Bikulide

Biculide is an anti-androgenic medicine of non-steroid nature. Does not affect the endocrine system.

The drug is synthesized with androgenic endings, without causing active gene expression, which leads to inhibition of androgenic stimuli. Such suppression leads to the development of regression of tumors in the prostate. In the case of drug withdrawal, some patients may develop drug withdrawal syndrome.

Indications Cut out

It is used for prostate carcinoma (in the later stages) in combination with the use of analogs of the releasing factor of lyutropin or with surgical castration.

Release form

The release of the drug component is made in tablets - 50 pieces inside the bottle. Also implemented within cellular packaging - 15 pieces. In the box - 2 such packages.

Pharmacodynamics

Biculide is a racemic mixture with antiandrogenic properties. It appears almost exclusively in the form of (R) -enantiomer.

Pharmacokinetics

The drug is well absorbed by oral administration. There is no proven information that food has a clinically significant effect on the bioavailability of a drug.

(S) -enantiomer is excreted much faster (R) -enantiomer; the term of the plasma half-life of the latter is approximately 7 days.

In the case of daily administration of the drug, (R) -enantiomer (due to the long half-life) accumulates within the blood plasma at a 10-fold amount.

A plateau of (R) -enantiomer indicators of approximately 9 μg / ml is observed after administration of 50 mg of the drug per day. At the stable stage, the predominantly active (R) -enantiomer makes up 99% of the total enantiomers circulating inside the organism.

There is information that in individuals with severe liver disease (R) -enantiomer is excreted from the plasma more slowly.

Biculide has a high rate of protein synthesis (the racemate is 96%, and the (R) enantiomer is> 99%); he also participates in intensive metabolic processes (glucuronization with oxidation). Metabolic components are equally excreted in the bile and urine.

In clinical tests, the mean values of (R) -bikalutamide inside the male sperm (patients took 0.15 g of the drug) were equal to 4.9 µg / ml. The volume of bicalutamide, which theoretically penetrate into the female body during sexual contact, is low and equals approximately 0.3 μg / ml. This indicator is below the level that led to negative consequences for the fetus in animals.

Dosing and administration

Adult men (also elderly) are required to apply orally 50 mg (corresponding to the 1st tablet), 1 time per day.

Reception of Biculide should be started no earlier than 3 days before the start of treatment with analogs of the lutropin releasing factor, or simultaneously with performing surgical castration.

[1]

Use Cut out during pregnancy

Biculide is used to treat the prostate, so it is not indicated for women. 

Contraindications

Among the contraindications:

• the presence of intolerance symptoms in relation to the active element or other auxiliary components that are part of the drug;
• combined use with astemizole, terfenadine or cisapride.

Side effects Cut out

The drug is usually tolerated without the appearance of complications. Only occasionally developing violations demanded the abolition of the drug.

The main side signs are:

Lesions of the lymph and blood system: anemia (this includes its iron-deficient and hypochromic forms);

Immune disorders: angioedema, personal intolerance and urticaria;

Metabolic and nutritional disorders: loss of appetite;

Mental problems: depression, decreased libido and anxiety;

Disorders associated with NA: drowsiness or insomnia, dizziness, paresthesias, and headaches;

Disorders of the work of the cardiovascular system: prolongation of the QT-interval, hot flashes, myocardial infarction (there is evidence of a fatal outcome) ⁴, hypertension and CH ⁴;

Lesions of the sternum, mediastinum and respiratory tract: dyspnea, pharyngitis, ILD (there is evidence of death), pneumonia, increased cough, rhinitis, bronchitis and flu-like syndrome;

Problems with digestive function: vomiting, bloating, pain in the abdominal area, dyspepsia, nausea, diarrhea, and constipation;

Hepatobiliary disorders: liver failure ² (there is information about deaths), hepatotoxicity, increased alkaline phosphatase, jaundice and increased transaminase ¹;

Lesions of the subcutaneous layers and the epidermis: itching, alopecia, dry epidermis, hirsutism or restoration of hair growth, photosensitivity and rashes;

Renal and urinary disorders: infection of the urethra, delay, incontinence, or increased frequency of urination, nocturia, or hematuria;

Problems with the work of the mammary glands and reproductive organs: impotence, gynecomastia and pain affecting the breasts ³;

Systemic manifestations: pain in the sternum area, systemic pain and asthenia;

Test data: loss or increase in weight;

Endocrine dysfunction: hyperglycemia or diabetes;

Lesions of the musculoskeletal structure: pain arising in the back, pelvis or bones, pathological fractures, arthritis or myasthenia.

¹ hepatic lesions only occasionally have a severe character and often disappear or are weakened with continued therapy or after its cancellation.

² insufficiency of the hepatic function was rarely observed when Biculid was administered, but it was not possible to establish a connection with the use of the drug in this case. Consideration should be given to periodic monitoring of hepatic activity.

³ during castration possible weakening.

⁴ was noted in pharmaco-epidemiological testing of the use of lutropin releasing factor agonists, as well as anti-androgens during the treatment of prostate carcinoma. The risk increases if the drug is used along with agonists of the lutropin releasing factor. When monotherapy with the reception of 0.15 g of Biculide for the treatment of prostate carcinoma, there was no increase in risk.

At the same time, it is necessary to indicate side effects that occurred during clinical testing with the administration of the drug along with an analogue of the lutropin releasing factor, but at the same time, the connection with the drug was not clearly established:

• disorders associated with cardiovascular disease: syncope, angina pectoris, cerebral or coronary blood flow disorder, arrhythmia, bleeding, deep nature thrombophlebitis, atrial fibrillation, cerebral ischemia and bradycardia;
• problems with NA function: neuropathy or confusion;
• disorders of the gastrointestinal tract: dryness that affects the oral mucous membranes, gastrointestinal cancer, melena, periodontal abscess, rectal hemorrhage, dysphagia, gastritis, rectal disease and intestinal blockage;
• lymph and blood lesions: thrombocytopenia or ecchymosis;
• metabolic disorders: an increase in creatinine or blood urea, gout, hypercalcemia or cholesterolemia, dehydration and hypoglycemia;
• problems with musculoskeletal function: myalgia, bone disease and cramps that affect the legs;
• respiratory disorders: sinusitis, voice changes, pulmonary disorders, pleural effusion, or asthma;
• epidermal lesions: skin cancer, herpes zoster, as well as epidermal hypertrophy or skin ulcers;
• disorders of visual work: vision problems, cataracts or conjunctivitis;
• problems with urinary or kidney function: balanitis, hydronephrosis, renal calculus, dysuria, prostate disorders, and bladder stenosis;
• systemic signs: neck pain or stiffness, chills, tumors, hernia, facial swelling, cysts, fever and sepsis.

Overdose

People have no information regarding drug poisoning.

There is no antidote; Symptomatic treatment procedures are performed. Dialysis will not have an effect, because the drug is significantly synthesized with protein, without being detected inside the urine in an unchanged state. In the case of intoxication, general supportive measures are performed (as well as tracking the work of life-critical systems).

Interactions with other drugs

There is no information confirming the pharmacokinetic or dynamic interaction of the drug and analogues of the lutropin releasing factor.

In vitro tests revealed that R-bicalutamide slows down the effect of CYP 3A4, also having a less pronounced inhibitory effect on CYP 2С9 activity, as well as 2C19 with 2D6.

While clinical testing, during which antipyrine was used as a marker of hemoprotein P450 (CYP) activity, does not show a theoretical interaction with drugs, the average values of midazolam (AUC) increased to 80% when combined with Biculid during the 28-day cycle. For drugs with a narrow pharmaceutical spectrum, such an increase may be important. Therefore, it is not possible to combine the drug with cisapride, astemizole or terfenadine.

At the same time, the drug is very carefully combined with blockers of Ca channel activity and cyclosporins. There may be a need to reduce a portion of these funds, especially if there are symptoms of potentiation of drug activity or when negative signs appear when it is administered. During the reception of cyclosporine, it is necessary to closely monitor its plasma parameters and the clinical condition of the patient (after the start and end of therapy with Biculide).

Caution is required when administering medication with medications that can inhibit the oxidation of products (among them ketoconazole with cimetidine). In theory, this may cause an increase in the Biculide plasma level, potentiating its side effects.

In vitro tests found that the drug is able to displace coumarin anticoagulants (warfarin) from their protein synthesis areas. Because of this, with the introduction of drugs to people already using such anticoagulants, you need to carefully monitor the values of PTV. If necessary, a portion of the anticoagulant change.

The combination of blocking androgens, antiandrogens, as well as an analogue of the lutropin releasing factor with drugs that prolong the values of the QTc interval, can lead to the development of tachycardia ("pirouette" type). This factor should be taken into account when using bicalutamide together with substances theoretically capable of prolonging the QTc interval. Among these drugs (incomplete list):

• antidepressants (nortriptyline with amitriptyline);
• antiarrhythmic substances of subcategory IA (disopyramide with quinidine);
• subcategories III (dofetilide, dronedarone with amiodarone, ibutilide, and sotalol);
• Ic subcategories (propafenone with flecainide);
• antimalarial drugs (quinine);
• antipsychotics (for example, chlorpromazine);
• antagonists of the endings of 5-hydroxytryptamine (ondsetron among them);
• opioids (for example, methadone);
• macrolides with their analogues (clarithromycin with erythromycin and azithromycin), as well as quinolines (for example, moxifloxacin);
• antimycotics from the azole subgroup;
• analogues of β2-adrenoreceptors (for example, salbutamol).

[2], [3]

Storage conditions

Biculide must be kept in a closed place from small children. Temperature indicators - no more than 30 ° C.

Shelf life

Biculide can be used within a 5-year (vials) and 3-year (blisters) term from the time the drug was manufactured.

Application for children

There is no evidence regarding the therapeutic efficacy and safety of bicalutamide (non-steroidal antiandrogen) administered to children. Because of this, Biculide is not used in pediatrics.

Analogs

Analogs of drugs are the substances Casodex, Flutamide, Areklok, Flutazine with Kalumid, and in addition to this Bicalutamide-Teva, Xgandi and Flutafarm.