The drug Darzalex is administered as an intravenous infusion.
The introduction should be carried out by a medical professional. At the same time, adequate support should be provided in case of development of infusion reactions. The use of appropriate drugs before and after infusion is necessary.
Doses
The recommended dose of Darzalex is 16 mg / kg of body weight as an intravenous infusion according to the following scheme:
Table 1. Scheme of therapy with Darzalex
| Mode of administration | Weeks |
| Weekly | Weeks 1-8 |
| Every 2 weeks | Weeks 9-24 |
| Every 4 weeks | Week 25 and further to the progression of the disease |
Dose skip
If you miss any planned dose of Darzalex, you must enter this dose as soon as possible and adjust the therapy schedule as appropriate to keep the interval between infusions.
Recommended concomitant medications
Drugs used before infusion
To reduce the risk of infusion reactions, all patients should receive a combination of the following drugs approximately 1 hour before each infusion of the drug Darzalex:
- corticosteroids intravenously (methylprednisolone 100 mg or equivalent dose of another corticosteroid with an average or long duration of action)
- oral antipyretic drug (paracetamol in a dose of 650-1000 mg)
- oral or intravenous antihistamine (diphenhydramine in a dose of 25 - 50 mg or equivalent drug).
After the second infusion, at the discretion of the doctor, a reduction in the dose of corticosteroids (60 mg of methylprednisolone intravenously) is allowed.
Drugs used after the infusion
To prevent delayed infusion reactions, all patients should take oral corticosteroids (20mg methylprednisolone or equivalent dose of another corticosteroid) on the first and second day after each infusion.
In addition, patients with obstructive pulmonary disease should consider the need for short-acting and long-acting bronchodilators after each infusion. or inhaled corticosteroids. If after the first four infusions the patient does not have any significant infusion reactions, the drugs used after the infusion can be canceled at the doctor's discretion.
Special patient groups
Children (17 years and under)
The safety and efficacy of Darzalex in children have not been confirmed.
Elderly patients (65 years and older)
Between the elderly and younger patients, there were no differences in terms of safety and efficacy of the drug. Correction of the dose is not required.
Patients with impaired renal function
Studies of daratumumab in patients with impaired renal function were not performed. Based on the population analysis of pharmacokinetics, it is established that dose adjustment in patients with impaired renal function is not required.
Patients with impaired hepatic function
Studies of daratumumab in patients with impaired liver function were not performed. Changes in liver function with a high probability will not affect the elimination of daratumumab, since the molecules IgG1, such as daratumumab. not metabolized in the liver. Based on the population analysis of pharmacokinetics, dose adjustment in patients with mild liver function disorder is not required (the concentration of total bilirubin is 1-1.5 upper limits of normal or aspartate aminotransferase activity above the upper limit of the norm). Therapy with daratumumab has not been studied in patients with impaired hepatic function moderate and severe (the concentration of total bilirubin is more than 1.5 times higher than the upper limit of the norm and any activity of aspartate aminotransferase).
Mode of application
The drug Darzalex is administered as an intravenous infusion after dilution with 0.9% sodium chloride solution.
After diluting the Darzalex drug, the infusion should be performed immediately at the appropriate initial rate (see Table 2). The gradual increase in infusion rate should be considered only if the previous infusion of daratumumab was well tolerated (see Table 2).
Table 2. The rate of infusion of the drug Darzalex
|
| Dilution volume | Initial infusion rate (first hour) | Increased rate of infusion | Maximum infusion rate |
| The first infusion | 1000 ml | 50 ml / hour | 50 ml / hour every hour | 200 ml / hour |
| The second infusiona | 500 ml | 50 ml / hour | 50 ml / hour every hour | 200 ml / hour |
| Subsequent infusionb | 500 ml | 100 ml / hr | 50 ml / hour every hour | 200 ml / hour |
a The change in infusion rate is allowed only if the first infusion of Darzalex is well tolerated, which is defined as the absence of infusion reactions of a degree> 1 during the first three hours.
b The rate of infusion should be changed only if the first two infusions of the drug Darzalex are well tolerated, which is defined as the absence of infusion reactions of a degree> 1 with a final infusion rate of ≥100 ml / h.
Tactics of management of patients with infusion reactions
To reduce the risk of infusion reactions before the introduction of Darzalex, premedication is necessary.
In case of occurrence of infusion reactions of any severity, it is required to immediately stop the infusion of the Darzalex drug and to conduct appropriate symptomatic therapy.
The tactics of action in the case of development of infusion reactions may include a reduction in the rate of infusion or withdrawal of therapy with Darzalex. as described below:
- Degree 1-2 (mild-moderate reactions): after stabilization of the patient's condition, infusion should be resumed at a rate no more than half of the rate at which the infusion reaction developed. If the patient does not subsequently have any symptoms of an infusion reaction, an increase in the infusion rate is allowed, with the appropriate steps and intervals being used (Table 2).
- Degree 3 (severe reactions): in the case of a decrease in the intensity of the infusion reaction to a degree of 2 or lower, the question of resuming the infusion at a rate of no more than half of the rate at which the reaction has occurred should be resolved. If the patient does not subsequently experience any additional symptoms of the infusion reaction, an increase in the infusion rate is allowed, with appropriate steps and intervals to be used (Table 2). In case of recurrence of symptoms of grade 3, repeat the procedure described above. If the patient has any infusion-related symptoms of grade 3 or higher with the next infusion, the drug Darzalex must be completely discontinued.
- Degree 4 (life-threatening reactions): it is absolutely necessary to cancel the drug Darzalex.
Instructions for preparing a solution, treatment and disposal
Solution for infusions must be prepared, following the requirements of aseptic, as follows:
- Based on body weight, you need to calculate the required dose (mg) and total volume (ml) of Darzalex, as well as the required number of Darzalex vials.
- Check the color of the drug Darzalex (it should be from colorless to yellow). Do not use a solution with a change in color, a strong cloudiness or the appearance of foreign particles.
- Observing the requirements of asepsis, it is necessary to extract from the infusion bag / container the volume of 0.9% sodium chloride solution, which is equal to the required volume of the Darzalex preparation.
- Extract the required amount of Darzalex and dilute it to the desired volume by adding to an infusion bag / container with 0.9% sodium chloride solution. Infusion bags / containers should be made of polyvinyl chloride (PVC), polypropylene (PP), polyethylene (PE) or a mixture of polyolefins (polyethylene with polypropylene). The drug should be diluted in aseptic conditions. Unused portion of the drug from the vial should be disposed of.
- Carefully turn over the package / container to mix the solution.Shaking or freezing is prohibited.
- After reconstitution, the infusion bag / container may be stored at a temperature of 2 to 8 ° C in the dark place for not more than 24 hours. Before use, the package / container should be warmed to room temperature, after which the prepared solution should be used immediately, since the drug Darzalex does not contain preservatives. From the microbiological point of view, the prepared solution should be used immediately. In the event that the drug has not been used immediately, the responsibility for compliance with the terms and conditions of storage after opening before use is borne by medical personnel.
- Before administration, parenteral preparations should be inspected for foreign matter content and discoloration (if the nature of the solution and packaging permits this). Diluted solutions can contain very small transparent or white protein particles, since daratumumab is a protein preparation. Do not use a solution with a change in color, a strong cloudiness or the appearance of foreign particles.
- A diluted solution is required to be administered by intravenous infusion using an infusion set with a flow rate regulator and an internal sterile pyrogen-free polyether sulfone filter (pore diameter 0.22-0.2 μm) with low binding to proteins. It is necessary to use kits for infusion of polyurethane, polybutadiene, polyvinyl chloride, polypropylene or polyethylene.
- Infusion should be completed within 15 hours.
- Do not store the unused portion of the infusion solution for further use. Any unused product or waste after its use must be disposed of in accordance with local requirements.
- Do not take infusion of the drug Darzalex simultaneously with other drugs in the same intravenous highway.