Is there a risk for a clinically important interaction between the new selective cyclooxygenase 2 i

Fråga: Is there a risk for a clinically important interaction between the new selective cyclooxygenase 2 inhibitor celecoxib and the beta-receptor antagonist atenolol? According to FASS 2000, concomitant treatment with beta-receptor antagonist and celecoxib should be avoided.

A 54-year-old women has been treated with Celebra (celecoxib) two times daily for a long time and was recently prescribed Tenormin (atenolol) 50 mg for mild hypertension.

Sammanfattning: There is no documentation on drug interaction between atenolol and celecoxib. No pharmacokinetic interaction is expected on the metabolic level. Celecoxib can have the same potential to increase blood pressure in hypertensive patients treated with betablockers as older NSAIDs. In the present case careful monitoring of blood pressure is recommended if celecoxib and atenolol are to be combined. Adjustment of the atenolol dose might be necessary.

Svar: There are currently no published studies concerning interactions between celecoxib and atenolol. This is probably due to the fact that celecoxib is a new drug on the market.

Celecoxib is metabolised mainly by the polymorphic cytochrome P450 isoenzyme CYP2C9 and partly by glucuronidation (1,2). Celecoxib can inhibit CYP2D6 isoenzyme and increase plasma concentration of other agents metabolised by this pathway (1). Atenolol is mainly excreted unchanged in the urine and a pharmacokinetic drug interaction is therefore not expected (3).

Treatment with celecoxib can worsen hypertension in some patients (4). In a study on

salt-depleted patients selective inhibition of COX-2 by celecoxib had no effect on systemic blood pressure at doses of 400mg (5). NSAIDs can antagonise the effect of beta-receptor antagonists in treatment of hypertension. This has been most thoroughly investigated for indomethacin. A possible mechanism is that NSAIDs inhibit the production of vasodilators and natriuretic prostaglandins stimulated by antihypertensive agents (6,7).

No cases of induced or worsened hypertension have been reported to the Swedish Adverse Drug Reactions Advisory Committee (SADRAC) in relation to celecoxib treatment. For the similar selective cyclooxygenas two inhibitor, rofecoxib, seven cases of hypertension (six possible, one probable) and three cases of worsening hypertension (two possible, one probable) have been reported (8). 1 Summary product characteristics (Searle) 2 Tang C, Shou M, Mei Q, Rushmore TH, Rodrigues AD: Major role of human liver microsomal cytochrome P450 2C9 (CPY2C9) in the oxidative metabolism of celecoxib, a novel cyclooxygenase-II inhibitor. J Pharmacol Exp Ther 2000; 293: 453-459 3 Dollery C Sir, editor. Therapeutic drugs. 2nd ed. Edinburgh: Churchill Livingstone; 1999, p. A224-A227 4 Davies NM, McLachlan AJ, Day OR, Williams KM: Clinical Pharmacokinetics and pharmacodynamics of celecoxib. Clin Pharmacokinet 2000; 38: 225-242 5 Rossat J, Maillard M, PharmD, Nussberger J, MD, Brunner HR, Burnier M.: Renal effects of selective cyclooxygenase-2 inhibition in normatonsive salt-depleted subjects. Clin Pharmacol 1999; 66: 77-84 6 Drugline no 16742 (year 2000) 7 Drugline no 05558 (year 1987) 8 Swedis (The Swedish Drug Information System)