APR ACLOMEE ADVANCE -MR

INFORMATION FOR THE USER

Aceclofenac 100mg + Paracetamol 325mg + Serratiopeptidase 10mg 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.

COMPOSITION:
Each tablet contains:
Aceclofenac – 100mg
Paracetamol – 325mg
Serratioppeptidase – 10mg

For oral use only.

DESCRIPTION:
Aceclofenac is an analgesic, antipyretic and anti-inflammatory drug and belongs to a class of drugs called NSAID’s (Non-steroidal anti-inflammatory drug). Paracetamol is also an NSAID. Serratiopeptidase is a proteolytic enzyme that breaks down swelling and eases relief from pain and inflammation.
Together these drugs help to relieve inflammation, pain, swelling and related symptoms.

PHARMACOLOGICAL ACTION:
Aceclofenac is a non-steroidal agent with marked anti-inflammatory and analgesic properties. The mode of action of aceclofenac is largely based on the inhibition to prostaglandin synthesis. Aceclofenac is a potent inhibitor of the enzyme cyclo-oxygenase, which is involved in the production of prostaglandins.
Paracetamol acts predominantly by inhibiting prostaglandin synthesis in the central nervous system (CNS) and 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.
Serratiopeptidase binds to 2-macroglobulin. Levels are slowly transferred to the exudates at the site of infection and inflammation. The mechanism of action is hydrolysis of histamine, bradykinin and serotonin and a proteolytic and fibrinolytic effect. This is achieved by dissolving the complement and increasing the plasmin activity by inhibiting the plasmin inactivators. It reduces capillary permeability induced by histamine, bradykinin and serotonin; breaks down abnormal exudates and proteins; facilitates the absorption of decomposed products through blood and lymphatics thereby promoting wound healing and repair and restoring the skin temperature of the inflamed area, burn or trauma to normal.
CLINICAL PHARMACOKINETICS:
After oral administration, aceclofenac is rapidly and completely absorbed as unchanged drug. Peak plasma concentrations are reached approximately 1.25 to 3.00 hours following ingestion. It penetrates into the synovial fluid, where the concentrations reach approximately 57% of those in plasma. The volume of distribution is approximately 25 L. The mean plasma elimination half-life is around 4 hours. It is highly protein- bound (>99%). Aceclofenac circulates mainly as unchanged drug. 4′- hydroxyaceclofenac is the main metabolite detected in plasma. Approximately two-thirds of the administered dose is excreted via the urine, mainly as hydroxymetabolites. No changes in the pharmacokinetics of aceclofenac have been detected in the elderly.
Paracetamol is readily absorbed from the gastro-intestinal tract with peak plasma concentrations occurring about 30 minutes to 2 hours after ingestion. It is metabolised in the liver and excreted in the urine mainly as the glucuronide and sulphate conjugates. Less than 5% is excreted as unchanged paracetamol. The elimination half-life varies from about 1 to 4 hours. Plasma-protein binding is negligible at usual therapeutic concentrations but increases with increasing concentrations. A minor hydroxylated metabolite produced in very small amounts by mixed-function oxidases in the liver and which is usually detoxified by conjugation with liver glutathione may accumulate following paracetamol overdose and cause liver damage.
Serratiopeptidase has been shown to be absorbed from the digestive tract. On oral administration, it is absorbed unchanged into the systemic circulation, from where it penetrates into all the tissues. It reaches higher concentrations in the inflamed tissues. It attains peak levels in one hour.

INDICATIONS:
Aceclofenac + Paracetamol + Serratiopeptidase tablets are indicated for the relief of pain and inflammation in:
Resolution of inflammation due to bone and soft tissue injury.
Resolution of post-operative pain, inflammation and oedema.

CONTRAINDICATIONS:
Aceclofenac + Paracetamol tablets are contraindicated in the following cases:

Hypersensitivity to Aceclofenac/Paracetamol/Serratiopeptidase or to any of the excipients in the tablets.
Active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
Patients who have previously shown hypersensitivity reactions (eg. Asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin, or other non-steroidal anti-inflammatory drugs.
Hepatic failure and renal failure.
Patients with established congestive heart failure (NYHA II-IV), ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease.
History of gastrointestinal bleeding or perforation, related to previous NSAIDS therapy.
Active bleedings or bleeding disorders.
Note:
Aceclofenac should not be prescribed during pregnancy, especially during the last trimester of pregnancy, unless there are compelling reasons for doing so. In such cases the lowest effective dosage should be used.
Aceclofenac is not recommended for use in children.

WARNINGS AND PRECAUTIONS:
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms.
The use of Aceclofenac 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 and 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 and 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, and the elderly.
Renal: Patients with mild to 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 and cerebrovascular effects: Appropriate monitoring is required for patients with a history of hypertension and/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 with aceclofenac + paracetamol after careful consideration. Should also be administered with caution and under close medical surveillance to patients with a history of cerebrovascular bleeding.
Gastrointestinal bleeding, ulceration and 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 and mixed connective tissue disease: May cause an increased risk of aseptic meningitis.
Dermatological: Serious skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and 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 first 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: Aceclofenac + Paracetamol tablets 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) and blood counts.

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:
Non-specific allergic reactions & anaphylaxis.
Respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea.
Assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angiodema.
Cardiovascular and cerebrovascular: Oedema, hypertension and cardiac failure have been reported.
Aceclofenac is both structurally related and metabolised to diclofenac for which a greater amount of clinical trial and epidemiological data consistently point towards an increased risk of general arterial thrombotic events (for example myocardial infarction or stroke , particularly at high doses or in long treatment). Epidemiological data has also found an increased risk of acute coronary syndrome & myocardial infarction associated with the use of aceclofenac.
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 and Toxic Epidermal Necrolysis, Photosensitivity.
If serious adverse reactions occur, treatment should be withdrawn.
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: Aceclofenac may inhibit the activity of diuretics. Diuretics can increase the risk of nephrotoxicity of NSAIDs.
Cardiac glycosides like digoxin: May exacerbate cardiac failure, reduce GFR (glomerular filtration rate) and 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 and Aceclofenac Tablets therapy should be undertaken.
Quinolone antibiotics: Can increase the risk of convulsions associated with quinolone antibiotics.
Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal 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 and hyperglycaemic effects.
Cholestyramine: The speed of absorption of paracetamol is reduced by cholestyramine. Therefore, the cholestyramine should not be taken within one hour if maximal analgesia is required.
Metoclopramide and Domperidone: The absorption of paracetamol is increased by metoclopramide & domperidone. Concurrent use need not be avoided.
Chloramphenicol: Increases plasma concentration of chloramphenicol.
DOSAGE:
Adults: The recommended dose is 2 tablets daily; one tablet in the morning and one in the evening.
Paediatric population: There are no clinical data on the use in children; is not recommended for use in children.
Elderly: The elderly, who are more likely to be suffering from impaired renal, CV or hepatic function and 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: There is no evidence that the dosage of needs to be modified in patients with mild renal impairment.
Hepatic insufficiency: should be reduced in patients with hepatic impairment.
ADMINISTRATION:
Aceclofenac + Paracetamol + Serratiopeptidase tablets are supplied for oral administration and 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.
PRESENTATION:
STORAGE:
Store below 25°C in a cool and dry pace. Protect from direct sunlight. Keep away from the reach of children.

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This leaflet was last revised on May 2019.