APR DIANAREST (BLUE)

AF-06:

INFORMATION FOR THE USER

Diclofenac potassium50mg + Paracetamol 325mg Tablets

Read all of this information carefully before you start taking this medicine because it contains important information for you.
• Keep this information. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine is prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this information.

1. COMPOSITION:
Each tablet contains:
Diclofenac potassium – 50mg
Paracetamol – 325mg

For oral use only.

2.DESCRIPTION:
Diclofenac is an analgesic, antipyretic & anti-inflammatory drug & belongs to a class of drugs called NSAID’s (Non-steroidal anti-inflammatory drug). Paracetamol is also an NSAID.
Together both the drugs help to relieve inflammation, pain, swelling & related symptoms.

3.PHARMACOLOGICAL ACTION:
Diclofenac is a non-steroidal compound with pronounced & clinically demonstrable analgesic, anti-inflammatory & anti-pyretic properties. It is a potent inhibitor of prostaglandin biosynthesis & modulator of arachidonic acid release & uptake. It has a rapid onset of action &is suitable for the treatment of acute episodes of pain & inflammation. In vitro it does not suppress proteoglycan biosynthesis in cartilage at conc. eq. to the concentrations reached in human beings.
Paracetamol acts predominantly by inhibiting prostaglandin synthesis in the central nervous system (CNS) & to a lesser extent, through a peripheral action by blocking pain-impulse generation. The peripheral action may also be due to inhibition of prostaglandin synthesis or to inhibition of the synthesis or actions of other substances that sensitise pain receptors to mechanical or chemical stimulation.
4. CLINICAL PHARMACOKINETICS:
Diclofenac is rapidly & completely absorbed. Food intake does not affect absorption. Peak plasma conc. was 3.9 µmol/l after 20-60 min. Plasma conc. show a linear relationship to the size of the dose. It undergoes first-pass metabolism & is extensively metabolised. It is highly bound to plasma proteins (99.7%), chiefly albumin (99.4%). It is detected in a low conc. (100ng/mL) in breast milk. The estimated amount ingested by an infant consuming breast milk is eq. to a 0.03 mg/kg/day dose. The total systemic clearance in plasma is 263 ± 56 ml/min. The terminal half-life in plasma is 1-2 hrs. Repeated oral administration does not lead to accumulation in the plasma. Approx. 60% of the dose is excreted in urine in the form of metabolites& less than 1% as unchanged substance. The remainder is eliminated as metabolites through the bile in the faeces. The biotransformation of involves partly glucuronidation of the intact molecule but mainly single & multiple hydroxylation followed by glucuronidation.
Paracetamol is readily absorbed from the GI tract with peak plasma conc. occurring about 30 min-2 hrs after ingestion. It is metabolised in the liver & excreted in the urine mainly as the glucuronide & sulphate conjugates. Less than 5% is excreted as unchanged paracetamol. The elimination half-life varies from about 1-4 hrs. Plasma-protein binding is negligible at usual therapeutic conc. but increases with increasing conc.A minor hydroxylated metabolite produced in very small amounts by mixed-function oxidases in the liver & which is usually detoxified by conjugation with liver glutathione may accumulate following overdose&j cause liver damage.
5. INDICATIONS:
Diclofenac + Paracetamol tablets are indicated for the relief of pain & inflammation in:
1.Rheumatoid arthritis
2.Osteoarthrosis
3.Low back pain
4.Acute musculo-skeletal disorders & trauma such as periarthritis, tendinitis, tenosynovitis, bursitis, sprains, strains & dislocations; relief of pain in fractures
5.Ankylosing spondylitis
6.Acute gout
7.Control of pain & inflammation in orthopaedic, dental & other minor surgery
8.Pyrophosphate arthropathy& associated disorders

6.CONTRAINDICATIONS:
Diclofenac + Paracetamol tablets are contraindicated in the following cases:

1. Hypersensitivity to the Diclofenac/paracetamol or any of the excipients.
2.Active, gastric or intestinal ulcer, bleeding or perforation.
3.Active, or history of recurrent peptic ulcer / haemorrhage.
4.Patients who have previously shown hypersensitivity reactions in response to other NSAIDs.
5. Established congestive heart failure (NYHA II-IV), ischemic heart disease, peripheral arterial disease &/or cerebrovascular disease.
6.Severe heart failure, hepatic failure & renal failure.
7.History of GI bleeding or perforation, relating to previous NSAID therapy.
8.During the last trimester of pregnancy.

7.WARNINGS AND PRECAUTIONS:
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms.
Use with concomitant NSAIDs including cyclooxygenase- 2 selective inhibitors should be avoided.
Elderly:The elderly have an increased frequency of adverse reactions to NSAIDs especially GI bleeding & perforation.
Respiratory disorders:Caution is required if administered to patients suffering from, or with a previous history of, bronchial asthma since NSAIDs have been reported to precipitate bronchospasm in such patients.
Cardiovascular, Renal & Hepatic Impairment:The administration of an NSAID may cause a dose dependent reduction in prostaglandin formation & precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics or recovering from major surgery& the elderly.
Renal:Patients with mild-moderate renal impairment should be kept under surveillance, since the use of NSAIDs may result in deterioration of renal function.
Hepatic:If abnormal liver function tests persist or worsen, clinical signs or symptoms consistent with liver disease develop or if other manifestations occur (eosinophilia, rash), the medication should be discontinued. Close medical surveillance is necessary in patients suffering from mild to moderate impairment of hepatic function. Hepatitis may occur without prodromal symptoms. Use in patients with hepatic porphyria may trigger an attack.
Cardiovascular & cerebrovascular effects:Appropriate monitoring is required for patients with a history of hypertension &/or mild to moderate congestive heart failure as fluid retention & oedema have been reported in association with NSAID therapy. Patients with congestive heart failure (NYHA-I) & patients with significant risk factors for CV events (e.g. hypertension) should only be treated after careful consideration. Should also be administered with caution & under close medical surveillance to patients with a history of cerebrovascular bleeding.
Gastrointestinal bleeding, ulceration & perforation:GI bleeding, ulceration/perforation has been reported with all NSAIDs at any time during treatment, with/without warning symptoms or a previous history of serious GI events.
SLE & mixed connective tissue disease:May cause an increased risk of aseptic meningitis.
Dermatological:Serious skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome& toxic epidermal necrolysis, have been reported very rarely. Patients appear to be at highest risk for these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the 1st month of treatment. Treatment should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.
Hypersensitivity reactions:Allergic reactions, including anaphylactic/anaphylactoid reactions, can also occur.
Haematological:May reversibly inhibit platelet aggregation.
Long-term treatment:All patients who are receiving NSAIDs should be monitored as a precautionary measure e.g. renal, hepatic function (elevation of liver enzymes may occur) & blood counts.
Infection: May mask the signs & symptoms of infection due to their pharmacodynamic properties.

8. ADVERSE EFFECTS:
Gastrointestinal: Peptic ulcers, perforation or GI bleeding, particularly in the elderly, may occur. Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain.
Hypersensitivity: Hypersensitivity reactions have been reported following treatment with NSAIDs&may consist of:
1. Non-specific allergic reactions & anaphylaxis.
2. Respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea.
3. Assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angiodema.
Cardiovascular & cerebrovascular: Oedema, hypertension & cardiac failure have been reported.
Increased risk of general arterial thrombotic events (for example myocardial infarction or stroke , particularly at high doses or in long treatment).
Renal: Interstitial nephritis
Neurological & special senses:Optic neuritis, reports of aseptic meningitis (especially in patients with existing auto-immune disorders, such as systemic lupus erythematosus), with symptoms such as stiff neck, headache, nausea, vomiting etc.
Haematological: Agranulocytosis, aplastic anaemia
Dermatological: Bullous reactions including Stevens Johnson Syndrome & Toxic Epidermal Necrolysis, Photosensitivity.
If serious adverse reactions occur, treatment should be withdrawn.
9.DRUG INTERACTIONS:
Other analgesics including cyclooxygenase-2 selective inhibitors: Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects including GI bleeding.
Anti-hypertensives: May reduce the effect of antihypertensives. The risk of acute renal insufficiency which is usually reversible, may be increased in some patients with compromised renal function (e.g. dehydrated patients or elderly patients) when ACE- inhibitors or angiotensin II receptor antagonists are combined with NSAIDs.
Diuretics: May inhibit the activity of diuretics. Can increase the risk of nephrotoxicity of NSAIDs.
Cardiac glycosides like digoxin: May exacerbate cardiac failure, reduce GFR (glomerular filtration rate) & inhibit the renal clearance of glycosides, resulting in increased plasma glycoside levels.
Lithium: Can inhibit renal clearance of lithium, resulting in increased serum concentrations of lithium. The combination should be avoided unless frequent monitoring of lithium can be performed.
Methotrexate: Renal function should be monitored when used with methotrexate.
Mifepristone: Should not be used for 8-12 days after mifepristone administration as it can reduce the effect of mifepristone.
Corticosteroids: Increased risk of GI ulceration or bleeding.
Anti-coagulants:May enhance the effects of anti-coagulants, such as warfarin. Close monitoring of patients on combined anti-coagulants &diclofenac Tablets therapy should be undertaken.
Quinolone antibiotics: Can increase the risk of convulsions associated with quinolone antibiotics.
Anti-platelet agents & selective serotonin reuptake inhibitors (SSRIs): Increased risk of GI bleeding.
Ciclosporin, Tacrolimus: Administration together with ciclosporin/tacrolimus is thought to increase the risk of nephrotoxicity.
Zidovudine: Increased risk of haematological toxicity when given with zidovudine.
Antidiabetic agents: Isolated reports of hypoglycaemic & hyperglycaemic effects.
Cholestyramine:Absorption of paracetamol is reduced by cholestyramine. Cholestyramine should not be taken within 1 hr if maximal analgesia is required.
Metoclopramide & Domperidone:Absorption of paracetamol is increased by metoclopramide & domperidone. Concurrent use need not be avoided.
Chloramphenicol: Increases plasma concentration of chloramphenicol.
10.DOSAGE:
Adults:2-3 tablets daily.
Paediatric population: 1-2 tablets daily.
Elderly:The elderly, who are more likely to be suffering from impaired renal, CV or hepatic function & receiving concomitant medication, are at increased risk of adverse reactions. The patient should be monitored regularly for GI bleeding.
The pharmacokinetics are not altered in elderly patients; it is not necessary to modify the dose/dose frequency.
Renal insufficiency:No adjustment of the starting dose is required for renally impaired patients.

Hepatic insufficiency:No adjustment of the starting dose is required for hepatically impaired patients.

11. ADMINISTRATION:
Diclofenac + Paracetamol tablets are supplied for oral administration & should be swallowed whole with a sufficient quantity of liquid. Do not crush or chew the tablets. Never change the dose of your medicine without talking to your doctor first. Continue to take your tablets for as long as your doctor recommends.
12.PRESENTATION:
13.STORAGE:
Store below 25°C in a cool & dry pace. Protect from direct sunlight. Keep away from the reach of children.

14.MANUFACTURED BY:
15.MARKETED BY:

This leaflet was last revised on October 2020.