Active ingredients: Niflumic acid
NIFLAM 250 mg hard capsules
Niflam package inserts are available for pack sizes:- NIFLAM 250 mg hard capsules
- NIFLAM 500 mg adult suppositories
- NIFLAM 285 mg suppositories for children
Indications Why is Niflam used? What is it for?
Niflam contains the ingredient niflumic acid and belongs to a group of drugs known as non-steroidal anti-inflammatory drugs (NSAIDs).
Niflam is indicated in adults and children over 12 years to reduce inflammation, pain and the accumulation of fluid in the tissues (edema) that accompany various diseases and in particular:
- diseases affecting the joints of the bones: chronic inflammation of the joints manifested by pain and swelling (rheumatoid arthritis and acute gouty arthritis), degeneration of the cartilage of the joints (osteoarthritis of the hip and osteoarthritis), inflammation of the spine (rheumatoid spondylitis and ankylosing spondylitis), chronic inflammation of the joints associated with a "chronic inflammation of the skin (arthritis associated with psoriasis)
- diseases that do not affect the joints of the bones: inflammation of the fluid-filled sacs, called "bursae", which protect the joints (bursitis), inflammation of the tendons (tenositis), inflammation of the membrane that lines the inner surface of the joints (synovitis), inflammation of the elbow tendons (epicondylitis)
- trauma: partial or total ruptures of a bone (fractures), trauma to a joint (sprains), bruises
- in sports medicine: joint pain, inflammation affecting the membrane surrounding the tibia (tibial periostitis), soft tissue injuries, etc.
- post-operative inflammatory states: dental extractions and other dental or mouth interventions, obstetric-gynecological interventions, nose and throat surgery
- acute and subacute diseases of the ear, nose and throat (ENT system)
- diseases of the bronchi and lungs: chronic inflammation of the lung tissue (bronchus pneumopathies), inflammation of the pulmonary pleura (pleurisy)
- other diseases: acute inflammation of the superficial veins (acute superficial thrombophlebitis).
In children, Niflam is indicated for the treatment of pain associated with inflammation of the ear, nose and throat (ENT system) or the mouth and its appendages (stomatological system).
Contraindications When Niflam should not be used
Do not use Niflam
- If you are allergic to niflumic acid or any of the other ingredients of this medicine (listed in section 6)
- If you have previously experienced allergy or asthma caused by the administration of niflumic / morniflumate acid or substances with similar activity, such as acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (NSAIDs).
- If you suffer from injuries to the inner walls of the stomach and duodenum (gastroduodenal ulcer).
- If you have a history of bleeding (haemorrhage) or perforation of the gastrointestinal tract.
- If you have a history of frequent gastroduodenal bleeding / ulcer (two or more distinct episodes of proven ulceration or bleeding).
- If you have severe liver, kidney and heart problems.
- If you are more than 6 months pregnant (see section "Fertility, pregnancy and breastfeeding").
- If you are under 12 years old (see section "Children and adolescents")
Precautions for use What you need to know before taking Niflam
Talk to your doctor or pharmacist before taking Niflam:
- if you have a history of high blood pressure (hypertension) and / or heart problems, as Niflam could lead to the development of hypertension or worsening of pre-existing hypertension and increased side effects affecting the heart and / or Your blood pressure will be monitored by your doctor during the initial phase of treatment and throughout the duration of therapy.
- if you suffer from digestive disorders (eg peptic ulcer, hiatal hernia, gastrointestinal bleeding) and gastrointestinal diseases (eg ulcerative colitis, Crohn's disease (chronic inflammatory bowel disease)), especially the elderly.
- if you are undergoing or have had surgery to restore normal blood flow to the heart in case of blocked coronary arteries (coronary artery bypass grafting).
- if you have heart problems or a history of sudden closure or rupture of a brain vessel (stroke) or you may be at risk for it (for example if you have high blood pressure, diabetes or high cholesterol or smoke), as Niflam can lead to increased blood pressure risk of heart attack (myocardial infarction) or stroke.
- if you have an "ongoing infection or are at risk for infection as Niflam can mask the usual signs and symptoms of an" infection.
- if you have had chickenpox.
Urine volume and kidney function should be closely monitored at the initiation of niflumic acid / morniflumate treatment in patients with chronic heart problems, kidney or liver problems, taking diuretics, who have undergone surgery higher with consequent decrease in the volume of circulating blood, and in particular in elderly subjects.
There have been test changes (false positives) that detect the presence of drugs in the urine even in the absence of these substances, so please tell your doctor or laboratory staff that you are taking / have taken Niflam.
Children and adolescents
Niflam capsules are contraindicated in children under 12 years of age.
Interactions Which drugs or foods can modify the effect of Niflam
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Combinations not recommended
- with other medicines belonging to the same group, NSAIDs (including acetylsalicylic acid and other salicylates)
- with anticoagulants (medicines that can slow down or stop the blood clotting process), such as warfarin
- with heparin (a medicine that can slow down or stop the blood clotting process) and related products
- with lithium (a medicine used to treat psychiatric diseases)
- with methotrexate (a medicine used to treat some cancers and autoimmune diseases) at doses higher than 15 mg per week
Combinations requiring precautions for use
- with diuretics and drugs used to treat high blood pressure in the arteries (angiotensin converting enzyme inhibitors and angiotensin II antagonists)
- with methotrexate, used at doses below 15 mg per week
Combinations that your doctor will carefully consider
- with antiplatelet agents (medicines capable of blocking the aggregation of platelets in the blood by preventing the formation of thrombi and emboli), for example ticlopidine, clopidogrel, tirofiban, eptifibatide and abciximab, iloprost and with heparins used for preventive purposes
- with potassium salts, diuretic medicines that reduce the amount of potassium in the urine (potassium-sparing diuretics), medicines used to reduce the body's immune response (cyclosporine, tacrolimus) and trimethoprim (an antibiotic capable of inhibiting bacterial replication)
- with beta blockers, medicines used to treat high blood pressure and heart problems
- with medicines to treat inflammation given by mouth (corticosteroids)
- with medicines to treat depression (selective serotonin re-uptake inhibitors, SSRIs)
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
Niflam should not be used in pregnancy, so your doctor will carefully evaluate the benefits of therapy for you and the risks to the fetus. Niflam is contraindicated after the sixth month of pregnancy.
Feeding time
If you are breast-feeding, ask your doctor for advice who will evaluate whether to discontinue breast-feeding or treatment with Niflam.
Fertility
Niflam can cause female fertility problems and is not recommended for women trying to get pregnant.
In women who have difficulty getting pregnant or who are undergoing tests for infertility, discontinuation of Niflam should be considered.
Driving and using machines
You may experience dizziness and sleepiness while using Niflam which may affect your ability to drive or use machines.
Niflam contains azorubine (E122)
Azorubine can cause allergic reactions. If you have a known allergy to azorubine contact your doctor before taking this medicine.
Dosage and method of use How to use Niflam: Dosage
Always use this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
The recommended dose is generally 1 capsule of Niflam three times a day, to be taken with or immediately after meals. In the case of severe inflammations, especially those of long duration or which tend to worsen, a maximum daily dose of 4 capsules of Niflam (corresponding to 1000 mg of niflumic acid) can be administered.
As symptoms improve, the posology should be reduced to a maintenance dose that proves effective. Doses higher than four capsules per day (1000 mg of niflumic acid) do not significantly increase the therapeutic effects, but may cause the appearance of undesirable effects which rarely occur at the recommended dose. In acute gouty arthritis, an initial dose of 2 capsules (500 mg of niflumic acid) followed by one capsule (250 mg of niflumic acid) should be administered 2 to 4 hours after the start of therapy. From the next day on, we proceed with the normal dose of one capsule 3 or 4 times a day.
The capsule-suppository combination allows you to adapt the treatment to individual cases; obviously the dose is established on the basis of the symptoms manifested by the patient.
The suppository formulation is suitable for the treatment of patients who cannot feed themselves orally and who in any case have difficulty in swallowing and therefore in taking the capsule preparation.
Senior citizens
In the treatment of elderly patients, the posology must be carefully established by the doctor who will have to evaluate a possible reduction in the dose indicated above due to possible side effects, sometimes even serious ones.
Duration of treatment
The duration of treatment with Niflam should be as short as possible. In disorders affecting the ear, nose and throat (ENT system) or the mouth and its appendages (stomatological system), therapy cannot exceed 4-5 days.
Use in children and adolescents
Niflam capsules are contraindicated in children under 12 years of age.
Overdose What to do if you have taken too much Niflam
If you use more Niflam than you should
The manifestations of overdose with Niflam depend on the dose taken and in most cases are mild and have no symptoms.
Symptoms
Symptoms of mild overdose toxicity are:
- irritation of the stomach or intestines (nausea, vomiting, diarrhea, pain in the abdomen)
- drowsiness and headache
Symptoms of more advanced overdose toxicity are:
- increased nitrogen concentration in the blood (azotemia)
- increase in blood creatinine, indicating extensive damage to the kidneys
- increased liver function test
- increased prothrombin time (plasma protein involved in blood clotting)
- reduction in the amount of platelets circulating in the blood (thrombocytopenia)
- slow heart rate (bradycardia)
- low blood pressure (hypotension)
- excessive sleepiness usually associated with an increase in the amount of acids in the blood (metabolic acidosis)
Symptoms of severe overdose toxicity are:
- kidney problems
- increase in the amount of acids in the blood (metabolic acidosis)
- seizures
- sleepiness progressing to coma
- vision and hearing disorders
More rarely, the following have been observed:
- bleeding from the walls of the stomach or intestines (gastrointestinal haemorrhage)
- inflammation of the kidneys (glomerulus nephritis)
Treatment
If you are taking high doses of Niflam, notify your doctor immediately or go to the nearest hospital as appropriate measures may be needed.
If you forget to use / give Niflam to your baby
Do not use / give your child a double dose to make up for a forgotten dose.
If you stop taking Niflam
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 Niflam
Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you experience the following side effects during treatment with Niflam, please contact your doctor immediately, who will STOP the treatment with Niflam:
- bleeding and lesions of the walls of the stomach or intestines (gastrointestinal ulceration), particularly in the elderly, in debilitated subjects, in people with low body weight and in patients treated with anticoagulants or antiplatelet agents (see section "Other medicines and Niflam ")
- increase in liver enzymes (evaluated in a blood test). Increased liver enzyme values are symptoms of impaired liver function
- rash (skin rash), destruction and detachment of the skin and mucous membranes following an allergic reaction (Stevens-Johnson syndrome and Lyell syndrome)
- severe allergic reaction (anaphylactic shock)
In addition, the following side effects have been observed and reported during treatment with Niflam:
Effects affecting the mouth, stomach and intestines
- Injury to the internal walls of the stomach and duodenum (gastroduodenal ulcer), particularly in the elderly, in debilitated subjects, in people with low body weight and in patients who are receiving anticoagulants or antiplatelet agents (see section "Other medicines and Niflam" )
- Nausea, vomiting, diarrhea, excessive gas formation in the stomach or intestines (flatulence), constipation, persistent or recurrent pain and / or discomfort in the upper abdomen (dyspepsia), abdominal pain, dark stools due to the presence of of blood (melena), emission from the mouth of blood from the digestive system (haematemesis), inflammation of the oral mucosa with the formation of small lesions (ulcerative stomatitis), intensification of inflammation of the colon and chronic inflammatory disease of the intestine (disease by Crohn)
- Inflammation of the gastric mucosa (gastritis)
Effects affecting the immune system
- Appearance of red or white bumps of various sizes (urticaria), inflammation of the blood vessels (vasculitis), appearance of purple (purple) skin patches of various sizes, itching, appearance of bright red rosette lesions (erythema multiforme) and manifestations bubble-shaped on the skin (bullous eruptions), increased sensitivity of the skin to the harmful action of the sun's rays (photosensitization)
- Asthma crisis, in patients who have asthma associated with chronic inflammation of the nasal mucosa (chronic rhinitis), chronic inflammation of the mucous membranes and sinuses (chronic sinusitis) and / or with growths in the nasal cavity or sinuses (polyposis nasal), in particular subjects allergic to acetylsalicylic acid or other NSAIDs
- Malaise with lowering of blood pressure.
Effects affecting the nervous system
- Headache (headache) and dizziness (vertigo)
Effects affecting the kidneys and bladder
- Altered functioning of the kidneys (acute renal dysfunction), inflammation involving the renal interstitium (interstitial nephritis), alteration of the renal glomeruli resulting in a loss of protein in the urine (nephrotic syndrome)
Effects affecting the bones
- Accumulation of fluoride in the bones (bone fluorosis) after high dose treatment for several years
Effects affecting the skin and underlying tissue
- Accumulation of fluid in the tissues (edema)
- Serious complications of skin infections in case of chickenpox
Effects affecting the heart and blood vessels
- increased blood pressure and heart problems (heart failure)
- Diseases related to the formation of blood clots inside the arteries (for example myocardial infarction or stroke)
Changes in blood test results
- Alteration of the test that measures the functioning of the liver
- Decrease in the number of platelets in the blood
- Decrease in the number of white blood cells in the blood
- Alteration of the test (false positive) that detects the presence of drugs in the urine
Side effects can be reduced by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms.
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.agenziafarmaco.gov.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
This medicine does not require any special storage conditions.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.
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.
Composition and pharmaceutical form
What Niflam contains
- The active ingredient is 250 mg niflumic acid
- The other ingredients are: talc, corn starch and magnesium stearate
- The components of the empty capsule are: gelatin, titanium dioxide and azorubine (E122) (see section Niflam contains azorubine (E122)).
Description of what Niflam looks like and contents of the pack
Hard capsules for oral use of 250 mg of niflumic acid, packed in boxes of 30 capsules.
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
NIFLAM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
NIFLAM 250 mg hard capsules: one capsule contains: 250 mg niflumic acid.
NIFLAM 500 mg adult suppositories: a suppository contains: beta - morpholinoethyl ester of niflumic acid 700 mg (equal to 500 mg of niflumic acid).
NIFLAM 285 mg suppositories for children: one suppository contains: beta-morpholinoethyl ester of niflumic acid 400 mg (equal to 285 mg of niflumic acid).
03.0 PHARMACEUTICAL FORM
Hard capsules for oral use of 250 mg of niflumic acid; adult suppositories for rectal use of 500 mg of niflumic acid; children's suppositories for rectal use from 285 mg of niflumic acid.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Niflam is indicated to alleviate the inflammation, pain and edema that accompany acute and chronic inflammatory states linked to various diseases, and in particular:
- Joint diseases: rheumatoid arthritis, coxarthrosis, osteoarthritis, rheumatoid spondylitis, ankylosing spondylitis, psoriatic arthritis, acute gouty arthritis.
- Non-joint diseases: bursitis, tenositis, synovitis, epicondylitis.
- Traumatic conditions: fractures, sprains, soft tissue contusions, and in sports medicine (joint pain, tibial periostitis, soft tissue injuries, etc.).
- Post-operative inflammatory states: dental extractions and other dental operative procedures, obstetric-gynecological interventions, nose and throat surgeries.
- Acute and subacute ENT affections.
- Bronchopulmonary affections: bronchopneumopathies, pleurisy.
- Other morbid conditions: acute superficial thrombophlebitis.
In children NIFLAM is indicated in the symptomatic treatment of pain during inflammatory manifestations of the ENT and stomatological system.
04.2 Posology and method of administration
Hard capsules
Typically, 1 capsule of NIFLAM is given three times a day, with or immediately after meals. In severe inflammatory states, especially those of long duration or with acute exacerbations, a maximum daily dose of 4 capsules of NIFLAM (1000 mg of niflumic acid) can be administered. As symptoms improve, the dosage should be reduced to the maintenance level that proves effective. Doses higher than four capsules per day (1000 mg) do not significantly increase the therapeutic effects, but can cause the appearance of side effects that rarely occur at the recommended dosage regimen.
In acute gouty arthritis, an initial dose of 2 capsules (500 mg of niflumic acid) followed by one capsule (250 mg) should be administered 2 to 4 hours after the start of therapy. From the following day onwards, the normal dosage regimen of one capsule is carried out 3 or 4 times a day.
Suppositories
Adults: two suppositories a day, one in the morning and one in the evening, of NIFLAM adult suppositories. The capsule-suppository combination allows a suitable treatment for each case; obviously the dose depends on the clinical picture.
Children: children aged 6 - 12 months: 1 child suppository per day. Children over 12 months of age: from 1 to a maximum of 3 suppositories per day according to age and weight. On average, in these cases, the daily dosage is 1 suppository (285 mg) per 10 kg of weight per acid. niflumico corresponding to 400 mg / 10 kg / day of morniflumate.
Do not administer the product under six months of age. In ENT diseases and in stomatology do not exceed 4-5 days of therapy.
The formulation in suppositories, particularly studied for pediatric use, also allows the treatment of patients who cannot feed themselves orally and who in any case have difficulty in swallowing and therefore to take the preparation in capsules. Due to local toxicity, administration by rectal route must be as short as possible.
In the treatment of elderly patients the posology must be carefully established by the doctor who will have to evaluate a possible reduction of the dosages indicated above.
Undesirable effects can be minimized with the use of the shortest possible duration of treatment that is needed to control symptoms (see section 4.4).
04.3 Contraindications
History of gastrointestinal haemorrhage or perforation related to previous active treatments, or history of recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
NIFLAM is contraindicated in subjects with gastroduodenal ulcer and in subjects with hypersensitivity, a history of allergy or "asthma caused by the administration of niflumic acid / morniflumate or substances with similar activity such as other NSAIDs and aspirin. Hypersensitivity to any of the excipients or closely related substances. from the chemical point of view (see also 4.5).
Contraindicated in cases of severe hepatic and renal insufficiency and severe heart failure.
Contraindicated in pregnancy after 24 weeks of amenorrhea (see 4.6).
In children it is also contraindicated in cases with ulcerative history, rectitis or rectitis and under six months of age.
04.4 Special warnings and appropriate precautions for use
The use of NIFLAM should be avoided in conjunction 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).
Like other NSAIDs, niflumic acid / morniflumate may contribute to an asthma crisis in patients with asthma associated with chronic rhinitis, chronic sinusitis and / or nasal polyposis.
The administration of niflumic acid / morniflumate can cause an asthma attack, particularly in certain subjects allergic to acetylsalicylic acid or to an NSAID.
Literature data suggest that the use of niflumic acid in children may be associated with an increased risk of severe mucocutaneous reactions. Since children between the ages of 6 and 12 months appear to be at greater risk of such reactions, administration of niflumic acid / morniflumate in this age group should only take place after a careful assessment of the risk / benefit ratio in each individual. patient.
Senior citizens: Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section 4.2).
Gastrointestinal bleeding, ulceration and perforationGastrointestinal 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
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 bleeding, ulceration or perforation is higher with increasing doses of NSAIDs. These patients should start treatment with the lowest available dose. 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 below and 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.
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).
When gastrointestinal bleeding or ulceration occurs in patients taking NIFLAM 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).
Gastrointestinal bleeding or ulcers / perforations may occur during treatment with niflumic acid / morniflumate, but similar events have not previously occurred.
The relative risk increases in the elderly, in debilitated subjects, in people with low body weight and in patients who are treated with anticoagulants or antiplatelet agents (see 4.5). Treatment should be stopped immediately in case of gastrointestinal bleeding or ulcer.
Niflumic / morniflumate acid should be administered with caution and under strict medical supervision in patients with a history of digestive disorders (peptic ulcer, hiatal hernia, gastrointestinal haemorrhage, etc.).
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 niflumic acid / morniflumate.
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with niflumic / morniflumate acid 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).
Caution should be exercised in patients with a history of hypertension and / or heart failure as fluid retention and edema have been reported in association with NSAID therapy.
Niflumic acid / morniflumate may mask the usual signs and symptoms of an infection, therefore it should be used with caution in patients with current infections or in those at risk of infection, even if well controlled.
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. NIFLAM should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
Exceptionally, chickenpox can cause severe infectious complications of the skin and soft tissues. At the moment it cannot be excluded that NSAIDs may favor the aggravation of these infections. Consequently, it is advisable to avoid the use of niflumic acid / morniflumate in case of chickenpox (see 4.8).
The physician should be alert to cases of secondary non-ovulatory infertility caused by non-rupture of the Graafian follicle, which have been reported in patients taking prostaglandin synthesis inhibitors as long-term treatment.
This infertility is reversible upon discontinuation of treatment.
Precautions for use
Urinary volume and renal function should be closely monitored at the initiation of niflumic acid / morniflumate treatment in patients with chronic heart failure, renal or hepatic insufficiency, taking diuretics, who have undergone major surgery resulting in hypovolaemia, and particularly in elderly subjects.
04.5 Interactions with other medicinal products and other forms of interaction
Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see section 4.4.).
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4).
Risk linked to hyperkalaemia
Some medicinal products or therapeutic classes may favor the onset of hyperkalaemia: potassium salts, diuretics, ACE inhibitors (angiotensin converting enzyme), angiotensin II inhibitors, NSAIDs, heparins (both low molecular weight and not fractional), cyclosporine, tacrolimus and trimethoprim.
The onset of hyperkalaemia may depend on the existence of associated factors. This risk increases when there is a combination with the medicinal products mentioned above.
Risk related to the antiplatelet effect
Many substances are involved in interactions due to their antiplatelet properties: aspirin and NSAIDs, ticlopidine and clopidogrel, tirofiban, eptifibatide and abciximab, iloprost.
The use of many anti-platelet aggregating agents increases the risk of bleeding as does their combination with heparins, oral anticoagulants and thrombolytics. Such use should be subject to regular clinical and biological monitoring.
? The simultaneous administration of niflumic acid / morniflumate with the following products requires close clinical and biological monitoring of the patient.
Combinations not recommended
With other NSAIDs (including acetylsalicylic acid and other salicylates)
There was an increased risk of gastrointestinal ulcers and bleeding (additive synergy).
With other anticoagulants
NSAIDs may enhance the effects of anticoagulants, such as warfarin (see section 4.4).
If this combination cannot be avoided, close clinical and laboratory monitoring of the patient is required.
With heparin in curative doses or in elderly patients
There was an increased risk of bleeding (inhibition of platelet function and irritation of the gastroduodenal mucosa caused by NSAIDs).
If this combination cannot be avoided, close clinical and laboratory monitoring of the patient is required.
NSAIDs should be administered for a few days.
With lithium
Blood lithium levels are increased and toxic concentrations (reduced renal excretion of lithium) may be reached.
Where necessary, blood lithium levels should be closely monitored and the lithium dosage adjusted during combination treatment and after NSAID treatment has been discontinued.
With methotrexate, used at doses above 15 mg per week
There was an increased risk of haematological toxicity caused by methotrexate (anti-inflammatories reduce the renal clearance of methotrexate).
Combinations requiring precautions for use
With diuretics, ACE inhibitors, and angiotensin II antagonists
NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (eg dehydrated patients or elderly patients with impaired renal function) co-administration of an ACE inhibitor or an angiotensin antagonist II and agents that inhibit the cyclo-oxygenase system can lead to further deterioration of renal function, including possible acute renal failure, usually reversible. These interactions should be considered in patients taking NIFLAM 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.
With methotrexate, used at doses below 15 mg per week
There was an increased risk of haematological toxicity caused by methotrexate (anti-inflammatories reduce the renal clearance of methotrexate).
Blood counts should be checked weekly during the first few weeks of combination treatment.
In case of renal insufficiency (even if mild), and in elderly patients, close monitoring is required.
Combinations that need to be considered
With other antiplatelet agents (ticlopidine, clopidogrel, tirofiban, eptifibatide and abciximab, iloprost) and with heparins at prophylactic doses: an increased risk of haemorrhage was found.
With other agents that cause hyperkalaemia (potassium salts, potassium-sparing diuretics, ACE inhibitors (angiotensin converting enzyme), angiotensin II inhibitors, other NSAIDs, heparins (both low molecular weight and unfractionated), cyclosporine, tacrolimus and trimethoprim)
An increased risk of hyperkalaemia was found.
With beta blockers (by extrapolation from indomethacin data)
A reduction in the antihypertensive effect (NSAIDs inhibit vasodilating prostaglandins) has been reported.
With cyclosporine
Risk of potentiation of nephrotoxic effects, particularly in the elderly patient.
04.6 Pregnancy and lactation
Pregnancy
Inhibition of prostaglandin synthesis can adversely affect pregnancy and / or embryo / fetal development.
Results of epidemiological studies suggest an increased risk of miscarriage and cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiac malformations increased from less than 1% to approximately 1.5%. The risk has been considered to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased loss of pre- and post-implantation and of embryo-fetal mortality.
In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period.
During the first and second trimester of pregnancy, NIFLAM should not be administered except when strictly necessary.
If NIFLAM is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose and duration of treatment should be kept as low as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose the fetus to:
cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension);
renal dysfunction, which can progress to renal failure with oligo-hydroamnios;
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.
Consequently, NIFLAM is contraindicated during the third trimester of pregnancy.
Feeding time
The concentration of niflumic / morniflumate acid in milk is low. However, as a precaution, breastfeeding should be stopped.
04.7 Effects on ability to drive and use machines
The patient should be advised of the possibility of manifestations such as dizziness or drowsiness.
04.8 Undesirable effects
For suppositories, effects related to the route of administration: there was a risk of local toxicity which increases in frequency and severity with increasing duration of treatment, frequency of administration and dosage.
Gastrointestinal system: the most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, gastrointestinal perforation or haemorrhage, sometimes fatal, may occur, particularly in the elderly (see section 4.4.).
Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration of NIFLAM (see section 4.4. - special warnings and precautions for use ).
Gastritis has been observed less frequently.
Increases in dosage and duration of treatment influence the increased frequency of these effects.
Hypersensitivity:
skin and mucus skin reactions: cases of skin rash, urticaria, vasculitis, purpura, pruritus, rare cases of erythema multiforme and bullous eruptions, Stevens-Johnson syndrome, Lyell syndrome, photosensitization in rare cases have been described;
respiratory reactions: asthma attacks in some subjects, especially those allergic to acetylsalicylic acid or other NSAIDs;
general reactions: malaise with hypotension, anaphylactic shock.
Due to the presence of azorubine (E122) in the capsules there is a risk of allergic reactions with the use of this pharmaceutical form.
Central nervous system: Headache and dizziness may rarely occur.
Renal system: acute renal dysfunction, interstitial nephritis, exceptional cases of nephrotic syndrome.
Musculoskeletal system: Few cases of bone fluorosis have been reported after high dose treatment for several years.
Laboratory tests: exceptionally, abnormal liver function tests, thrombocytopenia and leukopenia.
Others: exceptionally, in case of chickenpox, serious skin infectious complications may occur (see 4.4).
Bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rarely).
Edema, hypertension and heart failure have been reported in association with NSAID treatment.
Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially at high doses and for long-term treatment) may be associated with a modest increased risk of arterial thrombotic events (eg, myocardial infarction or stroke) ( see section 4.4).
04.9 Overdose
In the event of an overdose with niflumic acid / morniflumate the foreseeable symptoms are: gastrointestinal irritation, drowsiness (5%) and headache. One subject who ingested 7.5 g of niflumic acid showed glomerulonephritis, which resolved without sequelae. In the event of an overdose, symptomatic treatment is indicated, in addition to gastric lavage and administration of activated charcoal (capsules only).
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Non-steroidal anti-inflammatories.
ATC code: M01AX02 (niflumic acid, capsules) and M01AX22 (morniflumate, suppositories).
NIFLAM is a specialty containing niflumic acid (or trifluoromethyl-3-phenyl-amino-2 nicotinic acid), a non-steroidal compound with marked anti-inflammatory and analgesic activity.
Extensive research in animals has shown that niflumic acid, variously conveyed (esterified in suppositories or formulated in capsules) and administered by different routes (oral, rectal, ip) is capable of effectively inhibiting or even suppressing the inflammatory state, the Experimentally induced pain and edema. Clinical studies have shown that niflumic acid is effective in a wide range of indications and is well tolerated. Its therapeutic efficacy is comparable, and in some cases superior, to that of other anti-inflammatory and analgesic compounds. Niflumic acid does not normally cause sodium retention so it can be used in elderly patients without fear of edematous events. The use of niflumic acid can allow a considerable reduction in the dosage of corticosteroids in patients who require such therapy. Clinical experience has highlighted both the constant efficacy of niflumic acid in morbid conditions that require prolonged treatment, and its rapid and intense anti-inflammatory and analgesic action in numerous inflammatory diseases and in acute post-operative states. and post-traumatic This action occurs after both oral and rectal and / or local administration.
05.2 Pharmacokinetic properties
Niflumic acid, administered as such orally or in its esterified form rectally (beta-morpholinoethyl ester specially designed for its absorption via the rectum), is readily absorbed and made available: in rabbits, high blood concentrations of niflumic acid are found already in the first hour after rectal administration. After administration by this route, once released by the action of specific esterases, its concentrations remain elevated for much longer periods than oral administration.
05.3 Preclinical safety data
Acute treatments show a relative low toxicity of the product (LD50 os 1400 mg / kg in the mouse and 580 mg / kg os in the rat). Repeated oral treatments (25 mg / kg / day in rats and dogs and 200 mg / kg / day in monkeys) have demonstrated the high tolerability of niflumic acid administered for up to one year. In particular the tests have shown a good gastric tolerability (critical aspect of all products with anti-inflammatory activity) at doses that correspond to 20-40 times the human therapeutic dose. The rectal tolerability of the esterified form was good after one month in the rabbit. Specific studies carried out in the rat treated orally with doses up to 400 mg / kg they demonstrated an absolute lack of negative effects on the central nervous and cardiovascular systems: this leads us to believe that niflumic acid does not have similar behavior with drugs that act on the CNS or that can induce habituation or dependence.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Capsules: talc, corn starch, magnesium stearate.
Composition of the empty capsule: gelatin, titanium dioxide (E 171), azorubine (E 122).
Suppositories: solid semisynthetic glycerides.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
Capsules: in intact packaging: 3 years.
Suppositories: in intact packaging: 3 years.
06.4 Special precautions for storage
Capsules: no special storage precautions
Suppositories: store at a temperature not exceeding 25 ° C
06.5 Nature of the immediate packaging and contents of the package
Capsules: Carton containing 3 blisters of 10 capsules each.
Adult suppositories: Box containing 10 suppositories in heat-sealed P.V.C.
Suppositories for children: Box containing 10 suppositories in heat-sealed P.V.C.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Bristol-Myers Squibb S.a.r.l. - Rueil Malmaison (France), represented in Italy by Bristol-Myers Squibb S.r.l., Via del Murillo, km 2,800 - Sermoneta (LT)
08.0 MARKETING AUTHORIZATION NUMBER
Capsules: AIC n. 022824015
Suppositories AD: AIC n. 022824066
Suppositories BB: AIC n. 022824078
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
May 2005.
10.0 DATE OF REVISION OF THE TEXT
November 2008
