Source: Health Products Regulatory Authority (ZA) Revision Year: 2022 Publisher: Adcock Ingram Limited, 1 New Road, Erand Gardens, Midrand 1685, South Africa
In orthopaedic surgery, 40 mg (0,4 ml) once daily by subcutaneous injection.
The first injection should be given, 12 hours pre-operatively.
Treatment is continued for as long as the risk of thromboembolism persists; in general, from 7 to 10 days after surgery or as long as there is a risk of venous thromboembolism until the patient is ambulatory.
Continued therapy with 40 mg once daily for 3 weeks following the initial therapy has been proven to be beneficial in total hip replacement.
In general surgery, 20 mg (0,2 ml) once daily by subcutaneous injection. The first injection should be given 2 hours pre-operatively.
Treatment is continued for as long as the risk of thromboembolism persists; in general, from 7 to 10 days after surgery or as long as there is a risk of venous thromboembolism and until the patient is ambulatory. For special recommendations concerning dosing intervals for spinal/epidural anaesthesia and percutaneous coronary revascularisation procedures (see section 4.4).
The recommended dose of CRUSIA is 40 mg once daily by subcutaneous injection. CRUSIA treatment is prescribed for a minimum of 6 days and continued until the return to full ambulation, for a maximum of 14 days.
A dose of 1 mg/kg should be given subcutaneously every 12 hours. Oral anticoagulant therapy should be initiated when appropriate and CRUSIA treatment should be continued until a therapeutic anticoagulant effect has been achieved (International Normalised Ratio 2 to 3). CRUSIA treatment is usually prescribed for between 5 and 10 days.
The recommended dose of CRUSIA is 1 mg/kg every 12 hours by subcutaneous injection, administered concurrently with aspirin (100 to 325 mg once daily). Treatment with CRUSIA in these patients should be prescribed for a minimum of 2 days and continued until clinical stabilisation. The usual duration of treatment is 2 to 8 days.
The recommended dose is 1 mg/kg of CRUSIA. For patients with a high risk of haemorrhage, the dose should be reduced to 0,5 mg/kg for double vascular access or 0,75 mg/kg for single vascular access. During haemodialysis, CRUSIA should be introduced into the arterial line of the circuit at the beginning of the dialysis session. The effect of this dose is usually sufficient for a 4 hour session; however, if fibrin rings are found, for example after a longer than normal session, a further dose of 0,5 to 1 mg/kg may be, given.
The recommended dose of enoxaparin is a single IV bolus of 30 mg plus a 1 mg/kg subcutaneous dose, followed by 1 mg/kg, administered subcutaneously every 12 hours (maximum 100 mg for the first two doses only, followed by 1 mg/kg dosing for the remaining doses). For dosage in patients >75 years of age; refer to the section on the elderly.
When administered in conjunction with a thrombolytic (fibrin specific or non-fibrin specific), CRUSIA should be given between 15 minutes before and 30 minutes after the start of fibrinolytic therapy. All patients should receive aspirin as soon as they are identified as having STEMI and maintained on an appropriate dose once daily, unless contraindicated.
The recommended duration of CRUSIA treatment is 8 days or until hospital discharge, whichever comes first.
If the last CRUSIA subcutaneous administration was given less than 8 hours before balloon inflation, no additional dosing is needed. If the last subcutaneous administration was given more than 8 hours before balloon inflation, an IV bolus of 0,3 mg/kg of CRUSIA should be administered.
For treatment of acute ST-segment Elevation Myocardial Infarction in elderly patients >75 years of age, do not use an initial IV bolus. Initiate dosing with 0,75 mg/kg subcutaneous every 12 hours (maximum 75 mg for the first two doses only, followed by 0,75 mg/kg dosing for the remaining doses).
For other indications, no dose reduction is necessary in the elderly, unless kidney function is impaired (see sections 4.4 (haemorrhage in the elderly); and 4.2 (renal impairment), 5.1 (Elderly).
The efficacy of CRUSIA injection in the elderly (>65 years) was similar to that seen in younger patients (<65 years). The incidence of bleeding complications was similar between elderly and younger patients when 30 mg every 12 hours or 40 mg once a day doses of CRUSIA injection were employed. The incidence of bleeding complications was higher in elderly patients as compared to younger patients when CRUSIA injection was administered at doses of 1,5 mg/kg once a day or 1 mg/kg every 12 hours. The risk of CRUSIA injectionassociated bleeding increased with age.
Serious adverse events increased with age for patients receiving CRUSIA injection. Other clinical experience (including post-marketing surveillance and literature reports) has not revealed additional differences in the safety of CRUSIA injection between elderly and younger patients. Careful attention to dosing intervals and concomitant medications (especially anti-platelet medications) is advised. Monitoring of geriatric patients with low body weight (<45 kg) and those predisposed to decreased renal function should be considered (see sections 5.1 and 4.4).
In the absence of safety data on dosages more than 80 mg daily and delayed elimination in patients with severe renal impairment, dosages of more than 60 mg daily should be used with caution. Special safety vigilance is warranted in patients with severe renal impairment, as there may be an increased bleeding tendency due to the renal failure.
See section 4.4 (Special warnings and precautions for use) and 5.1 (Pharmacological properties).
A dosage adjustment is required for patients with severe renal impairment (creatinine clearance <30 ml/min), according to the following tables since CRUSIA exposure is significantly increased in this patient population.
The following dosage adjustments are recommended for therapeutic dosage ranges:
| Standard dosing: | Severe renal impairment: |
|---|---|
| 1 mg/kg SC twice daily | 1 mg/kg SC once daily |
| 1,5 mg/kg SC once daily | 1 mg/kg SC once daily |
| 30 mg single IV bolus plus | 30 mg single IV bolus plus |
| a 1 mg/kg SC dose followed by | a 1 mg/kg SC dose followed |
| 1 mg/kg SC twice daily | by 1 mg/kg SC once daily |
Elderly patients >75 years of age (for acute STEM/indication only):
| 0,75 mg/kg SC twice daily without initial bolus | 1 mg/kg SC once daily without initial bolus |
The following dosage adjustments are recommended for prophylactic dosage ranges:
| Standard dosing: | Severe renal impairment: |
|---|---|
| 40 mg SC once daily | 20 mg SC once daily |
| 20 mg SC once daily | 20 mg SC once daily |
The recommended dosage adjustments do not apply to the haemodialysis indication.
Although no dose adjustment is recommended in patients with moderate (creatinine clearance 30-50 ml/min) and mild (creatinine clearance 50-80 ml/min) renal impairment, careful clinical monitoring is advised.
CRUSIA is administered by subcutaneous injection for the prevention of venous thromboembolic disease; treatment of deep vein thrombosis; treatment of unstable angina and non-Q-wave myocardial infarction and treatment of acute ST-segment Elevation Myocardial Infarction.
For acute ST-segment Elevation Myocardial Infarction, treatment is to be initiated with a single IV bolus injection immediately followed by a subcutaneous injection.
It is administered through the arterial line of a dialysis circuit for the prevention of thrombus formation in the extra-corporeal circulation during haemodialysis.
CRUSIA must never be injected intramuscularly. The prefilled disposable syringe is ready for immediate use.
Injections should be made preferably when the patient is lying down. CRUSIA is administered by deep subcutaneous injection. Do not expel the air bubble from the syringe before injecting to avoid the loss of medicine, when using the 20 mg and 40 mg prefilled syringes. The administration should be alternated between the left and right anterolateral or posterolateral abdominal wall.
The prefilled syringes fitted with an automatic safety device avoid accidental needle pricks after injecting. When the protective cap is removed off the needle, a drop may appear at the end of the needle. If so, remove it before injecting the medicine by lightly tapping the body of the syringe with the needle pointing down. The prefilled syringe is ready to use. Do not press on the plunger to expel any air bubbles before administering the injection.
The injection must be given with the patient preferably lying down. The whole length of the needle should be introduced perpendicularly, not from the side, into a skin fold held between the thumb and index finger. This skin fold should be held throughout the injection. Do not rub the injection site after administration. The safety device is automatically activated once the plunger is fully depressed, thus completely protecting the used needle and without causing discomfort to the patient. Activation of the safety device is only possible if the plunger is fully depressed.
The safety device can only be activated once the syringe is completely empty.
For intravenous injection, the pre-filled syringe can be used. CRUSIA should be administered through an IV line. It should not be mixed or co-administered with other medications. To avoid the possible mixture of CRUSIA with other medicines, the IV access chosen should be flushed with a sufficient amount of saline or dextrose solution prior to and following the IV bolus administration of CRUSIA to clear the port of medicine. CRUSIA may be safely administered with normal saline solution (0,9%) or 5% dextrose in water.
Accidental overdose with enoxaparin sodium after IV, extracorporeal or SC administration may lead to haemorrhagic complications. Following oral administration of even large doses, it is unlikely that CRUSIA will be absorbed.
The anticoagulant effects can be largely neutralised by the slow IV injection of protamine. The dose of protamine depends on the dose of CRUSIA injected; 1 mg protamine neutralises the anticoagulant effect of 100 IU (1 mg) of enoxaparin sodium, if CRUSIA was administered in the previous 8 hours. An infusion of 0,5 mg protamine per 100 IU (1 mg) of enoxaparin sodium may be administered if enoxaparin sodium was administered greater than 8 hours previous to the protamine administration, or if it has been determined that a second dose of protamine is required. After 12 hours of the CRUSIA injection, protamine administration may not be required. However, even with high doses of protamine, the anti-Xa activity of CRUSIA is never completely neutralised (maximum about 60%) (see the prescribing information for protamine salts).
3 years.
Store at or below 25°C.
Do not freeze.
CRUSIA solution for injection is packed in prefilled syringes.
CRUSIA is packed in clear, transparent Type I glass pre-filled syringes with black chlorobutyl rubber stopper fitted with injection needle with or without an automatic safety device for some presentations. The needle shield is made of synthetic rubber and a rigid cover of polypropylene.
Prefilled syringes are stored in plastic trays and carton boxes.
CRUSIA 20: 0,2 mL solution for injection in a 0,5 mL pre-filled syringe without scale. Pack sizes of 2, 10 and 50 syringes.
CRUSIA 40: 0,4 mL solution for injection in a 0,5 mL pre-filled syringe without scale. Pack sizes of 2, 10, 30 and 50 syringes.
CRUSIA 60: 0,6 mL solution for injection in a 1,0 mL graduated pre-filled syringe. Pack sizes of 2, 10 and 30 syringes.
CRUSIA 80: 0,8 mL solution for injection in a 1,0 mL graduated pre-filled syringe. Pack sizes of 2, 10 and 30 syringes.
CRUSIA 100: 1,0 mL solution for injection in a 1,0 mL graduated pre-filled syringe. Pack sizes of 2, 10 and 30 syringes.
Not all pack sizes may be marketed.
Pre-filled syringes are ready for immediate use. For method of administration see section 4.2.
Use only clear, colourless solutions.
Pre-filled syringes are supplied with or without an automatic safety system. The instructions for use are presented in the package leaflet.
Each syringe is for single use only. Any unused medicine or waste material should be disposed of in accordance with local requirements.
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