Active ingredients: Mesalazine)
Mesavancol 1200 mg gastro-resistant prolonged-release tablets
Why is Mesavancol used? What is it for?
Pharmacotherapeutic group: aminosalicylic acid and analogues
Mesavancol®, in prolonged-release gastro-resistant tablets, contains the active ingredient mesalazine, which is an anti-inflammatory drug for the treatment of ulcerative colitis.
Ulcerative colitis is a disease of the colon (large intestine) and rectum in which the inner lining of the intestine becomes red and swollen (inflamed), with symptoms such as frequent bowel movements and bloody stools, accompanied by stomach cramps.
When given for an acute episode of ulcerative colitis, Mesavancol® works along the entire colon and rectum to treat inflammation and reduce symptoms. The tablets can also be taken to help prevent ulcerative colitis from returning.
Contraindications When Mesavancol should not be used
Do not take Mesavancol®
- If you are allergic (hypersensitive) to a class of drugs known as salicylates (which includes aspirin).
- If you are allergic (hypersensitive) to mesalamine or any of the other ingredients of this medicine (listed in section 6 of this leaflet).
- In case of severe kidney or liver problems.
Precautions for use What you need to know before taking Mesavancol
Talk to your doctor before using Mesavancol
- If you have any kidney or liver problems.
- If you have previously had heart inflammation (which could be the result of a heart infection).
- If you have previously had allergies to sulfasalazine (another medicine used to treat ulcerative colitis).
- If you have a narrowing or closing of the stomach or intestines.
- If you have lung problems.
Before and periodically during treatment with Mesavancol, your doctor may order urine and blood tests to check that the kidneys and liver are working well and that the blood tests are normal.
Children and adolescents
Mesavancol is not recommended for children and adolescents below 18 years of age due to a lack of data on safety and efficacy.
Interactions Which drugs or foods can modify the effect of Mesavancol
Other medicines and Mesavancol
Studies have shown that Mesavancol does not interfere with the following antibiotics, used to treat infections: amoxicillin, metronidazole or sulfamethoxazole.
However, Mesavancol can interact with other medicines. Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
- Mesalazine or sulfasalazine (for the treatment of ulcerative colitis).
- Non-steroidal anti-inflammatory drugs (for example drugs containing aspirin, ibuprofen or diclofenac).
- Azathioprine or 6-mercaptopurine (known as 'immunosuppressive' drugs which reduce the activity of your immune system).
- Coumarin anticoagulants (medicines that increase the time it takes for blood to clot). For example warfarin.
Mesavancol® with food and drink
Mesavancol® should be taken at the same time each day with meals. The tablets must be swallowed whole, the tablets must not be chewed or crushed.
Warnings It is important to know that:
Pregnancy and breastfeeding
Since mesalamine crosses the placenta during pregnancy and is excreted in small amounts in breast milk, caution should be exercised when taking Mesavancol® during pregnancy or breastfeeding.
If you are pregnant or breastfeeding, think you are pregnant, or are planning to have a baby, ask your doctor for advice on whether you can take Mesavancol®.
Interference with laboratory tests
If you have had urine tests, it is important to tell your doctor or nurse that you are taking, or have recently taken, the drug as it may affect the results of some tests.
Driving and using machines
Mesavancol® is unlikely to affect your ability to drive or operate machinery.
Dose, Method and Time of Administration How to use Mesavancol: Posology
Always take this medicine exactly as your doctor has told you. If in doubt, you should consult your doctor or pharmacist.
The recommended adult dose is 2.4 g - 4.8 g (two to four tablets) to be taken once daily for an acute episode of ulcerative colitis. If you are taking the higher dose of 4.8g / day, your doctor will need to see you after 8 weeks of treatment.
Once your symptoms have resolved, and to help prevent another episode from coming back, your doctor may prescribe 2.4 g (two tablets) to be taken once a day.
Remember to take your tablets at the same time every day with meals. The tablets must be swallowed whole and must not be chewed or crushed.
During treatment with this medicine be sure to drink fluids to stay well hydrated especially after severe or prolonged episodes of vomiting and / or diarrhea, high fever or heavy sweating.
Use in children and adolescents
It is recommended not to give Mesavancol® to children and adolescents under 18 years of age due to a lack of data on safety and efficacy.
Overdose What to do if you have taken too much Mesavancol
If you take more Mesavancol® than you should
If you take too much Mesavancol®, you may experience one or more of the following symptoms: tinnitus (ringing or ringing in the ears), dizziness, headache, confusion, sleepiness, "shortness of breath", excessive water loss (associated with sweating, diarrhea and vomiting ), decreased blood sugar levels (which can cause you to feel unwell), faster breathing, changes in blood chemistry and an increase in body temperature.
If you take too many tablets, contact a doctor, pharmacist or emergency room immediately. Take the pack of tablets with you.
If you forget to take Mesavancol®
It is important that you take your Mesavancol® tablets every day, even when you are not experiencing symptoms of ulcerative colitis. You will always have to finish the prescribed course of treatment.
If you forget to take your tablets, take them as usual the next day. Do not take a double dose to make up for a forgotten dose.
If you stop using Mesavancol®
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 Mesavancol
Tell your doctor immediately
- If you experience symptoms such as cramps, severe stomach pain, excessive stools (diarrhea) and with blood, fever, headache or rash. These symptoms could be a sign of Acute Intolerance Syndrome which can occur during an acute episode of ulcerative colitis. This is a serious condition that occurs rarely, but indicates that treatment must be stopped immediately.
- If you develop unexplained bruising (without trauma), skin rash, anemia (feeling tired, weak and pale, especially on the lips, nails and inside the eyelids), fever (rise in temperature), sore throat or unusual bleeding (e.g. nosebleed).
- If you develop allergic swelling of the tongue, lips and around the eyes.
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Common side effects, which occur in less than 1 in 10 patients: headache; change in blood pressure, flatulence (excessive passage of gas through the rectum), nausea (feeling sick), stomach bloating or pain, inflammation causing abdominal pain or diarrhea; diarrhea, indigestion, vomiting, abnormal liver function tests, itchy skin, rash, joint pain, back pain, weakness, fatigue (excessive tiredness); fever (rise in temperature).
Uncommon side effects, which have been seen in less than 1 in 100 patients: reduction in platelets which increases the risk of bleeding and bruising; dizziness feelings of sleepiness or tiredness; tremors or tremors; ear pain; increased heart rate; sore throat; inflammation of the pancreas (associated with pain in the upper abdomen and back and feeling unwell); rectal polyp (benign type of tumor in the rectum which can cause symptoms such as constipation and / or bleeding); acne; hair loss; muscular pain; urticaria; swelling of the face.
Rare side effects, seen in less than 1 in 1000 patients are: kidney failure, severe reduction in the number of white blood cells which increases the chances of infections.
The following side effects have been reported, but it is not known exactly how often they occur:
Severe decrease in the number of blood cells which can cause weakness or bruising; reduction of blood cells; allergic reaction (hypersensitivity); severe allergic reaction which causes difficulty in breathing or dizziness; severe illness with blistering of the skin, mouth, eyes and genitals; allergic reaction that causes skin rashes, fever and inflammation of internal organs; neuropathy (nerve damage or abnormality causing a feeling of numbness and tingling); inflammation of the heart and the outer lining of the heart; lung inflammation; difficulty breathing or wheezing; gallstones; hepatitis (inflammation of the liver which produces flu-like symptoms and jaundice); allergic swelling of the tongue, lips and area around the eyes; redness of the skin; kidney problems (such as inflammation and kidney damage).
If you get any side effects, contact your doctor. 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 or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information on safety. of this medicine.
Expiry and Retention
- Keep this medicine out of the sight and reach of children.
- Store at a temperature below 25 ° C.
- Store in the original package to protect the medicine from moisture.
- Do not use this medicine after the expiry date which is stated on the package after "Expiry". 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.
Composition and pharmaceutical form
What Mesavancol® contains
The active ingredient is Mesalazine 1200 mg
The other ingredients are: Carmellosa sodium; Carnauba wax; Stearic Acid; Colloidal hydrated silica; Sodium starch-glycolate (Type A); Talc; Magnesium stearate; Methacrylic acid-methyl methacrylate copolymer (1: 1); Methacrylic acid-methyl methacrylate copolymer (1: 2); Triethyl citrate; Titanium dioxide (E171); Red Iron Oxide (E172); Macrogol 6000.
Description of what Mesavancol® looks like and contents of the pack
Mesavancol® is available in aluminum-coated blisters, contained in a cardboard box. The package can contain 60 or 120 tablets. Not all pack sizes may be marketed.
The red-brown tablets are oval in shape and marked S476
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
MESAVANCOL
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 1200 mg mesalamine
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Gastro-resistant, prolonged-release tablets.
Red-brown, ellipsoidal shaped, coated tablet, debossed with S476 on one side.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Induction of clinical and endoscopic remission in patients with mild to moderate ulcerative colitis. Maintaining remission.
04.2 Posology and method of administration
Mesavancol is administered orally once a day. The tablets should not be chewed or crushed and should be taken with meals.
Adults, including the elderly (> 65 years)
To induce remission: 2.4 to 4.8 g (two to four tablets) to be taken once daily.
The higher dose of 4.8 g / day is recommended in patients unresponsive to low doses of Mesavancol.
When the highest dose (4.8 g / day) is used the treatment effect should be evaluated at the eighth week.
For maintenance of remission: 2.4g (two tablets) to be taken once daily.
Children and adolescents:
Mesavancol is not recommended for use in children and adolescents below 18 years of age due to a lack of data on safety and efficacy.
No specific studies have been performed on the use of Mesavancol in patients with hepatic or renal insufficiency (see sections 4.3 and 4.4).
04.3 Contraindications
Hypersensitivity to mesalamine or to any of the excipients of Mesavancol.
Patients with severe renal impairment (glomerular filtration rate 2) and / or severe hepatic impairment.
04.4 Special warnings and appropriate precautions for use
Cases of renal impairment, minimal changes in patients with pre-existing nephropathy and acute / chronic interstitial nephritis have been reported in association with mesalamine-containing preparations and mesalamine prodrugs. Mesavancol should be used with caution in patients with known mild to moderate renal dysfunction. Renal function assessment is recommended for all patients prior to initiation of therapy, and at least twice a year during treatment.
Patients with chronic impaired lung function, especially with asthma, are at risk of developing sensitization reactions and should be closely monitored.
Rare cases of severe blood dyscrasias have been reported following mesalamine treatment. In the event that the patient develops haemorrhages of unclear etiology, hematomas, purpura, anemia, fever or laryngitis, haematological investigations should be conducted. If blood dyscrasia is suspected, treatment should be stopped. (see sections 4.5 and 4.8).
Rare mesalamine-induced cardiac hypersensitivity reactions (myocarditis and pericarditis) have been reported with other mesalamine-containing preparations. Caution should be exercised when prescribing this drug to patients with conditions predisposing to myocarditis or pericarditis. If such a hypersensitivity reaction is suspected, products containing mesalamine should not be reintroduced.
Mesalamine has been associated with an acute intolerance syndrome that may be difficult to distinguish from a relapse of inflammatory bowel disease. Although the exact frequency has not yet been determined, it occurred in 3% of patients in controlled clinical trials of mesalamine or sulfasalazine. Symptoms include cramps, acute abdominal pain and bloody diarrhea, sometimes fever, headache and erythema. In case of suspected acute intolerance syndrome, treatment should be stopped immediately and products containing mesalamine should not be reintroduced.
There have been reports of elevated liver enzyme levels in patients treated with mesalamine-containing preparations. Caution is advised when administering Mesavancol to patients with hepatic impairment.
Caution should be used when treating patients allergic to sulfasalazine due to a potential risk of cross-hypersensitivity reactions between sulfasalazine and mesalamine.
Organic and functional obstructions of the upper gastrointestinal tract can delay the action of the product.
04.5 Interactions with other medicinal products and other forms of interaction
No interaction studies have been performed between Mesavancol and other drugs. However, interactions have been reported between other mesalamine-containing products and other drugs.
Caution is advised in concomitant use of mesalamine and agents known to be renal toxic, including non-steroidal anti-inflammatory drugs (NSAIDs) and azathioprine, as these drugs may increase the risk of adverse kidney reactions.
Mesalamine inhibits thiopurine methyltransferase. In patients treated with azathioprine or 6-mercaptopurine, caution is recommended in concomitant use of mesalazine, as it may increase the risk of blood dyscrasias (see sections 4.4 and 4.8).
Co-administration with coumarin anticoagulants such as warfarin, may result in a decrease in anticoagulant activity. The prothrombin time should be closely monitored if this association cannot be avoided.
Administration of Mesavancol with meals is recommended (see sections 4.2 and 5.2).
04.6 Pregnancy and lactation
Pregnancy
Data on a limited number of exposed pregnancies indicate no undesirable effects of mesalamine on pregnancy or on the health of the fetus / newborn. Mesalazine crosses the placenta but is found in concentrations in the fetus much lower than those found in adults after therapeutic use. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal / fetal development, parturition or postnatal development. Mesalamine should not be used during pregnancy unless absolutely necessary. Caution should be exercised when using high doses of mesalamine.
Feeding time
Mesalamine is excreted in breast milk in low concentrations. The acetylated form of mesalamine is excreted in breast milk at higher concentrations. Caution should be used if mesalamine is administered during lactation and only if the benefit outweighs the risk. Acute sporadic diarrhea has been reported in nursing infants.
Fertility
Studies on mesalamine have not shown sustained effects on male fertility
04.7 Effects on ability to drive and use machines
No studies on the ability to drive and use machines have been performed. Mesavancol is thought to have negligible influence on the ability to drive or use machines.
04.8 Undesirable effects
Approximately 14% of subjects experienced adverse drug reactions (ADRs) associated with the use of Mesavancol. No new events occurred with an incidence ≥1% during maintenance therapy. Most events were transient in nature. , and mild or moderate in severity None of the adverse drug reactions were reported with a frequency greater than 10%.
The most commonly reported adverse drug reactions during acute treatment were flatulence, nausea or headache; these reactions were not dose related and occurred in less than 3% of patients treated with Mesavancol.
Other events reported with Mesavancol were less frequent and the incidences are shown in the table below:
Mesalamine has been associated with the following events:
Mesalamine induces nephrotoxicity and caution should be exercised in patients who develop renal insufficiency during treatment.
See also section 4.4 Special warnings and precautions for use.
04.9 Overdose
No cases of overdose have been reported.
Mesavancol contains an aminosalicylate, and symptoms of salicylate toxicity include tinnitus, dizziness, headache, confusion, somnolence, pulmonary edema, dehydration following sweating, diarrhea and vomiting, hypoglycemia, hyperventilation, disturbed electrolyte balance and blood pH and hyperthermia.
Although there is no direct experience with Mesavancol, conventional therapy in case of salicylate toxicity could be of benefit in the presence of acute overdose. Hypoglycemia, fluid and electrolyte decompensation must be corrected by administering appropriate therapy. Adequate renal function must be maintained.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Aminosalicylic acid and analogues, ATC code: A07EC02
Mesalamine is an aminosalicylate. The mechanism of action of mesalamine is not fully understood, but it appears to act topically. The mucosal production of arachidonic acid metabolites, through both the cyclooxygenase and lipooxygenase mechanisms, increases in patients suffering from chronic inflammatory bowel disease, and it is possible that mesalazine reduces inflammation by blocking cyclooxygenase and inhibiting production of prostaglandins in the colon. Recent data also suggest that mesalazine may inhibit the activation of NFκB, a nuclear transcription factor that regulates the transcription of many genes that code for pro-inflammatory proteins, which in turn has led to suggest that this action may be the underlying cause of the drug's effects.
Mesavancol tablet contains a core with 1.2 g of mesalamine in a multi-matrix system formulation. This system involves coating with copolymers of methacrylic acid, Type A and Type B, which have been formulated to dissolve at pH levels equal to or greater than 7, thus facilitating the sustained release of effective concentrations of mesalamine through the colon and limiting its concentration. "systemic absorption.
Mesavancol was the subject of two Phase 3, placebo-controlled studies of a similar design, in which 623 patients with mild to moderate, active ulcerative colitis were randomized. Mesavancol 2.4 g / day and 4.8 g / day given with meals was statistically superior to placebo in terms of the number of patients who achieved remission of ulcerative colitis after 8 weeks of treatment. Based on the Ulcerative Colitis Disease Activity Index (UC-DAI), remission is defined as a UC-DAI score ≤ 1 with a score of 0 for rectal haemorrhage and number of bowel movements and the reduction of at least 1 point in the sigmoscopy score from baseline. Study 302 involved the use of a drug of control, modified-release mesalamine 2.4 g / tid, in the reference inner arm. Regarding the primary variable of remissions, the following results were achieved:
# Based on the ITT population;
* Statistically different from placebo (p
NS Not significant (p> 0.05)
05.2 "Pharmacokinetic properties
The mechanism of action of mesalamine (5-ASA) is believed to be topical, and therefore the clinical efficacy of Mesavancol is not correlated with the pharmacokinetic profile. A major route of elimination of mesalamine is metabolism to N-acetyl-5- acid. aminosalicylic (Ac 5-ASA), which is pharmacologically inactive.
Absorption
Gamma-scintigraphy studies demonstrated that a single 1.2 g dose of Mesavancol passed rapidly and without alteration through the upper gastrointestinal tract of fasted healthy volunteers. The scintigraphic images showed a trail of radiolabelled tracer along the colon, indicating that mesalamine has spread throughout this region of the gastrointestinal tract.
In a single and multiple dose study of Mesavancol 2.4 and 4.8 g administered with meals to 56 healthy volunteers, approximately 24% of the dose was absorbed; plasma mesalamine concentrations were measurable after 4 hours and were maximal within 8 hours of single dose administration. At steady state (generally achieved after 2 days of treatment) the accumulation of 5-ASA was 1.1 to 1.4 times for the 2.4g and 4.8g doses, respectively, above based on single dose pharmacokinetics. At the maximum dose, 4.8 g QD, the mean maximum plasma concentration of mesalamine was 5280 ± 3146 ng / mL and the mean area under the plasma concentration-time curve in the " dose interval was 49559 ± 23 780 ng.h / mL.
Accumulation of Ac-5-ASA was below that expected based on single dose pharmacokinetics by factor 0.9 and 0.7 for the 2.4g dose and 4.8g dose respectively.
This effect is probably due to a lower drug-metabolite ratio at high doses and to the steady state, due to the saturation of the 5-ASA metabolism.
After a single dose of Mesavancol, total systemic 5-ASA exposure appeared to increase in a slightly more than dose proportional manner, with an area under the plasma concentration-time curve increasing approximately 2.5-fold with dose increase. 2-fold, 2.4g to 4.8g. However, there was no evidence of the over-proportionality observed at steady state.
In a food interaction study conducted in 34 healthy volunteers, administration of a single 4.8 g dose of Mesavancol with a high-fat diet resulted in delayed and even prolonged absorption. Under these conditions, mesalamine plasma levels were measurable after approximately 6 hours, and maximum plasma levels were detected after approximately 24 hours. Following a single 4.8 g dose of Mesavancol mesalazine levels remained measurable in plasma until the last withdrawal time, ie 72 hours post dose.
Furthermore, systemic exposure was reduced under feeding, although the effect was less pronounced in women than in men.
Distribution
Mesalamine has a relatively small volume of distribution, approximately 18 L.
Mesalazine binds plasma proteins for 43% and N-acetyl-5-aminosalicylic acid for 78 - 83%, with in vitro plasma concentrations up to 2.5mcg / mL and 10mcg / mL, respectively.
Biotransformation
The only relevant metabolite of mesalazine is N-acetyl-5-aminosalicylic acid, which is pharmacologically inactive. Its formation is due to the action of N-acetyltransferase-1 in the liver and in the cells of the intestinal mucosa. There is no information on whether this enzyme is subject to genetic polymorphism.
Elimination
The elimination of absorbed mesalazine is mainly via the renal pathway following the metabolism of N-acetyl-5-aminosalicylic acid (acetylation). However, there is also limited urine excretion of the unchanged drug. Following administration of Mesavancol 2.4 g or 4.8 g once daily, on average, 2-3% of the dose was excreted unchanged in the urine after 24 hours, compared with 13-17% of N-acetyl-5-aminosalicylic acid.
Although the half-lives of pure mesalazine and N-acetyl-5-aminosalicylic acid are short (approximately 40 and 70 minutes respectively), the apparent half-lives after administration of Mesavancol 2.4 g and 4.8 g are dependent on the rate of absorption in consequence of prolonged release, averaging 6-7 hours and 10-13 hours respectively.
Special patient populations
There are no data in patients with renal or hepatic insufficiency taking Mesavancol. In patients with renal insufficiency, the resulting decrease in elimination rate and increased systemic concentration of mesalazine may constitute an increased risk of nephrotoxic-type adverse reactions (see section 4.4).
In further clinical studies with Mesavancol, the plasma AUC of mesalamine in women was up to 2-fold higher than in males.
Based on limited pharmacokinetic data, the pharmacokinetics of 5-ASA and Ac-5-ASA appear comparable between Caucasian and Hispanic subjects.
Pharmacokinetics have not been investigated in the elderly.
05.3 Preclinical safety data
Effects in non-clinical studies were observed only at exposures considered significantly in excess of the maximum human exposure, indicating little clinical relevance.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Tablet core:
Carmellose sodium
Carnauba wax
Stearic acid
Colloidal silica hydrates
Sodium starch-glycolate
Talc
Magnesium stearate
Coating:
Talc
Copolymer type A and type B of methacrylic acid
Triethyl citrate
Titanium dioxide (E171)
Red iron oxide (E172)
Macrogol 6000
06.2 Incompatibility
Not relevant.
06.3 Period of validity
2 years.
06.4 Special precautions for storage
Do not store above 25 ° C
Store in the original packaging.
06.5 Nature of the immediate packaging and contents of the package
The tablets are packed in polyamide / aluminum / PVC blisters with perforable aluminum film.
The packs contain 60 or 120 tablets. Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Giuliani S.p.A.
Via P. Palagi 2
20129 Milan
Italy
08.0 MARKETING AUTHORIZATION NUMBER
AIC n. 037734011 / M - 60 gastro-resistant prolonged-release tablets of 1200 mg
AIC n. 037734023 / M - 120 gastro-resistant prolonged-release tablets of 1200 mg
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
1 December 2009
10.0 DATE OF REVISION OF THE TEXT
Determination of November 6, 2009
