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

Olive Oil and Mediterranean Diet

The following research article and discussion with Dr. Vogel highlight the disadvantages of fast foods and the beneficial effects of importance of Olive oil.
http://www.nejm.org/doi/full/10.1056/NEJMoa1200303

http://www.medscape.com/viewarticle/803568?nlid=31268_763&src=wnl_edit_medp_imed&uac=73164EG&spon=18 

Canagliflozin: New drug for management of type 2 diabetes mellitus

The U.S. Food and Drug Administration approved Invokana (canagliflozin) tablets, to be used with diet and exercise, to improve glycemic control in adults with type 2 diabetes on 30^th March, 2013.¹

Canagliflozin is a sodium-glucose co-transporter2 (SGLT2) inhibitor, a new group of oral hypoglycemic drugs.

Invokana works by blocking the reabsorption of glucose by the kidney, increasing glucose excretion, and lowering blood glucose levels in diabetics who have elevated blood glucose levels. Its safety and effectiveness were evaluated in nine clinical trials involving over 10,285 patients with type 2 diabetes. The trials showed improvement in hemoglobin A1c levels and fasting plasma glucose levels.

Invokana has been studied as a stand-alone therapy and in combination with other type 2 diabetes therapies including metformin, sulfonylurea, pioglitazone, and insulin.

Invokana should not be used to treat people with type 1 diabetes; patients having diabetic ketoacidosis; severe renal impairment, end stage renal disease, or in patients on dialysis.

Most common side effects of Invokana are vulvovaginal candidiasis and urinary tract infection. As Invokana is associated with a diuretic effect, it can cause a reduction in intravascular volume leading to orthostatic or postural hypotension. This may result in symptoms such as dizziness or fainting, and is most common in the first three months of therapy.

SGLT2 inhibitors:²

Glucose is reabsorbed from the proximal tubule of kidneys via family of membrane proteins (or transporters) called SGLTs. Approximately 180 g of glucose is filtered daily in a healthy adult and most of this is reabsorbed by SGLTs, with, 1% being excreted in the urine. Although there are several dif­ferent types of SGLTs, the two most studied are SGLT1 and SGLT2. The latter is responsible for reabsorption of over 90% of the glucose filtered while SGLT1, located in the distal segments, absorbs the remainder. SGLT2 inhibitors block the reabsorption of filtered glucose leading to glycosuria and improvement in glycemic control. These are also associated with a potential for weight loss.

A rare genetic condition, familial renal glucosuria, has served as a model for SGLT2 inhibition. In this dis­order, due to a mutation of SLCA2 gene there is impaired functioning of SGLT2, secondary to mutation of the SLCA2 gene, leading to daily urinary excretion of up to 100 g of glucose. Such patients are generally asymptomatic.

Inhibition of glucose uptake by the kidneys appears to be a new, unique, and promising insulin-independent approach to the treatment of type 2 diabetes.

References:

1.     US FDA. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm345848.htm

2.     Kim Y, Babu AR. Clinical potential of sodium-glucose cotransporter 2 inhibitors in the management of type 2 diabetes. Diabetes Metab Syndr Obes 2012;5:313-27.