Non-selective COX inhibitor with COX-2 predominance, phenylacetic acid derivativeHIGHEST CARDIOVASCULAR RISK AMONG NSAIDsPRESCRIPTION-ONLY SINCE 2020

Diclofenac

Voltaren · Diklofenak Orifarm · Eeze

Potent NSAID with good effect in musculoskeletal and postoperative pain, but with the most unfavourable cardiovascular profile in the class — the increase in risk for myocardial infarction, stroke, and heart failure resembles that of selective COX-2 inhibitors and is seen already at doses below 100 mg/day and with short treatment duration. Oral diclofenac therefore requires a prescription in Sweden since 1 June 2020, while topical formulations remain non-prescription because systemic exposure is low.

BOXED WARNING

Contraindicated in established ischaemic heart disease, cerebrovascular disease, peripheral arterial disease, and heart failure NYHA II–IV. Beyond this, the full NSAID problem applies: peptic ulcer bleeding, acute kidney injury in dehydrated or RAAS-treated patients, and contraindication from gestational week 20.

Dosing in adults

By indicationuppdaterad 2026-08-22

Indication	Regimen	Comment
Acute musculoskeletal pain, adult	50 mg × 2–3, maximum 150 mg/day	shortest possible treatment duration
Maintenance treatment in osteoarthritis or arthritis	75–100 mg/day divided into 2–3 doses	only when another NSAID has not worked
Renal colic	50 mg orally or 75 mg im	effective but do not give to the anuric or hypovolaemic patient
Local pain in superficial joint or muscle	Gel 1–2 % applied 3–4 times daily	systemic exposure below 10 % — first choice when this suffices
Patient with cardiovascular disease	Should not be given	choose naproxen or low-dose ibuprofen if an NSAID is required

Renal impairment

eGFR 30–60 ml/min: avoid; if necessary, lowest dose with creatinine monitoring. eGFR < 30 ml/min: contraindicated.

Hepatic impairment

Diclofenac causes transaminase elevation more often than other NSAIDs. Check ALT within 4–8 weeks with longer treatment. Contraindicated in severe hepatic failure.

Children

In juvenile idiopathic arthritis from age 1, 1–3 mg/kg/day divided into 2–3 doses. Not used as a general analgesic or antipyretic in children.

Pitfall

Diclofenac is no longer a reasonable first-line NSAID. If an NSAID must be given to a patient with cardiovascular disease, naproxen or low-dose ibuprofen is the choice — diclofenac is precisely the drug for which the risk increase is greatest, and this increase is visible already after a few days of treatment.

Pharmacokinetics

BIOAVAIL.: 50 % oral (marked first-pass metabolism)
Vd: 0,12–0,17 l/kg
t½: 1–2 h
PROTEIN BINDING: > 99 %
METABOLISM: Hepatic, mainly CYP2C9
EXCRETION: Renal approximately 65 %, biliary approximately 35 %
ONSET: 30 min oral · 15–30 min im
DURATION: 6–8 h

Adverse effects by frequency

≥ 10 %

Dyspepsia, abdominal pain, nausea, headache

1–10 %

Transaminase elevation, dizziness, oedema, blood pressure rise, rash, creatinine elevation

< 1 %

Myocardial infarction and stroke, heart failure decompensation, peptic ulcer with bleeding or perforation, acute kidney injury, hepatitis, Stevens-Johnson syndrome

Monitoring schedule

Cardiovascular history and risk profile: before every initiation — determines whether the drug may be given
ALT: within 4–8 weeks with treatment lasting more than a few weeks
Creatinine and blood pressure: before initiation and after 1–2 weeks
Gastrointestinal symptoms and haemoglobin: with longer treatment

Interaction burden

28clinically significant

3 contraindicated · 11 major · 14 moderate. Triple whammy with ACE inhibitor or ARB and diuretic causes acute kidney injury. CYP2C9 inhibitors such as fluconazole and voriconazole increase exposure. Additive bleeding risk with warfarin, DOACs, antiplatelet agents, and SSRIs. Combination with another NSAID or analgesic-dose aspirin should be avoided entirely.

Formulation & cost

Enteric-coated tablet and sustained-release tablet: 25, 50, 75 and 100 mg
Gel for topical use: 1 % and 2 %
Restriction: oral diclofenac requires a prescription; topical formulations remain non-prescription