Kalumid - instructions for use, doses, side effects, contraindications

Excipients: silicon dioxide colloid 1.5 mg; magnesium stearate 1,875 mg; povidone 12 mg; sodium carboxymethyl starch, type A 18 mg; lactose monohydrate 191.625 mg;

shell composition: Opadri II.33G28523 white 7.5 mg (glyceryl triacetate 6%, macrogol 3000 8%, lactose monohydrate 21%, titanium dioxide 25%, hypromellose 40%).

Description:

Round, biconvex tablets white or almost white, film-coated, with an engraved "XL" on one side and "RG" on the other.

Pharmacotherapeutic group:Antitumor agent - antiandrogen

ATX: & nbsp

L.02.B.B.03 Bicalutamide

Pharmacodynamics:

Bicalutamide is a racemic mixture with non-steroidal anti-androgenic activity predominantly (R) -enantiomer, does not have a different endocrine activity. Bicalutamide binds to androgen receptors and, without activating the expression of genes, suppresses the stimulating effect of androgens. The result is regression of malignant neoplasms of the prostate gland.

In some patients, discontinuing bicalutamide may lead to the development of a clinical "anti-androgen withdrawal syndrome".

Pharmacokinetics:

After oral administration, it is quickly and completely absorbed from the gastrointestinal tract. Food intake does not affect suction.

(S) -enantiomer is eliminated much faster from the body (R) -enantiomer, the half-life of the latter is about 7 days.

With daily intake of bicalutamide, the concentration (R) -enantiomer in plasma increases approximately 10-fold due to a long half-life.

With a daily intake of bicalutamide at a dose of 150 mg per day, the equilibrium concentration (R) enantiomer in plasma is about 22 μg / ml. At an equilibrium state, about 99% of all enantiomers circulating in the blood is active (R) -enantiomer.

On the pharmacokinetics (R) -enantiomer do not affect age, impaired renal function, mild and moderate impairment of liver function. There is evidence that in patients with severe impairment of liver function, elimination is slowed (R) -enantiomer from the plasma.

The association with plasma proteins is high (for a racemic mixture of 96%, for (R) -enantiomer 99.6%). Intensively metabolized in the liver (by oxidation and the formation of conjugates with glucuronic acid). Metabolites are excreted in urine and bile approximately in equal proportions.

Indications:

- Calumid® 150 mg is indicated for the treatment of locally advanced prostate cancer (T3-T4, any N, M0; T1-T2, N+, M0) as monotherapy or adjuvant therapy in combination with radical prostatectomy or radiotherapy;

- Calumid® 150 mg is also indicated for the treatment of locally advanced, non-metastatic prostate cancer in cases where surgical castration or other medical interventions are unacceptable or not applicable.

Contraindications:

- Hypersensitivity to bicalutamide or other components of the drug;

- simultaneous reception with terfenadine, astemizole and cisapride;

- Calumid® should not be assigned to children and women.

Carefully:Violation of the function of the liver.

Pregnancy and lactation:Bicalutamide is contraindicated in women and should not be given to pregnant and lactating mothers.

Dosing and Administration:

Adults and elderly men: inside by 150 mg once a day. Kalumid® should be taken for a long time, at least for 2 years. If signs of disease progression appear, the drug should be discontinued.

Renal impairment: correction of the dose is not required.

Dysfunction of the liver: with mild violations of the liver, dose adjustment is not required. In patients with moderate to severe hepatic impairment, an increased cumulation of Kalumida® can be observed.

Side effects:

The pharmacological action of bicalutamide can cause the following side effects:

- very often (> 10%): gynecomastia (can persist even after cessation of therapy, especially in case of taking the drug for a long time), tenderness of the mammary glands, hot flushes;

- often (≥1% and <10%): diarrhea, nausea, transient increase in the activity of "liver" transaminases,cholestasis and jaundice (described changes in liver function were rarely evaluated as serious, transient, completely disappeared or decreased with continued therapy or after withdrawal), itching, asthenia; when using the drug in a daily dose of 150 mg - alopecia or hair regrowth, decreased sexual desire, sexual dysfunction, weight gain;

- rarely (≥0,1% - <1%): hypersensitivity reactions, including angioedema and hives, interstitial lung diseases; when using the drug in a daily dose of 150 mg - abdominal pain, depression, dyspepsia, hematuria;

- rarely (≥0,01% - <0,1%): vomiting, dry skin (with the use of the drug in a daily dose of 150 mg, dry skin is often observed), liver failure (the cause-and-effect relationship with bicalutamide is not established reliably).

With the simultaneous use of bicalutamide and gonadotropin-releasing hormone analogues (GnRH), the following adverse events with a frequency of ≥ 1% can also be observed (a causal relationship with the drug intake has not been established, some of the noted: side effects were found in elderly patients):

From the side of the cardiovascular system: heart failure.

From the digestive system: anorexia, dry mouth, indigestion, constipation, flatulence.

From the nervous system: dizziness, headache, insomnia, increased drowsiness.

From the respiratory system: dyspnea.

From the genitourinary system: sexual dysfunction, nocturia.

From the hematopoietic system: anemia.

From the skin and its appendages: alopecia, rash, excessive sweating, hirsutism.

Other: diabetes, hyperglycemia, increased or decreased body weight, abdominal pain, chest pain, pelvic pain, chills.

Overdose:

Cases of overdose in humans are not described.

The specific antidote is not known.

Treatment symptomatic. Dialysis is ineffective, because bicalutamide strongly binds to proteins and is not excreted in the urine unchanged. Recommended general supportive treatment and strict control of vital body functions.

Interaction:

There is no evidence of pharmacokinetic or pharmacodynamic interactions between bicalutamide and GnRH analogues.

In studies in vitro shown, that (R) -enantiomer of bicalutamide inhibits CYP 3A4, to a lesser extent, affect the activity CYP 2С9, 2С19 and 2D6.

The potential for bicalutamide to interact with other drugs has not been detected, however, when bicalutamide is used for 28 days against the background of taking midazolam, the area under the curve AUC Midazolam increases by 80%.

Incompatible with terfenadine, astemizole, cisapride.

Caution should be exercised in prescribing bicalutamide simultaneously with cyclosporine or calcium channel blockers. It may be necessary to reduce the dose of these drugs, especially in the case of potentiation or the development of side effects. After the beginning of the use or elimination of bicalutamide, it is recommended that the concentration of cyclosporin in the plasma be carefully monitored and the patient's clinical condition monitored.

The simultaneous use of bicalutamide and drugs that inhibit microsomal oxidation of drugs, for example with cimetidine or ketoconazole, can lead to an increase in plasma bicalutamide concentration and, possibly, an increase in the incidence of side effects.

Strengthens the effect of anticoagulants coumarin series, warfarin (competition for the connection with proteins).

Special instructions:

Given the possibility of slowing the excretion of bicalutamide and its cumulation in patients with impaired liver function, it is advisable to periodically evaluate liver function. Most changes in liver function occur during the first six months of treatment with Kalumide®.

In case of pronounced changes in liver function, Kalumida® should be discontinued.

In patients with progression of the disease against a background of increased levels of prostate-specific antigen (PSA), consideration should be given to discontinuing treatment with Kalumide®.

When appointing Kalumida®, patients receiving anticoagulants of the coumarin series are advised to regularly monitor prothrombin time.

Given the possibility of inhibition of the activity of cytochrome by Kalumid® P450 (CYP 3A4), caution should be exercised in the simultaneous administration of Kalumida® with preparations predominantly metabolized with participation CYP 3A4.

Patients with lactose intolerance should be informed that each 150 mg Kalumida tablet contains 183 mg of lactose monohydrate.

Effect on the ability to drive transp. cf. and fur:

Kalumid® does not affect the ability of patients to manage, transport, or engage in other potentially hazardous activities requiring increased concentration and speed of psychomotor reactions.

Form release / dosage:Tablets, film-coated, 150 mg.

Packaging:

For 10 tablets in a blister of PVC / PVDH-film and aluminum foil.

3 blisters with instructions for use in a cardboard bundle.

Storage conditions:

Store at a temperature of 15-30 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006592/08

Date of registration:14.08.2008 / 03.12.2008

Expiration Date:Unlimited

The owner of the registration certificate:GEDEON RICHTER, OJSC GEDEON RICHTER, OJSC Hungary

Manufacturer: & nbsp

GEDEON RICHTER, Ltd. Hungary

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsp26.11.2017

Illustrated instructions

Instructions

Calumid® (Calumid®)