AUDIENCE: Health Professional, Internal Medicine, Cardiology, Patient
ISSUE: FDA is advising caution before prescribing the antibiotic clarithromycin (Biaxin) to patients with heart disease because of a potential increased risk of heart problems or death that can occur years later. FDAs recommendation is based on a review of the results of a 10-year follow-up study of patients with coronary heart disease from a large clinical trial that first observed this safety issue.
The large clinical trial, called the CLARICOR trial, observed an unexpected increase in deaths among patients with coronary heart disease who received a two-week course of clarithromycin that became apparent after patients had been followed for one year or longer. There is no clear explanation for how clarithromycin would lead to more deaths than placebo. Some observational studies also found an increase in deaths or other serious heart-related problems, while others did not. All the studies had limitations in how they were designed. Of the six observational studies published to date in patients with or without coronary artery disease, two found evidence of long-term risks from clarithromycin, and four did not. Overall, results from the prospective, placebo-controlled CLARICOR trial provide the strongest evidence of the increase in risk compared to the observational study results. Based on these studies, FDA is unable to determine why the risk of death is greater for patients with heart disease.
As a result, FDA added a new warning about this increased risk of death in patients with heart disease, and advised prescribers to consider using other antibiotics in such patients. FDA also added the study results to the clarithromycin drug labels. As part of FDA's usual ongoing safety monitoring of drugs, we are continuing to monitor safety reports in patients taking clarithromycin.
BACKGROUND: Clarithromycin is used to treat many types of infections affecting the skin, ears, sinuses, lungs, and other parts of the body, including Mycobacterium avium complex (MAC) infection, a type of lung infection that often affects people with human immunodeficiency virus (HIV). Clarithromycin is not approved to treat heart disease.
RECOMMENDATION: Healthcare professionals should be aware of these significant risks and weigh the benefits and risks of clarithromycin before prescribing it to any patient, particularly in patients with heart disease and even for short periods, and consider using other available antibiotics. Advise patients with heart disease of the signs and symptoms of cardiovascular problems, regardless of the medical condition for which you are treating them with clarithromycin.
Patients should tell your healthcare professionals if you have heart disease, especially when you are being prescribed an antibiotic to treat an infection. Talk to them about the benefits and risks of clarithromycin and any alternative treatments. Do not stop taking your heart disease medicine or antibiotic without first talking to your healthcare professionals. Doing so could be harmful without your health care professionals' direct supervision. Seek medical attention immediately if you experience symptoms of a heart attack or stroke, such as chest pain, shortness of breath or trouble breathing, pain or weakness in one part or side of your body, or slurred speech.
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
Why is this medication prescribed?
Clarithromycin is used to treat certain bacterial infections, such as pneumonia (a lung infection), bronchitis (infection of the tubes leading to the lungs), and infections of the ears, sinuses, skin, and throat. It also is used to treat and prevent disseminated Mycobacterium avium complex (MAC) infection [a type of lung infection that often affects people with human immunodeficiency virus (HIV)]. It is used in combination with other medications to eliminate H. pylori, a bacterium that causes ulcers. Clarithromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.
Antibiotics such as clarithromycin will not work for colds, flu, or other viral infections. Taking antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.
How should this medicine be used?
Clarithromycin comes as a tablet, an extended-release (long-acting) tablet, and a suspension (liquid) to take by mouth. The regular tablet and liquid are usually taken with or without food every 12 hours (twice a day) for 7 to 14 days. The long-acting tablet is usually taken with food every 24 hours (once a day) for 7 to 14 days. Your doctor may tell you to take clarithromycin for a longer time depending on your condition. Take clarithromycin at around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take clarithromycin exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Shake the suspension well before each use to mix the medication evenly.
The tablets should be taken with a full glass of water. Swallow the long-acting tablets whole; do not split, chew, or crush them.
You should begin to feel better during the first few days of treatment with clarithromycin. If your symptoms do not improve or get worse, call your doctor.
Take clarithromycin until you finish the prescription, even if you feel better. If you stop taking clarithromycin too soon, or skip doses, your infection may not be completely treated and the bacteria may become resistant to antibiotics.
Other uses for this medicine
Clarithromycin also is used sometimes to treat other types of infections including Lyme disease (an infection that may develop after a person is bitten by a tick), cryptosporidiosis (an infection that causes diarrhea), cat scratch disease (an infection that may develop after a person is bitten or scratched by a cat), Legionnaires' disease, (type of lung infection), and pertussis (whooping cough; a serious infection that can cause severe coughing). It is also sometimes used to prevent heart infection in patients having dental or other procedures. Talk to your doctor about the possible risks of using this medication for your condition.
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Before taking clarithromycin,
- tell your doctor and pharmacist if you are allergic to clarithromycin, azithromycin (Zithromax, Zmax), dirithromycin (Dynabac) (not available in the U.S.), erythromycin (E.E.S., E-Mycin, Erythrocin), telithromycin (Ketek), any other medications, or any of the ingredients in clarithromycin tablets or suspension. Ask your pharmacist for a list of the ingredients.
- tell your doctor if you are taking astemizole (Hismanal) (not available in the U.S.),cisapride (Propulsid), colchicine (Colcrys), dihydroergotamine (DHE 45, Migranal), ergotamine (Ergomar, in Cafergot, in Migergot), lovastatin (Mevacor, in Advicor) pimozide (Orap), simvastatin (Zocor, in Vytorin), or terfenadine (Seldane) (not available in the U.S.). Your doctor will probably tell you not to take clarithromycin if you are taking one or more of these medications.
- tell your doctor if you have or have ever had prolonged QT interval (a rare heart problem that may cause fainting or irregular heartbeat) or ventricular arrhythmia (abnormal heart rhythms) or if you have ever had jaundice (yellowing of the skin or eyes) or other liver problems while taking clarithromycin, Your doctor will probably tell you not to take clarithromycin.
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: anticoagulants ('blood thinners') such as warfarin (Coumadin); certain benzodiazepines such as alprazolam (Xanax), midazolam (Versed), and triazolam (Halcion); bromocriptine (Parlodel); calcium channel blockers such as amlodipine (Norvasc, in Caduet, in Lotrel), diltiazem (Cardizem, Dilacor, Tiazac), and verapamil (Calan, Covera, Isoptin, Verelan, in Tarka); carbamazepine (Tegretol); certain medications for HIV such as atazanavir (Reyataz), didanosine (Videx), efavirenz (Sustiva, in Atripla), nevirapine (Viramune), nelfinavir (Viracept), ritonavir (Norvir, in Kaletra), saquinavir (Invirase), and zidovudine (AZT, Retrovir); certain medications for irregular heartbeat such as amiodarone (Cordarone, Pacerone), disopyramide (Norpace), dofetilide (Tikosyn), procainamide (Procanbid), quinidine, and sotalol (Betapace); cholesterol-lowering medications (statins) such as atorvastatin (Lipitor, in Caduet) and pravastatin (Pravachol); cilostazol (Pletal); cyclosporine (Neoral, Sandimmune); darifenacin (Enablex); digoxin (Digitek, Lanoxin); erlotinib (Tarceva); eszopiclone (Lunesta); fluconazole (Diflucan); insulin; itraconazole (Sporanox); methylprednisolone (Medrol); omeprazole (Prilosec); oral medications for diabetes such as nateglinide (Starlix), pioglitazone (Actos, in Actoplus Met, in Duetact), repaglinide (Prandin, in Prandimet), and rosiglitazone (Avandia, in Avandamet, in Avandaryl); phenytoin (Dilantin); ranitidine (Zantac); rifabutin (Mycobutin); rifampin (Rifadin, Rifamate, rifampicin, Rimactane); rifapentine (Priftin); sildenafil (Viagra); tacrolimus (Prograf); theophylline (Theo-Dur); tadalafil (Cialis, Adcirca); tolterodine (Detrol); valproate (Depacon); valproic acid (Depakote); vardenafil (Levitra); and vinblastine. Many other medications may also interact with clarithromycin, so tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor if you have a low level of magnesium or potassium in your blood, or if you have or have ever had an irregular heartbeat, or kidney, or liver disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking clarithromycin, call your doctor.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking clarithromycin.
What special dietary instructions should I follow?
Unless your doctor tells you otherwise, continue your normal diet.
What should I do if I forget a dose?
Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
What side effects can this medication cause?
Clarithromycin may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- stomach pain
- change in taste
Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately or get emergency medical treatment:
- swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
- difficulty breathing or swallowing
- peeling or blistering skin
- yellowing of the skin or eyes
- extreme tiredness
- unusual bleeding or bruising
- lack of energy
- loss of appetite
- pain in the upper right part of the stomach
- dark-colored urine
- flu-like symptoms
- fast, pounding, or irregular heartbeat
- muscle weakness such as difficulty chewing, talking, or performing daily activities
- double vision
Clarithromycin may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).
What should I know about storage and disposal of this medication?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store the tablets at room temperature and away from light, excess heat, and moisture (not in the bathroom). Do not refrigerate the suspension. Keep it at room temperature and away from excess heat and moisture. Throw away any unused suspension after 14 days.
It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org
Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.
In case of emergency/overdose
In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.
Symptoms of overdose may include the following:
- stomach pain
What other information should I know?
Keep all appointments with your doctor and the laboratory. Your doctor may order certain lab tests to check your body's response to clarithromycin.
The extended-release tablet does not dissolve in the stomach after swallowing. It slowly releases the medication as it passes through your digestive system. You may notice the tablet coating in the stool. This is normal and does not mean that you did not get the full dose of medication.
Do not let anyone else take your medication. Your prescription is probably not refillable. If you still have symptoms of infection after you finish the clarithromycin, call your doctor.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
- Biaxin® Filmtab®
- Biaxin® Granules
- Biaxin® XL Filmtab
- Biaxin® XL Pac
- Prevpac® (as a combination product containing amoxicillin and lansoprazole)