Macrolides (Erythromycin, Clarithromycin, Azithromycin)

The macrolides are antibiotics with a spectrum of coverage similar to penicillin, with the addition of some penicillanase-producing staphylococci, chlamydiae, Legionella, mycoplasma and others. Erythromycin is the most popular macrolide. In its free base form it is unstable at gastric pH so it is administered as a salt form (stearate or estolate) or with an enteric coating. (Note: Due to differences in absorption the three forms have different dosages). Its most common side effect is gastrointestinal upset. Clarithromycin and azithromycin are structural derivates of erythromycin with a broader spectrum of activity and increased bioavailability. Both agents exhibit less gastrointestinal upset than erythromycin. Macrolides are bacteriostatic rather than bacteriocidal and thus are not recommended in immuno-compromised patients.

In the past, macrolides were considered highly effective antibiotics for treating dental infections and frequently substituted in penicillin allergy. Currently, however, the high resistance rates of oral streptococci and oral anaerobes to the macrolides has reduced their use in dental infections. For patients with a penicillin allergy clindamycin is the preferred alternative antibiotic for treating dental infections.

Contraindications: Hypersensitivity to erythromycin or any component of the formulation.

Warnings/Precautions: Use with caution in patients with hepatic impairment. Administration may be accompanied by malaise, nausea, vomiting, abdominal colic and fever. Discontinue use if these occur. Avoid using erythromycin lactobionate in neonates since formulations may contain benzyl alcohol which is associated with toxicity in neonates. Use in infants has been associated with infantile hypertrophic pyloric stenosis. Interacts with numerous other drugs increasing the serum levels of the drugs. Confirm patient’s medical history before prescribing.

The oral dosages and dosage forms of the macrolides are:

Erythromycin

Infants and children < 12 years
Base: 30-50 mg/kg/day in 2-4 divided does; do not exceed 2 g/day.
Estolate: 30-50 mg/kg/day in 2-4 divided doses; do not exceed 2 g/day
Ethylsuccinate: 30-50 mg/kg/day in 2-4 divided doses; do not exceed 3.2 g/day
Stearate: 30-50 mg/kg/day in 2-4 divided doses; do not exceed 2 g/day

Adults and children > 12 years
Base: 250-500 mg every 6-12 hours
Ethylsuccinate: 400-800 mg every 6-12 hours

Supplied as:
Capsules, delayed release enteric coated tablets as base (Eryc®) 250 mg
Suspension, oral, as estolate: 125 mg/5 ml, 250 mg/5 ml
Suspension, oral, as ethylsuccinate: 200 mg/5 ml, 400 mg/5 ml
Tablet, chewable, ethylsuccinate: 200 mg
Tablet, as base: 250 mg, 500 mg
Tablet, as ethylsuccinate: 400 mg
Tablet as stearate: 250 mg, 500 mg

Sample erythromycin estolate prescription for a 3-year-old patient weighing 12 kg (25 lb) with facial swelling:

Rx: Erythromycin estolate 125 mg/5 ml
Disp: 200 ml
Sig: 5 ml every 6 hours for 10 days

Clarithromycin (Biaxin®)

Children ≥ 1 month: 15 mg/kg/day divided every 12 hours for 7 days; maximum 1 gm/day
Adults: 250-500 mg every 12 hours or 1000 mg (Two 500 mg extended release tablets) once daily for 7-14 days

Supplied as:
Granules for oral suspension: 125 mg/5 ml, 250 mg/5 ml (50 ml, 100 ml)
Tablet: 250 mg, 500 mg
Tablet, extended release: 500 mg

Sample clarithromycin prescription for a 3-year-old patient weighing 12 kg (25 lb) with facial swelling:

Rx: Clarithromycin 125 mg/5 ml
Disp: 100 ml
Sig: 5 ml every 12 hours for 7 days

Azithromycin (Zithromax®)

Children > 6months: 10 mg/kg - day 1, followed by 5 mg/kg/day for 4 days. Dose should be given 1 hour before a meal or 2 hours after. Maximum 250 mg/day
Adolescents ≥ 16 years or adult: 500 mg – day 1 then 250 mg days 2-5

Supplied as:
Powder for oral suspension: 100 mg/5 ml, (15 ml)
200 mg/5 ml (15 ml, 22.5 ml, 30 ml)
Tablets: Zithromax®, Z-Pak® 250 mg (6 tablets)

Sample azithromycin prescription for a 3-year-old patient weighing 12 kg (25 lb) with facial swelling:

Rx:Azithromycin 100 mg/5 ml
Disp: 30 ml