Ketoconazole-Anti Fungal Medication Should Not Be Distributed

A consumer advocacy group has asked the FDA to immediately withdraw oral formulations of a decades-old fungal medicine over concerns that serious liver damage outweighs “questionable” benefits. And to reinforce its assertion, the consumer group cites an internal FDA memo in which agency staffers two years ago wrote that they did not view the risks associated with ketoconazole as “tolerable.”

The medicine was approved in 1981 to treat various fungal infections and several generic versions are currently available, although the original brand-name medicine is no longer sold. In its petition to the FDA, however, Public Citizen notes the FDA required a so-called black box warning – the most serious safety alert – for the drug in 1983 due to potentially fatal liver damage.

By July 2013, growing concerns prompted the FDA to issue a safety notice that removed several approved uses from the product labeling because of the risk of liver injury, adrenal gland dysfunction and troubling interactions with other medicines. The agency allowed oral versions of the drug to remain available for five fungal infections in the event other treatments fail or are not tolerated.

On the same day, though, the European Medicines Agency recommended all oral formulations be removed from the market over concerns about liver damage. The EMA review committee “could not identify a fungal infection where the level of hepatotoxicity of the drug could be balanced by an adequately substantiated benefit,” according to its report.

What was not previously known is that in January 2013, 14 staffers in the FDA Office of Surveillance and Epidemiology wrote a memo that the “overall benefit-risk assessment… is negative in the context of all of the drug’s labeled indications.” The 48-page review was undertaken after French regulators in 2011 suspended marketing authorization for the tablets due to safety concerns.

“The FDA’s own experts concluded that ketoconazole was too dangerous to remain on the market for any of its approved uses, yet the agency continues to allow hundreds of thousands of prescription for the medication to be filled each year,” says Sammy Almashat of Public Citizen in a statement. The consumer group says 462,000 prescriptions were written in 2014, citing IMS Health data.

An FDA spokeswoman would only say that the agency “will review the petition and respond directly to the petitioner.” We asked the three generic drug makers that sell ketoconazole in the U.S. – Teva Pharmaceuticals, Mylan Laboratories and Taro Pharmaceuticals – for comment, but no one has responded.

Heritage Pharmaceuticals Doing The Right Thing--

 

Heritage Pharmaceuticals has initiated a nationwide voluntary

recall of ten lots of colistimethate for injection (150 mg) and

three lots of rifampin for injection (600 mg) because of

concerns over lack of  sterility.

 

Colistimethate is indicated for the treatment of acute or

chronic infections due to sensitive strains of certain gram-

negative bacteria.

 

 Rifampin is indicated for the treatment of all forms of 

tuberculosis.The recalled colistimethate has national drug code

(NDC) 23155-193-31, and the recalled rifampin has NDC

23155-340-31.

Both products are sold in single-vial monocartons in case packs

of ten. The recall (to the user level) stems from observations by

the US Food and Drug Administration (FDA) regarding aseptic

and general manufacturing practices at the manufacturer's site

potentially affecting product sterility, according to a company

news release posted on the FDA website. "Intravenous

administration of nonsterile injection products to a normally

sterile site may result in a site-specific or systemic infection,

which in turn may cause hospitalization, significant morbidity

(permanent organ damage), or fatal outcome. To date, Heritage

 is not aware of any adverse patient events resulting from the

use of the subject product lots," the release says.

 

The recalled products were distributed to hospitals, wholesalers, and distributors nationwide from December 2012 through January 2015 for colistimethate and from October 2014 through January 2015 for rifampin.

Customers are being notified by fax, email, United Parcel Service, and/or certified mail to return all recalled product.

Heritage asks all customers to check their inventory "immediately and to quarantine, discontinue distribution of, and return the recalled lots of product. Customers who may have further distributed these products have been requested to identify their customers and notify them at once of this product recall."

Questions regarding this recall can be directed to the customer call center at (866) 901-1230 Monday through Friday from 9:00 am to 5:00 pm Eastern Standard Time.

Adverse reactions or quality problems experienced with the use of these products should be reported to MedWatch, the FDA's safety information and adverse event reporting program, by telephone at 1-800-FDA-1088; by fax at 1-800-FDA-0178; online at https://www.accessdata.fda.gov/scripts/medwatch/medwatch- online.htm; with postage-paid FDA form 3500, available at http://www.fda.gov/MedWatch/getforms.htm; or by mail to MedWatch, 5600 Fishers Lane, Rockville, Maryland 20852-9787.

 

 

 

 

	

Health Canada VS FDA Did They Really Think They'd Win?



Whatever the FDA told Health Canada has had an effect. Days after Health Canada said it would talk to the FDA about Apotex, the regulator has banned the import of finished dosage forms and APIs from two of the drugmaker's plants in India.

Health Canada initially responded to the FDA putting Apotex's finished dose plant in Bangalore, India under import alert by asking the company to quarantine products manufactured at the facility. The quarantine bought Health Canada time to learn why the FDA issued the import alert and formulate its own response. Six days after calling for the quarantine, Health Canada has banned the import of 30 finished products--and a similar number of APIs--that Apotex manufactures at its Bangalore plants.

The regulator has also banned almost 20 APIs--and 50 products in which they are used--from IPCA Laboratories. A common thread links the regulatory actions: Data integrity. "This latest information puts into question Health Canada's trust in the reliability of data that all three plants are required by law to provide to demonstrate the safety and quality of their products," Canadian health minister Rona Ambrose said in a statement.

Reports of data integrity failings at IPCA emerged after FDA visited a plant in July and issued a Form 483. Staff at the IPCA site allegedly falsified temperature records, tweaked integration parameters and overwrote raw data. FDA inspectors visited Apotex around the same time, leading to a warning letter detailing the discarding of undesirable assay results and other data integrity problems.

FDA Warns of NuVision Contamination!

Connecticut health care providers are being urged by the FDA to cease using sterile products from NuVision Pharmacy. The FDA discovered poor sterilization practices being used by NuVision Pharmacy during an inspection that took place in April. Due to the findings of the inspection, the FDA has called upon the pharmaceutical manufacturer to issue a recall for all their sterile products that have not yet passed their expiration dates.


The FDA believes the products made by NuVision Pharmacy may be dangerous and defective drugs due to their possible lack of sterility. According to the FDA, if drugs that are marketed as sterile actually contain a microbial contamination, patients who are given the drugs may be at risk of infection, which can be life-threatening in some cases. The drug manufacturer has repeatedly declined to issue a recall for their sterile products.


Since the FDA does not have the authority to demand a recall of products from NuVision Pharmacy, the manufacturer is not required to do so. However, to deal with the issue, the FDA has called upon health care providers to stop using products labeled sterile by the company. So far, NuVision Pharmacy is not aware of any adverse events related to their sterilized products, but they did end up recalling two other drugs earlier in the year due to sterility concerns. Individuals who have been injected with products made by the company should contact their health care provider if they have any concerns.