Telithromycin warnings and precautions

# Warnings And Precautions

## WARNINGS

### Hepatotoxicity
Acute hepatic failure and severe liver injury, in some cases fatal, have been reported in patients treated with KETEK. These hepatic reactions included fulminant hepatitis and hepatic necrosis leading to liver transplant, and were observed during or immediately after treatment. In some of these cases, liver injury progressed rapidly and occurred after administration of a few doses of KETEK. (See ADVERSE REACTIONS)
Physicians and patients should monitor for the appearance of signs or symptoms of hepatitis, such as fatigue, malaise, anorexia, nausea, jaundice, bilirubinuria, acholic stools, liver tenderness or hepatomegaly. Patients with signs or symptoms of hepatitis must be advised to discontinue KETEK and immediately seek medical evaluation, which should include liver function tests. (See ADVERSE REACTIONS, PRECAUTIONS, Information to Patients.) If clinical hepatitis or transaminase elevations combined with other systemic symptoms occur, KETEK should be permanently discontinued.
Ketek must not be re-administered to patients with a previous history of hepatitis and/or jaundice associated with the use of KETEK tablets, or any macrolide antibiotic. (SeeCONTRAINDICATIONS)
In addition, less severe hepatic dysfunction associated with increased liver enzymes, hepatitis and in some cases jaundice was reported with the use of KETEK. These events associated with less severe forms of liver toxicity were reversible.

### QTc prolongation
Telithromycin has the potential to prolong the QTc interval of the electrocardiogram in some patients. QTc prolongation may lead to an increased risk for ventricular arrhythmias, including torsades de pointes. Thus, telithromycin should be avoided in patients with congenital prolongation of the QTc interval, and in patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, and in patients receiving Class IA (e.g., quinidine and procainamide) or Class III (e.g., dofetilide) antiarrhythmic agents.
Cases of torsades de pointes have been reported post-marketing with KETEK. In clinical trials, no cardiovascular morbidity or mortality attributable to QTc prolongation occurred with telithromycin treatment in 4780 patients in clinical trials, including 204 patients having a prolonged QTc at baseline.

### Visual disturbances
KETEK may cause visual disturbances particularly in slowing the ability to accommodate and the ability to release accommodation. Visual disturbances included blurred vision, difficulty focusing, and diplopia. Most events were mild to moderate; however, severe cases have been reported.

### Loss of Consciousness
There have been post-marketing adverse event reports of transient loss of consciousness including some cases associated with vagal syndrome.
- Because of potential visual difficulties or loss of consciousness, patients should attempt to minimize activities such as driving a motor vehicle, operating heavy machinery or engaging in other hazardous activities during treatment with KETEK. If patients experience visual disorders or loss of consciousness while taking KETEK, patients should not drive a motor vehicle, operate heavy machinery or engage in other hazardous activities.
(See PRECAUTIONS, Information for Patients)

### Pseudomembranous colitis
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including KETEK, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C difficile, and surgical evaluation should be instituted as clinically indicated.

## PRECAUTIONS

### General
Prescribing KETEK in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Telithromycin is principally excreted via the liver and kidney. Telithromycin may be administered without dosage adjustment in the presence of hepatic impairment. In the presence of severe renal impairment (CLCR < 30 mL/min), a reduced dosage of KETEK is recommended. (See DOSAGE AND ADMINISTRATION)

### Information for patients
A Medication Guide is provided to patients when Ketek is dispensed. Patients should be instructed to read the MedGuide when Ketek is received. In addition, the complete text of the MedGuide is reprinted at the end of this document.
The following information and instructions should be communicated to the patient.
- KETEK may cause problems with vision particularly when looking quickly between objects close by and objects far away.  These events include blurred vision, difficulty focusing, and objects looking doubled. Most events were mild to moderate; however, severe cases have been reported. Problems with vision were reported as having occurred after any dose during treatment, but most occurred following the first or second dose. These problems lasted several hours and in some patients came back with the next dose. (See WARNINGSand ADVERSE REACTIONS.)
Patients should be advised that avoiding quick changes in viewing between objects in the distance and objects nearby may help to decrease the effects of these visual difficulties.
- Because of potential visual difficulties, loss of consciousness, confusion or hallucinations, patients should attempt to minimize activities such as driving a motor vehicle, operating heavy machinery or engaging in other hazardous activities during treatment with KETEK.
If patients experience visual difficulties, loss of consciousness / fainting, confusion or hallucination
- patients should seek advice from their physician before taking another dose
- patients should not drive a motor vehicle, operate heavy machinery, or engage in otherwise hazardous activities.
Patients should also be advised:
- Ketek is contraindicated in patients with myasthenia gravis.
(See CONTRAINDICATIONS)
-f the possibility of liver injury, associated with KETEK, which in rare cases may be severe. Patients developing signs or symptoms of liver injury should be instructed to discontinue *KETEK and seek medical attention immediately. Symptoms of liver injury may include nausea, fatigue, anorexia, jaundice, dark urine, light-colored stools, pruritus, or tender abdomen. *Ketek must not be taken by patients with a previous history of hepatitis/jaundice associated with the use of KETEK or macrolide antibiotics.
(See CONTRAINDICATIONS and WARNINGS)
antibacterial drugs including KETEK should only be used to treat bacterial infections.  They do not treat viral infections (e.g., the common cold).  When KETEK is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed.  Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by KETEK or other antibacterial drugs in the future.
- KETEK has the potential to produce changes in the electrocardiogram (QTc interval prolongation) and that they should report any fainting occurring during drug treatment.
- KETEK should be avoided in patients receiving Class 1A (e.g., quinidine, procainamide) or Class III (e.g., dofetilide) antiarrhythmic agents.
- to inform their physician of any personal or family history of QTc prolongation or proarrhythmic conditions such as uncorrected hypokalemia, or clinically significant bradycardia.
diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.
- simvastatin, lovastatin, or atorvastatin should be avoided in patients receiving KETEK.  If KETEK is prescribed, therapy with simvastatin, lovastatin, or atorvastatin should be stopped during the course of treatment. (See CLINICAL PHARMACOLOGY, Drug-drug interactions)
- colchicine should be avoided in patients receiving KETEK. If KETEK is prescribed in patients with normal kidney and liver function, the dose is colchicine should be reduced. Concomitant treatment with KETEK and colchicine is contraindicated in patients with kidney or liver impairment. (See CONTRAINDICATIONS and WARNINGS, Drug interactions.)
- KETEK tablets can be taken with or without food.
- to inform their physician of any other medications taken concurrently with KETEK, including over-the-counter.