By William Elliott, MD, FACP, and James Chan, PharmD, PhD

Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.

Drs. Elliott and Chan report no financial relationships relevant to this field of study.

The FDA has approved a single tablet combination of amlodipine (AML) and celecoxib (CEL) for use in patients with hypertension and osteoarthritis. AML is a calcium channel blocker, and CEL is a selective cyclooxygenase inhibitor nonsteroidal anti-inflammatory drug (NSAID) marketed since 1992 and 2006, respectively. The combination is marketed as Consensi.

INDICATION

AML/CEL is indicated for patients for whom the treatment with AML for hypertension and CEL for osteoarthritis is appropriate.1

DOSAGE

The recommended starting dose is 2.5 mg of AML and 200 mg of CEL taken once daily.1 The AML dose can be titrated to 5 mg or 10 mg daily. AML/CEL is available as a single tablet combination of 2.5 mg/200 mg, 5 mg/200 mg, and 10 mg/200 mg tablets.

POTENTIAL ADVANTAGES

AML/CEL provides a convenient single-tablet treatment in appropriate patients.

POTENTIAL DISADVANTAGES

AML/CEL carries a boxed warning for risk of serious cardiovascular and gastrointestinal events associated with NSAIDs.1

COMMENTS

The approval of the combination AML/CEL was based on a randomized, double-blind, placebo- and active-controlled study in 152 subjects with newly diagnosed hypertension.1 Subjects were randomized to four treatment arms, 10 mg AML + 200 mg CEL, 10 mg AML, 200 mg CEL, or placebo (no AML or CEL). The results showed that the combination provided similar blood pressure reduction to the same dose of AML alone. There are no studies on the AML/CEL combination regarding reducing the signs and symptoms of osteoarthritis, so effectiveness of CEL in the combination is inferred from placebo-controlled studies of CEL alone.

CLINICAL IMPLICATIONS

AML/CEL is an interesting fixed combination. It combines two drugs that exhibit different treatment paradigms, a chronically administered drug and one in which the lowest dose and shortest duration of treatment may be appropriate based on individual treatment goals. Intermittent dosing of acetaminophen and over-the-counter NSAIDs are the initial recommended pharmacologic treatments by the American College of Rheumatology, after nonpharmacologic modalities, for both osteoarthritis of the knee and hip.2 This is followed by full-dose acetaminophen. If there is inadequate response, oral NSAIDs may be considered in patients < 75 years of age and without contraindications. In a recent Cochrane analysis, the authors found no clear evidence of differences between CEL and other NSAIDs in reducing pain and improving physical function in osteoarthritis, although they cited data quality issues due to pharmaceutical industry involvement and limited data.3 In patients with established cardiovascular disease or an increased risk of the development of cardiovascular disease, CEL appears to pose no greater risk than ibuprofen or naproxen.4 However, the risk of gastrointestinal toxicity was lower with CEL compared to ibuprofen and naproxen. This “protective” effect decreases in patients taking low-dose aspirin for cardioprotective effect, in which case a concomitant proton pump inhibitor is recommended. Oral NSAIDs should not be used in patients with stage IV or V chronic kidney disease and should be used with caution in patients with stage III chronic kidney disease.2 Given these considerations, the applicability of the single-tablet AML/CEL appears to be quite limited. The cost for AML/CEL is not available at the time of this review.

REFERENCES

  1. Consensi Prescribing Information. Kitov Pharma LTD, June 2018. Available to view online at: https://bit.ly/2yF5XNr. Accessed June 25, 2018.
  2. Hochberg MC, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res 2012;64:465-474.
  3. Puljak L, et al. Celecoxib for osteoarthritis. Cochrane Database Syst Rev 2017 May 22;5:CD009865.doi:1002/14651858.
  4. Nissen SE, et al. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. N Engl J Med 2016;375:2519-2529.