Naysulid

General characteristics. Structure:

Active ingredient: 100 mg of Nimesulide in 2 g of powder.

Excipients: xanthane gum, silicon dioxide colloid anhydrous, calcium stearate, anhydrous citric acid, aspartame (Е 951), oil lemon, granulated sugar.

The non-steroidal anti-inflammatory drug having soothing, febrifugal and antiinflammatory properties.

Pharmacological properties:

Pharmacodynamics. Nimesulide has big affinity to cyclooxygenase-2, at the inhibiting activity which was less expressed cyclooxygenase-1. Slows down synthesis of prostaglandins, suppresses education of free oxygen radicals without influence on a hemostasis and phagocytosis. Inhibits myeloperoxidase enzyme release.

Pharmacokinetics. Absorption. After intake Nimesulide is well soaked up from a GIT. The maximum concentration in a blood plasma is reached in 2 – 3 h after reception.

Distribution. Linkng with proteins of plasma – 97,5%. Metabolism. Nimesulide is metabolized with participation of an isoenzyme of P450 (CYP2C9) cytochrome therefore at reception of Nimesulide concentration of this enzyme falls. Thereof concentration of medicines in a blood plasma which are substrate for CYP2C9 enzyme increases if they were accepted along with Nimesulide.

The only metabolite of Nimesulide which is in a blood plasma – para-hydroxynimesulide is pharmacological active. Its T1/2 makes 3,2-6 hours.

Removal. About 50% of the accepted Nimesulide are removed with urine. About 29% of the accepted dose are removed with a stake. Only 1 - 3% of Nimesulide is removed in steady-state condition. Gidroksinimesulid is brought in the form of a glyukoronat.

Indications to use:

- treatment of an acute pain;
- primary dysmenorrhea.

Найсулид® it can be appointed only as means of therapy of the second line. The decision on purpose of Nimesulide has to be based on the general assessment of risk for each patient.

Route of administration and doses:

Before use it is necessary to prepare suspension. For this purpose contents of a package are dissolved in 100 ml of the svezheprokipyachenny, cooled to room temperature drinking water and intensively shaken up. After that suspension is ready to the immediate use.

Suspension is accepted after food. The adult medicine is appointed in a single dose on 100 mg (1 bag of powder).

And to elderly patients correction of a dose is not required to patients aged from 12 up to 18 years. Medicine is contraindicated to children up to 12 years.

At the easy and moderated forms of a renal failure (clearance of creatinine of 30 - 80 ml/min.) correction of a dose is not required. At a heavy renal failure (clearance of creatinine less than 30 ml/min.) medicine is contraindicated.

Nimesulide is accepted during shorter period to minimize risk of development of side reactions.

The maximum duration of reception of Nimesulide should not exceed 15 days.

Features of use:

When using Naysulida® it is necessary to avoid its combination to non-steroidal anti-inflammatory drugs (NPVS), including the selection inhibitors of cyclooxygenase. It is necessary to abstain from reception of other accompanying analgetics.

Undesirable effects can be minimized when using the lowest effective dose during the minimum time necessary for elimination of symptoms. If the condition of the patient does not improve, treatment needs to be stopped.

Hepatic effects. In rare instances there can be serious hepatic reactions connected using Naysulida®, including seldom or never with a lethal outcome. At emergence in the patients accepting Naysulid®, symptoms indicating injury of a liver (anorexia, nausea, vomiting, an abdominal pain, increased fatigue, urine darkening) or increases in level of hepatic transaminases, drug should be cancelled. Such patients are not recommended to accept Nimesulide further. If at the patients accepting Naysulid® fever and/or grippopodobny symptoms began, treatment has to be stopped immediately!

At short reception of Naysulida® damage of a liver usually is reversible.

Gastrointestinal disturbances. Найсулид® it is necessary to use with care at patients with chronic gastrointestinal diseases, including with a peptic ulcer, gastrointestinal bleedings, ulcer colitis or a disease Krone (in connection with risk of an exacerbation of the specified diseases). Also with care the patients taking other medicine which can increase risk of an ulceration or bleeding should appoint it: oral corticosteroids, anticoagulants: (warfarin), selective serotonin reuptake inhibitors or antiagregant (aspirin).

Gastrointestinal bleeding or ulcer, perforation of a stomach or dveyonadtsatiperstny gut can develop against the background of use of drug and can be asymptomatic (including painful).

The risk of gastrointestinal bleedings, ulcers or perforation is increased at reception of high doses of Naysulida®, at patients with an ulcer in the anamnesis, at elderly people. These patients have to begin treatment with the lowest dose. At these patients, and also persons who accept Naysulid® together with cardiological doses of acetylsalicylic acid the combination therapy together with gastroprotektor has to be applied (inhibitors of the proton pump or мизопростол).
Patients with gastrointestinal disturbances in the anamnesis and elderly people have to report about any unusual abdominal symptoms (including bleedings), especially at early stages of treatment. At emergence of cankers or hemorrhagic complications it is necessary to stop treatment of Naysulidom®.

Elderly people. Elderly people have the increased frequency of side reactions on NPVS, high risk of gastrointestinal bleedings and perforation which can be fatal. It is necessary to provide careful control of side effects at this group of patients.

Cardiovascular and cerebrovascular effects. The delay of liquid and hypostases in connection with use of NPVS were described. Careful control and consultations are necessary for patients with a hypertension and/or heart failure.

Clinical trials and epidemiological data show that use of some NPVS (especially in high doses and it is long) can be connected with small increase in risk of arterial thromboembolic events (for example, a myocardial infarction and a stroke). There are not enough data to exclude such risk at reception of Naysulida®.

To patients with uncontrollable arterial hypertension, congestive heart failure, coronary heart disease, diseases of peripheral arteries and/or cerebrovascular diseases medicine is appointed after ratio assessment risk/advantage. Similarly it is necessary to arrive before prolonged treatment at patients with risk factors of cardiovascular diseases (a hypertension, epilepsy, a diabetes mellitus, smoking).

Найсулид® can influence activity of thrombocytes, it should be used with care at patients with hemorrhagic diathesis, Naysulid® is not replacement of acetylsalicylic acid for the purpose of prevention of cardiovascular diseases.

Renal failure. Найсулид® it is necessary to take with caution at patients with renal or heart failure since it can lead to injury of kidneys. In such cases treatment has to be stopped.

Skin effects. Heavy skin reactions (including potentially lethal): dermatitis, Stephens-Johnson's syndrome and a toxic epidermal necrolysis, in connection with reception of NPVS develop very seldom. The probability of their development at early stages of therapy in most cases within the first month of treatment is highest. Use of Nimesulide has to be stopped at the first emergence of skin rash, damages of mucous membranes or any other sign of intolerance.

Use at pregnancy and a lactation. As well as other non-steroidal anti-inflammatory drugs (NPVS) Nimesulide is not recommended to the women planning pregnancy.

The Nimesulide inhibiting a prostaglandinsintetaza can be the cause of premature closing of a botallov of a channel, pulmonary hypertensia, an oligouriya, an oligoamniya, the risk of bleedings and peripheral hypostases increases. Also there are messages on the birth of children with a renal failure at the women accepting Nimesulide in the III trimester of pregnancy.

Tests on rabbits revealed toxicity of Nimesulide on reproductive function. It is not possible to obtain adequate data on women. Therefore the potential risk for the person is not known and purpose of Nimesulide in the I-II trimester is not recommended.

It is unknown whether Nimesulide in breast milk is excreted. Therefore a contraindication for reception of Nimesulide is breastfeeding.

Influence on ability of control of vehicles and other difficult mechanisms. Were not conducted researches on influence of Naysulida® on ability of control of motor transport or work with cars and mechanisms. If when using drug there are undesirable phenomena from the central nervous system and sense bodys, it is necessary to refrain from driving by motor transport and occupations the types of activity demanding the increased concentration attention and speed of psychomotor reactions.

Side effects:

The following list of side reactions is based on results of controlled clinical tests * (with participation about 7800 people) and pharmacological data. Cases of side reactions are classified as it is very frequent (> 1/10), is frequent (> 1/100, <1/10), infrequently (> 1/1000 to <1/100), is rare (> 1/10000, <1/1000), is very rare (<1/10 000), including separate messages:

From system of blood and lymphatic system: seldom – anemia *, an eosinophilia *; very seldom – thrombocytopenia, a pantsitopenichesky purpura.

From immune system: seldom – hypersensitivity *, it is very rare – an anaphylaxis.

From metabolism and food: seldom – гиперкалиемия*.

From mentality: seldom – alarm *, nervousness *, nightmares *; not often – golovokru-zheniye*.

From a nervous system: very seldom – a headache, a somnolention, encephalopathy (a syndrome to Reja).

From eyes: seldom – sight opacification *; very seldom – a vision disorder.

From a hearing and vestibular mechanism: very seldom – dizziness.

From heart: seldom – tachycardia *; not often – hypertensia.

From cardiovascular system: seldom – hemorrhages *, fluctuations of arterial pressure, inflows.

From respiratory organs, a thorax and mediastinum: not often – an asthma *, it is very rare – a bronchospasm, asthma attack, diarrhea *, is frequent – nausea *, vomiting *, a lock *, a meteorism *, гастрит*.

From digestive tract: not often – gastrointestinal bleeding, an ulcer and perforation of an ulcer of a 12-perstny gut, an ulcer and perforation of stomach ulcer; very seldom – abdominal pain, dyspepsia, stomatitis, a melena.

From gepato-biliary system: often – increase in level of "liver enzymes"; very seldom – hepatitis, fulminintny hepatitis (including lethal outcomes), cholestatic jaundice; not often – an itch *, irritation *, the increased sweating *; seldom – an eritrema *, дерматит*.

From skin and hypodermic cellulose: very seldom – a small tortoiseshell, a Quincke's disease of Quincke, a face edema, a multiformny erythema, Stephens-Johnson's syndrome, a toxic epidermal necrolysis.

From kidneys and urinary tract: seldom – a dysuria *, a hamaturia *, an ischuria *; very seldom – a renal failure, an oliguria, intersticial nephrite; not often – отеки*.

General disturbances: seldom – an indisposition *, an adynamy *; very seldom – a hypothermia.

Interaction with other medicines:

Simultaneous use of Nimesulide with warfarin or other anticoagulants, and also acetylsalicylic acid provokes risk of emergence of bleedings. Therefore such combination is not recommended and serves as a contraindication for patients with various disturbances of a blood coagulation. If such combination is inevitable, then anticoagulating activity has to be controlled carefully.

Nimesulide inhibits CYP2C9 owing to what concentration in plasma of the medicines which are substrates of this enzyme can increase.

The concomitant use of Nimesulide with diuretic can negatively affect a renal hemodynamics. Usual concentration of unsaturated fatty acids do not influence communication of Nimesulide with albumine. At patients with reduced synthetic function of a liver or the expressed renal failure linkng of Nimesulide with proteins of plasma (however, as well as other NPVP) considerably decreases, leading to emergence of free fraction of drug which can strengthen the frequency and expressiveness. At simultaneous use of Nimesulide and furosemide removal of sodium and potassium quickly decreases, and, therefore, the effect of diuretics decreases. Result of a combination of Nimesulide and furosemide is decrease (to 20%) the areas under a kinetic curve and total excretion of furosemide by renal clearance. Simultaneous use of furosemide and Nimesulide requires special attention at patients with heart diseases or kidneys. The concomitant use of Nimesulide with diuretic can negatively affect a renal hemodynamics.

Nimesulide promotes accumulation of lithium in plasma therefore its toxicity increases.

Pharmacokinetic interaction with glibenclamide, theophylline, digoxin, Cimetidinum and antacids in vivo were also studied, however clinically significant interaction was not revealed.

Nimesulide reception less than in 24 hours prior to or after treatment by a methotrexate leads to increase in concentration of the last in blood serum that increases its toxicity.

Effect of Nimesulide on a prostaglandinsintetaza and on renal prostaglandins can lead to increase in nephrotoxicity of cyclosporine.

Contraindications:

- hypersensitivity to Nimesulide or other components of drug;
- in the anamnesis hypersensitivity (a bronchospasm, rhinitises, a small tortoiseshell, etc.) to acetylsalicylic acid and other derivatives of sulfonamides, other nonsteroid protivospalitelny means, "aspirinovy asthma";
- in the anamnesis hepatotoxic reactions to Nimesulide;
- the expressed abnormal liver functions, a liver failure;
- renal failure (clearance of creatinine <30ml/mines); heavy renal failure;
- stomach ulcer or a duodenum in an aggravation phase, recurrent ulcers or bleedings in digestive tract, the cerebral hemorrhages or disturbances which are followed by bleeding;
- heavy disturbances of coagulability of blood;
- heavy heart failure;
- fenilketonuriya;
- pregnancy and period of a lactation;
- children's age up to 12 years;
- co-administration with other potentially hepatotoxic medicines;
- alcoholism, medicinal dependence;
- fervescence or grippopodobny syndrome.

Overdose:

Symptoms of acute overdose of Nimesulide are shown by apathy, drowsiness, nausea and vomiting, pain in epigastric area which decreases at a symptomatic treatment. The overdose can be shown by gastrointestinal bleedings, is rare – hypertensia, an acute renal failure, decrease in respiratory activity and a coma.

At overdose of Nimesulide the symptomatic or maintenance therapy is shown.

Nimesulide has no specific antidote. There is no information on removal of Nimesulide at a hemodialysis, but since it has high extent of linkng with proteins of plasma (97,5%), the hemodialysis at overdose treatment most likely is useless. Nimesulide is also not removed at acceptance of diuretic drugs and at use of hemoperfusion, urine alkanization, an artificial diuresis.

If the overdose happened within the last 4 hours, then it is necessary to accept absorbent carbon (60-100 g for adults), the medicine causing vomiting or osmotic laxative.

At overdose functions of kidneys and a liver have to be controlled carefully.

Storage conditions:

To store in the place protected from light at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity 2 years.

Issue conditions:

Without recipe

Packaging:

On 2,0 g of powder in the thermowelded packages placed together with a leaf insert in packs from a cardboard No. 10 and No. 20.