Prescription only medicine
Each Tablet contains: Meloxicam …… 7.5mg
Excipients. Microcrystalline Cellulose, Pregelatinised Maize Starch, Lactose Monohydrate, Maize Starch, Sodium Citrate, Colloidal Anhydrous Silica, Magnesium Stearate
Please read carefully this leaflet before you start taking the medicine.
– Keep this leaflet in a safe place. You may need to read it again.
If you have any questions ask your doctor or your pharmacist.
– This medicine was prescribed for you personally and you should not pass it on to others. It can be harmful, even when their symptoms are the same as yours.
WHAT IS Melorich AND WHAT ARE ITS USES
Melorich is a non-steroidal anti-inflammatory drug of the Oxicam family, with anti-inflammatory, analgesic and antipyretic properties.
Melorich is indicated for the short-term symptomatic treatment of exacerbations of osteoarthrosis and the long term symptomatic treatment of rheumatoid arthritis and ankylosing spondylitis
3. DOSAGE AND ADMINISTRATION
Follow your doctor’s instructions.
Exacerbations of osteoarthrosis: 7.5 mg/day.
If necessary, (in the absence of improvement), the dose may be increased to 15 mg/day.
Rheumatoid arthritis, ankylosing spondylitis: 15 mg/day.
According to the therapeutic response, the dose may be reduced to 7.5 mg/day.
DO NOT EXCEED THE DOSE OF 15 mg/day.
The total daily amount should be taken as a single dose, with water or another liquid, during a meal.
As the risks of Melorich may increase with dose and duration of administration, the shortest duration possible and the lowest effective daily dose should be used. The patient’s need for symptomatic relief and response to therapy should be re-evaluated periodically, especially in patients with osteoarthritis.
The recommended dose for long term treatment of rheumatoid arthritis and ankylosing spondylitis in elderly patients is 7.5 mg per day
In dialysis patients with severe renal failure, the dose should not exceed 7.5 mg per day.
No dose reduction is required in patients with mild to moderate renal impairment (i.e. patients with a creatine clearance of greater than 25 ml/min).
Hepatic impairment: No dose reduction is required in patients with mild to moderate hepatic impairment
Children:Melorich should not be used in children aged under 15 years.
What you should know if you forget to take a dose:
If you have to take the medicine continuously and you miss taking a dose, take the missed dose as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses. Consult your doctor in case you missed more than one dose.
This medicinal product is contra-indicated in the following situations:
Pregnancy and lactation;
Hypersensitivity to meloxicam or to one of the excipients or hypersensitivity to substances with a similar action, e.g. NSAIDs, aspirin. Melorich should not be given to patients who have developed signs of asthma, nasal polyps, angioneurotic edema or urticaria following the administration of aspirin or other NSAIDs;
History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy;
Active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding);
Severely impaired liver function;
Non-dialysed severe renal failure;
Gastrointestinal bleeding, cerebrovascular bleeding or other bleeding disorders;
Severe heart failure.
5. WARNINGS & PRECAUTIONS:
The use of meloxicam with concomitant NSAIDs including cyclooxygenase-2-selective inhibitors should be avoided.
Undesirable effects may be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.
The recommended maximum daily dose should not be exceeded in case of insufficient therapeutic effect, nor should an additional NSAID be added to the therapy because this may increase the toxicity while therapeutic advantage has not been proven. The use of Melorich with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided.
In the absence of improvement after several days, the clinical benefit of the treatment should be reassessed.
Any history of esophagitis, gastritis and/or peptic ulcer must be sought in order to ensure their total cure before starting treatment with meloxicam. Attention should routinely be paid to the possible onset of a recurrence in patients treated with meloxicam and with a past history of this type.
Elderly: the elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.
Gl bleeding, ulceration or perforation, which can be fatal, have been reported with all NSAIDs at anytime during treatment, with or without warning symptoms or a previous history of serious Gl events.
The risk of Gl bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation 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.
Patients with a history of Gl toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially Gl bleeding) particularly in the initial stages of treatment. Caution should be advised in patients receiving concomitant medications which could 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.
When Gl bleeding or ulceration occurs in patients receiving Melorich, the treatment should be withdrawn.
NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn’s disease) as this condition may exacerbate.
Cardiovascular and cerebrovascular effects:
Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAIDs therapy.
Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infraction or stoke). There are insufficient data to exclude such a risk of meloxicam.
Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with meloxicam after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cerebrovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs. Patients appear to be at highest risk of 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. Melorich should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
As with most NSAIDs, occasional increases in serum transaminase levels, increases in serum bilirubin or other liver function parameters, as well as increases in serum creatinine and blood urea nitrogen as well as other laboratory disturbances, have been reported. The majority of these instances involved transitory and slight abnormalities. Should any such abnormality prove significant or persistent, the administration of Melorich should be stopped and appropriate investigations undertaken.
Functional renal failure:
NSAIDs, by inhibiting the vasodilating effect of renal prostaglandins, may induce a functional renal failure by reduction of glomerular filtration. This adverse event is dose-dependent. At the beginning of the treatment, or after dose increase, careful monitoring of diuresis and renal function is recommended in patients with the following risk factors:
Concomitant treatments such as ACE inhibitors, angiotensin-II antagonists, sartans, diuretics
Hypovolemia (whatever the cause)
Congestive heart failure
Severe hepatic dysfunction (serum albumin <25 g/l or Child-Pugh score ³ 10).
In rare instances may be the cause of interstitial nephritis, glomerulonephritis, renal medullary necrosis or nephrotic syndrome.
Sodium and water retention:
Sodium and water retention with possibility of oedema, hypertension or hypertension aggravation, cardiac failure aggravation. Clinical monitoring is necessary, as soon as starting therapy in case of hypertension or cardiac failure. A decrease of the antihypertensive effect can occur.
Induction of sodium, potassium and water retention and interference with the natriuretic effects of diuretics and consequently possible exacerbations of the condition of patients with cardiac failure or hypertension may occur with NSAIDs.
Hyperkalaemia can be favoured by diabetes or concomitant treatment known to increase kalaemia. Regular monitoring of potassium values should be performed in such cases.
Adverse reactions are often less well tolerated in elderly, fragile or weakened individuals, who therefore require careful monitoring. As with other NSAIDs, particular caution is required in the elderly, in whom renal, hepatic and cardiac functions are frequently impaired. The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.
Meloxicam, as any other NSAID may mask symptoms of an underlying infectious disease.
The use of meloxicam, as with any drug known to inhibit cyclooxygenase / prostaglandin synthesis, may impair fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving, or who are undergoing investigation of fertility, withdrawal of meloxicam should be considered.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
6. PREGNACY AND LACTATION:
Melorich should not be administered during the first and second trimester of pregnancy unless it is absolutely necessary, whilst it is totally contra-indicated during the third trimester.
Consult your doctor or pharmacist before taking any medicine.
Melorich is excreted into human milk and it should not be taken during lactation.
Consult your doctor or pharmacist before taking any medicine.
7. EFFECTS ON ABILITY TO DRIVE OR OPERATE MACHINERY:
Melorich has no or negligible influence on the ability to drive or operate machinery. However, in case of visual disturbances or drowsiness, vertigo or other disorders of the central nervous system it is advisable to refrain from driving and operating machinery.
8. UNDESIRABLE EFFECTS
As with all medicines Melorich may cause undesirable effects.
Medicines like Melorich may be associated with a small increased risk of heart attack (myocardial infraction) or stroke.
The following side effects have also been reported:
Very common (³ 1/10); common (³1/100, <1/10); uncommon (³ 1/1000, <1/100); rare (³ 1/10000, <1/1000); very rare (<1/10000).
Blood and the lymphatic system disorders
Uncommon: Disturbances of blood count: leucocytopenia; thrombocytopenia; agranulocytosis (see section c)
Immune system disorders
Rare: Anaphylactic / anaphylactoid reactions
Rare: Mood disorders, insomnia and nightmares.
Nervous system disorders
Common: Light-headedness, headache
Uncommon: Vertigo, tinnitus, drowsiness
Rare: Visual disturbances including blurred vision
Uncommon: Increases in blood pressure, flushes
Respiratory, thoracic and mediastinal disorders
Rare: Onset of asthma attacks in certain individuals allergic to aspirin or other NSAIDs
Common: Dyspepsia, nausea and vomiting symptoms, abdominal pain, constipation, flatulence, diarrhea
Uncommon: Gastrointestinal bleeding gastroduodenal ulcers, esophagitis, stomatitis
Rare: Gastrointestinal perforation, gastritis, colitis
The peptic ulcers, perforation or gastrointestinal bleeding, that may occur can be sometimes severe, especially in elderly.
Skin and subcutaneous tissue disorders
Common: Pruritus, rash
Rare: Stevens – Johnson Syndrome and toxic epidermal necrolysis, angioedema, bullous reactions such as erythema multiform, photosensitivity reactions.
Renal and urinary disorders
Uncommon: Sodium and water retention, hyperkalaemia.
Rare: Acute functional renal failure in patients with risk factors.
General disorders and administration site conditions
Common: Edema including edema of the lower limbs.
Uncommon: Transitory disturbance of the liver function test (e.g. raised transaminases or bilirubin)
Uncommon: Disturbances of laboratory tests investigating renal function (e.g. raised creatinine or urea)
isolated cases of agranulocytosis have been reported in patients treated with meloxicam and other potentially myelotoxic drugs.
Adverse reactions which have not been observed yet in relation to the product, but which are generally accepted as being attributable to other compounds in the class
organic renal injury probably resulting in acute renal failure: isolated cases of intersticial nephritis, acute tubular necrosis, nephrotic syndrome, and papillary necrosis have been reported.
9. DRUG INTERACTIONS:
A number of medicines interact with Melorich and should not be used concomitantly. However, a few of them can be used concomitantly under special precautions. In this case, your doctor can change the posology or take other precautions if needed.
If you are about to take Melorich it is important to inform your doctor or pharmacist about any other medications you are taking such as: Corticosteroids, anti-coagulants (warfarin), anti-platelet agents (aspirin) and selective serotonin reuptake inhibitors, other NSAID’s (including acetylsalicylic acid), oral anticoagulants, thrombolytics and anti platelet drugs, diuretics, ACE inhibitors and angiotensin-II antagonists, other antihypertensive drugs (Beta-blockers), cyclosporines, intrauterine devices, lithium, methotrexate, cholestyramine.
10. PHARMACOLOGICAL PROPERTIES
10.1. Pharmacodynamic Properties
Pharmacotherapeutic group: Non Steroidal, Anti-Inflammatory agent, Oxicams.
ATC Code: M01AC06
Melorich is a non-steroidal anti-inflammatory drug (NSAID) of the oxicam family, with anti-inflammatory, analgesic and antipyretic properties.
The anti-inflammatory activity of meloxicam has been proven in classical models of inflammation. As with other NSAIDs, its precise mechanism of action remains unknown. However, there is at least one common mode of action shared by all NSAIDs (including meloxicam): inhibition of the biosynthesis of prostaglandins, known inflammation mediators.
10.2. Pharmacokinetic Properties
Meloxicam is well absorbed from the gastrointestinal tract, which is reflected by a high absolute bioavailability of 89% following oral administration (capsule). Tablets, oral suspension and capsules were shown to be bioequivalent.
Following single dose administration of meloxicam, mean maximum plasma concentrations are achieved within 2 hours for the suspension and within 5-6 hours with solid oral dosage forms (capsules and tablets).
With multiple dosing, steady state conditions were reached within 3 to 5 days. Once daily dosing leads to drug plasma concentrations with a relatively small peak-trough fluctuation in the range of 0.4-1.0 mg/ml for 7.5 mg doses and 0.8-2.0 mg/ml for 15 mg doses, respectively (Cmin and Cmax at steady state, respectively). Maximum plasma concentrations of meloxicam at steady state are achieved within five to six hours for the tablet, capsule and the oral suspension, respectively. Continuous treatment for periods of more than one year results in similar drug concentrations to those seen once steady state is first achieved. Extent of absorption for meloxicam following oral administration is not altered by concomitant food intake.
Meloxicam is very strongly bound to plasma proteins, essentially albumin (99%). Meloxicam penetrates into synovial fluid to give concentrations approximately half of those in plasma. Volume of distribution is low, on average 11%. Interindividual variation is the order of 30-40%.
Meloxicam undergoes extensive hepatic bio transformation. Four different metabolites of meloxicam were identified in urine, which are all pharmacodynamically inactive. The major metabolite, 5’-carboxymeloxicam (60% of dose), is formed by oxidation of an intermediate metabolite 5’hydroxymethylmeloxicam, which is also excreted to a lesser extent (9% of dose). In vitro studies that CYP 2C9 plays an important role in this metabolic pathway, with a minor contribution from the CYP 3A4 isoenzyme. The patient’s peroxidase activity is probably responsible for the other two metabolites, which account for 16% and 4% of the administered dose respectively.
Meloxicam is excreted predominantly in the form of metabolites and occurs to equal extents in urine and faeces. Less than 5% of the daily dose is excreted unchanged in faeces, while only traces of the parent compound are excreted in urine.
The mean elimination half-life is about 20 hours. Total plasma clearance amounts on average 8 ml/min.
Meloxicam demonstrates linear pharmacokinetics in the therapeutic dose range of 7.5 mg and 15 mg following per oral or intramuscular administration.
Neither hepatic, mild nor moderate renal insufficiency have a substantial effect on meloxicam pharmacokinetics. In terminal renal failure, the increase in the volume of distribution may result in higher
free meloxicam concentrations, and a daily dose of 7.5 mg must not be exceeded (see section 4.2).
Mean plasma clearance at steady state in elderly subjects was slightly lower than that reported for younger subjects.
10.3. Preclinical Safety Data
The toxicological profile of meloxicam has been found in preclinical studies to be identical to that of NSAIDs: gastrointestinal ulcers and erosions, renal papillary necrosis at high doses during chronic administration in two animal species.
Oral reproductive studies with meloxicam in the rat have shown a decrease of ovulations and inhibition of implantations and embryotoxic effects (increase of resorptions) at maternotoxic dose levels at 1mg/kg and higher. Studies of toxicity on reproduction in rats and rabbits did not reveal teratogenicity up to oral doses of 4 mg /kg in rats and 80 mg/kg in rabbits.
The affected dose levels exceeded the clinical dose (7.5 – 15 mg) by a factor of 10 to 5-fold on a mg/kg dose basis (75 kg person). Fetotoxic effects at the end of gestation, shared by all prostaglandin synthesis inhibitors, have been described. No evidence has been found of any mutagenic effect, either in vitro or in vivo. No carcinogenic risk has been found in the rat and mouse at doses far higher than those used clinically.
Symptoms following acute NSAID overdose are usually limited to lethargy, drowsiness, nausea, vomiting and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur. Severe poisoning may result in hypertension, acute renal failure, hepatic dysfunction, respiratory depression, coma, convulsions, cardiovascular collapse and cardiac arrest. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs and may occur following an overdose.
Patients should be managed with symptomatic and supportive care following an NSAID overdose. Accelerated removal of meloxicam by 4 g oral doses of cholestyramine given three times a day was demonstrated in a clinical trial.
12. SHELF LIFE: 36 months from the date of manufacture.
13. STORAGE: Keep below 25° C, away from light and moisture .
14. SPECIFICATION: BP Current Edition
Name and Address of Manufacturer
Limassol Industrial Estate, Limassol, Cyprus, EU
Name and Address of Registrationer
Nhat Anh Pharmaceutical Co., Ltd.
122/7-9 Dang Van Ngu, ward 14, Phu Nhuan district, HCM city.
Please read carefully before use.
Further more information please ask your doctor or pharmacist