Diclofenac Sodium 1% Gel Minimizes Drug-Drug Interaction-Related Adverse Events

HONOLULU, HI—Minimal systemic distribution of topical diclofenac sodium gel resulted in a lower incidence of major or moderate drug-drug interactions associated with oral diclofenac and reduced the risk of drug interaction-related adverse events. Study results were reported by Matthew Wieman, MD, from Endo Pharmaceuticals, John H. Peniston, DO, from Novartis Consumer Health, and colleagues at the American Pain Society’s 31^st Annual Scientific Meeting.

In a post hoc analysis of a 12-week, randomized, double-blind, vehicle-controlled, parallel-group trial, investigators examined the tolerability of diclofenac sodium 1% gel in 492 patients ≥35 years with osteoarthritis (OA) of the knee pain. Patients were eligible if they had OA in one or both knees, but with clinical OA symptoms in only one knee, diagnosed ≥6 months before screening. Patients were divided into two groups: those receiving one or more medications with a potentially major or moderate interaction with diclofenac sodium (n=132) or those not receiving medications with the potential for a drug interaction with diclofenac sodium (n=122). Concomitant medications that could potentially cause major or moderate drug-drug interactions with diclofenac sodium gel were identified by Drugs.com criteria. 

Following a 7-day washout of analgesics, patients were randomized in a 1:1 ratio to receive diclofenac sodium gel (n=254) or vehicle (n=238). Treatment was applied topically to the target knee 4 times daily for 12 weeks. The incidence of interactions was recorded and patients were subsequently divided into two groups: those with ≥1 drug-drug interaction and those with none. A total of 136 (53.5%) patients experienced ≥1 drug-drug interaction and 118 (46.5%) patients did not have a drug-drug interaction.

The overall occurrence of adverse events did not differ significantly between the two patient groups: ≥1 adverse event was recorded in 82 (62.1%) patients who experienced a drug-drug interaction and in 71 (58.2%) patients with no drug-drug interaction. The most commonly occurring adverse events in both groups were headache, arthralgia, and back pain. The incidence rates of individual classes of adverse events in patients with ≥1 drug-drug interaction were not elevated. Comparing patients with ≥1 drug-drug interaction to those with none, cardiac events were reported in 2.2% (n=3) vs. 4.9% (n=6), gastrointestinal events in 4.5% (n=6) vs. 7.4% (n=9), and hypertension in 0.8% (n=1) vs. 2.5% (n=3), respectively. Incidences of hepatic and renal adverse events were low in both groups.

Drs. Wieman and Peniston concluded that concurrent administration of diclofenac sodium gel 1% with medications that could result in an interaction had no noticeable impact on the tolerability. Additionally, the minimal systemic absorption of topical diclofenac may have reduced the risk of drug interaction-related adverse events.