Drug reference

Diclofenac + Paracetamol

NSAID · Analgesic, Antipyretic, Anti-inflammatory

Also known as Voveran Plus, Dolokind Plus, Combiflam, Diclomol, Dicloran P

NSAIDAnalgesic, Antipyretic, Anti-inflammatory

CDSCO approved

Pharmacokineticsplasma · t hours

ONSET: 30min · Diclofenac: 30 minutes to 1 hour. Paracetamol: 30 minutes to 1 hour.
PEAK: 1.5h · Diclofenac: 1-2 hours. Paracetamol: 0.5-2 hours.
t½: 1.5h · Diclofenac: 1-2 hours. Paracetamol: 2-3 hours (unaffected by renal impairment for therapeutic doses, but toxic metabolites accumulate in overdose).
DURATION: 5h · Diclofenac: 4-6 hours. Paracetamol: 4-6 hours.

EXCRETION

—

not curated

INTERACTIONS

12 major

incl. contraindicated

PREGNANCY

—

not curated

Top interactionssee all 12 →

SulfasalazineContraindicatedTextbookG&G 14e · p1112
AminoglycosideSevereTextbookKDT 7e · p746
AminoglycosidesSevereTextbookKDT 7e
AnticoagulantsSevereTextbookKDT 7e

Mechanism

Diclofenac is an NSAID that primarily inhibits cyclooxygenase (COX-1 and COX-2) enzymes, thereby reducing the synthesis of prostaglandins, which are mediators of inflammation, pain, and fever. Paracetamol (acetaminophen) is believed to act predominantly through central inhibition of prostaglandin synthesis, likely via a COX-3 mechanism or modulation of serotonergic pathways, leading to analgesic and antipyretic effects without significant anti-inflammatory action at therapeutic doses. The combination provides synergistic pain relief and anti-inflammatory effects by targeting different pain pathways. Combination rationale: This fixed-dose combination leverages the complementary mechanisms of action of diclofenac and paracetamol. Diclofenac provides potent anti-inflammatory and analgesic effects by inhibiting prostaglandin synthesis, while paracetamol offers additional analgesic and antipyretic benefits through its central action. This combination can result in enhanced pain relief and fever reduction, potentially allowing for lower doses of each component, which might reduce the risk of dose-related side effects compared to higher doses of a single agent, thereby offering a broader spectrum of action against pain and inflammation.

Indications

Pain and inflammation associated with musculoskeletal disorders (e.g., sprains, strains, low back pain, arthritis)Post-operative painPost-traumatic painHeadacheDental painDysmenorrheaFever with pain

Dosing

Adult: Typically, Diclofenac 50 mg + Paracetamol 325 mg or Diclofenac 50 mg + Paracetamol 500 mg, orally, 2 to 3 times a day after meals. The dosage should be individualized based on the patient's condition and response, using the lowest effective dose for the shortest possible duration.
Pediatric: Generally not recommended for children under 12 years due to the diclofenac component. Specific pediatric formulations and dosing exist for paracetamol alone, but this FDC is primarily for adult use. Consult a pediatrician for use in adolescents.
Renal adjustment: Use with caution in mild to moderate renal impairment. Avoid in severe renal impairment (CrCl <30 mL/min). Lower doses may be required, and renal function should be closely monitored. Both components are primarily renally excreted. Paracetamol dose may need adjustment in severe renal failure (prolonged dosing interval).…

Pharmacokinetics

Onset

Diclofenac: 30 minutes to 1 hour. Paracetamol: 30 minutes to 1 hour.

Peak effect

Diclofenac: 1-2 hours. Paracetamol: 0.5-2 hours.

Duration

Diclofenac: 4-6 hours. Paracetamol: 4-6 hours.

Half-life

Diclofenac: 1-2 hours. Paracetamol: 2-3 hours (unaffected by renal impairment for therapeutic doses, but toxic metabolites accumulate in overdose).

Bioavailability

Diclofenac: Approximately 50-60% (due to first-pass metabolism). Paracetamol: Approximately 60-90% (oral).

Protein binding

Diclofenac: >99% (primarily to albumin). Paracetamol: 10-25% (at therapeutic concentrations).

Metabolism

Diclofenac: Extensively metabolized in the liver by hydroxylation and glucuronidation, primarily via CYP2C9. Paracetamol: Extensively metabolized in the liver mainly by glucuronidation and sulfation, and to a lesser extent by CYP450 enzymes (CYP2E1, CYP1A2, CYP3A4) to a toxic intermediate (NAPQI) which is detoxified by glutathione.

Excretion

Diclofenac: Primarily renal (approximately 60% as metabolites), biliary/fecal (approximately 35% as metabolites). Paracetamol: Primarily renal (90-100% as metabolites and unchanged drug).

Contraindications

Hypersensitivity to diclofenac, paracetamol, or any excipients
Active gastrointestinal bleeding or peptic ulceration
History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs
Severe hepatic impairment
Severe renal impairment (creatinine clearance <30 mL/min)
Severe heart failure
Third trimester of pregnancy
Coronary artery bypass graft (CABG) surgery (peri-operative pain)

Side effects

Common

NauseaVomitingDyspepsiaAbdominal painDiarrheaConstipationHeadacheDizzinessRashElevated liver enzymes

Serious

Gastrointestinal bleeding, ulceration, or perforation
Acute renal failure
Hepatotoxicity (including hepatic failure, particularly with paracetamol overdose)
Anaphylactic or anaphylactoid reactions
Severe cutaneous adverse reactions (e.g., Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis)
Cardiovascular thrombotic events (e.g., myocardial infarction, stroke, particularly with diclofenac)
Hypertension
Fluid retention and edema
Agranulocytosis, thrombocytopenia, aplastic anemia (rare, but possible with both components)