Professional Information

Azithromycin

Pronunciation: (ay-ZITH-roe-MYE-sin)
Class: Macrolide

Trade Names:
Azithromycin
- Injection, lyophilized powder for solution 2.5 g

Trade Names:
AzaSite
- Solution, ophthalmic 1%

Trade Names:
Zithromax
- Tablets 250 mg (as dihydrate)
- Tablets 500 mg (as dihydrate)
- Tablets 600 mg (as dihydrate)
- Injection, lyophilized powder for solution 500 mg
- Powder for oral suspension 100 mg per 5 mL
- Powder for oral suspension 200 mg per 5 mL
- Powder for oral suspension 1 g/packet (as dihydrate)

Trade Names:
Zmax
- Powder for oral suspension, ER 2 g

CO Azithromycin (Canada)
Z-Pak (Zithromax) (Canada)

Pharmacology

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Compare with other drugs.

Interferes with microbial protein synthesis.

Pharmacokinetics

Absorption

Oral

Rapidly absorbed.

Oral, immediate-release (IR)

Bioavailability is 38%.

Oral, ER suspension

Bioavailability is 83% relative to the oral immediate-release suspension.

C _max is approximately 3.63 mcg/mL; C _min is approximately 0.2 mcg/mL (at 24 h); AUC ₂₄ is approximately 9.6 mcg•h/mL.

Distribution

Widely distributed into body (skin, lung, sputum, cervix, tonsils) but distributes poorly in the CSF. Higher concentrations in tissues than in plasma or serum. Vd is 31.1 L/kg (oral) and 33.3 L/kg (IV). Protein binding is 7% to 50% (concentration dependent).

Elimination

The half-life is approximately 68 h. Plasma Cl is 630 mL/min (oral) and 10.18 mL/min/kg (IV). Excreted primarily in the bile, predominantly as unchanged drug. Approximately 6% is excreted in urine as unchanged drug (oral); approximately 11% is excreted in the urine after first dose and 14% after fifth dose (IV).

Special Populations

Renal Function Impairment

C _max and AUC increased 61% and 35%, respectively in subjects with severe renal impairment; use with caution.

Hepatic Function Impairment

Pharmacokinetics have not been established.

Elderly

Pharmacokinetic parameters in men 65 to 85 yr of age are similar to younger adults; however, in elderly women, a higher C _max was observed but there was no change in drug accumulation.

Gender

No differences in drug disposition between men and women. No dosage adjustment is needed based on gender.

Indications and Usage

Adults Oral tablets and oral suspension (immediate-release)

Treatment of acute bacterial exacerbation of COPD, acute bacterial sinusitis, community-acquired pneumonia, pharyngitis/tonsillitis caused by Streptococcus pyogenes in patients who cannot use first-line therapy, uncomplicated skin and skin structure infections, urethritis and cervicitis, and genital ulcer disease (in men) caused by susceptible organisms.

Oral suspension (ER)

Treatment of acute bacterial sinusitis and community-acquired pneumonia caused by susceptible organisms.

Ophthalmic solution

Treatment of bacterial conjunctivitis caused by susceptible organisms.

IV infusion

Treatment of community-acquired pneumonia and pelvic inflammatory disease caused by susceptible organisms.

Children Oral tablets and oral suspension (IR)

Treatment of acute bacterial sinusitis, acute otitis media caused by susceptible organisms, community-acquired pneumonia, pharyngitis/tonsillitis caused by S. pyogenes in patients who cannot use first-line therapy.

Oral suspension (ER)

Treatment of community-acquired pneumonia caused by susceptible organisms.

Ophthalmic solution

Bacterial conjunctivitis caused by susceptible organisms.

Unlabeled Uses

Acne vulgaris (topical), acute pharyngitis or tonsillitis (group A streptococcal) in children, acute skin and soft tissue infections, babesiosis, lower respiratory tract infections, prevention of coronary events, rosacea, rosacea (topical), traveler's diarrhea, treatment of cholera in adults, Chlamydial infections caused by Chlamydia trachomatis , granuloma inguinale caused by Klebsiella granulomatis , early lime disease, and prophylaxis after a sexual assault.

Contraindications

Hypersensitivity to azithromycin, erythromycin, or to any macrolide antibiotic.

Dosage and Administration

Acute Bacterial Sinusitis
Adults

PO (IR) 500 mg every day for 3 days; (ER) single 2 g dose, taken on an empty stomach, at least 1 h before or 2 h after a meal.

Children 6 mo of age and older

PO (IR) 10 mg/kg oral suspension once daily for 3 days.

Acute Otitis Media
Children 6 mo of age and older

PO 30 mg/kg given as a single dose or 10 mg/kg once daily for 3 days or 10 mg/kg as a single dose on the first day (not to exceed 500 mg/day) followed by 5 mg/kg on days 2 through 5 (not to exceed 250 mg/day).

Community-Acquired Pneumonia
Adults

PO (IR) 500 mg as a single dose on the first day followed by 250 mg once daily on days 2 through 5; (ER) single 2 g dose.

Adults and Children 16 yr of age and older

IV 500 mg as a single daily dose for at least 2 days. Follow IV therapy by the oral route at a single daily dose of 500 mg to complete 7- to 10-day course of therapy.

Children 6 mo of age and older

PO (IR) 10 mg/kg as a single dose on the first day (not to exceed 500 mg/day), followed by 5 mg/kg on days 2 through 5 (not to exceed 250 mg/day).

Children 6 mo of age and older

PO (ER) single dose of 60 mg/kg (equivalent to 27 mg/lb). The Zmax dose in mL is equivalent to the child's weight in lb (ie, 1 mL/lb dose). Thus, for a child weighing less than 75 lb (34 kg), the dose in mL is equivalent to the child's weight in pounds (ie, a 20 lb child should receive a single 20 mL dose [540 mg]). Children weighing 75 lb (34 kg) or more should receive the adult dose (2 g).

Conjunctivitis
Adults and Children 1 yr of age and older

Ophthalmic Instill 1 drop in affected eye(s) twice daily, 8 to 12 hours apart for the first 2 days, then 1 drop in affected eye(s) once daily for the next 5 days.

Genital Ulcer Disease Caused by Haemophilus ducreyi (chancroid) Nongonococcal Urethritis and Cervicitis Caused by C. trachomatis
Adults

PO Single 1 g dose.

Gonorrhea
Adults

PO Single 2 g dose.

Mild to Moderate Acute Bacterial Exacerbations of COPD
Adults

PO 500 mg/day for 3 days or 500 mg as a single dose on the first day followed by 250 mg once daily on days 2 through 5.

Pelvic Inflammatory Disease
Adults

IV 500 mg as a single daily dose for 1 to 2 days. Follow IV therapy by the oral route at a single daily dose of 250 mg to complete a 7-day course of therapy.

Pharyngitis/Tonsillitis
Adults

PO 500 mg as a single dose on the first day followed by 250 mg once daily on days 2 through 5.

Children 2 yr of age and older

PO 12 mg/kg/day for 5 days, not to exceed 500 mg/day.

Uncomplicated Skin and Skin Structure Infections
Adults

PO 500 mg as a single dose on the first day followed by 250 mg once daily on days 2 through 5.

General Advice

Oral suspension/Tablets (IR)
Administer prescribed dose without regard to meals. Administer with food if GI upset occurs.
Administer tablets with a full glass of water.
Shake suspension well before measuring dose. Administer prescribed dose of suspension using dosing syringe, dosing spoon, or medicine cup.
When administering 1,000 mg single-dose packet, thoroughly mix entire contents of packet with 60 mL (2 oz) water and drink immediately. Add an additional 60 mL of water, mix, and have patient drink immediately to ensure complete consumption of dosage.
Administer azithromycin 2 h before or after antacids containing aluminum or magnesium.
Azithromycin IR oral suspension and ER oral suspension are not interchangeable.

Injection
For administration by IV infusion only. Not for intradermal, subcutaneous, IM, IV bolus, or intra-arterial administration.
Reconstitute powder for injection with 4.8 mL of sterile water for injection. Shake vial until all of the drug has dissolved. Reconstituted solution contains 100 mg/mL.
Further dilute reconstituted solution with sodium chloride 0.9% injection, sodium chloride 0.45% injection, dextrose 5% in water, Ringer's lactate solution, dextrose 5% in Normosal-M , dextrose 5% in Ringer's lactate solution, dextrose 5% in Normosal-R . Adding 5 mL of reconstituted solution to 500 mL of diluent provides a final concentration of 1 mg/mL; adding 5 mL of reconstituted solution to 250 mL of diluent provides final concentration of 2 mg/mL.
Infuse prescribed dose over a period of not less than 60 min.
Inspect solution visually before administration. Do not administer if solution is cloudy, discolored, or contains particulate matter.
Discard any unused product. Vials are for single use only. Do not save medication for future use.

Ophthalmic solution
For topical ophthalmic use only; not to be administered systemically, or by subconjunctival injection, or introduced directly into the anterior chamber of the eye.

ER, oral
Take on an empty stomach, at least 1 h before or 2 h after a meal.
Reconstitute bottles containing azithromycin ER 2 g for oral suspension with 60 mL of water.
Shake bottle well before dispensing.
Do not refrigerate.
Constituted suspension should be consumed within 12 h.
Any suspension remaining after dosing should be discarded.
In the event that the patient vomits within 5 min of administration, additional antibiotic treatment should be considered because there would be minimal absorption of azithromycin. In patients with healthy gastric emptying, alternative therapy or a second dose is not warranted if vomiting occurs 60 min or more following administration. In patients with delayed gastric emptying, consider alternative therapy.

Storage/Stability

Store oral tablets at 59° to 86°F. Store dry powder for oral suspension below 86°F.

Oral suspension packets

Store reconstituted suspension at 41° to 86°F and discard when full dosing is completed.

Zmax

Store reconstituted suspension at 59° to 86°F. Do not freeze. Administer within 12 h of constitution.

Ophthalmic solution

Store refrigerated at 36° to 46°F. Once opened, store at 36° to 77°F for up to 14 days. Discard after 14 days.

Injection

Store powder for injection at 59° to 86°F. Store reconstituted solution below 86°F for up to 24 h. Diluted infusion solution may be stored for up to 24 h at or below 86°F or for 7 days if stored in refrigerator (41°F).

Drug Interactions

Aluminum- and magnesium-containing antacids

May reduce the peak serum levels but not the AUC of azithromycin.

Class IA (eg, procainamide, quinidine) or class III (eg, dofetilide, sotalol) antiarrhythmic agents, quinolone antibiotics (eg, levofloxacin, moxifloxacin)

Risk of life-threatening cardiac arrhythmias, including torsades de pointes, may be increased. Use with caution.

Cyclosporine, pimozide, theophyllines

Levels may be elevated by azithromycin, increasing the risk of toxicity.

Digoxin

Digoxin plasma concentrations may be elevated, increasing the risk of toxicity. Monitor for increased digoxin levels and signs of digoxin toxicity.

Food

Rate and extent of absorption is increased by a high-fat meal.

Nelfinavir

Azithromycin levels may be elevated, increasing the risk of side effects.

Warfarin

The anticoagulant effect may be increased, increasing the risk of hemorrhage.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Chest pain, palpitations (1% or less); arrhythmias including ventricular tachycardia, hypotension, QT prolongation, syncope, torsades de pointes (postmarketing).

CNS

Dizziness, headache (1%); agitation, fatigue, hyperkinesia, insomnia, malaise, nervousness, somnolence, vertigo (1% or less); aggressive reaction, anxiety, asthenia, convulsions, hyperactivity, paresthesia (postmarketing).

Dermatologic

Rash (5%); dermatitis, pruritus (2%); eczema, fungal dermatitis, photosensitivity, swelling, urticaria, vesiculobullous rash (1% or less); erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (postmarketing).

EENT

Eye irritation with ophthalmic solution (1% to 2%); conjunctivitis, pharyngitis, rhinitis (1% or less); deafness, hearing disturbances including hearing loss, smell perversion or loss, taste perversion or loss, tinnitus (postmarketing).

Ophthalmic

Blurring vision, eye pain, eyelid swelling, itching eye, reduced visual acuity (postmarketing).

GI

Nausea (18%); diarrhea/loose stools, vomiting (14%); abdominal pain (5%); anorexia (2%); dyspepsia (1%); constipation, enteritis, flatulence, gastritis, melena (1% or less); oral candidiasis, pancreatitis, pseudomembranous colitis, tongue discoloration (postmarketing).

Genitourinary

Vaginitis (3%); monilia, nephritis (1% or less); acute renal failure, interstitial nephritis (postmarketing).

Hepatic

Cholestatic jaundice, jaundice (1% or less); abnormal liver function including hepatic failure, hepatic necrosis, hepatitis (postmarketing).

Hematologic-Lymphatic

Decreased lymphocytes, decreased neutrophils, increased eosinophils, lymphocytes, neutrophils and platelet count (at least 1%); anemia, leukopenia (1% or less); thrombocytopenia (postmarketing).

Hypersensitivity

Angioedema (1% or less); anaphylaxis (postmarketing).

Ophthalmic

Allergic reactions including facial swelling, hives, periocular swelling, rash, and urticaria (postmarketing).

Lab Tests

Elevated ALT, AST, and creatinine (4% to 6%); elevated bilirubin and LDH (1% to 3%); decreased hematocrit, hemoglobin, and blood glucose; increased blood glucose, BUN, gamma-glutamyl-transferase, serum creatine, phosphokinase, and potassium (at least 1%).

Local

Pain at injection site (7%); local inflammation (3%).

Musculoskeletal

Arthralgia (postmarketing).

Respiratory

Cough, pleural effusion (1% or less).

Miscellaneous

Fever (2%); face edema, fungal infection, pain (1% or less); edema (postmarketing).

Precautions

Monitor

Sensitivity

Review results of culture and sensitivity testing as appropriate.

STD testing

Ensure patient being treated for sexually transmitted urethritis or cervicitis has serologic test for syphilis and cultures for gonorrhea performed at time of diagnosis and that appropriate antimicrobial therapy and follow-up tests are initiated if infection is confirmed.

Therapy response

Monitor patient's response to therapy.

Pregnancy

Category B .

Lactation

Undetermined.

Children

Acute bacterial sinusitis, acute otitis media, community-acquired pneumonia

Safety and efficacy not established in children younger than 6 mo of age.

Pharyngitis/Tonsillitis

Safety and efficacy not established in children younger than 2 yr of age.

Ophthalmic solution

Safety and efficacy not established in children younger than 1 yr of age.

IV infusion

Safety and efficacy not established in children younger than 16 yr of age.

Hypersensitivity

Serious, life-threatening reactions, including anaphylaxis, angioedema and dermatologic reactions (including Stevens Johnson syndrome and toxic epidermal necrolysis), have occurred.

Renal Function

Use cautiously.

Hepatic Function

Use cautiously.

Superinfection

Prolonged use of antibiotics may result in bacterial or fungal overgrowth of nonsusceptible microorganisms.

Cardiac effects

Serious CV events have occurred with other macrolide antibiotics, including prolonged cardiac repolarization and QT interval.

Myasthenia gravis

New onset and exacerbation of symptoms of myasthenia gravis have been reported.

Pseudomembranous colitis

May be factor in patients who develop diarrhea.

Patient Information

Review dosing schedule and prescribed length of therapy with patient. Advise patient that dose, dosing frequency, and duration of therapy are dependent on site and cause of infection.
Advise patient or caregiver that injection will be prepared by a health care provider and administered in a health care setting.
Instruct patient using tablets to take prescribed dose with a full glass of water.
Instruct patient or caregiver using oral suspension to shake suspension well and then measure and administer prescribed dose using dosing spoon, dosing syringe, or medicine cup.
Advise patient to take prescribed dose without regard to meals, but to take with food if stomach upset occurs.
Instruct patient to take Zmax ER suspension on an empty stomach, at least 1 h before or 2 h after a meal.
Advise patient to take 2 h before or after antacids containing aluminum or magnesium.
Instruct patient to consume reconstituted Zmax ER suspension within 12 h and to discard any suspension remaining after dosing.
Instruct patient to complete entire course of therapy, even if symptoms of infection have disappeared.
Advise patient to discontinue therapy and contact health care provider immediately if skin rash, hives, itching, or shortness of breath occur.
Advise patient to report signs of superinfection to health care provider: black, “furry” tongue; white patches in mouth; foul-smelling stools; vaginal itching or discharge.
Warn patient that diarrhea containing blood or pus may be a sign of a serious disorder and to seek medical care if noted and to not treat at home.
Instruct patient or caregiver to contact health care provider for further treatment if the patient vomits within the first hour.
Advise patients that Zmax ER suspension may be taken without regard to antacids containing magnesium and/or aluminum hydroxide.
Advise patients using the ophthalmic solution not to wear contact lenses if they have signs or symptoms of bacterial conjunctivitis.
Advise patients to wash their hands prior to use of the ophthalmic solution.
Advise patients using the ophthalmic solution to invert closed bottle and shake once before each use.