Recently, the US Food and Drug Administration (USFDA) has approved Consensi which is an oral fixed combination drug product (FCDP) of amlodipine and celecoxib for the treatment of hypertension and osteoarthritis pain.1
Consensi has been developed as a “convenience reformulation” FDCP to facilitate and improve compliance with once a day administration for the treatment of hypertension in patients who also require use of a nonsteroidal anti‐inflammatory drug (NSAID) for relief of the signs and symptoms of osteoarthritis.2 In one phase 3 clinical trial conducted, Consensi was found to be equally efficacious in blood pressure reduction as compared to amlodipine alone.2, 3
Celecoxib can lead to new onset hypertension or worsening of pre‐existing hypertension, either of which may contribute to the increased incidence of cardiovascular (CV) events. There is increased risk of serious CV thrombotic events which began as early as the first few weeks of treatment. Even in the absence of previous CV symptoms, physicians and patients are advised to be alert for the development of such events throughout the entire treatment course. Thus, in subjects with hypertension, celecoxib has to be prescribed at the lowest effective dose for the shortest possible period of time.2 Hence, combining amlodipine with celecoxib, which may not only reduce its therapeutic effect but also increase CV risks, does not make sound therapeutic sense.
The total numbers of subjects in the two phase 3 trials conducted on Consensi were merely 256, with study duration of 14 days only.2, 3 This raises concerns over the robustness of the results of the two trials. There are no long‐term studies on Consensi evaluating CV safety or reductions in the signs and symptoms of osteoarthritis.
Hypertension and osteoarthritis are two entirely unrelated conditions requiring different treatment approaches. Hypertension is a chronic condition requiring long‐term treatment adherence. Switching the patient on an antihypertensive drug to Consensi for a short duration and then again switching to the same antihypertensive drug will add complexity as well as inconvenience to the treatment which can adversely affect the adherence.4
The validity of PRECISION trial supported by Pfizer (which concluded that CV risks associated with moderate doses of celecoxib were not greater than that associated with nonselective NSAIDs) has been questioned by Fitzgerald on multiple issues.5 So, even if celecoxib has to be prescribed for osteoarthritis, it should better be prescribed as a separate formulation.
Compliance is an issue for medications which are prescribed for long duration of time. The improved compliance which is being projected as an advantage is also dubious as Consensi has to be prescribed for the shortest possible period of time.
Thus, in the FDCP Consensi, the component celecoxib has potential inadvertent effect on the clinical condition for the treatment of which the other component amlodipine is being prescribed. To conclude, Consensi, instead of offering any advantage, has serious safety concerns.
COMPETING OF INTERESTS
There are no competing interests to declare.
Shukla AK, Jhaj R. Consensi: Is it a conscientious combination?. Br J Clin Pharmacol. 2019;85:1044–1044. 10.1111/bcp.13909
REFERENCES
- 1. FDA Approves Consensi [Internet] . [cited 2019 Jan.5]. Available from: https://www.drugs.com/consensi.html.
- 2. LabelingFinalConsensi.pdf [Internet] . [cited 2019 Jan 5]. Available from: http://kitovpharma.com/wp‐content/uploads/2018/06/LabelingFinalConsensi.pdf.
- 3. Study to evaluate the effect of celecoxib on the efficacy and safety of amlodipine in subjects with hypertension requiring antihypertensive therapy—study results—ClinicalTrials.gov [Internet]. [cited 2019 Jan 5]. Available from: https://clinicaltrials.gov/ct2/show/results/NCT02172040.
- 4. Adherence to long‐term therapies—evidence for action: section III—disease‐specific reviews: chapter xi—epilepsy: 4. Factors affecting adherence and interventions used to improve it [Internet]. [cited 2019 Jan 5]. Available from: http://apps.who.int/medicinedocs/en/d/Js4883e/8.5.4.html
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