Arthritis/rheumatic disorders:

Indications for: PENNSAID 2%

To treat signs/symptoms of osteoarthritis of the knee(s).

Clinical Trials:

Study in Osteoarthritis of the Knee

A single double-blind controlled trial conducted in the US evaluated the use of Pennsaid for the treatment of pain of osteoarthritis of the knee. Patients were treated with either Pennsaid at a dose of 2 pumps twice a day applied directly to the study knee for 4 weeks or topical vehicle. 

Results showed that patients treated with Pennsaid experienced a greater reduction in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale after 4 weeks compared to patients treated with vehicle, -4.5 vs -3.6, respectively.

Adult Dosage:

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. 

For relief of the pain of osteoarthritis (OA) of the knee(s):  

  • The recommended dose is 40 mg of diclofenac sodium (2 pump actuations) on each painful knee, 2 times a day. Apply Pennsaid to clean, dry skin evenly around front, back, and sides of the knee. 

  • Application of Pennsaid in an amount exceeding or less than the recommended dose has not been studied and is therefore not recommended.

Children Dosage:

Not established.

PENNSAID 2% Contraindications:

Aspirin allergy. Coronary artery bypass graft surgery.

Boxed Warning:

Risk of serious cardiovascular and gastrointestinal events.

PENNSAID 2% Warnings/Precautions:

Increased risk of serious cardiovascular events (including MI, stroke). Avoid in recent MI, severe heart failure; if necessary, monitor. Increased risk of serious GI adverse events (including inflammation, bleeding, ulceration, perforation). History of ulcer disease and/or GI bleeding. Hypertension; monitor BP closely. Hepatic or renal impairment. Discontinue if signs/symptoms of liver disease develop, or if abnormal LFTs persist or worsen. Dehydration. Hypovolemia. Advanced renal disease: not recommended. Hyperkalemia. Coagulation disorders. Monitor CBCs, blood chemistry, hepatic, and renal function in long-term therapy. Pre-existing asthma. May mask signs of infection or fever. Discontinue at 1st sign of rash or any other hypersensitivity. Do not apply to open wounds, infections, inflammations, exfoliative dermatitis. Avoid eyes, mucous membranes, external heat and/or occlusive dressings, sunlight. Elderly. Debilitated. Labor & delivery. Pregnancy (avoid during ≥30 weeks gestation): increased risk of premature closure of the fetal ductus arteriosus; (20–30 weeks gestation): may cause fetal renal dysfunction/oligohydramnios; if treatment needed, limit dose and duration of use. Nursing mothers.

See Also:

PENNSAID 2% Classification:

NSAID (benzeneacetic acid deriv.).

PENNSAID 2% Interactions:

Avoid concomitant aspirin, salicylates (eg, diflunisal, salsalate) or other NSAIDs. Increased risk of GI bleed with anticoagulants, antiplatelets, oral corticosteroids, SSRIs, SNRIs, smoking, alcohol, or prolonged NSAID therapy; monitor. May antagonize, or increase risk of renal failure with diuretics (eg, loop or thiazides), ACE inhibitors, ARBs, or β-blockers; monitor closely. Potentiates digoxin; monitor levels. May potentiate lithium, methotrexate, cyclosporine; monitor for toxicity. Concomitant with pemetrexed may increase risk of pemetrexed-associated myelosuppression, renal, and GI toxicity. Caution with other hepatotoxic drugs (eg, acetaminophen, certain antibiotics, antiepileptics).

Adverse Reactions:

Application site reactions (eg, dry skin, contact dermatitis, pruritus, vesicles), GI upset; cardiovascular thrombotic events, GI ulcer/bleed, edema, hepatotoxicity, renal toxicity, hypersensitivity reactions, serious skin reactions (eg, Stevens-Johnson Syndrome, toxic epidermal necrolysis), Drug Reaction with Eosinophilia and Systemic Symptoms (discontinue if occurs), anemia.


Formerly known under the brand name Pennsaid.


Five diclofenac metabolites have been identified in human plasma and urine. The metabolites include 4'-hydroxy-, 5­ hydroxy-, 3'-hydroxy-, 4',5-dihydroxy- and 3'-hydroxy-4'-methoxy diclofenac. The formation of 4'-hydroxy diclofenac is primarily mediated by CYP2C9. 

Both diclofenac and its oxidative metabolites undergo glucuronidation or sulfation followed by biliary excretion. Acylglucuronidation mediated by UGT2B7 and oxidation mediated by CYP2C8 may also play a role in diclofenac metabolism. CYP3A4 is responsible for the formation of minor metabolites, 5-hydroxy and 3'-hydroxydiclofenac. 

Drug Elimination:

Diclofenac is eliminated through metabolism and subsequent urinary and biliary excretion of the glucuronide and the sulfate conjugates of the metabolites. Little or no free unchanged diclofenac is excreted in the urine.

Generic Drug Availability:

Soln 1.5% (YES); Pump 2% (NO)

How Supplied:

Soln 1.5%—contact supplier; Pump 2%—112g