Abiratred Dr. Reddy treat prostate cancer (120 tablets)

Abirateron reduces serum testosterone and other androgen to a lower level of achieved when using a single substance similar to LHRH or removing testicles. These results are due to the selective inhibition of CYP17 enzyme needed for Androgen biosynthesis. Prostate specific antigen (PSA) acts as a biological marker in prostate cancer patients. In a clinical study phase 3 in patients who have failed with chemotherapy with the previous Taxan, 38% of the patient received treated with Abirateron Acetate, compared to 10% of placebo patients, at least one 50% decline in PSA compared to the basic value.

Dynamic pharmacokinetics

After taking Abirateron Acetate, the dynamic of Abirateron and Abirateron Acetate is studied on healthy people, prostate cancer patients with progressive and metastatic metastases and non -cancer objects but liver failure or kidney failure. In Vivo, Abirateron Acetate is rapidly converted into Abirateron, an Androgen biosynthetic inhibitor.

absorb

After taking Abirateron Acetate in hunger, the time to reach the highest Abirateron concentration in plasma is about 2 hours.

The use of Abirateron Acetate along with food, compared to the use of anger, increases 10 times the AUC and increases to 17 times cmax, increases the average contact of the body with Abirateron, depending on the amount of fat of the meal. With the reward changes of meal composition, using Abirateron along with food capable of making high -rise exposure. Therefore, do not use Abirateron with food. Should take the medicine for at least 2 hours after eating and not eat at least 1 hour after taking the medicine. The pills are swallowed in the whole tablet with water.

distribution

The cohesion with the plasma protein of 14C-Birateron in human plasma is 99.8%. Integral.

transformation

After taking 14C-Abirateron acetate hard capsules, Abirateron Acetate is hydrated into Abirateron, this substance undergo metabolism including sulphate, hydroxylation and oxidation mainly in the liver. The majority of radioactive activity during the circulation (about 92%) is found in the form of metabolites of Abirateron. With 15 detected metabolites, including 2 main metabolites: Abirateron Sulphate and N-Oxide Abirateron Sulphate, each present is about 43% of the total radioactive activity.

Elimination

Abirateron average selling time in plasma is about 15 hours based on healthy research data. After drinking 14C-Abirateron acetate 1000 mg, about 88% of the dose of radioactive activity is found in the section and about 5% in the urine. Most of the compounds found in feces in feces are Abirateron Acetate and Abirateron in unchanged forms (equivalent to about 55% and 22% dose).

Patients with liver failure

In another test, Abirateron's pharmacokinetics are surveyed on people with a history of severe liver failure (n = 8) (C-Pough C) and on healthy people with normal liver function. The contact of the body (AUC) with Abirateron increases by about 600% and the free 80% increase in people with severe liver failure for people with normal liver function.

Do not adjust the dose in patients with a history of mild liver failure. The use of Abirateron should be carefully evaluated in medium liver failure patients, who are whose benefits are clearer than the risk. Abirateron should not be used for severe liver failure.

For patients developing toxicity in the liver during treatment, the dose stop and adjustment may require dosage.

Patients with renal failure

The following level 3 adverse adverse reactions (version 3.0) have occurred in patients treated with Abirateron Acetate: 3%hypoglycemia; Urinary tract infections, hyperlemen aminotransferase, hypertension, increased aspartate aminotransferase, 2% fracture, peripheral edema, heart failure and atrial fibrillation 1% per type. Increasing blood triglycerides and acute angina according to CTCAE (version 3.0) occurs on

Notify the physician the unwanted effects when using the drug.

Be cautious when using

Hypertension, hypokalemia, water retention and heart failure related to excessive increase in mineralcorticoid

Abirateron can cause hypertension, hypotension and water retention as a result of increased mineralocorticoid concentration from CYP17 inhibition. Used in combination with a corticosteroid will prevent the secretion of adrenocorticotropic hormones (ACTH), leading to reduced effects and worsen these adverse reactions. Be careful when treating patients whose medical problems may be dangerous by hypertension, hypokalemia (for example, glycoside support medication), or water retention (for example, patients with heart failure), severe or non -recovery of angina, close myocardial infarction or ventricular arrhyths and patients with severe renal insufficiency.

Abirateron should be used carefully in patients with cardiovascular problems. Phase 3 studies have been conducted with Abirateron eliminating non -controlled hypertension patients, obvious sieve heart disease with evidence of myocardial infarction, or arterial thrombosis in the previous 6 months, intense angina and non -recovery, or level III or IV heart failure according to the New York NYHA cardiovascular Association (301) or a level of heart failure from II to II (302), or measurement of blood pressure. In study 302, patients with atrial fibrillation, or arrhythmia need to be excluded. Safety in patients with the total sample of the left belt (LVEF) toxicity on the liver and liver failure

Increasing enzymgans leading to the discontinuation of the dose treatment or adjustment must have controlled clinical studies. Serum transaminase concentration should be measured before starting treatment, every 2 weeks in the first 3 months and monthly. If clinical symptoms or signs of suggesting liver toxicity develop, Transaminase levels must be measured immediately. If at any time, ALT or AST increases over 5 times the upper limit of the normal level, the treatment must be used immediately and closely monitor the liver function. Treatment load with reduced dose may occur only when the liver function tests return to the basic value of the patient.

If the patient develops a severe liver toxicity (ALT or AST 20 times higher than the upper limit of normal levels) whenever during treatment, stop treatment and no re -treatment. Patients with viral hepatitis or symptoms are excluded from clinical trials, so there is no data that supports the use of Abirateron in this group.

There is no safe and clinical data on the use of Abirateron Acetate doses when treating patients with medium and severe liver impairments (acid-pgh or c). The use of Abirateron should be carefully evaluated in medium liver failure patients, who are whose benefits are clearer than the risk. Abirateron should not be used for severe liver failure.

There are rare reports after bringing the drug to the market for acute hepatic and acute hepatitis, some deaths.

Corticosteroid stops and stress scope

Recommendations should be cautious and monitor adrenal shells may occur if the patient stops using Prednison or Prenisolon. If Abirateron is continued to be used after corticosteroids, patients should be monitored with symptoms due to excessive mineralcorticoid increase.

In patients with Prednison or Prenisolon subject to abnormal stress, corticosteroid increasing dose may have been specified earlier, while or after stress.

A decrease in bone density may occur on prostate cancer people (prostate cancer resistant to male sex hormone removal therapy). The use of Abirateron in combination with glucocorticoid may increase this side effect.

The use of ketoconazole earlier

Lowering speed may be expected in patients who have been treated in advance with ketoconazole for prostate cancer.

Hyperglycemia

Using glucocorticoid may increase blood sugar, so blood sugar should be measured regularly in diabetes patients.

Use with chemotherapy

Safety and effectiveness of Abirateron use simultaneously with non -established cytotoxic chemotherapy.

Potential risks

Anemia and sexual dysfunction can occur in men of prostate cancer that is meticulously resistant to the male sex hormone removal therapy is being treated with Abirateron.

Surgery effects

Bone muscle cases have been reported in patients treated with Abirateron. Some patients have rhabdomyolysis (Rhabdomyolysis) with kidney failure. Most cases developed in the first month of treatment and re -treatment after stopping Abirateron. It is recommended to be careful in patients treated in combination with drugs that are known to be related to muscle globin muscle disease.

Interaction with other drugs

Avoid using strong induction drugs with CYP3A4 during treatment except no other treatment options, due to the risk of reducing exposure to Abirateron.

The effect of drugs on driving and operating machinery

Abirateron does not affect or negligible on the ability to drive and operate machinery.

Using drugs for women during pregnancy and lactation

Women of reproductive age

There is no human data for Abirateron use during pregnancy and this drug is not used for women of reproductive age.

contraceptive contraception on men and women

It is unknown about Abirateron or its metabolic product is present in semen. Need to use condoms if the patient has sexual activity with pregnant women. If the patient has sexual activity with women of reproductive age, the condom should be used in combination with effective contraception. Animal research shows reproductive toxicity.

pregnancy

Abirateron is not used for women and contraindicated for pregnant women or may be able to get pregnant.

breastfeeding

Abirateron is not for women

Reproduction

Abirateron has an influence on the fertility of male and female mice, but these effects are not completely reversible.

Drug interaction

The effect of food

The use of drugs and food significantly increases the absorption of Abirateron Acetate. Effective and safe when used with food that has not been established so this drug is not used with food.

interact with other drugs

Potential effects on other drugs on Abirateron

In a clinical pharmacokinetic interaction study on healthy subjects that were previously treated with strong CYP3A4 induction Rifampicin, 600 mg/day for 6 days, then taking a single dose of Abirateron Acetate 1000 mg, AUC∞ plasma of Abirateron has dropped by 55%.

Avoid using strong CYP3A4 induction drugs (such as Phenytoin, Carbamazepin, Rifampicin, Rifabutin, Rifapentin, Phenobarbital, St John's World [Hypericum Perforatum]) During treatment, except no other treatment options.

In a separate clinical interactive study on healthy subjects, in combination with Ketoconazole, a strong CYP3A4 inhibitor, does not show clinical impact on pharmacokinetics of Abirateron.

Potentially influenced other drugs

Abirateron is an inhibitor of drug metabolic enzymes in CYP2D6 and CYP2C8 liver. In a study to determine the effect of Abirateron Acetate (combined with Prednison) on the single dose of a CYP2D6 substrate, Dextromethorphan, the AUC of Dextromethorphan has increased to about 2.9 times. AUC24 for dextrorphan, a metabolic substance with the activity of dextromethorphan, increased to about 33%.

recommendations should be cautious when used with active or metabolized drugs by CYP2D6, especially with drugs with narrow treatment (Therapeutic Index). The dose of drugs should be considered for narrowed treatment indicators metabolized by CYP2D6. For example, drugs metabolized by CYP2D6 include Metoprolol, Propranolol, Desipramin, Venlafaxin, Haloperidol, Risperidon, Propafenon, Flecainid, Codeine, Oxycodon and Tramadol (the following 3 drugs also need CYP2D6 to create painful metabolites).

In a drug interaction test-CYP2C8 on healthy objects, Pioglitazon's AUC has increased by 46% and AUCs for M-III and M-IV, which are the activated metabolites of Pioglitazon, each AUC increases 10% when Pioglitazon is used with an Abirateron Acetat 1000mg single dose. Although these results show that no clinical contact is expected when Abirateron combines with drugs excreted mainly by CYP2C8, patients should still be monitored toxicity signs related to CYP2C8 substrate with narrow treatment index if used simultaneously.

In vitro, the main metabolites of Abirateron Sulphat and N-Oxide Abirateron Sulphat manifest that it prevents the absorption agent of OATP1B1 liver and as a consequence, it can cause the concentration of drugs excreted by OATP1B1. There is no clinical data available to confirm the transportation based on interaction.

Use along with the drugs that are known to extend the QT range

Because the treatment of eliminating androgen can extend the QT range, it is recommended to be careful when using Abirateron along with the known drugs that extend the QT or drugs that can cause IA level torsion (such as Quinidin, Disopyramid) or level III (such as Amiodaron, Sotalol, Dofetilid, IButilid) Methadon, moxifloxacin, antipsychotics, ...

Use with Spironolacton

Spironolacton is linked to Androgen receptors and may increase the prostate -specific antigen level (PSA). Use with Abirateron is not recommended.