Capsules hard gelatinous, в„–2, cylindrical, opaque, with body and lid white or almost white, with black marking "5 mg" (on the body) and "REV" (on the lid); the contents of the capsules are powder from almost white to pale yellow.
1 caps.
lenalidomide 5 mg
[PRING] lactose, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, titanium dioxide, gelatin, black ink (TekPrint SW-9008 / SW-9009) - shellac, ethanol, isopropanol, butanol, propylene glycol, water, ammonia water, potassium hydroxide, ferric oxide black oxide.
7 pcs. - blisters (3) - packs of cardboard.
Capsules hard gelatinous, в„–0, cylindrical, opaque, with pale yellow body and blue-green lid, labeled black "10 mg" (on the body) and "REV" (on the lid); the contents of the capsules are powder from almost white to pale yellow.
1 caps.
lenalidomide 10 mg
[PRING] lactose, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, indigo carmine dye FD & c Blue 2, iron oxide yellow oxide, titanium dioxide, gelatin, black ink (TekPrint SW-9008 / SW-9009) - shellac, ethanol, isopropanol, butanol , propylene glycol, water, ammonia water, potassium hydroxide, iron dye oxide black.
7 pcs. - blisters (3) - packs of cardboard.
Capsules hard gelatinous, в„–0, cylindrical, opaque, with white or almost white body and blue lid, with black marking "15 mg" (on the body) and "REV" (on the lid);the contents of the capsules are powder from almost white to pale yellow.
1 caps.
lenalidomide 15 mg
[PRING] lactose, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, indigo carmine dye FD & c Blue 2, titanium dioxide, gelatin, black ink (TekPrint SW-9008 / SW-9009) - shellac, ethanol, isopropanol, butanol, propylene glycol, water, Ammonia water, potassium hydroxide, ferric oxide black oxide.
7 pcs. - blisters (3) - packs of cardboard.
Capsules hard gelatinous, в„–0, cylindrical, opaque, with body and lid white or almost white, with black marking "25 mg" (on the body) and "REV" (on the lid); the contents of the capsules are powder from almost white to pale yellow.
1 caps.
lenalidomide 25 mg
[PRING] lactose, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, titanium dioxide, gelatin, black ink (TekPrint SW-9008 / SW-9009) - shellac, ethanol, isopropanol, butanol, propylene glycol, water, ammonia water, potassium hydroxide, ferric oxide black oxide.
7 pcs. - blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
PHARMACHOLOGIC EFFECT
Antitumor drug, immunomodulator. Revlimid is the representative of a new class of immunomodulators (IMiDsSM), which has both immunomodulatory and anti-angiogenic properties.
Lenalidomide inhibits the secretion of proinflammatory cytokines, including TNF-О±, interleukin-1? (IL-1?), IL-6 and IL-12, from liposaccharides (LPS) -stimulated peripheral mononuclear blood cells (PMCC).
Lenalidomide increases the production of anti-inflammatory cytokine IL-10 from LPS-stimulated PMCK, resulting in inhibition of expression, but not of the enzymatic activity of COX-2.
Lenalidomide induces the proliferation of T cells and increases the synthesis of IL-2 and interferon-1 ?, and also increases the cytotoxic activity of its own killer cells.
Lenalidomide inhibits the proliferation of cells of various lines of hematopoietic tumors, mainly those that have cytogenetic defects of the chromosome 5.
In the differentiation model of erythroid progenitor cells, lenalidomide induces fetal hemoglobin expression, judging by the differentiation of CD34 + stem hemopoietic cells.
Lenalidomide inhibits angiogenesis, blocking the formation of microvessels and endothelial canals, as well as migration of endothelial cells in the in vitro angiogenesis model. In addition, lenalidomide inhibits the synthesis of proangiogenic vascular endothelial growth factor by means of PC-3 prostate cancer cells.
Clinical efficacy and safety of Revlimid was confirmed by the results of two multicenter random phase III trials in which patients with multiple myeloma received Revlimid together with dexamethasone or only one dexamethasone as 2nd line therapy. For all the efficacy criteria, including the percentage of complete and partial responses, combined therapy with Rewlimide and dexamethasone was superior to dexamethasone monotherapy.
PHARMACOKINETICS
Suction
Lenalidomide is a racemic mixture of two optically active forms: S (-) and R (+) with a total optical rotation equal to zero.
After ingestion by healthy volunteers, lenalidomide is rapidly absorbed. In this case, Cmax is achieved 0.5-2.0 h after a single dose. The pharmacokinetic distribution is linear. C max and AUC increase in proportion to the dose increase. Repeated drug administration does not lead to its cumulation. Eating does not affect the degree of absorption. C max and AUC increase proportionally both with single and repeated administration of the drug.
According to C max and AUC, lenalidomide exposure in patients with multiple myeloma is higher than in healthy volunteers, which is explained by a lower ratio of clearance to filtration (CL / F) in patients with multiple myeloma compared to healthy volunteers.
Distribution
In vitro binding of ( 14 C) -lenalidomide to plasma proteins in patients with multiple myeloma and healthy volunteers was 23% and 29%, respectively.
Lenalidomid is present in the seminal fluid (<0.01% of the dose) after taking it at a dose of 25 mg / day, but is not detected in the seminal fluid 3 days after discontinuation of the drug.
There is no data on lenalidomide intake in breast milk.
Metabolism and excretion
Lenalidomide is practically not metabolized in the body, as 82% of its dose is excreted in the urine unchanged. Thus, the renal clearance exceeds the rate of glomerular filtration, however, the excretion process is also of an active nature.
When taken in recommended doses (5-25 mg / day), T 1/2 of the drug is approximately 3 hours in healthy volunteers and patients with multiple myeloma.
Pharmacokinetics in special clinical cases
C max does not differ in patients with normal and impaired renal function. In this case, the excretion of lenalidomide slows in proportion to the degree of renal function impairment. Reducing the CC below 50 ml / min is accompanied by an increase in AUC. T 1/2 lenalidomide rises from about 3.5 hours (in patients with QC above 50 mL / min) to about 9 hours (in patients with SC less than 50 mL / min).
The pharmacokinetics of lenalidomide in patients with impaired liver function has not been studied.
INDICATIONS
- in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least one line of therapy.
DOSING MODE
Revlimate is intended only for oral administration.
Capsules Revlimid can not be broken or chewed. It is recommended to take the drug every day at the same time before or after eating, squeezed with water.
The recommended initial dose of Revlimide is 25 mg 1 time / day in 1-21 days of repeated 28-day cycles.
Dexamethasone 40 mg is prescribed 1 time per day at 1-4, 9-12 and 17-20 days of each 28-day cycle during the first 4 cycles of therapy, and then at 40 mg 1 time / day in 1-4 days each subsequent 28-day cycle.
Modification of the dose should be made on the basis of clinical and laboratory data. The doctor should carefully select the dose of dexamethasone, taking into account the condition of the patient and the stage of the disease.
If less than 12 hours have passed after the missed Rewlimide dose, the patient may take this missed dose of the drug, and if more than 12 hours have elapsed, the missed dose should not be taken. The next dose of Revlimid should be taken the next day, at the usual time.
Lenalidomide treatment should not be started if the absolute number of neutrophils is <1.0 Г— 10 9 / L and / or the platelet count is <75 Г— 10 9 / L or, depending on the infiltration of the bone marrow by plasma cells, the platelet count is <30 Г— 10 9 / l.
Modification of the dose during treatment or its resumption
Below are the possibilities of dose modification in the development of neutropenia, thrombocytopenia or other types of toxicity of 3 and 4 severity, the relationship of which with the use of Revlimide can not be ruled out.
Step-by-step dose reduction
Initial dose of 25 mg
Dose 1 level 15 mg
Dose Level 2 10 mg
Dose 3 levels 5 mg
Thrombocytopenia
Platelet Count
Decreased <30? 10 9 / L Stop treatment with Rewlimide
Restored? 30? 10 9 / l Resume treatment with Rewlimide at a dose of 1 level 1 time / day
Each subsequent decrease of <30? 10 9 / L Stop treatment Rewlimide
Restored? 30? 10 9 / l Resume treatment with Rewlimide in a smaller dose (dose of 2 or 3 levels) 1 time / day. Do not use a dose of less than 5 mg / day
Neutropenia
Number of neutrophils
Decreased <0.5? 10 9 / L Stop treatment with Rewlimide
Restored? 0.5? 10 9 / L and neutropenia - the only manifestation of toxicity Resume treatment Rewlimide in the initial dose 1 time / day
Restored? 0.5? 10 9 / l and there are other manifestations of toxicity Resume treatment with Rewlimide at a dose of 1 level 1 time / day
For each subsequent decrease <0.5? 10 9 / L Stop treatment with Rewlimide
Restored? 0.5? 10 9 / l Resume treatment Rewlimide in a smaller dose (dose of 2 or 3 levels) 1 time / day. Do not use doses less than 5 mg / day
In the case of neutropenia, the physician should consider the possibility of assigning a growth factor to the patient.
The safety and effectiveness of lenalidomide in children and adolescents under the age of 18 years has not been studied.
The pharmacokinetics of lenalidomide in elderly patients (over 65 years of age) has not been studied. In clinical trials, lenalidomide was prescribed to patients with multiple myeloma before the age of 86 years. The percentage of patients over the age of 65 who received lenalidomide / dexamethasone or placebo / dexamethasone was comparable. There was no difference in the efficacy and safety of lenalidomide depending on age, although it is impossible to exclude a greater sensitivity to the drug in patients of the older age group. Since elderly patients are more likely to have impaired renal function, the dose of the drug should be carefully selected, while monitoring of renal function is recommended during treatment.
The pharmacokinetics of lenalidomide has not been studied in patients with impaired hepatic function , so it is not possible to provide recommendations for dose adjustment in this category of patients.
Lenalidomide is excreted mainly by the kidneys. In this regard, the risk of toxic reactions can increase with a violation of kidney function . When administering Revlimid, patients with impaired renal function are recommended to follow the recommendations below.
For patients with mild impairment of renal function, no dose change of Revlimide is required. The table shows the initial dose of the drug, recommended depending on the degree of impaired renal function (for patients with moderate and severe renal dysfunction, as well as terminal stage of renal failure).
The initial dose of lenalidomide, depending on the degree of impaired renal function
Kidney function status (QC) The recommended dose of Revlimide
Moderate impairment of kidney function (30 ml / min? KK <50 ml / min) 10 mg 1 time / day *
Severe renal dysfunction (<30 mL / min, dialysis not required) 15 mg every other day **
Terminal stage of renal failure (<30 mL / min, dialysis is required) 5 mg 1 time per day of dialysis. The drug should be taken after a hemodialysis session
* The dose of the drug can be increased to 15 mg 1 time / day after 2 cycles of therapy in the absence of response to therapy, but its good tolerability.
** The dose of the drug can be increased to 10 mg 1 time / day with good tolerability of therapy.
After the initiation of lenalidomide treatment, a subsequent dose modification in patients with impaired renal function should be based on individual tolerability of treatment as previously indicated.
SIDE EFFECT
In patients receiving Revlimid / dexamethasone, the following adverse reactions were most common : neutropenia (39.4%), muscle weakness (27.2%), asthenia (17.6%), constipation (23.5%), muscle cramps (20.1%), thrombocytopenia (18.4% %), anemia (17%), diarrhea (14.2%), rash (10.2%).
The most severe adverse reactions: venous thromboembolism (deep vein thrombosis, pulmonary embolism, pulmonary embolism), grade 4 neutropenia.
The greatest dependence of the development of neutropenia and thrombocytopenia on the dose of the drug is shown, which allows them to be successfully controlled by reducing the dose of Revlimide / dexamethasone.
Determination of the frequency of the following adverse reactions: very often: (? 1/10), often (? 1/100, <1/10), infrequently (? 1/1000, <1/100), rarely (? 1 / 10,000 , <1/1000), very rarely (<1/10 000, including isolated cases), the frequency is unknown (can not be determined from available data).
Adverse reactions noted in clinical studies in patients with multiple myeloma receiving lenalidomide
System-Organ Class Adverse reactions (total), frequency Adverse reactions 3-4 degrees of severity, frequency
Infectious and parasitic diseases Very often: pneumonia, upper respiratory tract infection. Often: sepsis, bacterial, viral and fungal infections (including opportunistic infections), sinusitis. Often: pneumonia, bacterial, viral and fungal infections (including opportunistic)
Benign, malignant and unspecified neoplasms infrequently: basal cell carcinoma, squamous cell carcinoma 1, *
Violations from the blood and lymphatic system Very often: thrombocytopenia 1 , neutropenia 1 , anemia, hemorrhagic disorders 1 , leukopenia. Often: pancytopenia.Infrequently: hemolysis, autoimmune hemolytic anemia, hemolytic anemia. Often: thrombocytopenia 1 , neutropenia 1 , and leukopenia. Often: febrile neutropenia, anemia. Infrequently: hypercoagulation, coagulopathy.
Immune system disorders Infrequent: hypersensitivity reactions 1 . -
Disorders from the endocrine system Often: hypothyroidism. -
Disorders from the metabolism Very often: hypokalemia, decreased appetite. Often: hypomagnesemia, hypocalcemia, dehydration. Often: hypokalemia, hypocalcemia, hypophosphataemia
Disorders of the psyche infrequently: loss of libido. Often: depression.
Violations from the nervous system Very often: peripheral neuropathy (with the exception of motor neuropathy), dizziness, tremor, taste distortion, headache. Often: ataxia, imbalance. Often: stroke, dizziness, fainting. Infrequently: intracranial hemorrhage 1 , transient ischemic attack, ischemia of the brain.
Disorders from the side of the organ of vision Very often: blurred vision. Often: reduced visual acuity, cataract. Often: cataract. Infrequently: blindness.
Hearing disorders and labyrinthine disorders Often: deafness (including hearing loss), tinnitus. -
Heart Diseases Often: atrial fibrillation, bradycardia. Infrequent: arrhythmia, lengthening of the QT segment, atrial flutter, ventricular extrasystole. Often: myocardial infarction 1 , atrial fibrillation, congestive heart failure, tachycardia.
Vascular disorders Very often: thromboembolic disorders (mainly deep vein thrombosis and pulmonary embolism) 1 . Often: arterial hypotension, arterial hypertension, ecchymosis 1 . Very often: thromboembolic disorders (mainly deep vein thrombosis and pulmonary embolism) 1 . Infrequent: ischemia, peripheral ischemia, thrombosis of the intracranial venous sinus.
Disturbances from the respiratory system Very often: dyspnea, nasopharyngitis, pharyngitis, bronchitis, nosebleed 1 . Often: respiratory distress syndrome.
Disorders from the digestive tract Very often: constipation, diarrhea, nausea, vomiting. Often: gastrointestinal bleeding (including rectal, hemorrhoidal, gingival bleeding and bleeding in a peptic ulcer 1 ), abdominal pain, dry mouth, stomatitis, dysphagia. Infrequently: colitis, tiflitis Often: diarrhea, constipation, nausea.
Disturbances from the liver and bile ducts Often: deviation of the values ​​of functional liver samples from normal. Often: deviation of the values ​​of functional liver samples from normal.
Impaired skin and subcutaneous tissue Very often: rash. Often: urticaria, hyperhidrosis, dry skin, skin itching, hyperpigmentation of the skin, eczema. Infrequent: skin color disorder, photosensitivity reaction. Often: rash.
Disturbances from the musculoskeletal system Very often: muscle cramps, bone pain, pain and discomfort from the osteomuscular and connective tissue. Often: swelling of the joints. Often: muscle weakness, pain in the bones. Infrequent: swelling of the joints.
Disorders from the kidney and urinary tract Often: hematuria 1 , urinary retention, urinary incontinence. Infrequently: acquired Fanconi syndrome. Often: kidney failure. Infrequently: tubular renal necrosis.
Violations of the genitals and mammary glands Often: erectile dysfunction -
General disorders and at the injection site Very common: fatigue, edema (including peripheral), fever, flu-like symptoms (including fever, myalgia, musculoskeletal pain, headaches and chills). Common: chest pain, lethargy. Common: fatigue.
Injury, poisoning and complications manipulation Common: contusion 1 . -
Summary of adverse reactions were detected between post-registration period monitoring patients treated with lenalidomide
system-organ class Adverse reactions frequency
benign, malignant neoplasms and unspecified Rare: tumor lysis syndrome.
Violations by the respiratory frequency is unknown: interstitial pneumonitis.
Violations of the gastrointestinal tract Frequency not known: pancreatitis.
Violations of the skin and subcutaneous tissue disorders Uncommon: angioedema. Rare: Stevens-Johnson syndrome 1 , toxic epidermal necrolysis 1 .
* Detailed information is provided at the end of this section.
1 Below is a description of the marked side reactions:
Teratogenicity
Lenalidomide is a structural analogue of thalidomide - substances having active teratogenic effect and causing life-threatening severe developmental abnormalities. Lenalidomide induced in monkeys appearance of congenital malformations similar to those described for thalidomide. If lenalidomide is taken during pregnancy, it is possible to predict the teratogenic effect, so lenalidomide is contraindicated during pregnancy.
Neutropenia and thrombocytopenia
Use of a combination of lenalidomide and dexamethasone in patients with multiple myeloma was accompanied by an increase in the incidence of neutropenia 4 severity (at 5.1% in patients treated with lenalidomide plus dexamethasone compared with 0.6% in patients treated with a combination of dexamethasone and placebo). Febrile neutropenia 4 severity in patients treated with the combination of lenalidomide with dexamethasone, observed infrequently - 0.6% (in patients treated with a combination of dexamethasone and placebo - 0.0%).
Use of a combination of lenalidomide and dexamethasone in multiple myeloma accompanied by increased likelihood of developing thrombocytopenia 3 and 4 severity (respectively 9.9% and 1.4% in patients treated with lenalidomide plus dexamethasone respect 2.3% and 0.0% in patients treated with a combination of dexamethasone and placebo).
Venous thromboembolism
The use of the combination of lenalidomide with dexamethasone in multiple myeloma patients was accompanied by an increased risk of deep vein thrombosis and pulmonary embolism. The simultaneous appointment of erythropoietic agents or the presence of deep vein thrombosis in history may also increase the risk of thrombotic complications in this group of patients.
myocardial infarction
In patients taking lenalidomide, there have been cases of myocardial infarction, especially in the presence of known risk factors.
Hemorrhagic complications
Hemorrhagic complications are listed in the appropriate system-organ classes: disorders of the blood and lymphatic system; disorders of the nervous system (intracranial hemorrhage); the respiratory system (nosebleeds); from the gastrointestinal tract (rectal, hemorrhoids, gingival bleeding); the kidneys and the urinary tract (haematuria); from the vessels (ecchymosis); injury, poisoning and complications of manipulation (bruises).
Allergic reactions
There are reports of the development of allergic reaction / hypersensitivity reactions. Describes the possibility of cross-reactivity between lenalidomide and thalidomide.
Severe skin reactions
have been reported on the development of Stevens-Johnson syndrome and toxic epidermal necrolysis. Lenalidomide should not be administered to patients, all of whom had severe rash while taking thalidomide history.
Primary malignant tumors of other localization
* New malignancies, according to a clinical trial in patients with myeloma after applying the combination of lenalidomide with dexamethasone compared to controls, were mainly basal cell or squamous cell skin cancer.
CONTRAINDICATIONS
- Pregnancy;
- the period of lactation (breastfeeding);
- saved childbearing potential, except in cases when it is possible that all prerequisites from pregnancy prevention program;
- the inability or failure to comply with the required contraceptive measures;
- Children ages (insufficient clinical use experience);
- hereditary lactose intolerance, lactase deficiency or malabsorption of glucose-galactose because Revlimid capsules contain lactose;
- Hypersensitivity to the components of the drug.
With caution should use the drug in elderly patients with renal insufficiency and in patients with multiple myeloma taking lenalidomide with dexamethasone, as drugs with eritropoeticheskoy activity, as well as hormone replacement therapy may increase the risk of thrombosis.
PREGNANCY AND LACTATION
The drug is contraindicated in pregnancy and lactation (breastfeeding).
Lenalidomide - structural analogue of thalidomide, which has a pronounced teratogenic. It is known that thalidomide by pregnant women causes serious and life-threatening disorders of the internal organs of the fetus. Experimental studies in monkeys showed results similar to the results previously described for thalidomide. The risk of birth defects is very high, if Revlimid is taken during pregnancy.
Women of reproductive ageduring the treatment with Revlimid should use effective methods of contraception. The use of lenalidomide should be discontinued if a woman's pregnancy is diagnosed, and the patient should be sent to a doctor who is experienced surveillance of pregnant women and to evaluate the clinical guidelines. In a case where the woman is a sexual partner of a patient receiving treatment lenalidomide, diagnose pregnancy, the woman is also directed to a specialist in the field to evaluate the situation teratological and clinical recommendations.
It is not known whether lenalidomide into breast milk. In this regard, during the treatment of lenalidomide breast-feeding should be discontinued.
Strict adherence to all the requirements of the protection program of pregnancy, should also apply to women and men.
For women, nedetorodnogo aged
female patient or female sexual partner, a male patient, are not considered capable of procreation in the presence of at least one of the following factors:
- age? 50 years and duration of amenorrhea natural? 1 year *;
- early failure of the ovaries, confirmed by a gynecologist;
- bilateral salpingooforektomiya hysterectomy or history;
- the XY genotype, Turner syndrome, uterine anatomic defect.
* - amenorrhea due to cancer therapy does not rule out the existence of child-bearing potential.
The use of lenalidomide in women of childbearing age are contraindicated in cases where one is not true of the following statements:
Women of childbearing potential must:
- be aware of teratogenicity Revlimid on the fetus;
- understand the need for continuous use effective contraception for 4 weeks before treatment, during treatment and 4 weeks after treatment Revlimid;
- even in the case of amenorrhea following all the rules of effective contraception;
- be able to comply with all rules of effective contraception;
- know and understand the potential consequences of pregnancy and the need for rapid treatment advice for suspected a pregnancy;
- understand the need for immediate receiving Revlimid after receiving negative pregnancy test result;
- aware of the need to test and perform a pregnancy test every 4 weeks;
- confirm that he understood the risk of potential adverse effects and the need to prevent them during treatment Revlimid.
Application men:
These study the pharmacokinetics of lenalidomide have male volunteers indicate that lenalidomide is present in the semen of patients during treatment in extremely low concentrations and is not determined 3 days after the termination of the application in healthy volunteers. As a precaution, given the possible decrease in the rate of excretion of lenalidomide in special patient groups (patients with impaired renal function), all male patients taking Revlimid, should be the following statements are true:
men taking Revlimid should:
- understand the potential risk of teratogenicity Revlimid actions during sexual contact with a pregnant woman or a woman of childbearing age;
- the need to understand the use of condoms during sexual contact with pregnant women or women of childbearing age who are not using reliable methods of contraception during treatment, with a break in the treatment and within 1 week after completion of treatment.
Doctor prescribe Revlimid women of childbearing potential must:
- be sure that the patient meets all the conditions of the Pregnancy Prevention Program, including confirmation that she adequately understands the situation;
- the informed consent of the patient for mandatory compliance with it all the conditions of the above programs.
Terms of contraception
Women of childbearing ageYou must use one of the highly effective methods of contraception for 4 weeks before therapy, during therapy Revlimid and for 4 weeks after treatment, even in the case of interruption of the treatment. The only exceptions are patients who abstain from heterosexual relationships throughout this period that is documented on a monthly basis. If the patient is not picked up by an effective contraceptive method, it should be sent to the gynecologist for the selection of the effective contraception. The patient should immediately start using an effective method of contraception.
For a highly effective method of contraception include:
- Subcutaneous hormonal implants;
- intrauterine system releasing levonorgestrel;
- depot medroxyprogesterone acetate formulations;
- tubal ligation;
- vasectomy of the partner (confirmed by two negative semen analysis);
- progesterone-containing tablets which inhibit ovulation (e.g., desogestrel).
Acceptance of COCs is not indicated for patients with multiple myeloma due to the increased risk of thromboembolic complications during treatment with Revlimid and dexamethasone. For effective contraception these patients it is recommended to use one of the methods listed above. The increased risk of thromboembolism persists for 4-6 weeks after discontinuation of combined contraceptives. The efficacy of hormonal contraceptives may be reduced with concomitant administration of dexamethasone.
Patients with neutropenia are used as a contraceptive subcutaneous implants or hormonal intrauterine system releasing levonorgestrel, it is necessary to prescribe antibiotics prophylactically in connection with an increased risk of infection at the time of the installation of these therapeutic systems.
The use of intrauterine systems that produce copper, are generally not recommended due to the high risk of infection at the time of implantation and increased blood loss during menstruation, which may enhance the severity of neutropenia or thrombocytopenia in a patient.
Pregnancy tests (sensitivity is not less than 25 mIU / ml) should be carried out in the presence of a physician for all women of childbearing age, including those that are fully exclude and long refrain from heterosexual relations. After the patient using an effective method of contraception for 4 weeks or more, the tests are carried out on the day of the appointment or treatment 3 days prior to the visit to the doctor, and then every 4 weeks, including and after receiving Revlimid. Test results should confirm the absence of pregnancy in a patient during treatment with Revlimid.
Male patients should use condoms throughout the course of Revlimid treatment and for 1 week after interruption or discontinuation of treatment in case a sexual partner - a pregnant woman or a woman of childbearing age, not using highly effective methods of contraception.
Educational materials
To increase security, Revlimid therapy and reduce the risk of teratogenic effects in the patient care provided teaching materials, which include all the necessary information about the drug, as well as protection against pregnancy program. The owner of the registration certificate provides physicians necessary for their patient materials. For more information about the teratogenic risk of Revlimid and measures for prevention of pregnancy the doctor sends patients of childbearing age and sexually active men.
APPLICATION FOR FUNCTIONS OF THE LIVER
Lenalidomide is released mainly by the kidneys. In this connection, the risk of toxic reactions may increase with impaired renal function . In the appointment of Revlimid in patients with impaired renal function is recommended to follow the guidelines listed below.
The starting dose of lenalidomide depending on the degree of renal impairment
Creatinine clearance recommended dose of Revlimid
? 50 mL / min 25 1 mg once / day (total dose) of
30 ml / min? CC <50 mL / min 10 1 mg once / day *
<30 ml / min and dialysis is not needed 15 mg every other day
<30 ml / min, dialysis requires 15 mg 3 times per week after each hemodialysis session
* The dose of drug may be improved 1 to 15 mg once / day after 2 cycles of therapy in the absence of response to therapy, but its good tolerability.
Given the preferential allocation of Revlimid kidneys, in patients with renal impairment should be carefully monitored renal function, and dose of Revlimid.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
The pharmacokinetics of lenalidomide have not been studied in patients with hepatic impairment , therefore, not possible to submit recommendations on dose adjustment in these patients.
APPLICATION FOR CHILDREN
Contra: infancy (insufficient clinical application experience).
APPLICATION IN ELDERLY PATIENTS
The pharmacokinetics of lenalidomide in elderly patients has not been studied. In clinical trials, lenalidomide administered to patients under the age of 95 years .There were no differences in the efficacy and safety of lenalidomide according to age, although we can not exclude a greater sensitivity to the drug patients with older age group. Because elderly patients the likelihood of renal function is greater dose of the drug must be chosen very carefully, at the same time during treatment is recommended to monitor renal function
SPECIAL INSTRUCTIONS
Revlimid treatment must be about
The information is provided for your information, do not self-medicate, it is dangerous for your health.
