Active ingredients: Piroxicam (Piroxicam -? - cyclodextrin)
BREXIN 20 mg tablets
BREXIN 20 mg effervescent tablets
BREXIN 20 mg granules for oral solution
BREXIN 20 mg suppositories
Why is Brexin used? What is it for?
Before prescribing BREXIN, your doctor will evaluate the benefits of this medicine against the risk of side effects. Your doctor may need to review you periodically and will tell you how often you will need to be checked while you are being treated with BREXIN.
BREXIN is an anti-inflammatory and pain reliever medicine which is used to relieve certain symptoms caused by osteoarthritis (osteoarthritis: degenerative joint disease), rheumatoid arthritis and ankylosing spondylitis (rheumatism of the spine), such as swelling, stiffness and pain in the joints. BREXIN does not cure arthritis and will only relieve you as long as you continue to take it.
Your doctor will only prescribe BREXIN when other non-steroidal anti-inflammatory medicines (NSAIDs) are no longer helpful in relieving your symptoms.
Contraindications When Brexin should not be used
DO NOT TAKE BREXIN
- If you are allergic (hypersensitive) to piroxicam or any of the other ingredients of BREXIN
- If you have ever had an ulcer or bleeding or perforation in the stomach or intestines,
- If you have an ulcer or bleeding or perforation in the stomach or intestines
- If you have or have had previous gastrointestinal disorders (inflammation of the stomach or intestines) which predispose to bleeding disorders such as ulcerative colitis, Crohn's disease, gastrointestinal cancer, diverticulitis (inflamed or infected pockets / cavities in the colon).
- If you are taking other NSAIDs, including selective COX-2 inhibitors and acetylsalicylic acid (found in many medicines used to relieve pain and lower fever). Remember that many NSAIDs are also available without a prescription.
- If you are taking blood thinners, such as warfarin, to prevent blood clots.
- If you have ever had a severe allergic reaction to piroxicam, other NSAIDs and other medicines, especially severe skin reactions (regardless of their intensity), such as erythema multiforme, exfoliative dermatitis (intense redness of the skin, with flaky or layered peeling ), vesiculo-bullous reactions: Stevens-Johnson syndrome, characterized by blistered, red, corroded, bloody, or crusted skin, and necrotic epidermolysis, characterized by blistering and peeling of the surface layer of the skin.
- If you have had symptoms of asthma, rhinitis, nasal polyposis, angioedema or urticaria during treatment with acetylsalicylic acid or other NSAIDs
- If you are pregnant or if you are in doubt as to whether you are pregnant.
- If you are breastfeeding.
- If you are under the age of 18.
- If you have severe liver disease.
- If you have severe kidney disease.
- If you have moderate or severe heart failure.
- If you have severe hypertension.
- If you have severe blood disorders.
- If you have a bleeding diathesis (a predisposition to bleed frequently).
If any of these conditions exist, BREXIN should not be prescribed for you. Tell your doctor immediately.
Precautions for use What you need to know before taking Brexin
Take special care with BREXIN and always tell your doctor before using BREXIN; like all non-steroidal anti-inflammatory drugs, BREXIN can cause severe stomach and bowel reactions such as pain, bleeding and ulceration.
You must stop taking BREXIN immediately and contact your doctor if you have stomach pain or if you have any signs of stomach or bowel bleeding, such as passing black or bloodstained stools or vomiting blood. .
You should stop using BREXIN immediately and contact your doctor if you have an allergic reaction such as a rash, swelling of the face, wheezing or difficulty in breathing.
If you are over 70, your doctor may wish to minimize the duration of your treatment and visit you more often when you are being treated with BREXIN.
If you are over 70 or are taking other medicines such as corticosteroids or certain medicines to treat depression called selective serotonin reuptake inhibitors (SSRIs), or acetylsalicylic acid to prevent blood clots, your doctor may prescribe them. together with BREXIN a medicine to protect the stomach and intestines.
You should not take this medicine if you are over 80 years old.
If you have or have had any medical problems or any form of allergy or if you are not sure whether you can take BREXIN please tell your doctor before taking this medicine.
Tell your doctor if you are taking any other medicines, including medicines obtained without a prescription.
Medicines such as BREXIN may be associated with an increased risk of heart attack ("myocardial infarction") or stroke. Any risk is more likely with high doses and prolonged treatments. Do not exceed the recommended dose or duration of treatment.
If you have heart problems, have a history of stroke or think you may be at risk for these conditions (for example if you have high blood pressure, diabetes or high cholesterol or smoke) you should discuss your treatment with your doctor or pharmacist.
BREXIN, like other non-steroidal anti-inflammatory drugs, decreases platelet aggregation and lengthens clotting time; this eventuality should be remembered when carrying out haematological tests and requires vigilance when being treated simultaneously with drugs that inhibit platelet aggregation.
Caution should be exercised if you have a history of hypertension and / or heart failure as fluid retention and edema have been reported in association with NSAID therapy.
Particular caution is required if you have cardiovascular insufficiency, arterial hypertension, reduced hepatic or renal function, renal hypoperfusion, current or previous blood changes, and if you are on diuretic therapy.
If you are asthmatic, due to the interaction of the drug with the metabolism of arachidonic acid, crises of bronchospasm and possibly shock and other allergic phenomena may arise.
Since ocular alterations have been detected during NSAID therapy, it is recommended, in case of prolonged treatments, to carry out periodic ophthalmological checks.
As with other substances with similar action, increases in azotemia (levels of nitrogen in the blood) have been observed which do not progress beyond a certain level with continued administration and return to normal values once therapy is discontinued.
If you are diabetic it is advisable to have frequent blood tests.
Life-threatening skin rashes (Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported with the use of BREXIN, these initially appear as round red spots or circular patches often accompanied by blisters in the central part of the trunk.
Additional signs to note include ulcers in the mouth, throat, nose, genitals and conjunctivitis (red and swollen eyes).
These life-threatening rashes are often accompanied by flu-like symptoms. The rash may progress to the development of widespread blistering or peeling of the skin.
The highest risk of severe skin reactions occurs within the first few weeks of treatment.
If you have developed Stevens-Johnson syndrome or toxic epidermal necrolysis, BREXIN should no longer be used with the use of BREXIN.
If you develop a rash or these skin symptoms, stop taking BREXIN, consult a doctor urgently and inform him that you are taking this drug.
If you are planning to become pregnant, have fertility problems or are investigating fertility, you should discuss your therapy with your doctor.
Interactions What drugs or foods can change the effect of Brexin
Tell your doctor about any other medicines you are taking or have recently taken (in the last week) - even those bought without a prescription. Medicines can sometimes interfere with each other. Your doctor may restrict the use of BREXIN or other medicines, or you may need to take a different medicine. It is especially important to report the following cases:
- if you are taking aspirin or other non-steroidal anti-inflammatory medicines to relieve pain
- if you are taking corticosteroids, medicines used to treat a variety of conditions such as allergies and hormone imbalances
- if you are taking blood thinners such as warfarin to prevent blood clots
- if you are taking certain medicines for depression called selective serotonin reuptake inhibitors (SSRIs)
- if you are taking any medicines, such as aspirin, to prevent blood clots
- if you are taking diuretics, ACE inhibitors and angiotensin II antagonists
- used in cases of high blood pressure and heart disease
- if you are taking lithium
- used for the treatment of depression
- if you are taking quinolone antibacterials, used to treat bacterial infections
- if you use intrauterine devices
If you have any of these conditions, tell your doctor immediately.
USE OF BREXIN WITH FOOD AND BEVERAGE
It is advisable not to drink alcohol while taking BREXIN.
Warnings It is important to know that:
PREGNANCY AND BREASTFEEDING
Ask your doctor or pharmacist for advice before taking any medicine.
- If you are pregnant or if you are not sure whether you are pregnant, please tell your doctor as BREXIN is not suitable for you. If you are planning to become pregnant, have fertility problems or are investigating fertility, please inform your doctor anyway, as BREXIN may not be suitable for you.
- If you are breastfeeding, you should not take BREXIN. Ask your doctor for advice: it may be better to stop breastfeeding.
DRIVING VEHICLES AND USING MACHINERY
If you feel dizzy or unusually tired, take special care when driving or using machines.
IMPORTANT INFORMATION ABOUT SOME EXCIPIENTS OF BREXIN
The formulations in effervescent tablets and in sachets contain aspartame as a sweetener and therefore its use is contraindicated in cases of phenylketonuria.
The tablet and effervescent tablet formulations contain lactose and the sachet formulation contains sorbitol: if you have been diagnosed with "intolerance to some sugars, contact your doctor before taking this medicine.
Dosage and method of use How to use Brexin: Dosage
Always take BREXIN exactly as your doctor has told you. If in doubt, you should consult your doctor or pharmacist.
Your doctor will check you regularly to make sure you are taking the optimal dose of BREXIN. Your doctor will adjust your treatment to the lowest dose that best controls your symptoms. Under no circumstances should you change your dose without first informing your doctor.
Adults and the elderly:
The maximum daily dose of BREXIN is 20 milligrams to be taken as a single daily dose.
If you are over 70, your doctor may prescribe a lower daily dose and shorten the duration of treatment.
Your doctor may prescribe BREXIN together with another medicine to protect the stomach and intestines from possible side effects.
Do not increase the dose:
If you feel that the medicine is not very effective, always talk to your doctor.
If you forget to take BREXIN:
Take the medicine as soon as you remember. If it is almost time for your next dose, do not take the missed dose, but take the next dose at the correct time. Do not take a double dose.
Instructions for Use
Tablets:
To split the tablet, it should be placed on a flat surface with the median notch facing up. With a light pressure of the thumb, the tablet breaks into two equal parts.
Effervescent tablets: dissolve the effervescent tablet completely in a glass of water.
Sachets: by opening the sachet along the line indicated "half dose" a dose of 10 mg is obtained. Opening the sachet along the line indicated "full dose" gives a dose of 20 mg.
Overdose What to do if you have overdosed on Brexin
If you take more BREXIN than prescribed:
Symptoms: The most indicative symptoms of overdose are headache, vomiting, sleepiness, dizziness and syncope.
If you accidentally take an overdose of BREXIN, notify your doctor immediately or go to the nearest hospital.
If you have any further questions on the use of this product, ask your doctor.
Side Effects What are the side effects of Brexin
Like all medicines, BREXIN can cause side effects, although not everybody gets them.
There are prerequisites for BREXIN to be better tolerated at the gastrointestinal level than uncomplexed piroxicam; the less persistence of the active principle in the gastrointestinal lumen reduces, in fact, the risk of contact irritation.
Stop taking BREXIN immediately and contact your doctor:
- if you develop blisters, redness or peeling of the skin (skin rash), an "ulceration in any part of the body (eg skin, mouth, eyes, lips or tongue), or any other signs of an allergic reaction such as rash, swelling of the face , lips or tongue which may cause difficulty in breathing or wheezing
- if the skin or whites of the eyes are yellow (jaundice)
- if you have any signs of bleeding in your stomach or intestines, such as passing black or bloodstained stools or vomiting blood
All the side effects related to BREXIN are listed below.
Most common effects
- Digestive tract ulcers and gastrointestinal bleeding
- nausea, vomiting, diarrhea, flatulence, constipation, stomach acid, abdominal pain, ulcerative stomatitis, inflammatory bowel disease (colitis and Crohn's disease)
- Swelling of the ankles, legs and feet (fluid retention)
- Increased blood pressure
- Heart failure (difficulty in breathing and fatigue)
Less common effects
- Heart attack (myocardial infarction)
- Stroke
- Anorexia
- Tiredness
- Anemia
- Blisters, redness or peeling of the skin (rash) or ulceration anywhere on the body (e.g. skin, mouth, eyes, lips or tongue), or any other signs of allergic reactions such as skin rash, swelling of the face, lips, tongue , wheezing
- Yellow discoloration of the skin and eyes (jaundice)
- Increase in normal liver function values
- Pancreatitis
- Acute kidney failure, blood in the urine, difficulty urinating
- Increase in non-protein nitrogen in the blood (increased blood urea nitrogen)
- Swelling of the ankles, legs and feet (fluid retention)
- Increased blood pressure (hypertension)
- Nosebleeds
- Headache
- Drowsiness
- Deafness or ringing in the ear
- Dizziness
- Visual disturbances
- Malaise
- Changes in the blood and lymphatic system
- Gastritis
Rare effects
- Appearance of bruises
- Alteration of blood sugar values (hypo and hyperglycemia)
- Sweating
- Change in body weight
- Insomnia
- Depression
- Swelling, blistering or peeling of the skin
- Skin photosensitivity
- Dry mouth
- Erethism
- Alterations in the functioning of the bladder
- Shock
- Alopecia
- Nail growth alterations
- Fatal hepatitis
Very rare effects
Life-threatening skin rashes (Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Expiry and Retention
Keep BREXIN out of the reach and sight of children.
Do not use BREXIN after the expiry date stated on the outer carton and inner label. The expiry date refers to the last day of the month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What BREXIN contains
BREXIN contains the active ingredient Piroxicam-β-cyclodextrin
Each tablet contains: Piroxicam-β-cyclodextrin 191.2 mg equal to piroxicam 20 mg.
The other ingredients are: Lactose, Crospovidone, Sodium carboxymethyl starch, Hydrated colloidal silica, Modified starch, Magnesium stearate.
Each effervescent tablet contains: Piroxicam-β-cyclodextrin 191.2 mg equal to piroxicam 20 mg.
The other ingredients are: Lactose monohydrate, Glycine sodium carbonate, Fumaric acid, Aspartame, Macrogol 6000, Lemon flavor.
Each bipartite sachet of granules contains: Piroxicam-ß-cyclodextrin 191.2 mg equal to piroxicam 20 mg.
The other ingredients are: Sorbitol, Citrus flavor, Aspartame, Silica, colloidal anhydrous.
Each suppository contains: Piroxicam-ß-cyclodextrin 191.2 mg equal to piroxicam 20 mg.
The other ingredients are: Anhydrous colloidal silica, Solid semisynthetic glycerides.
Description of what BREXIN looks like and contents of the pack
BREXIN tablets: pale yellow, hexagonal tablets with division mark; cartons of 6, 10 and 30 tablets.
BREXIN effervescent tablets: pale yellow round tablets; cartons of 6, 10, 20 and 30 effervescent tablets
BREXIN granules for oral solution: pale yellow powder for extemporaneous solution contained in bipartite sachets; box of 20 sachets.
BREXIN suppositories: suppositories with cylindrical-conical shape and citrine yellow color; box of 10 suppositories.
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
BREXIN
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Tablets
One tablet contains:
Piroxicam-β-cyclodextrin 191.2 mg (equal to piroxicam 20 mg).
Effervescent tablets
One effervescent tablet contains:
Piroxicam-β-cyclodextrin 191.2 mg (equal to piroxicam 20 mg).
Granules for oral solution
A bipartite sachet of granules contains:
Piroxicam-β-cyclodextrin 191.2 mg (equal to piroxicam 20 mg).
Suppositories
One suppository contains:
Piroxicam-β-cyclodextrin 191.2 mg (equal to piroxicam 20 mg).
For excipients, see 6.1
03.0 PHARMACEUTICAL FORM
Tablets, effervescent tablets, granules for oral solution, suppositories.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Piroxicam is indicated for the symptomatic treatment of osteoarthritis, rheumatoid arthritis or ankylosing spondylitis. Due to its safety profile piroxicam is not a first choice NSAID (see sections 4.2, 4.3 and 4.4). The decision to prescribe piroxicam should be based on an assessment of the individual patient's overall risks (see sections 4.3 and 4.4).
04.2 Posology and method of administration
Prescribing for piroxicam should be initiated by a physician experienced in the diagnosis and treatment of patients with inflammatory or degenerative rheumatic diseases.
The maximum recommended daily dose is 20 mg.
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms. The benefit and tolerability of treatment should be reassessed within 14 days. If continued treatment is necessary. , the latter must be associated with frequent re-evaluation.
Since the use of piroxicam has been shown to be associated with an increased risk of complications affecting the gastrointestinal tract, the possible need for combined therapy with gastro-protective agents (eg misoprostol or proton pump inhibitors) should be carefully evaluated, particularly in elderly patients.
Dosage and indications in children have not yet been established.
In the treatment of elderly patients the posology must be carefully established by the doctor who will have to evaluate a possible reduction of the dosages indicated above.
Tablets and sachets: 1 tablet or 1 effervescent tablet or 1 full dose sachet (20 mg) per day.
Suppositories: one suppository of 20 mg per day.
Instructions for Use:
Tablets - To split the tablet, place it on a flat surface with the median notch facing up. With a light pressure of the thumb, the tablet breaks into two equal parts.
Effervescent tablets - Dissolve the effervescent tablet completely in a glass of water.
Sachets - Opening the sachet along the line indicated "half dose" gives a dose of 10 mg. Opening the sachet along the line indicated "full dose" gives a dose of 20 mg.
04.3 Contraindications
• Hypersensitivity to the active substance or to any of the excipients.
• Previous history of gastrointestinal ulcer, bleeding or perforation.
• Previous gastrointestinal disorders that predispose to bleeding disorders such as ulcerative colitis, Crohn's disease, gastrointestinal cancer or diverticulitis.
• Patients with active peptic ulcer, gastrointestinal inflammatory disorders or gastrointestinal bleeding.
• Patients with gastritis, dyspepsia, severe liver and kidney disorders, moderate or severe heart failure, severe hypertension, severe blood disorders, bleeding diathesis
• Concomitant use of other NSAIDs, including selective COX-2 inhibitors and acetylsalicylic acid, administered at analgesic doses.
• Concomitant use of anticoagulants.
• History of severe drug allergic reactions of any kind, particularly skin reactions such as erythema multiforme, Stevens-Johnson syndrome, necrotic epidermolysis.
• Previous skin reactions (regardless of severity) to piroxicam, other NSAIDs and other medicines.
• Known or suspected pregnancy, during lactation and in children (see 4.6).
There is a possibility of cross-sensitivity with acetylsalicylic acid or other non-steroidal anti-inflammatory drugs. The product must not be administered to patients in whom acetylsalicylic acid or other non-steroidal anti-inflammatory drugs cause symptoms of asthma, rhinitis, nasal polyposis, angioedema, urticaria.
The formulations in effervescent tablets and in sachets contain aspartame as a sweetener and therefore its use in cases of phenylketonuria is contraindicated.
04.4 Special warnings and appropriate precautions for use
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms.
The clinical benefit and tolerability of the treatment should be reassessed periodically and the treatment should be stopped immediately upon the appearance of the first signs of skin reactions or major gastrointestinal events.
Gastrointestinal (GI) effects, risk of gastrointestinal ulceration, bleeding and perforation
NSAIDs, including piroxicam, can cause serious gastrointestinal events including bleeding, ulceration and perforation of the stomach, small intestine or colon, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients being treated with NSAIDs.
Both short and long-term exposure to NSAIDs carries an increased risk of serious GI events. Evidence from observational studies suggests that piroxicam, compared to other NSAIDs, may be associated with an increased risk of severe gastrointestinal toxicity. .
Patients with significant risk factors for serious GI events should be treated with piroxicam only after careful consideration (see section 4.3 and section below).
The possible need for combined therapy with gastro-protective agents (eg misoprostol or proton pump inhibitors) must be carefully considered (see section 4.2).
Serious gastrointestinal complications
Identification of subjects at risk
The risk of developing serious gastrointestinal complications increases with age. An age over 70 is associated with a higher risk of complications. Administration to patients over 80 years of age should be avoided.
Patients on concomitant treatment with oral corticosteroids, selective serotonin reuptake inhibitors (SSRIs), anticoagulants such as warfarin or antiplatelet agents, such as low-dose acetylsalicylic acid, have an increased risk of serious gastrointestinal complications (see below and par. 4.5). As with other NSAIDs, the use of piroxicam in combination with gastro-protective agents (eg misoprostol or proton pump inhibitors) should be considered in these at-risk patients.
Patients and physicians should pay attention to the signs and symptoms of gastrointestinal ulcer and / or bleeding during treatment with piroxicam. Patients should be asked to report any new or unusual abdominal symptoms that occur during treatment. If a gastrointestinal complication is suspected during the course of treatment, the use of piroxicam should be discontinued immediately and further clinical evaluation and alternative treatment considered.
Cardiovascular and cerebrovascular effects
Adequate monitoring and instruction are required in patients with a history of hypertension and / or congestive heart failure as fluid retention and edema have been reported in association with NSAID treatment.
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). There are insufficient data to exclude a similar risk for piroxicam.
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with piroxicam after careful consideration. Similar considerations should be made before initiating long-term treatment in patients with risk factors for cardiovascular disease (eg hypertension, hyperlipidaemia, diabetes mellitus, smoking).
Piroxicam decreases the platelet aggregating power and lengthens the coagulation time; this characteristic must be considered when haematological tests are performed and when a patient is being treated with other substances that inhibit platelet aggregation.
Patients in whom renal function is impaired should be periodically monitored as the inhibition of prostaglandin synthesis caused by piroxicam in these patients can lead to a severe decrease in renal perfusion which may lead to acute renal failure. In this regard, elderly patients and those on diuretic therapy are considered at risk.
Caution should also be taken when treating patients with impaired liver function. Also for these it is advisable to resort to periodic monitoring of clinical and laboratory parameters, especially in case of prolonged treatment.
For the interaction of the drug with the metabolism of arachidonic acid, bronchospasm crises and possibly shock and other allergic phenomena may arise in asthmatics and predisposed subjects.
Since ocular alterations have been detected during NSAID therapies, it is recommended, in case of prolonged treatments, to carry out periodic ophthalmological checks. It is also advisable to frequently check the glycemic rate in diabetic patients and the prothrombin time in subjects undergoing a concomitant anticoagulant treatment with dicumarol derivatives.
Skin reactions
Evidence from observational studies suggests that piroxicam, compared to other non-oxicam NSAIDs, may be associated with a higher risk of severe skin reactions.
The following life-threatening skin reactions have been reported with the use of BREXIN: 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 and TEN occurs in the first few weeks of treatment.
If symptoms or signs of SJS or TEN occur (e.g. progressive skin rash often with blistering or mucosal lesions) BREXIN treatment should be discontinued.
The best results in the management of SJS and TEN are obtained with an early diagnosis and immediate discontinuation of therapy with any suspect drug. Early discontinuation is associated with a better prognosis.
If the patient has developed SJS or TEN with the use of BREXIN, BREXIN should no longer be used in this patient.
The use of piroxicam, like any drug that inhibits prostaglandin synthesis and cyclooxygenase, is not recommended in women intending to become pregnant.
Piroxicam administration should be discontinued in women who have fertility problems or who are undergoing fertility investigations.
The tablet and effervescent tablet formulations contain lactose: patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
The sachet formulation contains sorbitol: patients with rare hereditary problems of fructose intolerance should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
Acetylsalicylic acid or other NSAIDs . As with other NSAIDs, the use of piroxicam together with acetylsalicylic acid or other NSAIDs, including other formulations of piroxicam, should be avoided as available data do not allow to demonstrate that these combinations produce a greater improvement than that obtained with piroxicam. alone; furthermore, the possibility of adverse reactions is increased (see section 4.4.). Studies in humans have shown that concomitant use of piroxicam and acetylsalicylic acid reduces the plasma concentration of piroxicam by approximately 80% of the usual value.
Piroxicam interacts with acetylsalicylic acid, with other non-steroidal anti-inflammatory substances and with substances that inhibit platelet aggregation (see 4.3 and 4.4).
Corticosteroids : increased risk of gastrointestinal ulcer or bleeding (see section 4.4).
Anticoagulants : NSAIDs, including piroxicam, may potentiate the effects of anticoagulants, such as warfarin. Therefore, the use of piroxicam together with anticoagulants such as warfarin should be avoided (see section 4.3).
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs) : increased risk of gastrointestinal bleeding (see section 4.4.).
Diuretics, ACE inhibitors and angiotensin II 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 antagonist angiotensin II and agents that inhibit the cyclo-oxygenase system may lead to further deterioration of renal function, including possible acute renal failure, usually reversible. These interactions should be considered in patients taking piroxicam concomitantly with ACE inhibitors or angiotensin II antagonists.
Therefore, the combination should be administered with caution, especially in elderly patients.
Patients should be adequately hydrated and monitoring of renal function should be considered after initiation of concomitant therapy.
In case of concomitant use of drugs containing potassium or diuretics that cause potassium retention there is an additional risk of an increase in the serum potassium concentration (hyperkalaemia).
Lithium : The concomitant administration of lithium and NSAIDs causes an increase in plasma lithium levels.
Piroxicam binds a lot to proteins and is therefore likely to displace other protein-bound drugs. Doctors will need to monitor patients on piroxicam and high protein binding drugs for any dose adjustments. Following administration of cimetidine, the absorption of piroxicam shows a slight increase. This increase, however, has not been shown to be clinically significant.
Avoid alcohol intake.
Piroxicam can "decrease" the effectiveness of intrauterine devices.
The use of non-steroidal anti-inflammatory drugs at the same time as quinolone drugs is not recommended.
04.6 Pregnancy and lactation
Piroxicam is contraindicated during pregnancy, established or suspected, and breastfeeding.
Pregnancy
Inhibition of prostaglandin synthesis can adversely affect pregnancy and / or embryo / fetal development.
Results of epidemiological studies suggest an increased risk of miscarriage and cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiac malformations increased from less than 1% to approximately 1.5%. The risk has been considered to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased loss of pre- and post-implantation and of embryo-fetal mortality.
In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period.
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 progress to renal failure with oligo-hydroamniosis;
the mother and the newborn, at the end of pregnancy, to:
- possible prolongation of bleeding time, and antiplatelet effect which may occur even at very low doses;
- inhibition of uterine contractions resulting in delayed or prolonged labor.
04.7 Effects on ability to drive and use machines
Piroxicam can modify the state of vigilance in such a way as to compromise the driving of motor vehicles and the engagement in activities that require alertness.
04.8 Undesirable effects
Gastrointestinal: the most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, gastrointestinal perforation or haemorrhage, sometimes fatal, may occur, particularly in the elderly (see section 4.4).
Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration of piroxicam (see section 4.4).
Gastritis has been observed less frequently.
There are conditions for BREXIN to be better tolerated in the gastrointestinal tract than uncomplexed piroxicam; the less persistence of the active principle in the gastrointestinal lumen reduces, in fact, the risk of contact irritation.
Edema, hypertension and heart failure have been reported in association with NSAID treatment.
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 Section 4.4).
Other side effects reported: anorexia, hypersensitivity phenomena such as skin rashes, headache, dizziness, drowsiness, malaise, tinnitus, deafness, asthenia, changes in haematological parameters, decreased hemoglobin and hematocrit, anemia.
As with other substances with similar action, increases in azotemia have been observed in some patients which do not progress beyond a certain level with continued administration; they return to normal values once therapy is discontinued.
Rarely, allergic edema of the face and hands, increased skin photosensitivity, visual disturbances, aplastic anemia, haemolytic anemia, pancytopenia, thrombocytopenia, Schoenlein-Henoch purpura, eosinophilia, increased liver function indices, jaundice may occur with rare cases of fatal hepatitis.
However, piroxicam therapy should be discontinued if clinical signs and symptoms of hepatic disorders occur.
Rare cases of pancreatitis have been reported. Some cases of haematuria, dysuria, acute renal failure, water retention, which can manifest itself in the form of edema, especially in the sloping regions of the lower limbs, or cardiocirculatory disorders (hypertension, decompensation) have been reported.
Serious skin adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported very rarely (see section 4.4).
In sporadic cases: epistaxis, dry mouth, erythema multiforme, ecchymosis, skin peeling, sweating, hypoglycemia, hyperglycemia, changes in body weight, erethism, insomnia, depression, and very rarely bladder dysfunction, shock and warning symptoms, alopecia have been reported , disorders of nail growth.
04.9 Overdose
Symptoms: The most indicative symptoms of overdose are headache, vomiting, drowsiness, dizziness and syncope.
In the event of an overdose, symptomatic supportive therapy is indicated.
Although no studies have been performed so far, hemodialysis is unlikely to be useful in facilitating the elimination of piroxicam, as the drug is characterized by high plasma protein binding.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: non-steroidal anti-inflammatory / antirheumatic drugs.
ATC code: M01AC01.
Piroxicam, belonging to the class of benzothiazine carboxiamides-N-heterocyclics, is the first compound of a new class of NSAIDs, the oxicams. Piroxicam has anti-inflammatory, analgesic and antipyretic activity, pharmacological actions similar to those of other non-steroidal anti-inflammatory drugs. Animal studies have shown that piroxicam affects cell migration to sites of inflammation. Like other NSAIDs, piroxicam interferes with prostaglandin synthesis by inhibiting cyclooxygenase. Unlike indomethacin, piroxicam is a reversible inhibitor of prostaglandin synthesis. In a study of 9 patients with active rheumatoid arthritis, piroxicam (20 mg / day for 15 days) was shown to markedly lower the function of polymorphonuclear cells (PMN), the production of superoxide anions in peripheral blood and synovial fluid and the concentration of PMN and PMN elastase in the synovial fluid. The modulation of PMN responses may contribute to the anti-inflammatory action of piroxicam.
BREXIN is a new formulation of piroxicam in which the active compound is complexed with β-cyclodextrin.
The β-cyclodextrin, a cyclic oligosaccharide deriving from the enzymatic hydrolysis of common starch, thanks to its particular chemical structure, can "form inclusion complexes (" molecular encapsulation ") with various drugs, improving the characteristics of solubility, stability and bioavailability.
Piroxicam-β-cyclodextrin was found to have high water solubility and faster absorption than piroxicam after oral and rectal administration.
The better solubility leads to a rapid increase in the plasma levels of piroxicam and to an early reaching of the peak value which is clinically manifested with a more rapid onset and a greater intensity of the analgesic and anti-inflammatory effect.
On the other hand, the prolonged plasma half-life in BREXIN is unchanged compared to piroxicam, which makes it possible to administer a single daily dose.
BREXIN, thanks to its pharmacodynamic and pharmacokinetic properties, is suitable for the treatment of rheumatic and / or inflammatory diseases with a marked painful component, such as to seriously compromise the general conditions and normal activity of patients and in which an intervention is necessary. therapeutic of rapid and intense efficacy.
In the carrageenan-induced plantar edema test, BREXIN showed an earlier anti-inflammatory activity than that of piroxicam; in the first hours after administration, in fact, BREXIN was 2-3 times more active than piroxicam both orally and rectally. .
The analgesic activity was studied in mice, orally, in the phenylquinone seizure test; after 5 minutes from treatment, 99% was obtained with BREXIN and 78% of the maximum inhibitory effect with piroxicam. it is kept constant, for both preparations, in the two hours following the treatment.
The therapeutic index values for BREXIN and piroxicam were calculated on the basis of the comparisons between the anti-inflammatory effects, evaluated in rats by means of the carrageenan-induced plantar edema test, and the gastrologic effects observed in the same animal species.
BREXIN orally was found to have a therapeutic index 2.65 times higher than oral piroxicam; the therapeutic index of BREXIN by rectal route was 2.31 times higher than the same BREXIN by oral route.
The improvement in gastrointestinal tolerability of BREXIN was confirmed in humans by three double-blind controlled studies in which the presence of blood in the faeces was assessed using the 51Cr-labeled erythrocyte technique. In all studies the duration of treatment was was 28 days Two studies demonstrated significantly less blood loss in stool with BREXIN towards the end of the 4-week study period, while a similar trend was observed in the third study.
In a further study, a comparison of the gastric tolerability of BREXIN, piroxicam, indomethacin and placebo after administration for a period of 14 days was carried out: the potential difference in the gastric wall (GPD max) was also evaluated. BREXIN produced fewer effects on this parameter than piroxicam and indomethacin with a positive correlation between GPD max and endoscopic examination results.
BREXIN therefore has a more favorable relationship between pharmacodynamic activity and gastrotoxicity, compared to piroxicam.
05.2 Pharmacokinetic properties
By oral or rectal administration of BREXIN only the active substance (piroxicam) is absorbed into the circulation and not the complex as such.
In healthy volunteers, with BREXIN, compared to an equidose of piroxicam (20 mg), a significant advance in the onset of the plasma peak of piroxicam (within 30 "-60" compared to the mean time of 2 hours observed with uncomplexed piroxicam was observed , orally, and within 2 hours, compared to 6-7 hours for piroxicam as it is, by rectal route). The elimination parameters, Kel and half-life, do not show variations with respect to the values of piroxicam, as the complexation with β-cyclodextrin affects only the absorption kinetics but not the elimination kinetics.
The urinary excretion of the active principle over 72 hours was approximately 10% of the administered dose for all BREXIN formulations and for piroxicam as it is.
The β-cyclodextrin as such after oral administration of the complex was not found either "in the plasma or" in the urine. B-cyclodextrin is metabolized in the colon by the bacterial microflora into linear dextrins, maltose and glucose.
05.3 Preclinical safety data
Non-clinical data reveal no special hazard to humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential and reproductive toxicity.
As with other substances that inhibit prostaglandin synthesis, piroxicam also increases the incidence of dystocia and post-term births in animals when the drug continues during pregnancy. The administration of NSAIDs to pregnant rats can cause constriction. of the fetal ductus arteriosus. Furthermore, in the last trimester of pregnancy, gastroduodenal toxicity increases.
In non-clinical studies, some effects such as gastrointestinal lesions and renal papillary necrosis were observed, detected at the maximum dose used, which is approximately 60 times greater than the indicated dose for humans.
This exposure to piroxicam is therefore considered to be sufficiently in excess of the maximum exposure in humans, indicating little relevance of these effects for the clinical use of the drug.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Tablets: lactose, crospovidone, sodium carboxymethyl starch, colloidal hydrated silica, modified starch, magnesium stearate.
Effervescent tablets: lactose monohydrate, sodium carbonate glycine, fumaric acid, aspartame, macrogol 6000, lemon flavor.
Granules for oral solution: sorbitol, citrus flavor, aspartame, anhydrous colloidal silica.
Suppositories: anhydrous colloidal silica, solid semisynthetic glycerides.
06.2 Incompatibility
Not known.
06.3 Period of validity
Tablets, sachets, suppositories: 3 years.
Effervescent tablets: 2 years.
The period of validity indicated refers to the product in intact packaging, correctly stored.
06.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Tablets - Inner package: tablets in blister packs of PVC / PVDC coupled closed with Al / PVDC. External packaging: printed cardboard box.
Effervescent tablets - Inner package: Al / PE strip. External packaging: printed cardboard box.
Sachets - Inner packaging: heat-sealable sachets in Al-sized paper coupled with low density polyethylene (LDPE) with separation and pre-cut septum. External packaging: printed cardboard box.
Suppositories - Inner package: suppositories in PVC / PE blisters. External packaging: printed cardboard box.
Box of 6 tablets 20 mg
Box of 10 tablets 20 mg
Box of 30 tablets 20 mg
Box of 6 effervescent tablets 20 mg
Box of 10 effervescent tablets 20 mg
Box of 20 effervescent tablets 20 mg
Box of 30 effervescent tablets 20 mg
Box of 20 bipartite sachets 20 mg
Box of 10 suppositories 20 mg
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
PROMEDICA S.r.l. - Via Palermo 26 / A - 43100 Parma
08.0 MARKETING AUTHORIZATION NUMBER
BREXIN 20 mg tablets - 6 tablets: 026446118
BREXIN 20 mg tablets - 10 tablets: 026446120
BREXIN 20 mg tablets - 30 tablets: 026446056
BREXIN 20 mg effervescent tablets - 6 effervescent tablets: 026446070
BREXIN 20 mg effervescent tablets - 10 effervescent tablets: 026446082
BREXIN 20 mg effervescent tablets - 20 effervescent tablets: 026446094
BREXIN 20 mg effervescent tablets - 30 effervescent tablets: 026446106
brexin 20 mg granules for oral solution - 20 bipartite sachets: 026446031
brexin 20 mg suppositories - 10 suppositories: 026446043
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
30 tablets - bipartite sachets - suppositories: 07/27/1987
6 and 10 tablets: 02/07/1999
Effervescent tablets: 22/12/1999
10.0 DATE OF REVISION OF THE TEXT
January 2012
