Active ingredients: Parecoxib
Dynastat 40 mg powder for solution for injection
Indications Why is Dynastat used? What is it for?
Dynastat contains the active substance parecoxib.
Dynastat is used for the short-term treatment of postoperative pain in adults.
It belongs to a category of medicines called COX-2 inhibitors (short for cyclooxygenase-2 inhibitors). Pain and swelling are sometimes caused by certain substances produced by the human body called prostaglandins. Dynastat works by decreasing the levels of these prostaglandins.
Contraindications When Dynastat should not be used
Do not use Dynastat
- if you are allergic to parecoxib or any of the other ingredients of this medicine (listed in section 6)
- if you have ever had a severe allergic reaction (especially a severe skin reaction) to any medicine
- if you have had an allergic reaction to a group of medicines called "sulphonamides" (for example some antibiotics used to treat certain infections)
- if you have an active stomach or intestinal ulcer or bleeding in the stomach or intestines
- if you have ever had an allergic reaction to acetylsalicylic acid (aspirin) or to other non-steroidal anti-inflammatory drugs (eg ibuprofen) or to COX-2 inhibitors. Reactions after taking this medicine may include breathing difficulties (bronchospasm), congestion nasal, itching, rash or swelling of the face, lips or tongue, other allergic reactions or nasal polyps
- if you are in the last trimester of pregnancy
- if you are breastfeeding
- if you have severe liver disease
- if you suffer from inflammatory bowel disease (ulcerative colitis or Crohn's disease)
- if you have heart failure
- if you are about to have heart or arterial surgery (including coronary artery surgery)
- if you have overt heart disease and / or cerebrovascular disease, for example if you have had a heart attack, stroke, mild stroke (Transient Ischemic Attack) or blockages in the blood vessels of the heart or brain or if you have had to an intervention to eliminate these obstructions or remedy them
- if you have or have ever had circulation problems (peripheral artery disease)
If you find yourself in any of these cases, you will not need to have the injection. Tell your doctor or nurse immediately.
Precautions for use What you need to know before taking Dynastat
Do not use Dynastat if you have an active stomach or intestinal ulcer or gastrointestinal bleeding
Do not use Dynastat if you have severe liver disease
Talk to your doctor or nurse before using Dynastat:
- If you have previously had an ulcer, bleeding or perforation of the gastrointestinal tract
- If you are taking acetylsalicylic acid (aspirin) or other non-steroidal anti-inflammatory drugs (NSAIDs) (e.g. ibuprofen)
- If you smoke
- If you have diabetes
- If you have angina, blood clots, high blood pressure or raised cholesterol levels
- If you are taking medicines that affect platelet aggregation (eg acetylsalicylic acid)
- If you have fluid retention (edema)
- If you have liver or kidney disease.
- If you are dehydrated - this can happen if you have diarrhea or if you have vomited or are unable to drink fluids
- If you have an "infection, as this can mask a feverish state (which is a sign of infection)
- If you are using medicines to reduce blood clotting (e.g. warfarin / warfarin-like anticoagulants or new oral anticoagulants, e.g. apixaban)
- If you are using medicines called corticosteroids (for example prednisone)
- If you are using a class of medicines given to treat depression called selective serotonin reuptake inhibitors (e.g. sertraline).
Dynastat can cause an increase in blood pressure or worsening of pre-existing hypertension which can lead to an increase in side effects associated with heart conditions. While you are being treated with Dynastat, your doctor may want to check your blood pressure.
Children and adolescents
Children and adolescents under 18 years of age should not take Dynastat.
Interactions Which drugs or foods may change the effect of Dynastat
Tell your doctor or nurse if you are taking or have taken or might take any other medicines. Medicines can sometimes interfere with each other. Your doctor may reduce the dose of Dynastat or other medicines or recommend that you take different medicines. Especially. it is important for your doctor to know if you are taking:
- Acetylsalicylic acid (aspirin) or other anti-inflammatory medicines
- Fluconazole - used for fungal infections
- ACE inhibitors, Angiotensin II inhibitors, beta blockers and diuretics - used in case of high blood pressure and heart disease
- Ciclosporin or tacrolimus - used after transplants
- Warfarin or other warfarin-like medicines - used to prevent blood clots, including newer medicines such as apixaban
- Lithium - used for the treatment of depression
- Rifampicin - used for bacterial infections
- Antiarrhythmics - used to treat an irregular heartbeat
- Phenytoin or carbamazepine - used in epilepsy
- Methotrexate - used in rheumatoid arthritis and cancer
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
- If you are pregnant or planning to become pregnant, please tell your doctor. Dynastat is not recommended in the first 6 months of pregnancy and you should not be given Dynastat during the last trimester of pregnancy.
- If you are breastfeeding, you should not take Dynastat, as small amounts of Dynastat will pass into the milk.
- NSAIDs, including Dynastat, could make conception more difficult. Tell your doctor if you are planning to become pregnant or have difficulty becoming pregnant.
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or nurse for advice before taking this medicine.
Driving and using machines
If you feel dizzy or tired after the injection, do not drive or operate machinery until you feel better again.
Dynastat contains
This medicine contains less than 1 mmol (23 mg) sodium per dose, ie it is essentially 'sodium-free'.
Dose, Method and Time of Administration How to use Dynastat: Posology
Dynastat will be given to you by a doctor or nurse. They will dissolve the powder before giving you the injection and inject the solution into a vein or muscle. The injection can be done quickly and directly into a vein or into an existing line (into a thin tube that flows into a vein), or it can be done slowly and deep into the muscle. Dynastat can only be given to you for short periods and for pain relief only.
The normally recommended starting dose is 40 mg.
A subsequent dose of 20 mg or 40 mg can be given to you 6-12 hours after the first dose.
You cannot be given more than 80 mg in a 24 hour period.
Some people may need smaller doses:
- People with liver problems
- People with severe kidney problems
- Patients over 65 years of age with a body weight of less than 50 kg
- People being treated with fluconazole
If Dynastat is used together with strong painkillers (called opioid painkillers) such as morphine the dose of Dynastat will be the same as above.
Overdose What to do if you have taken too much Dynastat
If you take more Dynastat than you should, you may experience side effects that have been reported with recommended doses.
If you are unsure about the use of this medicine, consult your doctor or nurse.
Side Effects What are the side effects of Dynastat
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking Dynastat immediately and contact your doctor:
- if you develop a skin rash or "ulceration in any part of the body (for example, skin, mouth, eyes, lips or tongue), or develop any other signs of an allergic reaction such as a rash, swelling of the face, lips or tongue which can cause wheezing, difficulty breathing or swallowing - this rarely occurs
- if you have blisters or peeling of the skin - this is rarely the case
- The onset of skin reactions can occur at any time, but more often occurs in the first month of treatment; the frequency of these events appears to be higher for valdecoxib, a parecoxib-like medicine, compared to other COX-2 inhibitors
- if you have jaundice (the skin or whites of the eyes are yellow)
- if you have any signs of bleeding in your stomach or intestines, such as passing black or bloodstained stools or vomiting blood
Very common: may affect more than 1 in 10 people
? Nausea (feeling sick)
Common: may affect up to 1 in 10 people
- Changes in blood pressure (increase or decrease)
- Backache
- Swelling of the ankles, legs and feet (fluid retention)
- Numbness - the skin may lose sensitivity to pain or touch
- Vomiting, stomach pain, digestive upset, constipation, bloating and flatulence
- Alteration of normal renal function values
- Agitation or difficulty in falling asleep
- Dizziness
- Risk of anemia - changes in red blood cells after surgery that can cause fatigue and shortness of breath
- Sore throat or difficulty in breathing (shortness of breath)
- Itchy skin
- Reduction in the amount of urine
- Post-extraction alveolitis (inflammation and pain after tooth extraction)
- Increased sweating
- Low potassium levels on blood tests
Uncommon: may affect up to 1 in 100 people
- Heart attack
- Risk of cerebrovascular disorders eg. stroke, or transient ischemic attack (transient reduction in blood flow to the brain) / minor stroke or angina, or blockage of blood vessels to the heart or brain
- Blood clots in the lungs
- Further increase in blood pressure
- Ulcers of the digestive tract, chronic gastric acid reflux
- Slowing of the heartbeat
- Low blood pressure when standing
- Alteration of normal liver function values
- Evidence of bruising due to low platelet count
- Risk of surgical wound infection, abnormal discharge from surgical wounds
- Skin discolouration or bruising
- Complications in wound healing after surgery
- Elevated blood sugar levels
- Injection site pain or injection site reaction
- Rash, itchy rash (hives)
- Anorexia (loss of appetite)
- Pain in the joints
- Elevated levels of enzymes in the blood resulting from tests indicating heart, brain, or muscle tissue injury or stress
- Dry mouth
- Muscle weakness
- Pain in the ears
- Unusual abdominal noises
Rare: may affect up to 1 in 1000 people
- Rash or ulceration in any part of the body (e.g. skin, mouth, eyes, lips or tongue), or any other signs of allergic reactions such as rash, swelling of the face, lips and tongue, wheezing,
- difficulty in breathing or swallowing (potentially fatal)
- Swelling, blistering or peeling of the skin
- Acute renal failure
- Hepatitis (inflammation of the liver)
- Inflammation of the throat (esophagus)
- Inflammation of the pancreas (can lead to stomach pain)
Not known: frequency cannot be estimated from the available data
- Collapse due to severe drop in blood pressure
- Heart failure
- Kidney failure
- Increased frequency or irregular heartbeat
- Wheezing
Reporting of side effects
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the carton and vial after EXP. The expiry date refers to the last day of that month.
This medicinal product does not require any special storage conditions prior to reconstitution.
It is recommended to use Dynastat as soon as possible after mixing it with the solvent, although it can be stored if the instructions at the end of the package leaflet are strictly followed. The solution to be injected must be clear and colorless.
Do not use the solution if the solution to be injected has residues of particulate matter or if the powder or solution has discolored.
Deadline "> Other information
What Dynastat contains
- The active substance is parecoxib (like parecoxib sodium). Each vial contains 40 mg of parecoxib, as 42.36 mg of parecoxib sodium. After reconstitution with 2 ml of solvent, a concentration of 20 mg / ml of parecoxib is obtained. After reconstitution in sodium chloride 9 mg / ml (0.9%) solution, Dynastat contains approximately 0.44 mEq of sodium per vial.
- The other ingredients are: Disodium phosphate anhydrous Phosphoric acid and / or sodium hydroxide (to adjust the acidity of the solution)
What Dynastat looks like and contents of the pack
Dynastat is available as a white to off-white powder.
The powder is contained in clear glass vials (5 ml) with a stopper, sealed with a purple flip-off cap placed on the aluminum over-seal.
Deadline "> Information for healthcare professionals
The following information is intended for healthcare professionals only.
Dosage
The recommended dose is 40 mg, administered intravenously (i.v.) or intramuscularly (i.m.); it can be followed at intervals of 6-12 hours by doses of 20 mg or 40 mg as needed, provided that the daily dose of 80 mg is not exceeded. Intravenous bolus injection can be given quickly and directly into a vein or into an existing line. Intramuscular injection should be done slowly and deeply into the muscle.
Clinical experience with Dynastat beyond three days is limited.
Since the cardiovascular risk of specific cyclooxygenase-2 (COX-2) inhibitors may increase with dose and duration of exposure, the duration of treatment should be as short as possible and the lowest effective daily dose should be used.
There have been post-marketing reports of severe hypotension occurring soon after administration of parecoxib. Some of these occurred with no other signs of anaphylaxis. Physicians must be prepared to treat severe hypotension.
Administration is via intramuscular (i.m.) or intravenous (i.v.) injection.
The i.m. injection should be done slowly and deeply into the muscle and the i.v. bolus can be delivered quickly and directly into a vein or into an existing intravenous line.
Methods of administration other than intravenous or intramuscular
Routes of administration (e.g. intra-articular, intrathecal) other than intravenous or intramuscular have not been studied and should not be used.
Solvents for reconstitution
This medicinal product must not be mixed with other medicinal products. The medicine should only be reconstituted with one of the following solutions:
- sodium chloride 9 mg / ml (0.9%) solution for injections / infusion
- glucose solution for infusion 50 mg / ml (5%); or
- 4.5 mg / ml (0.45%) sodium chloride and 50 mg / ml (5%) glucose solution for injections / infusion
The following solvents cannot be used for reconstitution:
- The use of lactated Ringer's solution for injections or glucose 50 mg / ml (5%) in lactated Ringer's solution for injections for reconstitution of parecoxib is not recommended as it causes the formation of a precipitate of parecoxib.
- The use of sterile water for injections is not recommended because the resulting solution is not isotonic.
Procedure for reconstitution
Aseptic technique should be used for reconstitution of lyophilized parecoxib (such as parecoxib sodium).
40 mg vial: remove the purple flip-off cap until the central part of the rubber stopper of the 40 mg parecoxib vial is visible. Withdraw, using a sterile needle and syringe, 2 ml of a suitable solvent and insert the needle through the central part of the rubber stopper in order to transfer the solvent into the 40 mg parecoxib vial.
Completely dissolve the powder with a gentle twisting motion and check the reconstituted product before use.
The reconstituted solution should not be used if discolored or cloudy or if particulate residues are found.
The entire contents of the vial should be withdrawn for a single administration. If a dose of less than 40 mg is required, excess medicinal product should be discarded.
Compatibility of the intravenous solution
Dynastat in solution with other medicinal products can cause precipitate formation and therefore Dynastat must not be mixed with other medicinal products, neither during the reconstitution step nor at the time of administration. In patients where the same infusion line is to be used for the administration of another medicinal product, the infusion line should be flushed before and after administration of Dynastat with a compatible solution.
After reconstitution with suitable solvents, Dynastat can be injected intravenously or intramuscularly or only into intravenous lines that administer:
- sodium chloride 9 mg / ml (0.9%) solution for injections / infusion
- glucose solution for infusion 50 mg / ml (5%)
- 4.5 mg / ml (0.45%) sodium chloride and 50 mg / ml (5%) glucose solution for injections / infusion; or
- lactated Ringer's solution for injections
Administration of Dynastat in the same infusion line with glucose 50 mg / ml (5%) in lactated Ringer's solution or other intravenous fluids not listed in this section is not recommended as it causes the formation of a precipitate of parecoxib.
The solution is for single use only and should not be stored in the refrigerator or freezer.
Chemical and physical stability of the reconstituted solution, which must not be refrigerated or frozen, has been demonstrated for up to 24 hours at 25 ° C. Therefore 24 hours should be considered as the maximum shelf life of the reconstituted product. However, due to the importance of the risk of microbiological infection for injectable products, the reconstituted solution should be used immediately unless the reconstitution is done under validated and controlled aseptic conditions. If these requirements are not met, the storage times and conditions prior to use are the responsibility of the user and should normally not exceed 12 hours at 25 ° C.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT -
DYNASTAT POWDER AND SOLVENT
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
40 mg vial: Each vial contains 40 mg of parecoxib (equivalent to 42.36 mg of parecoxib sodium) to be reconstituted. After reconstitution, the final concentration of parecoxib is 20 mg / ml.
After reconstitution in sodium chloride 9 mg / ml (0.9%) solution, Dynastat contains approximately 0.22 mEq of sodium per vial.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Powder and solvent for solution for injection.
White to off-white powder.
Solvent: clear, colorless solution.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Short-term treatment of postoperative pain.
The decision to prescribe a selective COX-2 inhibitor should be based on an assessment of the individual patient's overall risks (see sections 4.3 and 4.4).
04.2 Posology and method of administration -
The recommended dose is 40 mg, administered intravenously (i.v.) or intramuscularly (i.m.); it can be followed by doses of 20 mg or 40 mg at intervals of 6-12 hours as needed, provided that the daily dose of 80 mg is not exceeded. Intravenous bolus injection can be given quickly and directly into a vein or into an existing line. Intramuscular injection should be done slowly and deeply into the muscle (see section 6.6 for reconstitution instructions).
Concomitant use with opioid analgesics: Opioid analgesics can be used in combination with parecoxib at the dosage described in the section above. In all clinical evaluations, parecoxib was given in fixed doses while opioids were given as needed (PRN).
Since the cardiovascular risk of specific cyclooxygenase-2 (COX-2) inhibitors may increase with dose and duration of exposure, the duration of treatment should be as short as possible and the lowest effective daily dose should be used.
Dynastat in solution with other medicinal products can cause precipitate formation and therefore Dynastat must not be mixed with other medicinal products, either during the reconstitution step or at the time of administration. In patients where the same infusion line must be used for the administration of another medicinal product, the infusion line should be adequately flushed with a compatible solution before and after administration of Dynastat.
Compatibility of the i.v. infusion line
After reconstitution with suitable solvents, Dynastat can only be injected intravenously or intramuscularly or into intravenous lines that administer:
sodium chloride solution 9 mg / ml (0.9%)
glucose solution 50 g / l (5%) for infusion
4.5 mg / ml (0.45%) sodium chloride and 50 g / l (5%) glucose solution for injections
Ringer-lactate solution for injections
Injection in line i.v. which administers glucose 50 g / l (5%) in lactated Ringer's solution or other intravenous liquids not listed in the previous paragraph is not recommended as it can cause precipitation of the product in solution.
Senior citizens: Dosage adjustment is not usually necessary in elderly patients (≥ 65 years of age). However, in elderly patients with a body weight of less than 50 kg, treatment should be started with half the normally recommended dosage of Dynastat and the maximum daily dose should be reduced to 40 mg (see section 5.2).
Altered liver function: In patients with mild hepatic impairment (Child-Pugh score 5-6) a dosage adjustment is generally not necessary. Patients with moderate hepatic impairment (Child-Pugh Score 7-9) should start therapy with caution and half the normally recommended dosage of Dynastat and reduce the maximum daily dose to 40 mg. No clinical data are available in patients with severe hepatic impairment (Child-Pugh score ≥ 10), therefore the use of Dynastat is contraindicated in this patient category (see sections 4.3 and 5.2).
Altered renal function: based on pharmacokinetic results, no dosage adjustment is required in patients with mild to moderate renal impairment (creatinine clearance 30-80 ml / min.). In patients with severe renal impairment (creatinine clearance fluid retention treatment with parecoxib should be initiated at the lowest recommended dose and the patient's renal function should be carefully monitored (see sections 4.4 and 5.2).
Children and adolescents: there is no experience of use in children. Therefore the use of Dynastat is not recommended in these patients.
04.3 Contraindications -
Hypersensitivity to the active substance or to any of the excipients (see section 6.1).
History of severe allergic drug reactions of any type, particularly skin reactions such as Stevens-Johnson syndrome, epidermal necrolysis, erythema multiforme or patients with known hypersensitivity to sulphonamides (see sections 4.4 and 4.8).
Active peptic ulcer or gastrointestinal bleeding.
Subjects in whom bronchospasm, acute rhinitis, nasal polyps, angioneurotic edema, urticaria or other allergic-type reactions have occurred after taking acetylsalicylic acid or non-steroidal anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors (cycle- oxygenase-2).
Third trimester of pregnancy and lactation (see sections 4.6 and 5.3).
Severe hepatic insufficiency (serum albumin
Chronic inflammation of the intestine.
Congestive heart failure (NYHA II-IV).
Treatment of post-operative pain following coronary artery bypass grafting (see sections 4.8 and 5.1).
Established ischemic heart disease, peripheral arterial disease and / or cerebral vascular disease.
04.4 Special warnings and appropriate precautions for use -
Clinical experience with Dynastat beyond three days is limited.
Since adverse reactions may increase with increasing doses of parecoxib, other COX-2s and NSAIDs, patients receiving parecoxib should be monitored following dose increases and in the absence of increased efficacy of the drug. , other therapeutic alternatives should be considered (see section 4.2).
Long-term treatment with COX-2 inhibitors has been associated with the risk of cardiovascular and thrombotic adverse events. Neither the exact magnitude of the risk associated with a single dose nor the exact duration of therapy associated with an increased risk have been established.
Patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, cigarette smoking) should only be treated with parecoxib after careful consideration (see section 5.1).
Appropriate measures should be taken and discontinuation of parecoxib should be considered if worsening of specific clinical symptoms is observed in these patients (see section 5.1). Dynastat has not been studied in cardiovascular revascularization procedures other than coronary artery bypass grafting. Studies of surgical interventions other than coronary artery bypass grafting included only American Society of Anaesthesiology (ASA) I-III patients.
Selective COX-2 inhibitors are not a substitute for acetylsalicylic acid for the prophylaxis of cardiovascular thromboembolic diseases because they have no effect on platelet function. Therefore, antiplatelet therapy should not be discontinued (see section 5.1).
Upper gastrointestinal complications (perforations, ulcers or bleeding), some of them fatal, have been reported in patients treated with parecoxib. Caution is advised in the treatment of patients who have an increased risk of gastrointestinal complications associated with the use of NSAIDs: the elderly, patients who are taking any other NSAIDs or acetylsalicylic acid at the same time or patients with a history of gastrointestinal diseases, such as ulcers and gastrointestinal bleeding. When parecoxib sodium is co-administered with acetylsalicylic acid (even at low doses) there is an increased risk of gastrointestinal adverse events (gastrointestinal ulceration or other gastrointestinal complications).
Dynastat has been studied in dental, orthopedic and gynecological surgery (mainly in case of hysterectomy) and in coronary artery bypass surgery. Experience in other types of surgery, such as gastrointestinal or urological surgery, is limited.
Serious skin reactions, including erythema multiforme, exfoliative dermatitis and Stevens-Johnson syndrome (some cases with fatal outcome) have been reported in post-marketing surveillance in patients receiving parecoxib. In addition, cases of necrotic epidermolysis with fatal outcome have been reported in patients receiving valdecoxib (the active metabolite of parecoxib) and cannot be excluded for parecoxib (see section 4.8). Patients appear to be most at risk for these adverse reactions in the early stages of treatment: in most cases, the onset of symptoms occurs within the first month of treatment.
Physicians should take appropriate measures to monitor for any severe skin reactions during therapy (e.g. additional patient visits). Patients should be advised to report any skin reactions to their physician immediately.
Parecoxib treatment should be discontinued at the appearance of the first signs of rash, mucosal lesions or any other signs of hypersensitivity. It is known that severe skin reactions can occur with NSAIDs, including selective COX-2 inhibitors as well as with other drugs. However, the frequency of severe skin reactions appears to be higher for valdecoxib (the active metabolite of parecoxib) than for other selective COX-2 inhibitors. Patients with a history of allergic-type reactions to sulphonamides may be at increased risk of skin reactions (see section 4.3). Patients who do not have a history of sulfonamide allergy may also be at risk for severe skin reactions.
Hypersensitivity reactions (anaphylaxis and angioedema) have been reported from post-marketing experience with valdecoxib and parecoxib (see section 4.8). Some of these reactions have occurred in patients with a history of allergic-type reactions to sulphonamides (see section 4.3). Administration with parecoxib should be discontinued at the first signs of hypersensitivity.
Episodes of acute renal failure have been reported in post-marketing surveillance in patients receiving parecoxib (see section 4.8). Since inhibition of prostaglandin synthesis may lead to deterioration of renal function and fluid retention, caution should be exercised when administering Dynastat to patients with renal impairment (see section 4.2) or hypertension, or to patients with impaired heart or liver function or if they have other conditions that predispose to fluid retention.
Caution is advised when initiating Dynastat therapy in dehydrated patients. In this case it is advisable to rehydrate them before starting Dynastat therapy.
Water retention and edema
As with other prostaglandin synthesis inhibitor medicinal products, fluid retention and edema have been observed in some patients receiving parecoxib. Parecoxib should therefore be used with caution in patients with impaired cardiac function, pre-existing edema or other predisposing conditions or which may worsen fluid retention, including patients on diuretics or otherwise at risk of hypovolaemia.
In the event that there is clinical evidence of deterioration in the condition of these patients, appropriate measures should be taken, including discontinuation of parecoxib.
Hypertension
As with all other NSAIDs, parecoxib can lead to new or worsening of pre-existing hypertension and both can contribute to an increased incidence of cardiovascular events.
NSAIDs, including parecoxib, should be used with caution in hypertensive patients. Blood pressure should be closely monitored during initiation and during the course of parecoxib therapy. If blood pressure rises significantly, alternative treatment should be considered.
It is recommended that Dynastat be used with caution in patients with moderate hepatic impairment (Child-Pugh Score 7-9) (see section 4.2).
If deterioration of the patient's clinical condition of any of the organ systems described above occurs during the course of treatment, appropriate measures should be taken and discontinuation of parecoxib sodium therapy should be considered.
Dynastat may mask febrile states and other signs of inflammation (see section 5.1). There have been isolated reports of aggravation of soft tissue infections in conjunction with the use of NSAIDs and in preclinical studies with Dynastat (see section 5.3). Caution is advised in monitoring the surgical incision in patients treated with Dynastat for any signs of infection.
Caution is advised when administering Dynastat concomitantly with warfarin and other oral anticoagulants (see section 4.5).
The concomitant use of parecoxib with other NSAIDs (excluding aspirin) should be avoided.
Like any drug that inhibits cyclooxygenase / prostaglandin synthesis, Dynastat is not recommended for use in women planning pregnancy (see sections 4.6 and 5.1).
04.5 Interactions with other medicinal products and other forms of interaction -
Interaction studies have only been performed in adults.
Pharmacodynamic interactions
Anticoagulant therapy should be monitored, particularly during the first days of Dynastat therapy in patients already being treated with warfarin or other oral anticoagulants, as these patients have a higher risk of bleeding complications. Therefore, patients on oral anticoagulants should be closely monitored for prothrombin time (INR), particularly in the first few days of therapy when parecoxib treatment is initiated or when the parecoxib dosage is changed (see section 4.4).
Dynastat had no effect on acetylsalicylic acid-mediated inhibition of platelet aggregation or bleeding time. Clinical studies have shown that Dynastat can be used in combination with low-dose acetylsalicylic acid (≤ 325 mg). In pivotal studies , as with other NSAIDs, concomitant administration of low dose acetylsalicylic acid has shown an increased risk of gastrointestinal ulcers or other gastrointestinal complications when compared to the use of parecoxib alone (see section 5.1).
Concomitant administration of parecoxib sodium and heparin had no effect on the pharmacodynamics of heparin (activated partial thromboplastin time) compared to heparin alone.
NSAIDs may reduce the effect of diuretics and antihypertensives. Like NSAIDs, the risk of acute renal failure may be increased when ACE inhibitors or diuretics are co-administered with parecoxib sodium.
The combination of NSAIDs with cyclosporine or tacrolimus may enhance the nephrotoxic effect of cyclosporine and tacrolimus. Renal function should be monitored when parecoxib sodium and any of these substances are administered concomitantly.
Dynastat can be used in combination with opioid analgesics. In clinical trials, the daily requirement for opioids given as needed was significantly reduced when these drugs were co-administered with parecoxib.
Effects of other medicinal products on the pharmacokinetics of parecoxib (or its active portion valdecoxib)
Parecoxib is rapidly hydrolyzed into the active substance valdecoxib. Studies in humans have shown that the metabolism of valdecoxib is mediated primarily by cytochromial isoenzymes 3A4 and 2C9.
The plasma exposure (AUC and Cmax) to valdecoxib was increased (62% and 19% respectively) when the latter was administered in combination with fluconazole (predominantly a CYP2C9 inhibitor) indicating that the dose of parecoxib sodium should be reduced in patients treated with fluconazole.
The plasma exposure (AUC and Cmax) to valdecoxib was increased (38% and 24% respectively) when administered concomitantly with ketoconazole (CYP3A4 inhibitor), however a dosage adjustment is not generally considered necessary for treated patients. with ketoconazole.
The effects of enzyme induction have not been studied. The metabolism of valdecoxib may be increased when it is co-administered with enzyme-inducing drugs such as rifampicin, phenytoin, carbamazepine or dexamethasone.
Effects of parecoxib (or its active metabolite valdecoxib) on the pharmacokinetics of other medicinal products
Treatment with valdecoxib (40 mg twice daily for 7 days) increased the plasma concentration of dextromethorphan (substrate of cytochrome CYP2D6) by 3-fold. Therefore, caution is advised when administering Dynastat together with other medicinal products metabolised predominantly by cytochrome CYP2D6 that have narrow therapeutic margins (eg flecainide, propafenone and metoprolol).
The plasma exposure of omeprazole (substrate of cytochrome CYP2C19) administered at a dose of 40 mg once daily increased by 46% following administration of valdecoxib 40 mg twice daily for 7 days, while the plasma exposure to valdecoxib remained unaffected. These results demonstrate that although valdecoxib is not metabolised by cytochrome CYP2C19, valdecoxib may be an inhibitor of this isoenzyme. Therefore caution is recommended when administering Dynastat in combination with drugs known to be substrates of cytochrome CYP2C19 (e.g. phenytoin, diazepam or imipramine).
In interaction studies in rheumatoid arthritis patients treated weekly with intramuscular methotrexate, valdecoxib administered orally (40 mg twice daily) did not induce clinically significant effects on plasma methotrexate concentrations. However, adequate monitoring of methotrexate toxicity should be considered when these two medicinal products are administered in combination.
Concomitant administration of valdecoxib and lithium resulted in significant reductions in serum clearance (25%) and renal clearance (30%) of lithium with a 34% higher serum exposure than lithium alone. Serum lithium concentrations should be carefully considered. monitored when parecoxib sodium therapy is initiated or monitored in patients receiving lithium.
Concomitant administration of valdecoxib and glibenclamide (CYP3A4 substrate) had no effect on the pharmacokinetics (exposure) or pharmacodynamics (blood glucose and insulin levels) of glibenclamide.
Injectable anesthetics: concomitant administration of 40 mg intravenous parecoxib sodium and propofol (CYP2C9 substrate) or midazolam (CYP3A4 substrate) did not change the pharmacokinetics (metabolism and exposure) or pharmacodynamics (effects on electrocardiogram, psychomotor testing and recovery time sedation) of propofol or midazolam administered intravenously. In addition, concomitant administration of valdecoxib had no significant effect on the hepatic or intestinal CYP3A4 mediated metabolism of orally administered midazolam. Parecoxib sodium 40 mg per intravenously did not alter the pharmacokinetics of fentanyl or alfentanyl (CYP3A4 substrates) administered intravenously.
Inhalable anesthetics: No specific interaction studies have been conducted. In surgical studies where parecoxib sodium was administered preoperatively, no pharmacodynamic interaction was observed in patients treated with parecoxib sodium and inhaled anesthetic substances such as nitrous oxide and isoflurane (see section 5.1).
04.6 Pregnancy and breastfeeding -
Pregnancy:
It is believed that parecoxib sodium can cause serious birth defects when given in the last trimester of pregnancy because
similar to other drugs that inhibit prostaglandin synthesis, it can cause premature closure of the arterial duct or uterine inertia (see sections 4.3, 5.1 and 5.3).
Dynastat is contraindicated (see section 4.3) in the last trimester of pregnancy.
Like other COX-2 inhibitors, Dynastat is not recommended for use in women planning pregnancy (see sections 4.4, 5.1 and 5.3).
Like other COX-2 inhibitors, Dynastat is not recommended for use in women planning pregnancy (see sections 4.4, 5.1 and 5.3).
There are no adequate clinical data on the use of parecoxib sodium in pregnancy or during labor. Studies in animals have shown reproductive toxicity (see sections 5.1 and 5.3). The potential risk for humans is unknown. Dynastat should not be used during the first two trimesters of pregnancy or during labor unless absolutely necessary (i.e. the potential benefit to the patient outweighs the potential risk to the fetus).
Feeding time:
Parecoxib, valdecoxib (its active metabolite) and an active metabolite of valdecoxib are excreted in the milk of rats. It is unknown whether valdecoxib is excreted in human milk. Dynastat must not be administered during lactation (see sections 4.3 and 5.3).
04.7 Effects on ability to drive and use machines -
No studies on the effect of Dynastat on the ability to drive and use machines have been performed. However, patients who experience dizziness, vertigo or somnolence following the administration of Dynastat should avoid driving or operating machinery.
04.8 Undesirable effects -
Within each frequency class, undesirable effects are reported in descending order of severity.
The following adverse reactions were reported in patients who received parecoxib (N = 5,402) in 28 placebo-controlled clinical trials.
[Very common (≥ 1/10), Common (≥ 1/100,
Infections and infestations
Common: pharyngitis, alveolar osteitis (post-extraction alveolitis)
Uncommon: abnormal drainage of serum from the sternal wound, wound infection
Disorders of the blood and lymphatic system
Common: postoperative anemia
Uncommon: thrombocytopenia
Immune system disorders
Rare: anaphylactoid reactions
Metabolism and nutrition disorders
Common: hypokalaemia
Uncommon: anorexia, hyperglycemia
Psychiatric disorders
Common: agitation, insomnia
Nervous system disorders
Common: hypoesthesia, dizziness
Uncommon: cerebrovascular disorders
Ear and labyrinth disorders
Uncommon: ear pain
Cardiac pathologies
Uncommon: myocardial infarction, bradycardia
Vascular pathologies
Common: hypertension (aggravated), orthostatic hypotension
Uncommon: aggravated hypertension
Respiratory, thoracic and mediastinal disorders
Common: respiratory failure
Uncommon: pulmonary embolism
Gastrointestinal disorders
Very common: nausea
Common: abdominal pain, vomiting, constipation, dyspepsia, flatulence
Uncommon: gastroduodenal ulceration, gastroesophageal reflux disorder, dry mouth, abnormal gastrointestinal sound.
Rare: pancreatitis, oesophagitis, edema of the mouth (perioral swelling)
Skin and skin tissue disorders
Common: pruritus, hyperhidrosis
Uncommon: ecchymosis, rash, urticaria
Musculoskeletal and connective tissue disorders
Common: back pain
Uncommon: arthralgia
Renal and urinary disorders
Municipality: oliguria
Rare: acute renal failure
General disorders and administration site conditions
Common: peripheral edema
Uncommon: asthenia, injection site pain, injection site reaction
Diagnostic tests
Common: blood creatinine increased
Uncommon: creatine phosphokinase increased, lactate dehydrogenase increased, SGOT increased, SGPT increased, blood urea increased
Injury, poisoning and procedural complications
Uncommon: post-treatment complications (skin)
The following serious adverse reactions have rarely been reported in association with NSAIDs and cannot be excluded for Dynastat: bronchospasm and hepatitis.
Patients treated with Dynastat undergoing coronary artery bypass surgery are exposed to a higher risk of adverse events such as cardiovascular / thromboembolic events, deep surgical infections and complications of sternal wound repair processes. Thromboembolic / cardiovascular events include myocardial infarction, stroke / TIA, pulmonary embolism and deep vein thrombosis (see sections 4.3 and 5.1).
The following reactions have been reported in association with the use of parecoxib during the post-marketing period:
Rare: renal failure, congestive heart failure, dyspnoea, tachycardia and Stevens-Johnson syndrome.
Very rare: erythema multiforme, exfoliative dermatitis and hypersensitivity reactions, including anaphylaxis and angioedema (see section 4.4).
The following reaction has been reported during the post-marketing setting in association with the use of valdecoxib and cannot be excluded for parecoxib: necrotic epidermolysis (see section 4.4).
04.9 Overdose -
Cases of parecoxib overdose have been associated with adverse events also described with recommended doses of parecoxib.
In the event of an overdose, patients should be treated with symptomatic and supportive treatment. Valdecoxib is not eliminated by hemodialysis. Diuresis or alkalinization of urine may not be effective methods due to the high binding of valdecoxib to plasma proteins.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: Coxib, ATC code: M01AH04
Parecoxib is a prodrug of valdecoxib. Valdecoxib is a selective inhibitor of cyclo-oxygenase-2 (COX-2), effective orally, when administered in the clinical efficacy range. Cyclo-oxygenase is responsible for the formation of prostaglandins. Two isoforms of the cyclo-oxygenase have been identified. oxygenase, COX-1 and COX-2. COX-2 has been shown to be the isoform of the enzyme induced in response to pro-inflammatory stimuli and is believed to be primarily responsible for the synthesis of pain-causing prostanoids. inflammation and fever. COX-2 is also involved in the processes of ovulation, ovum implantation and closure of the arterial duct, in the regulation of renal function and in the activity of the central nervous system (induction of fever, pain perception and cognitive function ). It could also play a role in the healing of ulcers: it has in fact been isolated in the tissues surrounding gastric ulcers in humans, but its importance in the healing process of the ulcers has not been established.
The difference in antiplatelet activity between some COX-1 inhibitory NSAIDs and selective COX-2 inhibitors may be clinically significant in patients at risk for thromboembolic reactions. Selective COX-2 inhibitors reduce the formation of systemic prostacyclin (and hence perhaps also of the endothelial one) without affecting platelet thromboxane. The clinical importance of these observations has not been established.
The effectiveness of Dynastat was established in clinical trials in which a painful component was present in the field of dental, gynecological (hysterectomy), orthopedic (insertion of knee and hip prostheses) and by-pass surgery. The onset of the first perceptible analgesic effect occurred in 7-13 minutes, the clinically significant analgesic effect in 23-39 minutes and the peak effect within 2 hours following administration of single dose Dynastat 40 mg per route. intravenous or intramuscular. The extent of analgesic effect of the 40 mg dose was comparable to that of ketorolac 60 mg administered intramuscularly or ketorolac 30 mg administered intravenously. After single administration, the duration of the analgesic effect was shown to be dependent on the dose and clinical pattern of pain and ranged from 6 hours to more than 12 hours.
Saving effects on opiates : In a placebo-controlled clinical study in orthopedics and general surgery, patients (n = 1050) received parenteral Dynastat at a starting dose of 40 mg IV, followed by 20 mg twice daily for a minimum of 72 hours. , in addition to standard treatment that included patient-controlled supplemental opioid administration. The reduction in opioid use during Dynastat treatment on Days 2 and 3 was 7.2 mg and 2.8 mg (37% and 28% respectively). This reduction in opioid use was associated with reductions in opioid use. significant symptoms of distress due to opioid use reported by patients. Additional pain relief was observed compared to the use of opioids alone. Additional studies conducted in other surgical settings have provided similar observations. No data are available indicating a better overall adverse event profile with the use of parecoxib compared to to placebo when used in combination with opioids.
Studies on the gastrointestinal system: in short-term studies (7 days), the incidence of gastroduodenal ulcers or erosions observed endoscopically in healthy young or elderly subjects (age ≥ 65 years) after administration of Dynastat (5-21%), although it was higher than that found with placebo (5-12%), is significantly lower from a statistical point of view than the incidence observed with NSAIDs (66-90%).
Postoperative safety studies following coronary artery bypass grafting: As part of two placebo-controlled safety studies in which patients received parecoxib sodium for at least 3 days, then switched to oral valdecoxib for a total duration of 10-14 days, in addition to reporting adverse events previously specified categories of events were routinely reviewed and identified by an independent expert committee During treatment, all patients received standard pain relief.
Patients were treated with low-dose acetylsalicylic acid prior to randomization and during the two coronary artery bypass graft trials.
In the first coronary artery bypass surgery study, a double-blind, placebo-controlled 14-day study, patients treated intravenous parecoxib sodium 40 mg twice daily for a minimum of 3 days were evaluated. followed by treatment with valdecoxib 40 mg twice daily (parecoxib sodium / valdecoxib) (n = 311) or placebo / placebo (n = 151). 9 categories of previously specified events (cardiovascular thromboembolic events, pericarditis, new onset or exacerbation of heart failure, renal dysfunction / failure, complications of the upper gastrointestinal tract, major bleeding without affecting the gastrointestinal tract, infections, pulmonary complications of unrelated origin were evaluated. infectious and death). A significantly higher incidence (p ischaemia, cerebrovascular accidents, deep vein thrombosis and pulmonary embolism) was observed in the parecoxib / valdecoxib treatment group compared to the placebo / placebo treatment group in the intravenous administration period (2.2% and 0 respectively). , 0%) and for the entire duration of the study (4.8% and 1.3%, respectively). Complications of surgical wounds (most involving the sternal wound) were observed with a higher frequency in the parecoxib / valdecoxib treatment group.
In the second coronary artery bypass surgery study, four previously specified event categories were evaluated (cardiovascular / thromboembolic; renal dysfunction / renal failure; upper gastrointestinal ulcers / bleeding; sternal wound complications). Patients were randomized within 24 hours after coronary artery bypass grafting as follows: starting dose of parecoxib 40 mg intravenously followed by 20 mg intravenously every 12 hours for a minimum of 3 days, followed by valdecoxib orally 20 mg every 12 hours (n = 544) for a total of 10 days of treatment; intravenous placebo followed by oral valdecoxib (n = 544); or intravenous placebo followed by oral placebo (n = 548 A significantly higher incidence (p = 0.033) of events in the cardiovascular / thromboembolic category was detected in the parecoxib / valdecoxib treatment group (2.0%) compared to the placebo / placebo treatment group (0.5%). Treatment with placebo / valdecoxib was also associated with a higher incidence of cardiovascular thromboembolic events than with placebo, but this difference did not reach statistical significance. Three of the six cardiovascular thromboembolic events in the placebo / valdecoxib treatment group occurred during the placebo treatment period; these patients did not receive valdecoxib. The previously specified events that occurred with the highest incidence in all three treatment groups were in the surgical wound complication category, including deep surgical infections and sternal wound repair processes.
No significant differences were observed between active treatments and placebo for any of the other previously specified event categories (renal dysfunction / failure, upper gastrointestinal complications or sternal wound complications.
Safety Studies in General Surgery: In a large (n = 1,050) major orthopedic / general surgery study, patients were treated with a starting dose of parecoxib 40 mg intravenously followed by 20 mg intravenously every 12 hours for a minimum of 3 days, followed by by oral valdecoxib (20 mg every 12 hours) (n = 525) for a total treatment of 10 days, or intravenous placebo followed by oral placebo (n = 525). In these patients undergoing surgery, there was no significant difference in the overall safety profile for parecoxib sodium / valdecoxib compared to placebo, including the four categories of events previously specified and described above for the second bypass study. aorto-coronary.
Platelet Studies: In a series of small, multiple-dose clinical trials conducted in healthy young and elderly subjects, administration of Dynastat 20 mg or 40 mg twice daily showed no effect on platelet aggregation or bleeding compared to In young subjects, administration of Dynastat 40 mg twice daily did not have a clinically significant effect on acetylsalicylic acid-mediated inhibition of platelet function (see section 4.5).
05.2 "Pharmacokinetic properties -
Following intravenous or intramuscular administration, parecoxib is rapidly converted to valdecoxib, the pharmacologically active moiety, by enzymatic hydrolysis in the liver.
Absorption
The exposure of valdecoxib following single dose administration of Dynastat, as determined by both the area under the plasma concentration versus time (AUC) and peak plasma concentration (Cmax) curve, is approximately linear over the clinical dose range. AUC and Cmax values after twice daily dosing were linear up to 50 mg intravenously and 20 mg intramuscularly. steady state were achieved within 4 days on a double daily dosing regimen.
The maximum plasma concentration of valdecoxib was reached in approximately 30 minutes and approximately 1 hour after administration of single intravenous and intramuscular doses of 20 mg parecoxib sodium, respectively. Valdecoxib exposure after intravenous and intramuscular administration was similar in terms of AUC and Cmax. Parecoxib exposure was similar in terms of AUC after both intravenous and intramuscular administration.
The mean Cmax of parecoxib following intramuscular administration was lower than intravenous bolus administration, a factor attributable to slowed extravascular absorption following intramuscular administration. These reductions are not considered to be of clinical significance since the valdecoxib Cmax value is comparable following intramuscular and intravenous administration.
Distribution
The volume of distribution of valdecoxib following intravenous administration is approximately 55 liters. Plasma protein binding is approximately 98% over the concentration range achieved with the highest recommended dosages, ie 80 mg / day. Valdecoxib, but not parecoxib, is extensively distributed in erythrocytes.
Metabolism
In vivo parecoxib is rapidly converted almost completely to valdecoxib and propionic acid with a plasma half-life of approximately 22 minutes. The elimination of valdecoxib is due to an intense hepatic metabolism involving multiple metabolic pathways including that of cytochrome P 450 (CYP) fractions 3A4 and 2C9 and the glucuronidation of the sulfonamide portion (about 20%). A hydroxylated metabolite of valdecoxib has been identified in human plasma (via the cytochromial pathway) which is active as a COX-2 inhibitor. This metabolite represents approximately 10% of the valdecoxib concentration; due to the low concentration of this metabolite, this is not expected to have a clinically significant effect following the administration of therapeutic doses of parecoxib sodium.
Elimination
Valdecoxib is eliminated by hepatic metabolism and less than 5% of valdecoxib is recovered unchanged in the urine. No trace of parecoxib was found unchanged in the urine while only traces were found in the faeces. Approximately 70% of the dose is excreted in the urine in the form of inactive metabolites. The plasma clearance (CLp) of valdecoxib is approximately 6 liters / hour. The elimination half-life (t½) of valdecoxib following intravenous or intramuscular administration of parecoxib sodium is approximately 8 hours.
Senior citizens: Dynastat has been administered in pharmacokinetic and clinical studies to 335 elderly subjects (aged 65 to 96 years). In healthy elderly subjects, the apparent clearance of oral valdecoxib was reduced demonstrating approximately 40% higher plasma exposure of valdecoxib compared to healthy young subjects.
The plasma exposure of valdecoxib allo steady state adjusted for body weight, it was approximately 16% higher in elderly women than in elderly males (see section 4.2).
Altered kidney function: In patients with varying degrees of renal insufficiency administered Dynastat 20 mg intravenously, parecoxib was rapidly cleared from plasma. Since elimination of valdecoxib is not primarily renal, no change in valdecoxib clearance has been found even in patients with severe renal impairment or in patients on dialysis (see section 4.2).
Altered liver function: Moderate impairment of liver function did not result in reduced speed or efficiency of the conversion mechanisms of parecoxib to valdecoxib. Patients with moderate hepatic impairment (Child-Pugh Score 7-9) should start treatment at half the usual recommended dose of Dynastat and the maximum daily dose should be reduced to 40 mg, since in this category of patients concentrations of valdecoxib were more than doubled (130%). Patients with severe hepatic impairment have not been studied and therefore the use of Dynastat in patients with severe hepatic impairment is not recommended (see sections 4.2 and 4.3).
05.3 Preclinical safety data -
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology or repeated dose toxicity at 2 times the maximum human exposure to parecoxib. However, in repeat dose toxicity studies in dogs and rats, systemic exposure to valdecoxib (the active metabolite of parecoxib) was approximately 0, 8 times greater than the systemic exposure in the elderly at the maximum recommended therapeutic dose of 80 mg per day. Higher doses have been associated with worsening and slower healing of skin infections, an effect likely associated with COX-2 inhibition.
In reproductive toxicity studies, the incidence of post-implantation product loss of conception, resorption and fetal growth retardation occurred at dosages that did not result in maternal toxicity in studies conducted. on the rabbit. Parecoxib did not affect the fertility of male or female rats.
The effects of parecoxib sodium have not been evaluated in late pregnancy or in the prenatal and postnatal period. Following single dose intravenous administration of parecoxib sodium to lactating rats, concentrations of parecoxib, valdecoxib and milk were found in milk. an active metabolite of valdecoxib similar to those in maternal plasma.
The carcinogenic potential of parecoxib sodium has not been evaluated.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Dust
Anhydrous disodium phosphate.
Phosphoric acid and / or sodium hydroxide (to adjust the pH).
Solvent
Sodium chloride
Hydrochloric acid or sodium hydroxide (to adjust the pH)
Water for injections.
06.2 Incompatibility "-
This medicinal product must not be mixed with medicinal products except those mentioned in section 6.6.
Dynastat and opioids must not be administered together in the same syringe.
Use for reconstitution of lactated Ringer's solution for injections or glucose 50 g / l (5%) in lactated Ringer's solution for injections causes precipitation of parecoxib from the solution and is therefore not recommended.
The use of sterile water for injections is not recommended as the resulting solution is not isotonic.
Dynastat must not be administered through the same infusion line used to administer other medicinal products. The infusion line should be flushed before and after administration of Dynastat with a compatible solution (see section 6.6).
In-line i.v. injection administering glucose 50 g / l (5%) in lactated Ringer's solution or other intravenous fluids not listed in section 6.6 is not recommended as it may cause precipitation of the product in solution.
06.3 Period of validity "-
3 years.
The chemical and physical stability of the reconstituted solution has been demonstrated for 24 hours at 25 ° C. From a microbiological point of view, the product prepared under aseptic conditions should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not exceed 12 hours at 25 ° C unless reconstitution has taken place under conditions. of controlled and validated asepsis.
06.4 Special precautions for storage -
This medicinal product does not require any special storage conditions before reconstitution.
Reconstituted solutions should not be stored in the refrigerator or freezer.
For storage conditions of the reconstituted medicinal product see section 6.3.
06.5 Nature of the immediate packaging and contents of the package -
Parecoxib sodium vials
40 mg vials: Type I clear colorless glass vials (5 ml) with laminated stopper, sealed with a purple flip-off cap mounted on an aluminum cap.
Solvent vials
2 ml vial: colorless neutral glass, Type I.
Dynastat is available as a sterile single-use vial packed with a 2 ml vial filled with a volume of 2 ml of sodium chloride 9 mg / ml (0.9%) solution (see different pack sizes and configurations below).
Packs
Pack of 1 + 1: contains 1 vial with 40 mg parecoxib and 1 ampoule with 2 ml of sodium chloride 9 mg / ml (0.9%) solution.
Pack of 3 + 3: contains 3 vials with 40 mg parecoxib and 3 ampoules with 2 ml of sodium chloride 9 mg / ml (0.9%) solution.
Pack of 5 + 5: contains 5 vials with 40 mg parecoxib and 5 ampoules with 2 ml of sodium chloride 9 mg / ml (0.9%) solution.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling -
Dynastat must be reconstituted before use. Dynastat does not contain preservatives. Aseptic techniques must be used for product preparation.
Solvents for reconstitution
Reconstitute Dynastat 40 mg with 2 ml of sodium chloride 9 mg / ml (0.9%) solution.
The only other solvents suitable for reconstitution are:
glucose solution 50 g / l (5%) for infusion
4.5 mg / ml (0.45%) sodium chloride and 50 g / l (5%) glucose solution for injections
Procedure for reconstitution
Use aseptic technique to reconstitute lyophilized parecoxib (such as parecoxib sodium). Remove the purple flip-off cap until the central part of the rubber stopper of the 40 mg parecoxib vial is visible. Withdraw, using a sterile needle and syringe, 2 ml of a suitable solvent and insert the needle through the central part of the rubber stopper of the vial in order to transfer the solvent into the 40 mg vial. Completely dissolve the powder with a gentle twisting motion and check the reconstituted product before use. The entire contents of the vial should be aspirated for a single administration.
Once reconstituted, Dynastat should be visually inspected for particulate matter and discoloration prior to administration. The solution should not be used if it is discolored or cloudy or if the presence of residues of particulate matter is found. Dynastat must be administered within 24 hours of reconstitution (see section 6.3) or else it must be discarded.
The reconstituted product is isotonic.
Compatibility of the intravenous solution
After reconstitution with suitable solvents, Dynastat can only be injected intravenously or intramuscularly or into intravenous lines that administer:
sodium chloride solution 9 mg / ml (0.9%)
glucose solution 50 g / l (5%) for infusion
4.5 mg / ml (0.45%) sodium chloride and 50 g / l (5%) glucose solution for injections
Ringer-lactate solution for injections
For single use only. Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
Pfizer Limited
Sandwich
Kent CT13 9NJ
UK
08.0 MARKETING AUTHORIZATION NUMBER -
EU / 1/02/209 / 006-008
035631062
035631074
035631086
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
Date of first authorization: 22 March 2002
Renewal of the authorization: 22 March 2007
10.0 DATE OF REVISION OF THE TEXT -
February 21, 2011