Dinastat (Dynastat)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
Read on
Active substanceParecoxibParecoxib
Similar drugsTo uncover
  • Dinastat
    lyophilizate w / m in / in 
    Pfizer IFG Belgium N.V.     Belgium
    • Dosage form: & nbsplyophilizate for the preparation of solution for intravenous and intramuscular administration
    Composition:

    Each bottle contains:

    Active substance:

    Bottles of 20 mg: parecoxib sodium - 21.18 mg (corresponding to 20 mg of parecoxib). After dissolution in 1 ml of solvent, the final concentration of parecoxib is 20 mg / ml.

    Bottles of 40 mg: parecoxib sodium - 42.36 mg (corresponding to 40 mg of parecoxib). After dissolution in 2 ml of solvent, the final concentration of parecoxib is 20 mg / ml.

    Excipients: sodium hydrogen phosphate heptahydrate, phosphoric acid and / or sodium hydroxide (for pH adjustment)

    Composition of solvent

    Sodium chloride, water for injection.

    Description:loose porous mass or tablet of white or almost white color. Solvent: Clear colorless solution.
    Pharmacotherapeutic group:Non-steroidal anti-inflammatory drug (NSAID)
    ATX: & nbsp

    M.01.A.H   Coxiba

    M.01.A.H.04   Parecoxib

    Pharmacodynamics:

    After the administration of the drug Dynastat, its active ingredient parecoxib quickly hydrolyzed with the formation of valdecoxib. The mechanism of action of valdecoxib is associated with the inhibition of the synthesis of prostaglandins with the participation of cyclooxygenase-2 (COX-2).Valdecoxib acts as a selective COX-2 inhibitor against both peripheral and central action of prostaglandins; while it does not inhibit COX-1, and has virtually no effect on the physiological processes in the tissues, especially in the mucous membrane of the stomach and intestine, that depend on COX-1, and also does not affect the platelet aggregation and bleeding time. Due to the selective effect on COX-2 and the absence of influence on COX-1, the frequency of formation of endoscopically confirmed ulcers and erosions of the stomach and duodenum with the use of Dynastat is lower than that of nonselective NSAIDs.

    Pharmacokinetics:

    After intravenous (iv) or intramuscular (IM) administration parecoxib as a result of enzymatic hydrolysis in the liver is rapidly metabolized to valdecoxib, which is a pharmacologically active component.

    Suction

    After intravenous administration of Dynastat in the dose range of 20, 50 and 80 mg per day, changes in such pharmacokinetic indices of valdecoxib as the area under the concentration-time curve (AUC) and the maximum concentration (Stach) are linear.Equilibrium concentrations of valdecoxib in plasma when administered 2 times a day are achieved within 4 days.

    After a single IV or IM injection of sodium parecoxib at a dose of 20 mg, the valdecoxib stach is reached after approximately 30 minutes and 1 hour, respectively. Values AUC and the stalks of valdecoxib are similar after IV and IM.

    Distribution

    The volume of distribution of valdecoxib after intravenous administration is approximately 55 liters. The association with plasma proteins is approximately 98% at concentrations that are reached when applying the maximum recommended dose (80 mg / day). Valdecoxib, but not parecoxib, mainly accumulates in erythrocytes. Metabolism

    Parecoxib rapidly and almost completely converted into valdecoxib and propionic acid, while the half-life (T1/2) of valdecoxib from plasma is approximately 22 minutes. The excretion of valdecoxib occurs by intensive metabolism in the liver in many ways, including metabolism involving cytochrome P450 isoenzymes: CYP3A4 and CYP2C9, as well as CYP-independent glucuronidation (about 20%) of the sulfonamide moiety.In the plasma, a hydroxylated metabolite of valdecoxib is found, which exhibits activity as an inhibitor of COX-2. It accounts for approximately 10% of the valdecoxib concentration; due to the fact that the concentration of this metabolite is low, it can be considered that it has no significant clinical effect after the administration of therapeutic doses of parecoxib sodium.

    Excretion

    Valedecoxib is excreted by metabolic transformation in the liver, and only less than 5% of valdecoxib is unchanged in urine. Unchanged parecoxib in urine is not found, but in feces it is found only in trace amounts. Approximately 70% of the dose is excreted in the urine in the form of inactive metabolites.

    Plasma clearance (CLR) for valdecoxib is about 6 l / h. After intravenous or intravenous injection of parecoxib sodium T1/2 valdecoxib is about 8 hours. Older patients: It was noted that in elderly patients the clearance of valdecoxib is reduced, therefore the concentration of valdecoxib in plasma is approximately 40% higher than in young patients. The equilibrium concentration of valdecoxib in plasma is 16% higher in elderly women than in elderly men.

    Patients with impaired renal function: In patients with impaired renal function of varying severity with the administration of 20 mg of dinastat IV parecoxib is rapidly eliminated from the plasma. Since valdecoxib kidneys do not play a significant role in removing, and therefore, the state of their function has no significant effect on the pharmacokinetics of the drug, not detected changes clearance valdecoxib even in patients with severe renal impairment, as well as in patients on hemodialysis.

    Patients with hepatic impairment: When the average severity of liver lesions not marked decrease rate and degree of conversion of parecoxib to valdecoxib. Because such patients valdecoxib effect is enhanced by more than 2-fold (130%) necessary to decrease the dosage (See. "Dosage and Administration").

    The drug is not excreted during hemodialysis.

    Indications:

    Acute pain:

    - to prevent or reduce postoperative pain;

    - to reduce the need for opioid analgesics;

    Contraindications:

    Hypersensitivity to the active ingredient, as well as to any of the components included in the preparation;

    Allergic reactions to sulfonamides;

    Bronchospasm, acute rhinitis, angioedema, hives, or other allergic reactions after taking acetylsalicylic acid or other NSAIDs, including other selective inhibitors of COX-2;

    III trimester of pregnancy and lactation;

    Severe hepatic insufficiency (no experience of use);

    Erosive-ulcerative lesions of the gastrointestinal tract in the phase of exacerbation (including acute peptic ulcer);

    Severe congestive heart failure;

    Age under 18 years (no experience of using Dynastat in patients).

    Carefully:

    Aorto-coronary bypass surgery, fluid retention in the body (including conditions arising or worsening due to it, including chronic heart failure and arterial hypertension), dehydration, erosive-ulcerative lesions of the gastrointestinal tract in an anamnesis, inflammatory bowel diseases, operations on the organs of the gastrointestinal tract, urological operations, hepatic insufficiency of moderate severity, severe renal failure.

    Pregnancy and lactation:

    There is no experience of using Dynastat in pregnant women.

    Dinastat should be used during pregnancy only if the potential benefit to the patient exceeds the potential risk to the fetus.

    The use of dinastat is contraindicated in the last trimester of pregnancy, because due to inhibition of the synthesis of prostaglandins, it can cause a decrease in uterine contractility, as well as a premature closure of the Botallov duct.

    Unknown is allocated or not parecoxib in breast milk, therefore, taking into account the potential risk of side effects from parecoxib in a breastfed baby and considering the importance of the drug for the mother, it is worth assessing whether to continue breastfeeding or to begin therapy with Dynastat by interrupting feeding for the duration of treatment.

    Dosing and Administration:

    Dinastat may be administered intravenously or intramuscularly as a single dose, or as regular repeated injections or as needed. After the start of therapy, the dose should be adjusted depending on the patient's response. There is an experience of using the drug for 7 days.

    Acute pain: The recommended single or initial dose is 40 mg for intravenous administration (iv) or intramuscular (IM), then, if necessary,you can continue to administer every 6-12 hours for 20-40 mg; while the daily dose should not exceed 80 mg. Intravenous bolus injection can be done quickly and directly into the vein, or into the tube of a pre-established system for intravenous infusions. In / m administration should be done slowly and deeply into the muscle.

    For prevention or reduction of postoperative pain:

    The recommended dose is 40 mg IV or IM (preferably IV), which is administered 45 to 30 minutes before surgery. To maintain analgesia, it may be necessary to repeat the postoperative administration of the drug, as described for the treatment of acute pain.

    To reduce the need for opioid analgesics: Dinastat can

    Use in combination with opioid analgesics according to the scheme described for the treatment of acute pain. The daily need for opioids is reduced by 20-40% in case of their simultaneous appointment. The optimal effect is achieved when Dynastat® is administered before the administration of opioids.

    Elderly patients: Elderly patients are not required to adjust the dose. However, in older patients with a body weight of less than 50 kg, treatment should begin with the introduction of 1/2 the recommended dose; while the maximum daily dose should not exceed 40 mg.

    Patients with hepatic impairment: Patients with a slight violation of liver function dose adjustments are usually not required. Patients with a moderate liver function disorder should be administered with caution, the administration should begin with 1/2 the recommended dose, and the maximum daily dose should be reduced to 40 mg. Experience with the use of dinastat in patients with severe liver damage is absent; because the appointment of the drug to such patients is not recommended.

    Patients with impaired renal function: in patients with severe renal insufficiency (creatinine clearance <30 ml / min) or with conditions,

    predisposing to fluid retention in the body, parecoxib should be prescribed at the lowest recommended dose and carefully monitor the kidney function. Joint application with fluconazole: When combined with parecoxib with fluconazole, parecoxib should be administered at the lowest recommended dose.

    Preparing the preparation for the introduction: Parecoxib sodium - lyophilizate, which does not contain preservatives, 1 ml (for vials of 20 mg) or 2 ml (for vials of 40 mg) of a solution of sodium chloride for injection (0.9%) is used to prepare a solution for injections.

    The following solvents can also be used: 0.9% sterile sodium chloride solution, 5% dextrose (glucose) injection, 5% dextrose (glucose) solution with 0.45% sodium chloride for injection (solution, prepared with the use of these solvents, is isotonic).

    The use of Lactate Ringer's (Hartman's) injectable solutions or Lactate Ringer's for injection with 5% dextrose (glucose) for the preparation of Dynastat® solution is not recommended, as this results in precipitation.

    The use of sterile water for injection as a solvent is also not recommended, as the resulting solution will not be isotonic.

    The prepared solution can not be cooled or frozen.

    After dissolution, dinastat can be injected into the tubes of the IV infusion system containing the following solvents: sodium chloride solution for injection (0.9%), dextrose (glucose) injection solution (5%), Ringer's injection for injection, 5% Dextrose (glucose) solution with 0.45% sodium chloride.

    The administration of Dynastat solution to IV infusion systems containing a solution of 5% dextrose (glucose) in Ringer's Lactate or others not listed here is not recommended, as this can cause precipitation.

    Dinastat should not be mixed with other drugs.

    Side effects:

    Frequent (> = 1/100, <1/10)

    From the cardiovascular system: decrease or increase in blood pressure;

    Co side central and peripheral nervous system: dizziness, hypoesthesia;

    Co side of the digestive system: postextraction lunechke alveolitis, constipation, flatulence, indigestion;

    Co side of metabolism: increased levels of creatinine, hypokalemia;

    Co the respiratory system: respiratory insufficiency;

    Co side of mental status: anxiety, insomnia;

    Co skin: increased sweating, itching;

    Other: back pain, peripheral edema, postoperative anemia; ecchymosis.

    Infrequent (> = 1/1000, <1/100)

    Local reactions: pain at the injection site, pathological detachment from the drainage, established after the operation, accompanied by dissection of the sternum, wound infection (including during coronary artery bypass surgery);

    Co the sides of the autonomic nervous system: dry mouth;

    Co side of the digestive system: ulcers and erosion of the stomach and duodenum;

    Co side of the hepatobiliary system: increased activity of ALT transaminases and ACT;

    Co side of the senses: ear pain;

    Co cardiovascular system: bradycardia, cerebrovascular disorders;

    Co side of metabolism: hyperglycemia, increased levels of urea nitrogen in the blood;

    Co side of the musculoskeletal system: arthralgia;

    Co upper respiratory tract: pharyngitis;

    Co skin: rash, postoperative complications in the wound site (delay of wound healing);

    Co hematopoiesis side: thrombocytopenia;

    Co side of the urinary system: ol and huriyah;

    Other: asthenia.

    The following rare serious side effects were noted against the background of NSAID administration and also can not be completely excluded for Dynastat. acute renal failure, congestive heart failure, anaphylactic shock, bronchospasm, hepatitis.

    Against the background of the use of valdecoxib, the metabolic precursor of which is parecoxib, the following reactions are also noted: angioedema, anaphylactic reactions, erythema multiforme, exfoliative dermatitis,Stevens-Johnson syndrome and toxic epidermal necrolysis, these reactions are also not excluded and with the administration of parecoxib.

    Overdose:

    Single doses up to 200 mg of parecoxib were administered to / in healthy volunteers without the occurrence of clinically significant side effects. Parecoxib in a dose of 50 mg was administered iv / 2 times a day (100 mg / day) for 7 days with no signs of toxicity.

    Data on the clinical symptoms of overdose are absent.

    In case of suspicion of an overdose of Dinastat, symptomatic treatment is indicated. Dialysis is unlikely to be effective for removing the drug, since parecoxib is characterized by a high degree of binding to plasma proteins.

    Interaction:

    Warfarin and other anticoagulants:

    The combined use of parecoxib with warfarin causes a slight increase AUC warfarin, as well as prothrombin time (See "Special instructions").

    Fluconazole, ketoconazole: Value AUC parecoxib in plasma is increased by 62% with its simultaneous application with fluconazole (CYP2C9 - inhibitor), and 38% - with simultaneous application with ketoconazole (CYP3A4 - inhibitor).

    ACE inhibitors: Inhibition of prostaglandin synthesis by parecoxib can reduce the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors (See "Specific guidance").

    Lithium: Valedecoxib (an active metabolite of parecoxib) causes a significant decrease in serum (25%) and renal (30%) lithium clearance and as a result - an increase of 34% AUC lithium in serum (See "Special instructions").

    Other drugs: There are no clinically significant pharmacokinetic interactions between parecoxib and intravenous or intravenous midazolam, heparin, propofol, fentanyl or alfentanil. There were no clinically significant interactions between valdecoxib and glibenclamide (glyburide), methotrexate, oral contraceptives (ethinyl estradiol / norethindrone).

    There is no evidence of the interaction of parecoxib and inhalational anesthetics, such as nitrous oxide and isoflurane.

    Parecoxib does not affect the antithrombotic effect of acetylsalicylic acid (See "Special instructions").

    The metabolism of valdecoxib can increase with its simultaneous administration with enzyme inducers: rifampicin, phenytoin, carbamazepine or dexamethasone.

    The administration of valdecoxib is accompanied by an increase in the concentration in the plasma of dextromethorphan (substrate CYP2D6) in 3 times. Caution should be exercised with the simultaneous appointment of dinastat and drugs, the metabolism of which is carried out primarily with the participation of the enzyme CYP2D6, and which are characterized by a narrow therapeutic index (flecainide, propafenone, metoprolol).

    Simultaneous administration with naloxone has no effect on the severity of the analgesic effect of valdecoxib, therefore it is assumed that simultaneous administration with opioid analgesics does not cause an increase in sedation and additional inhibition of the respiratory center.

    Diuretics: NSAIDs can reduce the effectiveness of furosemide and thiazides by reducing renal synthesis of prostaglandins.

    With the simultaneous use of NSAIDs and cyclosporine or tacrolimus, the nephrotoxic effect of the latter is enhanced.

    Special instructions:

    In the treatment with the drug Dynastat, there were cases of formation (ulcers including perforating) and bleeding from the upper gastrointestinal tract.In this regard, caution should be exercised in prescribing NSAIDs to patients with gastrointestinal diseases such as ulcers, bleeding and inflammatory conditions in the active form and history, as well as the elderly, patients with cardiovascular diseases and patients taking aspirin.

    In case of appearance of the first signs of a skin rash or other signs of hypersensitivity, the Dynasty should be canceled (See "Side effect").

    With the use of valdecoxib, the development of hypersensitivity reactions (anaphylactoid reactions and angioedema) in patients taking valdecoxib is noted, they are also not excluded for parecoxib. (See "Side effect"). These reactions were noted in patients with already known and yet not allergic reactions to sulfonamides (see "Contraindications"),

    After the appointment of parecoxib, anticoagulant activity should be carefully monitored for the first few days in patients taking warfarin or similar drugs, since such patients may be at greater risk of bleeding (see "Interaction with other drugs").

    Due to the inhibition of prostaglandin synthesis, a number of patients receiving parecoxib, fluid retention and swelling may occur, so caution should be exercised in appointing Dynastat to patients with conditions that develop or worsen due to fluid retention. Patients with a history of heart failure or hypertension should be closely monitored.

    Caution should be exercised when administering parecoxib therapy to patients with severe dehydration. In such cases, it is advisable to first rehydrate, and then begin therapy with parecoxib.

    There is no experience of using the drug in patients with severe impairment of liver function. The use of parecoxib in them is not recommended. Parecoxib should be used with caution in the treatment of patients with impaired liver function of moderate severity and prescribe at the lowest recommended dose (See "Dosage and route of administration").

    The condition of patients with symptoms and / or signs of liver dysfunction, or those with a test showing a deviation of liver function, should be carefully monitored during treatment with parecoxib.

    Because of the anti-inflammatory effect parecoxib can reduce the significance of diagnostic signs, such as fever, in determining the infection.

    Dinastat should be used with caution after aorto-coronary bypass surgery, as this category of patients has a higher risk of developing serious adverse reactions, especially in patients with a history of cerebrovascular disease, as well as those whose body mass index> 30 kg / m2.

    For patients receiving fluconazole therapy, dinastat should be given at the lowest recommended dose. When co-administered with ketoconazole, no dose adjustment is required.

    Caution should be exercised while prescribing the drug Dynastat and drugs, the mechanism of action of which is associated with inhibition of enzymes P450 CYP3A4 and CYP2C9, as this may cause an increase AUC parecoxib.

    The possibility of reducing the antihypertensive effect by inhibiting the synthesis of prostaglandins should be taken into account when administering parecoxib in conjunction with ACE inhibitors (see "Interaction with other drugs").

    Serious monitoring of lithium serum concentrations after the initiation of therapy with parecoxib or after changing the dosage regimen in patients receiving lithium therapy should be carefully monitored (see "Interaction with other drugs").

    Because of insufficient influence on the function of platelets, parecoxib It can not be regarded as a substitute for acetylsalicylic acid, prescribed for the prevention of cardiovascular diseases (see "Interaction with other drugs").

    Caution should be exercised while prescribing Dynastat with drugs that are substrates CYP2C19 (eg, phenytoin, diazepam, imipramine).

    Effect on the ability to drive transp. cf. and fur:

    During the period of treatment, dizziness, drowsiness and anxiety may occur, therefore, it is necessary to refrain from engaging in potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

    Form release / dosage:

    Liofilizate for the preparation of a solution for intravenous and intramuscular administration 40 mg.

    Packaging:

    40 mg of parecoxib per vial of transparent colorless glass (type I), ukuporenny rubber stopper, run-in aluminum cap with plastic a lid-type flip-off.

    2 ml of solvent in an ampoule of transparent colorless glass (type I).

    1 bottle with lyophilizate and 1 ampoule with solvent together with the the application is placed in a cardboard box;

    5 vials with lyophilizate into the contour cell packing, 5 ampoules solvent into the contour mesh packing.

    1 circuit cell pack with lyophilizate and 1 contiguous cell Packaging with solvent is placed together with instructions for use in cardboard pack;

    5 vials with lyophilizate in a contour cell package.

    2 contour cell packs with lyophilizate together with instructions for use are placed in a cardboard box.

    Storage conditions:

    List B.

    Store at a temperature not exceeding 30 0 C, in places inaccessible to children.

    Shelf life:

    3 years. Do not use after the date shown on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:П N015824 / 01
    Date of registration:28.12.2009
    The owner of the registration certificate:Pfizer IFG Belgium N.V.Pfizer IFG Belgium N.V. Belgium
    Manufacturer: & nbsp
    Representation: & nbspPfizer LtdPfizer LtdUSA
    Information update date: & nbsp19.08.2015
    Illustrated instructions
      Instructions
      Up