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

Bicalutamide is a racemic mixture with non-steroidal antiandrogenic 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 rapidly and completely absorbed from the gastrointestinal tract. Eating does not affect absorption.

(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 the drug Kalumid® concentration (R) -enantiomer in plasma increases approximately 10-fold due to a long half-life, which makes it possible to take the drug once a day.

With a daily intake of bicalutamide in a dose of 50 mg, the equilibrium concentration (R) -enantiomer in plasma is about 9 μg / ml. When 150 mg of bicalutamide is taken daily, the equilibrium concentration (R) -enantiomer 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 blood plasma.

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

Indications:

- Common prostate cancer in combination with an analogue of GnRH (gonadotropin-releasing hormone) or surgical castration;

- 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;

- Locally disseminated nonmetastatic prostate cancer in cases where surgical castration or other medical interventions are not applicable or are unacceptable.

Contraindications:

- Hypersensitivity to bicalutamide and / or other components of the drug;

- simultaneous reception with terfenadine, astemizole and cisapride;

- Kalumid® should not be administered to women or children.

Carefully:

- Impaired liver function;

- Lactase insufficiency, lactose intolerance, glucose-galactose malabsorption (in the drug form of the drug contains lactose).

Dosing and Administration:

Adult males (including the elderly):

When a common prostate gland in combination with an analogue of GnRH or surgical castration: inside by 50 mg once a day. Treatment with Kalumid® should be started simultaneously with the onset of GnRH analogue or surgical castration.

When locally advanced prostate cancer: inwards by 150 mg once at 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: dose adjustment is not required.

Dysfunction of the liver: with a mild violation of liver function correction of the dose is not required. In patients with moderate to severe hepatic impairment, an increased cumulation of the Kalumid® preparation may 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, "tides" of blood to the face;

- often (≥1% and <10%): diarrhea, nausea, transient increase in the activity of "liver" transaminases, cholestasis and jaundice (these changes in liver function were rarely estimated 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 restoring hair growth, reducing sexual desire; sexual dysfunction, weight gain;

- rarely (≥0,1% - <1%): hypersensitivity reactions, including angioedema and urticaria, interstitial lung diseases; angina, lengthening of the QT interval, heart rhythm disturbances; 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 observedoften), hepatic insufficiency (cause-and-effect relationship with bicalutamide is not established reliably), thrombocytopenia.

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

From the cardiovascular system: heart failure.

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

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

From the respiratory system: dyspnea.

From the urinary system: nocturia, polyuria.

From the hematopoietic system: anemia, and leukopenia.

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

From the laboratory indicators: hyperglycemia, increased activity "hepatic" transaminases.

Other: abdominal pain, chest pain, pelvic pain, decreased or increased body weight, swelling, diabetes, fever.

Overdose:

Cases of overdose in humans are not described.

There is no specific antidote.

Treatment symptomatic. Dialysis is not effective, because bicalutamide strongly binds to proteins: and is not excreted by the kidneys in unchanged form. It shows general supportive therapy and monitoring 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 affecting the activity of CYP 2С9, 2С19 and 2D6. The potential for bicalutamide to interact with other drugs has not been revealed, however, when bicalutamide is used for 28 days against the background of midazolam, the area under the concentration-time curve (AUC) midazolam increases by 80%.

Incompatible with terfenadine, astemizole, cisapride.

Caution should be used when administering Calumid® concomitantly 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 use or discontinuation of the preparation, Calumid® is recommended to carry out a careful monitoring of the plasma cyclosporin concentration and the clinical state of the patient.

Simultaneous use of the preparation Kalumid® and drugs that inhibit microsomal oxidation of drugs, for example, with cimetidine or ketoconazole, may lead to an increase in the concentration of the drug Kalumid® in blood plasma and, possibly, an increase in the incidence of side effects.

Strengthens the effect of anticoagulants coumarinovogo number, incl. warfarin (competition for communication with proteins).

Special instructions:

Given the possibility of slowing the withdrawal of the drug Kalumid®, 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 Kalumid®.

In case of pronounced changes in liver function, the preparation of Kalumid® 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 Kalumid®.

When appointing the drug Kalumid ® patients receiving anticoagulants coumarinic series, it is recommended to monitor prothrombin time on a regular basis.

Patients with lactose intolerance should be informed that each tablet of the preparation Kalumid® 50 mg contains 63.875 mg of lactose monohydrate.

Taking into account the possibility of bicalutamide inhibition of cytochrome P450 (CYP 3A4) caution should be exercised with simultaneous appointment preparation of Kalumid® with drugs predominantly metabolized with CYP 3A4.

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

During the treatment period, care should be taken when driving a car and engaging in potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:Tablets, film-coated, 50 mg.

Packaging:

For 15 tablets in a blister of PVC /AL.

2 or 6 blisters with instructions for use in a cardboard bundle.

Storage conditions:

Store at a temperature not exceeding 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:LS-000199

Date of registration:11.03.2010

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®)