The US Food and Drug Administration (FDA) yesterday approved a combination of amlodipine besylate and the nonsteroidal anti-inflammatory drug (NSAID) celecoxib (Consensi, Kitov Pharma) for individuals with osteoarthritis pain and hypertension.
The company says that although celecoxib — a cyclooxygenase 2 inhibitor — does not reduce blood pressure when given alone, it appears to act synergistically with the antihypertensive calcium channel blocker amlodipine besylate to enhance amlodipine besylate’s blood pressure–lowering ability.
“Consensi provides a safe and effective combination treatment option for the millions of Americans who suffer from osteoarthritis pain and hypertension,” J. Paul Waymack, MD, ScD, chairman of Kitov’s board and chief medical officer, said in a company news release.
Amlodipine and celecoxib are already approved individually by the FDA.
The combo will be available in three dosage forms, in line with the currently approved dosages of both drugs. Each will have 200 mg of celecoxib; however, the dosages of amlodipine besylate will be 2.5, 5, and 10 mg. Consensi is intended to be taken once daily.
“Over 50 million Americans suffer from osteoarthritis. About 1 of 3 U.S. adults or about 75 million people have high blood pressure, known as the ‘silent killer’ due to the absence of noticeable symptoms. As a result, patients’ adherence to the hypertension treatment regimen is low. We believe that Consensi, as a single pill combination treatment for osteoarthritis and hypertension, presents a unique value proposition of potentially increasing treatment adherence,” Isaac Israel, chief executive officer, Kitov, said in the news release.
The approval follows the FDA’s consideration of data from a phase 3 clinical trial that met its primary endpoint of demonstrating that the combination medication lowers daytime systolic blood pressure by 50% or more of that achieved in patients who took amlodipine besylate only (P = .001).
The company also reported results from its randomized, double-blind, placebo-controlled renal function phase 3/4 trial, which it claims validated the primary efficacy endpoint met in the phase 3 clinical trial. Patients who took the combination pill experienced a statistically significant reduction of serum creatinine from its value at baseline (P = .0005). The reduction of serum creatinine shows the medication improves renal function, the researchers say. Serum creatinine did not significantly decrease in those who received either amlodipine besylate alone or placebo.
Boxed Warning for Potentially Fatal CV and GI Events
Because Consensi contains an NSAID, the prescribing information will include a boxed warning for potentially fatal cardiovascular (CV) and gastrointestinal (GI) events, including serious CV thrombotic events such as myocardial infarction and stroke, and GI events such as bleeding, ulceration, and perforation of the stomach or intestines. CV events can occur early in treatment, and the risk may increase over time. GI events can also occur without warning at any time. The risk for serious GI events is higher among the elderly and those with a history of peptic ulcer disease and/or GI bleeding.
The celecoxib/amlodipine combination is contraindicated in patients undergoing coronary artery bypass graft surgery and those with hypersensitivity to either drug or any of the inactive ingredients. It is also contraindicated in patients who have a known history of asthma, urticaria, or other allergic-type reactions to aspirin, other NSAIDs, or sulfonamides.
Clinicians should warn their patients about potential signs and symptoms of hepatotoxicity or liver failure and should discontinue the medication if abnormal liver test results continue or get worse, or if clinical signs and symptoms of liver disease develop.
Clinicians should monitor blood pressure closely because some patients who take antihypertensive medications may experience an impaired response to them while taking NSAIDs. Patients, especially those with severe aortic stenosis, may develop symptomatic hypotension. Patients may also experience increasing angina and acute myocardial infarction, and this risk is higher in those with severe obstructive coronary artery disease. The drug combination should not be used in patients with severe heart failure.
It should also be avoided in patients who are poor metabolizers of CYP2C9 substrates.
Clinicians should monitor hemoglobin or hematocrit in those who have any signs or symptoms of anemia.
Pregnant women should avoid taking this medication beginning at 30 weeks of gestation.
Suspected adverse reactions should be reported to Kitov Pharma at 1-800-651-6606 or to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.