Diclofenac Potassium 50 mg
1. NAME OF THE MEDICINAL PRODUCT :
dimra Tablets (Diclofenac Potassium 50 mg & Methocarbamol 500
2. QUALITATIVE AND QUANTITATIVE COMPOSITION :
Each film-coated tablet oontains 50 mg of diclofenac potassium & 500 mg methocarbamol This medicine contains potassium per tablet. For a full list of exdplents, see section 6.1
3. PHARMACEUTICAL FORM :
Film-coated tablets, white, capsule-shaped tablet
4. CLINICAL PARTICULARS :
4.1 Therapeutic Indications
DIMRA is A combination of Oiclofenac potassium 50mg & Methocarbamol 500mg. Then DIMRA combines the action of both diclofenac Potassium, and methocarbamol for treatment of :
To relieve pain in Musculo-skeletal conditions associated with muscle spasm and trauma such as:
– Tense neck muscles
4.2 Posology and method of administration
– Unless otherwise prescribed by the physician 1 to 3 tablets daily, in
divideO doses to be taken after meals.
– For oral administration.
– To be taken preferably with or after food.
– The tablets should be swallowed whole with liquid.
– Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4). Always take Dlclofenac potalllum exactly as your doctor has told you:
The recommended daily dose Is 100 – 150 mg in two or three divided doses. For milder cases, 75 -100 mg daily In two or three divided doses is usually sufficient. If needed, further doses of 50 mg may be taken at intervals of 4 – 6 hours, not exceeding a total dose of 200 mg per day.
For children of 12 years and over, the recommended daily dose Is 75 -100 mg In two or three divided doses: OIMRA contains (Oiclofenac Potassium 50 mg) should not be Indicated for use In children under 12 years of age.
The elderly are at increased risk of tile serious consequences of adverse reactions. If an NSAIO Is considered necessary, the lowest effective dose should be used and for the shortest possible duration. The patient should be monitored regularly for GI bleeding during NSAID therapy. Always take Methocarqamol.soO exactly as your doctor has told you:
Adults: The usual dose Is 2 tablets four times dally but therapeutic
response has been achieved with doses as low as 1 tablet three times
Elderly: Half the maximum dose or less may be sufficient to produce a therapeutic response.
Children: Not recommended.
Hepatlcally Impaired: In patients with chronic hepatic disease the
elimination half-life may be prolonged. Therefore, consideration should be given to increasing the dose level.
• Hypersensi!lvity to diclofenac methocarbamol or any of the exciplents. Due to presence of Dlclofenac potassium
• Active, or history of recurrent peptic ulcer I haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
• NSAIDs are contraindicated In patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema, or urticaria) in response to Ibuprofen, aspirin, or other non-steroldal antl-inflammatory drugs.
• Severe heart failure, hepatic failure and renal failure (see section 4.4).
• History of gastro-Intestinal bleeding or perforation, relating to previous NSAIO therapy.
• This product contains soya If you are allergic to peanut or soya do not use this medicinal product.
4.4 Special Warning
Gastrointestinal (GI) effects risk of GL ulceration, bleeding, and
perforation: NSA1DS cause en Increased risk of serious gastrointestinal adverse events Including Inflammation, bleeding, ulceration ,and perforation of the stomach or Intestine which can be fatal. these events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gsstrointestlnal event.
Undesirable effects may be minimised by using the lowest e’ectlve dose for the shortest duration necessary to control symptoms (see section 4.2, and GI and cardiovascular risks below).
The use of Diclofenac potassium with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided (see section 4.5).
Elderly: The elderiy have increased frequency of adverse reactions to NSAlOs especially gastro intestinal bleeding and perforation which may be fatal (see section 4.2).
– Close medical surveillance is imperative in patients with symptoms Indicative of gastrointestlnat disorders, with a history suggestive of gastric or intestinal ulceration, with ulcerative colitis, or with Crohn’s disease as these conditions may be exacerbated (see section 4.8 Undesirable affects).
– Patients with a history of GI toxicity, particulariy when elderly, should report any unusual abdominal symptoms (especially GI bleeding). Gastrolntestinal bleeding, ulceration and perforation:
– GI bleeding, ulceration or perforation, which can be fatal, has been
reported with all NSAIOs at any time during treatment, with or without warning symptoms or a previous history of serious GI events.
– The risk of GI bleeding, ulceration or perforatlon Is higher with increasing NSAID doses, in patients with a history of ulcer, particularly If complicated with haemorrhage or perforation (see section 4.3), and In the elderly.
– These patients should commence treatment on the lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton pump Inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin, or other drugs likely to Increase gastrointestinal risk (see below and sectfon 4.5).
– Patients with ‘a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.
– Caution should be advised in patients receiving concomitant medications which increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective
serotonin-reuptake inhibitors or anti-platelet agents such as aspirin (see section 4.5).
– When GI bleeding or ulceration occurs in patients receiving diclofenac potassium, the treatment should be withdrawn.
– NSAlOs should be given with care to patients with a history of
gastrointestinal disease (ulcerative colitis. Crohn’s disease) as these
conditions may be exacerbated (see section 4.8).
– Hepatic Close medical surveillance is imperative in patients suffering from severe impainnent of hepatic function.
– As with other non-steroidsl anti-inflammatory drugs, allergic reactions, including anaphylacticJanaphytactotd reactions, can occur without earlier exposure to the drug (see section 4.8).
– Like other NSAlOs. Oidofenac Potassium tablets may mask the signs and symptoms of infection due to their pharmacodynamic properties.
– SLE and mixed connective tissue disease: In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis (see section 4.8 I.
Cardiovascular affect. NSAIOs may cause an increased risk of serious cardiovascular (CV) thrombotic events, myocardial Infarction. and stroke, which can be fatal. This risk may Increase with duration of use. Patients with cardiovascular disease or risk of factors for cardiovascular disease may be at greater risk. NSAIDs is contraindicated for the treatment of pre-operatiye pain In the setting of conmaryart&ly bypass graft (CABG) surgery
Gastrolntestinal (GI) effects-risk of GI ulceration, bleeding, and
perforation: NSAIDs cause an Increased risk of serious gastrointestinal adverse events including innammation. bleeding. ulceration ,and perforation of the stomach or Intestine which can be fatal. these events can occur at any time during use and without wamlng symptoms. Elderiy patients are at greater risk for serious gastrolntestlnal event.
Cardiovascular, Renal and Hepatic Impairment:
The administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with Impaired renal functlcn. cardiac Impairment. liver dysfunction, those taking diuretics and the elderiy. Renal function should be monitored In these patients (see also section 4.3).
– If abnormal liver function tests persist or worsen, clinical signs or
symptoms consistent with liver disease develop or If other manifestations occur (eosinophllla. rash), Olclofenac Potassium tablets should be discontinued, HepaUtls may occur without prodromal symptoms.
– Use of Oiclofenac Potassium tablets In patients with hepatic porphyria may trigger an attack. Haematologlcal DlcIofenac Potassium tablets may reversibly inhibit platelet aggregation (see section 4.5 -Interactions-). Patients with defects of haemostasis, bleeding diathesis or haematological abnormalities should
be carefully monitored.
– Long term treatment All patients who are receiving long term treatment with non-steroidal anti-inflammatory agents should be monitored as a precautionary measure eg renal function, hepatic function (elevation of liver enzymes may occur) and flood counts. Thi$ Is partlcularty important In the elderly.
– 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 precfpftate bronchospasm in such patients.
Cardiovascular and cerebrovascular effect.:
– Appropriate monitoring and advice are required for patients with 8 history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been~ In association with NSAID therapy.
– Clinical trial and epidemiological data suggest that use of diclofenac, particularly at high dosa (150mg daily) and In long term treatment may be associated with a small increased risk of art.eriai thrombotic events (for example myocardial Infarction or stroke).
– Patients with uncontrolled hypertension, congestlve heart failure,
4.5 Interaction with other medicinal products and other forms of Interaction
Due to presence of Diclofenac potassium :
Other analgesics Including cyclooxygenas -2 selective lnhibitors :
Avoid concomitant use of two or more NSAlDs (Including aspiriri as this may increase the risk of adverse effects (see section 4.4).
Ante-hypertensives: Reduced anti-hypertensive effect.
Diuretics: Reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of NSA1Ds.
Cardiac glycoaldes: NSAlOs may exacerbate cardiac failure, reduce GFR and increase plasma gtycoside levels.
Lithium: Decreased elimination of lithium
Methotrexate: Decreased elimination of methotrexate.
Corticosteroids: Increased risk of nephrotoxicfty.
Mifepristone: NSAJOs should not be used for 8-12 days after mifepristone administration as NSAID sican reduce the effect of mifepristone
Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding (see section 4.4).
Anti-coagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (see section 4.4).
Quinolone antibiotics: Animal data indicate that NSAlDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAlDs and quinokmes may have an increased risk of developing convulsions.
Anti platelet agents and selective serotonin reuptake Inhibitors (SSRls): Increased risk of gastrointpstinal bleeding (see section 4.4).
Tacrolimus: Possible increased n,k of nephrotoxkity when NSAlDs are given with tacrolimus.
Zidovudine: 1nct88sed risk of haematotogk:af toxicity when NSAlDs are given with zidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV(+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.
Anti diabetic agents: Clinical studies have shown that DicIofenac
Potassium in the tablets can be given together with oral antidiabetic agents without Influencing their clinical effect. However there have been Isolated reports of hypoglycaemic and hyperglycaemic effects which have required adjustment to the dosage of hypoglycaemic agents. Methocarbamol :may potentiate the effects of other central nervous system depressants and stimulants including alcohol, barbiturates. anaesthetics and appetite suppressants. The effects of anticholinergics, e.g. atropine and some psychotropk:: drugs may be potentiated by methocarbamol. Methocarbamol may inhibit the effect of pyridostigmine bromide. Therefore methocarbamol should be used with caution in patients with myasthenia gravis receMng anticholinesterase agents. Little is known about the possibility of Interactions wfth other drugs. Methocarbamol may cause colour interference In certain screening tests for 5-hydroxylndolacetlc ackf (S-HIM) u!lng nltrosoaphthol reaqent and In screening tests for urinary vanitlymandeiic acid (VMA) using the Gitlow method.
4.6. Pregnancy and lactation
Due to presence of diclofenac potassium;
Congenital abnormalities have been reported in association with NSAIO administration in man; however. these are low in frequency and do not appear to follow any discernltu8 pattern. In view of the known effects of NSAIDs on the foetal cardiovascular system (risk of closure of the ductus arteriosus), use In the last trimester of pregnancy is contraindicated. The onset of labour may be delayed and the duration increased with an increased bleeding tendoncy in both mother and child (see sectJon 4.3). NSAIDs shoufd not be used during the first two trimesters of pregnancy or labour unless the potential benefit to the patient outweighs the potential risk to foetus.
In limited studies so far available, NSAIDs can appear In breast milk In very low concentrations. NSAlDs should, If possible, be avoided when breastfeedlng. See section 4.4 Special warnings and precautions for use, regarding female fertilit Due to presence of Methocarbamol;
Animal reproductive studies have not been conducted with
methocarbamol. It Is also not known whether methocarbamol can cause foetal harm when administered to a pregnant woman or can affect reproduction capacity. Safe use of methocarbamol has not been established with regard to possible adverse effects upon foetal development. There have been very rare reports of foetal and congenital abnormalities following In utero exposure to methocarbamol. Therefore methocarbamol tablets should not be used In women who are or may become pregnant and partlcular1y
during eariy pregnancy unless In the judgement of the physician the
potential benefits outweigh the possible hazards.
Lactation: Methocarbampl and/or its metabolites are excreted in the milk of dogs: however, it Is not known whether methocarbamoJ or its
metabolites are excreted in human milk. Because many drugs are
excreted in human milk, caution should be exercised when
Methocarbamol-SOO Is administered to a nursing woman.
4.7 Effects on ability to drive and u.e machines
– Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.
– This product may cause drowsiness and patients receiving it should not drive nor operate machinery unless their physical and mental capabilities remain unaffected – especially If other medication capable of causing drowsiness Is also being taken.
4.8 Undesirable effects :
– If serious sida-effects occur, Olclotenac Pota •• lum should be
– Clinical Trial and epidemiological data suggest that use of dldofenac, particulariy at high doses (150 mg dally) and in long term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial Infarction or stroke) (see section 4.4)
Due to presence of Diclofenac potassium;
a) Symptom. Symptoms include headache, nausea, vomiting, epigastricpain. gastrolntestinal bleeding, rarely diarrhoea, disorientation, excitation, coma, droWSiness, tinnitus, fainting, occasionally convulsions. In rare cases of significant poisoning acute renal failure and liver damage are possible.
b) Therapeutic measure
– Patients should be treated symptomatically as required.
– Within one hour of ingestion of a potentially toxic amount, activated charcoal should be considered. Alternatively, in adults. gastric lavage should be considered within one hour of ingestion of a potentially life-threatening overdose. – Good urine output should be ensured.
– Renal and liver function should be closely monitored.
– Patients should be observed for at least four hours after Ingestion of potentially toxic amounts.
– Frequent or prolonged convulsions should be treated with intravenous diazepam.
– Other measures may be Indicated by the patient’s clinical condition.
Due to presence of Methocarbamol;
– Limited information Is available on the acute toxicity of methocarbamol. Overdose of methocarbamolls frequently In conjunction with alcohol or other eNS depressants and Includes the following symptoms: nausea, drowsiness, blurred vision. hypotension, seizures and coma. One adult survived the deliberate Ingestion of 22 to 30 grams of methocarbamol without serious toxicity. Another adult survived a dose of 30 to 50 grams.
The principal symptom In both cases was extreme drowsiness. Treatment
– Management of overdose Includes symptomatic and supportive
treatment. Supportive measures Include maintenance of an adequate airway, monitoring urinary output and vital signs, and administration of intravenous fluids If necessary. The usefulness of haemodialysis in managing overdose Is unknown. 11-
5. PHARMACOLOGICAL PROPERTIES :
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Non-steroidal anti-inflammatory drug
(NSAID). dIMRA tablets contain the potassium salt of diclofenac, a ncn-steroldat compound with pronounced and clinically demonstrable analgesic, anti-inflammatory and anti-pyretic properties. Diclofenac Is a potent inhibitor of prostaglandin biosynthesis and a modulator of arachidonic acid release and uptake. Diclofenac Potassium have a rapid onset of action and are therefore suitable for the treatment of acute episodes of pain and inflammation. Diclofenac In vitro does not suppress proteoglycan biosynthesis in cartilage at concentrations equivalent to the concentrations reached In human beings.
Methocarbamol 500 is used as a short-term adjunct to the symptomatic treatment of acute musculoskeletal disorders associated with painful muscle spasms.
The mechanism of action of methocarbamol in humans has not been established, but may be due to general central nervous system
depression it has no direct action on the contracile mechanism of striatad muscle, the motor end plate or the nerve fibre.
5.2 Pharmacokinetic properties
Absotptlon Oiclofenac is rapidly and completely absorbed from
sugar-coated tablets. Food intake does not affect absorption.
Peak plasma concentration after one 50 mg sugar-coated tablet was 3.9 umoI/l after 20-00 minutes. The plasma concentrations show a linear relationship to the size of the dose.
diclofenac undergoes first-pass metabolism and is extensively
Distribution : diclofenac is highly bound to plasma proteins (99.7%), chiefly albumin (99.4%)
Elimination: The total systemic clearance of diclofenac in plasma is 263 t 56 mUmin (mean ± SO).
The terminal half-life in plasma is 1 – 2 hours.
Repeated oral administration of Oiclofenac Potassium tablets for 8 days in daily doses of 50 mg t.d.s does not lead to accumulation of diclofenac in the plasma. Approx. 60% of the dose administered is excreted in the urine In the form of metaboiftes, and less than 1% as unchanged substance. The remainder of the dose is eliminated as metabolites through the bile in the faeces.
Biotransformation : The biotransformation of diclofenac involves partly glucuronidatlon of the intact molecule but mainly single and multiple hydroxylation followed by glucuronidation.
Character/stlcs /n patients The age of the patient has no influence on the absorption, metabolism, or excretion of diclofenac. In patients suffering from renal impairment, no accumulation of the
unchanged active substance can be inferred from the single-dose kinetics when applying the usual dosage schedule. At a creatinine clearance of <10 mllmln the theoretical steady-state plasma levels of metabolites are about four times higher than in normal subjects. However, the metabolites are ultimately cleared through the bile.
In the presence of impaired hepatJc function (chronic hepatitJs,
non-decompensated cirrhosis) the kinetics and metabolism are the same as for patients without Uver disease.
Methocarbamol : is absorbed from the gastro-intestinal tract and produces peak plasma concentrations after about 1′-3 hours. Its activity derives from the Intact molecule and only a small proportion is converted to guaiphenesin.
Renally Impaired : The clearance of methocarbamol in renally-impaired patients on maintenance haemodialysis was reduced about 40% compared to a normal population. although the mean elimination half-life in these two groups was similar (1.2 versus 1.1 hours, respectively).
Hepatically Impaired : In patients with cirrhosis secondary to alcohol abuse, the mean total clearance of methocarbamol was reduced approximately 70% compared to a normal population (11.9 Uhr), and the mean elimination half-life was extended to approximately 3.4 hours. The fraction of methocarbamol bound to plasma proteins was decreased to approximately 40 to 45% compared to 46 to 50% in an age- and weight-matched normal population.
5.3 Preclinical safety data
Relevant information on the preclinical safety of Dlclofenac Potassium Tablets is included in previous sections of this Summary of Product Characteristics. Methocarbamol Nothing of note to the prescriber.
6. PHARMACEUTICAL PARTICULARS :
6.1 list of excipients
The active substance: the ingredient that makes the tablet is Diclofenac and Methocarbamol. Each tablet contains 50 mg Oiclofenac potassium, 500 mg Methocarbamol
The Inactive substance: Core: The tablets also contain Maize starch, Sodium lauryl sulphate, Croscarmellose Sodium. povidone K 30 , Magnesium stearate. Coat: Eudragit (EPO), Sodium lauryl
sulphate,Triethyl citrate, talc, Titanium dioxide.
6.2 Special precautions for storage
No special storage precautions
6.3 Nature and contents of container
The tablets are Oblong scored, biconvex film coated tablets.
Pack sizes Blister packs: carton box 2 Alum I PVC srtips each containing 10 film- coated tablets. And insert leaflet
6.6 Special precautions for disposal and other handling
7. Manufactured by :
October pharma S.A.E – Egypt