PENNSAID

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PENNSAID (PENNSAID).

How it works

Nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, reducing prostaglandin synthesis, thereby decreasing pain, inflammation, and fever.

What the body does with it

Metabolism	Hepatic metabolism via CYP2C9 (major) and CYP3A4 (minor); also undergoes glucuronidation.
Excretion	Primarily renal excretion of metabolites and conjugates; less than 1% excreted unchanged. Biliary/fecal excretion accounts for approximately 1%.
Half-life	Terminal elimination half-life is approximately 74 hours (range 53–97 hours) for diclofenac epolamine topical system. With repeated dosing, steady state is reached within 7 days.
Protein binding	99% bound to albumin. Diclofenac is highly bound to plasma proteins.
Volume of Distribution	Volume of distribution is approximately 0.12 L/kg. This low Vd indicates limited extravascular distribution, consistent with high protein binding.
Bioavailability	Topical administration: Systemic bioavailability is approximately 1–3% compared to oral diclofenac. The drug is designed to deliver active drug locally with minimal systemic absorption.
Onset of Action	Topical application: Onset of analgesia occurs within 1 hour post-application, with peak effect at 4 hours.
Duration of Action	Duration of analgesia is approximately 12 hours, allowing twice-daily application. Clinical effect persists throughout dosing interval.

Classification & Brands

Dosing & administration

Apply 1 sachet (50 mg diclofenac sodium) to each affected knee twice daily; total daily dose not to exceed 100 mg.

Dosage form	SOLUTION
Renal impairment	Contraindicated in patients with advanced renal disease (CrCl <30 mL/min). No specific dose adjustment for mild to moderate impairment, but use with caution.
Liver impairment	Contraindicated in Child-Pugh Class C. For mild to moderate impairment (Child-Pugh A or B), no dose adjustment; monitor for signs of hepatotoxicity.
Pediatric use	Safety and efficacy not established in pediatric patients. Not recommended for use in children.
Geriatric use	Elderly patients may be more sensitive to NSAID effects; use the lowest effective dose. Monitor renal function and gastrointestinal status.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PENNSAID (PENNSAID).

Breastfeeding	Diclofenac is excreted into breast milk in low amounts with a relative infant dose <1% of maternal weight-adjusted dose. M/P ratio not established. Usually considered compatible with breastfeeding; however, use lowest effective dose for shortest duration and monitor infant for gastrointestinal or renal effects.
Teratogenic Risk	NSAIDs including diclofenac (PENNSAID) should be avoided after 30 weeks' gestation due to risk of premature closure of ductus arteriosus and oligohydramnios. Use in first and second trimesters is associated with increased risk of miscarriage and congenital malformations, particularly cardiac defects and gastroschisis. Avoid during pregnancy unless clearly necessary.

Warnings & precautions

■ FDA Black Box Warning

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. PENNSAID is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to diclofenac or any component of the formulation; history of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; peri-operative pain in the setting of CABG surgery; advanced renal disease; patients with active gastrointestinal bleeding or perforation.

Clinical Precautions

Precautions

Cardiovascular thrombotic events, gastrointestinal bleeding/ulceration/perforation, hypertension, congestive heart failure, renal toxicity, anaphylactoid reactions, serious skin reactions, and anemia.

Clinical Tips & Counseling

Drug interactions

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PENNSAID

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PENNSAID (PENNSAID).

How it works

What the body does with it

Metabolism	Hepatic metabolism via CYP2C9 (major) and CYP3A4 (minor); also undergoes glucuronidation.
Excretion	Primarily renal excretion of metabolites and conjugates; less than 1% excreted unchanged. Biliary/fecal excretion accounts for approximately 1%.
Half-life	Terminal elimination half-life is approximately 74 hours (range 53–97 hours) for diclofenac epolamine topical system. With repeated dosing, steady state is reached within 7 days.
Protein binding	99% bound to albumin. Diclofenac is highly bound to plasma proteins.
Volume of Distribution	Volume of distribution is approximately 0.12 L/kg. This low Vd indicates limited extravascular distribution, consistent with high protein binding.
Bioavailability	Topical administration: Systemic bioavailability is approximately 1–3% compared to oral diclofenac. The drug is designed to deliver active drug locally with minimal systemic absorption.
Onset of Action	Topical application: Onset of analgesia occurs within 1 hour post-application, with peak effect at 4 hours.
Duration of Action	Duration of analgesia is approximately 12 hours, allowing twice-daily application. Clinical effect persists throughout dosing interval.

Classification & Brands

Dosing & administration

Apply 1 sachet (50 mg diclofenac sodium) to each affected knee twice daily; total daily dose not to exceed 100 mg.

Dosage form	SOLUTION
Renal impairment	Contraindicated in patients with advanced renal disease (CrCl <30 mL/min). No specific dose adjustment for mild to moderate impairment, but use with caution.
Liver impairment	Contraindicated in Child-Pugh Class C. For mild to moderate impairment (Child-Pugh A or B), no dose adjustment; monitor for signs of hepatotoxicity.
Pediatric use	Safety and efficacy not established in pediatric patients. Not recommended for use in children.
Geriatric use	Elderly patients may be more sensitive to NSAID effects; use the lowest effective dose. Monitor renal function and gastrointestinal status.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PENNSAID (PENNSAID).

Breastfeeding	Diclofenac is excreted into breast milk in low amounts with a relative infant dose <1% of maternal weight-adjusted dose. M/P ratio not established. Usually considered compatible with breastfeeding; however, use lowest effective dose for shortest duration and monitor infant for gastrointestinal or renal effects.
Teratogenic Risk	NSAIDs including diclofenac (PENNSAID) should be avoided after 30 weeks' gestation due to risk of premature closure of ductus arteriosus and oligohydramnios. Use in first and second trimesters is associated with increased risk of miscarriage and congenital malformations, particularly cardiac defects and gastroschisis. Avoid during pregnancy unless clearly necessary.