Lutarun 50 – Barter & Marcin Pharma

Lutarun

Description

Bicalutamide tablets for oral administration contain 50 mg of bicalutamide, a nonsteroidal antiandrogen with no other known endocrine activity. The chemical name is propanamide, N-[4-cyano-3-(trifluoromethy1)pheny1]-3-[4-fluoropheny1)sulfony1]-2-hydroxy-2-methy1-,(+-). Bicalutamide molecular formula is C18H14N2O4F4S.

Bicalutamide is a racemate with its antiandrogenic activity being almost exclusively exhibited by the R-enantiomer of bicalutamide; the S-enantiomer is essentially inactive.

Pharmacology

Mechanism Of Action

Bicalutamide is a non-steroidal antiandrogen. It competitively inhibits the action of androgens by binding to cytosol androgen receptors in the target tissue. Prostatic carcinoma is known to be androgen sensitive and responds to treatment that counteracts the effect of androgen and/or removes the source of androgen.

Pharmacokinetics

Absorption

Bicalutamide is well-absorbed following oral administration, although the absolute bioavailability is unknown. Co-administration of bicalutamide with food has no clinically significant effect on the rate or extent of absorption.

Distribution

Bicalutamide is highly protein-bound (96%).

Metabolism and Excretion

Bicalutamide undergoes stereo specific metabolism. The S (inactive) isomer is metabolized primarily by glucuronidation. The R (active) isomer also undergoes glucuronidation but is predominantly oxidized to an inactive metabolite followed by glucuronidation. Both the parent and metabolite glucuronides are eliminated in the urine and feces. The S-enantiomer is rapidly cleared relative to the R-enantiomer, with the R-enantiomer accounting for about 99% of total steady-state plasma levels.

Indications

Bicalutamide is indicated for use in combination therapy with a luteinizing hormone-releasing hormone (LHRH) analogue for the treatment of Stage D2 metastatic carcinoma of the prostate.

Contraindications

Bicalutamide is contraindicated in any patient who shown a hypersensitivity reaction to the drug or any of the tablet’s components.
Bicalutamide is not indicated in women. Further, Bicalutamide is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient become pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Bicalutamide may cause fetal harm when administered to pregnant women.

Dosage & Administration

The recommended dose for Bicalutamide therapy in combination with LHRH analogue is one 50 mg tablet once daily (morning or evening), with or without food, It is recommended that Bicalutamide be taken at the same time each day. Treatment with Bicalutamide should started at the same time as treatment with an LHRH analogue.

Dosage Adjustment in Renal Impairment

No dosage adjustment is necessary for patients with renal impairment.

Dosage Adjustment in Hepatic Impairment

No dosage adjustment is necessary for patients with mild to moderate hepatic impairment. Although there is a 76% (5.9 and 10.4 days for normal and impaired patients respectively) increase in the half-life of the active enantiomer of bicalutamide in patients with severe liver impairment (m=4), no dosage adjustment is necessary.

Precautions (General)

Bicalutamide should be used with caution in patients with moderate-to-severe hepatic impairment. Bicalutamide is extensively metabolized by the liver. Limited data in subjects with severe hepatic impairment suggest that excretion of Bicalutamide may be delayed and could lead to further accumulation. Periodic liver function tests should be considered for patients on long-term therapy.
In clinical trials with Bicalutamide as a single agent for prostate cancer, gynecomastia and breast pain have been reported in up to 38% and 39% of patients, respectively.
Regular assessments of serum prostate Specific Antigen (PSA) may be helful in monitoring the patient’s response. If PSA levels rise during Bicalutamide therapy, the patient should be evaluated for clinical progression. For patients who have objective progression of disease together with an elevated PSA, a treatment-free period of antiandrogen, while continuing the LHRH analogue, may be considered.
Since transaminase abnormalities and, rarely, jaundice have been reported with the use of Bicalutamide, periodic liver function tests should be considered. If clinically indicated, e.g.. When the patient has jaundice or laboratory evidence of liver injury in the absence of liver merastases, Bicalutamide therapy should be discontinued. If transaminases increase over 2 times the upper limit of normal, treatment should be discontinued. Abnormalities are usually reversible upon discontinuation.

Pregnancy: Pregnancy Category X

Nursing Mothers: Bicalutamide is not indicated for use in women. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Bicalutamide is administered to a nursing woman.
Paediatric Use: Safety and effectiveness of Bicalutamide in pediatric patients have not been established.

Patient Information

Patients should be informed that therapy with Bicalutamide and the LHRH analogue should be initiated concomitantly, and that they should not interrupt or stop taking these medications without consulting their physician. Treatment with Bicalutamide should be started at the same time as treatment with an LHRH analogue.

Drug Interaction

In vitro studies have shown that Bicalutamide can displace coumarin anticoagulants, such as warfarin, from their protein-binding sites. It is recommended that if Bicalutamide is started in patients already receiving coumarin anticoagulants, prothrombin times should be closely monitored, and adjustment of the anticoagulant dose may be necessary.

Adverse Reactions

In patients with advanced prostate cancer treated with Bicalutamide in combination with an LHRH analogue, the most frequent adverse experience was hot flashes (53%). Other adverse effects are pain (General), Back Pain, Asthenia, Constipation and Nausea.

Overdosage

There is no specific antidote; treatment of an overdose should be symptomatic. In the management of an overdose with Bicalutamide, vomiting may be induced if the patient is alert. It should be remembered that, in this patient population, multiple drugs may have been taken. Dialysis is not likely to be helpful since Bicalutamide is highly protein bound and is extensively metabolized. General supportive care, including frequent monitoring of vital signs and close observation of the patient, is indicated.