clarithromycin, Biaxin, Biaxin XL

 Indications

Respiratory tract infections including streptococcal

pharyngitis, sinusitis, bronchitis, and pneumonia.

Treatment (with ethambutol) and prevention of disseminated

Mycobacterium avium complex (MAC). Treatment

of following pediatric infections: Otitis media, Sinusitis,

Pharyngitis, Skin/skin structure infections. Part

of a combination regimen for ulcer disease due to Helicobacter

pylori. Endocarditis prophylaxis.

Action

Inhibits protein synthesis at the level of the 50S bacterial

ribosome. Therapeutic Effects: Bacteriostatic

action. Spectrum: Active against these gram-positive

aerobic bacteria: Staphylococcus aureus, S. pneumoniae,

S. pyogenes (group A strep). Active against these

gram-negative aerobic bacteria: Haemophilus influenzae,

Moraxella catarrhalis. Also active against: Mycoplasma,

Legionella, H. pylori, M. avium.

Pharmacokinetics

Absorption: Rapidly absorbed (50%) after oral administration.

Distribution: Widely distributed; tissue levels may

exceed those in serum.

Protein Binding: 65–70%.

Metabolism and Excretion: 10–15% converted

by the liver to 14-hydroxyclarithromycin, which has

anti-infective activity; 20–30% excreted unchanged in

urine. Metabolized by and also inhibits the CYP3A enzyme

system.

Half-life: Dose-dependent and prolonged with renal

dysfunction 250-mg dose—3–4 hr; 500-mg dose—

5–7 hr.

TIME/ACTION PROFILE (serum levels)

ROUTE ONSET PEAK DURATION

PO unknown 2 hr 12 hr

PO-XL unknown 4 hr 24 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity to clarithromycin,

erythromycin, or other macrolide anti-infectives;

History of cholestatic jaundice or hepatic dysfunction

with clarithromycin; Concurrent use of pimozide, ergotamine,

dihydroergotamine, lovastatin, simvastatin,

quinidine, procainamide, dofetilide, amiodarone, or

sotalol; Concurrent use of colchicine in patients with

hepatic or renal impairment; QT interval prolongation,

hypokalemia, hypomagnesemia, or bradycardia; OB:

Avoid use during pregnancy unless no alternatives are

available; Lactation: Not recommended for breast-feeding

women.

Use Cautiously in: Severe liver or renal impairment

(dose adjustment required if CCr 30 mL/min); Myasthenia

gravis; Geri: May haveqrisk of QT interval prolongation.

Adverse Reactions/Side Effects

CNS: headache. CV: TORSADES DE POINTES, QT interval

prolongation. Derm: STEVENS-JOHNSON SYNDROME,

pruritus, rash. GI: HEPATOTOXICITY, CLOSTRIDIUM DIFFICILE-

ASSOCIATED DIARRHEA (CDAD), abdominal pain/discomfort,

abnormal taste, diarrhea, dyspepsia, nausea.

Misc: ANGIOEDEMA.

Interactions

Drug-Drug: Clarithromycin is an inhibitor of the

CYP3A enzyme system. Concurrent use with other

agents metabolized by this system canqlevels and risk

of toxicity. May prolong the QT interval andqrisk of arrhythmias

with pimozide; concurrent use contraindicated.

Mayqlevels of ergotamine and dihydroergotamine

and risk for acute ergot toxicity; concurrent

use contraindicated. Quinidine, procainamide, dofetilide,

sotalol, and amiodarone mayqrisk of QT

interval prolongation; concurrent use should be

avoided.qrisk of rhabdomyolysis with lovastatin and

simvastatin; concurrent use contraindicated. Mayq

serum levels and the risk of toxicity from carbamazepine,

some benzodiazepines (midazolam, triazolam,

alprazolam), cyclosporine, disopyramide,

quinidine, ergot alkaloids, felodipine, omeprazole,

tacrolimus, digoxin, quetiapine, or theophylline.

Mayqlevels and effects of omeprazole. Ritonavirqblood

levels (pclarithromycin dose in patients

with CCr 60 mL/min).qlevels and risk of myopathy

from atorvastatin and pravastatin; use lowest dose

of these agents; do not exceed atorvastatin dose of 20

mg/day or pravastatin dose of 40 mg/day. Mayqorpeffects of zidovudine. Blood levels areqby delavirdine

and fluconazole. Blood levels may bepby rifampin,

rifabutin, efavirenz, and nevirapine. May

qlevels and risk of toxicity from colchicine;pcolchicine

dose in patients with normal renal and hepatic

function; concurrent use is contraindicated in patients

with renal or hepatic impairment. Mayqverapamil

levels and the risk for hypotension, bradycardia, and

lactic acidosis. Concomitant use with calcium channel

blockers metabolized by CYP3A4, including verapamil,

diltiazem, amlodipine, and nifedipine mayq

the risk of acute kidney injury, especially in patients

older than 65 yr. Mayqwarfarin levels and the risk

for bleeding. Mayqblood levels and effects of sildenafil,

tadalafil, and vardenafil; concurrent use not

recommended. Mayqlevels of tolterodine. Concurrent

use with atazanavir mayqclarithromycin and

atazanavir levels;pclarithromycin dose by 50%. Concurrent

use with itraconazole mayqclarithromycin

and itraconazole levels. Concurrent use with saquinavir

mayqclarithromycin and saquinavir levels.

Route/Dosage

PO (Adults): Pharyngitis/tonsillitis—250 mg every

12 hr for 10 days; Acute maxillary sinusitis—500 mg

every 12 hr for 14 days or 1000 mg once daily for 14

days as XL tablets; Acute exacerbation of chronic

bronchitis—250–500 mg every 12 hr for 7–14 days

or 1000 mg once daily for 7 days as XL tablets; Community-

acquired pneumonia—250 mg every 12 hr

for 7–14 days or 1000 mg once daily for 7 days as XL

tablets; Skin/skin structure infections—250 mg

every 12 hr for 7–14 days; H. pylori—500 mg 2–3

times daily with a proton pump inhibitor (lansoprazole

or omeprazole) or ranitidine with or without amoxicillin

for 10–14 days; Endocarditis prophylaxis—500

mg 1 hr before procedure; MAC prophylaxis/treatment—

500 mg twice daily, for active infection another

antimycobacterial is required.

PO (Children): Most infections—15 mg/kg/day divided

every 12 hr for 7–14 days (up to 500 mg/dose

for MAC). Endocarditis prophylaxis—15 mg/kg 1 hr

before procedure.

Renal Impairment

PO (Adults): CCr 30 mL/min—250 mg 1–2 times

daily, a 500-mg initial dose may be used.

PO (Children): CCr 30 mL/min—pdose by 50%

or double dosing interval.

Availability (generic available)

Tablets: 250 mg, 500 mg. Extended-release tablets:

500 mg. Oral suspension (fruit punch and

vanilla flavors): 125 mg/5 mL, 250 mg/5 mL. In

combination with: amoxicillin and lansoprazole as

part of a compliance package (Prevpac); See

Appendix B.