Hydroxyethyl Starch Solutions: FDA Safety Communication – Boxed Warning on Increased Mortality and Severe Renal Injury and Risk of Bleeding

June 26, 2013

June 26, 2013 – The American Food and Drug Administration (FDA) has just released (June 06 2013) the following important information concerning patients who receive hydroxyethyl Starch (HES) solutions in the course of their treatment.

ISSUE: FDA has analyzed recent data that indicate an increased risk of (i) mortality and renal injury requiring renal replacement therapy in critically ill adult patients, including patients with sepsis and those admitted to the ICU; and (ii) excess bleeding particularly in patients undergoing open heart surgery in association with cardiopulmonary bypass. Refer to the FDA Safety Communication for more details about the data analysis.

FDA has concluded that HES solutions should not be used in critically ill adult patients, including patients with sepsis and those admitted to the ICU, and a Boxed Warning to include the risk of mortality and severe renal injury is warranted. In addition, FDA has reviewed a meta-analysis of studies conducted in patients undergoing open heart surgery in association with cardiopulmonary bypass and has determined that an additional warning about excessive bleeding is needed in the Warnings and Precautions Section of the package insert.

BACKGROUND: Hydroxyethyl starch (HES) solutions are used for the treatment of hypovolemia (low blood volume) when plasma volume expansion is desired. Recent data have associated the use of these products with an increased risk of severe adverse events when used in certain patient populations.

RECOMMENDATION: Patients should be aware of the risks associated with the use of HES solutions and discuss these risks with their healthcare provider (refer to the FDA Safety Communication for detailed recommendations for patients).

Recommendations for Health Professionals include the following:

– Do not use HES solutions in critically ill adult patients including those with sepsis, and those admitted to the ICU.
– Avoid use in patients with pre-existing renal dysfunction.
– Discontinue use of HES at the first sign of renal injury.
– Need for renal replacement therapy has been reported up to 90 days after HES administration. Continue to monitor renal function for at least 90 days in all patients.
– Avoid use in patients undergoing open heart surgery in association with cardiopulmonary bypass due to excess bleeding.
– Discontinue use of HES at the first sign of coagulopathy.

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: www.fda.gov/MedWatch/report.htm
Download form 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
[06/24/2013 – FDA Safety Communication – FDA]


Incretin Mimetic Drugs for Type 2 Diabetes: Early Communication – Reports of Possible Increased Risk of Pancreatitis and Pre-cancerous Findings of the Pancreas

May 9, 2013

May 09, 2013 – We have just stumbled upon a recent press release to the public by the American Food and Drug Administration (FDA) on a looming drug safety problem of incretin mimetic drugs related to the pancreas. Find here the unedited press releaase in full:

[Posted 03/14/2013]

AUDIENCE: Gastroenterology, Endocrinology, Oncology, Patient

ISSUE: FDA is evaluating unpublished new findings by a group of academic researchers that suggest an increased risk of pancreatitis and pre-cancerous cellular changes called pancreatic duct metaplasia in patients with type 2 diabetes treated with a class of drugs called incretin mimetics. These findings were based on examination of a small number of pancreatic tissue specimens taken from patients after they died from unspecified causes. FDA has asked the researchers to provide the methodology used to collect and study these specimens and to provide the tissue samples so the Agency can further investigate potential pancreatic toxicity associated with the incretin mimetics.

BACKGROUND: Drugs in the incretin mimetic class include exenatide (Byetta, Bydureon), liraglutide (Victoza), sitagliptin (Januvia, Janumet, Janumet XR, Juvisync), saxagliptin (Onglyza, Kombiglyze XR), alogliptin (Nesina, Kazano, Oseni), and linagliptin (Tradjenta, Jentadueto). These drugs work by mimicking the incretin hormones that the body usually produces naturally to stimulate the release of insulin in response to a meal. They are used along with diet and exercise to lower blood sugar in adults with type 2 diabetes.

RECOMMENDATIONS: FDA has not reached any new conclusions about safety risks with incretin mimetic drugs. This early communication is intended only to inform the public and health care professionals that the Agency intends to obtain and evaluate this new information. FDA will participate in the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Cancer Institute’s (NCI) Workshop on Pancreatitis-Diabetes-Pancreatic Cancer in June 2013 to gather and share additional information. FDA will communicate its final conclusions and recommendations when its review is complete or when the Agency has additional information to report.

The Warnings and Precautions section of drug labels and patient Medication Guides for incretin mimetics contain warnings about the risk of acute pancreatitis. FDA has not previously communicated about the potential risk of pre-cancerous findings  of the pancreas with incretin mimetics. FDA has not concluded these drugs may cause or contribute to the development of pancreatic cancer.

At this time, patients should continue to take their medicine as directed until they talk to their health care professional, and health care professionals should continue to follow the prescribing recommendations in the drug labels.

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 form 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


EMA: Recommendation to suspend tetrazepam-containing medicines

May 8, 2013

May 09, 2013 – This is from the News and Press Release Archive of the European Medicines Agency (EMA) as of April 29, 2013.  Find here the unedited release in full:

29/04/2013

Recommendation to suspend tetrazepam-containing medicines endorsed by CMDh

Following the recent recommendation by the Pharmacovigilance Risk Assessment Committee (PRAC), the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) has endorsed by majority the PRAC recommendation to suspend the marketing authorisations of tetrazepam-containing medicines across the European Union (EU). The CMDh, a body representing EU Member States, is responsible for ensuring harmonised safety standards for medicines authorised via national marketing authorisation procedures across the EU.

Tetrazepam, a medicine of the benzodiazepine class, is used in several EU Member States to treat painful contractures (such as in low back pain and neck pain) and spasticity (excessive stiffness of muscles).

The CMDh position will now be sent to the European Commission, which will take a legally binding decision throughout the EU.

The review of tetrazepam was triggered by the French National Agency for the Safety of Medicine and Health ProductsExternal link icon (ANSM), following reports of serious skin reactions with this medicine in France. Having assessed all available data on the risk of skin reactions, including post-marketing data in the EU and the published literature, the PRAC concluded that tetrazepam is associated with a low but increased risk of serious skin reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis and DRESS syndrome) compared with other benzodiazepines. The Committee also noted that, in the light of the risks identified, the available data on the effectiveness of tetrazepam were not sufficiently robust to support its use in the authorised indications.

The CMDh agreed with the PRAC conclusion that the benefits of these medicines do not outweigh their risks, and adopted a final position that the marketing authorisations should be suspended throughout the EU.

The suspension of the marketing authorisations can be lifted if the companies that market these medicines provide data identifying a specific group of patients for whom the benefits of tetrazepam-containing medicines outweigh the risks.

Information to patients

  • Tetrazepam is a muscle relaxant used in painful conditions such as low back pain and neck pain as well as spasticity (excessive stiffness of muscles).
  • As a result of the risk of unpredictable, serious skin reactions identified, the CMDh position is that tetrazepam-containing medicines should no longer be used in the EU.
  • If you are taking a tetrazepam-containing medicine, you should not suddenly stop taking tetrazepam without your doctor’s advice. You should make an appointment with your treating doctor to discuss your treatment. Your doctor may also consider an appropriate alternative treatment for you.

Information to healthcare professionals

  • In light of the unfavourable benefit-risk balance, doctors should review their patients’ treatment at their next appointment, and may consider an appropriate alternative treatment.
  • Pharmacists should refer patients on a new or repeat prescription for tetrazepam to their treating physician.

The CMDh position is based on the PRAC review of all available data on the risk of skin reactions with tetrazepam, including post-marketing data in the EU and the published literature, and the available information on efficacy in licensed indications:

  • The review found that half of the reported reactions with tetrazepam are skin disorders, which are sometimes serious, life-threatening or fatal. Serious skin reactions include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), erythema multiforme and drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. They are unpredictable and can occur at any stage during treatment, including after short-term treatment, and at recommended doses.
  • In the pharmacovigilance database of the originator product, Myolastan, a total of 513 cutaneous (or allergic) reactions were identified. 65 cases of SJS and TEN were reported. Although the majority of cases occurred in patients taking concomitant medications, the causal link with tetrazepam was strong in a high number of cases.
  • The risk of skin reaction is higher with tetrazepam than with other benzodiazepines. This is possibly explained by a structural difference between tetrazepam and other benzodiazepines (i.e. the substituted cyclohexenyl ring of tetrazepam).
  • Regarding its efficacy, four studies showed no difference between tetrazepam and other active medicines when used for spasticity. The efficacy of tetrazepam for painful contractures is supported mainly by two small double-blind placebo-controlled clinical trials showing limited efficacy.

In view of the serious, potentially fatal, skin reactions and the limited efficacy of tetrazepam, the benefit-risk balance of tetrazepam-containing medicines is considered no longer favourable.


More about the medicine

Tetrazepam belongs to a group of medicines called benzodiazepines. It is taken by mouth to treat painful contractures (sustained shortening of muscle tissue), and spasticity (excessive stiffness of muscles).

Tetrazepam-containing medicines have been approved since the 1960s via national procedures in several EU Member States (Austria, Belgium, Bulgaria, Czech Republic, France, Germany, Latvia, Lithuania, Luxembourg, Poland, Romania, Slovakia and Spain), and are available on prescription under various trade names, including Epsipam, Miozepam, Musapam, Musaril, Myolastan, Myopam, Panos, Relaxam, Spasmorelax, Tetra-saar, Tetramdura and Tetraratio. The full list is available in Annex I on the EMA website.

Benzodiazepines work by attaching to certain receptors in the brain, thereby increasing the activity of a substance called gamma-amino butyric acid (GABA). GABA decreases the excitability of many brain cells. By increasing GABA activity, benzodiazepines have a calming effect on various functions of the brain. In particular, tetrazepam is used for its muscle relaxant effects.

More about the procedure

The review of tetrazepam-containing medicines was initiated in January 2013 at the request of France, under Article 107i of Directive 2001/83/EC, also known as the urgent Union procedure.

The review was first conducted by the Pharmacovigilance Risk Assessment Committee (PRAC), the Committee responsible for the evaluation of safety issues for human medicines, which made a set of recommendations. As tetrazepam-containing medicines are all authorised nationally, the PRAC recommendations were sent to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which adopted a final position. The CMDh is composed of representatives of all EU Member States. Its main responsibility is to resolve disagreements between Member States involved in mutual recognition or decentralised procedures, to ensure that patients have the same level of protection, no matter where they are in the EU.

As the CMDh position was adopted by majority vote, the CMDh position will now be sent to the European Commission, which will take an EU-wide legally binding decision.


FDA limits duration and usage of Tolvaptan (Samsca) due to possible liver injury leading to organ transplant or death

May 2, 2013

April 30, 2013 –   The U.S. Food and Drug Administration (FDA) has determined that the drug Tolvaptan (Samsca) should not be used for longer than 30 days and should not be used in patients with underlying liver disease because it can cause liver injury, potentially requiring liver transplant or death.  Tolvaptan (Samsca) is used to treat low sodium levels in the Tolvapanblood. An increased risk of liver injury was observed in recent large clinical trials evaluating Tolvaptan (Samsca) for a new use in patients with autosomal dominant polycystic kidney disease (ADPKD. FDA has worked with the manufacturer to revise the Tolvaptan (Samsca) drug label to include these new limitations.

The Tolvaptan (Samsca) drug label has been updated to include the following information:

  • Limitation of the duration of Samsca treatment to 30 days. (Dosage and Administration and Warnings and Precautions sections)
  • Removal of the indication for use in patients with cirrhosis, a condition that involves scarring of the liver due to injury or long-term disease.  Use of Samsca in patients with underlying liver disease, including cirrhosis, should be avoided because the ability to recover from liver injury may be impaired. (Indications and Usage and Use in Specific Populations sections)
  • Description of liver injuries seen in clinical trials of patients with autosomal dominant polycystic kidney disease (ADPKD).
  • Recommendation to discontinue Samsca in patients with symptoms of liver injury.

The manufacturer of Tolvaptan (Samsca), Otsuka American Pharmaceutical, Inc., issued a Dear Health Care Provider letter on the potential risk of liver injury on January 22, 2013FDA is reviewing the information from clinical trials of patients with ADPKD and will update the public on the risk of liver injury with Tolvaptan (Samsca) if more information becomes available.


Fatal Adverse Events with Pazopanib [Votrient], Sorafenib [Nexavar], and Sunitinib [Sutent]

February 12, 2012

February 12, 2012 – From an article published in Medscape Oncology News on February 9, 2012, we learn the following (article in full, all rights resting with Medscape Oncology News):

_______________

February 9, 2012— New details on the risk for fatal adverse events associated with several targeted cancer drugs have come from a large meta-analysis of clinical trials, which was published online February 6 in the Journal of Clinical Oncology.

The drugs investigated were pazopanib (Votrient, GlaxoSmithKline), which is approved for use in renal cell carcinoma; sorafenib (Nexavar, Bayer & Onyx), which is approved for use in renal cell carcinoma and hepatocellular cancer; and sunitinib (Sutent, Pfizer), which is approved for use in hepatocellular cancer and gastrointestinal stromal tumors. All 3 products are vascular endothelial growth-factor (VEGF) receptor tyrosine kinase inhibitors.

The meta-analysis, which examined data on 4679 patients from 10 clinical trials, found that these 3 drugs were associated with fatal adverse events at a rate that was about twice that seen in the placebo groups. The crude incidence of fatal adverse events was 1.5% in patients taking these drugs, compared with 0.7% in patients in the placebo or control groups (relative risk [RR], 2.23; P = .023).

The most common cause of death was hemorrhage; the second most common was myocardial ischemia. Liver failure and congestive heart failure were also reported.

Senior author Toni Choueiri, MD, from the Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, said that clinicians need to be aware of the risks associated with these drugs.

“There is no doubt that for the average patient, these drugs have benefits,” Dr. Choueiri said in a statement. In fact, these drugs represent a major step forward in the treatment of several malignancies, and they have led to significant improvements in patient outcomes.

However, they are associated with a significant increase in the risk of developing fatal drug-related events, and “practitioners must be aware of the risks associated with their use and must provide rigorous monitoring to continue to improve patient outcomes,” the researchers note.

“While the absolute incidence of these fatal side effects is very small, the relative risks are higher,” Dr. Choueiri noted. In addition, the patients in this meta-analysis were participating in clinical trials and all had adequate organ function at study entry, so the overall incidence and risk for unreported fatal adverse events could be higher in common medical practice.


Patients on Vemurafenib [Zelboraf] Need Testing for RAS Mutations: Secondary Cancers a Major Concern

January 26, 2012

January 26, 2012 – A January 20, 2012 article in Medscape Medical New illustrates how personalized medicine can be tricky. The case is Vemurafenib [Zelboraf], which was introduced to the market together with an companion genetic test mid 2011 for the treatment of advanced melanoma in suitable BRAF mutation (V600E) positive patients only. In these patients, while melanoma therapy response rates are impressive, a new problem seems to arise, namely secondary tumours. Please read the article published  by Medscape Medical News on this topic.

_____________________________

Patients with advanced melanoma who are treated with Vemurafenib [Zelboraf ]  should be tested for RAS mutations, according to an editorial published in the January 19 issue of the New England Journal of Medicine.

A study that accompanies the editorial reports that RAS mutations frequently occur in secondary skin tumors that develop in vemurafenib-treated patients.

The testing is necessary because there is “potential for secondary tumor development” that arises from treatment with vemurafenib and other BRAF inhibitors, writes Ashani T. Weeraratna, PhD, from the molecular and cellular oncogenesis program at The Wistar Institute in Philadelphia, Pennsylvania, in her editorial. These secondary skin tumors — namely, cutaneous squamous cell carcinomas and keratoacanthomas — are relatively benign, compared with melanoma, and are no reason to discontinue vemurafenib, said Dr. Weeraratna. However, testing will alert clinicians to which patients have RAS-driven secondary tumors.

The testing is important because patients with RAS mutations could also develop secondary cancers in organs beyond the skin, advised Dr. Weeraratna. “If patients have RAS mutations they should be monitored closely for any development of cutaneous squamous cell carcinomas in all organs,” she told Medscape Medical News.

“Although cutaneous squamous cell carcinomas are not deadly, these lesions can be life-threatening when they occur in other organs,” Dr. Weeraratna writes in her editorial. She discussed other potentially affected organs. “Squamous cell carcinomas can potentially arise in any organ with a squamous epithelium, essentially a layer of flattened epithelial cells that line the basement membranes of organs. A squamous epithelium is found most often in organs where rapid filtration and diffusion is necessary, such as the alveolar lining of the lungs and the glomerulus (kidney). Thus, squamous cell carcinomas can be found in organs such as the lungs, cervix, and esophagus, and also account for a large proportion of head and neck cancers,” Dr. Weeraratna explained.

Importantly, there is no evidence that vemurafenib triggers tumors in other organs. “It is as yet unclear whether the generation of squamous cell carcinomas in these organs, upon BRAF inhibitor therapy, occurs, but these data certainly alert us to that potential risk,” she said.

MEK Inhibitors May Help

In this study of melanoma patients, the investigators sought to characterize the molecular mechanism behind the development of secondary skin cancers in patients treated with vemurafenib.

They admit that a skin cancer drug that causes other skin cancers is unexpected. The development of cutaneous squamous cell carcinomas and keratoacanthomas “is the opposite of what would be expected from a targeted oncogene inhibitor,” write the study authors, led by Fei Su, PhD, from Hoffman-La Roche Pharmaceuticals in Nutley, New Jersey. In their search to understand this toxicity, the investigators analyzed the DNA of a sampling of these tumors and found a high rate of RAS mutations (21 of 35 tumors; 60%). “Mutations in RAS, particularly HRAS, are frequent in cutaneous squamous cell carcinomas and keratoacanthomas that develop in patients treated with vemurafenib,” write the authors.

“This study points out that BRAF inhibitors should only be used in patients who have cancers driven by BRAF mutations, and it raises the concern that cancers driven by RAS mutations (KRAS, HRAS, or NRAS) can be paradoxically activated instead of inhibited with this class of drugs,” said coauthor Antoni Ribas, MD, PhD, in email correspondence with Medscape Medical News. He is from the division of hematology–oncology at the UCLA Medical Center in Los Angeles, California.

Why patients treated with vemurafenib have such a high rate of RAS mutations in these secondary cancers is not known. However, the investigators performed animal-model studies that suggest that the development of RAS-mutation-driven secondary tumors might be prevented with a MEK inhibitor, another class of drugs. There might be “usefulness of combining a BRAF inhibitor with a MEK inhibitor to prevent this toxic effect” of secondary cancers, write the authors.

There has already been clinical investigation of this concept — a phase 2 study of the combination of the MEK inhibitor GSK1120212 and the RAF inhibitor GSK2118436 in metastatic melanoma. That study, which was presented at the 2011 annual meeting of the American Society of Clinical Oncology, and reported at that time by Medscape Medical News, showed that the toxicity of the combination seemed to be lower than that of either agent used alone.

____________________________

NEJM: Study

NEJM: Editoral

Medscape Medical News: Article


Drug Safety Communication on Brentuximab Vedotin [Adcetris] – Progressive Multifocal Leukoencephalopathy (PML) and Pulmonary Toxicity

January 17, 2012

January 16, 2012 – The American Food and Drug Administration ( FDA) released on January 13, 2012 the following drug safety communication:

_________________

ISSUE: FDA notified healthcare professionals that two additional cases of progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection that can result in death, have been reported with the lymphoma drug Adcetris (brentuximab vedotin). Due to the serious nature of PML, a new Boxed Warning highlighting this risk has been added to the drug label.

In addition, a new Contraindication warning was added against use of Adcetris with the cancer drug bleomycin due to increased risk of pulmonary (lung) toxicity.

The signs and symptoms of PML may develop over the course of several weeks or months. They may include changes in mood or usual behavior, confusion, thinking problems, loss of memory, changes in vision, speech, or walking, and decreased strength or weakness on one side of the body.

BACKGROUND: Adcetris (brentuximab vedotin) is used to treat Hodgkin lymphoma and a rare lymphoma known as systemic anaplastic large cell lymphoma. At the time of Adcetris’ approval in August 2011, one case of PML was described in the Warnings and Precautions section of the label.

RECOMMENDATION: Patients who develop any signs and symptoms of PML should notify their healthcare professional immediately. Healthcare professionals should hold Adcetris dosing if PML is suspected and discontinue Adcetris if a diagnosis of PML is confirmed. See the Data Summary in the Drug Safety Communication for additional information.

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: www.fda.gov/MedWatch/report.htm1
  • Download form2 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 as of 01/13/2012 – Drug Safety Communication3 – FDA]


Dabigatran [Pradaxa]: Drug Safety Communication – Safety Review of Post-Market Reports of Serious Bleeding Events

December 13, 2011

December 12, 2011 – This is from a press release from December 07, 2011: FDA is evaluating post-marketing reports of serious bleeding events in patients taking Pradaxa (dabigatran etexilate mesylate). Bleeding that may lead to serious or even fatal outcomes is a well-recognized complication of all anticoagulant therapies. The Pradaxa drug label contains a warning about significant and sometimes fatal bleeds. In a large clinical trial (18,000 patients) comparing Pradaxa and warfarin, major bleeding events occurred at similar rates with the two drugs.

FDA is working to determine whether the reports of bleeding in patients taking Pradaxa are occurring more commonly than would be expected, based on observations in the large clinical trial that supported the approval of Pradaxa.

BACKGROUND: Pradaxa is a blood thinning (anticoagulant) medication used to reduce the risk of stroke in patients with non-valvular atrial fibrillation (AF), the most common type of heart rhythm abnormality.

RECOMMENDATION: At this time, FDA continues to believe that Pradaxa provides an important health benefit when used as directed and recommends that healthcare professionals who prescribe Pradaxa follow the recommendations in the approved drug label.

Patients with AF should not stop taking Pradaxa without talking to their healthcare professional. Stopping use of blood thinning medications can increase their risk of stroke. Strokes can lead to permanent disability and death.

FDA will communicate any new information on the risk of bleeding and Pradaxa when it becomes available.

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:


Drug Safety Communication: Zoledronic Acid [Reclast] Associated with New Contraindication and Updated Warning on Kidney Impairment

September 2, 2011

September 01, 2011 – Risk factors for developing renal failure include underlying moderate to severe renal impairment, use of kidney-damaging (nephrotoxic) or diuretic medications at the same time as Zoledronic Acid [Reclast], or severe dehydration occurring before or after Zoledronic Acid [Reclast] is given. The risk of developing renal failure in patients with underlying renal impairment also increases with age.

The American Food and Drug Administration (FDA) has now notified healthcare professionals and patients of an update to the drug label for Zoledronic Acid [Reclast] regarding the risk of kidney failure. Cases of acute renal failure requiring dialysis or having a fatal outcome following Zoledronic Acid [Reclast] use have been reported to FDA. The revised label states that Zoledronic Acid [Reclast] is contraindicated in patients with creatinine clearance less than 35 mL/min or in patients with evidence of acute renal impairment. The label also recommends that healthcare professionals screen patients prior to administering Zoledronic Acid [Reclast] in order to identify at-risk patients.

The Zoledronic Acid [Reclast] Medication Guide for patients is being updated to contain information about the risk of severe kidney problems. In addition, the manufacturer of Zoledronic Acid [Reclast] will issue a Dear Healthcare Provider letter to inform healthcare professionals about this risk.

These labeling changes are being made to the Zoledronic Acid [Reclast] label only, although Zoledronic Acid, also sold as  [Zometa], is approved for treatment of cancer-related indications. Renal toxicity is already addressed in the Warnings and Precautions section of the [Zometa] label. Dose reductions for [Zometa] are provided for patients with renal impairment.

Recommendation:

Zoledronic Acid [Reclast] is contraindicated in patients with creatinine clearance less than 35 mL/min, or in patients with evidence of acute renal impairment. Healthcare professionals should screen patients prior to administering Zoledronic Acid [Reclast] in order to identify at-risk patients. Healthcare professionals should also monitor renal function in patients who are receiving Zoledronic Acid [Reclast].

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 by completing and submitting the report online at www.fda.gov/MedWatch/report.htm. Alternatively, download the form 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.

Read here the MedWatch safety alert, including links to the Drug Safety Communication, including a Data Summary, and prescribing information.


Drug Safety Communication: Asenapine Maleate [Saphris] Associated with Serious Allergic Reactions

September 2, 2011

September 01, 2011 – Asenapine Maleate [Saphris] is used to treat symptoms of schizophrenia and bipolar disorder. The American Food and Drug Administration (FDA) has notified healthcare professionals and patients that serious allergic reactions have been reported with the use of Asenapine Maleate [Saphris]. The Contraindications, Warnings and Precautions, Adverse Reactions, and Patient Counseling Information sections have been revised to include information about type I hypersensitivity reactions which may include anaphylaxis, angioedema, low blood pressure, rapid heart rate, swollen tongue, difficulty breathing, wheezing, or rash. In several cases, these reactions occurred after the first dose.

Healthcare professionals should be aware of the risk of hypersensitivity reactions with Asenapine Maleate [Saphris] and counsel patients who are receiving the drug about how to recognize the signs and symptoms of a serious allergic reaction. Asenapine Maleate [Saphris] should not be used in patients with a known hypersensitivity to the drug.

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 as follows: Complete and submit the report online at www.fda.gov/MedWatch/report.htm. Alternatively, download form 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. Read here the MedWatch safety alert, including links to the Drug Safety Communication with Data Summary,  and prescribing information.


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