azithromycin

REMS

Treatment of the following infections due to susceptible organisms:
- Upper respiratory tract infections, including streptococcal pharyngitis, acute bacterial exacerbations of chronic bronchitis and tonsillitis,
- Lower respiratory tract infections, including bronchitis and pneumonia,
- Acute otitis media,
- Skin and skin structure infections,
- Nongonococcal urethritis, cervicitis, gonorrhea, and chancroid.
Prevention of disseminated
Mycobacterium avium
complex (MAC) infection in patients with advanced HIV infection.

Unlabeled Use:

Prevention of bacterial endocarditis.
Treatment of cystic fibrosis lung disease.
Treatment and post-exposure prophylaxis of pertussis in infants.

Action ⬆ ⬇

Inhibits protein synthesis at the level of the 50S bacterial ribosome.

Therapeutic effects:

Bacteriostatic action against susceptible bacteria.

Spectrum:

Active against the following gram-positive aerobic bacteria:
- Staphylococcus aureus,
- Streptococcus pneumoniae,
- S. pyogenes (group A strep).
Active against these gram-negative aerobic bacteria:
Also active against:
- Bordetella pertussis
- Mycoplasma,
- Legionella,
- Chlamydia pneumoniae,
- Ureaplasma urealyticum,
- Borrelia burgdorferi,
- M. avium.
Not active against methicillin-resistant S. aureus.

Pharmacokinetics ⬆ ⬇

Absorption: Rapidly absorbed (40%) after oral administration. IV administration results in complete bioavailability.

Distribution: Widely distributed to body tissues and fluids. Intracellular and tissue levels exceed those in serum; low CSF levels.

Protein Binding: 7–51%.

Metabolism/Excretion: Mostly excreted unchanged in bile; 4.5% excreted unchanged in urine.

Half-Life: 11–14 hr after single dose; 2–4 days after several doses.

Time/Action Profile ⬆ ⬇

(serum)

ROUTE	ONSET	PEAK	DURATION
PO	rapid	2.5–3.2 hr	24 hr
IV	rapid	end of infusion	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to azithromycin, erythromycin, or other macrolide anti-infectives;
History of cholestatic jaundice or hepatic dysfunction with prior use of azithromycin;
QT interval prolongation, hypokalemia, hypomagnesemia, or bradycardia;
Concurrent use of quinidine, procainamide, dofetilide, amiodarone, or sotalol.

Use Cautiously in:

Severe hepatic impairment (dose adjustment may be required);
Severe renal impairment (CCr <10 mL/min);
Myasthenia gravis (may worsen symptoms);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Neonates ( risk of infantile hypertrophic pyloric stenosis at up to 42 days of life);
Geri: Older adults may have risk of QT interval prolongation.

Adv. Reactions/Side Effects ⬆ ⬇

CV: CARDIOVASCULAR DEATH, chest pain, hypotension, palpitations, QT interval prolongation, TORSADES DE POINTES

Derm: ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), photosensitivity, rash, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS

EENT: ototoxicity

F and E: hyperkalemia

GI: abdominal pain, diarrhea, nausea, ↑liver enzymes, cholestatic jaundice, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), dyspepsia, flatulence, HEPATOTOXICITY, melena, oral candidiasis, pyloric stenosis

GU: nephritis, vaginitis

Hemat: anemia, leukopenia, thrombocytopenia

Neuro: dizziness, drowsiness, fatigue, headache, seizures

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

Quinidine, procainamide, dofetilide, sotalol, and amiodarone may ↑ risk of QT interval prolongation; concurrent use should be avoided.
Aluminum- and magnesium-containing antacids↓ peak levels.
Nelfinavir↑ levels (monitor carefully); azithromycin also ↓ nelfinavir levels.
Efavirenz↑ levels.
May ↑ the effects and risk of toxicity of warfarin and zidovudine.
Other macrolide anti-infectives have been known to ↑ levels and effects of digoxin, theophylline, ergotamine, dihydroergotamine, triazolam, carbamazepine, cyclosporine, tacrolimus, and phenytoin; careful monitoring of concurrent use is recommended.

Route/Dosage ⬆ ⬇

Most Respiratory and Skin Infections

Otitis Media

Acute Bacterial Exacerbations of Chronic Bronchitis

Community-Acquired Pneumonia

Pelvic Inflammatory Disease

Endocarditis Prophylaxis

Nongonococcal Urethritis, Cervicitis, Chancroid, Chlamydia

Gonorrhea

Prevention of Disseminated MAC Infection

Cystic Fibrosis

PO (Adults ): 500 mg on 1st day, then 250 mg/day for 4 more days (total dose of 1.5 g); Acute bacterial sinusitis: 500 mg once daily for 3 days.
PO (Children ≥6 mo): Pneumonia/Pertussis: 10 mg/kg (not to exceed 500 mg/dose) on 1st day, then 5 mg/kg once daily (not to exceed 250 mg/dose) for 4 more days. Pharyngitis/tonsilitis: 12 mg/kg once daily for 5 days (not to exceed 500 mg/dose); Acute bacterial sinusitis: 10 mg/kg once daily for 3 days.
PO (Neonates ): Pertussis, treatment and post-exposure prophylaxis: 10 mg/kg once daily for 5 days.
PO (Children ≥6 mo): 30 mg/kg single dose (not to exceed 1500 mg/dose) or 10 mg/kg once daily (not to exceed 500 mg/dose) for 3 days or 10 mg/kg (not to exceed 500 mg/dose) on 1st day, then 5 mg/kg once daily (not to exceed 250 mg/dose) for 4 more days.
PO (Adults ): 500 mg on 1st day, then 250 mg once daily for 4 more days (total dose of 1.5 g) or 500 mg once daily for 3 days.
IV PO (Adults ): More severe: 500 mg IV every 24 hr for at least 2 doses, then 500 mg PO every 24 hr for a total of 7–10 days; Less severe: 500 mg PO, then 250 mg/day PO for 4 more days.
PO (Children >6 mo): 10 mg/kg on 1st day, then 5 mg/kg once daily for 4 more days.
IV PO (Adults ): 500 mg IV every 24 hr for 1–2 days, then 250 mg PO every 24 hr for a total of 7 days.
PO (Adults ): 500 mg 1 hr before procedure.
PO (Children ): 15 mg/kg 1 hr before procedure.
PO (Adults ): Single 1-g dose.
PO (Children ): Chancroid: Single 20-mg/kg dose (not to exceed 1000 mg/dose). Urethritis or cervicitis: Single 10-mg/kg dose (not >1000 mg/dose).
PO (Adults ): Single 2-g dose.
PO (Adults ): 1.2 g once weekly (alone or with rifabutin).
PO (Children ): 5 mg/kg once daily (not >250 mg/dose) or 20 mg/kg (not >1200 mg/dose) once weekly (alone or with rifabutin).
PO (Children ≥6 yrs, ≥40 kg): 500 mg every Monday, Wednesday, and Friday.
PO (Children ≥6 yrs, 25 kg to <40 kg): 250 mg every Monday, Wednesday, and Friday.

Availability ⬆ ⬇

(Generic available)

Tablets: 250 mg; 500 mg; 600 mg
Powder for oral suspensioncherry and banana flavor : 1 g/pkt
Powder for oral suspensioncherry, creme de vanilla, and banana flavor : 100 mg/5 mL; 200 mg/5 mL
Powder for injection : 500 mg/vial

Assessment ⬆ ⬇

Assess patient for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and throughout therapy.
Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results.
Observe for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Notify health care professional immediately if these occur.
Assess patient for skin rash frequently during therapy. Discontinue azithromycin at first sign of rash; may be life-threatening. Stevens-Johnson syndrome or toxic epidermal necrolysis may develop. Treat symptomatically; may recur once treatment is stopped.

Lab Test Considerations:

May cause ↑ serum bilirubin, AST, ALT, LDH, and alkaline phosphatase concentrations.
- May cause ↑ creatine phosphokinase, potassium, prothrombin time, BUN, serum creatinine, and blood glucose concentrations.
- May occasionally cause ↓ WBC and platelet count.

Implementation ⬆ ⬇

PO: Administer 1 hr before or 2 hr after meals.
- For administration of single 1-g packet, thoroughly mix entire contents of packet with 2 oz (60 mL) of water. Drink entire contents immediately; add an additional 2 oz of water, mix and drink to assure complete consumption of dose. Do not use the single packet to administer doses other than 1000 mg of azithromycin. 1-g packet is not for pediatric use.

IV Administration:

Intermittent Infusion: Reconstitution: Reconstitute each 500-mg vial with 4.8 mL of sterile water for injection to achieve a concentration of 100 mg/mL. Reconstituted solution is stable for 24 hr at room temperature.Diluent: Further dilute the 500-mg dose in 250 mL or 500 mL of 0.9% NaCl, 0.45% NaCl, D5W, LR, D5/0.45% NaCl, or D5/LR. Infusion is stable for 24 hr at room temperature or for 7 days if refrigerated.Concentration: Final concentration of infusion is 1–2 mg/mL.
Rate: Administer the 1-mg/mL solution over 3 hr or the 2-mg/mL solution over 1 hr. Do not administer as a bolus.

Patient/Family Teaching ⬆ ⬇

Instruct patients to take medication as directed and to finish the drug completely, even if they are feeling better. Take missed doses as soon as possible unless almost time for next dose; do not double doses. Advise patients that sharing of this medication may be dangerous.
Instruct patient not to take azithromycin with food or antacids.
May cause drowsiness and dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
Advise patient to report symptoms of chest pain, palpitations, yellowing of skin or eyes, or signs of superinfection (black, furry overgrowth on the tongue; vaginal itching or discharge; loose or foul-smelling stools) or rash.
Instruct patient to notify health care professional if fever and diarrhea develop, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without advice of health care professional.
Advise patients being treated for nongonococcal urethritis or cervicitis that sexual partners should also be treated.
Instruct parents, caregivers, or patient to notify health care professional if symptoms do not improve.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Advise women to monitor breastfed infant for diarrhea, vomiting, or rash.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇