Biaxin XL

Dosage Forms & Strengths

oral suspension

• 125mg/5mL
• 250mg/5mL

tablet

• 250mg
• 500mg

tablet, extended release

• 500mg

Acute Exacerbation of Chronic Bronchitis

250-500 mg PO q12hr for 7-14 days

Extended release: 1000 mg PO once daily for 7 days

Acute Maxillary Sinusitis

500 mg PO q12hr for 14 days

Extended release: 1000 mg PO once daily for 14 days

Mycobacterial Infection

Prophylaxis and treatment

500 mg PO q12hr for 7-14 days

Use with antimycobacterial drugs such as rifampin and ethambutol

Peptic Ulcer Disease

500 mg PO q8-12hr for 10-14 days

Administer as part of 2- or 3-drug combination regimen with bismuth subsalicylate, amoxicillin, H2 receptor antagonist, or proton pump inhibitor

Pharyngitis, Tonsillitis

250 mg PO q12hr for 10 days

Community-Acquired Pneumonia

250 mg PO q12hr for 7-14 days

Extended release: 1000 mg PO once daily for 7 days

Pertusis (Off-label)

500 mg PO twice daily for 7 days

Skin/Skin Structure Infection

250 mg PO q12hr for 7-14 days

Endocarditis

Prophylaxis

500 mg PO 30-60 minutes before surgical procedure

Crohn Disease (Orphan)

Treatment of pediatric Crohn disease in combination with rifabutin and clofazimine

Orphan indication sponsor

• RedHill Biopharma Ltd; 42 Givati St; Israel

Dosing Modifications

Renal impairment (CrCl <30 mL/min): Reduce normal dose by 50%

In combination with atazanavir: CrCl 30-60 mL/min decrese, dose by 50%; CrCl <30 mL/min, decrease dose by 75%

Dosing Considerations

Susceptible organisms

• Actinobacillus actinomycetemcomitans, Actinomyces israelii, Actinomyces naeslundii, Actinomyces odontolyticus, Afipia felis, Arachnia propionica, Bartonella henselae, Bartonella quintana, Chlamydia pneumoniae (TWAR agent), Bordetella pertussis, Borrelia recurrentis, Calymmatobacterium granulomatis, Campylobacter jejuni, Chlamydia spp, Haemophilus ducreyi, Haemophilus influenzae, Helicobacter pylori, Legionella pneumophila, Mycobacterium avium complex (MAC), Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium genavense, Mycobacterium gordonae, Mycobacterium kansasii, Mycobacterium leprae, Mycobacterium marinum, Mycobacterium scrofulaceum, Mycobacterium simiae, Mycobacterium szulgai, Mycobacterium ulcerans, Mycobacterium xenopi, Mycoplasma pneumoniae, Moraxella (Branhamella) catarrhalis, Staphylococcus aureus, Streptococcus (group C, G), Streptococcus agalactiae (group B), Streptococcus bovis (group D), Streptococcus intermedius group (Streptococcus anginosus, Streptococcus intermedius, Streptococcus constellatus), Streptococcus pneumoniae (penicillin sensitive; minimal inhibitory concentration [MIC] <0.1 mcg/mL), Streptococcus pyogenes (group A), viridans streptococci, Ureaplasma urealyticum
• H pylori (with lansoprazole and amoxicillin)
• First-line: A felis, B henselae, B quintana, B pertussis, C jejuni, C pneumoniae, H ducreyi, H pylori, Legionella spp, MAC, M chelonae, M fortuitum, M genavense, M gordonae, M marinum, M scrofulaceum, M simiae, M xenopi; no unanimity on others (eg, H influenzae)

Dosage Forms & Strengths

oral suspension

• 125mg/5mL
• 250mg/5mL

tablet

• 250mg
• 500mg

Extended-release tablets: Safety and efficacy not established in children

Community-Acquired Pneumonia, Sinusitis, Bronchitis, Skin Infections

15 mg/kg/day PO divided q12hr for 10 days  

Mycobacterial Infection

Prophylaxis and treatment

7.5 mg/kg PO q12hr; individual dose not to exceed 500 mg

<20 months: Safety of clarithromycin for MAC not studied

Endocarditis

Prophylaxis

15 mg/kg PO 30-60 minutes before surgical procedure; individual dose not to exceed 500 mg 

Streptococcal Pharyngitis

7 mg/kg q12hr for 10 days; individual dose not to exceed 500 mg

Pertussis

<1 month: Safety and efficacy not established

1-6 months: 7.5 mg/kg/dose PO q12hr for 7 days

>6 months: 7.5 mg/kg/dose PO q12hr for 7 days

Contraindications

Documented hypersensitivity

Coadministration with pimozide, cisapride, ergotamine, and dihydroergotamine

History of cholestatic jaundice or hepatic dysfunction associated with previous use of clarithromycin

Coadministration with colchicine in patients with renal or hepatic impairment

Coadministration with HMG-CoA reductase inhibitors (statins) that are extensively metabolized by CYP3A4 (lovastatin, simvastatin), due to the increased risk of myopathy, including rhabdomyolysis

Cautions

Severe renal impairment

Oral solution must not be refrigerated

Not for use in pregnancy, except when there is no alternative therapy; apprise patient about potential hazard to fetus if pregnancy occurs while in therapy

Use for endocarditis prophylaxis is appropriate only for high-risk patients, per American Heart Association (AHA) guidelines

Associated with QT interval prolongation and infrequent cases of arrhythmias, including torsade de pointes; avoid using with ongoing proarrhythmic conditions (eg, uncorrected hypokalemia or hypomagnesemia), clinically significant bradycardia; do not coadminister with class IA (eg, quinidine, procainamide) or class III (dofetilide, amiodarone, sotalol) antiarrhythmics

Elderly patients may be more susceptible to drug-associated QT prolongation

Use caution in patients with coronary artery disease; postmarketing trials suggest increased risk of cardiovascular mortality

Discontinue immediately if severe hypersensitivity reactions occur (eg, anaphylaxis, Stevens-Johnson syndrome, TEN, drug reaction with eosinophilia and systemic symptoms [DRESS] syndrome, Henoch-Schonlein purpura)

Clostridium difficile associated diarrhea reported with use of nearly all antibacterial agents, including clarithromycin

May cause kidney injury when administered concomitantly with calcium channel blockers metabolized by CYP3A4

Do not coadminister with ranitidine/bismuth citrate with history of acute porphyria or if CrCl <25 mL/min

Coadministration with quetiapine may result in quetiapine related toxicities including neuroleptic malignant syndrome, QT prolongation, somnolence, orthostatic hypotension, altered state of consciousness

Exacerbation of myasthenia gravis or new onset of symptoms reported

Hepatic dysfunction

• Increased liver enzyme activity and hepatocellular or cholestatic hepatitis, with or without jaundice, have been reported; this may be severe and is usually reversible
• In some instances, hepatic failure with fatal outcome has been reported, generally in association with serious underlying diseases or concomitant medications
• Discontinue clarithromycin immediately if signs and symptoms of hepatitis occur (eg, anorexia, jaundice, dark urine, pruritus, or tender abdomen)

Clarithromycin may be taken with or without food. For most infections the recommended adult dose is 250-500 mg of immediate release tablets twice daily or 1000 mg of extended release tablets once daily for 7-14 days.

Some clarithromycin side effects can be serious. See "Drug Precautions" section.

Most side effects are mild. During clinical trials, the most frequently reported side effects of clarithromycin in adults included:

• diarrhea
• nausea
• abnormal taste
• indigestion
• stomach pain or discomfort
• headache (2%)

In children, the most frequently reported side effects were:

• diarrhea
• vomiting 
• stomach pain 
• rash
• headache 

This is not a complete list of clarithromycin side effects. Ask your doctor or pharmacist for more information.

It is very important that your doctor check the progress of you or your child at regular visits to make sure this medicine is working properly. Blood and urine tests may be needed to check for unwanted effects.

Do not use this medicine if you or your child are also using astemizole (Hismanal®), cisapride (Propulsid®), lovastatin (Mevacor®), pimozide (Orap®), simvastatin (Zocor®), terfenadine (Seldane®), or certain ergot medicines (eg, dihydroergotamine, ergotamine, D.H.E. 45®, Ergomar®, Ergostat®, or Migranal®). If you have kidney or liver disease, do not take this medicine together with colchicine (Colcrys®). Using these medicines together may increase the risk for more serious side effects.

If your or your child's symptoms do not improve within a few days, or if they become worse, check with your doctor.

Make sure your doctor knows if you are pregnant or planning to become pregnant. If you become pregnant while using this medicine, tell your doctor right away.

This medicine may cause serious allergic reactions, including anaphylaxis. This can be life-threatening and requires immediate medical attention. Call your doctor right away if you or your child have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, mouth, or throat while you or your child are using this medicine.

Serious skin reactions can occur with this medicine. Check with your doctor right away if you or your child have blistering, peeling, or loosening of the skin, red skin lesions, severe acne or skin rash, sores or ulcers on the skin, or fever or chills while you or your child are using this medicine.

Check with your doctor right away if you or your child have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, unusual tiredness or weakness, or yellow eyes or skin. These could be symptoms of a serious liver problem.

Contact your doctor right away if you have any changes to your heart rhythm. You might feel dizzy or faint, or you might have a fast, pounding, or uneven heartbeat. Make sure your doctor knows if you or anyone in your family has ever had a heart rhythm problem, such as QT prolongation.

Clarithromycin may increase the risk for heart and blood vessel problems in patients with these conditions. It may occur a year or 10 years after the use of this medicine. Talk to your doctor if you have concerns about this risk.

This medicine may cause diarrhea, and in some cases it can be severe. It may occur 2 months or more after you or your child stop taking this medicine. Do not take any medicine to treat diarrhea without first checking with your doctor. Diarrhea medicines may make the diarrhea worse or make it last longer. If you have any questions or if mild diarrhea continues or gets worse, check with your doctor.

Make sure any doctor or dentist who treats you knows that you or your child are using this medicine. This medicine may affect the results of certain medical tests.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Immediate-release: 500 mg orally every 12 hours for 14 days
Extended-release: 1000 mg orally every 24 hours for 14 days

Uses: For the treatment of acute maxillary sinusitis due to Haemophilus influenzae, Moraxella catarrhalis, or S pneumoniae

Immediate-release:
-Due to H influenzae: 500 mg orally every 12 hours for 7 to 14 days
-Due to H parainfluenzae: 500 mg orally every 12 hours for 7 days
-Due to M catarrhalis or S pneumoniae: 250 mg orally every 12 hours for 7 to 14 days

Extended-release: 1000 mg orally every 24 hours for 7 days

Uses: For the treatment of acute bacterial exacerbation of chronic bronchitis due to H influenzae, H parainfluenzae, M catarrhalis, or S pneumoniae

Immediate-release: 500 mg orally twice a day

Use: For the prevention of disseminated Mycobacterium avium complex (MAC) disease in patients with advanced HIV infection

US CDC, National Institutes of Health (NIH), and HIV Medicine Association of the Infectious Diseases Society of America (HIVMA/IDSA) Recommendations for HIV-infected Patients:
-Primary prevention of disseminated MAC disease: 500 mg orally twice a day
-Chronic maintenance therapy (secondary prophylaxis) for disseminated MAC disease: 500 mg orally twice a day

Comments:
-Primary prophylaxis against disseminated MAC disease recommended for patients with CD4 count less than 50 cells/mm3 (after active disseminated MAC disease has been ruled out based on clinical assessment).
-This drug is a preferred prophylactic agent for primary prevention of disseminated MAC disease (except during pregnancy).
-The combination of this drug and rifabutin should not be used for primary MAC prophylaxis; not more effective than this drug alone.
-Primary MAC prophylaxis should be discontinued in patients responding to antiretroviral therapy (ART) with increase in CD4 count to greater than 100 cells/mm3 for at least 3 months; should restart if CD4 count declines to less than 50 cells/mm3.
-This drug should be used with ethambutol for chronic maintenance therapy; same regimen as for treatment.
-Patients with disseminated MAC disease should continue chronic maintenance therapy (secondary prophylaxis) unless immune reconstitution occurs due to ART.
-Chronic maintenance therapy may be stopped in patients at low risk of MAC recurrence; such patients have completed at least 12 months of MAC therapy, have no signs/symptoms of MAC disease, and have an increase in CD4 count to greater than 100 cells/mm3 for more than 6 months in response to ART; should restart if CD4 count declines to less than 100 cells/mm3.

US CDC recommendations:
Immediate-release: 500 mg orally every 12 hours for 7 days

Comments:
-Recommended for treatment and postexposure prophylaxis
-Macrolides are preferred agents for the treatment of pertussis.

Immediate-release:
6 months or older: 7.5 mg/kg orally every 12 hours for 10 days
Maximum dose: 500 mg/dose

Uses: For the treatment of acute maxillary sinusitis due to H influenzae, M catarrhalis, or S pneumoniae

AHA recommendations:
Immediate-release: 15 mg/kg orally as a single dose 30 to 60 minutes before procedure
Maximum dose: 500 mg/dose

Comments:
-Recommended for children allergic to penicillins