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

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.

Association between omega 3 fatty acid supplementation and risk of major CV events

Omega-3 PUFA supplementation is not associated with a lower risk of all-cause mortality, cardiac death, sudden death, myocardial infarction, or stroke based on relative and absolute measures of association according to a recent systemic review and meta-analysis.
http://www.ncbi.nlm.nih.gov/pubmed/22968891?dopt=Abstract

http://www.ncbi.nlm.nih.gov/pubmed/22968891?dopt=Abstract

Tudorza- New dry powder inhaler for chronic obstructive pulmonary disease

FDA approves Tudorza Pressair to treat chronic obstructive pulmonary disease
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm313052.htm

New drug for obesity- Qsymia

FDA approves new drug for management of obesity.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm312468.htm

Association between chronic use of proton pump inhibitors (PPIs) and risk of hip fracture.

Proton pump inhibitors (PPIs) are among the most commonly used drugs worldwide.

Although short term use of PPIs is generally well tolerated, concern has grown over potential association between long term use and bone fractures, especially of the hip, which is known to be associated with substantial morbidity and mortality.  PPIs may inhibit calcium absorption, directly interfere with osteoclast function, or induce hypergastrinaemia, resulting in reductions in bone mineral density related to hyperparathyroidism.

·       The association between long term PPI use and risk of hip fracture among postmenopausal women was studied in a large prospective cohort, the Nurses’ Health Study, where detailed information about dietary and lifestyle factors are collected biennially.

Main outcome measure Incident hip fracture

Results

·       During 565,786 person years of follow-up, 893 incident hip fractures were documented.

·       The absolute risk of hip fracture among regular users of PPIs was 2.02 events per 1000 person years, compared with 1.51 events per 1000 person years among non-users.

·       Compared with non-users, the risk of hip fracture among women who regularly used PPIs for at least two years was 35% higher, with longer use associated with increasing risk (P_trend<0.01).

·       Adjustment for risk factors, including body mass index, physical activity, and intake of calcium did not materially alter this association (hazard ratio 1.36 (1.13 to 1.63)). These associations were also not changed after accounting for reasons for PPI use.

·       The relation between PPI use and fracture differed by smoking history (P_interaction=0.03). Among current and former smokers, PPI use was associated with greater than 50% increase in risk of fracture.

·        In contrast, among women who never smoked there was no association.

·       In a meta-analysis of these results with 10 prior studies, the pooled odds ratio of hip fracture associated with PPI use was 1.30 (1.25 to 1.36).

Among postmenopausal women, regular use of proton pump inhibitors was associated with a 35% increased risk of hip fracture. The risk seemed to be confined to women with a history of smoking

Smoking cessation

http://www.dovepress.com/articles.php?article_id=9502

Bevacizumab- change in label

On 30^th September, 2011, US FDA informed that changes in bevacizumab (Avastin, Genentech, Inc.) package insert regarding: risk of ovarian failure, osteonecrosis of the jaw, risk of venous thromboembolic event (VTE) and bleeding in patients receiving anticoagulation therapy after first VTE event have been made.

These changes include the following:

• Warning subsection added- increased risk of ovarian failure in premenopausal patients receiving bevacizumab and chemotherapy. It also states a recommendation that females of reproductive potential be informed of the increased risk of ovarian failure prior to starting treatment with bevacizumab,
• Osteonecrosis of the jaw is an adverse reaction of bevacizumab,
• new information regarding the risks of venous thromboembolic events and bleeding in patients receiving anti-coagulation therapy after first VTE event while receiving bevacizumab.

http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm274394.htm

High olive oil consumption has a protective role

A protective role for high olive oil consumption on the risk of stroke in older subjects has been suggested by a study published online on 15^th June, 2011 in Neurology 2011;77:1–1

Sameiri C from From the Research Center INSERM, U897, Department of Nutritional Epidemiology, France determined whether high olive oil consumption, and high plasma oleic acid (as an indirect biological marker of olive oil intake), are associated with lower incidence of stroke in older subjects. They enrolled participants from the Three-City Study with no history of stroke at baseline.

They found that in the main sample, 148 incident strokes occurred. After adjustment for sociodemographic and dietary variables, physical activity, body mass index, and risk factors for stroke, a lower incidence for stroke with higher olive oil use was observed (p for trend = 0.02). Compared to those who never used olive oil, those with intensive use had a 41% lower risk of stroke. It was also seen that higher plasma oleic acid was associated with lower stroke incidence. Compared to those in the first tertile, participants in the third tertile of plasma oleic acid had a 73% reduction of stroke risk.

The authors concluded that in the present population-based study, intensive olive oil use was prospectively associated with a lower stroke risk after controlling for numerous confounding factors, including lifestyle and nutritional factors, main stroke risk factors, and blood lipids.

Statin therapy associated with excess risk of developing diabetes mellitus

Priess D and colleagues from BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom conducted a meta-analysis to investigate whether intensive-dose statin therapy is associated with increased risk of new-onset diabetes compared with moderate-dose statin therapy. They included all randomized controlled end-point trials (January 1, 1996, through March 31, 2011) that compared intensive-dose statin therapy with moderate-dose statin therapy and had more than 1000 participants with > 1 year follow-up.

They found that in 5 statin trials with 32 752 participants without diabetes at baseline, 2749 developed diabetes (2.0 additional cases in the intensive-dose group per 1000 patient-years) and 6684 experienced cardiovascular events (6.5 fewer cases in the intensive-dose group per 1000 patient-years) over a weighted mean (SD) follow-up of 4.9 (1.9) years. Odds ratios were 1.12 for new-onset diabetes and 0.84 for cardiovascular events for participants receiving intensive therapy compared with moderate-dose therapy.

The authors concluded that in a pooled analysis of data from 5 statin trials, intensive-dose statin therapy was associated with an increased risk of new-onset diabetes compared with moderate-dose statin therapy.

http://www.ncbi.nlm.nih.gov/pubmed/21693744

PPI use associated with antifracture activity of Alendronate

The use of PPIs to control upper GIT complaints in patients treated with oral bisphosphonates should be discouraged according to a study published on 13^th June, 2011 online in Archives of Internal Medicine.

Bo Abrahamsen, MD, PhD from Institute of Clinical Research, Denmark and colleagues conducted a population-based, national register–based, open cohort observational study of 38 088 new alendronate sodium users with a mean duration of follow-up of 3.5 years.  They related risk of hip fracture to recent pharmacy records of refill of prescriptions for alendronate.

They found that for hip fractures, there was a statistically significant interaction with alendronate for PPI use (P < .05). The treatment response associated with complete refill compliance to alendronate was a 39% risk reduction (P < .001) in patients who were not PPI users, while the risk reduction in concurrent PPI users was not significant (P = .06). It was found that decrease of the risk reduction was dependent on dose and age. In contrast, there was no significant impact of concurrent use of histamine H₂ receptor blockers.

The authors concluded that the concomitant use of PPI and alendronate was associated with a dose-dependent loss of protection against hip fracture with alendronate in elderly patients.

http://archinte.ama-assn.org/cgi/content/abstract/171/11/998?etoc.