KALUMID
Active material: Bikalutamid
When ATH: L02BB03
CCF: Non-steroidal anti-androgen drug with anti-tumor activity
ICD-10 codes (testimony): C61
When CSF: 15.13.03.02
Manufacturer: RICHTER RICHTER Ltd. (Hungary)
Pharmaceutical form, composition and packaging
Pills, coated white or nearly white, round, Engraved “L” on one side and “RG” – another.
| 1 tab. | |
| ʙikalutamid | 50 mg |
Excipients: colloidal silicon dioxide, magnesium stearate, povidone, sodium carboxymethyl starch type A, lactose monohydrate.
The composition of the shell: Opadry II 33G28707 White, glycerol triacetate, macrogol 3000, lactose monohydrate, Titanium dioxide, gipromelloza.
15 PC. – blisters (2) – packs cardboard.
15 PC. – blisters (6) – packs cardboard.
Pills, Film-coated white or nearly white, round, lenticular, engraved sign “XL” on one side and “RG” – another.
| 1 tab. | |
| ʙikalutamid | 150 mg |
Excipients: colloidal silicon dioxide, magnesium stearate, povidone, sodium carboxymethyl starch type A, lactose monohydrate.
The composition of the shell: Opadry II.33G28523 White (glyceryl triacetate, macrogol 3000, lactose monohydrate, Titanium dioxide, gipromelloza).
15 PC. – blisters (2) – packs cardboard.
Pharmacological action
Non-steroidal anti-androgen drug. Is a racemic mixture, and the anti-androgen activity has mostly (R)-enantiomer. It does not have other types of endocrine activity.
It binds to the androgen receptor and, without activating gene expression, It inhibits the stimulatory effect of androgens. This results in a regression of prostate tumors.
Some patients stopping bicalutamide can lead to clinical “antiandrogen withdrawal”.
Pharmacokinetics
Absorption
After taking the drug inside bicalutamide is rapidly and completely absorbed from the gastrointestinal tract. Eating does not affect the absorption.
Distribution
Communication with high plasma protein (for the racemic mixture 96%, to (R)-enantiomer 99.6%). Intensively metabolized in the liver by oxidation and formation of conjugates with glucuronic acid.
When taken daily Kalumida® concentration (R)-enantiomer in the plasma increases about 10 time due to the long T1/2, that allows the drug 1 time / day.
When taken daily Kalumida® dose 50 mg Css (R)-enantiomer in the plasma is about 9 ug / ml, and when receiving 150 mg Kalumida® – 22 ug / ml. When the equilibrium state around 99% all circulating enantiomers is active (R)-enantiomer.
Metabolism
It is extensively metabolized in the liver (by oxidation and formation of conjugates with glucuronic acid).
Deduction
The metabolites are excreted in the urine and bile in approximately equal proportions.
(S)-enantiomer is eliminated from the body much faster (R)-enantiomer, T1/2 last about 7 days.
Pharmacokinetics in special clinical situations
Pharmacokinetics (R)-enantiomer does not depend on the age, renal dysfunction, and also from mild to moderate liver dysfunction.
There is evidence, In patients with moderate or severe hepatic impairment slows elimination (R)-enantiomer from plasma and can be observed accumulation of bicalutamide.
Testimony
- A common prostate cancer in a combination therapy with a GnRH analogue (gonadotropin-releasing gormon) or in combination with surgical castration (Pill 50 mg);
- Locally advanced prostate cancer (T3-T4, Any N, M0; T1-T2, N , M0) as monotherapy or adjuvant therapy in combination with radiotherapy or radical prostatectomy;
- Locally advanced non-metastatic prostate cancer in cases, when surgical castration or other medical intervention inapplicable or unacceptable.
Dosage regimen
Adult men (incl. Seniors) at disseminated prostate cancer in combination with a GnRH analogue or surgical castration the drug is prescribed in a dose 50 mg 1 time / day. Treatment Kalumidom® should begin simultaneously with the start of the reception of GnRH analogue or surgical castration.
At locally advanced prostate cancer appoint 150 mg 1 time / day. Kalumid® should be long-term, for at least a 2 years. If signs of disease progression receiving the drug should be discontinued.
At kidney function and minor hepatic dysfunction dose adjustment is required.
Side effect
The pharmacological action of bicalutamide may account for the following side effects:
On the part of the endocrine system: Often (>10%) – gynecomastia (It can be maintained even after cessation of therapy, especially in the case of long-term use of the drug), breast tenderness, tides; often (≥1% and <10%) when applied in a daily dose of the drug 150 mg – decreased libido, sexual dysfunction, weight gain.
From the digestive system: often – diarrhea, nausea, increase in transaminases, jaundice, cholestasis (These changes in liver function were often transient and disappeared completely or diminished, despite continued therapy or after cessation); rarely (And ≥0.1% <1%) when applied in a daily dose of the drug 150 mg – abdominal pain, dyspepsia; rarely (≥0.01% and <0.1%) – vomiting, hepatic failure (a causal relationship with the reception of bicalutamide is not installed).
Dermatological reactions: often – itch; when applied in a daily dose of the drug 150 mg – Alopecia or hair regrowth; rarely – xerosis (when applied in a daily dose of the drug 150 mg of dry skin is often observed).
Allergic reactions: rarely – angioedema, hives.
CNS: often – asthenia; rarely (when applied in a daily dose of the drug 150 mg) – depression.
Other: rarely – interstitial lung disease, when applied in a daily dose of the drug 150 mg – hematuria.
In an application Kalumida® and GnRH analogues may experience the following side effects with a frequency ≥1% (a causal relationship to drug intake is not installed, Some of the noted side effects in older patients without receiving Kalumida)
Cardio-vascular system: heart failure.
From the digestive system: anorexia, dry mouth, dyspepsia, constipation, flatulence.
CNS: dizziness, headache, insomnia, drowsiness.
The respiratory system: breathlessness.
From the urinary system: nocturia.
From the hematopoietic system: anemia.
Dermatological reactions: alopecia, rash, increased sweating, girsutizm.
Metabolism: diabetes, giperglikemiâ, increase or decrease in body weight.
Other: sexual dysfunction, abdominal pain, chest pain, pelvic pain, chills.
Contraindications
- Simultaneous reception with terfenadine, astemizolom, cizapridom;
- Hypersensitivity to bicalutamide and / or other ingredients.
Kalumid® not prescribed for women and children.
FROM caution should be prescribed with abnormal liver function.
Pregnancy and lactation
Kalumid® contraindicated for women and should not be given to pregnant and nursing mothers.
Cautions
Given the possibility of slowing excretion of bicalutamide in patients with impaired hepatic function it is advisable during treatment Kalumidom® periodically evaluate the function of the liver. Most liver function changes are noted within the first 6 months of treatment. In case of severe liver dysfunction should stop taking Kalumida®.
Patients with progressive disease on the background of increasing prostate-specific antigen level (PSA) should consider discontinuing treatment Kalumidom®.
In appointing Kalumida® patients, receiving coumarin anticoagulants, to regularly monitor the prothrombin time.
Given the possibility of inhibiting the activity of cytochrome P450 Kalumidom (CYP 3A4), caution should be exercised with concomitant administration with drugs Kalumida, mainly metabolized by the CYP3A4.
Patients with lactose intolerance should be informed about, that each tablet Kalumida® 50 mg comprises 63.875 mg lactose monohydrate, and each tablet Kalumida® 150 mg – 183 mg lactose monohydrate.
Effects on ability to drive vehicles and management mechanisms
Kalumid® It does not affect the patients' ability to drive vehicles or engage in other potentially hazardous activities, require high concentration and speed of psychomotor reactions.
Overdose
Cases of overdose have not been described in humans. There is no specific antidote, so if necessary spend symptomatic therapy. Dialysis nyeeffyektivyen, since bicalutamide is closely associated with proteins and excreted in the urine as unchanged. Shown general supportive therapy, Heart rate monitors, respiration rate and blood pressure.
Drug Interactions
There is no evidence of any pharmacodynamic or pharmacokinetic interactions between Kalumidom® and GnRH analogues.
In in vitro studies show, what (R)-enantiomer of bicalutamide is an inhibitor of CYP3A4, less affecting the activity of CYP2C9, CYP2C19, CYP2D6. Bicalutamide potentially capable of interacting with other drugs were found, However, when applying Kalumida® during 28 days in patients receiving midazolam AUC of midazolam was increased by 80%. Concomitant use with terfenadine Kalumida, astemizole, and cisapride.
Care should be taken when appointing Kalumida® concurrently with cyclosporine or calcium channel blockers. Maybe, We need to reduce the dose of these drugs, especially in the case of potentiation or unwanted reactions. Once you start using or cancel Kalumida® recommend careful monitoring of cyclosporine concentrations in blood plasma and clinical condition of the patient.
Concomitant use Kalumida® and preparations, oppressing microsomal oxidation (cimetidine, ketoconazole), It can lead to an increase in plasma concentrations of bicalutamide and, perhaps, an increase in the incidence of adverse reactions.
Kalumid® It enhances the effect of coumarin anticoagulants (competition for protein binding).
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
List B. The drug should be stored out of reach of children at temperature from 15 ° to 30 ° C. Shelf life Tablets 50 mg – 3 year, tablets 150 mg – 2 year.
