Azithromycin

Trade Names:AzaSite- Solution, ophthalmic 1%

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

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

Pharmacology

Interferes with microbial protein synthesis.

Pharmacokinetics

Absorption

Rapidly absorbed.

Bioavailability is 38%.

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 (cervix, lung, skin, sputum, 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

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

Pharmacokinetics have not been established.

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.

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

Indications and Usage

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.

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

Treatment of bacterial conjunctivitis caused by susceptible organisms.

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

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.

Treatment of community-acquired pneumonia caused by susceptible organisms.

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, chlamydial infections caused by Chlamydia trachomatis , granuloma inguinale caused by Klebsiella granulomatis , early lime disease, lower respiratory tract infections, prevention of coronary events, prophylaxis after a sexual assault, rosacea (topical), rosacea (oral), traveler's diarrhea, and treatment of cholera in adults.

Contraindications

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

Dosage and Administration

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

PO 10 mg/kg oral suspension once daily for 3 days (immediate-release).

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).

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

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

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.

PO 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).

PO 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).

PO Single 1 g dose.

PO Single 2 g dose.

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.

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.

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

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

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

General Advice

• Immediate-release oral suspension/Tablets
• 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) of water and drink immediately. Add an additional 60 mL of water, mix, and drink immediately to ensure complete consumption of dosage.
• Administer azithromycin 2 h before or after antacids containing aluminum or magnesium.
• Azithromycin immediate-release 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 suspension
• Take on an empty stomach, at least 1 h before or 2 h after a meal.
• Reconstitute bottles containing azithromycin 2 g ER 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 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).

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

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

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

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

Drug Interactions

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

Serum concentrations of these agents have been elevated by azithromycin, increasing the pharmacologic effects and risk of adverse reactions. Monitor serum concentrations of these agents and observe the patient for adverse reactions. Adjust the dose as needed.

Levels may be elevated by azithromycin, increasing the risk of toxicity. Monitor drug levels and adjust the dose as needed.

Digoxin plasma concentrations may be elevated, increasing the risk of toxicity. Monitor digoxin levels and observe the patient for signs of digoxin toxicity. Adjust the digoxin dose as needed.

Dronedarone plasma concentrations and pharmacologic effects may be increased. Avoid coadministration.

Acute ergotism manifested as peripheral ischemia has been reported. Closely monitor for ergotism.

Azithromycin levels may be elevated, increasing the risk of adverse reactions (eg, abnormal LFTs, hearing impairment). Monitor for azithromycin adverse reactions.

Increased nilotinib plasma concentrations with cardiotoxicity may occur. Avoid coadministration.

Pimozide plasma concentrations may be elevated, increasing the risk of cardiotoxicity. Coadministration is contraindicated.

Risk of life-threatening cardiac arrhythmias, including torsades de pointes, may be increased. Use with caution. Avoid coadministration with paliperidone or propafenone. Close clinical and ECG monitoring is advised.

Risk of neutropenia may be increased.

Plasma concentrations may be elevated by azithromycin, increasing the pharmacologic effect and risk of adverse reactions. Observe the clinical response of the patient and adjust the triazolam dose as needed.

The anticoagulant effect may be increased, increasing the risk of hemorrhage. Monitor anticoagulant parameters and adjust the warfarin dose as needed.

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, TEN (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).

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

Hypersensitivity

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

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, GGT, 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

Pregnancy

Category B .

Lactation

Undetermined.

Children

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

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

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

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 TEN), 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, including prolonged cardiac repolarization and QT interval, have occurred with other macrolide antibiotics.

Myasthenia gravis

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

Pseudomembranous colitis

May be a 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 oral 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 oral 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 to avoid contaminating the applicator tip by not allowing it to touch the eye, fingers, or other surfaces.
• Advise patients using the ophthalmic solution to invert closed bottle and shake once before each use.

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