Tolerability of diclofenac sodium 1% gel with concomitant medications known to interact with diclofenac

Figures & data

Figure 1 Disposition of patients.

Notes:^aDiscontinuation for unsatisfactory therapeutic effect occurred upon request of the patient; ^bdiscontinuation for protocol deviation was to occur only when the deviation created a safety issue in the judgment of the investigator.

Table 1 Baseline demographic characteristics by treatment group

Characteristic	All randomized patients
	Diclofenac sodium 1% gel (n = 254)	Vehicle (n = 238)
Women, %	67.3	65.5
White, %	75.2	80.3
Age, years
Mean (SD)	59.7 (10.5)	59.2 (10.6)
Range	36–90	35–92
BMI, kg/m^2
n	250	235
Mean (SD)	30.9 (6.2)	31.8 (7.0)
Range	18.4–53.2	18.5–57.7
WOMAC pain subscale scorea
Mean (SD)	11.7 (2.4)	11.7 (2.5)
Range	5–18	5–18
WOMAC physical function scorea
Mean (SD)	38.0 (10.0)	37.9 (10.7)
Range	4–65	9–64
Global rating of diseaseb
Mean (SD)	62.3 (19.4)	61.9 (19.5)
Range	9–100	1–100
Pain on movementc
Mean (SD)	71.3 (11.8)	71.4 (12.7)
Range	47–99	40–100

Notes:

a Pain, 0–20; physical function, 0–68;

b 0 = very good, 100 = very poor;

c 0 = no pain, 100 = most pain possible.

Abbreviations: BMI, body mass index; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index; SD, standard deviation.

Table 2 Diclofenac drug interactions identified among clinical trial patients treated with topical diclofenac sodium 1% gel by drug class and risk

Concomitant drug with diclofenac interaction	Number of patients with this drug interaction (n = 171)	Potential adverse event^Citation13
Antibiotics
Fluoroquinolone antibiotics	16	CNS toxicity
Levofloxacin	9
Ciprofloxacin	6
Moxifloxacin	1
Anticoagulants		Gastrointestinal bleed
Clopidogrel sulfate	1
Warfarin	1
Heparin-fraction sodium salt	1
Antidepressants
SSRIs	53	Gastrointestinal bleed
Escitalopram	16
Fluoxetine	14
Citalopram	6
Sertraline	9
Paroxetine	8
SNRIs	11	Gastrointestinal bleed
Venlafaxine hydrochloride	11
Lithium	1	Lithium toxicity
Antihypertensives
Angiotensin-converting enzyme inhibitors	63	Hypertension Renal failure
Lisinopril	25
Quinapril	9
Benazepril	8
Ramipril	8
Captopril	5
Fosinopril	4
Enalapril	3
Trandolapril	1
Beta blockers	74	Hypertension
Metoprolol	33
Atenolol	29
Timolol	4
Carvedilol	2
Propranolol	2
Labetalol	1
Angiotensin receptor blockers	40	Hypertension Renal failure
Valsartan	14
Irbesartan	8
Losartan	6
Candesartan cilexetil	5
Olmesartan medoxomil	4
Telmisartan	3
Calcium channel blockers	47	Hypertension
Amlodipine	27
Diltiazem	7
Nifedipine	7
Felodipine	5
Isradipine	1
Diuretics	63	Renal failure Heart failure Hypertension
Hydrochlorothiazide	42
Furosemide	9
Triamterene	6
Bumetanide	3
Torasemide	1
Indapamide	1
Spironolactone	1
Combination products	41
Triamterene plus hydrochlorothiazide	14
Amlodipine plus benazepril	12
Hydrochlorothiazide plus losartan	7
Hydrochlorothiazide plus lisinopril	5
Telmisartan plus hydrochlorothiazide	2
Spironolactone plus hydrochlorothiazide	1
Anti-inflammatories
Corticosteroids	26	Gastrointestinal bleed
Methylprednisolone	9
Prednisone	6
Triamcinolone	5
Dexamethasone	4
Cortisone	3
Hydrocortisone	2
NSAIDs	152	Gastrointestinal bleed
Acetylsalicylic acid	125a
Celecoxib	38
Ketorolac tromethamine	1
Antiinflammatory/ antirheumatic nonsteroids	1
Bisphosphonates	36	Gastrointestinal bleed
Alendronate sodium	32
Risedronate sodium	4
Digitalis alkaloids		Cardiac arrhythmia
Digoxin	2
Glucose-lowering drugs	16	Hypoglycemia
Glipizide	9
Glimepiride	6
Nateglinide	1

Note:

a Includes combination products Alka Seltzer^® and butalbital/aspirin/caffeine.

Abbreviations: CNS, central nervous system; NSAID, nonsteroidal anti-inflammatory drug; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.

Table 3 Total and most frequent AEs among clinical trial patients treated with topical diclofenac sodium 1% gel by presence of drug interaction

	Without DDIs, n (%) (n = 83)	With DDIs, n (%) (n = 171)
Any AE	46 (55.4)	107 (62.6)
Treatment-emergent AEs reported in ≥3% of either treatment group
Headache	7 (8.4)	28 (16.4)
Arthralgia	7 (8.4)	27 (15.8)
Back pain	9 (10.8)	14 (8.2)
Application-site dermatitis	6 (7.2)	5 (2.9)
Pain	3 (3.6)	8 (4.7)
Pain in untreated extremity	3 (3.6)	7 (4.1)
Nasopharyngitis	3 (3.6)	6 (3.5)
Sinusitis	3 (3.6)	6 (3.5)
Upper respiratory tract infection	3 (3.6)	6 (3.5)
Application-site pruritus	3 (3.6)	1 (0.6)
Sinus congestion	3 (3.6)	4 (2.3)
Myalgia	4 (4.8)	2 (1.2)
Neck pain	0	6 (3.5)

Abbreviations: AE, adverse event; DDI, drug–drug interaction with diclofenac.

Table 4 Gastrointestinal, cardiovascular, renal, and hepatic AEs among clinical trial patients treated with topical diclofenac sodium 1% gel by presence of drug interaction

	Without DDIs, n (%) (n = 83)	With DDIs, n (%) (n = 171)
Gastrointestinal AE, n (%)	6 (7.2)	9 (5.3)
Toothache	2 (2.4)	3 (1.8)
Dyspepsia	2 (2.4)	2 (1.2)
Diarrhea	1 (1.2)	1 (0.6)
Vomiting	0	2 (1.2)
Inguinal hernia	0	1 (0.6)
Nausea	0	1 (0.6)
Rectal hemorrhage	0	1 (0.6)
Upper abdominal pain	1 (1.2)	0
Cardiovascular AE, n (%)	1 (1.2)	8 (4.7)
Angina pectoris	0	1 (0.6)
Atrial fibrillation	0	1 (0.6)
Hematoma	0	1 (0.6)
Orthostatic hypotension	0	1 (0.6)
Palpitations	0	1 (0.6)
Ventricular fibrillationa	1 (1.2)	0
Tachycardia	0	1 (0.6)
Hypertension	0	4 (2.3)
Renal AE, n (%)	0	2 (1.2)
Blood creatinine increased	0	1 (0.6)
Blood urea increased	0	1 (0.6)
Pollakiuria	0	1 (0.6)
Hepatic AE, n (%)	1 (1.2)	0
Gamma glutamyltransferase increased	1 (1.2)	0

Note:

a 1 fatal, non–treatment-related cardiovascular AE (ventricular fibrillation) occurred in a 76-year-old man.

Abbreviations: AE, adverse event; DDI, drug–drug interaction with diclofenac.

BarkinRLReducing cardiovascular risks of nonsteroidal anti-inflammatory drugs by using topical formulationsAm J Cardiol20091049131519840584

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