Showing posts with label drugs. Show all posts
Showing posts with label drugs. Show all posts

Tuesday, December 20, 2011

Novartis halts late-stage Aliskiren trial due to lack of benefit, adverse events

Novartis will terminate the late-stage ALTITUDE study investigating Rasilez (aliskiren) in patients with type 2 diabetes and renal impairment on the recommendation of an independent data monitoring committee. The company indicated that the committee concluded that "patients were unlikely to benefit" from the addition of Rasilez to standard anti-hypertensives and also identified higher adverse events in this group.
"The finding comes very unexpected," commented Vontobel analyst Andrew Weiss, who had forecast peak annual sales for Rasilez of as much as $2.9 billion, assuming that the drug would have additional benefits for key organs if taken over a long period of time. Weiss said he now plans to reduce his sales estimate for the product. Meanwhile, there were suggestions that Novartis could accelerate plans to reduce its US workforce, with Deutsche Bank predicting that the drugmaker may cut up to 1000 sales jobs as a direct result of the study failure.
The trial, which included 8,606 patients with type 2 diabetes and renal impairment, was designed to evaluate the potential benefits of Rasilez to reduce the risk of cardiovascular and renal events. In the study, Rasilez was given in addition to optimal cardiovascular treatment including an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Novartis said the trial was the first to investigate Rasilez for more than one year in this specific patient group.
However, the drugmaker noted that in patients given Rasilez in combination with standard of care, "there was an increased incidence after 18-24 months of non-fatal stroke, renal complications, hyperkalemia and hypotension." Novartis indicated that it is in talks with health authorities regarding the implications of the findings, and in the meantime will stop promotion of products containing Rasilez for use in combination with an ACE-inhibitor or ARB. Spokesman Eric Althoff said the company is also looking at the data of other similar trials, which are currently ongoing.
Novartis suggested that sales of Rasilez, which is marketed as Tekturna in the US, "are likely to be negatively impacted by the study results going forward." According to the company, revenue for Rasilez-based products for the first nine months of 2011 reached $449 million, although "product profitability" in the year was negative.
The product was approved in 2007 in the EU and US for the treatment of hypertension either as a monotherapy or in combination with other therapies. The drugmaker has been looking to expand use of the agent, and has launched several trials to examine if the compound could protect organs such as kidneys and the heart if taken over a longer period of time.

Tuesday, December 28, 2010

Another Triple Drug Pill for HTN Gains FDA Nod

You knew it was just a matter of time...

After the barrage for angiotensin receptor blocker combination pills, here comes more of the same with the renin inhibitor, aliskiren.

Meet AMTURNIDE, a combination of the direct renin inhibitor, aliskiren - calcium channel blocker, amlodipine - diuretic, hydrochlorothiazide.

Not surprisingly, the adverse reactions mirror that of each of its three components.

The available doses will come in the following flavors:

  • 150 / 5/ 12.5 mg
  • 300 / 5/ 12.5 mg
  • 300 / 5/ 25 mg 
  • 300 / 10 / 12.5 mg
  • 300 / 10 / 25 mg

Monday, July 26, 2010

New "Me Too" Polypill for Hypertension Approved by FDA

Me too! Me too!

While not the first of its type, we welcome today another new combination pill for the treatment of hypertension, Tribenzor. Tribezor is a combination of three anti-hypertension medications in one pill. It is simply Azor plus HCTZ. Azor is a combination of the two medications: Benicar and Norvasc. Benicar is olmesartan. Olmesartan is an angiotensin receptor blocker or ARB. Norvasc is amlodipine. Amlodipine is a calcium channel blocker. HCTZ is hydrochlorothiazide. Hydrochlorothiazide is a thiazide type diuretic. Got it?

This ARB-CCB-HCTZ combo is actually useful and convenient. The polypill combines three classes of drugs commonly used in combination therapy to combat stage 2 hypertension. It is not approved for the initial treatment of HTN and is somewhat difficult as one can imagine to titrate. This offering follows the arrival of Exforge HCT (Diovan-Norvasc-HCTZ) to the market. The addition of HCTZ is an obvious one. Diuretics are cheap, effective and work well particularly in combination with the ARBs. The biggest surprise here is the name. I guess Azor HCT was just too easy.

Now the biggest questions is.... What is Twynsta going to call itself when it adds HCTZ? Trypsta?

Saturday, June 26, 2010

Digoxin Increases Risk of Death in Dialysis


An upcoming article published in the Journal of the American Society of Nephrology reveals a possible increased risk of premature death in hemodialysis patients who take the widely prescribed medication, digoxin. Digoxin is a purified extract from the foxglove plant (see left). Digoxin (or as it is affectionately known, "dig" (pronounced dij)) is commonly used in the treatment of congestive heart failure and atrial fibrillation. 

The researchers monitored more than 120,000 dialysis patients drawn from over 1,800 clinics across North America for up to four years. “We were surprised to find that digoxin use increased death risk in dialysis patients, especially in patients on higher doses," said  Kevin Chan, MD, MSci, Fresenius Medical Care North America, Waltham, MA.

The risk of death was 28 percent higher for dialysis patients taking digoxin, after adjustment for other factors. The increase in risk was greater for patients with higher levels of digoxin in their blood and in patients who had lower serum potassium levels, which is a well-known factor that contributes to digoxin toxicity.

Over 400,000 Americans currently live with dialysis for end-stage renal disease, which in itself, magnifies the risk for concurrent heart disease. When heart disease is present, it is sometimes treated with digoxin, for the of regulation heart rate in atrial fibrillation or the augmentation of overall pump function in heart failure.

Four percent of dialysis patients in the study were taking digoxin. "Although digoxin has been prescribed by doctors for over 200 years, widespread monitoring studies have not been conducted to examine the penetration, effectiveness, and safety of the drug among patients on dialysis," said Dr. Chan.

Monday, June 21, 2010

Novel ARB Mixes Best with Chlorthalidone

ARBs and Cancer?

Whoa... the darling of the hypertension world, the angiotensin receptor blockers (ARBs) have taken a hit. It doesn't seem to be a knock out blow, but a meta-analysis published in the Lancet Oncology has rocked the hypertension community with a study showing an association of ARBs and cancer.

The study casts doubts on this class of anti-hypertensives which has traditionally been used for its efficacy and favorable side effect profile. In addition to the indication for hypertension, ARBs as also used in the treatment of heart failure, diabetic nephropathy, and, recently, for cardiovascular risk reduction.


In an analysis of five studies following about 60,000 patients, researchers found a rise of 11 percent in cancer over all and 25 percent in lung cancer among patients who took ARBs.

Meta-analysis studies such as these are flawed and further investigation is warranted. For now, most experts are not recommending a change in prescribing habits or for people to cease using ARBs. Nevertheless, the safety profile of ARBs needs to be re-examined. More studies will surely follow.. stay tuned.

Wednesday, May 19, 2010

Is Generic Sensipar on the Way?

Jerusalem, May 14, 2010 - Teva Pharmaceutical Industries Ltd. (Nasdaq:TEVA) announced today that the U.S. Food and Drug Administration (FDA) has granted tentative approval for the Company's Abbreviated New Drug Application (ANDA) for Cinacalcet HCl Tablets 30, 60 & 90 mg.

Upon final approval, Teva's Cinacalcet HCl Tablets will be the AB-rated generic equivalent of Amgen's Sensipar®, indicated for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis.

The brand product had annual sales of approximately $458 million in the United States, based on IMS sales data.

Teva is currently involved in patent litigation concerning this product in the U.S. District Court for the District of Delaware. A trial date has not been set.

My friends at AMGEN just can't be too happy with this news..... Let's get ready to ruuuummmmmbbblllllleeeeeeee

Sunday, April 11, 2010

New UroCit K Extended Release Formulation

Mission Pharmacal Company has introduced the Urocit-K 15 mEq (potassium citrate) extended-release tablet.

Urocit-K is a commonly used urine alkalizing agent. It is used to prevent certain types of kidney stones.

The new formulation, which uses a wax-matrix delivery system to allow for extended-release of potassium citrate, provides a higher concentration of potassium citrate and has more active ingredient per tablet than other Urocit-K formulations, such as Urocit-K 10 mEq and Urocit-K 5 mEq.

However please note, although this is an improvement and it is extended release. The new Urocit K ER it is still meant to be used twice a day (BID). This is better than the previous three time a day (TID) formulation... but, still not as good as a once daily would be.

New Drug For HD Catheter Clotting

We all know, Fistula First... but, that still hasn't changed the fact that catheters are here to stay. Although they are rarely the first choice, despite best efforts, they are not uncommon in our hemodialysis units today. After the dreaded infectious complications of catheters, the next most significant complication of the HD catheter is clotting. These catheters can clot and blood flow can slow or cease.

Tenecteplase (TNKase)  is a recombinant fibrin-specific plasminogen activator and is currently under FDA review. It is derived from tissue plasminogen activator, with modifications at three sites of the protein structure. Tenecteplase binds to the fibrin component of the thrombus and selectively converts thrombus-bound plasminogen to plasmin. This subsequently degrades the fibrin matrix of the thrombus. The agent is indicated as a thrombolytic therapy for the acute phase of myocardial infarction (MI) for reduction of mortality associated with acute MI. TNKase, may significantly improve the function of HD catheters blocked by blood clots, according to data from a phase 3 open-label trial.

Study investigator Steven Fishbane, MD, Chief of Nephrology at Winthrop University Hospital in Mineola, N.Y. and his colleagues conducted a study with 223 patients to determine the safety and efficacy of tenecteplase for the treatment of dysfunctional HD catheters. The mean age of the patients was 61 years (range 16-97 years). Patients with cuffed, tunneled HD catheters and a blood flow rate (BFR) of less than 300 mL/min at an arterial pressure of -240 to -280 mm Hg received 2 mg/2 mL of tenecteplase in each lumen for a one hour intracatheter dwell. The investigators defined treatment success as achieve a BFR of 300 mL/min or greater with a 25 mL/min or greater increase from baseline BFR, without line reversal, at 30 minutes prior to HD and at the end of HD. Patients who did not achieve treatment success at the end of the initial visit received another 2 mg of tenecteplase. This second dose was given for an extended dwell period of up to 72 hours. The primary efficacy end point was the proportion of patients with treatment success at the end of the first HD visit.
Following the one hour tenecteplase dwell, 76 patients (34%) achieved treatment success, with a mean standard deviation increase from baseline BFR of 82 mL/min. Of the 116 patients who received extended-dwell tenecteplase, 57 (49%) had treatment success at the end of the next HD session, with a mean standard deviation increase from baseline BFR of 117 mL/min.

Here Comes the First Generic ARB...

WASHINGTON -- The FDA has approved generic versions of two antihypertensives: losartan potassium (Cozaar) and the combination drug losartan potassium and hydrochlorothiazide (Hyzaar).

The two drugs are the first generic angiotensin receptor blockers (ARBs) to win FDA approval.
Both drugs are indicated as standalone therapy for hypertension and stroke prevention in patients with a history of hypertension and left ventricular hypertrophy.

The losartan/hydrochlorothiazide combination is not indicated as initial therapy except in severe cases.
The drugs are contraindicated in patients with hypersensitivity to any of their components, and the combination is contraindicated in patients with anuria or hypersensitivity to other sulfonamide derivatives.

The generic drugs will also carry the same warnings as the brand name products, including a black box warning against use during the second and third trimesters of pregnancy.

Other warnings include impaired hepatic function, impaired renal function, and adverse reactions with lithium.
Generic losartan has been approved in 25, 50, and 100 mg doses, while the losartan/hydrochlorothiazide combination has been approved in 50/12.5, 100/12.5, and 100/25 mg doses.

Drug manufacturer TEVA Pharmaceutical will make generic versions of both generic products.
The FDA also gave the go-ahead to Mylan Pharmaceuticals, Roxane Laboratories, and Torrent Pharmaceuticals to manufacture the losartan/hydrochlorothiazide combination in the 100/12.5 mg dose.
The original drug application was held by Merck.

Drug patents for two other angiotensin receptor blockers -- eprosartan (Teveten) and irbesartan (Avapro) -- also expire in 2010.

Thursday, December 17, 2009

Clevidipine Recalled

FROM THE FDA FOR IMMEDIATE RELEASE - December 16, 2009 - Parsippany, N.J. - The Medicines Company (NASDAQ: MDCO) announced today that it is voluntarily recalling eleven (11) lots of Cleviprex ® (clevidipine butyrate) injectable emulsion due to the potential presence of visible particulate matter which has been observed in some vials during a routine annual inspection.

The affected Cleviprex lots are 61-978-DW, 61-979-DW, and 61-980-DW, Exp. 01/2010; 68-404-DJ, 68-405-DJ, and 68-406-DJ, Exp. 08/2010; 69-830-DJ, 63-385-DJ, 63-386-DJ, and 63-266-DJ, Exp 03/2011; and 64-453-DJ, Exp. 04/2011. No other lots are affected by this recall.

The Medicines Company has not received any product complaints or reports of adverse events related to this issue. The Company is cooperating with the U.S. Food and Drug Administration on this recall.

The particulate matter comprises sub-visible inert stainless steel particles of around 2.5 microns. When present in low numbers as observed, particles of this size are not known to constitute a health hazard. Experimental animal and human data indicate that they are scavenged by macrophages and other cells of the reticuloendothelial system without adverse effects. Although aggregates have not been observed, if the sub-visible particles were to aggregate, or if larger particles were present, then they could become visible and could theoretically reduce blood flow in capillaries, cause mechanical damage to some tissues, or initiate acute or chronic inflammatory reactions. Reduced blood supply to tissues may lead to ischemia or organ insufficiency in the brain, kidney, liver, heart or lungs.

Anyone with inventory from the affected lots of Cleviprex should arrange for its return through their pharmaceutical wholesaler/distributor. Unaffected product from lots 68-407-DJ, 68-408-DJ, 71-101-DJ and 71-106-DJ is being shipped to wholesalers and can be ordered by hospitals.

For medical inquiries, adverse event reporting or quality issues related to Cleviprex, please contact The Medicines Company Medical Information at 1-888-977-6326 Monday to Friday 8:00am-5:30pm EST or cleviprexrecall@themedco.com.

Any adverse reactions associated with the use of Cleviprex may also be reported to the FDA’s MedWatch Program by fax at 1-800-FDA-0178, by mail at MedWatch, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787, or on the MedWatch website at www.fda.gov/medwatch.

Tuesday, December 8, 2009

FDA Recommends Everolimus in Kidney Transplant


A federal advisory panel recommended the Food and Drug Administration approve a new anti-rejection drug from Novartis, everolimus.

From Dow Jones Newswires: The panel of outside medical experts voted 11 to 1 in favor of a question that asked if the drug, everolimus, should be approved. The FDA typically follows its panels' advice but is not required to.


The drug was approved in March at a different dose to treat advanced kidney cancer and is sold under the brand name Afinitor. Novartis is seeking approval for everolimus in combination with two other drugs for kidney transplant patients.

FDA said a study comparing two doses of everolimus to Myfortic, another Novartis drug used in kidney-transplant patients, showed both drugs worked equally as well at preventing the body from rejecting a new kidney in a study that involved 1,335 patients.

However, the agency said there was a higher failure rate among women being treated with everolimus compared to Myfortic.
The agency said mortality rates were similar "with more deaths attributed by FDA to the study drug" in the lower-dose everolimus group. The agency said there were three times as many kidney rejections attributed to blood clots in the everolimus group compared to the Myfortic group.

But, the agency said there were fewer cases of cytomegalovirus infections and cancer in the everolimus group compared to the Myfortic group. Cytomegalovirus is a common infection associated with organ transplants that can lead to other infections and cause the body to reject the transplanted organ.

In its briefing document, Novartis said everolimus is a "meaningful alternative" therapy for kidney-transplant patients.





Wednesday, November 4, 2009

FDA Warns About Byetta Induced Renal Failure


FDA has notified healthcare professionals of revisions to the prescribing information for Byetta (exenatide) to include information on post-marketing reports of altered kidney function, including acute renal failure and insufficiency. 

From April 2005 through October 2008, FDA received 78 cases of altered kidney function (62 cases of acute renal failure and 16 cases of renal insufficiency), in patients using Byetta. The report states that, "Some cases occurred in patients with pre-existing kidney disease or in patients with one or more risk factors for developing kidney problems". However, as we know everyone who would be on Byetta has diabetes and thus inherently has at least one risk factor for CKD.

The labeling changes include:
  • Information regarding post-market reports of acute renal failure and insufficiency, highlighting that Byetta should not be used in patients with severe renal impairment (creatinine clearance <30 ml/min) or end-stage renal disease.
  • Recommendations to healthcare professionals that caution should be applied when initiating or increasing doses of Byetta from 5 mcg to 10 mcg in patients with moderate renal impairment (creatinine clearance 30 to 50 ml/min).
  • Recommendations that healthcare professionals monitor patients carefully for the development of kidney dysfunction, and evaluate the continued need for Byetta if kidney dysfunction is suspected while using the product.
  • Information about kidney dysfunction in the patient Medication Guide to help patients understand the benefits and potential risks associated with Byetta.
Cross off another diabetes medication for patients with advanced CKD....

Saturday, October 24, 2009

New Intravenous Thiazide, Coming to a Hospital Near You


I must admit, it is not readily obvious to me when or why I would use an intravenous thiazide over an IV loop diuretic... but nevertheless, it is pretty cool to have a new option.

The U.S. Food and Drug Administration has just approved APP Pharmaceutical’s Chlorothiazide Sodium (Diuril) for injection. The drug is approved for use in the treatment of high blood pressure , as well as fluid retention in people with congestive heart failure, cirrhosis of the liver, kidney disorders, or edema caused by taking steroids or estrogen.

APP is a subsidiary of Fresenius Kabi Pharmaceuticals, and they expect to launch the IV Chlorothiazide in the fourth quarter of 2009. It will come in single dose 500 mg vials. Maximum dose is 2000 mg / day.

Wednesday, September 23, 2009

New Phosphorous Binder in Pipeline

Keryx biopharmaceuticals has announced that their new phosphorous binder Zerenex is well tolerated, safe and effective for long term use.

Zerenex (ferric citrate) is an oral, iron-based compound that has the capacity to bind to phosphate and form non-absorbable complexes. Zerenex has recently completed a U.S. Phase 2 clinical program as a treatment for hyperphosphatemia (elevated phosphate levels) in patients with end-stage renal disease, and we are in the process of finalizing the U.S. Phase 3 program for Zerenex in consultation with the FDA. Zerenex is also in Phase 2 development in Japan.

Data from the mid-stage trial indicated that Zerenex could maintain phosphorus content at a normal level when used over an extended period of time. The data did not show signs of potential iron overload in the blood. The late-stage study for the kidney drug is expected to begin at the end of the year. More details to follow when available.