VOLTAREN-XR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VOLTAREN-XR (VOLTAREN-XR).

How it works

Nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2), reducing prostaglandin synthesis. This leads to anti-inflammatory, analgesic, and antipyretic effects.

What the body does with it

Metabolism	Hepatic metabolism primarily via CYP2C9, with minor contributions from CYP3A4. Conjugation with glucuronic acid and renal excretion of metabolites.
Excretion	Approximately 65% of a dose is excreted renally as unchanged drug and metabolites (primarily as glucuronide conjugates); about 35% is eliminated via bile in feces.
Half-life	The terminal elimination half-life is approximately 2 hours. The extended-release formulation (XR) does not alter the half-life; it maintains prolonged therapeutic plasma concentrations with twice-daily dosing.
Protein binding	Diclofenac is more than 99% bound to serum proteins, primarily albumin.
Volume of Distribution	The apparent volume of distribution is approximately 0.12–0.17 L/kg, indicating distribution primarily into extracellular fluid and high protein binding.
Bioavailability	Oral bioavailability is approximately 50% due to first-pass metabolism. With the XR formulation, absorption is complete but slower, yielding more sustained concentrations.
Onset of Action	Oral (XR tablet): Onset of analgesic effect is within 1 hour; peak effect occurs at 2-4 hours. For non-XR oral formulations, onset is within 30 minutes.
Duration of Action	Analgesic effect lasts up to 12 hours with the XR formulation due to sustained release; the extended duration allows twice-daily dosing. Anti-inflammatory effects are sustained with regular dosing.

Classification & Brands

Dosing & administration

100 mg orally once daily, extended-release formulation. Maximum 150 mg/day (divided as 75 mg twice daily or 100 mg once daily).

Dosage form	TABLET, EXTENDED RELEASE
Renal impairment	CrCl <30 mL/min: contraindicated. CrCl 30-59 mL/min: reduce dose to 50 mg once daily or 75 mg once daily; monitor renal function. CrCl >=60 mL/min: no adjustment.
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50% (maximum 100 mg/day) and monitor. Child-Pugh Class C: contraindicated.
Pediatric use	Not recommended for children <1 year. For children >=1 year (systemic juvenile idiopathic arthritis): 1-2 mg/kg/day in two divided doses, maximum 3 mg/kg/day. Extended-release formulation not recommended for pediatric use.
Geriatric use	Initiate at lowest effective dose, typically 75-100 mg once daily. Maximum 100 mg/day. Consider renal function, increased risk of GI bleeding, and cardiovascular events.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for VOLTAREN-XR (VOLTAREN-XR).

Breastfeeding	Limited data; diclofenac excreted in breast milk at low levels (M/P ratio ~0.015). Considered compatible with breastfeeding due to low infant dose.
Teratogenic Risk	First trimester: Increased risk of miscarriage and cardiac defects. Second and third trimesters: Premature closure of ductus arteriosus, oligohydramnios, neonatal renal impairment. Avoid after 30 weeks.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. Risk increases with duration of use and in patients with cardiovascular disease or risk factors. Also, increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to diclofenac or any component, history of asthma/urticaria/allergic reaction after taking aspirin or other NSAIDs, coronary artery bypass graft (CABG) surgery, advanced renal disease, patients with NSAID-induced GI bleeding or perforation, history of GI bleed or perforation related to previous NSAID therapy, active peptic ulcer disease, severe heart failure.

Clinical Precautions

Precautions

Cardiovascular events, GI injury/bleeding, hypertension, sodium and fluid retention, renal toxicity (especially in patients with impaired renal function, heart failure, liver dysfunction, or elderly), anaphylactoid reactions, skin reactions (e.g., Stevens-Johnson syndrome), hematologic events (anemia, bleeding), hepatic effects, asthma exacerbation, use in pregnancy (avoid in late pregnancy due to premature closure of ductus arteriosus).

Clinical Tips & Counseling

Drug interactions

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VOLTAREN-XR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VOLTAREN-XR (VOLTAREN-XR).

How it works

Nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2), reducing prostaglandin synthesis. This leads to anti-inflammatory, analgesic, and antipyretic effects.

What the body does with it

Metabolism	Hepatic metabolism primarily via CYP2C9, with minor contributions from CYP3A4. Conjugation with glucuronic acid and renal excretion of metabolites.
Excretion	Approximately 65% of a dose is excreted renally as unchanged drug and metabolites (primarily as glucuronide conjugates); about 35% is eliminated via bile in feces.
Half-life	The terminal elimination half-life is approximately 2 hours. The extended-release formulation (XR) does not alter the half-life; it maintains prolonged therapeutic plasma concentrations with twice-daily dosing.
Protein binding	Diclofenac is more than 99% bound to serum proteins, primarily albumin.
Volume of Distribution	The apparent volume of distribution is approximately 0.12–0.17 L/kg, indicating distribution primarily into extracellular fluid and high protein binding.
Bioavailability	Oral bioavailability is approximately 50% due to first-pass metabolism. With the XR formulation, absorption is complete but slower, yielding more sustained concentrations.
Onset of Action	Oral (XR tablet): Onset of analgesic effect is within 1 hour; peak effect occurs at 2-4 hours. For non-XR oral formulations, onset is within 30 minutes.
Duration of Action	Analgesic effect lasts up to 12 hours with the XR formulation due to sustained release; the extended duration allows twice-daily dosing. Anti-inflammatory effects are sustained with regular dosing.

Classification & Brands

Dosing & administration

100 mg orally once daily, extended-release formulation. Maximum 150 mg/day (divided as 75 mg twice daily or 100 mg once daily).

Dosage form	TABLET, EXTENDED RELEASE
Renal impairment	CrCl <30 mL/min: contraindicated. CrCl 30-59 mL/min: reduce dose to 50 mg once daily or 75 mg once daily; monitor renal function. CrCl >=60 mL/min: no adjustment.
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50% (maximum 100 mg/day) and monitor. Child-Pugh Class C: contraindicated.
Pediatric use	Not recommended for children <1 year. For children >=1 year (systemic juvenile idiopathic arthritis): 1-2 mg/kg/day in two divided doses, maximum 3 mg/kg/day. Extended-release formulation not recommended for pediatric use.
Geriatric use	Initiate at lowest effective dose, typically 75-100 mg once daily. Maximum 100 mg/day. Consider renal function, increased risk of GI bleeding, and cardiovascular events.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for VOLTAREN-XR (VOLTAREN-XR).

Breastfeeding	Limited data; diclofenac excreted in breast milk at low levels (M/P ratio ~0.015). Considered compatible with breastfeeding due to low infant dose.
Teratogenic Risk	First trimester: Increased risk of miscarriage and cardiac defects. Second and third trimesters: Premature closure of ductus arteriosus, oligohydramnios, neonatal renal impairment. Avoid after 30 weeks.
Fetal Monitoring