azithromycin (Rx) - Zithromax, Zmax

Dosing Forms & Strengths

Acute Bacterial Exacerbations of Chronic Obstructive Pulmonary Disease

500 mg PO x1, THEN

250 mg qDay x4 days

Acute Bacterial Sinusitis

500 mg/day PO for 3 days or a single 2 g dose

Acute Otitis Media

500 mg PO x1, THEN

250 mg qDay x4 days

Community-Acquired Pneumonia

500 mg PO x1, THEN

250 mg qDay x4 days

Genital Ulcer Disease (Chancroid)

1 g PO x1

Pharyngitis/Tonsillitis

500 mg PO x1, THEN

250 mg qDay x4 days

Uncomplicated Skin & Skin Structure Infections

500 mg PO x1, THEN

250 mg qDay x4 days

Gonococcal Urethritis/Cervicitis

2 g PO x1

Nongonococcal Urethritis/Cervicitis

1 g PO x1

Acute Pelvic Inflammatory Disease

500 mg IV over 1 hour qDay x1-2 days

STD Prevention

Indicated to prevent STD (eg, gonorrhea) following sexual assault

1 g PO as a single dose; part of a 3-drug regimen that includes either ceftriaxone or cefixime, PLUS metronidazole, PLUS either azithromycin or doxycycline (CDC STD guidelines, 2010)

Pneumonia (Inpatient)

500 mg IV over 1 hour qDay x1-2 days

Mycobacterium Avium Complex

Prevention: 1.2 g PO qWeek, may be used in combination with rifabutin 300 mg qDay

Endocarditis Prophylaxis

500 mg PO 1 hour before procedure

Recent AHA Guidelines recommend only for high risk patients

Administration

Take tablets without regard to food but food may enhance tolerability

Conventional oral suspension (100 mg/5 mL & 200 mg/5 mL) may be stored for 10 days post-reconstitution and taken without regard to food

Conventional 1 g package: take immed after reconstitution

Extended release oral suspension (Zmax): take on empty stomach within 12 hours of reconstitution

Extended release oral suspension is given single dose only

Other Indications & Uses

Actinobacillus actinomycetemcomitans, Actinomyces israelii, Actinomyces naeslundii, Actinomyces odontolyticus, Afipia felis, Arachnia propionica, Arcanobacterium (Corynebacterium) haemolyticum, Bartonella henselae, Bartonella quintana, Bordetella pertussis, Borrelia burgdorferi, Borrelia recurrentis, Klebsiella granulomatis, Campylobacter jejuni, Chlamydia pneumonia (TWAR agent), Chlamydia trachomatis, Haemophilus ducreyi , Haemophilus influenzae, Legionella sp., Mycobacterium simiae, Mycobacterium scrofulaceum, Mycobacterium xenopi, Mycoplasma pneumoniae, M. catarrhalis. N. gonorrhoeae, S. aureus,Streptococcus (Group C & G), Streptococcus agalactiae (Group B), Streptococcus bovis (Group D), Streptococcus intermedius group (S. anginosus, S intermedius, S. constellatus), Streptococcus pneumoniae, Streptococcus pyogenes (Group A), Viridans streptococci

First line: Afipia felis, Bartonella henselae, Bartonella quintana, Bordetella pertussis,Campylobacter jejuni, Chlamydia pneumonia (TWAR agent), Chlamydia trachomatis, Haemophilus ducreyi, Haemophilus influenzae, Legionella sp., Mycobacterium scrofulaceum, Mycobacterium simiae, Mycobacterium xenopi (others eg Haemophilus, influenzae, Legionella sp not unanimous)

Dosing Forms & Strengths

Acute Otitis Media

<6 months old: Safety & efficacy not established

>6 months old: 30 mg/kg oral suspension given x1 or 10 mg/kg PO qDay for 3 days or 10 mg/kg x1 on day 1, followed by 5 mg/kg days 2 through 5

M. avium complex prophylaxis: 20 mg/kg PO qWeek

Community-Acquired Pneumonia

<6 months old: Safety & efficacy not established

>6 months old: 10 mg/kg x1 PO on day 1, followed by 5 mg/kg days 2 through 5

>6 months old (Zmax): 60 mg/kg PO once as a single dose; not to exceed 2 g/dose

Acute Bacterial Sinusitis

10 mg/kg oral suspension PO qDay x3 days

Pharyngitis/Tonsillitis

<2 years old: Safety and efficacy not established

>2 years old: 12 mg/kg PO qDay x 5 days; maximum 500 mg/day

M. Avium Complex Prophylaxis

<6 years old: Safety and efficacy not established

>6 years old: 20 mg/kg PO qWeek

Administration

Take tablets without regard to food but food may enhance tolerability

Conventional oral suspension (100 mg/5 mL &200 mg/5 mL) may be stored for 10 days post-reconstitution & taken without regard to food

Conventional 1 g package is not for pediatrics

Extended release oral suspension (Zmax): take on empty stomach within 12 hours of reconstitution

Extended release oral suspension is given single dose only

>10%(especially with high single-dose regimens)

Diarrhea (52.8%)

Nausea (32.6%)

Abdominal pain (27%)

Loose stool (19.1%)

1-10%

Cramping (2-10%)

Vaginitis (2-10%)

Dyspepsia (9%)

Flatulence (9%)

Vomiting (6.7%)

Malaise (1.1%)

<1%

Agitation

Dizziness

Fatigue

Headache

Hyperkinesia

Insomnia

Malaise

Nervousness

Seizures

Somnolence

Vertigo

Allergic reaction

Pruritus

Rash

Urticaria

Anemia

Leukopenia

Melena

Anorexia

Constipation

Enteritis

Gastritis

Pseudomembranous colitis

Candidiasis

Dermatitis (fungal)

Mucositis

Oral candidiasis

Eczema

Chest pain

Hypotension

Palpitations

Edema

Facial edema

Conjunctivitis

Increased cough

Pharyngitis

Rhinitis

Pleural effusion

Pain

Postmarketing Reports

Angioedema

Anaphylaxis

Bronchospasm

Dermatologic reactions

Elevated liver enzymes

Erythema multiforme

Stevens-Johnson syndrome

Toxic epidermal necrolysis

Torsade de pointes

Gastrointestinal: Anorexia, constipation, dyspepsia, flatulence, vomiting/diarrhea rarely resulting in dehydration, pseudomembranous colitis, pancreatitis, oral candidiasis, pyloric stenosis, and rare reports of tongue discoloration

Contraindications

Documented hypersensitivity

Cholestatic jaundice/hepatic impairment

Do not administer with pimozide

Cautions

Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure have been reported, some of which have resulted in death; discontinue azithromycin immediately if signs and symptoms of hepatitis occur

Injection site reactions can occur with IV route

Bacterial or fungal overgrowth may result from prolonged antibiotic use

Prolonged QT interval: Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance; although the absolute risk is unknown, it appears to be low

Pneumonia: PO azithromycin safe and effective only for of CAP due to Chlamydia pneumoniae, H. influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae

Endocarditis prophylaxis: use only for high risk patients, per recent AHA Guidelines

Renal impairment (CrCl<10 mL/min)

Excretion

Feces: 50% as unchanged drug

Urine: 5-12%

Mechanism of Action

Acts by binding to 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected. Concentrates in phagocytes and fibroblasts as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues.

IV Incompatibilities

Y-site: amikacin, aztreonam, cefotaxime, ceftazidime, ceftriaxone, cefuroxime, ciprofloxacin, clindamycin, droperidol, famotidine, fentanyl, furosemide, gentamicin, imipenem, cilastatin, ketorolac, levofloxacin, morphine, piperacillin-tazobactam, ondansetron(?), KCl, ticarcillin-clavulanate, tobramycin

IV Compatibilities

Solution (partial list): SWI, D5W, LR, D5/LR, D5/½NS, NS, ½NS

Y-site: bivalirudin, dexmedetomidine, diphenhydramine, dolasetron, droperidol

IV Preparation

4.8 mL of SWI to 500 mg vial (100 mg/mL)

Dilute further to 1 mg/mL (500 mL) to 2 mg/mL (250 mL) in NS

IV Administration

Use standard syringe

1 mg/mL IV soln: infuse over 3 hr

2 mg/mL soln: infuse over 1 hr

500 mg dose solutions should be infused over at least 1 hr