Adult: For the acute or long-term relief of mild to moderate pain: Initially, 1,000 mg followed by 500 mg 12 hourly depending on severity. Some patients may require 500 mg 8 hourly after initial dose. A lower starting dose of 500 mg, followed by 250 mg 8-12 hourly may be given based on severity of pain, patient's response, weight or advanced age. Max: 1,500 mg daily. Use the lowest effective dose for the shortest possible duration based on individual patient treatment goals. Elderly: Use the lowest effective dose for the shortest possible duration.
Oral Osteoarthritis, Rheumatoid arthritis
Adult: For the symptomatic treatment of acute or chronic cases: 500-1,000 mg daily in 2 divided doses. May adjust dose according to patient's response and tolerability. Max: 1,500 mg daily. Use the lowest effective dose for the shortest possible duration based on individual patient treatment goals.
Renal Impairment
Severe: Contraindicated.
Administration
Should be taken with food.
Contraindications
Hypersensitivity. History of aspirin- or NSAID-induced acute asthma, urticaria, rhinitis or angioedema; previous or active peptic ulcer; history of, or active gastrointestinal bleeding or perforation related to previous NSAIDs treatment; severe heart failure, treatment of perioperative pain in the setting of CABG surgery. Pregnancy (3rd trimester). Severe renal (CrCl <30 mL/min) and hepatic impairment.
Special Precautions
Patient with risk factors for CV disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking), CHF, ischaemic heart disease, peripheral arterial disease, oedema, cerebrovascular disease, recent MI; history of gastrointestinal disease (e.g. ulcerative colitis, Crohn's disease), pre-existing asthma, coagulopathy. Alcohol use. Patients undergoing surgery or dental procedures. May mask signs and symptoms of infection. Not recommended for use as an antipyretic agent. Concomitant use of other NSAIDs, corticosteroids, anticoagulants, and antiplatelets. Mild to moderate renal and hepatic impairment. Elderly or debilitated patients. Pregnancy (1st-2nd trimester) and lactation.
Adverse Reactions
Significant: New onset or exacerbation of hypertension, Na and fluid retention, haematologic effects (e.g. anaemia, decreased platelet adhesion and aggregation, prolonged bleeding time), renal effects (e.g. interstitial nephritis with haematuria, proteinuria, nephrotic syndrome; renal papillary necrosis and other renal injury [long-term use]), hepatic effects (e.g. transaminase elevations, abnormal LFTs), increased risk of hyperkalaemia (particularly in elderly, diabetic and renal disease patients); may impair female fertility; blurred vision, Reye's syndrome. Rarely, severe bloody dyscrasias (e.g. agranulocytosis, thrombocytopenia, aplastic anaemia). Blood and lymphatic system disorders: Haemolytic anaemia. Cardiac disorders: Palpitation, chest pain. Ear and labyrinth disorders: Tinnitus, hearing loss. Gastrointestinal disorders: Nausea, vomiting, constipation, diarrhoea, dyspepsia, flatulence, gastrointestinal pain, stomatitis, peptic ulcer, anorexia, eructation, gastritis. General disorders and administration site conditions: Headache, fatigue, fever, oedema. Hepatobiliary disorders: Hepatitis, liver function abnormalities, jaundice, cholestasis. Metabolism and nutrition disorders: Anorexia. Nervous system disorders: Dizziness, drowsiness, vertigo, paraesthesia. Psychiatric disorders: Somnolence, insomnia, nervousness, depression, hallucinations, confusion, disorientation. Respiratory, thoracic and mediastinal disorders: Dyspnoea. Skin and subcutaneous tissue disorders: Rash, erythema multiforme, urticaria, pruritus, sweating, dry mucous membranes, photosensitivity. Potentially Fatal: Serious CV thrombotic reactions (including MI and stroke); serious gastrointestinal adverse events (e.g. inflammation, bleeding, ulceration, and perforation); drug reaction with eosinophilia and systemic symptoms, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, hypersensitivity syndrome; severe bronchospasm (in patients with aspirin-sensitive asthma). Rarely, severe hepatic reactions (e.g. fulminant hepatitis, hepatic necrosis, hepatic failure).
PO: C, Z (NSAIDs caused foetal ductus arteriosus premature closure, foetal renal impairment and persistent pulmonary hypertension. Avoid near term, else use lowest dose for shortest time.)
Patient Counseling Information
This drug may cause drowsiness, dizziness, blurred vision, fatigue, and other neurologic effects, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor CBC, chemistry profile, occult blood loss, blood pressure, and LFTs periodically; renal function (e.g. urine output, serum BUN and creatinine). Assess for signs and symptoms of gastrointestinal bleeding as clinically indicated. Perform periodic ophthalmic evaluation in patients who develop visual disturbances during long-term treatment.
Overdosage
Symptoms: Nausea, drowsiness, vomiting, diarrhoea, decreased urinary output, hyperventilation, tachycardia, sweating, tinnitus, disorientation, stupor, coma and cardiorespiratory arrest. Management: Supportive and symptomatic treatment. Perform gastric lavage or induce emesis.
Drug Interactions
Decreased plasma concentration with antacids. Increased plasma concentration of paracetamol. May enhance neuroexcitatory and/or seizure-potentiating effect of quinolones. May enhance nephrotoxic effects of ciclosporin and tacrolimus. Increased serum concentration of lithium. May decrease effect of antihypertensive agents (e.g. ACE inhibitors, angiotensin II antagonists) and diuretics (e.g. hydrochlorothiazide, furosemide). Potentially Fatal: May increase risk of gastrointestinal toxicity with other NSAIDs (e.g. indometacin, naproxen), corticosteroids, anticoagulants (e.g. warfarin), SSRIs, or antiplatelet agents (e.g. aspirin). May increase serum concentration of methotrexate.
Food Interaction
May enhance adverse effects with alcohol.
Lab Interference
May cause falsely elevated serum salicylate levels. May result in false-positive aldosterone/renin ratio (ARR).
Action
Description: Mechanism of Action: Diflunisal, a salicylic acid derivative, is a non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Its exact mechanism of action has not been clearly established, but it appears to reversibly inhibit cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, resulting in decreased formation of prostaglandin precursors. Onset: Analgesic: Approx 1 hour. Duration: 8-12 hours. Pharmacokinetics: Absorption: Rapidly and completely absorbed from the gastrointestinal tract. Time to peak plasma concentration: Approx 2-3 hours. Distribution: Enters breast milk. Volume of distribution: 7.53 L. Plasma protein binding: >99%. Metabolism: Extensively metabolised in the liver to glucuronide conjugates. Excretion: Via urine (approx 90% as glucuronide conjugates) and faeces (<5%). Plasma half-life: Approx 8-12 hours.
Chemical Structure
Diflunisal Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3059, Diflunisal. https://pubchem.ncbi.nlm.nih.gov/compound/Diflunisal. Accessed Feb. 26, 2024.
N02BA11 - diflunisal ; Belongs to the class of salicylic acids and derivatives agents. Used to relieve pain and fever.
References
Anon. Diflunisal. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 27/12/2023.Anon. Diflunisal. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 27/12/2023.Buckingham R (ed). Diflunisal. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 27/12/2023.Diflunisal Tablet (Zydus Lifesciences Limited). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 27/12/2023.Diflunisal Tablet, Film Coated (Chartwell RX, LLC.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 27/12/2023.Diflunisal. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 23/01/2024.Dolobid (Merck & Co., Inc.). U.S. FDA. https://www.fda.gov. Accessed 27/12/2023.
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