PENNSAID
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PENNSAID (PENNSAID).
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.
| 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. |
| Molecular Weight | 296.15 |
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. |
| 1st trimester | Risk of neural tube defects and cardiovascular malformations based on prostaglandin synthesis inhibition; avoid use. |
| 2nd trimester | Avoid use; potential for fetal renal dysfunction and oligohydramnios. |
| 3rd trimester | Contraindicated due to risk of premature closure of ductus arteriosus and neonatal pulmonary hypertension. |
Clinical note
Comprehensive clinical and safety monograph for PENNSAID (PENNSAID).
| Placental transfer | Diclofenac crosses the placenta; detectable in fetal plasma. Degree of transfer is moderate. |
| Breastfeeding | Diclofenac is excreted into breast milk in low concentrations (relative infant dose <1%). Use with caution, especially in neonates or infants with compromised renal function. |
| Lactation Rating |
■ 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.
| Serious Effects |
History of hypersensitivity to diclofenac or any component of PENNSAIDActive peptic ulcer disease or gastrointestinal bleedingSevere renal impairment (CrCl <30 mL/min)Severe hepatic impairment (Child-Pugh Class C)Third trimester pregnancy (risk of premature ductus arteriosus closure)
| Precautions | Cardiovascular thrombotic events, gastrointestinal bleeding/ulceration/perforation, hypertension, congestive heart failure, renal toxicity, anaphylactoid reactions, serious skin reactions, and anemia. |
| Food/Dietary | Avoid alcohol consumption, as it may increase risk of gastrointestinal bleeding., No specific food interactions; however, maintain adequate hydration to support renal function., Monitor for signs of bleeding if taking anticoagulants or antiplatelet agents. |
Loading safety data…
| L2 (Safer) |
| 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. |
| Fetal Monitoring | Monitor for oligohydramnios and ductus arteriosus constriction if used beyond 30 weeks. Assess maternal renal function, hepatic function, and signs of bleeding. In chronic use, monitor fetal growth and amniotic fluid volume via ultrasound. |
| Fertility Effects | NSAIDs including diclofenac can impair female fertility through inhibition of prostaglandin synthesis affecting ovulation and implantation. Reversible upon discontinuation. Effects on male fertility are not well established but may affect sperm parameters. |
| Clinical Pearls | PENNSAID (diclofenac sodium topical solution) is indicated for the treatment of osteoarthritis pain in joints amenable to topical therapy, such as knees and hands., Apply to clean, dry skin; avoid application on open wounds, cuts, or areas with active infection., Maximum dose is 40 drops per joint per day (2 mL); do not exceed doses recommended for other NSAIDs., Do not use with other oral NSAIDs concurrently; contraindicated in patients with aspirin/NSAID allergy or history of asthma, urticaria, or other allergic reactions after NSAID use., Apply at least 10 minutes before covering with clothing or using heat; avoid exposure to sunlight or tanning beds., Monitor for signs of gastrointestinal bleeding, renal impairment, and cardiovascular events, especially in elderly or patients with comorbidities. |
| Patient Advice | Apply the medication exactly as prescribed, usually four times daily to the affected joint. · Do not apply to areas that are cut, infected, or have rashes. · Wash hands immediately after applying, unless treating the hands. · Do not use heating pads, bandages, or occlusive dressings over the treated area. · Avoid contact with eyes, nose, and mouth; if contact occurs, rinse thoroughly with water. · Limit sun exposure and do not use tanning beds while using this medication. · Inform your doctor about all other medications you take, especially NSAIDs, anticoagulants, and antihypertensives. · Seek medical attention if you experience severe stomach pain, black stools, vomiting blood, or shortness of breath. |