SERACTIL - PACKAGE LEAFLET - LEAFLETS

Home / leaflets / 2021

Seractil - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf life and Storage Composition and pharmaceutical form

Active ingredients: Dexibuprofen

SERACTIL 300 mg powder for oral suspension

Seractil package inserts are available for pack sizes:

SERACTIL 300 mg powder for oral suspension
SERACTIL 400 mg powder for oral suspension
SERACTIL 200 mg film-coated tablets
SERACTIL 300 mg film-coated tablets
SERACTIL 400 mg film-coated tablets

Why is Seractil used? What is it for?

Dexibuprofen, the active substance in Seractil, belongs to a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs, like dexibuprofen, are used as pain relievers and to reduce inflammation. Their action consists in decreasing the amount of prostaglandins (substances that control inflammation and pain) produced by our body.

What is Seractil used for?

Seractil helps relieve:

pain and inflammation caused by osteoarthritis (when the joints are worn out);
pains during the menstrual period;
other forms of mild to moderate pain, such as muscle and joint pain and toothache.

Contraindications When Seractil should not be used

Do not take Seractil:

if you are allergic to dexibuprofen itself or any of the other ingredients of this medicine (listed in section 6);
if you are allergic to acetylsalicylic acid or any other pain reliever (allergy may cause you to have difficulty breathing, asthma, runny nose, skin rash or swelling of the face);
if you have a history of gastrointestinal bleeding or perforation caused by NSAIDs (painkillers);
if you have recurrent stomach or duodenal ulcers (vomit containing blood, black stools or bloody diarrhea which may indicate that your stomach or intestines are bleeding);
in the presence of cerebral haemorrhage (cerebrovascular haemorrhages) or other active haemorrhages;
in the presence of inflammatory bowel diseases (ulcerative colitis, Crohn's disease);
in the presence of severe heart failure or severe liver or kidney dysfunction;
starting from the 6th month of pregnancy.

Precautions for use What you need to know before taking Seractil

Talk to your doctor or pharmacist before taking Seractil, if you have ever suffered from:

gastric or duodenal ulcer;
intestinal ulcers, ulcerative colitis or Crohn's disease;
liver, kidney disease or alcohol addiction;
blood clotting disorders (see also section "Taking Seractil with other medicines");
edema (when fluid accumulates in the tissues of the body);
heart disease or high blood pressure;
asthma or other breathing difficulties;
systemic lupus erythematosus (a disease affecting the joints, muscles and skin) or collagenopathy (a collagen disease affecting connective tissue);
difficulty in conception (in rare cases, drugs such as Seractil can affect a woman's fertility. Fertility returns to normal when you stop taking Seractil).

If you need higher doses of the drug, particularly if you are over the age of 60 or have a stomach or duodenal ulcer, the risk of gastrointestinal side effects is increased. Your doctor may prescribe them together with Seractil agents. protective.

Medicines such as Seractil may be associated with a small increased risk of heart attack ('myocardial infarction') or stroke. Risks are more likely if the doses are high and the treatment period is long. Therefore, do not exceed the recommended dose or extend the duration of treatment.

If you have heart problems, a previous stroke or think you may be at risk for these conditions (for example, if you have high blood pressure, have diabetes or high cholesterol levels, or are a smoker) you should discuss treatment with your doctor or pharmacist.

Your doctor may consider it appropriate to have you checked regularly if:

have heart, liver or kidney problems;
is "over 60 years of age;
needs this treatment for a long time.

Your doctor will tell you how often to get checked.

If you take high doses of a pain reliever for an extended period of time (unlike what is expected) you may experience a headache. In this case, you should not take any further doses of Seractil for the headache.

You should avoid taking NSAIDs if you have varicella zoster (chickenpox) infection.

Delayed onset of activity may occur in some patients if Seractil is taken for quick pain relief in the treatment of acute pain, particularly if it is taken with food (see also section 3).

Interactions Which drugs or foods can change the effect of Seractil

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

You should not take the following medicines concomitantly with Seractil unless under close medical supervision:

NSAIDs (medicines to treat pain, fever and inflammation). Taking Seractil with other NSAIDs or with acetylsalicylic acid (aspirin) increases the risk of gastrointestinal ulcer or bleeding. However, your doctor may allow you to take low doses of acetylsalicylic acid (up to 100 mg per day) at the same time as Seractil.
Warfarin or other medicines used to thin the blood or prevent clotting. If you take this medicine with Seractil, the bleeding time may be prolonged or "bleeding" may occur.
Lithium, which is used to treat certain mood disorders. Seractil may increase the effect of lithium.
Methotrexate. Seractil can increase the side effects of methotrexate.

You can take the following medicines together with Seractil but for safety reasons you should tell your doctor:

Medicines used to treat high blood pressure or heart problems (for example, beta blockers). Seractil may reduce the benefits of these medicines.
Some heart medicines, called ACE inhibitors or angiotensin II receptor antagonists. These can in rare cases increase the risk of kidney problems.
Diuretics.
Corticosteroids. It can increase the risk of ulcer and bleeding.
Some antidepressants (selective serotonin reuptake inhibitors) can increase the risk of gastrointestinal bleeding.
Digoxin (a heart medicine). Seractil may increase the undesirable effects of digoxin.
Immunosuppressants such as cyclosporine.
Aminoglycoside antibiotics (medicines to treat infections)
Medicines that increase blood potassium levels: ACE inhibitors, angiotensin II receptor antagonists, cyclosporine, tacrolimus, trimethoprim and heparin.
Medicines used to modify blood clotting. Seractil can cause an extension of the time it takes to stop bleeding.
Phenytoin, used to treat epilepsy. Seractil may accentuate the unwanted effects of phenytoin.
Phenytoin, phenobarbital and rifampicin. Co-administration may reduce the effects of dexibuprofen.
Low dose acetylsalicylic acid. Dexibuprofen can interfere with the effect that acetylsalicylic acid has on blood thinning.
Sulphonylurea (some oral antidiabetic medicines).
Pemetrexed (medicine to treat some forms of cancer).
Zidovudine (medicine to treat HIV / AIDS).

Seractil with food, drink and alcohol

You can also take Seractil between meals, however it is best to take it after meals to try to avoid stomach problems, especially if it is a long-lasting treatment. Limit or avoid alcohol intake when taking Seractil as it can increase gastrointestinal effects.

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 for advice before taking this medicine. You should not take Seractil from the beginning of the 6th month of pregnancy, as it can be seriously dangerous for the fetus, even at very low doses. In the first 5 months of pregnancy, you should only take Seractil after consulting your doctor.

You should also not take Seractil if you are planning to become pregnant, as the medicine can make it more difficult to conceive.

Only small amounts of Seractil pass into breast milk. However, if you are breastfeeding, you should not take Seractil for a long time or in high doses.

Driving and using machines

If you experience feelings of dizziness, sleepiness, tiredness or blurred vision after taking Seractil, you should avoid driving or using dangerous machinery (see section 4 "Possible side effects").

Important information about some of the ingredients of Seractil

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

Dosage and method of use How to use Seractil: Dosage

Always take Seractil exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.

Pour the contents of the sachet into a glass of water (about 200 ml).

Mix well until you get a cloudy suspension. Take immediately after preparation.

Seractil works faster when taken without food. However, it is recommended to take Seractil after meals, as this can help avoid stomach upset, especially if the treatment is long-lasting.

Do not take more than 1 sachet of Seractil of 300 mg per single dose. Do not take more than 4 sachets of Seractil of 300 mg per day.

For osteoarthritis

The usual dose is 1 sachet of Seractil 300 mg 2 to 3 times a day. For acute symptoms, your doctor may increase the dose up to 4 sachets of Seractil 300 mg per day.

For menstrual pains

The usual dose is 1 sachet of Seractil 300 mg 2 to 3 times a day.

For mild and moderate pain

The usual dose is 1 sachet of Seractil 300 mg twice a day. For acute symptoms, your doctor may prescribe up to 4 sachets of Seractil 300 mg per day.

Patients with liver or kidney disease: Your doctor may have prescribed you a lower than normal dose of Seractil. You should not increase the dose your doctor has prescribed.

Elderly patients: If you are over the age of 60, your doctor may have prescribed you a lower than normal dose. If you do not experience any problems taking Seractil, your doctor may subsequently increase the dose.

Use in children and adolescents: As there are insufficient data on its use in children and adolescents, Seractil should not be used in patients below 18 years of age.

Duration of treatment: You should not take this medicine for longer than two weeks. If you need treatment for a longer period of time, your doctor may prescribe Seractil film-coated tablets.

If you think the effects of Seractil 300 mg powder for oral suspension sachets are too light or too strong, talk to your doctor or pharmacist.

Overdose What to do if you have taken too much Seractil

If you take more Seractil than you should

If you have accidentally taken too many sachets, contact your doctor immediately.

If you forget to take Seractil

Do not take a double dose to make up for a forgotten dose. Take the next sachet as usual.

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 Seractil

Like all medicines, this medicine can cause side effects, although not everybody gets them. These effects generally do not appear as often when taking Seractil in low doses or only for a short period of time.

Stop taking Seractil and call a doctor if you have:

severe stomach pain, particularly when starting Seractil treatment.
dark stools, bloody diarrhea or bloody vomit.
skin rash, the appearance of numerous painful blisters and / or peeling skin, mucosal lesions or any symptoms of hypersensitivity.
symptoms such as fever, sore throat and mouth, flu-like symptoms, feeling tired, nose or skin bleeding. These may be caused by a decrease in white blood cells in the body (agranulocytosis).
severe or persistent headache.
yellowing of the skin and whites of the eyes (jaundice).
swelling of the face, tongue or pharynx, difficulty swallowing or breathing (angioedema).

Very common: affects more than 1 in 10 people.

Digestion problems, stomach pains.

Common: affects 1 to 10 in 100 people.

diarrhea, vomiting and nausea;
feeling tired or sleepy, dizziness, headache;
rash.

Uncommon: affects 1 to 10 in 1,000 people.

Local burning in the mouth and throat, ulcer and bleeding of the stomach or intestines, black stools, mouth ulcers, gastritis;
purpura (ecchymosis), itchy, itchy rash;
swelling of the face or throat (angioedema);
insomnia, restlessness, anxiety, blurred vision, sensation of ringing or ringing in the ears (tinnitus);
runny nose, breathing difficulties.

Rare: affects 1 to 10 in 10,000 people.

severe allergic reaction;
psychotic reactions, depression, irritability;
confusion, disorientation or agitation;
hearing difficulties;
flatulence, constipation, gastrointestinal perforation (symptoms are severe stomach pain, fever, feeling sick), inflamed esophagus, sudden flare-up of diverticular disease (small pockets in the intestine that can become infected or inflamed), colitis or Crohn's disease;
liver problems, hepatitis (inflamed liver) and jaundice (yellowing of the skin or eyes);
blood disorders, including those that cause a reduction in the number of white or red blood cells or platelets.

Very rare: affects less than 1 in 10,000 people.

hypersensitivity reactions including symptoms such as fever, rash, abdominal pain, headache, malaise and vomiting;
photosensitivity;
aseptic meningitis (symptoms are headache, fever, neck stiffness, general malaise), severe allergic reactions (difficulty in breathing, asthma, rapid heart beat, low blood pressure and shock), allergic reactions with inflammation of small blood vessels ;
redness of the skin, mucous membranes or throat;
blisters in the hands and feet (Stevens-Johnson syndrome);
peeling of the skin (epidermal necrolysis);
hair loss;
kidney inflammation, kidney disease or kidney failure;
systemic lupus erythematosus (autoimmune disease);
aggravation of very rare bacterial infections, which attack the lining tissue of the muscle;

Edema (swelling of the limbs), high blood pressure and heart failure can occur during treatment with NSAIDs.

Medicines such as Seractil may be associated with a small increased risk of heart attack ("myocardial infarction") or stroke.

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 Italian Medicines Agency, website: 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.

Do not store above 25 ° C.

Do not use this medicine after the expiry date which is stated on the carton and sachet.

Composition and pharmaceutical form

What Seractil 300 mg powder for oral suspension contains

the active ingredient is dexibuprofen. One sachet contains 300 mg of dexibuprofen.
The other ingredients are: Sucrose, citric acid, orange flavor, saccharin, silica, sodium lauryl sulfate.

What Seractil 300 mg powder for oral suspension looks like and contents of the pack

This pack contains 30 sachets of Seractil 300 mg powder for oral suspension as a yellowish powder.

Not all pack sizes may be marketed.

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.

More information about Seractil 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 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 Incompatibilities 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 MARKETING AUTHORIZATION HOLDER 08.0 MARKETING AUTHORIZATION NUMBER CIO 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIO DRUGS, FULL DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON PREPARATION AND QUALITY CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

SERACTIL - Oral suspension

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

Seractil 200 mg powder for oral suspension

Each sachet contains 200 mg of dexibuprofen.

Excipients: 1.2 g of sucrose. For the full list of excipients, see section 6.1.

Seractil 300 mg powder for oral suspension

Each sachet contains 300 mg of dexibuprofen.

Excipients: 1.8 g of sucrose. For the full list of excipients, see section 6.1.

Seractil 400 mg powder for oral suspension

Each sachet contains 400 mg of dexibuprofen.

Excipients: 2.4 g of sucrose. For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM

Seractil 200 mg powder for oral suspension

Yellowish powder for oral suspension.

Seractil 300 mg powder for oral suspension

Yellowish powder for oral suspension.

Seractil 400 mg powder for oral suspension

Yellowish powder for oral suspension.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Symptomatic treatment of pain and inflammation associated with osteoarthritis.

Acute symptomatic treatment of pain during the menstrual period (primary dysmenorrhea).

Symptomatic treatment of other forms of mild or moderate pain such as musculoskeletal pain and dental pain.

04.2 Posology and method of administration

Dosage should be adjusted according to the severity of the disorder and the patient's condition.

Undesirable effects can be reduced by using the lowest effective dose for the shortest time necessary to control symptoms (see section 4.4).

The maximum single dose is 400 mg, the maximum daily dose is 1200 mg of dexibuprofen.

Dexibuprofen is available in sachets of 200, 300 and 400 mg. The 400 mg sachets are available as a full dose in a sachet or as a bipartite sachet containing two half doses of 200 mg of dexibuprofen each.

The duration of treatment should not exceed two weeks. In the case of treatments of longer duration, alternative products are available, for example dexibuprofen film-coated tablets.

Osteoarthritis

The recommended daily dose is 600-900 mg of dexibuprofen, divided up to three doses, for example 400 mg twice a day or 300 mg two or three times a day. The daily dose can be increased up to 1200 mg of dexibuprofen, in patients with acute symptoms or in the course of an exacerbation.

Mild or moderate pain

The recommended daily dose is 600 mg of dexibuprofen, divided up to three single doses. If necessary, the dose of dexibuprofen can be temporarily increased up to 1200 mg per day in patients suffering from acute pain (e.g. following surgical tooth avulsion).

Dysmenorrhea

A daily dose of 600 to 900 mg of dexibuprofen is recommended, divided up to three single doses, for example 400 mg twice a day or 300 mg two or three times a day.

Children and adolescents

No studies have been conducted on the use of dexibuprofen in children and adolescents (

Senior citizens

In the elderly, no particular modifications of the dosages described are necessary. However, individual dose assessment and reduction is appropriate due to the increased susceptibility of the elderly to gastrointestinal adverse reactions (see section 4.4).

Hepatic dysfunction

Patients with mild or moderate hepatic dysfunction should start therapy at reduced doses and should be closely monitored. Dexibuprofen must not be administered to patients with severe hepatic dysfunction (see section 4.3.).

Renal dysfunction

Patients with mild or moderate renal dysfunction should start therapy at reduced doses. Dexibuprofen must not be administered to patients with severe renal dysfunction (see section 4.3.).

The powder should be suspended in a glass of water, about 200 ml and should be drunk immediately after preparation. The sachets can be taken on a full or empty stomach (see section 5.2). Typically NSAIDs (non-steroidal anti-inflammatory drugs) they are preferably taken after meals to reduce gastrointestinal irritation, particularly during chronic use.

However, latency in the onset of the therapeutic effect is foreseeable in some patients if taken with meals or immediately afterwards.

04.3 Contraindications

Dexibuprofen should not be administered in the following cases:

• Patients with hypersensitivity to dexibuprofen, to any other NSAID or to any excipient contained in the product.

• Patients in whom substances with a similar mechanism of action (eg acetylsalicylic acid or other NSAIDs) can trigger asthma attacks, bronchospasm, acute rhinitis or cause nasal polyps, urticaria or angioneurotic edema.

• Patients with a history of gastrointestinal bleeding or perforation related to previous NSAID therapy.

• Patients with suspected or active or with a history of recurrent peptic / haemorrhagic ulcer (two or more distinct episodes of proven ulceration or bleeding).

• Patients with cerebrovascular haemorrhage or with other ongoing haemorrhages.

• Patients with active Crohn's disease or with active ulcerative colitis.

• Patients with severe heart failure.

• Patients with severe renal dysfunction (GFR

• Patients with severely impaired liver function.

• From the 6th month of pregnancy (see section 4.6).

04.4 Special warnings and appropriate precautions for use

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

The use of dexibuprofen should be avoided in conjunction with other NSAIDs, including selective cyclooxygenase-2 inhibitors.

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

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

The risk of gastrointestinal bleeding, ulceration or perforation increases with increasing NSAID dose, in patients with a history of ulcer, especially if complicated with haemorrhage or perforation (see section 4.3), alcoholism and in the elderly. These patients should initiate treatment. using the lowest available dose. Combination therapy of protective agents (e.g. misoprostol or proton pump inhibitors) should be considered in these patients, as well as in those patients taking low doses of acetylsalicylic acid, or other drugs that may increase the risk of gastrointestinal events (see below and section 4.5).

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

Particular caution is advised in patients taking concomitant medications that could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as acetylsalicylic acid (see paragraph 4.5).

When gastrointestinal bleeding or ulceration occurs in patients taking Seractil, the treatment should be discontinued.

Particular caution is recommended in the administration of NSAIDs in the case of subjects with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see section 4.8).

As with other NSAIDs, allergic reactions, including anaphylactic / anaphylactoid reactions, may occur, even without prior exposure to the drug.

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Steven-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in association with NSAID therapy (see section 4.8). Patients appear to be at higher risk in the early stages of therapy and the onset of reactions usually occurs within the first month of treatment. Dexibuprofen administration should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.

Dexibuprofen should be administered with caution to patients with systemic lupus erythematosus and various connective tissue diseases, as such patients may be predisposed to NSAID-induced renal and CNS side effects, including aseptic meningitis (see section 4.8). .

Cardiovascular and cerebrovascular effects

Adequate monitoring and appropriate advice are required for 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 ibuprofen, especially at high doses (2400 mg per day) and for long-term treatment, may be associated with a modest increased risk of arterial thrombotic events (eg myocardial infarction or stroke). Overall, epidemiological studies do not suggest that low doses of ibuprofen (≤ 1200 mg per day) are associated with an increased risk of myocardial infarction. There are insufficient data to exclude such a risk for dexibuprofen treatment.

Patients with uncontrolled arterial hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with ibuprofen after careful consideration. Similar considerations should be made before initiating long-term treatment in patients with risk factors for cardiovascular disease (eg arterial hypertension, hyperlipidaemia, diabetes mellitus, smoking).

Particular caution must be adopted in the treatment of patients suffering from kidney and liver diseases; The risk of fluid retention, edema and deterioration of renal function should be considered. When treating these patients with dexibuprofen, the lowest effective dose should be used and renal function should be regularly monitored.

Caution should be taken in subjects with a history of bronchial asthma or who suffer from it, since NSAIDs can cause bronchospasm in such subjects (see section 4.3.).

NSAIDs can mask the symptoms of an infection.

Like all NSAIDs, dexibuprofen can increase BUN and creatinine values. Like other NSAIDs, dexibuprofen may be associated with renal side effects which can lead to glomerulonephritis, interstitial nephritis, renal papillary necrosis, nephrotic syndrome and acute renal failure (see sections 4.2, 4.3 and 4.5).

Like other NSAIDs, dexibuprofen can cause a slight transient increase in some liver parameters and also significant increases in SGOT and SGPT. In the event of significant increases in these parameters, therapy must be discontinued (see sections 4.2 and 4.3).

Like other NSAIDs, dexibuprofen can reversibly inhibit platelet function and aggregation and prolong bleeding time. Caution should be exercised in patients with bleeding diathesis and other clotting disorders and when dexibuprofen is administered concomitantly with anticoagulants. oral (see section 4.5).

Patients treated for a long time with dexibuprofen, should be cautiously monitored (renal and hepatic function, haematological picture / complete blood count).

In the course of prolonged use, at high doses and outside the indications with analgesics, headache may occur which should not be treated by increasing the doses of the drug in question.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

In general, the habitual use of analgesics, especially the combination of different analgesic drugs, can lead to kidney lesions with the risk of renal failure (analgesic nephropathies). Therefore, the association with ibuprofen or other NSAIDs (including self-medication products and selective COX-2 inhibitors) should be avoided.

Drugs that inhibit cyclooxygenase / prostaglandin synthesis can reversibly impair fertility and are therefore not recommended in women attempting to conceive (see section 4.6).

Data from preclinical studies indicate that the inhibition of platelet aggregation caused by low doses of acetylsalicylic acid may be altered by the concomitant administration of NSAIDs such as dexibuprofen. This interaction could reduce the cardiovascular protective effect. Therefore in the case of concomitant administration of low dose acetylsalicylic acid, particular care should be taken if the duration of treatment exceeds the short term.

04.5 Interactions with other medicinal products and other forms of interaction

The information in this section is based on previous experience with other NSAIDs.

In general, NSAIDs should be used with caution when administered concomitantly with other drugs that may increase the risk of gastrointestinal ulcer or bleeding or impaired renal function.

It is not recommended to use it simultaneously with:

Anticoagulants: the effect of anticoagulants, such as warfarin (see section 4.4), may be potentiated by NSAIDs. Blood clotting tests (INR, bleeding time) should be performed at the start of treatment with dexibuprofen and dosage of anticoagulants , if necessary, it must be adapted.

Methotrexate in doses of 15 mg / week or higher: if NSAIDs and methotrexate are administered within 24 hours, plasma levels of methotrexate may increase due to a reduction in its renal clearance thereby increasing its potential toxicity. Therefore, concomitant use with dexibuprofen is not recommended in patients treated with high doses of methotrexate (see section 4.4).

Lithium: NSAIDs may increase plasma lithium levels by reducing its renal clearance. The combination is not recommended (see section 4.4). If the combination is necessary, frequent checks of lithium should be performed. Consideration should be given to reducing the dose of lithium.

Other NSAIDs and salicylates (acetylsalicylic acid at doses higher than those used for antithrombotic treatment, about 100 mg / day): Concomitant use with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided, as simultaneous administration of different NSAIDs may increase the risk of gastrointestinal ulcers and bleeding.

Precautions

Acetylsalicylic acid: concomitant administration may alter the inhibition of platelet aggregation caused by low-dose acetylsalicylic acid, through the competitive inhibition of the cyclooxygenase acetylation site in platelets (see section 4.4).

Antihypertensives: NSAIDs may decrease the efficacy of beta-blockers, possibly due to inhibition of the formation of vasodilating prostaglandins.

The concomitant use of NSAIDs and ACE inhibitors or angiotensin II receptor antagonists may be associated with an increased risk of acute renal failure, especially in patients with prior renal impairment. When administered to the elderly and / or to patients dehydrated, this combination can cause acute renal failure by acting directly on glomerular filtration. Close monitoring of renal function is recommended at the start of treatment.

Furthermore, chronic administration of NSAIDs can, in theory, reduce the antihypertensive effect of angiotensin II receptor antagonists, as reported for ACE inhibitors. Therefore caution is advised if this combination is required and careful monitoring of renal function is recommended at the start of treatment (patients should also be encouraged to take adequate amounts of fluids).

Ciclosporin, tacrolimus, sirolimus and aminoglycoside antibiotics: Concomitant treatment with NSAIDs may increase the risk of nephrotoxicity, due to the reduction of prostaglandin synthesis in the kidney. During concomitant treatment, renal function should be closely monitored, especially in the elderly.

Corticosteroids: increased risk of gastrointestinal ulcer or haemorrhage (see section 4.4).

Digoxin: NSAIDs may increase plasma digoxin levels in the blood and thus increase the risk of digoxin toxicity.

Methotrexate at doses lower than 15 mg / week: dexibuprofen can increase methotrexate levels.

If dexibuprofen is used in combination with low dose methotrexate, careful haematological monitoring should be performed in patients particularly in the first weeks of co-administration. In the presence of even mild renal impairment, especially in the elderly, greater monitoring is required and renal function should be monitored to prevent any reduction in methotrexate clearance.

Phenytoin: some NSAIDs can displace phenytoin from plasma protein binding sites, with the possibility of an increase in phenytoin serum levels and an increase in its toxicity.Although there is limited clinical evidence regarding this interaction, it is recommended that the dosage of phenytoin be adjusted based on the control of plasma concentrations and / or the signs of toxicity observed.

Phenytoin, phenobarbital and rifampicin: concomitant administration of CYP2C8 and CYP2C9 inducing agents may reduce the effects of dexibuprofen.

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

Thiazides, thiazide-related substances and loop diuretics and potassium-sparing diuretics: Concomitant use of an NSAID and a diuretic may increase the risk of renal failure secondary to decreased renal blood flow.

Drugs that increase plasma potassium levels: NSAIDs have been reported to increase plasma potassium levels. Therefore, special care should be taken during concomitant use with other drugs that increase plasma potassium levels (such as potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, immunosuppressive drugs such as cyclosporine or tacrolimus , trimethoprim and heparins) and plasma potassium levels should be monitored.

Thrombolytics, ticlopidine and antiplatelet agents: dexibuprofen inhibits platelet aggregation by inhibiting platelet cyclooxygenase.

Therefore, caution is recommended when dexibuprofen is administered concomitantly with thrombolytics, ticlopidine and other antiplatelet agents, due to the risk of increased antiplatelet effect.

04.6 Pregnancy and lactation

Pregnancy

Inhibition of prostaglandin synthesis can have negative effects on pregnancy and / or embryo-fetal development. Results of epidemiological studies suggest an increased risk of spontaneous abortion, cardiac malformations and gastroschisis following the use of prostaglandin synthesis inhibitors in early stages of pregnancy. The absolute risk of cardiovascular malformations increases from less than 1% to approximately 1.5%. The risk is thought 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 treated with prostaglandin synthesis inhibitors during the organogenetic period (see section 5.3).

During the first and second trimester of pregnancy, NSAIDs should not be administered unless clearly needed. If NSAIDs are used in the first and second trimester of pregnancy, the lowest effective dose and for the shortest possible duration of treatment should be used.

In the last trimester of pregnancy, all prostaglandin synthesis inhibitors can expose the fetus to:

• Cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension),

• Impaired renal function, which can progress to renal failure with oligohydroamnios, and can expose the mother and the newborn, at the end of pregnancy, to:

- possible prolongation of bleeding time, an antiplatelet effect which can occur even at very low doses,

- inhibition of uterine contractions and delay or prolongation of labor.

Therefore, dexibuprofen is contraindicated from the sixth month of pregnancy.

Feeding time

Ibuprofen has a negligible passage into breast milk. Breastfeeding is possible with dexibuprofen, if the dosage used is low and the treatment period is short.

Fertility

NSAIDs can reversibly impair fertility and are not recommended in women trying to conceive; if treatment with NSAIDs is necessary, the lowest effective dose should be used for the shortest possible treatment period (see section 4.4).

04.7 Effects on ability to drive and use machines

During treatment with dexibuprofen the patient's ability to react may be reduced when dizziness or fatigue appear as side effects. This should be taken into consideration when extra attention is required, for example when driving or operating machinery. For a single intake or for a short period of treatment with dexibuprofen no special precautions are necessary.

04.8 Undesirable effects

Clinical experience has shown that the risk of dexibuprofen-induced undesirable effects is comparable to that of racemic ibuprofen. The most frequent side effects are gastrointestinal in nature. Peptic ulcers, gastrointestinal perforation or bleeding, sometimes fatal, may occur, especially in elderly patients (see section 4.4).

Additional clinical studies and other studies lasting approximately 2 weeks show a frequency of approximately 8% to 20% of patients with predominantly mild gastrointestinal events and an even lower frequency in low-risk populations, for example during use for short or occasional periods.

Very common ≥ 1/10 common ≥ 1/100, Uncommon ≥ 1/1000, Rare ≥ 1/10.000, Very rare

Infections and infestations

Very rare: worsening of infection-related inflammation (necrotizing fasciitis).

Disorders of the blood and lymphatic system

The bleeding time can be prolonged.

Rare: haematological disorders including thrombocytopenia, leukopenia, granulocytopenia, pancytopenia, agranulocytosis, aplastic anemia or haemolytic anemia.

Disorders of the immune system

Uncommon: purpura (including allergic purpura), angioedema.

Rare: anaphylactic reaction.

Very rare: generalized hypersensitivity reaction, including symptoms such as fever with rash, abdominal pain, headache, nausea and vomiting, signs of liver damage and also aseptic meningitis. In most cases where aseptic meningitis has been reported with ibuprofen, some form of autoimmune disease (systemic lupus erythematosus or other collagen diseases) was present as a risk factor. swelling of the face, tongue and larynx, bronchospasm, asthma, tachycardia, hypotension and shock.

Psychiatric disorders

Uncommon: anxiety.

Rare: psychotic reaction, depression, irritability.

Nervous system disorders

Common: somnolence, headache, dizziness, vertigo.

Uncommon: insomnia, restlessness.

Rare: disorientation, confusion, agitation.

Very rare: aseptic meningitis (see immune system disorders).

Eye disorders

Uncommon: visual disturbances.

Rare: reversible toxic amblyopia

Ear and labyrinth disorders

Uncommon: tinnitus.

Rare: hearing impairment.

Gastrointestinal disorders

Very common: dyspepsia, abdominal pain.

Common: diarrhea, nausea, vomiting.

Uncommon: gastrointestinal ulcers and haemorrhages, gastritis, ulcerative stomatitis, melaena. Local burning sensation in the mouth or throat.

Rare: gastrointestinal perforation, flatulence, constipation, oesophagitis, esophageal stricture, recurrence of diverticular disease, nonspecific haemorrhagic colitis, ulcerative colitis or Crohn's disease. If gastrointestinal bleeding occurs, it can cause anemia and hematemesis.

Skin and subcutaneous tissue disorders

Common: rash.

Uncommon: urticaria, pruritus.

Very rare: erythema multiforme, epidermal necrolysis, systemic lupus erythematosus, alopecia, photosensitivity reactions, severe bullous-type skin reactions (Stevens-Johnson syndrome), acute toxic epidermal necrolysis (Lyell's syndrome) and allergic vasculitis.

Respiratory, thoracic and mediastinal disorders

Uncommon: rhinitis, bronchospasm.

Renal and urinary disorders

Very rare: interstitial nephritis, nephrotic syndrome and renal failure.

Hepatobiliary disorders

Rare: abnormal liver function, hepatitis and jaundice

Systemic pathologies

Common: fatigue.

Patients with high blood pressure or renal impairment appear to be predisposed to fluid retention.

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

04.9 Overdose

Dexibuprofen has low acute toxicity and some patients have survived even a single dose of 54 g of ibuprofen (equivalent to approximately 27 g of dexibuprofen). Most of the overdose cases were asymptomatic. Risk of symptoms is evident at doses> 80-100 mg / kg of ibuprofen.

The onset of symptoms usually occurs within the first 4 hours. Mild symptoms most common are: abdominal pain, nausea, vomiting, lethargy, drowsiness, headache, nystagmus, tinnitus and ataxia. Rarely, moderate or severe symptoms include gastrointestinal bleeding, hypotension. , hypothermia, metabolic acidosis, convulsions, impaired renal function, coma, adult respiratory failure syndrome and transient episodes of apnea (in younger children following ingestion of high doses).

Treatment is symptomatic and there is no specific antidote. Amounts that generally do not cause symptoms (less than 50 mg / kg dexibuprofen) can be diluted with water to minimize gastrointestinal disturbance. In case of ingestion of significant quantities, it should be administered activated charcoal.

Stomach emptying for emesis can only be considered if the procedure is performed within 60 minutes of ingestion. Gastric lavage should not be considered unless the subject has ingested a potentially threatening dose of drug. life and that the procedure can be performed within 60 minutes of ingestion. Forced diuresis, hemodialysis or hemoperfusion are useless because dexibuprofen binds strongly to plasma proteins.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: Non-steroidal anti-inflammatory and antirheumatic products, derivatives of propionic acid.

ATC code: M01AE14

Dexibuprofen (= S (+) - ibuprofen) is the pharmacologically active enantiomer of ibuprofen, a non-selective NSAID. Its mechanism of action is believed to be related to inhibition of prostaglandin synthesis. In humans, this reduces pain, inflammation and fever and reversibly inhibits ADP and collagen-stimulated platelet aggregation.

Additional clinical studies to compare the efficacy of ibuprofen and dexibuprofen in osteoarthritis with a treatment period of more than 15 days, in dysmenorrhea, including pain symptoms and dental pain have demonstrated at least non-inferiority of dexibuprofen compared to racemic ibuprofen at the recommended dose with a dose ratio of 1: 2.

05.2 Pharmacokinetic properties

Following oral administration, dexibuprofen is mainly absorbed in the "small intestine. After metabolic transformation in the liver (hydroxylation, carboxylation), pharmacologically inactive metabolites are completely excreted mainly by the kidneys (90%), but also in the bile. L" elimination half-life is 1.8 - 3.5 hours. Plasma protein binding is approximately 99%. Maximum plasma levels are reached approximately two hours after oral administration.

The concomitant intake of a high-fat meal with 400 mg of dexibuprofen as suspension prolongs the time to reach the maximum plasma concentration (from 2.5 hours after a high-fat meal to 2.0 hours fasting) and reduces the maximum plasma concentration (22 to 15 mcg / ml), but has no effect on the amount absorbed.

Pharmacokinetic studies with ibuprofen in patients with renal insufficiency recommend a dose reduction in these patients. Particular caution is also recommended due to inhibition of renal prostaglandin synthesis (see sections 4.2 and 4.4).

Elimination of dexibuprofen is slightly lower in patients with liver cirrhosis.

05.3 Preclinical safety data

Additional studies concerning single and repeated dose toxicity, reproductive toxicity and mutagenesis demonstrated that the toxicological profile of dexibuprofen is comparable to that of ibuprofen and did not reveal any other possible specific toxicological or carcinogenic risks for humans. Ibuprofen inhibited ovulation in rabbits and compromised implantation in several animal species (rabbit, rat, mouse). The administration of prostaglandin synthesis inhibitors, including ibuprofen (mainly at higher than therapeutic doses), to pregnant animals, caused an increase in pre- and post-implantation losses, embryo-fetal mortality and an increased incidence of malformations.