Active ingredients: Meloxicam
MOBIC 7.5 mg tablets
Mobic package inserts are available for pack sizes:- MOBIC 7.5 mg tablets
- MOBIC 15 mg tablets
- MOBIC 15 mg / 1.5 ml solution for injection
- MOBIC 7.5 mg suppositories
- MOBIC 15 mg suppositories
Indications Why is Mobic used? What is it for?
MOBIC contains the active substance meloxicam. Meloxicam belongs to a group of medicines called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) used to reduce inflammation and pain in the joints and muscles.
MOBIC is indicated for:
- the short-term treatment of exacerbations of osteoarthritis
long-term treatment of
- rheumatoid arthritis
- ankylosing spondylitis (also known as Bechterew's disease).
Contraindications When Mobic should not be used
Do not take MOBIC in the following cases:
- during the last three months of pregnancy
- children and adolescents under the age of 16
- allergy (hypersensitivity) to meloxicam
- allergy (hypersensitivity) to aspirin or other anti-inflammatory medicines (NSAIDs)
- allergy (hypersensitivity) to any of the other ingredients of this medicine)
if you have had any of the following signs after taking aspirin or other NSAIDs:
- wheezing, chest tightness, shortness of breath (asthma)
- nasal obstruction due to swelling of the nasal mucosa (nasal polyps)
- rash / hives
- sudden swelling of the skin or mucous membrane, such as swelling around the eyes, face, lips, mouth or throat which can make breathing difficult (angioneurotic edema)
after previous NSAID therapy and history of
- bleeding in the stomach or intestines
- perforations in the stomach or intestines
- ulcer or bleeding in the stomach or intestines
- recent history of peptic ulcer or stomach bleeding (ulceration or bleeding that has occurred at least twice)
- severe liver disease
- severe kidney disease not treated with dialysis
- recent brain bleeding (cerebrovascular bleeding)
- any bleeding disorders
- severe heart disease
- intolerance to some sugars as this medicine contains lactose (see also "MOBIC contains milk sugar (lactose)")
If you think any of the above events apply to you, contact your doctor.
Precautions for use What you need to know before taking Mobic
Warnings
Medicines such as MOBIC may be associated with a modest increased risk of heart attack (myocardial infarction) or stroke (apoplexy). Any risk is more likely with high doses and prolonged treatments. Do not exceed the prescribed dose or duration of treatment (see section "How to take MOBIC").
If you have heart problems, a history of stroke or think you may be at risk for these conditions, you should discuss your treatment with your doctor or pharmacist.
For example if:
- have high blood pressure (hypertension)
- have high blood sugar levels (diabetes mellitus)
- have high blood cholesterol levels (hypercholesterolemia)
- is a smoker
Stop taking MOBIC immediately as soon as you experience bleeding (causing tar-colored stools) or digestive tract ulceration (causing abdominal pain).
Life-threatening skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), initially manifesting as reddish patches or circular patches on the trunk, often accompanied by central blisters, have been reported with the use of MOBIC. to watch out for include ulcers in the mouth, throat, nose, genitals and conjunctivitis (red and swollen eyes). Such life-threatening skin reactions are often accompanied by flu-like symptoms. The rash may progress to diffuse blistering or exfoliation of the skin. skin. The highest risk of developing severe skin reactions occurs in the first few weeks of treatment
If you have developed Stevens-Johnson syndrome or toxic epidermal necrolysis with the use of MOBIC, you should no longer use MOBIC. If you develop a skin reaction or the skin symptoms described above, stop taking MOBIC, contact a doctor urgently and report that you are taking this medicine.
MOBIC is not indicated if immediate acute pain relief is required.
MOBIC can mask the symptoms (eg fever) of an "ongoing infection."
Therefore, if you think you have an infection, consult your doctor.
Precautions for use
As your dosage will need to be adjusted, it is important that you ask your doctor for advice before taking MOBIC in case of:
- a history of inflammation of the esophagus (esophagitis), inflammation of the stomach (gastritis) or a history of any other digestive tract disease, eg Crohn's disease or ulcerative colitis
- high blood pressure (hypertension)
- old age
- heart, liver or kidney disease
- high blood sugar levels (diabetes mellitus)
- reduced blood volume (hypovolaemia) which can occur in case of severe blood loss or a sunburn, surgery or low fluid intake
- intolerance to some sugars diagnosed by your doctor, as this medicine contains lactose
- high levels of potassium in the blood previously diagnosed by your doctor.
Your doctor will need to monitor your progress throughout your treatment
Interactions Which drugs or foods can change the effect of Mobic
As MOBIC can affect or be affected by other medicines, please tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
In particular, tell your doctor or pharmacist if you are taking or have taken any of the following medicines:
- other NSAIDs
- medicines that prevent blood clotting
- medicines that break blood clots (thrombolytics)
- medicines for the treatment of heart and kidney diseases
- corticosteroids (e.g. used against inflammation or allergic reactions)
- cyclosporine, used after organ transplants or for severe skin conditions, rheumatoid arthritis or nephrotic syndrome
- any diuretic Your doctor may monitor your kidney function if you are taking diuretics
- medicines to treat high blood pressure (e.g. beta blockers)
- lithium, used to treat mood disorders
- selective serotonin reuptake inhibitors (SSRIs) used to treat depression
- methotrexate, used to treat cancers or severe uncontrolled skin conditions and active rheumatoid arthritis
- cholestyramine, used to lower cholesterol levels
- if you are a woman using an intrauterine contraceptive device (IUD), usually known as a coil.
If you have any questions, consult your doctor or pharmacist
Warnings It is important to know that:
Fertility
MOBIC can impair your fertility. Therefore you should tell your doctor if you are planning to become pregnant or if you have problems getting pregnant.
Pregnancy
If you become pregnant while using MOBIC, inform your doctor. Your doctor may prescribe this medicine if necessary during the first six months of pregnancy.
During the last three months of pregnancy, do not use this medicine, because MOBIC can have serious effects on the baby, particularly on the cardiopulmonary and kidney levels, even after a "single administration.
Feeding time
This medicine is not recommended during breastfeeding.
Ask your doctor or pharmacist for advice before taking this medicine.
Driving and using machines
Visual disturbances, including blurred vision, dizziness, lethargy, vertigo or other central nervous system disturbances may occur with the intake of this product. If you experience such effects, do not drive or use machines.
MOBIC contains milk sugar (lactose)
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
Dosage and method of use How to use Mobic: Dosage
Always take this medicine exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.
The recommended dose is:
Exacerbations of osteoarthritis:
7.5 mg (one tablet) once a day. The dose can be increased to 15 mg (two tablets) once a day.
Rheumatoid arthritis:
15 mg (two tablets) once a day. The dose can be reduced to 7.5 mg (one tablet) once a day.
Ankylosing spondylitis:
15 mg (two tablets) once a day. The dose can be reduced to 7.5 mg (one tablet) once a day.
The tablets should be swallowed with water or other liquid during a meal.
The score line is only there to help you break the tablet if you have difficulty swallowing it whole.
DO NOT EXCEED THE MAXIMUM RECOMMENDED DOSE OF 15 mg PER DAY.
If any of the conditions listed in the 'Warnings and precautions' chapter apply to you, your doctor may reduce your dose to 7.5 mg (one tablet) once a day.
MOBIC should not be given to children and adolescents under 16 years of age.
Contact your doctor or pharmacist if you think the effect of MOBIC is too strong or too weak or if you feel no improvement after several days.
Overdose What to do if you have taken too much Mobic
If you have taken too many tablets or suspect an overdose, contact your doctor or go to the nearest hospital immediately. Symptoms of acute NSAID overdose usually are limited to:
- lack of energy (lethargy)
- drowsiness
- feeling sick (nausea) and vomiting
- pain in the stomach area (epigastric pain).
These symptoms are usually reversible when you stop taking MOBIC. You may experience bleeding from the stomach or intestines (gastrointestinal bleeding).
A severe overdose can induce severe adverse drug reactions:
- high blood pressure (hypertension)
- acute renal failure
- liver (hepatic) dysfunction
- reduction / flattening or stopping of breathing (respiratory depression)
- loss of consciousness (coma)
- convulsions
- collapse of blood circulation (cardiovascular collapse)
- arrest of the heart (cardiac arrest)
- immediate allergic reactions (hypersensitivity), including:
- fainting
- shortness of breath
- skin reactions
If you forget to take MOBIC
Do not take a double dose to make up for a forgotten tablet.
Take your next dose at the usual time.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Mobic
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking MOBIC and consult your doctor or nearest hospital immediately if you notice:
Any allergic (hypersensitivity) reaction, which can manifest itself in the form of:
- skin reactions such as itching, blistering or peeling, which can be life-threatening skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), soft tissue lesions (mucosal lesions) or erythema multiforme Erythema multiforme is a severe allergic reaction of the skin causing spots, red or purple blisters or blistering areas. It can also affect the mouth, eyes and other moist areas of the body surface. Erythema multiforme is a severe allergic skin reaction that causes spots, red or purple blisters. or bullous areas. It can also affect the mouth, eyes and other moist areas of the body surface.
- swelling of the skin or mucous membrane, such as swelling around the eyes, face, lips, mouth or throat, which may make it difficult to breathe, swollen ankles or legs (lower limb edema)
- shortness of breath or asthma attack
- inflammation of the liver (hepatitis). This can cause symptoms such as:
- yellowing of the skin and eyes (jaundice)
- abdominal pain
- loss of appetite.
Any undesirable effects of the digestive tract, especially:
- bleeding (causing tar-colored stools)
- ulceration of the digestive tract (causing abdominal pain)
Bleeding from the digestive tract (gastrointestinal bleeding), the formation of ulcers or perforations in the digestive tract can sometimes be serious and potentially fatal, especially in elderly patients.
If you have previously suffered from digestive tract symptoms due to long-term use of NSAIDs, tell your doctor immediately, especially if you are elderly. Your doctor can monitor the improvement during treatment.
If you experience visual disturbances, do not drive or use machines.
General side effects associated with non-steroidal anti-inflammatory drugs (NSAIDs)
The use of some non-steroidal anti-inflammatory drugs (NSAIDs) may be associated with a small increased risk of artery occlusion (thrombotic arterial events), eg heart attack (myocardial infarction) or stroke (apoplexy), particularly at high dosages and for long periods of treatment.
Fluid retention (edema), high blood pressure (hypertension) and heart failure (heart failure) have been reported in association with NSAID treatment.
The most commonly observed side effects are related to the digestive tract (gastrointestinal events):
- ulcers of the stomach and upper part of the small intestine (peptic / gastroduodenal ulcers)
- a perforation in the bowel wall or bleeding from the digestive tract (sometimes fatal, especially in the elderly)
The following side effects have been reported after NSAID administration:
- feeling sick (nausea) and vomiting
- poorly formed stools (diarrhea)
- flatulence
- constipation
- indigestion (dyspepsia)
- abdominal pain
- tar-colored stools due to bleeding in the digestive tract (melaena)
- vomiting of blood (hematemesis)
- inflammation with ulceration in the mouth (ulcerative stomatitis)
- worsening of inflammation of the digestive tract (such as exacerbation of colitis or Crohn's disease).
Stomach inflammation (gastritis) has been observed less frequently.
Side effects associated with meloxicam the active substance of MOBIC
Very common: affects more than 1 in 10 patients
- gastrointestinal adverse events such as indigestion (dyspepsia), feeling sick (nausea) and being sick (vomiting), abdominal pain, constipation, flatulence, poorly formed stools (diarrhea)
Common: affects 1 to 10 users in 100
- headache
Uncommon: affects 1 to 10 users in 1,000
- dizziness (confusion of mind)
- sensation of spinning or spinning head (vertigo)
- drowsiness (numbness)
- anemia (decreased concentration of hemoglobin in the blood)
- increased blood pressure (hypertension)
- flushing (temporary redness of the face and neck)
- sodium and water retention
- increased potassium levels (hyperkalaemia), which can lead to symptoms such as:
- changes in your heartbeat (arrhythmia)
- palpitations (when the heartbeat is heard more than usual)
- muscle weakness belching
- stomach inflammation (gastritis)
- bleeding from the digestive tract
- inflammation of the mouth (stomatitis)
- immediate allergic reactions (hypersensitivity)
- itch
- rash
- swelling caused by fluid retention (edema), including swelling of the ankles / legs (edema of the lower limbs)
- sudden swelling of the skin or mucous membranes, such as swelling around the eyes, face, lips, mouth or throat which can make breathing difficult (angioneurotic edema)
- transient changes in liver function tests (e.g. increase in liver enzymes such as transaminases or an increase in bile pigment bilirubin). Your doctor can check this by using a blood test
- abnormal kidney function tests (eg increased creatinine or urea)
Rare: affects 1 to 10 users in 10,000
- mood swings
- nightmares
- altered blood cell counts, including:
- altered differential blood cell count
- reduced number of white blood cells (leukocytopenia)
- low number of platelets (thrombocytopenia) These side effects can lead to an increased risk of infection and symptoms such as bruising or nosebleeds.
- ringing in the ears (tinnitus)
- sensation of feeling the heartbeat (palpitations)
- ulcers of the stomach or upper part of the small intestine (peptic / gastroduodenal ulcer)
- inflammation of the esophagus (esophagitis)
- onset of asthma attacks (found in people who are allergic to aspirin or other NSAIDs)
- severe blistering or peeling of the skin (Stevens-Johnson syndrome and toxic epidermal necrolysis)
- urticaria
- vision disturbances including:
- blurred vision
- conjunctivitis (inflammation of the eyes or eyelids)
- inflammation of the large intestine (colitis)
Very rare: affects less than 1 in 10,000 patients
- blistering of the skin (bullous reactions) and erythema multiforme. Erythema multiforme is a severe allergic skin reaction that causes spots, red or purple blisters, or blistering areas. It can also affect the mouth, eyes and other moist areas of the body surface.
- inflammation of the liver (hepatitis), which can cause symptoms such as:
- yellowing of the skin or eyes (jaundice)
- pain in the abdomen
- loss of appetite
- acute kidney failure (kidney failure) particularly in patients with risk factors such as heart disease, diabetes or kidney disease
- a perforation in the wall of the intestine.
Not known: frequency cannot be estimated from the available data
- state of confusion
- sense of disorientation
- shortness of breath and skin reactions (anaphylactic / anaphylactoid reactions) skin rash caused by exposure to sunlight (photosensitivity reactions)
- Heart failure (heart failure) associated with NSAID treatment has been reported
- total loss of a specific type of white blood cells (agranulocytosis), especially in patients taking MOBIC in combination with other medicines that are potentially inhibitory, depressant or destructive of a component of the bone marrow (myelotoxic medicines), this can cause:
- sudden fever
- sore throat
- infections
Side effects caused by non-steroidal anti-inflammatory drugs (NSAIDs), but not yet seen after taking MOBIC
Alteration of the structure of the kidney leading to acute renal failure:
- very rare cases of kidney inflammation (interstitial nephritis)
- death of some cells within the kidney (acute tubular or papillary necrosis)
- protein in the urine (nephrotic syndrome with proteinuria)
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system. : https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the container and carton. The expiry date refers to the last day of that month.
Store in the original package to keep it away from moisture.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What MOBIC contains
The active ingredient is:
- meloxicam
- one tablet contains 7.5 mg of meloxicam.
The other ingredients are:
- sodium citrate
- lactose monohydrate
- microcrystalline cellulose
- povidone
- anhydrous colloidal silica
- crospovidone
- magnesium stearate
Description of MOBIC appearance and contents of the package
MOBIC tablets are light yellow, round, with the company logo on one side and the code 59D / 59D on the other.
Each MOBIC tablet has a score line. The score line is only intended to allow the tablet to break to facilitate taking and not to divide it into equal parts.
MOBIC is available in PVC / PVDC / aluminum blisters
Packaging: boxes containing 1, 2, 7, 10, 14, 15, 20, 28, 30, 50, 60, 100, 140, 280, 300, 500 tablets.
Not all pack sizes may be marketed
Other strengths of MOBIC and other pharmaceutical forms of meloxicam
In some countries meloxicam is also available as:
- meloxicam 15 mg tablets
- meloxicam 7.5 mg suppositories
- meloxicam 15 mg suppositories
- meloxicam 15 mg per 1.5 ml solution for injection
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
MOBIC 7.5 MG TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 7.5 mg of meloxicam.
Excipients: lactose (22.3 mg)
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Tablet
Round, light yellow tablet engraved with the company logo on one side and the code 59D / 59D on the other.
The score line is only intended to allow the tablet to break to facilitate taking and not to divide it into equal parts.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
• Short-term symptomatic treatment of acute painful states in osteoarthritis.
• Long-term symptomatic treatment of rheumatoid arthritis or ankylosing spondylitis.
04.2 Posology and method of administration
Oral use
The total daily dose should be taken in a single administration, ingested with water or other liquid, during meals.
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see section 4.4). Patient symptomatic relief and response to therapy should be re-evaluated. periodically, especially in patients with osteoarthritis.
• Acute painful states in osteoarthritis: 7.5 mg / day (one 7.5 mg tablet).
If necessary, in the absence of improvement, the dosage can be increased to 15 mg / day (two 7.5 mg tablets).
• Rheumatoid arthritis, ankylosing spondylitis: 15 mg / day (two 7.5 mg tablets).
(see also the following section "Special patient groups").
Depending on the therapeutic response, the dose can be reduced to 7.5 mg / day (one tablet
from 7.5 mg).
Do not exceed the dose of 15 mg PER DAY.
Particular groups of patients
Elderly patients and patients at high risk of adverse reactions (see section 5.2):
In elderly patients, the recommended dose for the long-term treatment of rheumatoid arthritis and ankylosing spondylitis is 7.5 mg / day.
Patients at high risk of adverse reactions should initiate therapy with a dose of 7.5 mg / day (see section 4.4).
Renal impairment (see section 5.2):
For dialysis patients with severe renal insufficiency, the dosage of 7.5 mg / day should not be exceeded.
There is no need to reduce the dosage in patients with mild or moderate renal impairment (e.g. patients with creatinine clearance levels above 25 ml / min). (For non-dialysed patients with severe renal impairment, see section 4.3)
Hepatic impairment (see section 5.2):
There is no need to reduce the dosage in patients with mild or moderate hepatic impairment. (For patients with severely impaired hepatic function see section 4.3).
Children and adolescents:
Mobic 7.5 mg tablets are contraindicated in children and adolescents less than 16 years of age (see section 4.3).
This medicine is available in other strengths that may be more appropriate.
04.3 Contraindications
This medicine is contraindicated in the following cases:
- Third trimester of pregnancy (see section 4.6 "Fertility, pregnancy and lactation");
- Children and adolescents under the age of 16;
- Hypersensitivity to meloxicam or to any of the excipients listed in section 6.1 or hypersensitivity to substances with similar action, eg. non-steroidal anti-inflammatory drugs (NSAIDs), aspirin. Meloxicam must not be administered to patients who have experienced signs of asthma, nasal polyps, angioneurotic edema or urticaria following the intake of acetylsalicylic acid or other NSAIDs;
- History of gastrointestinal bleeding or perforation, related to previous NSAID therapy;
- History of recurrent or ongoing peptic ulcer / bleeding (two or more distinct, proven episodes of ulceration or bleeding);
- Severe impairment of liver function;
- Patients with severe renal insufficiency not undergoing dialysis;
• Gastrointestinal bleeding, history of cerebrovascular haemorrhage or other bleeding episodes;
• Severe heart failure.
04.4 Special warnings and appropriate precautions for use
Undesirable effects can be minimized with the use of the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see section 4.2 and the paragraphs below on gastrointestinal and cardiovascular risks).
In case of insufficient therapeutic effect, the maximum recommended daily dose should not be exceeded, nor should another NSAID be taken in addition, as this can increase toxicity, without any proven therapeutic benefit. The use of meloxicam in combination with NSAIDs, including selective cyclo-oxygenase 2 inhibitors, should be avoided.
Meloxicam is not indicated for the treatment of patients requiring acute pain relief.
If improvement does not occur after several days, the clinical benefit of the treatment should be reassessed.
Before starting treatment with meloxicam, any history of oesophagitis, gastritis and / or peptic ulcer should be evaluated in order to ascertain relative healing. The possible onset of relapse following treatment with meloxicam in patients with such a history should be routinely monitored.
Gastrointestinal effects
Gastrointestinal bleeding, ulceration or perforation, which can be fatal, have been reported with the use of all NSAIDs at any time during treatment, with or without prodromal symptoms or a previous history of serious gastrointestinal events.
The risk of gastrointestinal bleeding, ulceration or perforation increases with the dose of NSAID, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3) and in elderly patients. These patients should start treatment with the lowest available dosage. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients and also for those taking concomitantly low-dose aspirin or other drugs that similarly increase gastrointestinal risk (see below). below and paragraph 4.5).
Patients with a history of gastrointestinal toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding) especially in the initial stages of treatment.
The combination with meloxicam is not recommended in patients being treated concomitantly with medicinal products that may increase the risk of ulceration or bleeding such as heparin as treatment or given in geriatrics, anticoagulants such as warfarin, other non-steroidal anti-inflammatory drugs, or "acetylsalicylic acid given at doses ≥ 500 mg as a single dose or ≥ 3 g as a total daily amount (see section 4.5).
If gastrointestinal bleeding or ulceration occurs in patients taking meloxicam, the treatment should be discontinued.
NSAIDs should be administered with caution to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may worsen (see section 4.8 - Undesirable effects).
Cardiovascular and cerebrovascular effects
Adequate monitoring and instruction are required in patients with a history of mild to moderate hypertension and / or congestive heart failure as fluid retention and edema have been reported in association with NSAID treatment.
Clinical monitoring of blood pressure is recommended for patients at risk at baseline and particularly during the initial phase of treatment with meloxicam.
Clinical studies and epidemiological data suggest that the use of some NSAIDs including meloxicam (especially at high doses and for long-term treatment) may be associated with a modest increased risk of arterial thrombotic events (eg myocardial infarction or stroke). There are insufficient data to exclude a similar risk for meloxicam.
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with meloxicam after careful consideration. Similar considerations should be made before initiating long-term treatment in patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).
Skin reactions
The following life-threatening skin reactions have been reported with the use of meloxicam: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Patients should be informed of the signs and symptoms and monitored closely for skin reactions. The highest risk of developing SJS or TEN occurs in the first few weeks of treatment.
If symptoms or signs of SJS or TEN occur (e.g. progressive skin rash, frequently associated with blistering or mucosal lesions) treatment with meloxicam should be discontinued.
The best results in the management of SJS and TEN are obtained with early diagnosis and immediate discontinuation of therapy with any suspect drug. Early discontinuation is associated with a better prognosis.
If, with the use of meloxicam, the patient has developed SJS or TEN, meloxicam should no longer be used in this patient.
Hepatic and renal function parameters
As with most NSAIDs, increases in serum transaminase values, serum bilirubin or other liver function parameters have occasionally been observed, as well as increases in serum creatinine and blood urea nitrogen concentration and other changes in laboratory parameters. . In most cases these were minor and transient changes. In the event of significant or persistent changes, treatment with meloxicam should be discontinued and appropriate examinations prescribed.
Functional renal insufficiency
By inhibiting the vasodilator effect of renal prostaglandins, NSAIDs can induce functional renal failure by reduced glomerular filtration. This adverse event is dose dependent.At the start of treatment, or after a dose increase, careful monitoring of diuresis and renal function is recommended in patients with the following risk factors:
• Old age
• Concomitant treatments with drugs such as ACE inhibitors, angiotensin II receptor antagonists, sartans, diuretics (see section 4.5 Interactions with other medicinal products and other forms of interaction)
• Hypovolemia (regardless of the cause)
• Congestive heart failure
• Kidney failure
• Nephrotic syndrome
• Nephropathy in the course of nephropathic lupus
• Severe hepatic dysfunction (serum albumin
In rare cases, NSAIDs may be the cause of interstitial nephritis, glomerulonephritis, renal medullary necrosis or nephrotic syndrome.
The dose of meloxicam in patients with end-stage renal insufficiency undergoing hemodialysis should not exceed 7.5 mg. No dose reduction is required in patients with mild or moderate renal insufficiency (ie in patients with creatinine clearance. above 25 ml / min).
Retention of sodium, potassium and water
With the administration of NSAIDs, retention of sodium, potassium and water and interference with the natriuretic effects of diuretics may occur and also decrease in the antihypertensive effect of antihypertensive medicinal products (see section 4.5). Consequently in sensitive patients edema, heart failure or hypertension may precipitate or worsen, therefore clinical monitoring is required for patients at risk (see sections 4.2 and 4.3).
Hyperkalemia
Hyperkalaemia may be favored by diabetes or by concomitant therapies which are known to increase blood potassium concentrations (see section 4.5). In these cases, regular monitoring of potassium values should be performed.
Association with pemetrexed
In patients with mild and moderate renal impairment receiving pemetrexed therapy, meloxicam treatment should be stopped for at least 5 days before, on the same day and for at least 2 days after pemetrexed administration (see section 4.5).
Other warnings and precautions
Adverse reactions are often less tolerated in elderly, frail or debilitated patients, who must therefore be closely monitored. As with other NSAIDs, extreme caution is required in the treatment of elderly patients, who often have impaired renal, hepatic and cardiac function. Elderly patients have a higher frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which can be fatal (see section 4.2).
Meloxicam, like any other NSAID, can hide the symptoms of an ongoing infectious disease.
The use of meloxicam may reduce female fertility and is not recommended for women planning to conceive. In women who have difficulty conceiving or who are undergoing investigation for infertility, the option of discontinuing meloxicam therapy should be taken into account (see section 4.6).
Mobic 7.5 mg tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp-lactase deficiency or glucose-galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
Interaction studies have only been performed in adults.
Risk related to hyperkalaemia
Some drugs, or therapeutic classes, can promote hyperkalaemia: potassium salts, potassium-sparing diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory drugs, heparins (low molecular weight or unfractionated), cyclosporine, tacrolimus and trimethoprim.
The onset of hyperkalaemia may depend on the association of several factors.
The risk is higher when the above mentioned medicines are co-administered with meloxicam.
Pharmacodynamic interactions:
Other non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid:
Concomitant use of meloxicam with other NSAIDs, acetylsalicylic acid at doses ≥500 mg per single administration or ≥ 3 g as a total daily dose, is not recommended (see section 4.4).
Corticosteroids (eg. Glucocorticoids):
Concomitant use with corticosteroids requires caution due to an increased risk of gastrointestinal bleeding or ulcer.
Anticoagulants or heparin:
The risk of bleeding is greatly increased due to inhibition of platelet function and damage to the gastroduodenal mucosa. NSAIDs may enhance the effects of anticoagulant drugs such as warfarin (see section 4.4). Concomitant use of NSAIDs and anticoagulants or heparin administered in geriatrics or at curative doses (see section 4.4).
In other cases of heparin use (e.g. preventive doses) caution is required due to an increased risk of bleeding.
In cases where association cannot be avoided, close monitoring of the INR is essential.
Thrombolytics and antiplatelet drugs:
Increased risk of bleeding due to inhibition of platelet activity and damage to the gastroduodenal mucosa.
Selective Serotonin Reuptake Inhibitors (SSRIs):
Increased risk of gastrointestinal bleeding.
Diuretics, ACE inhibitors and angiotensin II receptor antagonists:
NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (eg dehydrated patients or elderly patients with impaired renal function) co-administration of an ACE inhibitor or antagonists of the renal receptor. angiotensin II and cyclooxygenase inhibiting agents may lead to further worsening of renal function, including possible acute renal failure, which is usually reversible. Therefore, the combination should be administered with caution especially in the elderly. Patients should be adequately hydrated and monitoring of renal function should be considered after initiating concomitant therapy, and then periodically (see also section 4.4).
Other antihypertensives (e.g. beta-blockers):
As with previous antihypertensive medicinal products, a decrease in the antihypertensive effect of beta-blockers may occur (due to inhibition of vasodilatory prostaglandins).
Calcineurin inhibitors (e.g. cyclosporine, tacrolimus):
Renal toxicity of calcineurin inhibitors may be increased by NSAIDs through a prostaglandin-mediated renal effect. Renal function should be monitored during combination treatment. Close monitoring of renal function is recommended, especially in elderly patients.
Deferasirox:
Concomitant administration of meloxicam and deferasirox may increase the risk of gastrointestinal adverse reactions. Caution should be exercised when combining these medicinal products.
Pharmacokinetic interactions: Effect of meloxicam on the pharmacokinetics of other medicinal products
Lithium:
NSAIDs have been observed to cause an increase in lithium levels (through decreased renal excretion of lithium), which may reach toxicity values. Concomitant use of NSAIDs and lithium is not recommended (see section 4.4). combination is required plasma lithium concentration should be regularly monitored at the start of treatment, whenever the dosage is changed and upon discontinuation of meloxicam treatment.
Methotrexate:
NSAIDs can reduce the tubular secretion of methotrexate thereby increasing its plasma concentration. For this reason, concomitant use of NSAIDs is not recommended in patients receiving high doses (more than 15 mg / week) of methotrexate (see section 4.4).
The risk of interaction between non-steroidal anti-inflammatory drugs and methotrexate should also be considered for patients receiving low doses of methotrexate, especially in those with impaired renal function. In case of combination, close monitoring of blood count and renal function is recommended. Extreme caution is required if combined NSAIDs and methotrexate are administered for a period of three days; in this case it can increase the concentration of methotrexate in the blood and, therefore, the toxicity.
Although no effective impairment of methotrexate pharmacokinetics (15 mg / week) has been observed with concomitant use of meloxicam, it should be taken into account that the blood toxicity of methotrexate may be amplified by treatment with NSAIDs (see above. ) (see section 4.8).
Pemetrexed:
For concomitant use of meloxicam with pemetrexed in patients with mild to moderate renal impairment (creatinine clearance 45 to 79 ml / min), meloxicam treatment should be stopped for 5 days earlier, on the same day and for 2 days. days after administration of pemetrexed. If the combined use of pemetrexed and meloxicam is necessary, patients should be closely monitored, especially for myelosuppression and gastrointestinal adverse reactions. Concomitant administration of meloxicam and pemetrexed is not recommended in patients with severe renal impairment (creatinine clearance less than 45 ml / min).
In patients with normal renal function (creatinine clearance ≥ 80 ml / min) doses of meloxicam of 15 mg may reduce the elimination of pemetrexed and consequently increase the incidence of adverse effects of pemetrexed. Therefore, caution should be exercised when administering meloxicam 15 mg concomitantly with pemetrexed to patients with normal renal function (creatinine clearance ≥ 80 ml / min).
Pharmacokinetic Interactions: Effect of other medicinal products on the pharmacokinetics of meloxicam
Cholestyramine:
Cholestyramine accelerates the elimination of meloxicam by interrupting the enterohepatic circulation so that clearance for meloxicam increases by 50% and the half-life decreases to 13 ± 3 hours. This interaction has clinical significance.
Concomitant administration of meloxicam and antacids, cimetidine and digoxin produced no relevant pharmacokinetic interactions.
04.6 Pregnancy and lactation
Fertility
The use of meloxicam, as well as any other medicine known to inhibit cyclooxygenase / prostaglandin synthesis, may reduce female fertility and is not recommended for women planning to conceive. In women who have difficulty conceiving or who are undergoing investigation for infertility, the possibility of discontinuing meloxicam therapy should be considered.
Pregnancy
Inhibition of prostaglandin synthesis may adversely affect pregnancy and / or embryo / fetal development. Data from epidemiological studies suggest an increased risk of spontaneous abortion, cardiac malformations and gastroschisis after use of a synthesis inhibitor. of prostaglandins in early pregnancy. The absolute risk of cardiovascular malformation is increased from less than 1% to approximately 1.5%. The risk is believed to increase with increasing dose and duration of therapy . In animals, administration of a prostaglandin synthesis inhibitor has resulted in increased pre- and post-implantation loss and lethal effects on the embryo and fetus have been reported. In addition, an increase in the incidence of various malformations, including malformations, has been reported. cardiovascular diseases in animals treated with a prostaglandin synthesis inhibitor during the period of organogenesis.
During the first and second trimester of pregnancy, meloxicam should not be given unless clearly necessary. If meloxicam is administered to women intending to conceive or during the first and second trimester of pregnancy, the dose should be kept as low as possible and the duration of treatment should be as short as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose the fetus to:
• cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension);
• renal dysfunction, which can worsen to renal failure with oligo-hydroamniosis;
At the end of pregnancy, the mother and the newborn may be exposed to the following risks:
• possible prolongation of bleeding time, an antiplatelet effect which can occur even at very low dosages;
• inhibition of uterine contractions which can result in a delay or prolongation of labor.
Consequently, administration of meloxicam is contraindicated during the third trimester of pregnancy.
Feeding time
Although there is no specific experience with meloxicam, NSAIDs are known to be excreted in breast milk. For this reason, use during lactation is not recommended.
04.7 Effects on ability to drive and use machines
No specific studies on the effect on the ability to drive and use machines have been performed. However, given the pharmacodynamic profile and reported adverse events, meloxicam is likely to have no or negligible effect on these activities.
However, when visual disturbances including blurred vision, dizziness, lethargy, dizziness or other central nervous system disturbances occur, it is advisable to refrain from driving and operating machinery.
04.8 Undesirable effects
a) General Description
Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially at high doses and for long-term treatment) may be associated with a modest increased risk of arterial thrombotic events (eg myocardial infarction or stroke) (see paragraph 4.4).
Edema, hypertension and heart failure have been reported in association with NSAID treatment.
The most commonly reported adverse events are gastrointestinal in nature. Peptic ulcer, gastrointestinal perforation or bleeding, sometimes fatal, especially in elderly patients, may occur (see section 4.4). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease (see section 4.4) have been reported following administration. Gastritis has been reported less frequently.
Severe cutaneous adverse reactions (SCARs): Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported (see section 4.4).
The frequencies listed below are based on the corresponding frequency of adverse events reported in 27 clinical studies with a treatment duration of at least 14 days. The information is based on clinical studies involving 15,197 patients who were treated with daily doses of 7.5 or 15 mg of meloxicam as tablets or capsules, for up to one year.
Adverse reactions emerged from reports received in connection with the administration of the marketed medicine are included.
Adverse reactions were ranked by frequency according to the following conventional scale:
Very common (≥1 / 10); common (≥1 / 100,
b) Table of adverse reactions
Disorders of the blood and lymphatic system
Uncommon: Anemia
Rare: Blood count changes (including white blood cell count differential), leukocytopenia, thrombocytopenia
Very rare: Cases of agranulocytosis have been reported (see section c)
Disorders of the immune system
Uncommon: Allergic reactions other than anaphylactic or anaphylactoid reactions
Not known: Anaphylactic reactions, anaphylactoid reactions
Psychiatric disorders
Rare: Mood altered, nightmares
Not known: Confusional state, disorientation
Nervous system disorders
Common: Headache
Uncommon: Vertigo, numbness
Eye disorders
Rare: Visual disturbances including blurred vision, conjunctivitis
Ear and labyrinth disorders
Uncommon: Vertigo
Rare: Tinnitus
Cardiac pathologies
Rare: Palpitations
Heart failure has been reported in association with NSAID treatment.
Vascular pathologies
Uncommon: Blood pressure increased (see section 4.4), flushing
Respiratory, thoracic and mediastinal disorders
Rare: Onset of asthma attacks in some individuals allergic to aspirin or other NSAIDs
Gastrointestinal disorders
Very common: gastrointestinal adverse events such as dyspepsia, nausea, vomiting, abdominal pain, constipation, flatulence, diarrhea
Uncommon: Occult or gross gastrointestinal bleeding, stomatitis, gastritis, belching
Rare: Colitis, gastroduodenal ulcer, esophagitis
Very rare: Gastrointestinal perforation
Gastrointestinal bleeding, ulceration or perforation can sometimes be serious and potentially fatal especially in elderly patients (see section 4.4).
Hepatobiliary disorders
Uncommon: Liver function disorder (e.g. increased transaminases or bilirubin)
Very rare: Hepatitis
Skin and subcutaneous tissue disorders
Uncommon: Angioedema, pruritus, skin rash
Rare: Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
Very rare: Bullous dermatitis, erythema multiforme
Not known: Photosensitization reactions
Renal and urinary disorders
Uncommon: Sodium and water retention, hyperkalaemia (see section 4.4 Special warnings and precautions for use and section 4.5), renal function abnormal tests (increase in serum creatinine and / or serum urea)
Very rare: Acute renal failure in patients with risk factors (see section 4.4)
General disorders and administration site conditions
Uncommon: Edema including lower limb edema
c ) Information on serious and / or frequently observed individual adverse reactions
Very rare cases of agranulocytosis have been reported in patients treated with meloxicam in combination with other potentially myelotoxic medicinal products (see section 4.5).
d) Adverse reactions that have not yet been observed in relation to the product, but which are generally attributable to other components of the same class
Organic renal injury which may lead to acute renal failure: very rare cases of interstitial nephritis, acute tubular necrosis, nephrotic syndrome and papillary necrosis have been reported (see section 4.4).
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address http://www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
Symptoms resulting from acute NSAID overdose are usually limited to lethargy, drowsiness, nausea, vomiting and epigastric pain and are generally reversible with supportive treatment. Gastrointestinal bleeding may occur. Severe intoxication can lead to hypertension, acute renal failure, liver dysfunction, respiratory depression, coma, seizures, cardiovascular collapse and cardiac arrest. Anaphylactoid reactions have been reported at therapeutic doses of NSAIDs and may occur following overdose.
In the event of NSAID overdose, patients should undergo symptomatic and supportive therapy. A clinical study has shown that 4 g of cholestyramine administered orally three times a day accelerates the elimination of meloxicam.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Non-steroidal anti-inflammatory drugs, Oxicam
ATC code: M 01AC06
Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) of the oxicam family, which possesses anti-inflammatory, analgesic and antipyretic activities.
The anti-inflammatory activity of meloxicam has been demonstrated in classical models of inflammation. As with other NSAIDs, the precise mechanism of action is not known. However, there is at least one common mechanism of action shared by all NSAIDs (including meloxicam): inhibition of the synthesis of prostaglandins, known mediators of inflammation.
05.2 Pharmacokinetic properties
Absorption
Meloxicam is well absorbed from the gastrointestinal tract, resulting in a high absolute bioavailability of approximately 90% after oral administration (capsules). The same bioavailability has been demonstrated after taking tablets, oral suspension and capsules.
After single administration of meloxicam, median maximum plasma concentrations are reached within 2 hours with suspension and within 5-6 hours with solid oral forms (capsules and tablets).
With multiple dosing, steady state conditions were achieved within 3-5 days. Once daily dosing results in mean plasma drug concentrations with relatively modest trough-to-peak fluctuation in the therapeutic range of 0.4 - 1.0 mcg / ml for the 7.5 mg and 0.8-2.0 mcg dose, respectively. / ml for the 15 mg dose (Cmin and Cmax at steady state, respectively).
Mean steady-state maximum plasma concentrations of meloxicam are achieved within five or six hours for the tablets, capsules and oral suspension, respectively.
The absorption of meloxicam after oral administration is not affected by concomitant food or by the use of inorganic antacids.
Distribution
Meloxicam binds strongly to plasma proteins, essentially albumin (99%). Meloxicam penetrates in large quantities into the synovial fluid reaching local concentrations equal to about half of those in plasma.
The volume of distribution is low, i.e. approximately 11 l after i.m. administration. or i.v. and exhibits interindividual variability in the order of 7-20%. The volume of distribution following oral administration of multiple doses of meloxicam (7.5 to 15 mg) is approximately 16 l with variance between 11 and 32%.
Biotransformation
Meloxicam undergoes "extensive hepatic biotransformation. Four different metabolites of meloxicam have been identified in the urine, all of which are pharmacodynamically inactive. The major metabolite, 5" -carboxymeloxicam (60% of the dose), is formed by oxidation of the intermediate metabolite 5 "- hydroxymethylmeloxicam, which, in turn, is excreted to a lesser extent (9% of the dose). In vitro studies suggest that CYP2C9 plays an important role in this metabolic pathway with a minor contribution from the CYP3A4 isoenzyme. The patient's peroxidase activity is likely responsible for the formation of the other two metabolites, which account for 16% and 4% of the total administered dose, respectively.
Elimination
Meloxicam is mainly excreted as metabolites and is found equally in faeces and urine. Less than 5% of the daily dose is eliminated unchanged in the faeces, while only traces are eliminated in the urine.
The mean elimination half-life varies between 13 and 25 hours after oral administration, i.m. and i.v ..
Total plasma clearance is approximately 7-12 mL / min after a single dose administered orally, intravenously or rectally.
Linearity / non-linearity
Meloxicam demonstrates linear pharmacokinetics over a therapeutic dose range of 7.5 mg / 15 mg after oral or intramuscular administration.
Particular groups of patients
Patients with renal / hepatic insufficiency
The pharmacokinetic parameters of meloxicam are not significantly changed in subjects with mild or moderate renal or hepatic impairment. Subjects with moderate renal impairment showed significantly higher total drug clearance. A decrease in protein binding was observed in patients with end stage renal failure.
In "end-stage renal failure" the increase in the volume of distribution may result in higher concentrations of free meloxicam, therefore the daily dose of 7.5 mg should not be exceeded (see section 4.2).
Senior citizens
Elderly male subjects exhibited mean pharmacokinetic parameters similar to those of younger male subjects. Elderly patients had higher AUC values and a prolonged elimination half-life than those of younger subjects of both genders.
Mean steady state plasma clearance in elderly subjects was slightly lower than that seen in younger individuals.
05.3 Preclinical safety data
In preclinical studies, the toxicological profile of meloxicam was identical to that of other NSAIDs: in chronic toxicity studies, gastrointestinal ulcers and erosions, renal papillae necrosis appeared at high doses in two species of animals.
Oral reproductive toxicity studies have shown decreased ovulation and "implantation inhibition" and embryotoxic effects (increased resorptions) at maternal toxic doses of 1 mg / kg / day and higher in the rat. Reproductive toxicity studies performed on rats and rabbits did not reveal teratogenicity up to doses of 4 mg / kg in rats and 80 mg / kg in rabbits.
The dosages involved exceeded 10 to 5 times the clinical dose (7.5-15 mg) calculated on the basis of the dose expressed in mg / kg (for a 75 kg person). As with all prostaglandin synthesis inhibitors, foetotoxic effects have been described at the end of gestation. No mutagenic effects were shown, either in vitro or in vivo.
In rats and mice, which were administered doses much higher than those used in humans, no carcinogenic effect was shown.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Sodium citrate, lactose monohydrate, microcrystalline cellulose, povidone K25, anhydrous colloidal silica, crospovidone, magnesium stearate.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years
06.4 Special precautions for storage
Store in the original package to protect the medicine from moisture.
06.5 Nature of the immediate packaging and contents of the package
PVC / PVDC / Aluminum blisters, packs of 1, 2, 7, 10, 14, 15, 20, 28, 30, 50, 60, 100, 140, 280, 300, 500, 1,000 tablets.
Not all pack sizes may be marketed
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Boehringer Ingelheim International GmbH
Binger Strasse 173
Ingelheim am Rhein - Germany
SALES REPRESENTATIVE IN ITALY
Boehringer Ingelheim Italia S.p.A.
Via Lorenzini 8
20139 Milan
08.0 MARKETING AUTHORIZATION NUMBER
10 tablets AIC n ° 031985106
30 tablets AIC n ° 031985157
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 26.04.1996
Date of latest renewal: 08.05.2010
10.0 DATE OF REVISION OF THE TEXT
Determination of 5 May 2015
