Pioglitazone Containing Medicines: Ongoing Safety Review For A Potential Increased Risk of Bladder Cancer

June 20, 2011

June 20, 2011 – The American Food and Drug Administration (FDA) informed recently (on June 15, 2011) that the  use of the diabetes medication Pioglitazone [Actos] for more than one year may be associated with an increased risk of bladder cancer. Information about this risk will be added to the Warnings and Precautions section of the drug labels for pioglitazone-containing medicines (see the graphic at left for brand names and compositions (double click the image for enlargement)). The patient Medication Guide for these medicines will also be revised to include information on the risk of bladder cancer. This safety information is based on FDA’s review of data from a five-year interim analysis of an ongoing, ten-year epidemiological study. The five-year results showed that although there was no overall increased risk of bladder cancer with pioglitazone use, an increased risk of bladder cancer was noted among patients with the longest exposure to pioglitazone, and in those exposed to the highest cumulative dose of pioglitazone.

FDA is also aware of a recent epidemiological study conducted in France which suggests an increased risk of bladder cancer with pioglitazone. Based on the results of this study, the French health authorities (AFSSAPS) have suspended the use of pioglitazone-containing medicines (i.e., Actos and Competact) in France.  Germany’s BfArM has recommended not to start pioglitazone-containing medicines in new patients. The European Medicines Agency (EMEA) is in the process of reviewing all available data on pioglitazone-containing medicines use and re-analyze the risk / benefit ratio shortly.

Additional Information for Patients, Information for Healthcare Professionals, and a Data Summary are provided in the Drug Safety Communication.

FDA recommends that healthcare professionals should:

  • Not use pioglitazone in patients with active bladder cancer.
  • Use pioglitazone with caution in patients with a prior history of bladder cancer.

The benefits of blood sugar control with pioglitazone should be weighed against the unknown risks for cancer recurrence. FDA will continue to evaluate data from the ongoing ten-year epidemiological study. The Agency will also conduct a comprehensive review of the results from the French study. FDA will update the public when more information becomes available.


Rituximab [Rituxan] – Fatal Infusion Related Reactions in Patients with Rheumatoid Arthritis

June 7, 2011

June 6, 2011 – Today, we learn from Health Canada the following very important safety information:

Hoffmann-La Roche Limited, in consultation with Health Canada, would like to inform you of important new safety information regarding fatal infusion related reactions following the use of RITUXAN® (rituximab) in RA patients.  Roche is issuing this letter to ensure that you have the most recent information available when considering RITUXAN as a treatment option in rheumatoid arthritis.

RITUXAN is a chimeric mouse/human monoclonal antibody that binds specifically to the transmembrane antigen CD20.  It is authorized to reduce the signs and symptoms in adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more tumour necrosis factor (TNF) inhibitor therapies.

Post-marketing cases of fatal infusion related reactions have been reported in patients with RA treated with RITUXAN.

If anaphylaxis or other serious hypersensitivity/infusion reaction occurs,

  • administration of RITUXAN should be stopped immediately, and
  • appropriate medical management should be initiated.

Infusions should not be administered unless they are in a setting where resuscitation equipment is easily and immediately available. Pre-medication prior to infusion of RITUXAN for RA should always be administered (see below).

Patients with pre-existing cardiac conditions and those who experienced prior cardiopulmonary adverse reactions need to be monitored closely following the RITUXAN infusion.

Among the patients with fatal reactions, it is not known if the patients had received the recommended premedication prior to the infusion of RITUXAN. Analgesic/anti-pyretic (e.g. acetaminophen) and an anti-histaminic drug (e.g. diphenhydramine) should always be administered before each infusion of RITUXAN. Patients should receive 100 mg IV methylprednisolone 30 minutes prior to each RITUXAN infusion.

Health care professionals must be vigilant for signs of hypersensitivity or anaphylaxis in all patients experiencing an infusion reaction during or following RITUXAN administration.

Available details of the spontaneous post marketing reports of fatal infusion related reactions, none of them originating from Canada, are as follows:

  • A patient, with a medical history of pericardial effusion and sleep apnoea syndrome, developed shortness of breath and weakness in his extremities after the fifth course of rituximab resulting in a cardiorespiratory arrest. CPR was unsuccessful.
  • A patient, with a history of aortic valve incompetence, developed an anaphylactic reaction during the second infusion of the first course of rituximab. The patient was transferred to the ICU. After initial improvement, the patient’s condition deteriorated resulting in death.
  • Two other patients died on the same day as having received a rituximab infusion. Symptoms suggestive of an anaphylactic reaction were not reported for either patient: however, based on the temporal relationship between the infusion and death, infusion related reactions could not be ruled out.

Roche will be working with Health Canada to update the Product Monograph to reflect new safety information. We encourage you to review this additional important safety information with your patients.

Managing marketed health product related adverse reactions depends on health care professionals and consumers reporting them. Reporting rates determined on the basis of spontaneously reported post marketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments. Any occurrence of serious and/or unexpected adverse reactions in patients receiving RITUXAN should be reported to Hoffmann-La Roche Limited, or Health Canada at the following addresses:

Hoffmann-La Roche Limited
Drug Safety Department
2455 Meadowpine Boulevard
Mississauga, Ontario, L5N 6L7
or call toll free at: 1-888-762-4388
or Fax at: 905-542-5864
or email to: mississauga.drug_safety@roche.com

You can report any suspected adverse reactions associated with the use of health products to the Canada Vigilance Program by one of the following 3 ways:

–  Report online at http://www.healthcanada.gc.ca/medeffect

– Call toll-free at 1-866-234-2345

– Complete a Reporting Form and:
o Fax toll-free to 1-866-678-6789, or
o Mail to: Canada Vigilance Program
Health Canada
Postal Locator 0701E
Ottawa, Ontario   K1A 0K9

The Reporting Forms, postage paid labels, and Guidelines can be found on the MedEffectTM Canada Web site in the Adverse Reaction Reporting section. The Reporting Form is also in the Canadian Compendium of Pharmaceuticals and Specialties.


The Pill: Possibly Increased Risk of Blood Clots with Birth Control Pills Containing Drospirenone

June 2, 2011

May 31, 2011 – The American Food and Drug Administration (FDA) has released today the following announcement aimed at physicians, family practices, and patients:

ISSUE: FDA is aware of two newly published studies that evaluated the risk of venous thromboembolism (VTE) in women who use birth control pills that contain drospirenone. The two recently published studies looked at whether there is a higher risk of blood clots in women taking birth control pills containing the progestin drospirenone when compared to similar women taking birth control pills containing a different progestin called levonorgestrel. These two new studies reported that there is a greater risk of VTE associated with birth control pills that contain drospirenone. This risk is reported to be up to 2 to 3 times greater than the risk of VTE associated with using levonorgestrel-containing pills. Other studies have not reported an increase in risk. The FDA is currently evaluating the conflicting results from these studies and will look at all currently available information to fully assess the risks and benefits of drospirenone-containing birth control pills. FDA will continue to communicate any new safety information to the public as it becomes available. Read the drug safety communication for more information on these studies.

BACKGROUND: Drospirenone is a type of female sex hormone called a progestin. Most birth control pills contain two types of hormones–estrogen and progestin. Birth control pills work by preventing the release of eggs from the ovaries (ovulation) and changing the cervical mucus and the lining of the uterus to prevent pregnancy. Brand names of drospirenone-containing products include Yaz (generics Gianvi and Loryna), Yasmin (generics Ocella, Syeda, and Zarah), Beyaz, and Safyral.

RECOMMENDATION: If your birth control pill contains drospirenone, do not stop taking it without first talking to your healthcare professional. Contact your healthcare professional immediately if you develop any symptoms of blood clots, including persistent leg pain, severe chest pain, or sudden shortness of breath. If you smoke and are over 35 years of age, you should not take combination oral contraceptives because they increase the risk that you could experience serious cardiovascular events, including blood clots.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program:

  • * Complete and submit the report Online: http://www.fda.gov/MedWatch/report.htm.
  • Download form1 or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178.

More information can be found here:  [Drug Safety Communication– FDA] and  [Questions and Answers – FDA].


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