on Day 1 followed by 5 mg/kg on Days 2–5) was compared to amoxicillin/clavulanate potassium (4:1). For the 553 patients who were evaluated for clinical efficacy, the clinical success rate (i.e., cure plus improvement) at the Day 11 visit was 88% for azithromycin and 88% for the control agent. For the 521 patients who were evaluated at the Day 30 visit, the clinical success rate was 73% for azithromycin and 71% for the control agent.
Trial 2
In a non-comparative clinical and microbiologic trial performed in the United States, where significant rates of beta-lactamase producing organisms (35%) were found, 131 patients were evaluable for clinical efficacy. The combined clinical success rate (i.e., cure and improvement) at the Day 11 visit was 84% for azithromycin. For the 122 patients who were evaluated at the Day 30 visit, the clinical success rate was 70% for azithromycin.
Microbiologic determinations were made at the pre-treatment visit. Microbiology was not reassessed at later visits. The following clinical success rates were obtained from the evaluable group:
| Pathogen | ||
|---|---|---|
| Day 11 | Day 30 | |
| Azithromycin | Azithromycin | |
S. pneumoniae | 61/74 (82%) | 40/56 (71%) |
H. influenzae | 43/54 (80%) | 30/47 (64%) |
M. catarrhalis | 28/35 (80%) | 19/26 (73%) |
S. pyogenes | 11/11 (100%) | 7/7 (100%) |
Overall | 177/217 (82%) | 97/137 (73%) |
Trial 3
In another controlled comparative clinical and microbiologic study of otitis media performed in the United States, azithromycin (10 mg/kg on Day 1 followed by 5 mg/kg on Days 2–5) was compared to amoxicillin/clavulanate potassium (4:1). This study utilized two of the same investigators as Protocol 2 (above), and these two investigators enrolled 90% of the patients in Protocol 3. For this reason, Protocol 3 was not considered to be an independent study. Significant rates of beta-lactamase producing organisms (20%) were found. Ninety-two (92) patients were evaluable for clinical and microbiologic efficacy. The combined clinical success rate (i.e., cure and improvement) of those patients with a baseline pathogen at the Day 11 visit was 88% for azithromycin vs. 100% for control; at the Day 30 visit, the clinical success rate was 82% for azithromycin vs. 80% for control.
Microbiologic determinations were made at the pre-treatment visit. Microbiology was not reassessed at later visits. At the Day 11 and Day 30 visits, the following clinical success rates were obtained from the evaluable group:
| Day 11 | Day 30 | |||
|---|---|---|---|---|
| Pathogen | Azithromycin | Control | Azithromycin | Control |
S. pneumoniae | 25/29 (86%) | 26/26 (100%) | 22/28 (79%) | 18/22 (82%) |
H. influenzae | 9/11 (82%) | 9/9 (100%) | 8/10 (80%) | 6/8 (75%) |
M. catarrhalis | 7/7 (100%) | 5/5 (100%) | 5/5 (100%) | 2/3 (66%) |
S. pyogenes | 2/2 (100%) | 5/5 (100%) | 2/2 (100%) | 4/4 (100%) |
Overall | 43/49 (88%) | 45/45 (100%) | 37/45 (82%) | 30/37 (81%) |
Efficacy using azithromycin given over 3 days (10 mg/kg/day).
Trial 4
In a double-blind, controlled, randomized clinical study of acute otitis media in pediatric patients from 6 months to 12 years of age, azithromycin (10 mg/kg per day for 3 days) was compared to amoxicillin/clavulanate potassium (7:1) in divided doses q12h for 10 days. Each patient received active drug and placebo matched for the comparator.
For the 366 patients who were evaluated for clinical efficacy at the Day 12 visit, the clinical success rate (i.e., cure plus improvement) was 83% for azithromycin and 88% for the control agent. For the 362 patients who were evaluated at the Days 24–28 visit, the clinical success rate was 74% for azithromycin and 69% for the control agent.
Efficacy using azithromycin 30 mg/kg given as a single dose
Trial 5
A double-blind, controlled, randomized trial was performed at nine clinical centers. Pediatric patients from 6 months to 12 years of age were randomized 1:1 to treatment with either azithromycin (given at 30 mg/kg as a single dose on Day 1) or amoxicillin/clavulanate potassium (7:1), divided q12h for 10 days. Each child received active drug, and placebo matched for the comparator.
Clinical response (Cure, Improvement, Failure) was evaluated at End of Therapy (Days 12–16) and Test of Cure (Days 28–32). Safety was evaluated throughout the trial for all treated subjects. For the 321 subjects who were evaluated at End of Treatment, the clinical success rate (cure plus improvement) was 87% for azithromycin, and 88% for the comparator. For the 305 subjects who were evaluated at Test of Cure, the clinical success rate was 75% for both azithromycin and the comparator.
Trial 6
In a non-comparative clinical and microbiological trial, 248 patients from 6 months to 12 years of age with documented acute otitis media were dosed with a single oral dose of azithromycin (30 mg/kg on Day 1).
For the 240 patients who were evaluable for clinical modified Intent-to-Treat (MITT) analysis, the clinical success rate (i.e., cure plus improvement) at Day 10 was 89% and for the 242 patients evaluable at Days 24–28, the clinical success rate (cure) was 85%.
| Presumed Bacteriologic Eradication | ||
|---|---|---|
| Day 10 | Days 24–28 | |
S. pneumoniae | 70/76 (92%) | 67/76 (88%) |
H. influenzae | 30/42 (71%) | 28/44 (64%) |
M. catarrhalis | 10/10 (100%) | 10/10 (100%) |
Overall | 110/128 (86%) | 105/130 (81%) |
PATIENT INFORMATION
Patient Information
ZITHROMAX® (Zith-roe-maks)
(azithromycin)
Tablets
ZITHROMAX®
(azithromycin)
Oral Suspension
Read this Patient Information leaflet before you start taking ZITHROMAX and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.
What is ZITHROMAX?
ZITHROMAX is a macrolide antibiotic prescription medicine used in adults 18 years or older to treat certain infections caused by certain germs called bacteria. These bacterial infections include:
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- acute worsening of chronic bronchitis
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- acute sinus infection
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- community-acquired pneumonia
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- infected throat or tonsils
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- skin infections
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- infections of the urethra or cervix
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- genital ulcers in men
ZITHROMAX is also used in children to treat:
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- ear infections
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- community-acquired pneumonia
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- infected throat or tonsils
Azithromycin should not be taken by people who cannot tolerate oral medications because they are very ill or have certain other risk factors including:
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- have cystic fibrosis
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- have hospital acquired infections
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- have known or suspected bacteria in the blood
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- need to be in the hospital
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- are elderly
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- have any medical problems that can lower the ability of the immune system to fight infections
ZITHROMAX is not for viral infections such as the common cold.
It is not known if ZITHROMAX is safe and effective for genital ulcers in women.
It is not known if ZITHROMAX is safe and effective for children with ear infections, sinus infections, and community-acquired pneumonia under 6 months of age.
It is not known if ZITHROMAX is safe and effective for infected throat or tonsils in children under 2 years of age.
Who should not take ZITHROMAX?
Do not take ZITHROMAX if you:
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- have had a severe allergic reaction to certain antibiotics known as macrolides or ketolides including azithromycin and erythromycin.
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- have a history of cholestatic jaundice or hepatic dysfunction that happened with the use of azithromycin.
What should I tell my healthcare provider before taking ZITHROMAX?
Before you take ZITHROMAX, tell your healthcare provider if you:
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- have pneumonia
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- have cystic fibrosis
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- have known or suspected bacteremia (bacterial infection in the blood)
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- have liver or kidney problems
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- have an irregular heartbeat, especially a problem called "QT prolongation"
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- have a problem that causes muscle weakness (myasthenia gravis)
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- have any other medical problems
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- are pregnant or plan to become pregnant. It is not known if ZITHROMAX will harm your unborn baby.
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- are breastfeeding or plan to breastfeed. ZITHROMAX has been reported to pass into breast milk. Talk to your healthcare provider about the best way to feed your baby while you take ZITHROMAX.
Contact your healthcare provider immediately if you are giving ZITHROMAX to a young child (less than 6 weeks of age) and he or she vomits or becomes irritable when fed.
Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.
ZITHROMAX and other medicines may affect each other causing side effects. ZITHROMAX may affect the way other medicines work, and other medicines may affect how ZITHROMAX works.
Especially tell your healthcare provider if you take:
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- nelfinavir
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- a blood thinner (warfarin)
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- digoxin
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- colchicine
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- phenytoin
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- an antacid that contains aluminum or magnesium
Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.
How should I take ZITHROMAX?
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- Take ZITHROMAX exactly as your healthcare provider tells you to take it.
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- ZITHROMAX can be taken with or without food.
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- If you take ZITHROMAX Oral Suspension, shake the bottle well just before you take it.
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- Do not skip any doses of ZITHROMAX or stop taking it, even if you begin to feel better, until you finish your prescribed treatment unless you have a serious allergic reaction or your healthcare provider tells you to stop taking ZITHROMAX. "See What are the possible side effects of ZITHROMAX?" If you skip doses, or do not complete the total course of ZITHROMAX your treatment may not work as well and your infection may be harder to treat. Taking all of your ZITHROMAX doses will help lower the chance that the bacteria will become resistant to ZITHROMAX.
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- If the bacteria becomes resistant to ZITHROMAX, ZITHROMAX and other antibiotic medicines may not work for you in the future.
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- If you take too much ZITHROMAX, call your healthcare provider or get medical help right away.
What are the possible side effects of ZITHROMAX?
ZITHROMAX can cause serious side effects, including:
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- Serious allergic reactions. Allergic reactions can happen in people taking azithromcyin the active ingredient in ZITHROMAX, even after only 1 dose. Stop taking ZITHROMAX and get emergency medical help right away if you have any of the following symptoms of a severe allergic reaction:
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- trouble breathing or swallowing
- o
- swelling of the lips, tongue, face
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- throat tightness, hoarseness
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- rapid heartbeat
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- faintness
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- skin rash (hives)
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- new onset of fever and swollen lymph nodes
- Stop taking ZITHROMAX at the first sign of a skin rash and call your healthcare provider. Skin rash may be a sign of a more serious reaction to ZITHROMAX.
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- Liver damage (hepatotoxicity). Hepatotoxicity can happen in people who take ZITHROMAX. Call your healthcare provider right away if you have unexplained symptoms such as:
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- Stop taking ZITHROMAX and tell your healthcare provider right away if you have yellowing of your skin or white part of your eyes, or if you have dark urine. These can be signs of a serious reaction to ZITHROMAX (a liver problem).
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- Serious heart rhythm changes that can be life-threatening, including heart stopping (cardiac arrest), QT prolongation, torsades de pointes, feeling that your heart is pounding or racing (palpitations), chest discomfort, or irregular heartbeat.
Tell your healthcare provider right away if you or your child feel a fast or irregular heartbeat, get dizzy or faint. ZITHROMAX may cause a rare heart problem known as prolongation of the QT interval. This condition can cause an abnormal heartbeat and can be very dangerous. The chances of this happening are higher in people:- o
- who are elderly
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- with a family history of prolonged QT interval
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- with low blood potassium
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- who take certain medicines to control heart rhythm (antiarrhythmics)
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- Worsening of myasthenia gravis (a problem that causes muscle weakness). Certain antibiotics like ZITHROMAX may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Call your healthcare provider right away if you have any worsening muscle weakness or breathing problems.
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- Diarrhea. Tell your healthcare provider right away if you have watery diarrhea, diarrhea that does not go away, or bloody stools. You may experience cramping and a fever. This could happen after you have finished your ZITHROMAX.
The most common side effects of ZITHROMAX include:- o
- nausea
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- stomach pain
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- vomiting
These are not all the possible side effects of ZITHROMAX. Tell your healthcare provider about any side effect that bothers you or that does not go away.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store ZITHROMAX?
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- Store ZITHROMAX Tablets at 59°F to 86°F (15°C to 30°C).
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- Store ZITHROMAX Oral Suspension at 41°F to 86°F (5°C to 30°C).
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- Keep ZITHROMAX Oral Suspension in a tightly closed container.
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- Safely throw away any medicine that is out of date or no longer needed.
Keep ZITHROMAX and all medicines out of the reach of children.
General information about the safe and effective use of ZITHROMAX.
Medicines are sometimes prescribed for purposes other than those listed in the Patient Information leaflet. Do not use ZITHROMAX for a condition for which it was not prescribed.
Do not give ZITHROMAX to other people, even if they have the same symptoms you have.
It may harm them.
This Patient Information leaflet summarizes the most important information about ZITHROMAX. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about ZITHROMAX that is written for health professionals.
For more information, go to www.zithromax.com or call 1-800-438-1986.
What are the ingredients in ZITHROMAX Tablets and Oral Suspension?
ZITHROMAX Tablets and Oral Suspension
Active ingredient: azithromycin dehydrate
ZITHROMAX Tablets:
Inactive ingredients: dibasic calcium phosphate anhydrous, pregelatinized starch, sodium croscarmellose, magnesium stearate, sodium lauryl sulfate, hypromellose, lactose, titanium dioxide, triacetin, and D&C Red #30 aluminum lake.
ZITHROMAX Oral Suspension:
Inactive ingredients: sucrose; sodium phosphate, tribasic, anhydrous; hydroxypropyl cellulose; xanthan gum; FD&C Red #40; and spray dried artificial cherry, creme de vanilla, and banana flavors.
This Patient Information has been approved by the U.S. Food and Drug Administration.
LAB-0372-7.0
Revised November 2021
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