Approvals,Submission,and Important Labeling Changes for US Marketed Pharmaceuticals

WARNINGS AND PRECAUTIONS

Renal Abnormalities

Deleted the statement, “Safety and effectiveness of Vidaza in patients with MDS and renal impairment have not been studied as these patients were excluded from the clinical trials.”

USE IN SPECIFIC POPULATIONS

Renal Impairment - new section added

Severe renal impairment has no major effect on the pharmacokinetic exposure of azacitidine after single and multiple subcutaneous (SC) administrations. Therefore, azacitidine can be administered to subjects with renal impairment without initial dose adjustment.

http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm289980.htm

CONTRAINDICATIONS: Table 2 added alfuzosin, doxazosin, silodosin, and tamsulosin.

DRUG INTERACTIONS

Added calcium channel blockers, amlodipine, diltiazem, nisoldipine, and verapamil

http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm303600.htm

WARNINGS AND PRECAUTIONS

Increased Mortality in Ventilator-Associated Bacterial Pneumonia

In a clinical trial of patients with ventilator-associated bacterial pneumonia comparing doripenem to imipenem, more subjects receiving doripenem died (23%; 31/135) compared to those receiving imipenem (16.7%; 22/132) based on 28-day all-cause mortality in the intent-to-treat population. Clinical response rates were also lower in the doripenem arm. Doripenem is not approved for the treatment of ventilator-associated bacterial pneumonia.

http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm351550.htm

WARNING AND PRECAUTIONS

Renal Impairment and Failure

Marked increase in serum creatinine, pre-renal azotemia, and acute renal failure, often in the setting of heart failure or hypovolemia, have been reported in patients taking Multaq. In most cases, these effects appear to be reversible upon drug discontinuation and with appropriate medical treatment.

Monitor renal function periodically.

Small increases in creatinine levels (about 0.1 mg/dL) following dronedarone treatment initiation have been shown to be a result of inhibition of creatinine's tubular secretion. The elevation has a rapid onset, reaches a plateau after 7 days, and is reversible after discontinuation.

http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm243762.htm

WARNINGS

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity, has been reported in patients taking antiepileptic drugs, including phenytoin and Cerebyx.

PRECAUTIONS

Drug Interactions: addition of tacrolimus and albendazole

http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm283239.htm

CONTRAINDICATIONS

Lidocaine hydrochloride is contraindicated in patients with a known history of hypersensitivity to local anesthetics of the amide type.

Lidocaine should not be used in patients with Stokes-Adams syndrome, Wolff-Parkinson-White syndrome, or with severe degrees of sinoatrial, atrioventricular, or intraventricular block.

Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.

WARNINGS

Constant monitoring with an electrocardiograph is essential to the proper administration of lidocaine hydrochloride intravenously. It is mandatory to have emergency resuscitative equipment and drugs immediately available to manage adverse reactions involving cardiovascular, respiratory, or central nervous systems. Anaphylactic reactions may occur following administration of lidocaine hydrochloride. In the case of severe reaction, discontinue the use of the drug.

PRECAUTIONS

General

Caution should be employed in the repeated use of lidocaine hydrochloride in patients with severe liver or renal disease because accumulation may occur and lead to toxic phenomena, since lidocaine hydrochloride is metabolized mainly in the liver and excreted by the kidneys. The drug should also be used with caution in patients with hypovolemia and shock and in all forms of heart block.

In patients with sinus bradycardia or incomplete heart block, the administration of lidocaine hydrochloride intravenously for the elimination of ventricular ectopic beats without prior acceleration in heart rate (eg, by isoproterenol or by electric pacing) may promote more frequent and serious ventricular arrhythmias or complete heart block.

Most potent anesthetic agents, local anesthetics of the amide type that includes lidocaine, and muscle relaxants of both depolarizing and nondepolarizing types have been associated with malignant hyperthermia.

Care should be taken in the administration of intravenous fluids in patients with compromised myocardial function to avoid fluid overload or disturbances of serum electrolyte concentrations which might interfere with cardiac conduction or result in congestive heart failure.

If administration is controlled by a pumping device, care must be taken to discontinue pumping action before the container runs dry or air embolism may result. If administration is not controlled by a pumping device, refrain from applying excessive pressure (>300 mm Hg) causing distortion to the container such as wringing or twisting. Such handling could result in breakage of the container.

These solutions are intended for intravenous administration using sterile equipment. It is recommended that intravenous administration apparatus be replaced at least once every 24 hours.

Use only if solution is clear and container and seals are intact.

Drug Interactions

Added: potential interactions with cimetidine and amiodarone.

ADVERSE REACTIONS

Systemic reactions of the following types have been reported:

Central Nervous System: Light-headedness; drowsiness; dizziness; apprehension; euphoria; tinnitus; blurred or double vision; vomiting; sensation of heat, cold, or numbness; twitching; tremors; convulsions; unconsciousness; respiratory depression and arrest.

Cardiovascular System: Hypotension, cardiovascular arrest, and bradycardia, which may lead to cardiac arrest.

Hematologic Effects: Methemoglobinemia.

Allergic reactions, including anaphylactic reactions, may occur but are infrequent. There have been no reports of cross-sensitivity between lidocaine hydrochloride and procainamide or between lidocaine hydrochloride and quinidine.

http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm342035.htm

BOXED WARNING

Warning: Fetal toxicity

When pregnancy is detected, discontinue Cozaar as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

WARNINGS

Fetal Toxicity: Pregnancy Category D - extensive revision to this section

PRECAUTIONS

Pregnancy:

Female patients of childbearing age should be told about the consequences of exposure to Cozaar during pregnancy. Discuss treatment options with women planning to become pregnant.

Neonates with a history of in utero exposure to Cozaar: If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.

http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm169666.htm

http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm169677.htm

WARNINGS AND PRECAUTIONS

Risk of Bleeding

Reversal of Anticoagulant Effect:

Use with P-gp and Strong CYP3A4 Inhibitors or Inducers

Patients with Prosthetic Heart Valves

Acute PE in Hemodynamically Unstable Patients or Patients Who Require Thrombolysis or Pulmonary Embolectomy

http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm367392.htm

WARNINGS AND PRECAUTIONS: Use of Sildenafil with Bosentan - section deleted

USE IN SPECIFIC POPULATIONS

Pregnancy - Pregnancy Category B: There are no adequate and well-controlled studies of sildenafil in pregnant women.

http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm319416.htm

WARNINGS AND PRECAUTIONS

Visual field defects have been reported in patients receiving topiramate independent of elevated intraocular pressure. In clinical trials, most of these events were reversible after topiramate discontinuation. If visual problems occur at any time during topiramate treatment, consideration should be given to discontinuing the drug.

http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm195797.htm