Instructions Remesulide Rapid granules for oral suspension 100 mg/2 g sachet 2 g No. 10
Composition
active ingredient: nimesulide;
1 sachet contains nimesulide in terms of 100% dry matter – 100 mg;
Excipients: granulated sugar (powder); corn starch; spray-dried glucose solution; polyethylene glycol (macrogol) cetostearyl ester; anhydrous citric acid; orange flavoring.
Dosage form
Granules for oral suspension.
Main physicochemical properties: light yellow granular powder with an orange odor.
Pharmacotherapeutic group
Other nonsteroidal anti-inflammatory and antirheumatic drugs, nimesulide. ATX code M01A X17.
Pharmacological properties
Pharmacodynamics
Nimesulide belongs to the group of nonsteroidal anti-inflammatory drugs (NSAIDs) with analgesic and antipyretic properties; nimesulide acts as an inhibitor of the enzyme cyclooxygenase, which is involved in the synthesis of prostaglandins.
Pharmacokinetics
Nimesulide is well absorbed after oral administration. After a single dose of 100 mg of nimesulide, the maximum plasma concentration (3–4 mg/l) is reached in adults in 2–3 hours. AUC is 20–35 mg*h/l per hour. No statistically significant difference was found between these indicators and similar indicators when using a dose of 100 mg of nimesulide 2 times a day for 7 days.
Binding to blood plasma proteins is 97.5%.
Nimesulide is extensively metabolized in the liver by various pathways, including the cytochrome P450 (CYP) 2C9 isoenzyme. Therefore, there is a possibility of its interaction with concomitantly administered drugs that are also metabolized by CYP2C9. The main metabolite is the parahydroxy derivative, which also has pharmacological activity. The time to appearance of this metabolite in the blood is short (about 0.8 hours), but the rate of its formation is low and significantly lower than the rate of absorption of nimesulide. Hydroxynimesulide is almost completely conjugated and is the only metabolite that can be detected in blood plasma. Its half-life (T½) is 3.2–6 hours.
Nimesulide is excreted mainly in the urine (about 50% of the dose taken). Only 1-3% is excreted unchanged. Hydroxynimesulide, the main metabolite, can only be detected as a glucuronide. Approximately 29% of the dose taken after biotransformation is excreted in the feces.
The kinetic profile of nimesulide in elderly patients did not change after single or repeated dosing.
When taking nimesulide in patients with mild to moderate renal insufficiency (creatinine clearance 30-80 ml/min) and healthy volunteers in studies, the maximum concentration of nimesulide and its main metabolite in the blood plasma in subjects with impaired renal function did not exceed that in healthy volunteers. The AUC and t1/2 beta (half-life, beta phase) values were 50% higher, but remained within the kinetic values observed when using nimesulide in healthy volunteers.
Repeated administration of the drug did not lead to its accumulation in the body.
Indication
Treatment of acute pain, primary dysmenorrhea.
Nimesulide should only be used as a second-line drug. The decision to prescribe nimesulide should be based on an overall risk assessment for the individual patient.
Contraindication
Hypersensitivity to nimesulide or to any of the excipients of this product; history of hypersensitivity reactions (e.g. bronchospasm, rhinitis, urticaria, nasal polyps), including reactions to acetylsalicylic acid or other NSAIDs; history of hepatotoxic reactions to nimesulide; concomitant use of other potentially hepatotoxic substances; alcoholism, drug addiction; history of gastrointestinal bleeding or perforation associated with previous NSAID therapy; history of active or recurrent peptic ulcer/bleeding (two or more distinct episodes of confirmed ulceration or bleeding); cerebrovascular bleeding or other active bleeding or bleeding disorders; severe coagulation disorders; severe heart failure; severe renal impairment; impaired liver function; patients with fever and/or flu-like symptoms; children under 12 years of age; third trimester of pregnancy and breastfeeding.
Interaction with other medicinal products and other types of interactions
Pharmacodynamic interactions:
Other NSAIDs: the simultaneous use of Remesulide® Rapid and other NSAIDs, including acetylsalicylic acid taken in anti-inflammatory doses (≥ 1 g - single dose or ≥ 3 g - total daily dose), is not recommended.
Corticosteroids: increase the risk of gastrointestinal ulcers and bleeding.
Patients taking warfarin or similar anticoagulants are at increased risk of bleeding when treated with Remesulide® Rapid. Therefore, such combinations are not recommended and are contraindicated in patients with severe coagulation disorders. If the combination of these substances cannot be avoided, blood coagulation parameters should be carefully monitored.
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): Concomitant use of antiplatelet agents or SSRIs increases the risk of gastrointestinal bleeding.
Diuretics, angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin II antagonists (AIIAs): NSAIDs may reduce the effectiveness of diuretics and antihypertensive drugs.
In some patients with reduced renal function (e.g. dehydrated patients or elderly patients with compromised renal function), concomitant use of ACE inhibitors and cyclooxygenase inhibitors may lead to worsening of renal function, including the possibility of acute renal failure, which is usually reversible.
The occurrence of such an interaction should be considered for patients who must take Remesulide® Rapid simultaneously with ACE inhibitors or angiotensin II antagonists. If these drugs are taken simultaneously, the following measures should be observed, especially in elderly patients: patients should be adequately hydrated, their renal function should be monitored from the start of combined treatment and periodically tested.
Pharmacokinetic interactions: the effect of nimesulide on the pharmacokinetics of other drugs
Furosemide. In healthy volunteers, nimesulide temporarily reduces the effect of furosemide on sodium excretion and, to a lesser extent, on potassium excretion, and also reduces the response to diuretic administration.
Concomitant use of nimesulide and furosemide leads to a decrease (by approximately 20%) in AUC and cumulative excretion of furosemide without changes in renal clearance.
Caution should be exercised when furosemide and nimesulide are used concomitantly in patients with renal and cardiac dysfunction.
Lithium: NSAIDs have been reported to reduce lithium clearance, leading to increased plasma lithium levels and toxicity. If nimesulide is prescribed to patients receiving lithium therapy, lithium levels should be closely monitored.
Possible pharmacokinetic interactions with glibenclamide, theophylline, warfarin, digoxin, cimetidine and antacids (aluminum hydroxide and magnesium hydroxide combination) were also studied in vivo. No clinically significant interactions were found.
Nimesulide inhibits CYP2C9. Plasma concentrations of drugs metabolized by this enzyme may increase with concomitant use of nimesulide.
Caution is required if nimesulide is administered less than 24 hours before or less than 24 hours after methotrexate, as serum levels of methotrexate may increase, thus increasing the toxicity of this medicinal product.
Due to their effect on renal prostaglandins, prostaglandin synthetase inhibitors, to which nimesulide belongs, may increase the nephrotoxicity of cyclosporines.
Pharmacokinetic interactions: the effect of other drugs on the efficacy of nimesulide
In vitro studies have shown that nimesulide is displaced from binding sites by tolbutamide, salicylic acid and valproic acid.
However, regardless of the possible effect on plasma levels, these interactions are of no clinical significance.
Application features
The risk of adverse reactions can be reduced by using the lowest effective dose for the shortest period sufficient to control the symptoms of the disease.
Nimesulide should not be used concomitantly with NSAIDs, including selective cyclooxygenase-2 inhibitors. In addition, patients should be advised to avoid concomitant use of other analgesics.
If no positive effect of treatment is observed, the drug should be discontinued.
Effects on liver function
There have been rare reports of serious hepatic reactions, including very rare fatal cases, with nimesulide. Patients who develop symptoms of hepatic disorders (e.g. anorexia, nausea, vomiting, abdominal pain, fatigue, dark urine) during treatment with Remesulide® Rapid or patients who develop abnormal liver function tests should have their treatment discontinued. Nimesulide should not be re-administered to such patients. Liver function abnormalities have been reported after short-term use of nimesulide, which were reversible in most cases.
In patients taking nimesulide who develop fever and/or flu-like symptoms, treatment should be discontinued.
Effects on the gastrointestinal tract
The risk of gastrointestinal bleeding, ulceration and perforation increases with increasing dose of NSAIDs in patients with a history of peptic ulcer, especially if the ulcer was complicated by bleeding or perforation, and in the elderly. Such patients should be treated with the lowest effective dose of the drug. The concomitant use of protective agents (e.g. misoprostol or proton pump inhibitors) should be considered in such patients, as well as in patients who are concomitantly treated with low-dose acetylsalicylic acid or other drugs that increase the risk of gastrointestinal damage.
Patients with a history of gastrointestinal toxicity, especially the elderly, should be instructed to report any unusual abdominal symptoms (including gastrointestinal bleeding), especially at the beginning of treatment.
Gastrointestinal bleeding or ulceration/perforation may occur at any time during treatment, with or without warning symptoms or a history of previous gastrointestinal disorders. If a patient develops gastrointestinal bleeding or ulceration, nimesulide should be discontinued. Nimesulide should be used with caution in patients with gastrointestinal disorders, including peptic ulcers, gastrointestinal bleeding, ulcerative colitis or Crohn's disease.
Caution should be exercised in patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants, particularly warfarin, SSRIs, or antiplatelet agents such as acetylsalicylic acid.
If gastrointestinal ulcers or bleeding occur during treatment with Remesulide® Rapid, treatment should be discontinued.
NSAIDs should be used with caution in patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease), as their condition may worsen.
Elderly patients: Elderly patients taking NSAIDs are more likely to experience adverse reactions, including gastrointestinal bleeding and perforation, which can be fatal. Therefore, clinical monitoring of these patients is recommended.
Effects on the cardiovascular and cerebrovascular systems.
Caution should be exercised and patients with a history of hypertension and/or mild to moderate heart failure should be monitored, as fluid retention and oedema have been reported with NSAIDs.
Clinical trials and epidemiological data suggest that the use of some NSAIDs (especially at high doses and over long periods) may be associated with a small increased risk of arterial thrombosis (e.g. myocardial infarction or stroke). There is insufficient data to exclude this risk with nimesulide.
The use of nimesulide should be carefully considered in patients with poorly controlled hypertension, congestive heart failure, ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease. Similarly, the initiation of long-term treatment in patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking) should be evaluated.
Since nimesulide may affect platelet function, it should be used with caution in patients with hemorrhagic diathesis. However, Remesulide® Rapid is not a substitute for acetylsalicylic acid in the prevention of cardiovascular diseases.
Effects on kidney function
Caution should be exercised in patients with impaired renal function and heart disease, as nimesulide may lead to deterioration of renal function. In the event of such deterioration, treatment should be discontinued.
Skin effects. Serious skin reactions, some of which were fatal, have been reported very rarely with NSAIDs. These reactions are most dangerous for patients at the beginning of treatment, with the onset of the reaction most often occurring within the first month of treatment. Remesulide® Rapid should be discontinued at the first sign of skin rash, mucosal lesions or any other sign of hypersensitivity.
Impact on fertility
The use of nimesulide may impair fertility in women, therefore it is not recommended to use the drug in cases where a woman is planning a pregnancy. In women who cannot become pregnant or who are suspected of infertility, discontinuation of treatment with Remesulide® Rapid should be considered.
Remesulide® Rapid granules for oral suspension contain sugar and are therefore contraindicated in patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase deficiency.
Ability to influence reaction speed when driving vehicles or other mechanisms
No studies have been conducted with nimesulide on the effects on the ability to drive and use machines. However, patients who experience dizziness, headache or drowsiness after taking Remesulide® Rapid should refrain from driving or operating machinery.
Use during pregnancy or breastfeeding
The use of Remesulide® Rapid is contraindicated during the last trimester of pregnancy.
As with other NSAIDs, the use of Remesulide® Rapid is not recommended in women attempting to become pregnant.
Inhibition of prostaglandin synthesis may have adverse effects on pregnancy and/or embryonal/fetal development. Epidemiological studies have shown an increased risk of spontaneous abortion, fetal cardiac malformations and gastroschisis after treatment with prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular malformation has increased from less than 1% to almost 1.5%. The risk is believed to increase with increasing dose and duration of treatment.
Animal studies have shown that the use of prostaglandin synthesis inhibitors leads to an increase in pre- and post-implantation losses and embryo/fetal lethality. In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals treated with a prostaglandin synthesis inhibitor during organogenesis.
Studies in rabbits have shown atypical reproductive toxicity, but there are no reliable data on the use of nimesulide in pregnant women. Therefore, the potential risk to humans is not determined, so the use of the drug during the first and second trimesters of pregnancy is not recommended unless clearly necessary.
If Remesulide® Rapid is used by women attempting to conceive or in the first and second trimesters of pregnancy, the effective dose should be kept as low and the treatment period as short as possible.
In the third trimester of pregnancy, all prostaglandin synthesis inhibitors may lead to the development of
in the fetus:
cardiopulmonary toxicity (premature closure of the ductus arteriosus and pulmonary hypertension); renal dysfunction with possible further development of renal failure with oligohydramnios;
in the mother and fetus at the end of pregnancy:
Possible increase in bleeding time and anti-aggregation effect, which may occur even when using very low doses of the drug; inhibition of uterine contractile activity, which may lead to a delay or prolongation of the period of labor.
For these reasons, Remesulide® Rapid is contraindicated in the third trimester of pregnancy.
It is not known whether nimesulide is excreted in human breast milk. Remesulide® Rapid is contraindicated in women who are breastfeeding.
Method of administration and doses
In order to minimize possible unwanted side effects, the minimum effective dose should be used for the shortest possible time.
It is recommended to use after eating.
The contents of the sachet are poured into a glass, dissolved in water and taken orally.
The maximum duration of treatment with nimesulide is 15 days.
Adults: one 100 mg sachet 2 times a day.
Elderly patients: no dose adjustment is required.
Children over 12 years of age: no dose adjustment is required.
Children under 12 years of age: nimesulide is contraindicated in children under 12 years of age.
Kidney dysfunction
Considering pharmacokinetics, no dose adjustment is required for patients with mild or moderate renal impairment (creatinine clearance 30–80 ml/min), however, in case of severe renal impairment (creatinine clearance < 30 ml/min), Remesulide® Rapid is contraindicated.
Liver dysfunction
Remesulide® Rapid is contraindicated in patients with impaired liver function.
Children
Use for children over 12 years of age.
Overdose
Symptoms of acute NSAID overdose are usually limited to apathy, drowsiness, nausea, vomiting, epigastric pain, which are usually reversible with supportive therapy. Gastrointestinal bleeding may occur. In addition, arterial hypertension, acute renal failure, respiratory depression and coma may occur, but these phenomena are rare. There have been reports of anaphylactoid reactions with therapeutic doses of NSAIDs, which may also occur in case of overdose.
In case of overdose with NSAIDs, patients may be prescribed symptomatic and supportive therapy. There are no specific antidotes. There is no information on the effectiveness of hemodialysis, but taking into account the high degree of binding of nimesulide to plasma proteins (up to 97.5%), dialysis is unlikely to be effective in overdose. If symptoms of overdose are present or after taking a large dose of the drug within 4 hours after its administration, patients may be prescribed activated charcoal (60-100 g for adults) and/or an osmotic laxative. Forced diuresis, increasing the alkalinity of the urine, hemodialysis and hemoperfusion may be ineffective due to the high degree of binding of nimesulide to plasma proteins. Kidney and liver function should be monitored.
Adverse reactions
Clinical trials and epidemiological data suggest that the use of some NSAIDs (especially at high doses and with long-term use) may be associated with a modest increased risk of arterial thrombotic complications (e.g. myocardial infarction or stroke).
There have also been reports of oedema, hypertension and heart failure with NSAIDs. Very rare reports of bullous skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis.
Gastrointestinal adverse reactions are the most common. Peptic ulcers, perforations or gastrointestinal bleeding may occur, sometimes fatal, especially in the elderly. Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, black stools, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have also been observed after treatment. Gastritis has been observed less frequently.
The following list of adverse reactions is based on the results of controlled clinical trials and post-marketing surveillance with subsequent assessment of the occurrence of side effects: 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 cases.
| From the blood system | Liquid | Anemia* Eosinophilia* |
| Very rare | Thrombocytopenia Pancytopenia Purpura | |
| On the part of the immune system | Liquid | Hypersensitivity* |
| Very rare | Anaphylaxis | |
| Metabolic and digestive disorders | Liquid | Hyperkalemia* |
| From the psyche | Liquid | Feeling anxious* Nervousness* Terrible dreams |
| From the nervous system | Infrequent | Dizziness* |
| Very rare | Headache Drowsiness Encephalopathy (Reye's syndrome) | |
| From the organs of vision | Liquid | Blurred vision* |
| Very rare | Vision impairment | |
| From the side of the organs of hearing and ear labyrinth | Very rare | Vertigo |
| Cardiac disorders | Liquid | Tachycardia* |
| From the vascular side | Infrequent | Arterial hypertension* |
| Liquid | Bleeding* Blood pressure fluctuations* Tides* | |
| Respiratory system | Infrequent | Dyspnea* |
| Very rare | Asthma Bronchospasm | |
| Gastrointestinal tract | Frequent | Diarrhea* Nausea* Vomiting* |
| Infrequent | Constipation* Flatulence* Gastrointestinal bleeding Duodenal ulcer and perforation Stomach ulcer and perforation | |
| Very rare | Gastritis* Abdominal pain Dyspepsia Stomatitis Black stools | |
| Liver and biliary tract | Frequent | Increased liver enzymes* |
| Very rare | Hepatitis Immediate (fulminant) hepatitis (including fatal) Jaundice Cholestasis |
| Skin and subcutaneous tissue disorders | Infrequent | Itch* Skin rashes* Increased sweating* |
| Liquid | Erythema* Dermatitis* | |
| Very rare | Urticaria Angioedema Facial swelling Erythema multiforme Stevens-Johnson syndrome Toxic epidermal necrolysis |
| Renal and urinary tract disorders | Liquid | Dysuria* Hematuria* |
| Very rare | Urinary retention* Kidney failure Oliguria Interstitial nephritis | |
| General violations | Infrequent | Edema* |
| Liquid | Malaise* Asthenia* | |
| Very rare | Hypothermia | |
*Frequency is based on clinical studies.
Expiration date
2 years.
Do not use after the expiry date stated on the packaging.
Storage conditions
Store in original packaging at a temperature not exceeding 25 ºС.
Keep out of reach of children.
Packaging
100 mg/2 g per sachet. 10 sachets per pack.
Vacation category
According to the recipe.
Producer
JSC "Farmak".
Location of the manufacturer and its business address
Ukraine, 04080, Kyiv, Kyrylivska St., 74.
