INSTRUCTION for medical use

Transcription

1 APPROVED Order of Ministry of Healthcare of Ukraine _127_ Registration certificate _UA/4240/01/02_ INSTRUCTION for medical use NIMID FORTE Composition: active substances: nimesulide, tizanidine hydrochloride; 1 tablet contains nimesulide 100 mg, tizanidine hydrochloride equivalent to tizanidine 2 mg; excipients: microcrystalline cellulose, croscarmellose sodium, magnesium stearate, silica colloidal anhydrous. Pharmaceutical Form: Tablets. Pharmacotherapeutic group: Nonsteroidal anti-inflammatory and anti-rheumatic drugs. Code АТС М01А. Clinical characteristics: Indications: Acute pain caused by skeletal muscle spasm. Bechterew's disease. Vertebroalgia. Contraindications. Hypersensitivity to the active substance or to any component of the drug. History of hypersensitivity reactions (bronchospasm, rhinitis, urticaria) to acetylsalicylic acid or to other non-steroidal antiinflammatory drugs. Active gastric or duodenal ulcer, history of recurrent ulcer or gastrointestinal bleeding, cerebrovascular bleeding or other active bleedings accompanying other diseases; pronounced hepatic impairment (liver failure) and hepatotoxic response to receiving the drug in history; coadministration with potentially hepatotoxic agents; severe impairment of kidney function (creatinine clearance < 30 ml/min), severe coagulation diseases; severe heart failure. Alcoholism, drug abuse. Hyperthermia, flu-like conditions, suspected acute surgical pathology. Concomitant use of fluvoxamine and ciprofloxacin. Administration and dosage. To prevent the development of side effects, to reduce their manifestations, the minimum effective dose should be used for the shortest time. The drug should be administered only after precise assessment of risk/advantage ratio. The drug is taken orally after meal with sufficient quantity of liquid. Adults are administered 1 tablet (100 mg) 2 times per day: in the evening and in the morning. Maximum duration of the treatment is 15 days. After achieving the analgesic effect, the drug should be stopped. The scheme of the treatment does not need to be adjusted for elderly patients. Side effects.

2 When evaluating the frequency of various side effects, the following criteria were used: very common ( 1/10); common ( 1/100 < 1/10); uncommon ( 1/1000 < 1/100); rare ( 1/10000 <1/1000); very rare (< 1/10000), including isolated reports. Nimesulide: Blood and lymphatic system Immune system Metabolic Anemia Eosinophilia Thrombocytopenia Pancytopenia Purpura Hypersensitivity Anaphylaxis Hyperkalemia Mental Apprehensiveness Irritability Nightmares Nervous system Dizziness Vision Blurred vision Ear and labyrinth Headache Sleepiness Encephalopathy (Reye s syndrome) Vertigo (dizziness) Cardiac Tachycardia Vascular Arterial hypertension Respiratory system Digestive system Hemorrhage Labile blood pressure Blush Dyspnea Asthma Bronchospasm Diarrhea Nausea Vomiting Constipation Flatulence Gastritis Abdominal pains Dyspepsia Stomatitis Black stool

3 Hepatobiliary system Disorders of cutaneous and subcutaneous tissues Kidney and urinary system Gastrointestinal bleeding Ulcer and perforated ulcer of stomach and duodenum Hepatitis Fulminant hepatitis (including cases with fatal outcome) Jaundice Cholestasis Itching Skin rash Excessive sweating Erythema Dermatitis General Edema Urticaria Angioneurotic edema Swelling of the face Poliform erythema Stevens-Johnson syndrome Toxic epidermal necrolysis Dysuria Hematuria Urinary retention Renal failure Oliguria Interstitial nephritis Weakness Asthenia Hypothermia Laboratory data Elevated liver enzymes Tizanidine: Blood and lymphatic system Immune system Petechiae or bruising Thrombocytopenia Hypersensitivity Anaphylaxis Mental Hallucinations Depression Nervous system Sleepiness Dizziness Insomnia

4 Cardio-vascular system Musculoskeletal system Digestive system Hepatobiliary system Disorders of cutaneous and subcutaneous tissues Sleep Syncope states (loss of consciousness, swoon) Excitation Nervousness Paresthesia Bradycardia Arterial hypotension Palpitation Prolongation of QT interval Muscular weakness Myalgia Back pain Muscular spasms Tremor Dry mouth Gastric pain Loss of appetite Nausea Vomiting Constipation Diarrhea Jaundice Hepatitis Hepatic failure Skin rash Itching Urticaria Alopecia General Weakness Flu-like condition Asthenia Increased fatigability Laboratory data Elevated liver transaminases Side effects occur very rarely when using low doses recommended for painful muscle spasm relief; they are usually low-grade and transitory. It was reported about possible somnolence, weakness, dizziness, dry mouth, blood pressure decreasing, gastro-intestinal tract and elevated liver transaminases. Above-mentioned side effects occur more often and they are more severe when using higher doses recommended for spasticity treatment, but they rarely can be so severe to stop the treatment. Overdose. Symptoms. In case of overdose, lethargy, somnolence, nausea, vomiting, abdominal pain may be observed, as well as gastrointestinal bleeding, arterial hypertension, acute kidney and liver failure, arterial hypotension, dizziness, myosis, excitation, respiratory depression, prolongation of QT interval, anaphylactoid reactions and coma.

5 Treatment. There is no specific antidote. In case of overdose, symptomatic treatment should be given. Patients need gastric lavage within the first four hours of overdose, and intake of activated carbon. Haemodialysis is non-effective. Careful monitoring of kidney and liver function is necessary. Pregnancy and lactation. Pregnancy. The drug is contraindicated in the 3 rd trimester of pregnancy. Using nimesulide may impair female fertility and is not recommended in women attempting to conceive. As with other nonsteroidal anti-inflammatory drugs, known to inhibit prostaglandin synthesis, nimesulide may cause premature closure of the ductus arteriosus, pulmonary hypertension, oliguria, oligoamnios. There is an increased risk of bleeding, uterine inertia and peripheral edema. Taking in the account the absence of data on the use of nimesulide in pregnant women, prescribing the drug during the 1 st and 2 nd trimesters of pregnancy is not recommended. Lactation. As it is not known whether nimesulide is excreted in human milk, nimesulide is contraindicated when breastfeeding. Children. The drug is contraindicated in children. Precautions for use. It is not recommended to use the drug synchronously with other nonsteroidal anti-inflammatory drugs. To decrease the risk of adverse effects, minimal effective dose should be used with minimal duration of the treatment course. If patient s state does not improve the treatment should be stopped. In case of elevation of liver enzymes or any signs of liver damage (such as anorexia, nausea, vomiting, gastric pain, fatigability, dark urine), the drug should be stopped. These patients should not be prescribed nimesulide in future. During the treatment with Nimid Forte, it is recommended to avoid concomitant usage of hepatotoxic drugs, analgesics and other nonsteroidal anti-inflammatory drugs and refrain from taking alcohol. Gastro-enteric bleeding or ulcer/perforation may develop at any moment of the drug therapy, with or without preventive symptoms, with or without gastro-enteric complications in anamnesis. In case of gastro-enteric bleeding or ulcer, the drug should be stopped. Caution should be exercised when prescribing Nimid in patients with gastro-enteric, ulcerous colitis or Crohn s disease in anamnesis. Caution should be exercised when prescribing the drug in patients with kidney or cardiac failure, as its use may impair the renal function. In case of impairment of liver function, the drug should be stopped. Adverse effects of the drug, including gastro-intestinal bleeding, perforations, cardiac and kidney function impairments, and compromised liver function, are more common in elderly patients. Therefore, regular clinical control of patient s status is recommended. As nimesulide may affect platelet function in patients with hemorrhagic diathesis, it should be used with caution and under permanent control. The use of nonsteroidal anti-inflammatory drugs may mask hyperthermia, which is due to background bacterial infection. In the case of increasing of body temperature or flu-like symptoms, the drug should be stopped. The drug may cause the prolongation of QT interval, especially in patients concomitantly using the drugs, which may provoke the prolongation of QT interval. Effects on ability to drive and operate machinery No studies on the effect of nimesulide on the ability to drive and perform the work requiring increased concentration of attention have been performed. However, patients experiencing dizziness or somnolence after receiving nimesulide should refrain from driving and performing the work requiring increased concentration of attention.

6 Interaction with other medicinal products and other forms of interaction. When concomitant use with warfarin and analogous anticoagulants, acetylsalicylic acid, there is an increased risk of bleeding. Concomitant use of nimesulide and furosemide requires caution in patients with kidney and heart function. Nonsteroidal anti-inflammatory drugs reduce clearance of lithium resulting in elevated plasma levels and lithium toxicity. Therefore in concomitant use of nimesulide and lithium therapy, lithium levels should be monitored closely. No clinically significant interactions were observed in case of concomitant use of nimesulide and digoxin, theophylline, glibenclamide, ranitidine and antacids. Nimesulide inhibits CYP 2C9 enzyme action. Therefore, plasma concentration of drugs that are substrates of this enzyme may be increased when nimesulide is used concomitantly. Caution is required when nimesulide is used less than 24 h before or after the intake of methotrexate, as the serum level of methotrexate and its toxicity may increase. Increased nephrotoxicity of cyclosporines is possible when concomitant use with nimesulide. Concomitant use of hypotensive agents potentiates the development of arterial hypotension and bradycardia. Sedatives and ethanol increase the pharmacologic effects of the drug. Concomitant use of tizanidine and fluvoxamine or cyprofloxacine, which inhibit CYP450 1A2, is contraindicated. Concomitant use of tizanidine and fluvoxamine or cyprofloxacine increases area under concentration/time curve of tizanidine by 33 and 10 times, correspondingly. Arterial hypotension might occur along with sleepiness, dizziness and decreased psychomotor reactions. Caution is necessary when using tizanidine with other CYP1A2 inhibitors, such as as antiarrhythmic drugs (amidarone, mexiletine, propafenone), cimetidine, fluoroquinolones (enoxacin, pefloxacin, norfloxacin), rofecoxib, oral contraceptives and ticlopidine. Pharmacological properties. Pharmacodynamics. This is a combined drug, the pharmacological properties of which depend on combined action of its components. Nimesulide is an active substance with anti-inflammatory, analgesic and antipyretic properties. Nimesulide selectively inhibits COG II (cyclooxygenase II) and depresses the synthesis of prostaglandins in the focus of inflammation. Nimesulide inhibits the release of myeloperoxidase and formation of free oxygen radicals without affecting phagocytosis and chemotaxis processes, it inhibits formation of tumor necrosis factor and other mediators of inflammation. Tizanidine is a central-acting myorelaxant. It selectively depresses polysynaptic reflexes of spinal cord, takes part in regulation of muscular tonus. It is effective in acute and painful muscular spasms and chronic spasms of spinal and cerebral origin. The drug depresses the formation of superoxide anion and thereby prevents the lesion of the tissues. Pharmacokinetics: Nimesulide is quickly absorbed from gastro-intestinal tract after oral intake. Peak concentrations in plasma occur after 2 to 3 hours. 97.5% of nimesulide are bound with plasma proteins. The drug is metabolized in liver; the main metabolism product is hydroxynimesulide? A pharmacologically active substance. Approximately 65% of the ingested dose of nimesulide is excreted with urine and the other 35% with faeces. Tizanidine is quickly and almost completely absorbed from gastro-intestinal tract after oral intake. Peak concentrations of tizanidine in plasma occur after 1 hour. 30% of tizanidine are bound with proteins of plasma. Tizanidine is metabolized in liver and its metabolites have no pharmacological activity. The elimination half-life of tizanidine is 2-4 hours. Tizanidine is mainly excreted through kidney (approximately 70%) as metabolites; approximately 2.7% of tizanidine are excreted unchanged Pharmaceutical characteristics:

7 general physical and chemical properties: round light-yellow tablets, smooth on one side and embossed NF on the other. Shelf-life. 3 years. Storage conditions. Store at the temperature not more than 25 С, in the original package. Keep out of reach of children. Package. 10 tablets are in a blister, each blister is packed in a carton package. 10 packages are in a carton box Conditions of supply. By prescription. Manufacturer: KUSUM HEALTHCARE PVT. LTD. Address. SP 289 (A), RIICO Indl. Area Chopanki, Bhiwadi (Raj.), India. Last revision date.