Ibranza
Ibransa: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Ibrance
ATX code: L01XE33
Active ingredient: palbociclib (Palbociclib)
Manufacturer: Pfizer Manufacturing Deutschland, GmbH (Pfizer Manufacturing Deutschland, GmbH) (Germany)
Description and photo update: 2018-27-11
Prices in pharmacies: from 84,500 rubles.
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Ibransa is an antineoplastic drug.
Release form and composition
Ibransu is produced in the form of capsules: hard gelatinous, with three dosages: 75 mg - size No. 2, the cap and body are light orange, on the body there is a white inscription "RBC 75"; 100 mg - size No. 1, light orange body with white lettering "PBC 100" and light red-brown cap, 125 mg - size No. 0, light red-brown cap and body, white lettering on the body " RVS 125 "; on the cap of all capsules there is an inscription in white "Pfizer"; the contents of the capsules are powder from yellow to almost white (21 pcs. in a polyethylene bottle, in a cardboard box 1 bottle; 7 pcs. in blisters, in a cardboard box 3 blisters; each pack also contains instructions for using Ibransa).
1 capsule contains:
- active substance: palbociclib - 75, 100 or 125 mg;
- auxiliary components: lactose monohydrate, microcrystalline cellulose, sodium carboxymethyl starch, magnesium stearate, colloidal silicon dioxide;
- capsule composition: gelatin, titanium dioxide (E171), iron dye red oxide (E172), iron dye yellow oxide (E172);
- ink composition: shellac, propylene glycol, titanium dioxide, 28% ammonia solution, isopropanol, simethicone, butanol.
Pharmacological properties
Pharmacodynamics
Ibransa is an anticancer drug that contains palbociclib as an active ingredient, which is a highly selective, reversible low molecular weight inhibitor of cyclin-dependent kinases (CDK) 4 and 6. Kinases CDK4 (6) and cyclin D1 are part of many signaling pathways that activate cell proliferation. As a result of inhibition of CDK4 (6), the transition of the cell from the G1-phase to the S-phase of the cell cycle is blocked, which causes suppression of cell proliferation.
The research results confirm the high efficacy of palbociclib against estrogen receptor positive (ER-positive) breast cancer and other luminal types of breast cancer.
Analyzing the mechanism of action of the drug, it was found that its combination with antiestrogenic agents enhances the reactivation of the Rb protein (retinoblastoma) through inhibition of Rb phosphorylation. This causes suppression of E2F signaling and delayed proliferation. Treatment of cancer cells with anti-estrogen agents and palbociclib, increasing the delay in proliferation of ER-positive breast cancer lines, causes an increase in cell aging. This causes long-term blockage of the cell cycle after the cancellation of Ibransa and an increase in cell size associated with the aging phenotype.
Experimental studies of the combination of palbociclib with letrozole outside the human body (in vitro) have confirmed that one of the mechanisms providing the antitumor efficacy of the combined action of palbociclib and an ER antagonist in models of ER-positive breast cancer is proliferation delay caused by cell aging.
Evaluation of the effectiveness of therapy with palbociclib in combination with fulvestrant for breast cancer, hormone receptor positive (HR) and receptor negative human epidermal growth factor II (HER2) in women, regardless of their menopausal status, with disease progression after previous endocrine therapy was given according to the results of an international multicenter double-blind randomized trial.
Pharmacokinetics
After oral administration, the maximum concentration (Cmax) of palbociclib is reached on average after 4-8 hours. The absolute bioavailability at a dose of 125 mg is 46%. With the use of doses in the range from 25 mg to 225 mg, there is an increase in the total concentration (AUC) of the drug in the blood plasma and Cmax in proportion to the dose. With the dosing regimen once a day, the Css (equilibrium concentration) of palbociclib in blood plasma is reached within 192 hours, while the accumulation coefficient can be up to 4.2 (average value 2.4).
Palbociclib should be taken with meals. When Ibransa is taken on an empty stomach, there is a very low degree of absorption and exposure of palbociclib compared with simultaneous intake with food. The values of Cmax and AUC depend, among other things, on the fat content in the food taken by the patient, so with a high concentration of fat in food, they increase by 38% and 21%, with a low - by 27% and 12%, respectively. If the drug is taken 1 hour after breakfast containing a moderate amount of fat, Cmax increases by about 24%.
Plasma protein binding is approximately 85% of the dose of palbociclib taken.
The geometric mean of the apparent volume of distribution (Vd / F) is 2583 liters or 25%.
Palbociclib is metabolized in the liver. The main pathways of the primary intensive biotransformation of palbociclib are oxidation and sulfonation, the secondary ones are acylation and glucuronidation. In the blood plasma, palbociclib mainly circulates in the form of a compound associated with a radioactive drug. The main circulating metabolite is the conjugate of palbociclib with glucuronic acid (1.5% of the administered dose).
Palbociclib metabolism is carried out mainly with the participation of the CYP3A isoenzyme and the SULT2A1 sulfotransferase enzyme.
The half-life (T 1/2) from blood plasma averages 29 hours. The excretion of the drug is carried out mostly through the intestines - 74.1% of the dose taken, of which: palbociclib conjugate with sulfamic acid - 25.8%, unchanged - 2.3%. Up to 17.5% of palbociclib is excreted through the kidneys, up to 6.9% unchanged.
Patient gender, age and body weight did not have a clinically significant effect on palbociclib exposure.
Pharmacokinetic studies on the use of Ibransa at the age of 18 years and younger have not been conducted.
In patients aged 65 and over, the safety and efficacy of Ibransa is similar to that in younger patients.
With a mild degree of liver dysfunction, the exposure of palbociclib does not change.
Mild to moderate renal impairment does not affect palbociclib exposure. The pharmacokinetics of the drug in moderate or severe liver dysfunction and severe renal dysfunction have not been studied.
With the average value of the observed maximum concentration of palbociclib in an equilibrium state during the administration of therapeutic doses of Ibransa daily for the recommended full cycle, a clinically significant lengthening of the QT interval and an increase in heart rate are unlikely.
Indications for use
The use of Ibransa is indicated after previous hormone therapy for locally advanced or metastatic breast cancer, hormone receptor positive (HR +) and human epidermal growth factor II receptor negative (HER2-), in combination with fulvestrant.
Contraindications
Absolute:
- moderate or severe liver dysfunction, if the total bilirubin indicator exceeds 1.5 times the ULN (upper limit of the norm) at any level of AST (aspartate aminotransferase) activity;
- severe renal dysfunction with creatinine clearance (CC) less than 30 ml / min, including if necessary, hemodialysis;
- simultaneous use of drugs that are powerful inducers and inhibitors of the CYP3A isoenzyme, proton pump inhibitors;
- period of pregnancy;
- breast-feeding;
- age up to 18 years;
- individual hypersensitivity to the components of the drug.
Ibrans should be used with caution according to indications for hereditary lactase deficiency, lactose intolerance or glucose-galactose malabsorption syndrome.
Ibransa, instructions for use: method and dosage
Ibrans capsules are taken orally with meals, swallowing whole, at the same time every day.
Do not allow capsules with broken shell integrity, therefore, chewing or opening them before swallowing is strictly prohibited!
The recommended therapy regimen: 125 mg once a day. The duration of the full cycle is 28 days, of which 21 days - taking Ibransa and 7 days - the subsequent break. Intramuscular administration of fulvestrant at a dose of 500 mg is performed on days 1, 15 and 29, then - once every 30 days.
If you accidentally skip the next dose or develop vomiting, you should not take an additional dose of the drug, the next dose should be taken at its usual time. The use of Ibransa should be continued until the positive effect of the treatment is observed.
In accordance with local clinical practice, prior to commencing combination therapy with fulvestrant, premenopausal and perimenopausal women should be treated with a luteinizing hormone releasing factor agonist.
Modification of the dose of Ibransa should be carried out taking into account the individual tolerance of the drug and the safety of its use.
With the development of adverse reactions, it may be necessary to temporarily discontinue therapy, postpone the intake to a later date and / or lower the dose, and in some cases, completely discontinue the drug.
To eliminate adverse events, it is recommended to first reduce the dose to 100 mg 1 time per day; in the absence of the desired result, the daily dose is reduced to 75 mg. If the correction of the dosage regimen was ineffective, you should stop taking Ibransa.
In order to establish the first symptoms of the development of hematological toxicity, a general blood test is shown before the start of drug use, on the first and fourteenth days of the first two cycles, then the blood is subject to research at the beginning of each cycle and according to clinical indications.
If the results of monitoring a complete blood count indicate the development of hematological toxicity (with the exception of lymphopenia, if it is not a clinical manifestation of opportunistic or other infections), dose modification is indicated taking into account the severity of neutropenia.
In the first and second severity, when the absolute neutrophil count (ANC) is less than the lower limit of normal (LBN) according to the Common Criteria for Adverse Event Terminology (CTCAE), dose adjustment is not required.
If hematological toxicity of the third degree is detected on the first day of the cycle, taking Ibransa should be suspended and an additional complete blood count should be performed for 7 days. If the symptoms of toxicity have decreased to the second degree of severity, it is indicated to resume taking the drug at the same dose. You should not continue therapy in the absence of a decrease in the severity of toxicity to the second or lower degree. If a fourth degree of hematological toxicity is detected, the beginning of the next cycle should be postponed; therapy should be resumed after reaching the second degree of toxicity with a lower dose than the previous one.
If hematological toxicity of the third degree is detected on the fourteenth day of the first two cycles, therapy should be continued at the current dose. A repeated general blood test is performed on day 21: if the severity is third, it is necessary to start taking Ibransa in the next cycle with the size of the current dose; if the severity is fourth, the dose of the next cycle should be reduced.
When the decrease to the second degree of neutropenia lasts more than 7 days or there are repeated increases to the third degree of intoxication, a careful assessment of the need for dose reduction in subsequent cycles of therapy is required.
If third-degree neutropenia is accompanied by an increase in body temperature to 38.5 ° C or higher and / or the development of infection, the use of Ibransa should be canceled until the symptoms resolve to the second degree of neutropenia. The therapy should be resumed at a lower dose.
With the fourth degree of hematological toxicity, a temporary cessation of therapy is required. After resolution of symptoms to the second level, treatment is resumed with the next lower dose.
With the development of non-hematological toxicity of the first and second severity, dose adjustment is not required.
When non-hematological toxic phenomena of the third and higher degree persist after the appropriate treatment, then taking Ibransa must be discontinued until the first degree of intoxication is reached. If the phenomena of non-hematological toxicity do not pose a risk to the safety of the patient, then the treatment can be resumed with a lower dose at the second (or lower) degree of toxicity.
In special cases, when it is impossible to avoid the simultaneous use of palbociclib with potent inhibitors of the CYP3A isoenzyme, the daily dose of the drug should be reduced to 75 mg. After the cancellation of a potent inhibitor of the isoenzyme CYP3A and after 3-5 periods of its half-life, the dose of Ibransa can be increased to the previously used one.
In case of mild hepatic dysfunction, renal failure with a CC of 30 ml / min or more (mild to moderate severity) or treatment of patients aged 65 years and older, dose adjustment is not required.
Side effects
As a result of clinical studies, the following adverse events have been established:
- on the part of the lymphatic system and the blood system: very often - anemia (decrease in hemoglobin and hematocrit), neutropenia with a decrease in the number of neutrophils, thrombocytopenia with a decrease in the concentration of platelets, leukopenia (decrease in the concentration of blood leukocytes); infrequently - febrile neutropenia;
- infectious and parasitic diseases: very often - infections;
- on the part of the organ of vision: often - dry eyes, increased lacrimation, blurred vision;
- from the nervous system: very often - headache, often - dysgeusia;
- from the gastrointestinal tract: very often - inflammation of the oral mucosa, nausea, vomiting, oral pain, stomatitis, aphthous stomatitis, ulcerative stomatitis, glossitis, cheilitis, glossodynia, discomfort and / or pain in the mouth and pharynx, diarrhea, constipation;
- on the part of metabolism and nutrition: very often - a decrease in appetite;
- from the respiratory system, chest and mediastinal organs: often - epistaxis;
- dermatological reactions: very often - rash (including maculopapular, itching, erythematous or papular rash), dermatitis, acne dermatitis, alopecia; often - dry skin;
- laboratory indicators: very often - a decrease in the number of neutrophils, a decrease in the concentration of blood leukocytes, a decrease in the level of hemoglobin, a decrease in the volume of hematocrit;
- general disorders: very often - increased fatigue; often - hyperthermia, general weakness.
The most frequent adverse reactions of any severity in more than 10% of patients receiving combination therapy with palbociclib were infections, leukopenia, thrombocytopenia, neutropenia, nausea, anemia, fatigue, stomatitis, alopecia, vomiting, diarrhea, decreased appetite, rash. Neutropenia of any severity was registered in 335 patients from the combination therapy group (78.3%), including the third degree of the disease was observed in 226 patients, which was 52.8%; the fourth degree of the disease was registered in 35 patients, which was 8.2%.
Diarrhea was the most common serious adverse reaction in patients receiving palbociclib in combination with letrozole (2.4%).
Infections (2.0%) were the most frequent serious side effects of palbociclib with fulvestrant.
Overdose
Overdose symptoms have not been established.
In case of accidental intake of an increased dose of the drug, the patient requires careful medical supervision and the appointment of general supportive therapy. The specific antidote for palbociclib is unknown.
special instructions
In the results of clinical studies, Ibransa indicates the existing risk of developing neutropenia. In this regard, careful monitoring of the number of neutrophils in the blood is required. A complete blood count should be performed before starting the drug, at the beginning of each cycle and according to clinical indications. In addition, in the first two cycles, an additional blood test is prescribed on the 14th day of therapy.
The ability of palbociclib to suppress bone marrow function may be the reason for the predisposition of patients to infections. Therefore, during the period of treatment, their condition should be carefully monitored in order to identify symptoms of infection and timely prescribe appropriate therapy.
Patients should be informed of the need to urgently inform the doctor about any increase in body temperature.
To prevent the development of pulmonary embolism, it is necessary to monitor to identify its symptoms.
The effect of palbociclib on reproductive function in women has not been established. Men should consider sperm preservation before using Ibransa.
Influence on the ability to drive vehicles and complex mechanisms
During the entire period of treatment, it is recommended to be careful when driving vehicles and mechanisms, especially for patients who experience increased fatigue and general weakness during therapy.
Application during pregnancy and lactation
The use of Ibransa is contraindicated during the gestation period and during breastfeeding.
During the period of taking palbociclib and within 90 days after its cancellation, conception should not be allowed.
During sexual intercourse during the period of treatment of one of the partners, reliable methods of barrier contraception should be used.
Pediatric use
Due to the lack of information on the safety and efficacy of using Ibransa according to indications in patients under the age of 18 years, the appointment of the drug for the treatment of this category of patients is contraindicated.
With impaired renal function
Palbociclib should not be prescribed for severe renal impairment (CC less than 30 ml / min) and, if necessary, hemodialysis.
With mild to moderate renal failure (CC 30 ml / min and above), dose adjustment of Ibransa is not required.
For violations of liver function
The use of Ibransa is contraindicated for moderate or severe liver dysfunction, if the total bilirubin indicator is 1.5 times higher than the upper limit of the norm at any level of ACT activity.
With mild liver dysfunction, dose adjustment is not required.
Use in the elderly
When treating patients aged 65 years and older, dose adjustment of Ibransa is not required.
Drug interactions
- ketoconazole, itraconazole, amprenavir, atazanavir, ritonavir, saquinavir, erythromycin, boceprevir, garithromycin, diltiazem, telithromycin, voriconazole, conivaptan, delavirdine, fosamprenavir, indinavir, telaprephine, nelaprutinavir and other inhibitors of the isoenzyme CYP3A: contribute to a clinically significant increase in the concentration of palbociclib in blood plasma;
- primidone, carbamazepine, rifampicin, rifapentine, enzalutamide, felbamate, phenobarbital, phenytoin, rifabutin, nevirapine, St.
- bosentan, efavirenz, modafinil, etravirine, nafcillin and other moderate CYP3A inducers: may cause a slight decrease in the plasma content of palbociclib, therefore, if necessary, the combination of palbociclib with moderate CYP3A inducers does not require dose adjustment;
- proton pump inhibitors (rabeprazole): drugs that reduce the acidity of gastric juice contribute to a significant decrease in Cmax of palbociclib, so this combination should be avoided;
- cyclosporine, midazolam, alfentanil, dihydroergotamine, pimozide, ergotamine, everolimus, fentanyl, quinidine, sirolimus, tacrolimus: after reaching an equilibrium state in the blood plasma, palbociclib has a weak inhibitory effect on drugs metabolized by the CYP3A isoenzyme, therefore, if necessary substances / preparations, their usual dose should be reduced;
- isoenzymes CYP1A2 - 2A6, 2B6, 2C8, 2C9, 2C19, 2D6: in vitro palbociclib does not inhibit these isoenzymes;
- isoenzymes CYP1A2 - 2B6, 2C8 and 3A4: in vitro palbociclib is not an inducer of these isoenzymes used in clinical concentrations;
- letrozole, fulvestrant, goserelin, tamoxifen: there are no clinically significant interactions between palbociclib and these agents.
In vitro studies have established the ability of palbociclib to weakly inhibit the activity of the following drug carrier proteins: P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic cation carrier OCT2, organic anion carriers - OAT1 and OAT3, polypeptide-transporter of organic anions OATP1B1 and OATP1B3, bile salts transporter protein (BSEP) at their concentration level used in clinical practice. The results of in vitro studies indicate the unlikely effect of transport mediated by P-gp and BCRP on the absorption period of palbociclib after oral administration at therapeutic doses.
Analogs
Ibransa's analogues are: Herceptin, Trastuzumab, Xeloda, Anastrozole, Arimidex, Doxorubicin, Epirubicin, Fulvestrant, Fluorouracil, etc.
Terms and conditions of storage
Keep out of the reach of children.
Store at temperatures up to 30 ° C.
Shelf life is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Ibrance
Considering that the drug was relatively recently (October 2016) appeared on the market, and its cost is quite high, patients have not yet left feedback about Ibranza.
It should be noted that the drug received the status of "breakthrough therapy". It has been honored with the prestigious Galen Prize, which is considered the equivalent of the Nobel Prize in Pharmacological Research and Development.
Price for Ibransa in pharmacies
The price of Ibransa for a package containing 21 capsules in a dose of 100 mg can range from 282,849 rubles.
Ibranza: prices in online pharmacies
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Drug name Price Pharmacy |
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Ibransa 125 mg capsule 21 pcs. RUB 84500 Buy |
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
