General

Pronunciation:
aye-zith-roe-mye-sin

Trade Name(s)

• Zithromax
• Zmax

Ther. Class.

agents for atypical mycobacterium

anti-infectives

Pharm. Class.

macrolides

Indications

• Acute bacterial exacerbations of chronic bronchitis.
• Acute bacterial sinusitis.
• Community-acquired pneumonia.
• Pharyngitis/tonsillitis (as alternative in patients who cannot use 1st line therapy).
• Acute otitis media.
• Uncomplicated skin/skin structure infections.
• Urethritis/cervicitis.
• Pelvic inflammatory disease.
• Genital ulcer disease in men with chancroid.

Unlabeled Use(s):

Prevention of disseminated Mycobacterium avium complex (MAC) infection in patients with advanced HIV infection.

Action

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

Therapeutic Effect(s):

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:

  • Haemophilus influenzae,
  • Moraxella catarrhalis,
  • Neisseria gonorrhoeae.

• 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 and 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 (plasma concentrations)

Contraindication/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.

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.

Adverse 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 (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

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)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

•  Quinidine,  procainamide,  dofetilide,  sotalol, and  amiodarone  may ↑ risk of QT interval prolongation; avoid concurrent use.
•  Aluminum-  and  magnesium-containing antacids  ↓ may levels and effectiveness.
•  Nelfinavir  may ↑ levels and risk of toxicity; azithromycin also ↓ nelfinavir levels and effectiveness.
•  Efavirenz  may ↑ levels and risk of toxicity.
• May ↑ the effects and risk of toxicity of  warfarin  and  zidovudine.
• Other macrolide anti-infectives have been known to ↑ levels and risk of toxicity of  digoxin,  theophylline,  ergotamine,  dihydroergotamine,  triazolam,  carbamazepine,  cyclosporine,  tacrolimus, and  phenytoin.

Route/Dosage

Acute Bacterial Exacerbations of Chronic Bronchitis

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.

Acute Bacterial Sinusitis

PO (Adults): 500 mg once daily for 3 days.

PO (Children  >6 mo): 10 mg/kg once daily for 3 days (not to exceed 500 mg/dose).

Community-Acquired Pneumonia

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 (not to exceed 500 mg/dose).

Pharyngitis/Tonsillitis

PO (Adults): 500 mg on 1st day; then 250 mg/day for 4 more days.

PO (Children ≥2 yr): 12 mg/kg once daily for 5 days (not to exceed 500 mg/dose);

Acute Otitis Media

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.

Uncomplicated Skin/Skin Structure Infection

PO (Adults): 500 mg on 1st day, then 250 mg/day for 4 more days.

Urethritis/Cervicitis

PO (Adults): Nongonococcal: Single 1-g dose.  Gonococcal: Single 2-g dose.

Pelvic Inflammatory Disease

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.

Genital Ulcer Disease in Men with Chancroid

PO (Adults): Single 1-g dose.

Prevention of Disseminated MAC Infection

PO (Adults): 1.2 g once weekly (as monotherapy or in combination with rifabutin).

PO (Children): 5 mg/kg once daily (not >250 mg/dose) or 20 mg/kg (not >1200 mg/dose) once weekly (as monotherapy or in combination with rifabutin).

Availability (generic available)

Tablets: 250 mg, 500 mg, 600 mg

Powder for oral suspension (cherry and banana flavor): 1 g/pkt

Powder for oral suspension (cherry, creme de vanilla, and banana flavor): 100 mg/5 mL, 200 mg/5 mL

Powder for injection : 500 mg/vial

Assessment

• Assess 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. 1st 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 for skin rash frequently during therapy. Discontinue azithromycin at first sign of rash; may be life-threatening. SJS or TEN may develop. Treat symptomatically; may recur once treatment is stopped.
• Assess cardiac history and ECG at baseline; optimally avoid use in patients with long QT syndrome or cardiac arrhythmias associated with prolonged QT interval or those on concomitant medications that can prolong the QT interval

Lab Test Considerations:

May ↑ serum bilirubin, AST, ALT, LDH, and alkaline phosphatase concentrations.

• May ↑ CK, potassium, PT, BUN, serum creatinine, and blood glucose.
• May occasionally cause ↓ WBC and platelet count.

Implementation

• PO Administer 1 hr before or 2 hr after meals. Do not give simultaneously with aluminum- or magnesium-containing antacids.
  • For administration of single 1-g packet, thoroughly mix entire contents of packet with 2 ounces (60 mL) of water. Drink entire contents immediately; add an additional 2 ounces 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. Pedi:  1-g packet is not for pediatric use.

Patient/Family Teaching

• Educate patient on reason for azithromycin and side effects. 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, even if others have similar symptoms. Advise patient to read  Patient Information  before starting.
• 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 women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Advise parents to monitor breastfed infant for diarrhea, vomiting, or rash.

Evaluation/Desired Outcomes

Resolution of the signs and symptoms of infection. Length of time for complete resolution depends on the organism and site of infection.