Treatment of thrombolytic occluded central venous catheters including those used in hemodialysis

The 2 mg vial is the only one, presentation of alteplase recommended for use in this indication.

Treatment with ACTILYSE 2 mg should be initiated as soon as possible after occlusion.

The following recommendations regarding dosage should be applied

A dose of alteplase, up to 2 mg administered up to two times for any occlusion, may be used to restore the permeability of catheters, orifice, single or multiple lumen, including those used in Hemodialysis, become dysfunctional due to an occlusion of origin, thrombotic.

The reconstitution of a final concentration of 1 mg alteplase per ml is recommended for use in this indication. In patients weighing at least 30 kg, a total dose of 2 mg of alteplase in 2 ml of reconstituted solution should be instilled into the central venous catheter, clogged.

In patients weighing less than 30 kg, the volume of the reconstituted solution to be instilled into the clogged central venous catheter should correspond to 110% of the internal lumen of the catheter. The total dose of alteplase should not exceed 2 mg. Thus, for a catheter with an internal volume of 1.0 ml, the total dose of ACTILYSE should be 1.1 mg for a volume of 1.1 ml.

If the permeability of the catheter is not restored after 120 minutes of contact with the first dose a second equivalent dose may be instilled
Method for restoring the permeability of a catheter

The reconstituted solution must be instilled into the central venous access device, which is not functioning properly.

The 2 mg vial is the only one recommended for use in this indication. For instructions on reconstitution, prior to administration, see section "Instructions for use, handling and disposal."

1. Reconstitute the contents of an injection bottle to obtain a final concentration of 1 mg alteplase per ml. For catheters with a volume greater than 2 ml, the reconstituted solution may be further diluted with a sterile solution of 9 mg / ml (0.9%) sodium chloride in order to inject the volume For a catheter with an internal volume of 2.5 ml, the total dose of ACTILYSE should be 2.0 mg in a volume of 2.5 ml.

2. Instill the appropriate dose of ACTILYSE into the central venous catheter, clogged

3. After 30 minutes of contact, evaluate the permeability of the catheter by attempting aspiration of blood. If the permeability is re-established, refer to step 6. Otherwise, continue to step 4.

4. After 120 minutes of contact, evaluate the permeability of the catheter by attempting aspiration of blood and catheter contents. If the permeability is restored, refer to step 6. Otherwise, continue to step 5.

5. If the permeability of the catheter is not restored after the first dose a second equivalent dose should be instilled Repeat the procedure starting with step 1. If after a second dose of alteplase The permeability is still not restored, consider replacing the catheter.

6. If the catheter's permeability has been restored, aspirate 4-5 ml of blood in patients weighing at least 10 kg or 3 ml in patients weighing less than 10 kg in order to remove ACTILYSE and the residual clot , And slowly irrigate the catheter with a sterile solution of sodium chloride 9 mg / ml (0.9%).

Pediatric population

The pediatric population is covered by the general scheme of administration described above.
The powder is in the form of a pale white to yellow lyophilization cake. The reconstituted preparation is a clear, colorless to pale yellow solution.

Class: Pharmacotherapeutic: THROMBOLYTICS, code: ATC: B 01 AD 02
Alteplase is a glycoprotein which activates the biotransformation of plasminogen into plasmin .; After intravenous administration, circulating alteplase remains relatively inactive. It is activated only after binding to fibrin and then induces the conversion of plasminogen into plasmin, thus causing the fibrin clot to dissolve
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Due to its relative specificity for fibrin, alteplase, at a dose of 100 mg, slightly decreases the levels of fibrinogen circulating to about 60% at 4 hours, but with a recovery to more than 80% At the end of 24 hours. Plasminogen and alpha-2-antiplasmin concentrations decreased approximately to levels of 20% and 35%, respectively, four hours after treatment, but increased again thereafter to more than 80% After 24 hours. A marked and prolonged decrease in circulating fibrinogen is observed only in a small number of patients.

Occluded central venous catheters, including those used in hemodialysis

In two clinical studies, more than 1,100 patients, mainly adults, with problems of central venous access devices, not functioning properly, were treated with alteplase. Catheter function recovery rates ranged from 74% to 77% after one dose and between 87% and 90% after two doses of alteplase. In studies of catheters used in hemodialysis using durations ranging from more than 2 hours to elapsed time until the next dialysis session comparable recovery rates were reported .

In a study of 310 children, the overall recovery rate of the catheter function was 83% similar to the rate observed in adults after two maximal doses of alteplase. A total of 432 elderly patients under 17 years of age received up to 2 mg of alteplase for up to two administrations in pivotal tests for permeabilization of catheters. The overall safety and efficacy results were similar in pediatric and adult patients.


ACTILYSE 2 mg should not be administered to patients with known hypersensitivity to the active substance, alteplase, gentamicin (a trace residue of the manufacturing process), or to one Of the excipients mentioned in the heading Composition.

The appropriate presentation of Actilyse should be carefully selected and in accordance with the intended use.

The presentation of 2 mg alteplase is not suitable for use in the acute phase of myocardial infarction, pulmonary embolism or stroke, ischemic cerebral (due to Risk of significant under-dosage). Only flasks of 10, 20 and 50 mg are indicated for these uses.

Warnings and Precautions, General

The concomitant administration of heparin with ACTILYSE 2 mg did not demonstrate an improvement in the rate of restoration of catheter function and is discouraged. If heparin is considered necessary, to prevent further occlusion, it must be administered separately after the restoration of the function of the catheter. >
Catheter dysfunction may be caused by a number of causes, other than thrombus formation, such as poor catheter positioning, mechanical failure, suture constriction, and lipid deposition Or precipitates of drugs within the lumen of the catheter. Due to the risk of lesions of the vascular wall or collapse of the catheter wall, it is not necessary to proceed by vigorous aspirations in attempts to determine the existence of a catheter occlusion. Any excess pressure should be avoided when ACTILYSE 2 mg is instilled into the catheter. Such a force could cause rupture of the catheter or expulsion of the clot in the circulation.

Special caution is necessary when used for the instillation of low volume syringes (≤ 1 ml), especially if low volume catheters are used, as is typically the case in the population Pediatric.


The most frequent adverse reaction associated with all thrombolytics, in all indications allowed is bleeding. ACTILYSE 2 mg has not been studied in patients with a catheter, occlus known to present risks, haemorrhagic events likely to be associated with the use of thrombolytics. Caution should be exercised with patients who have active internal bleeding or have undergone one of the following procedures within 48 hours: surgery, delivery, percutaneous biopsy of viscera or deep tissue, or puncture of non-compressible vessels . Caution should also be exercised in patients with thrombocytopenia, other hemostatic abnormalities (including secondary abnormalities, severe liver or kidney disease), or any other condition for which bleeding is a significant risk or Are likely to be particularly difficult to manage because of its location or at high risk of embolic complications (eg, thrombosis, venous localized near the catheter). Cases of death and permanent disability have been reported in patients who have had a stroke, cerebral and other events, severe bleeding during dose administration, pharmacological thrombolytic therapy

If severe bleeding occurs and is located at a critical location (eg intracranial, gastrointestinal, retroperitoneal, pericardial), ACTILYSE 2 mg should be discontinued and the product removed from the catheter

Infection

The use of ACTILYSE 2 mg in patients whose catheters are obstructed by infected thrombi is likely to release microorganisms into the general circulation leading to septicemia.

As with all catheterization operations, an aseptic technique should be carefully maintained and an appropriate antibiotic treatment should be used if necessary.


Antibody formation in patients who received one or more doses of alteplase to restore the permeability of occluded central venous catheters was not studied. Although a physiologically active plasma concentration is not reached, hypersensitivity may occur. Anaphylactoid reactions associated with the administration of Actilysis 2 mg may be caused by hypersensitivity to the active substance, alteplase, gentamicin (a trace residue of the manufacturing process), Or to any of the excipients. The cap of the ACTILYSE 2 mg powder vial contains natural rubber (a derivative of latex) which may cause allergic reactions.


There have been no formal interaction studies with ACTILYSE 2 mg

The risk of haemorrhage is increased by the administration of derivatives, coumarins, oral anticoagulants, antiaggregants, platelets, unfractionated heparin or low molecular weight heparin, or other inhibitors of Coagulation (before, during administration, ACTILYSE 2 mg or within 24 hours of treatment).
Concomitant treatment with angiotensin-converting enzyme inhibitors may increase the risk of an anaphylactoid reaction. Of the reported cases for such reactions, a relatively high proportion of patients were treated concomitantly with ACE inhibitors.
The reconstituted solution may be diluted in a sterile 0.9% sodium chloride solution to a minimum concentration of 0.2 mg alteplase per ml.

In the case of further dilution, the use of water for injections or in general the use of glucose solutions, for infusion, dextrose, for example, is not recommended, due to increased formation of turbidity in The reconstituted solution.

ACTILYSE 2 mg should not be mixed with other medicines (including, with heparin).
Despite the relative specificity of alteplase for fibrin, an overdose may cause a clinically significant decrease in fibrinogen levels and other factors of coagulation. >
In most cases, it is sufficient to wait for the physiological regeneration of these elements after the end of treatment with ACTILYSE 2 mg.
However, if severe haemorrhage occurs, transfusion of fresh, frozen plasma is recommended, as well as, if necessary, administration of synthetic antifibrinolytics.

The experience of administration of alteplase during pregnancy or lactation is very limited. Studies in animals have revealed reproductive toxicity (see section Preclinical safety data). In the event of a life threatening threat, the expected benefits and possible risks should be taken into account.
It is not known whether alteplase is excreted in human milk.

The adverse reactions listed below are presented by frequency and organ system class. Frequency (≥1 / 100,