Statins

One of the tops stories of Medscape is the increasing use of statins for primary prevention of coronary artery disease (CAD) and the adverse effects with these statins.

http://www.medscape.com/viewarticle/827675?nlid=60623_763&src=wnl_edit_medp_imed&uac=73164EG&spon=18#1

Afrezza

US FDA approved Afrezza (insulin human) Inhalation Powder, a rapid-acting inhaled insulin,  for use among adult patients of diabetes mellitus on 27th June, 2014
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm403122.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Safety update on Olmesartan

US FDA issued a safety announcement on 24th June, 2014 after completion of safety review of Olmesartan. No clear evidence of increased cardiovascular risks was found with use of olmesartan among diabetic patients. Thus, the recommendations for use of Olmesartan will remain, with the addition of results of some studies on drug labels.

This safety announcement follows the earlier two announcements made by US FDA, first in year 2010 and second one in year 2011.

The first safety communication was issued in November 2010, after evaluating the data of two long term clinical ROADMAP and ORIENT.

ROADMAP (Randomized Olmesartan and Diabetes Microalbuminuria Prevention) trial had examined the effects of olmesartan in patients with type 2 diabetes and whether olmesartan could delay kidney damage. Unexpectedly, there was an increased risk of cardiovascular deaths in olmesartan group as compared to placebo group. But, the risk of non fatal heart attack was less in the olmesartan group. At that time, no conclusion was made regarding the risks of death. The announcement mentioned about the ongoing safety review about use of olmesartan.

In April 2011, US FDA issued a safety review update specifying that the benefits of olmesartan use continue to outweigh its potential risks when used among hypertensive patients. Olmesartan is not recommended for delay or prevention of microalbuminuria among diabetic patients.

Safety announcement 6-24-2014 http://www.fda.gov/Drugs/DrugSafety/ucm402323.htm 

Drug safety communication 06-11-2010
 http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm215222.htm
Drug safety communication 04-14-2011 http://www.fda.gov/Drugs/DrugSafety/ucm251268.htm

http://www.fda.gov/downloads/Drugs/DrugSafety/UCM402339.pdf

Sovaldi for chronic hepatitis C

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm377888.htm

The U.S. Food and Drug Administration today approved Sovaldi (sofosbuvir) to treat chronic hepatitis C virus (HCV) infection.

Sovaldi is the first drug that has demonstrated safety and efficacy to treat certain types of HCV infection without the need for co-administration of interferon.

On November 22, FDA had approved Olysio (Simeprevir) for treatment of chronic HCV. 

Aralen (Chloroquine Phosphate) Tablets

US FDA has modified the section of Warnings and adverse reactions of Aralen (Chloroquine Phosphate) Tablets

The warnings section mentions that - retinopathy/maculopathy, as well as macular degeneration have been reported and irreversible retinal damage has been observed in some patients who had received long-term or high-dosage 4-aminoquinoline therapy. Retinopathy has been reported to be dose related. Risk factors for the development of retinopathy include age, duration of treatment, high daily and/or cumulated doses.

The adverse reactions section mentions that maculopathy and macular degeneration have been reported and may be irreversible.

Rosiglitazone -Modifications in the prescribing and dispensing restrictions

 Rosiglitazone is a thiazolidinedione, used in the management of type 2 diabetes mellitus, alone or in combination therapy.

The latest drug safety communication by US FDA on rosiglitazone containing diabetes medicines requires the removal of the prescribing and dispensing restrictions for rosiglitazone medicines that were put up in year 2010.

This is based on the recent re-evaluation of the Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes (RECORD) trial data by Duke Clinical Research Institute (DCRI) which did not show statistically significant differences between the rosiglitazone and the metformin/sulfonylurea groups for the composite end point of CV death, MI, or stroke and the individual components. Still the concerns about the cardiovascular safety remain due to this re-evaluation, but the prescribing information and Risk Evaluation and Mitigation Strategy (REMS), called the Rosiglitazone REMS program will be modified.

Health care professionals, pharmacies, and patients will no longer be required to enroll in the rosiglitazone REMS program to be able to prescribe, dispense, or receive rosiglitazone medicines.   

History of changes in the prescribing information

09/23/2010

US FDA restricted the use of rosiglitazone to patients of type 2 DM who cannot control their diabetes on other medications. This was following the data from a large, combined analysis of mostly short-term, randomized clinical trials of rosiglitazone which had suggested an elevated risk of heart attack.

FDA required a Rosiglitazone REMS program. The Rosiglitazone REMS program restricted the use of rosiglitazone medicines to help ensure that their benefits outweighed the risks. 

02/04/2011

Information on cardiovascular risks added to the physician label and medication guide.

05/18/2011

The new REMS included a restricted access and distribution program for all the three products containing rosiglitazone (Avandia, Avandamet and Avandaryl)

11/04/2011

Healthcare professionals to enroll in the Avandia-Rosiglitazone Medicines Access Program if they wished to prescribe rosiglitazone medicines to outpatients or patients in long-term care facilities.

References

1.      http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm376683.htm

2.      http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm226994.htm

3.      RECORD trial. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60953-3/abstract

4.      Results of a reevaluation of cardiovascular outcomes in the RECORD trial. http://www.ncbi.nlm.nih.gov/pubmed/23895806

FDA has recommended not to co- administer Aliskiren (Tekturna) with Ramipril in patients with diabetes.

 Safety Labeling Changes Approved By FDA CDER 

  http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm233254.htm

Ramipril is an ACE inhibitor indicated for the treatment of hypertension. It may be used alone or in combination with thiazide diuretics. The most common adverse reactions include headache, dizziness, fatigue, and cough.

Aliskiren is an orally active renin antagonist given in patients with hypertension with elevated plasma renin levels. 

Physicians are advised not to co-administer Aliskiren with Ramipril in patients with diabetes or in patients with renal impairment (GFR < 60 mL/min/1.73 m²).

Dual blockade of the Renin Angiotensin Aldosterone System (RAAS) with ACE inhibitors and Aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy.

Physicians should closely monitor blood pressure, renal functions and electrolytes in patients on Ramipril and other agents that affect the RAAS.

Glyburide and Metformin (Glucovance)

FDA has contraindicated the concomitant administration of Bosentan and Colesevelam with Glucovance.

Glyburide a sulfonylurea lowers blood glucose levels by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets.

Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.

Bosentan is an orally active competitive inhibitor of endothelin used for pulmonary arterial hypertension.

Colesevelam is a bile acid binding resin useful only for isolated increases in LDL.

Recommendations:

Concomitant use of these drugs can lead to an increased risk of liver enzyme elevations.

Glucovance should be administered at least 4 hours prior to Colesevelam as their concomitant administration reduces maximum plasma concentration and total exposure to glyburide.

http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm194334.htm

Lexiscan (regadenoson) and Adenoscan (adenosine): Drug Safety Communication - Rare but Serious Risk of Heart Attack and Death

1. Screen all nuclear stress test candidates for their suitability to receive Lexiscan or Adenoscan. 
2. Avoid using these drugs in patients with signs or symptoms of unstable angina or cardiovascular instability, as these patients may be at greater risk for serious cardiovascular adverse reactions. 
3. Cardiac resuscitation equipment and trained staff should be available before administering Lexiscan or Adenoscan.http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm375981.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery