winstrol cycle

It has anti-inflammatory, analgesic and antipyretic effect.Nimesulide acts as an inhibitor of the cyclooxygenase winstrol cycle enzyme responsible for prostaglandin synthesis and inhibits mainly cyclooxygenase 2.
It is metabolized in the liver using cytochrome P450 isoenzyme (CYP) 2C9. The main metabolite is the pharmacologically active paragidroksiproizvodnoe nimesulide – hydroxynimesulide. Hydroxynimesulide excreted in the bile to metabolize form (found exclusively in the form of glucuronate – about 29%). Nimesulide is excreted mainly by the kidneys (about 50% of the dose). The pharmacokinetic profile of nimesulide in the elderly does not change with the appointment of single and multiple / repeat dose.
According to the experimental studies carried out in patients with mild to moderate renal insufficiency (creatinine clearance 30-80 ml / min) and healthy volunteers, the maximum concentration nimesulide and its metabolite in plasma of patients did not exceed the concentration of nimesulide in healthy volunteers. The area under the curve “concentration-time» (AUC) and the half-life in patients with renal failure were higher by 50%, but within the pharmacokinetic values. When re-taking the drug accumulation was observed.

Indications

 

  • Treatment of acute pain (back pain, lower back, pain in the musculoskeletal system including trauma, sprains and dislocations of joints, tendinitis, bursitis, dental pain);
  • Symptomatic treatment of osteoarthritis pain syndrome;
  • Algomenorrhea.

The drug is intended for symptomatic therapy reduce pain and inflammation at the time of use.

 

Contraindications

 

  • Hypersensitivity to nimesulide or one of the formulation components.
  • Hyperergic response (history) such as bronchoconstriction, rhinitis, urticaria, associated with the intake of aspirin or other nonsteroidal anti-inflammatory drugs, including nimesulide. Hepatotoxic reactions to nimesulide (in history).
  • Related (simultaneously) receiving drugs with potential hepatotoxicity, such as paracetamol or other analgesics or nonsteroidal anti-inflammatory drugs.
  • Inflammatory bowel disease (Crohn’s disease, ulcerative colitis) in the acute phase. The period after coronary artery bypass grafting.
  • Feverish syndrome, colds and acute respiratory viral infections.
  • Full or partial combination of asthma, recurrent nasal polyposis, or paranasal sinuses with intolerance to acetylsalicylic acid and other NSAIDs (including history);
  • Gastric ulcer or duodenal ulcer in the acute phase, a history of ulcer, perforation or bleeding in the gastrointestinal tract.
  • A history of cerebrovascular bleeding or other bleeding, as well as diseases associated with bleeding.
  • Severe coagulation disorders.
  • Severe heart failure.
  • Severe renal insufficiency (creatinine clearance <30 mL / min), confirmed hyperkalemia.
  • Liver failure or any active liver disease.
  • Children under the age of 12 years.
  • Pregnancy and lactation.
  • Alcoholism, drug addiction.

 

Precautions: severe hypertension, type 2 diabetes, heart failure, ischemic heart disease, cerebrovascular disease, dyslipidemia / hyperlipidemia, peripheral artery disease, smoking, creatinine clearance less than 60 mL / min.

A history of the presence of ulcerative lesions gastrointestinal infection caused by winstrol cycle pylori; elderly age; long prior use of NSAIDs; severe somatic disease.

Concomitant therapy following drugs: anticoagulant (eg, warfarin), antiplatelet agents (for example, acetylsalicylic acid, clopidogrel), oral steroids (e.g., prednisone), selective serotonin reuptake inhibitor (such as citalopram, fluoxetine, paroxetine, sertraline). The decision on the appointment  should be based on an individual assessment of the “risk-benefit” while taking the drug.

Dosing and Administration

Nimesil taken orally, 1 sachet (100 mg of nimesulide) twice a day. The drug is recommended to be taken after meals. The contents of the sachet are poured into a beaker and dissolved in approximately 100 ml of water. The prepared solution must not be stored.

Adolescents (12 to 18 years): on the basis of pharmacokinetic profile and pharmacodynamic characteristics of nimesulide need for dose adjustment in adolescents there.

Patients with impaired renal function: on the basis of pharmacokinetic data, the need for dose adjustment in patients with mild to moderate renal insufficiency (creatinine clearance 30-80 ml / min) no.

Elderly patients: the treatment of elderly patients need to adjust the daily dose determined by the physician based on the possibility of interaction with other drugs.

The maximum duration of treatment with nimesulide is 15 days.

To reduce the risk of unwanted side effects, you should use the minimum effective dose, winstrol cycle short-course minimum.

Side effects

Violations of the blood and lymphatic system: rarely – anemia, eosinophilia, hemorrhage; very rarely – thrombocytopenia, pancytopenia, thrombocytopenic purpura.

Allergic reactions: rarely – itching, rash, excessive sweating; rarely – hypersensitivity reactions, erythema, dermatitis; very rare – anaphylactoid reactions, urticaria, angioedema, poliformnaya erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome).

Disorders of the central nervous system: Infrequent – dizziness; rarely – a sense of fear, nervousness, night nightmares; very rarely – headache, somnolence, encephalopathy (Reye’s syndrome).

Violations by the sensory organs: rarely – blurred vision.

Violations of the cardiovascular system: seldom – hypertension, tachycardia, labile blood pressure, “hot flashes.”

Disorders of the respiratory system: rarely – shortness of breath; very rarely – worsening of asthma, bronchospasm.

Disorders of the gastrointestinal tract: often – diarrhea, nausea, vomiting; rarely – constipation, flatulence, gastritis; very rare – abdominal pain, dyspepsia, stomatitis, tarry stools, gastrointestinal bleeding, ulcers and / or perforation of the stomach or duodenum.

Violations of the liver and biliary system: very rarely – hepatitis, fulminant hepatitis, jaundice, cholestasis, elevated liver enzymes.

Violations of the kidney and urinary system: rarely – dysuria, hematuria, urinary retention; very rarely – renal failure, oliguria, interstitial nephritis.

General disorders: rarely – malaise, asthenia; very rarely – hypothermia.

Other: rarely – hyperkalemia.

Overdose

Symptoms: lethargy, drowsiness, nausea, vomiting, epigastric pain. When maintenance therapy gastropathy these symptoms are usually reversible. You may experience gastrointestinal bleeding. In rare cases, may increase blood pressure, acute renal failure, respiratory depression and coma, anaphylactoid reactions.

Treatment: Symptomatic. No winstrol cycle specific antidote. If overdosage occurs during the last 4 hours necessary to induce vomiting and / or ensure the reception of activated charcoal (60 to 100 g per human adult), and / or an osmotic laxative. Forced diuresis, dialysis – are ineffective because of the high protein due to the drug (to 97.5%). Showed control function of the kidneys and liver.

Interaction with other drugs

Pharmacodynamic interactions:

Corticosteroids: increase the risk of gastrointestinal ulcers or bleeding.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine: increased risk of gastrointestinal bleeding.

Anticoagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin. Because of the increased risk of bleeding, such a combination is not recommended and is contraindicated in patients with severe coagulation disorders. If combination therapy still can not be avoided, it is necessary to carry out careful monitoring of indicators of blood coagulation.

Diuretics

NSAIDs may reduce the effect of diuretics.

In healthy volunteers nimesulide temporarily reduces the excretion of sodium by the action of furosemide, to a lesser extent – potassium excretion, and actually reduces the diuretic effect.

Co-administration of nimesulide and furosemide results in a decrease (about 20%) of the area under “concentration – time” curve (AUC) and the reduction in the cumulative excretion of unchanged furosemide furosemide renal clearance.

Co-administration of nimesulide and furosemide requires caution in patients with impaired renal or cardiac functions.

ACE inhibitors and angiotensin-II receptor

NSAIDs may reduce the effect of antihypertensive drugs. In patients with mild to moderate renal insufficiency (creatinine clearance 30-80 ml / min) with a joint appointment of ACE inhibitors, angiotensin II receptor antagonists or substances inhibiting the cyclooxygenase system (NSAIDs, antiplatelet agents) may further deterioration of renal function and the occurrence of acute renal insufficient, which tends to be reversible. These interactions should be considered in patients taking Nimesil in combination with ACE inhibitors or angiotensin receptor antagonists I. Therefore, co-administration of these drugs should be administered with caution, especially in elderly patients. Patients should receive a sufficient amount of fluid, and renal function should be carefully monitored after the start of combination therapy.

Pharmacokinetic interactions with other drugs:

There is evidence that NSAIDs reduce clearance of lithium, which leads to an increase in the concentration of lithium in the blood plasma and its toxicity. In the appointment of nimesulide in patients receiving therapy with lithium preparations should regularly monitor the concentration of lithium in plasma.

Clinically significant interactions with glibenclamide, theophylline, digoxin, cimetidine and antacids (for example, a combination of aluminum and magnesium hydroxide) were observed.

Nimesulide inhibits isoenzyme winstrol cycle. In simultaneous reception with nimesulide drugs that are substrates of this enzyme, the concentration of these drugs in the plasma can be increased.

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