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APPROVED
Order of the Ministry of
Health of Ukraine
17.02.2016 № 104
Registration certificate
№ UA/7649/02/01
INSTRUCTION
for medical use
NIMID®
Composition:
active substance: nimesulide;
1 tablet contains nimesulide 100 mg;
excipients: microcrystalline cellulose, croscarmellose sodium, magnesium stearate, silica colloidal
anhydrous.
Pharmaceutical form. Tablets.
General physical and chemical properties: round light-yellow tablets, smooth on both sides.
Pharmacotherapeutic group. Nonsteroidal anti-inflammatory and anti-rheumatic drugs.
Code АТС М01А X17.
Pharmacological properties.
Pharmacodynamics.
Nimid® is a nonsteroidal anti-inflammatory agent of methane-sulfonanilide group which has antiinflammatory, analgesic and antipyretic effect. The therapeutic effect of Nimid is the result of its
interaction with the arachidonic acid cascade and reduction of prostaglandin biosynthesis through
inhibition of cyclooxygenase.
Pharmacokinetics.
In human body, nimesulide is quickly absorbed after oral administration and achieves the peak plasma
concentrations after 2-3 hours. Up to 97.5% of nimesulide bind to plasma proteins. Nimesulide is
extensively metabolized in the liver by CYP2C9, the cytochrome P450 isoenzyme. The main metabolite
is a para-hydroxy derivative which also has pharmacological activity. The half-life is from 3.2 to 6 hours.
Nimesulide is excreted from the organism with the urine - approximately 50% of the administered dose.
About 29% of the administered dose are excreted with the feces in metabolized form. Only 1-3% is
excreted unchanged from the organism. Pharmacokinetic profile in elderly patients does not change.
Clinical characteristics.
Indications.
Treatment of acute pain, primary dysmenorrhea.
Nimesulide should be used only as a second-line drug.
The decision to administer nimesulide should be taken based on the assessment of all risks for the
individual patient.
Contraindications.
Known hypersensitivity to nimesulide or any other component of the drug.
History of hyperergic reactions (bronchospasm, rhinitis, urticaria) to the use of acetylsalicylic acid or
other nonsteroidal anti-inflammatory drugs. History of hepatotoxic reactions.
Concomitant use of other substances with potential hepatotoxicity.
Alcoholism and drug addiction.
History of gastro-intestinal bleedings or perforations associated with the previous use of nonsteroidal
anti-inflammatory drugs.
Gastric or duodenal ulcer in the acute phase, history of and ulcer, perforation or bleeding in the digestive
tract.
History of cerebrovascular bleedings or other bleedings, as well as diseases accompanied by bleeding.
Severe blood clotting disorders.
Severe heart failure.
Severe renal dysfunction.
Severe hepatic dysfunction.
Patients with increased body temperature and/or flu-like symptoms.
Children’s age less than 12 years.
III trimester of pregnancy and breast-feeding period.
Interaction with other medicinal products and other forms of interaction.
Pharmacodynamic interactions.
Corticosteroids: increased risk of gastrointestinal ulceration or bleeding.
Antiplatelet agents and selective serotonin reuptake inhibitors (SSSRIs): increased risk of bleeding in the
digestive tract.
Anticoagulants: NSAIDs may enhance the effects of anticoagulants such as warfarin or acetylsalicylic
acid, therefore such combination is contraindicated in patients with severe coagulation disorders. If such
combination therapy can not be avoided, it is necessary to carry out a careful monitoring of coagulation
parameters.
Diuretics, angiotensin-converting enzyme inhibitors and angiotensin II antagonists.
NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. Some patients with renal
dysfunction (e.g., patients with dehydration or elderly patients) the simultaneous use of ACE inhibitors,
angiotensin-II antagonists or substances that inhibit cyclooxygenase system may have further impairment
of renal function and occurrence of acute renal failure, which is generally reversible. These interactions
should be considered when a patient uses Nimid® together with ACE inhibitors or angiotensin II
antagonists. Caution should be exercised while administering this combination, especially in elderly
patients. Patients should drink plenty of fluids, and renal function should be carefully monitored after the
beginning of using such combination. Nimesulide temporarily reduces the effect of furosemide on the
excretion of sodium and in lesser degree, on excretion of potassium, as well as reduces the diuretic effect.
Concomitant administration of furosemide and Nimid® in patients with impaired renal or cardiac function
requires caution.
In healthy volunteers, nimesulide quickly reduces effect of furosemide aimed at excreting sodium and
in a lesser extent - on potassium excretion, and also reduces the diuretic effect. Concomitant
administration of nimesulide and furosemide causes a decrease (approximately 20%) of the area under
the curve “concentration-time” (AUC) and reduction of furosemide cumulative excretion with
unchanged renal clearance of furosemide.
Pharmacokinetic interactions with other medicinal products.
There were reports that NSAIDs reduces clearance of lithium resulting in increase of lithium levels in the
blood plasma and toxic effects of lithium. When prescribing Nimid® in patients receiving lithium therapy
lithium levels in blood plasma should be monitored closely.
There is no clinically significant interaction with glibenclamide, theophylline, warfarin, digoxin,
cimetidine and antacid drugs (combination of aluminum and magnesium hydroxide) in vivo. Nimesulide
inhibits CYP 2C9 enzyme activity. When using the drugs that are substrates of this enzyme with Nimid®,
their concentration in blood plasma may increase. Caution is necessary if nimesulide is prescribed less
than 24 hours before or less than 24 hours after using methotrexate, as the serum level of the latter may
grow, or its toxicity may increase.
Because of the effect on renal prostaglandins, inhibitors of synthetases, which include nimesulide, may
increase nephrotoxicity of cyclosporines.
Effect of other drugs on nimesulide.
Studies in vitro have shown that nimesulide is displaced from binding sites by tolbutamide, salicylic
acid and valproic acid. Despite the fact that these interactions have been identified in plasma, these
effects were not observed while the clinical use of the drug.
Administration details.
Adverse effects can be minimized by using the minimum effective dose during the shortest possible time
period required for symptoms control.
If the effect of treatment is absent (reduction of the disease symptoms), the drug therapy should be
stopped.
During the treatment with nimesulide, it is recommended to avoid concomitant use of hepatotoxic drugs,
as well as refrain from taking alcohol. The use of nonsteroidal anti-inflammatory drugs may mask the
temperature increase associated with the background bacterial infection. In case of body temperature
increase or flu-like symptoms in patients using nimesulide, the drug should be stopped.
Serious liver reactions, including a lethal outcome have been reported during nimesulide therapy. Patients
who have symptoms similar to the symptoms of liver damage, such as anorexia, nausea, vomiting,
abdominal pain, increased fatigability, dark urine, or patients whose laboratory data of liver function
deviate from normal values, should stop taking the drug. Re-administration of nimesulide in such patients
is contraindicated. During treatment with Nimid®, the patient should refrain from taking other analgesics.
Concomitant use of other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.
Patients using nimesulide who develop flu-like symptoms should discontinue using it.
Elderly patients have an increased frequency of adverse reactions to NSAIDs; this especially refers to the
possible gastrointestinal bleedings and perforations, which may lead to lethal outcome.
Ulcer, bleeding or perforation of the digestive tract might endanger the patient’s life, especially if a
history of the similar phenomena has been reported in a patient while using any other NSAID (no time
limitation). The risk of such events increases with increased doses of NSAIDs in patients with a history of
ulcers in the digestive tract especially complicated by bleeding or perforation, and in elderly patients.
Such patients should initiate treatment with the lowest possible effective dose. In these patients, as well as
in those, who co-administer low doses of acetylsalicylic acid or other drugs that increase the risk of
gastrointestinal tract complications, the combination therapy with the protective substances, such as
misoprostol or proton pump inhibitors, should be considered.
Patients with toxic lesion of the digestive tract, especially elderly ones, should inform about any unusual
symptoms that occur in the digestive tract, especially about bleeding. This is particularly important in the
initial stages of treatment. Patients who use concomitant drugs that may increase the risk of ulcers or
bleeding, such as corticosteroids, anticoagulants, selective serotonin reuptake inhibitors, antiplatelet
agents (acetylsalicylic acid), should be informed about the need of caution during the use of nimesulide.
In case of bleeding or gastrointestinal tract ulcers in patients who use Nimid ® the drug treatment should
be discontinued.
It is necessary to administer NSAIDs with caution to patients with Crohn's disease or ulcerative colitis in
anamnesis, since nimesulide may aggravate them.
Concomitant use of nimesulide with other drugs, such as oral contraceptives, anticoagulants, antiplatelet
agents, can cause exacerbation of Crohn's disease and other diseases of the digestive tract.
Patients with hypertension and/or heart failure in anamnesis, as well as those with water retention and
edema due to the use of NSAIDs, require an appropriate state monitoring and a doctor’s advice.
Clinical studies and epidemiological data suggest that some NSAIDs, especially at high doses and with
long-term use may lead to insignificant risk of development of arterial thrombotic episodes, for example,
myocardial infarction and stroke. There is no sufficient data concerning exclusion of the risk of such
events occurrence during nimesulide administration.
Nimesulide should be administered to patients with uncontrolled arterial hypertension, acute cardiac
insufficiency, known coronary heart disease, peripheral arterial disease and/or cerebrovascular disease
only after a precise assessment of their states. This also applies to patients with risk factors for
cardiovascular disease, such as hypertension, hyperlipidemia, diabetes and smoking
The drug should be administered to patients with renal dysfunction or heart failure with caution due to
possible worsening of renal functions. In case of recrudescence, the treatment should be stopped
Elderly patients should be carefully monitored due to possible development of bleeding and perforation of
the digestive tract, renal, liver or heart impairment. Since nimesulide may affect platelet function, it
should be administered with caution in patients with hemorrhagic diathesis. However, nimesulide does
not substitute acetylsalicylic acid in cardiovascular disease prevention
Rare cases of severe skin reactions, some of which can be deathful, e.g. exfoliative dermatitis, StevensJohnson syndrome, toxic epidermal necrosis, have been reported while using NSAIDs. In most cases, if
during the first month of the earlier course of treatment, these reactions occurred, the risk of their
occurrence in patients significantly increases. Nimid® should be withdrawn when the first signs of skin
rash, mucous membranes lesions and other phenomena of allergic reaction occur.
Use during pregnancy or breast-feeding.
Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or fetal development. The
epidemiological studies suggest that the use of drugs that inhibit prostaglandin synthesis in early
pregnancy may increase the risk of spontaneous abortion, the occurrence of fetal heart defects and
gastroschisis. The absolute risk of the cardiovascular system abnormalities increased from less than 1% to
about 1.5%. It is considered that the risk increases with increasing dose and duration of use.
Nimesulide administration is not recommended in I and II trimesters of pregnancy, unless it is absolutely
necessary. In the case of the drug administration in women who are trying to become pregnant, or in the I
and II trimesters of pregnancy, the smallest possible dose and the least possible duration of treatment
should be chosen.
During the III trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the fetus to the
development of:
• cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
• renal dysfunction, which may progress to renal failure with oligoamnios.
The mother and the fetus at the end of pregnancy may have:
• prolongation of bleeding time, antiaggregatory effect that can occur even when using very low doses;
• inhibition of uterine contractions resulting in delayed or prolonged labor.
Consequently, nimesulide is contraindicated during the III trimester of pregnancy.
As other NSAIDs that inhibit prostaglandin synthesis, nimesulide may cause premature closure of the
ductus arteriosus, pulmonary hypertension, oliguria, oligoamnios. The risk of bleeding, uterine inertia and
peripheral edema. There are several reports of renal failure in infants whose mothers used nimesulide in
late pregnancy. Animal studies have shown atypical reproductive toxicity of the drug, but there are no
reliable data on nimesulide administration in pregnant women. The potential rick for humans is not
defined, therefore, it is not recommended to prescribe nimesulide during the I and II trimester of
pregnancy. Since it is unknown whether nimesulide penetrates into the breast milk, its use is
contraindicated during breast-feeding.
Nimesulide may impair female fertility, therefore it is not recommended for use in women attempting to
conceive. Women having problems with getting pregnant or undergoing examination for infertility should
consider stopping the administration of nimesulide. If pregnancy is detected during nimesulide
administration, the doctor should be informed about it.
Effects on ability to drive and operate machinery.
No studies on the effect of nimesulide on the ability to drive motor transport or operate other mechanisms
have been performed, but if while using nimesulide, the patients had headache, dizziness or somnolence,
they should not drive motor transport or work with other mechanisms.
Administration and dosage.
To minimize the possible adverse effects, the minimum effective dose should be used for the shortest
time. It is recommended to use the drug after meal with sufficient quantity of liquid.
Maximum duration of treatment with Nimid is 15 days.
Adults. 1 tablet (100 mg) 2 times per day.
Elderly patients. No dosage adjustment is required.
Children aged from 12 years. No dosage adjustment is required.
Patients with impaired renal function. In patients with mild or moderate renal impairment (creatinine
clearance is 30-80 ml/min), dosage adjustment is not required, while severe renal impairment (creatinine
clearance <30 ml/h) is a contraindication for administration of Nimid®.
Children.
Nimid® is contraindicated in children aged less than 12 years.
Overdose.
The symptoms of acute overdose with nonsteroidal anti-inflammatory drugs (NSAIDs) are usually limited
to such ones: lethargy, somnolence, vomiting epigastric pain. These symptoms as a rule are reversible
with supportive treatment. Gastrointestinal bleeding, arterial hypertension, acute renal failure, respiratory
depression, coma are possible, however, such phenomena are rare. Anaphylactoid reactions have been
reported when using therapeutic doses of NDAIDs and when overdose. There is no specific antidote. The
treatment of overdose is symptomatic and supportive. There are no data on excretion of nimesulide with
hemodialysis, but if keeping in mind the high degree of binding of nimesulide to the plasma proteins (up
to 97.5%); it is unlikely that the dialysis will be effective. If there are symptoms of overdose or after using
a high dose of the drug, within 4 hours after the intake the patients may be prescribed: induction of
vomiting and/or taking activated carbon (60-100 g for adults) and/or osmotic laxative. Forced diuresis,
increasing alkalinity of the urine and hemoperfusion may be ineffective due to the high degree of binding
of nimesulide with blood plasma proteins. The renal and hepatic functions should be controlled.
Adverse reactions.
Blood and lymphatic system disorders: anemia, eosinophilia, thrombocytopenia, pancytopenia, purpura.
Immune system disorders: hypersensitivity, anaphylaxis.
Metabolic disorders: hyperkalemia.
Mental disorders: feeling of fear, nervousness, nightmares.
Nervous system disorders: dizziness, headache, somnolence, encephalopathy (Reye's syndrome).
Vision disorders: blurred vision, visual disturbances.
Ear and equilibration disorders: vertigo (dizziness).
Cardiovascular system disorders: tachycardia, hemorrhage, blood pressure lability, flushes, arterial
hypertension, increased risk of arterial thrombotic complications, such as myocardial infarction or stroke,
heart failure.
Respiratory system: dyspnea, asthma, bronchospasm.
Gastrointestinal tract disorders: diarrhea, nausea, vomiting, including vomiting blood, constipation,
flatulence, gastritis, abdominal pain, dyspepsia, stomatitis, black stool, gastrointestinal bleeding,
gastric/duodenal ulceration and perforation, recrudescence of colitis and Crohn's disease.
Hepatobiliary system disorders: hepatitis, fulminant (instant) hepatitis with fatal outcome, including
jaundice, cholestasis.
Skin disorders: pruritus, skin rash, increased sweating, erythema, dermatitis, urticaria, angioedema, face
edema, erythema multiform, Stevens–Johnson syndrome, toxic epidermal necrolysis.
Urinary system disorders: dysuria, hematuria, urinary retention, renal failure, oliguria, interstitial
nephritis.
General disorders: swelling, weakness, asthenia, hypothermia.
Laboratory data: increase in liver enzymes.
Shelf-life. 3 years.
Storage conditions.
Store at the temperature not more than 25 °С in the original package.
Keep it out of reach of children.
Package.
10 tablets are in a blister, 1 blister is in a carton package №10 (10х1).
10 tablets are in a blister, 1 blister is in a carton package, 10 packages are in a box №100 (10×1×10).
Conditions of supply.
By prescription.
Manufacturer.
KUSUM HEALTHCARE PVT LTD.
Address.
SP-289 (A), RIICO Industrial area, Chopanki, Bhiwadi, Dist. Alwar (Rajasthan), India.
Date of last revision.