Dynastat
Dinastat: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Dynastat
ATX code: M01AH
Active ingredient: Parecoxib (Parecoxib)
Manufacturer: PHARMACIA Ltd. (United Kingdom)
Description and photo update: 18.10.2018
Dinastat is a non-steroidal anti-inflammatory drug.
Release form and composition
Dynastat's dosage form is a lyophilisate for preparing a solution for injection: it is produced in the form of a tablet or a porous mass of white or almost white color; solvent - a clear, colorless liquid (1 bottle with a lyophilisate and 1 ampoule with a solvent in a carton box; 5 bottles with a lyophilisate in a contour cell package together with 5 ampoules of solvent in a contour cell package, 1 package with a lyophilisate and 1 package with a solvent in a pack of cardboard; 5 vials with lyophilisate in a blister strip packaging, 2 packages in a carton box).
The composition of 1 bottle (20/40 mg) includes:
- active substance: sodium parecoxib - 21.18 / 42.36 mg (corresponds to 20/40 mg parecoxib). The final concentration of parecoxib after dissolution in 1 ml (for 20 mg) and 2 ml (for 40 mg) solvent is 20 mg / ml;
- excipients: phosphoric acid and / or sodium hydroxide (to adjust the pH level), sodium hydrogen phosphate heptahydrate.
Solvent composition: water for injection, sodium chloride.
Pharmacological properties
Pharmacodynamics
Parecoxib - the active ingredient of the drug Dinastat - after the administration of the drug, it rapidly hydrolyzes to form valdecoxib. The principle of action of valdecoxib is explained by the inhibition of prostaglandin synthesis with the participation of cyclooxygenase-2 (COX-2). Valdecoxib acts as a selective inhibitor of COX-2 against prostaglandins of both peripheral and central action, while it does not inhibit COX-1 and practically does not affect physiological processes in tissues depending on COX-1, in particular in the intestinal and gastric mucosa, and also does not affect platelet aggregation and the duration of bleeding. Due to the absence of an effect on COX-1 and a selective effect on COX-2, the frequency of formation of endoscopically confirmed erosions, gastric and duodenal ulcers when using Dynastat is lower,than with the use of non-selective NSAIDs.
Pharmacokinetics
After intramuscular or intravenous administration, parecoxib is rapidly metabolized to valdecoxib, which is a pharmacologically active component, as a result of enzymatic hydrolysis in the liver.
Absorption: after intravenous administration of the drug in the dose range of 20, 50 and 80 mg per day, changes in valdecoxib pharmacokinetic parameters such as the area under the concentration-time curve (AUC) and maximum concentration (C max) are linear. Equilibrium concentrations of valdecoxib in blood plasma with the introduction of the drug 2 times a day are achieved within 4 days.
After a single injection of Dynastat at a dose of 20 mg, C max of valdecoxib is achieved within about 1 hour - for intramuscular administration, 30 minutes - for intravenous injection. After intramuscular and intravenous administration of valdecoxib, the AUC and C max values are similar.
Distribution: After intravenous administration, the volume of distribution of valdecoxib is approximately 55 liters. At concentrations achieved by using the maximum recommended dose (80 mg per day), the plasma protein binding is approximately 98%. Valdecoxib predominantly accumulates in erythrocytes, in contrast to parecoxib.
Metabolism: The plasma half-life (T 1/2) of valdecoxib is approximately 22 minutes. Parecoxib is rapidly and almost completely converted to valdecoxib and propionic acid. Excretion of valdecoxib occurs by intensive metabolism in the liver in many ways, including metabolism with the participation of cytochrome P450 isoenzymes CYP3A4 and CYP2C9, as well as by CYP-independent glucuronidation (approximately 20%) of the sulfonamide moiety. The hydroxylated metabolite of valdecoxib found in plasma is active as a COX-2 inhibitor. It accounts for approximately 10% of the concentration of valdecoxib; it has practically no significant clinical effect after the administration of therapeutic doses of parecoxib sodium, due to the fact that the concentration of this metabolite is low.
Excretion: Valdecoxib is excreted by metabolic conversion in the liver, and only less than 5% is excreted unchanged in the urine. Approximately 70% of the dose of the drug is excreted in the urine in the form of inactive metabolites, unchanged parecoxib is not found in urine, and in feces it appears only in trace amounts.
Plasma clearance (CLp) for valdecoxib is about 6 L / h. After intramuscular and intravenous administration of parecoxib sodium, the T 1/2 of valdecoxib is approximately 8 hours. In elderly patients, the plasma concentration of valdecoxib is approximately 40% higher than in younger patients, due to the fact that they have a reduced clearance of valdecoxib. The equilibrium plasma concentration of valdecoxib is 16% lower in older men than in older women.
Indications for use
Dinastat is used in acute pain to reduce the need for opioid analgesics and to reduce or prevent postoperative pain.
Contraindications
- angioedema, bronchospasm, acute rhinitis, urticaria or other allergic reactions after taking acetylsalicylic acid and other NSAIDs, including other selective COX-2 inhibitors;
- allergic reactions to sulfonamides;
- III trimester of pregnancy, lactation period;
- erosive and ulcerative lesions of the gastrointestinal tract during an exacerbation (including acute peptic ulcer);
- severe congestive heart failure;
- severe hepatic impairment (no experience with use);
- hypersensitivity to the active substance or any component of the drug;
- age up to 18 years (no experience of use).
Instructions for the use of Dynastat: method and dosage
Dinastat can be administered intramuscularly or intravenously, either as regular repeated injections, or at a time or as needed. Depending on the patient's response to the drug after the start of therapy, the dose is adjusted. There is experience of using Dynastat for 7 days.
In acute pain, the recommended initial single dose is 40 mg for intravenous or intramuscular administration, if necessary, repeated administrations are possible every 6-12 hours at 20-40 mg; the daily dose should not exceed 80 mg. An intravenous bolus injection can be given quickly, directly into a vein or into a pre-installed IV infusion tube. Intramuscular injection is recommended to be done deep into the muscle, slowly.
For postoperative pain (to prevent or reduce it), a dose of 40 mg intramuscularly or, preferably, intravenously is recommended. The drug is administered 30–45 minutes before surgery. To maintain the effect, Dynastat is administered repeatedly, according to the scheme presented for the relief of acute pain.
To reduce the need for opioid analgesics, Dynastat is used before their administration, in combination with them. In this case, the daily need for opioid analgesics is reduced by 20–40%.
In elderly patients, as a rule, dose adjustment of Dynastat is not required. If the body weight of an elderly patient is less than 50 kg, it is recommended to start the drug administration with a 0.5 dose; the maximum daily dose in this case is 40 mg.
In patients with impaired renal function with severe renal failure (creatinine clearance less than 30 ml / min) or with conditions predisposing to fluid retention in the body, it is recommended to prescribe parecoxib at the lowest recommended dose, as well as carefully monitor renal function.
For patients with impaired liver function, dose adjustment is usually not required. In case of violations of moderate severity, the introduction of the drug begins with a 0.5 dose, and the daily dose is reduced to 40 mg. In case of severe liver damage, the administration of the drug is not recommended due to the lack of experience with the use of Dynastat in this group of patients.
Preparation of the drug for administration
To prepare a solution for injection, use:
- for vials of 20 mg - 1 ml of sodium chloride solution for injection (0.9%);
- for vials of 40 mg - 2 ml of sodium chloride solution for injection (0.9%).
The following solvents can also be used: 5% dextrose (glucose) solution for injection, 0.9% sterile sodium chloride solution, 5% dextrose (glucose) solution with 0.45% sodium chloride for injection (when using the above solvents, the finished solution is isotonic).
Do not mix Dynastat with other medicines.
It is not recommended to use Lactate Ringer's (Hartman's) solutions for injection or Ringer's Lactate for injection with 5% dextrose (glucose) solution to prepare Dynastat solution, as this leads to precipitation.
Due to the fact that the resulting solution will not be isotonic, it is not recommended to use sterile water for injection as a solvent for Dynastat.
Do not freeze or refrigerate the prepared solution.
After dissolution, the drug can be injected into the tubes of the intravenous infusion system containing solvents: 5% dextrose (glucose) solution for injection, Lactate Ringer's solution for injection, sodium chloride solution for injection, 5% dextrose (glucose) solution with 0.45% chloride sodium.
Side effects
Often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1/100):
- cardiovascular system: often - increase or decrease in blood pressure; infrequently - cerebrovascular disorders, bradycardia;
- hematopoietic system: infrequently - thrombocytopenia;
- respiratory system: often - respiratory failure;
- upper respiratory tract: infrequently - pharyngitis;
- nervous system: often - hypesthesia, dizziness;
- autonomic nervous system: infrequently - dry mouth;
- metabolism: often - hypokalemia, increased creatinine levels; infrequently - an increase in the level of urea nitrogen in the blood, hyperglycemia;
- digestive system: often - dyspepsia, flatulence, constipation, postextraction alveolitis; infrequently - erosion, gastric and duodenal ulcers;
- psyche: often - insomnia, anxiety;
- urinary system: infrequently - oliguria;
- hepatobiliary system: infrequently - increased activity of transaminases ALT and AST;
- sense organs: infrequently - ear pain;
- skin: often - itching, increased sweating; infrequently - delayed healing of postoperative wounds, rash;
- musculoskeletal system: infrequently - arthralgia;
- local reactions: pain at the injection site, wound infection (including during coronary artery bypass grafting operations), pathological discharge from the drain established after surgery, accompanied by dissection of the sternum;
- others: often - ecchymosis, postoperative anemia, peripheral edema, back pain; infrequently - asthenia.
When taking Dynastat, rare severe side effects that were observed when taking NSAIDs cannot be completely ruled out: bronchospasm, hepatitis, anaphylactic shock, acute renal failure, congestive heart failure.
While taking valdecoxib and parecoxib, the following reactions were observed: exfoliative dermatitis, toxic epidermal necrolysis, Steven-Johnson syndrome, erythema multiforme, angioedema, anaphylactic reactions.
Overdose
There are no data on the clinical symptoms of an overdose of Dinastat.
If an overdose of Dynastat is suspected, symptomatic treatment is recommended. Due to the fact that parecoxib has a high degree of binding to plasma proteins, the effectiveness of dialysis for removing the drug from the body is insignificant.
special instructions
During the first few days after the appointment of parecoxib, careful monitoring of anticoagulant activity should be carried out in patients taking warfarin or similar drugs, due to the high risk of bleeding.
Dynastat should be used with caution in patients whose condition has arisen or worsens due to fluid retention, since a number of patients taking parecoxib may experience edema and fluid retention due to inhibition of prostaglandin synthesis. The condition of patients with a history of arterial hypertension and heart failure should be closely monitored.
In case of severe dehydration in a patient, it is advisable to rehydrate before prescribing therapy with Dynastat.
Due to the fact that during the treatment with Dynastat, there were cases of bleeding from the upper gastrointestinal tract, as well as ulcers, including perforated, the drug is prescribed with extreme caution for bleeding from the gastrointestinal tract, inflammatory processes in an active form and ulcers of the gastrointestinal tract, and also people taking aspirin, patients with cardiovascular disease and the elderly.
Parecoxib may reduce the importance of diagnostic features in detecting an infection, such as fever, due to its anti-inflammatory properties.
Simultaneous administration of Dynastat with drugs, whose mechanism of action is associated with inhibition of the P450 CYP3A4 and CYP2C9 enzymes, may cause an increase in the AUC of parecoxib.
When prescribing parecoxib together with ACE inhibitors, the possibility of reducing the antihypertensive effect by inhibiting prostaglandin synthesis should be taken into account.
In patients receiving lithium therapy, after starting parecoxib therapy, careful monitoring of the serum lithium concentration is necessary.
Due to its insufficient effect on platelet function, parecoxib cannot be considered as an alternative to acetylsalicylic acid for the prevention of cardiovascular diseases.
Caution is required when concomitantly administering Dynastat with CYP2C19 substrates.
Influence on the ability to drive vehicles and complex mechanisms
Due to the risk of drowsiness, anxiety and dizziness during treatment, it is necessary to refrain from activities that require increased attention, concentration and speed of reactions.
Application during pregnancy and lactation
There is no experience of using Dynastat in pregnant women.
According to the instructions, Dynastat should be prescribed only if the expected benefit to the woman outweighs the potential risk to the fetus. In the last trimester, the use of the drug is contraindicated due to the fact that it can cause premature closure of the Botallov duct and a decrease in the contractile activity of the uterus.
There is no data on whether parecoxib is excreted in breast milk. When deciding to start therapy with Dynastat, breastfeeding should be interrupted for the duration of treatment.
Pediatric use
The drug is contraindicated in patients under the age of 18.
With impaired renal function
Parecoxib is prescribed in the lower of the recommended doses in conditions that predispose to fluid retention in the body, as well as in severe renal failure, in cases where creatinine clearance is less than 30 ml / min. This requires careful monitoring of the patient's renal function.
For violations of liver function
The use of parecoxib is not recommended in patients with severely impaired liver function, as there is no experience with its use in this group of patients.
With caution and in the lowest recommended dose, the drug is prescribed to patients with moderate liver dysfunction.
Use in the elderly
In elderly patients, as a rule, dose adjustment of Dynastat is not required. However, if the body weight of an elderly patient is less than 50 kg, it is recommended to start the drug administration with a 0.5 dose; the maximum daily dose in this case is 40 mg.
Drug interactions
- ACE inhibitors: reducing the antihypertensive effect;
- warfarin: affects prothrombin time and warfarin AUC, causes them to slightly increase;
- fluconazole, ketoconazole: increase in plasma AUC of parecoxib by 62%, with ketoconazole by 38%;
- lithium: a decrease in renal (30%) and serum (25%) lithium clearance, resulting in an increase in serum lithium AUC by 34%;
- dexamethasone, carbamazepine, rifampicin, phenytoin: an increase in the metabolism of valdecoxib is allowed;
- diuretics: a decrease in the effectiveness of furosemide and thiazides due to a decrease in renal prostaglandin synthesis;
- inhalation anesthetics: no confirmed interactions;
- acetylsalicylic acid: parecoxib has no effect on its antithrombotic effect;
- naloxone: presumably not causing additional respiratory depression and increased sedation;
- cyclosporine or tacrolimus: enhances the nephrotoxic effect;
- other drugs: significant pharmacokinetic interactions between parecoxib and intravenous heparin, midazolam, propofol, alfentanil and fentanyl have not been observed. Significant interactions between valdecoxib and methotrexate, glibenclamide (glyburide), oral contraceptives, in particular norethindrone and ethinyl estradiol, have not been noted.
With the simultaneous appointment of valdecoxib with inducers of liver microsomal enzymes, its metabolism may increase.
Analogs
Arcoxia is an analogue of Dynastat.
Terms and conditions of storage
Store out of the reach of children, where the air temperature does not exceed 30 ° C.
The shelf life is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about the Dynastat
There are few reviews about Dynastat, in which patients note the rapid relief of pain after taking the drug, but at the same time indicate its high cost.
Dynastat price in pharmacies
The price for Dynastat in pharmacies is 2550 rubles.
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
