Category Archives: Info ADR

Mana yang lebih menguntungkan Rivaroxaban atau Warfarin pada Nonvalvular Atrial Fibrillation

Non valvular atrial fibrilasis merupakan salah satu faktor risiko stroke iskemia dan embolisme pada pembuluh darah. Selama ini warfarin merupakan salah satu obat pilihan untuk pencegahan strok iskemia maupun pembentukan emboli pada pasien dengan fibrilasis termasuk pasien dengan nonvalvular atrial fibrilasis. Hasil Uji klinis untuk membandingkan kemanjuran rivaroxaban dengan warfarin pada nonvalvular atrial fibrilasis telah dilaporkan oleh NEJM.

rivaroxaban

faktior risiko cvd

Original Article

Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation

Manesh R. Patel, M.D., Kenneth W. Mahaffey, M.D., Jyotsna Garg, M.S., Guohua Pan, Ph.D., Daniel E. Singer, M.D., Werner Hacke, M.D., Ph.D., Günter Breithardt, M.D., Jonathan L. Halperin, M.D., Graeme J. Hankey, M.D., Jonathan P. Piccini, M.D., Richard C. Becker, M.D., Christopher C. Nessel, M.D., John F. Paolini, M.D., Ph.D., Scott D. Berkowitz, M.D., Keith A.A. Fox, M.B., Ch.B., Robert M. Califf, M.D., and the ROCKET AF Steering Committee for the ROCKET AF Investigators

N Engl J Med 2011; 365:883-891September 8, 2011

Comments open through September 14, 2011

Abstract
Article
References
Citing Articles (1)
Comments (3)

Background

The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment. Rivaroxaban, an oral factor Xa inhibitor, may provide more consistent and predictable anticoagulation than warfarin.

Full Text of Background…

Methods

In a double-blind trial, we randomly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban (at a daily dose of 20 mg) or dose-adjusted warfarin. The per-protocol, as-treated primary analysis was designed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism.

Full Text of Methods…

Results

In the primary analysis, the primary end point occurred in 188 patients in the rivaroxaban group (1.7% per year) and in 241 in the warfarin group (2.2% per year) (hazard ratio in the rivaroxaban group, 0.79; 95% confidence interval [CI], 0.66 to 0.96; P<0.001 for noninferiority). In the intention-to-treat analysis, the primary end point occurred in 269 patients in the rivaroxaban group (2.1% per year) and in 306 patients in the warfarin group (2.4% per year) (hazard ratio, 0.88; 95% CI, 0.74 to 1.03; P<0.001 for noninferiority; P=0.12 for superiority). Major and nonmajor clinically relevant bleeding occurred in 1475 patients in the rivaroxaban group (14.9% per year) and in 1449 in the warfarin group (14.5% per year) (hazard ratio, 1.03; 95% CI, 0.96 to 1.11; P=0.44), with significant reductions in intracranial hemorrhage (0.5% vs. 0.7%, P=0.02) and fatal bleeding (0.2% vs. 0.5%, P=0.003) in the rivaroxaban group.

Full Text of Results…

Conclusions

In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism. There was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group. (Funded by Johnson & Johnson and Bayer; ROCKET AF ClinicalTrials.gov number, NCT00403767.)

 

Pengaruh informasi ADR dan kualitas laporan

Research article

Impact of information letters on the reporting rate of adverse drug reactions and the quality of the reports: a randomized controlled study

Marie-Louise Johansson email, Staffan Hagg email and Susanna M Wallerstedt email

BMC Clinical Pharmacology 2011, 11:14doi:10.1186/1472-6904-11-14

Published: 7 September 2011

Abstract (provisional)

Background

Spontaneous reporting of adverse drug reactions (ADRs) is an important method for pharmacovigilance, but under-reporting and poor quality of reports are major limitations. The aim of this study was to evaluate if repeated one-page ADR information letters affect (i) the reporting rate of ADRs and (ii) the quality of the ADR reports.

Methods

All 151 primary healthcare units in the Region Vastra Gotaland, Sweden, were randomly allocated (1:1) to an intervention (n=77) or a control group (n=74). The intervention consisted of one-page ADR information letters administered at three occasions during 2008 to all physicians and nurses in the intervention units. The number of ADR reports received from the 151 units was registered, as was the quality of the reports, which was defined as high if the ADR was to be reported according to Swedish regulations, that is, if the ADR was (i) serious, (ii) unexpected, and/or (iii) related to the use of new drugs and not labelled as common in the Summary of Product Characteristics. A questionnaire was administered to evaluate if the ADR information letter had reached the intended recipient.

Results

Before the intervention, no significant differences in reporting rate or number of high quality reports could be detected between the randomization groups. In 2008, 79 reports were sent from 37 intervention units and 52 reports from 30 control units (mean number of reports per unit+/-standard deviation: 1.0+/-2.5 vs. 0.7+/-1.2, P=0.34). The number of high quality reports was higher in intervention units than in control units (37 vs. 15 reports, 0.5+/-0.9 vs. 0.2+/-0.6, P=0.048). According to the returned questionnaires (n = 1,292, response rate 57%), more persons in the intervention than in the control group had received (29% vs. 19%, P<0.0001) and read (31% vs. 26%, P<0.0001) an ADR information letter.

Conclusions

This study suggests that repeated ADR information letters to physicians and nurses do not increase the ADR reporting rate, but may increase the number of high quality reports.

ADR Zolendronic Acid

zolendronic acid

zolendronic acid

Zolendronic acid dapat menimbulkan gagal ginjal. Berita selengkapnya sebagai berikut:

FDA Drug Safety Communication: New contraindication and updated warning on kidney impairment for Reclast (zoledronic acid)

Safety Announcement
Additional Information for Patients
Additional Information for Healthcare Professionals
Data Summary
References

 

Safety Announcement

[09-01-2011] The U.S. Food and Drug Administration (FDA) has approved an update to the drug label for Reclast (zoledronic acid) to better inform healthcare professionals and patients of the risk of kidney (renal) failure. Kidney failure is a rare, but serious, condition associated with the use of Reclast in patients with a history of or risk factors for renal impairment. Cases of acute renal failure requiring dialysis or having a fatal outcome following Reclast use have been reported to FDA.

 

Facts about Reclast (zoledronic acid)

  • Used to treat or prevent osteoporosis in women after menopause. Reclast helps reduce the chance of having a hip or spinal fracture (break).
  • Used to increase bone mass in men with osteoporosis.
  • Used to treat or prevent osteoporosis in either men or women who take corticosteroid medications for at least one year.
  • Used to treat men and women who have Paget’s disease of the bone.
  • Given as an intravenous infusion in a single dose, once every 1 to 2 years. The infusion time should be no less than 15 minutes.
  • Marketed under the brand name Aclasta outside the United States.

These labeling changes are being made to the 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 as well as in the Reclast label. Dose reductions for Zometa are provided for patients with renal impairment.

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 Reclast, or severe dehydration occurring before or after Reclast is given. The risk of developing renal failure in patients with underlying renal impairment also increases with age.

The revised drug label will enhance the safe use of Reclast by providing healthcare professionals updated instructions for prescribing and patient monitoring. The revised label states that Reclast should not be used (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 Reclast in order to identify at-risk patients. Healthcare professionals should also monitor renal function in patients who are receiving Reclast (see Additional Information for Healthcare Professionals below).

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

 

Additional Information for Patients 

  • Kidney failure is a rare, but serious, side effect associated with the use of Reclast.
  • Your healthcare professional will order a serum creatinine level (a blood test) before and after each dose of Reclast to assess how well your kidneys are functioning.
  • If you have kidney disease, discuss the necessity of Reclast treatment with your healthcare professional. There may be other treatment choices available to you.
  • Make sure your healthcare professional knows about all the medications you are taking. It is helpful to keep a list of all your current medications in your wallet or another location where it is easily retrieved.
  • Report any side effects with Reclast to FDA’s MedWatch program using the information at the bottom of the page in the “Contact Us” box.

 

Additional Information for Healthcare Professionals 

  • Reclast is contraindicated in patients with creatinine clearance less than 35 mL/min or in patients with evidence of acute renal impairment.
  • Continue to screen patients prior to each administration of Reclast to identify those with underlying acute or chronic renal impairment, advanced age, or dehydration. Patients with underlying renal impairment appear to be at highest risk for kidney failure. Reclast should be used with caution in this population.
  • The risk of acute renal failure may increase with underlying renal disease and dehydration secondary to fever, sepsis, gastrointestinal losses, diuretic therapy, etc. The risk of developing renal failure in patients with renal impairment also increases with age.
  • Calculate creatinine clearance before each dose of Reclast. Interim monitoring of creatinine clearance should be performed after Reclast dosing in at-risk patients. Creatinine clearance should be calculated based on actual body weight using the Cockcroft-Gault formula.
  • Report any adverse events with Reclast to FDA’s MedWatch program using the information at the bottom of the page in the “Contact Us” box

 

Data Summary 

A January 2009 FDA post-market safety review identified five deaths from acute renal failure following Reclast infusion. Based on that review, the Warnings and Precautions section of the Reclast label was updated in March 2009, with a recommendation to monitor serum creatinine before each dose of Reclast and included reports of renal impairment from clinical studies. An FDA Drug Safety Newsletter article was also published in 2009 reporting the post-marketing cases of renal impairment and acute renal failure.

FDA continued to note reports of renal failure to the Agency’s Adverse Event Reporting System (AERS) after the March 2009 label revision. A follow-up review in April 2011 showed an additional 11 cases of fatal acute renal failure and nine cases of renal injury requiring dialysis after Reclast infusion.

Based on the available information provided in the AERS cases, FDA concluded that several risk factors identified as promoting nephrotoxicity with the use of Reclast should be added to the label. Appropriate selection of patients and patient monitoring by healthcare professionals can reduce the likelihood of adverse events occurring and help ensure the safe use of Reclast.

 

References 

  1. National Center for Biotechnology Information. U.S. National Library of Medicine. PubMed Health Diseases and Conditions Monograph Kidney Failure. Available at: http://www.nlm.nih.gov/medlineplus/kidneyfailure.html. Accessed July 10, 2011

 

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ADR Asenapin Maleat

asenapin maleat

asaenapin maleat

Data dari FDA menunjukkan bahwa Asenapin maleat dapat menimbulkan reaksi alergi. Asenapin malet merupakan salah satu obat antipsikosis. Penggunaan bahan ini pada sebagian pasien terbukti dapat menimbulkan reaksi alergi. Berita selengkapnya sebagai berikut:

FDA Drug Safety Communication: Serious allergic reactions reported with the use of Saphris (asenapine maleate)

Safety Announcement
Additional Information for Patients
Additional Information for Healthcare Professionals
Data Summary
References

 

Safety Announcement

[09-01-2011] The U.S. Food and Drug Administration (FDA) is warning the public that serious allergic reactions have been reported with the use of the antipsychotic medication Saphris (asenapine maleate). The Contraindications, Warnings and Precautions, Adverse Reactions, and Patient Counseling Information sections of the Saphris drug label have been revised to include information about this risk and to inform healthcare professionals that Saphris should not be used in patients with a known hypersensitivity to the drug.

 

Facts about Saphris (asenapine maleate)

  • In a class of medications called atypical antipsychotics.
  • Used to treat symptoms of schizophrenia and bipolar disorder.
  • From approval in August 2009 to June 2011, approximately 235,000 prescriptions were dispensed for Saphris and approximately 87,000 patients received a dispensed prescription for Saphris from U.S. outpatient retail pharmacies.1,2

A search of the FDA’s Adverse Event Reporting System (AERS) database identified 52 cases of Type I hypersensitivity reactions (allergic reactions) with Saphris use (see Data Summary below). Hypersensitivity reactions can be classified into four categories (Type I to Type IV). Signs and symptoms of Type I hypersensitivity reactions may include anaphylaxis (a life-threatening allergic reaction), angioedema (swelling of the deeper layers of the skin), low blood pressure, rapid heart rate, swollen tongue, difficulty breathing, wheezing, or rash. These signs and symptoms are consistent with the reactions reported in the 52 cases. Several cases reported multiple hypersensitivity reactions occurring at the same time, with some of these reactions occurring after the first dose of Saphris.

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

Patients should seek emergency medical attention immediately if they develop any signs and symptoms of a serious allergic reaction while taking Saphris.

 

Additional Information for Patients

  • Serious allergic reactions have been reported in patients treated with Saphris.
  • Patients should seek emergency medical attention immediately if they develop any signs and symptoms of a serious allergic reaction such as:
    • Difficulty breathing
    • Swelling of the face, tongue or throat
    • Feeling lightheaded
    • Itching
  • Serious side effects from the use of Saphris should be reported to the FDA MedWatch program, using the information in the “Contact Us” box at the bottom of this page.

 

Additional Information for Healthcare Professionals

  • Type I hypersensitivity reactions, including anaphylaxis and angioedema, have been observed in patients treated with Saphris. In several cases, these reactions occurred after the first dose.
  • The hypersensitivity reactions included: anaphylaxis, angioedema, hypotension, tachycardia, swollen tongue, dyspnea, wheezing, and rash.
  • Saphris is contraindicated in patients with a known hypersensitivity to the product.
  • Patients should be educated to recognize the signs and symptoms of a serious allergic reaction and advised to contact a healthcare professional immediately if they experience any of these symptoms while taking Saphris.
  • Adverse events involving Saphris should be reported to the FDA MedWatch program using the information in the “Contact Us” box at the bottom of this page.

 

Data Summary

Saphris (asenapine maleate) was FDA-approved on August 13, 2009. A search of the AERS database from approval through September 7, 2010 identified 52 cases that reported Type I hypersensitivity reactions associated with Saphris use. Reported signs and symptoms included anaphylaxis, angioedema, hypotension, tachycardia, swollen tongue, dyspnea, wheezing, and rash. Some of the cases reported the occurrence of more than one hypersensitivity reaction following Saphris use. Eight cases reported hypersensitivity reactions after just one dose of Saphris. The reactions reported following one dose included possible angioedema, respiratory distress, and possible anaphylaxis.

Type I hypersensitivity reactions typically require a history of previous exposure to the drug. However, the absence of a known prior exposure does not exclude the reaction, because sensitization may have occurred to a cross-reactive compound in the past even if the patient showed no signs of allergy to the sensitizing product. To date, no specific drug has shown cross-reactivity with Saphris.

Of the 52 cases, 15 reported a resolution of symptoms following Saphris discontinuation, while two of these cases reported a reappearance of symptoms upon reintroduction of Saphris. Nineteen of the cases resulted in hospitalization or emergency room visits, and therapeutic interventions were reported in seven cases.

Although many of the cases have limited information, the findings from the cases are consistent with hypersensitivity reactions, including anaphylaxis, and support a temporal association between the onset of the reactions and Saphris use.

 

References

  1. SDI, Vector One®: National (VONA). August 2009-June 2011. Data extracted August 2011.
  2. SDI, Vector One®: Total Patient Tracker (TPT). August 2009-June 2011. Data extracted August 2011.