LIOMETACEN - PACKAGE LEAFLET - LEAFLETS

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Liometacen - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Unwanted Effects Shelf Life and Storage Other Information

Active ingredients: Indomethacin (Indomethacin meglumine)

LIOMETACEN 50 mg / 2 ml, powder and solvent for solution for injection for intravenous use
LIOMETACEN 25 mg / 2 ml powder and solvent for solution for injection for intravenous use

Indications Why is Liometacen used? What is it for?

This medicine contains the active substance indomethacin meglumine and belongs to a class of drugs called NSAIDs (non-steroidal anti-inflammatory drugs) that work against pain, fever and inflammation.

LIOMETACEN is used to reduce (acute) pain due to inflammation of the muscles and joints (musculoskeletal system).

Contraindications When Liometacen should not be used

Do not use LIOMETACEN if:

you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6);
had an allergic reaction after taking acetylsalicylic acid known as aspirin;
suffer from stomach and / or duodenal (peptic) or intestinal ulcer;
have had two or more distinct episodes of stomach or bowel ulcer, perforation or bleeding (including blood in vomit or bowel movement or black tarry stools);
have suffered from even a single episode of ulcer, perforation or bleeding in the stomach or intestines caused by taking medication;
suffer from severe heart problems (severe heart failure);
takes drugs that increase diuresis in high doses (intensive diuretic therapy);
you have bleeding or are prone to bleeding (bleeding diathesis), for example you are using blood thinning medications (anticoagulants);
suffer from epilepsy;
suffer from parkinsonism which can manifest itself with tremor at rest, muscle stiffness, slowing of movements, difficulty in maintaining balance;
are pregnant or breast-feeding.

LIOMETACEN should not be given to children and adolescents less than 14 years of age.

Precautions for use What you need to know before taking Liometacen

Talk to your doctor or nurse before you are given Liometacen Tell your doctor if:

you are taking other medicines that reduce pain (analgesics) and inflammation (NSAIDs);
have had stomach or intestinal disorders, eg Crohn's disease, ulcerative colitis;
you are elderly, as you are more likely to experience side effects from this medicine;
have asthma or are prone to asthma attacks;
have kidney problems (for example hypoperfusion);
have liver problems such as cirrhosis or severe hepatitis;
have problems with your heart or blood vessels, a history of stroke, heart attack, have heart failure or think you may be at risk for these conditions (for example if you have high blood pressure, diabetes or high cholesterol or smoke), as medicines such as LIOMETACEN may be associated with a modest increased risk of heart attack (myocardial infarction) or stroke.

IN ALL THESE CASES, YOUR DOCTOR WILL CONSIDER IF TO USE LIOMETACEN OR IF YOU NEED TO CHECK OUT DURING THERAPY.

BE CAREFUL, as during treatment with all pain and inflammation medications (NSAIDs):

bleeding, ulceration or perforation of the stomach or intestines, which can be fatal, has been reported at any time, with or without warning symptoms, even in patients without previous severe stomach or bowel (gastrointestinal) problems;
although very rarely, severe skin reactions, some of them fatal, have been reported, manifesting as redness, blistering and exfoliation (eg exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis). These events are more likely at the start of treatment, particularly in the first month of therapy.
signs of an infection can be masked. The risk of having side effects increases with high doses and prolonged treatments. LIOMETACEN will be given to you at the lowest effective dose and for the shortest duration. short-lived blood.

Talk to your doctor if during treatment with LIOMETACEN:

notice any symptoms affecting the stomach and intestines (gastrointestinal), especially if they are bleeding;
a "skin rash, mucosal lesions or any other sign of an allergic reaction (eg redness, itching, swelling of the face and throat, abrupt drop in blood pressure) appear;
have eye problems;
you notice headache (especially if very strong and persistent).

IN ALL THESE CASES THE DOCTOR WILL CONSIDER WHETHER TO MODIFY OR SUSPEND THE THERAPY.

Interactions Which drugs or foods can modify the effect of Liometacen

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Some drugs can interact with LIOMETACEN or increase the risk of adverse events, including serious ones. In particular, tell your doctor if you are taking:

drugs that contain cortisone (corticosteroids);
blood-thinning drugs (anticoagulants and antiplatelet agents), eg warfarin, acetylsalicylic acid (known as aspirin);
drugs against high blood pressure (hypertension) such as: diuretics, ACE inhibitors, furosemide, angiotensin II antagonists;
drugs called 'selective serotonin reuptake inhibitors' (SSRIs), used as antidepressants;
calcitonin, used to lower the level of calcium in the blood and to treat osteoporosis;
probenecid, a drug used in gout;
proglumide, a drug used to treat ulcers;
sulfonamide antibiotics, drugs used against infections;
other drugs that reduce pain and inflammation (NSAIDs, phenylbutazone).

Warnings It is important to know that:

Pregnancy, breastfeeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or nurse for advice before being given this medicine.

LIOMETACEN will not be given to you during pregnancy, as this treatment can cause problems with the heart, lungs or kidneys of the fetus and complications during delivery.

LIOMETACEN will not be given to you if you are breastfeeding.

The administration of LIOMETACEN will be suspended if you have problems with conceiving and if you are undergoing fertility investigations; it will also need to be administered with caution if it is to become pregnant. In all these cases, tell your doctor.

Driving and using machines

Indomethacin can cause dizziness, fatigue, lightheadedness and vision problems. Be careful before driving or using machines.

LIOMETACEN contains sodium. This medicine contains less than 1 mmol (23 mg) sodium per dose, ie it is essentially 'sodium-free'.

Dosage and method of use How to use Liometacen: Dosage

LIOMETACEN is for use in a hospital setting only. It will be given to you as an injection into a vein (intravenously) only by qualified personnel, such as a doctor or nurse.

The usual dose is 1-2 ampoules, to be diluted with 250 or 500 ml of saline or glucose solution.

Venous perfusion must be done "drop by drop"; infusion rate 25-35 drops / minute. It is preferable not to combine other preparations in the same container (eg bag, drip) used for the administration of LIOMETACEN.

Overdose What to do if you have taken too much Liometacen

If you use more LIOMETACEN than recommended

You may experience side effects affecting the stomach or intestines.

If you have any further questions on the use of this medicine, ask your doctor or nurse

Side Effects What are the side effects of Liometacen

Like all medicines, this medicine can cause side effects, although not everybody gets them. Compliance with the instructions contained in this leaflet reduces the risk of undesirable effects.

Taking LIOMETACEN should be stopped immediately if any of the following conditions occur:

severe allergic reactions such as: swelling (angioedema) of the face, eyes, lips, throat with difficulty in breathing, sudden drop in blood pressure (anaphylactic shock);
severe breathing difficulties (asthma, dyspnoea);
severe stomach problems, burning or abdominal pain due to stomach or duodenal (peptic) ulcer;
sudden violent pain in the pit of the stomach (ulcer perforation);
vomiting containing blood (haematemesis) or black stools (melaena), associated with bleeding from the stomach or intestines (gastrointestinal) or abnormal fatigue with reduced urine output (due to invisible bleeding);
severe skin rashes with redness, blistering and exfoliation (e.g. Steven-Johnson syndrome, toxic epidermal necrolysis). Other side effects
nausea, vomiting, diarrhea, intestinal gas (flatulence), difficulty in evacuation (constipation), indigestion (dyspepsia), pain in the abdomen, inflammation of the lining of the mouth with ulcers (ulcerative stomatitis), worsening of inflammation of the colon (colitis ) and Crohn's disease, gastritis;
changes in blood parameters such as decreased red blood cells (bleeding anemia, aplastic anemia, haemolytic anemia), decreased white blood cells (leukopenia, agranulocytosis), decreased platelets causing red spots on the skin or bleeding (thrombocytopenic purpura), increased blood blood sugar (hyperglycemia);
depression and confusion, headache, lightheadedness, dizziness, fainting (syncope);
visual disturbances, such as deposits in the cornea or retinal disease;
impaired hearing, ringing in the ears;
heart attack (myocardial infarction) or stroke, swelling (edema), high blood pressure (hypertension), impaired function (failure) of the heart;
bleeding from the nose (epistaxis);
inflammation of the liver (hepatitis) with yellowing of the skin or sclera of the eyes (jaundice), possibly fatal;
more or less sudden onset of skin lesions, eg spot or diffuse color changes (rash), hives, itching; ? presence of blood (haematuria) or sugar (glycosuria) in the urine, changes in kidney function (renal failure);
bleeding from the vagina;
tiredness.

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 “http://www.aifa.gov.it/responsabili.” 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 store above 30 ° C.

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month. This date refers to the product in intact packaging, correctly stored.

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.

Deadline "> Other information

What LIOMETACEN contains

The active ingredient is indomethacin meglumine.

The excipients are:

in the vial of powder: mannitol, meglumine, dibasic sodium phosphate dihydrate, monobasic potassium phosphate;
in the solvent ampoule: water for injections.

Each vial of LIOMETACEN 25 mg / 2 ml and 50 mg / 2 ml powder contains: 38.6 and 77.2 mg of indomethacin meglumine (equivalent to 25 and 50 mg of indomethacin).

Each vial contains 2 ml of solvent.

Description of the appearance of LIOMETACEN and contents of the pack

LIOMETACEN 25 mg / 2 ml and 50 mg / 2 ml is available in packs containing 6 vials of powder and 6 vials of 2 ml solvent.

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.

Further information on Liometacen can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT - 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION - 03.0 PHARMACEUTICAL FORM - 04.0 CLINICAL PARTICULARS - 04.1 Therapeutic indications - 04.2 Posology and method of administration - 04.3 Contraindications - 04.4 Special warnings and appropriate precautions for use - 04.5 Interactions with other medicinal products and other forms of interaction - 04.6 Pregnancy and lactation - 04.7 Effects on the ability to drive and use machines - 04.8 Undesirable effects - 04.9 Overdose - 05.0 PHARMACOLOGICAL PROPERTIES - 05.1 "Pharmacodynamic properties - 05.2 Pharmacokinetic properties" - 05.3 Preclinical safety data - 06.0 PHARMACEUTICAL PARTICULARS - 06.1 Excipients - 06.2 Incompatibility "- 06.3 Shelf life" - 06.4 Special precautions for storage - 06.5 Nature of the primary packaging and contents of the package - 06.6 Instructions for use and handling - 07.0 AUTHORIZATION HOLDER ALL "PLACING ON THE MARKET - 08.0 MARKETING AUTHORIZATION NUMBER - 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION - 10.0 DATE OF REVISION OF THE TEXT - 11.0 FOR RADIO DRUGS, COMPLETE DATA ON INTERNAL RADIATION DOSIMETRY - 12.0 INSTRUCTIONS FOR RADIOPHONES ON EXTEMPORARY PREPARATION AND QUALITY CONTROL -

01.0 NAME OF THE MEDICINAL PRODUCT -

LIOMETACEN POWDER AND SOLVENT FOR INJECTABLE SOLUTION FOR INTRAVENOUS USE

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -

A 50 mg vial of powder contains:

Active ingredient: Indomethacin meglumine 77.2 mg (equal to Indomethacin 50 mg).

A 25 mg vial of powder contains:

Active ingredient: Indomethacin meglumine 38.6 mg (equal to Indomethacin 25 mg).

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM -

Powder and solvent for solution for injection for intravenous use.

04.0 CLINICAL INFORMATION -

04.1 Therapeutic indications -

Symptomatic treatment of acute painful episodes in the course of inflammatory diseases of the musculoskeletal system.

04.2 Posology and method of administration -

The therapy is to be carried out only in hospital, and "it is advisable to dilute the content of 1-2 ampoules in 250-500 ml of physiological or glucose solution and perform venous perfusion" drop by drop "; infusion rate 25-35 drops / min The combination of other preparations in the same infusion bottle is not recommended.

Undesirable effects can be minimized with the use of the shortest possible duration of treatment needed to control symptoms (see section 4.4).

04.3 Contraindications -

Severe heart failure.

Children under 14 years of age. Pregnancy and breastfeeding.

Subjects with peptic ulcer or gastrointestinal ulcerative lesions in the active phase. History of gastrointestinal bleeding or perforation related to previous active treatments or history of recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding).

Hypersensitivity to acetylsalicylic acid, indomethacin or to any of the excipients listed in section 6.1.

Epilepsy. Parkinsonism.

Furthermore, the drug is contraindicated during intensive diuretic therapy, in subjects with ongoing bleeding and haemorrhagic diathesis, during treatments with anticoagulants as it synergizes their action.

04.4 Special warnings and appropriate precautions for use -

This product interferes with the synthesis of prostaglandins and their important intermediates, which participate in physiological functions.

The drug, therefore, requires special precautions or requires its exclusion from "use if" the following conditions are present in the patient: states of kidney hypoperfusion, kidney disease, heart failure, liver cirrhosis or severe hepatitis, advanced age.

The use of the drug in the vicinity of birth determines the delay of the birth itself; moreover, the drug can cause, if administered in this period, alterations in the haemodynamics of the small circulation in the unborn child, with serious consequences for respiration.

For the interaction with the metabolism of arachidonic acid, the drug can cause, in asthmatics and predisposed subjects, crises of bronchospasm and possibly shock and other allergic phenomena.

Since "the product is" characterized by high activity and by the variability of its tendency to cause side effects, it is advisable to adopt the lowest active dosage for each patient since increasing the dosage tends to increase the incidence of side effects.

Particular attention must be paid to detecting any gastrointestinal, ocular and nervous reactions of the drug as early as possible in order to be able to establish as early as possible, based on the severity of the reactions themselves and the risk-benefit ratio, whether it is appropriate to interrupt the treatment or continue it. if necessary with a reduced dosage.

Since "ocular reactions may be asymptomatic, it is desirable that periodic ophthalmological examinations be performed in subjects treated for prolonged periods of time. The "indomethacin can" mask infections possibly present and misrecognized already at the beginning of the treatment intervened during the latter.

During treatment, especially if prolonged, carry out periodic checks of liver function and blood count.

Following parenteral administration, mild hypotension of short duration may sometimes occur.

This drug cannot be considered a simple painkiller and must be used under the strict supervision of the doctor. Furthermore, once the acute painful episode is overcome, it is prudent to switch to the use of preparations for non-parenteral use, which, while offering qualitatively the same side effects are less prone to induce severe reactions. The use of the drug is allowed only in hospitals and nursing homes.

The use of LIOMETACEN, as with any drug that inhibits prostaglandin synthesis and cyclooxygenase, is not recommended in women who intend to become pregnant.

The use of LIOMETACEN should be avoided concomitantly with NSAIDs, including selective COX-2 inhibitors.

Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see section 4.2 and the paragraphs below on gastrointestinal and cardiovascular risks).

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 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 indomethacin.

Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with indomethacin 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).

Gastrointestinal bleeding, ulceration and perforation: Gastrointestinal bleeding, ulceration and perforation, which can be fatal, have been reported during treatment with all NSAIDs, at any time, with or without warning symptoms or a previous history of serious gastrointestinal events.

When gastrointestinal bleeding or ulceration occurs in patients taking LIOMETACEN 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 be exacerbated (see section 4.8 - undesirable effects).

Caution should be exercised in patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as aspirin (see section 4.5).

Elderly: Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section 4.2).

In the elderly and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), the risk of gastrointestinal haemorrhage, ulceration or perforation is higher with increased doses of NSAIDs. These patients should initiate treatment with the lowest dose available. Concomitant use of protective agents (misoprostol or proton pump inhibitors) should be considered for these patients and also for patients taking low doses of aspirin or other drugs that may increase the risk of gastrointestinal events (see section 4.5).

Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding) particularly in the initial stages of treatment.

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see section 4.8). In the early stages of therapy patients appear to be at higher risk: the onset of the reaction occurs in most cases within the first month of treatment. LIOMETACEN should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.

Keep this medicine out of the reach and sight of children.

04.5 Interactions with other medicinal products and other forms of interaction -

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 (e.g. dehydrated patients or elderly patients with impaired renal function) the co-administration of an ACE inhibitor or angiotensin II antagonist 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 indomethacin 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.

Anticoagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin (see section 4.4).

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4)

Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see section 4.4).

Calcitonin: reduced diuresis and natriuresis induced by calcitonin.

phenylbutazone: increased gastrolesivity.

furosemide: reduced action of furosemide.

probenecid: increased effect of indomethacin.

proglumide: improved gastric tolerance to indomethacin.

sulfonamides: increased blood levels of sulfonamides.

04.6 Pregnancy and breastfeeding -

Administration of LIOMETACEN should be discontinued in women who have fertility problems or who are undergoing fertility investigations.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and / or embryo / fetal development. Results from epidemiological studies suggest an increased risk of abortion and cardiac malformation and gastroschisis after the use of a prostaglandin synthesis inhibitor in early stages of pregnancy.

The absolute risk of cardiac malformations increased from less than 1% to approximately 1.5%. The risk was considered to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased pre- and post-implantation loss and 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.

LIOMETACEN is contraindicated during breastfeeding.

04.7 Effects on ability to drive and use machines -

Since indomethacin, in some patients, can "cause dizziness, dizziness and headache," those who might drive vehicles of any kind or attend to operations requiring integrity of the degree of vigilance must be warned.

04.8 Undesirable effects -

The most commonly observed adverse events with NSAIDs are gastrointestinal in nature. Peptic ulcers, gastrointestinal perforation or haemorrhage, sometimes fatal, may occur, particularly in the elderly (see section 4.4).

Edema, hypertension and heart failure have been reported in association with NSAID treatment.

The frequency of adverse events, listed below in the table, cannot be estimated from the available data, as they have been reported in post-marketing experience.

System and organ classification Adverse reaction Disorders of the blood and lymphatic system Aplastic or haemolytic anemia, agranulocytosis, leukopenia, thrombocytopenic purpura, anemia (following small and repeated manifest or inapparent gastrointestinal bleeding) System disturbances immune Hypersensitivity reactions, anaphylactic shock Metabolism and nutrition disorders Hyperglycemia Psychiatric disorders Mental depression, confusion, System disorders nervous Headache (sometimes severe and persistent such as to require dose reduction or discontinuation of treatment), lightheadedness Eye disorders (*) Visual disturbances, corneal deposits, retinopathy Ear and labyrinth disorders Vertigo, hearing disorder, ringing in the ears Cardiovascular pathologies Myocardial infarction or stroke ** (see section 4.4), edema, hypertension and heart failure, syncope Respiratory disorders, thoracic and mediastinal Dyspnea, asthma, epistaxis Gastrointestinal disorders Peptic ulcer, gastrointestinal perforation, gastrointestinal haemorrhage sometimes fatal (especially in elderly patients, see section 4.4), nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and disease Crohn's disease (see section 4.4), gastritis. Hepatobiliary disorders Hepatitis with jaundice (exceptionally fatal cases have been reported) Skin and subcutaneous tissue disorders Rash, urticaria, angioedema, purpura, bullous rash (including Stevens-Johnson syndrome and toxic epidermal necrolysis, which occur very rarely), pruritus Renal and urinary disorders Hematuria, glycosuria, renal failure Diseases of the apparatus reproductive and of the breast Vaginal bleeding General disorders and conditions related to administration site Asthenia

(*) Corneal deposits and retinopathies have been reported following prolonged treatments of subjects with rheumatoid arthritis. However, similar reactions have been described in patients with the same disease not treated with indomethacin.

(**) Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially at high doses and for long-term treatments) may be associated with a modest increased risk of arterial thrombotic events (eg myocardial infarction or stroke; 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" www.agenziafarmaco.gov.it/it/responsabili ".

04.9 Overdose -

There are no known cases of overdose with LIOMETACEN.

Should this happen, practice supportive therapy. It is advisable to follow the patient for a few days, monitoring the possible appearance of gastrointestinal disturbances.

05.0 PHARMACOLOGICAL PROPERTIES -

05.1 "Pharmacodynamic properties -

Pharmacotherapeutic group: Analgesic, anti-inflammatory and non-steroidal antirheumatic

ATC code: M01AB01

LIOMETACEN (indomethacin meglumine) is a product with high analgesic activity.

LIOMETACEN is in the form of water-soluble salt of indomethacin. The aqueous solution has a pH close to that of the tissues so it can be injected without danger of precipitation at the level of the tissues themselves; the salt, in circulation, hydrolyzes releasing indomethacin.

LIOMETACEN allows rapid intervention on acute painful forms.

The administration of LIOMETACEN is to be carried out intravenously and for hospital use only.

05.2 "Pharmacokinetic properties -

Pharmacokinetic investigations performed on human subjects treated intramuscularly with LIOMETACEN in doses equivalent to 50 mg of indomethacin have documented the presence of plasma indomethacin levels of 3.25 mg / ml 30 minutes after treatment. These values slowly decrease, but are still evident after 360 minutes (1.03 mg / ml). The drug is mainly eliminated as glucuronate by the kidney (about 70% of the administered dose).

05.3 Preclinical safety data -

Acute toxicity:

LD50 (rat for SC) 21.2 mg / kg

LD50 (rat for i.p.) 22.6 mg / kg

LD50 (rabbit for i.v.) 234.8 mg / kg.

Chronic toxicity

Rat, for i.m. (180 days): 3.86 mg / kg / day. Dog, for i.m. (60 days): 7.72 mg / Kg / day. Chronic treatment did not modify body weight, azotemia, glycaemia, peripheral blood count, hematopoietic marrow, SGPT, alkaline phosphatase, renal function.

Local tolerability

The preparation demonstrates an excellent local tolerability injected intravenously, into the skin tissue, into the subcutaneous tissue, into the conjunctival sac. Histolesive action at the muscle tissue level. Test of the Tripan-bleu according to Koelzer-Wehr modified by Gradnik. Rat, for im (180 days): dose 3.86 mg / kg / day.Rabbit, for i.m. (20 days): dose 7.72-15.44 mg / kg / day. No harmful action. Action on the gastrointestinal mucosa. Rat for i.m. (30 days): dose 7.72 mg / kg / day, rabbit for i.v. (30 days): dose 3.86 mg / kg / day. No modification of the macroscopic aspect and of the intimate histological structure of the gastrointestinal mucosa.

Regarding use in pregnancy and lactation, there is no further information on preclinical data other than that already reported elsewhere in this Summary of Product Characteristics (see section 4.6).