Selective inhibitor of tyrosine trenbolone enanthate 200 kinase epidermal growth factor receptor expression is observed in many solid tumors, inhibits tumor growth, metastasis and angiogenesis, and accelerates apoptosis of tumor cells. Inhibits the growth of different human tumor cell lines and enhances the antitumor activity of chemotherapeutic drugs, radiation and hormonal therapy.
Clinical data indicate that has the objective antitumor effect, a statistically significantly increase the time to disease progression in patients with locally advanced or metastatic non-small cell lung cancer. Phase III INTEREST study showed that , compared with docetaxel, provides a similar overall survival, a more favorable tolerability profile and superior quality of life in previously treated patients with advanced non-small cell lung cancer.
Following oral administration, absorption is relatively slow. The equilibrium concentration is reached after taking 7-10 doses. Regular use of the drug gefitinib 1 time per day leads to an increase in concentration of 2-8 fold compared to a single dose. Maximum plasma concentration of the drug attained within 3-7 hours.Mean absolute bioavailability in patients up to 59%. Food does not affect the bioavailability. With average gastric pH above 5, gefitinib bioavailability is reduced by 47%.
The volume of distribution of gefitinib when the equilibrium concentration is 1400 liters, which indicates extensive tissue distribution of the drug. Communication with plasma proteins (serum albumin and alpha-1 glycoprotein) amounts to approximately 90%.
Gefitinib undergoes oxidative metabolism by CYP3A4 isoenzyme of cytochrome P450.
In vitro studies showed that slightly gefitinib inhibits CYP2D6 enzyme. When assigning gefitinib together with metoprolol (substrate for CYP2D6) resulted in a slight increase (35%) concentrations of metoprolol, which is not clinically significant.
Gefitinib metabolism occurs in three ways: N-metabolism propilmorfolinovoy group, demethylating a methoxy group on the quinazoline portion and oxidative dephosphorylation trenbolone enanthate 200 halogenated phenyl group.
The primary metabolite in the plasma is determined krovi- O desmetilgefitinib which has 14 times less pharmacologically active than gefitinib in relation to cell growth stimulated by epidermal growth factor, making it unlikely that a substantial impact on the clinical activity of gefitinib. The total plasma clearance of gefitinib – about 500 ml / min. The average half-life of 41 hours. The drug is derived mainly from the faeces. The kidneys remove less than 4% of the administered dose.
Relations between the lower level of the equilibrium concentration of the drug and the age, body weight, gender, ethnicity or creatinine clearance is not revealed. Amid daily reception presses 250 mg, the time to reach equilibrium concentration of the total plasma clearance and the equilibrium concentration groups were similar for patients with normal hepatic function and moderate hepatic impairment. Data for 4 patients with severe liver failure due to: liver metastasis suggest that the equilibrium concentration in these patients is similar to that of patients with normal liver function. Features action presses in patients with hepatic impairment due to cirrhosis or hepatitis C has not been studied.
Indications for Use
Locally widespread or metastatic non-small cell lung cancer, refractory to chemotherapy regimens containing platinum derivatives.
: Hypersensitivity to gefitinib or other components of the preparation. Pregnancy and lactation. Children and teens (safety and efficacy in this group of patients not evaluated).
Precautions: idiopathic pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, pneumonia, post-radiation, drug pneumonia (marked by an increased mortality rate from these diseases during treatment with the press); with an increase in activity of “liver” transaminases.
Dosing and Administration
Inside, 250 mg 1 time per day regardless of the meal.
The tablet may also be dissolved in 100 ml of drinking (non-carbonated) water. Others can not use the liquid. For proper tablet dissolution should be lowered in water without kneading, stirring until completely dissolved (approximately 10 minutes) and then the resulting solution to drink. More Pour half a glass of water, washing the walls and enjoy the resulting solution. Iressa solution may also be administered through a naso-gastric tube.
You do not need dose adjustment Iressa depending on patient age, weight, ethnicity, gender, renal function, as well as in moderate and severe hepatic impairment due to liver metastases. Dose adjustment:in patients with poorly cropped diarrhea during treatment or side reactions of the skin can break the short-term treatment (14 days), followed by resumption of treatment iressa 250 mg / day.
The most common side effects observed in more than 20% of the cases, were diarrhea, skin and acne, itching, dry skin. Typically, adverse reactions occur within the first month of the drug and is usually reversible. Approximately 8% of patients had severe adverse reactions (Grade 3-4 toxicity in accordance with the common criteria).
However, only 1% of patients discontinued therapy due to side reactions. Observed adverse reactions are shown below. Determining the frequency of adverse reactions: very trenbolone enanthate 200 common (> 10%); common (> 1 – <10%); uncommon (> 0.1 – <1%); rarely (> 0.01 – <0.1%); very rare (<0.01%).
From the blood coagulation system: often – hematuria and epistaxis; infrequently – anticoagulation and / or an increase in the frequency of bleeding in patients receiving warfarin.
On the part of the digestive system: very often – diarrhea (in some cases – severe), nausea; often – vomiting, anorexia, stomatitis, dehydration, asymptomatic increased activity of “liver” transaminases;rarely – pancreatitis.
From the side of view: often – conjunctivitis, blepharitis; rarely – reversible corneal erosion, disturbance of growth of eyelashes.
From the respiratory system: rarely – interstitial pneumonia (grade 3-4 toxicity, or death).
Skin and skin: very often – rash (pustular), pruritus, dry skin on the background of erythema; often – nail changes, alopecia; very seldom – toxic epidermal necrolysis and erythema multiforme exudative.
Allergic reactions: seldom – angioedema, urticaria
Other: often – fatigue, fever.
Possible symptoms – increase in the frequency and severity of some adverse events, mainly diarrhea and skin rash. Treatment is symptomatic. The antidote is not known.
The interaction with other drugs.
Co-administration of gefitinib and rifampicin (a potent inducer isoenzyme CYP3A4) reduces the mean values ??of “area under curve» (AUC) for gefitinib 83%. Simultaneous administration of gefitinib and itraconazole (an inhibitor of isozyme CYP3A4) leads to an increase of 80% AUC of gefitinib that can be clinically significant because undesirable effects depend on the dose and concentration. Co-administration of gefitinib and products that contribute to a significant and sustained increase in gastric pH, decreased the AUC of gefitinib by 47%.
In a joint application of gefitinib and vinorelbine may trenbolone enanthate 200 increase neutropenic action vinorelbine.
Drugs that induce isoenzyme CYP3A4, can increase the metabolism of gefitinib and reduce the concentration in the blood plasma. Thus, co-administration with drugs gefitinib, isoenzyme inducers of CYP3A4, such as phenytoin, carbamazepine, barbiturates, St. John’s wort tincture may reduce the effectiveness of gefitinib.
Sometimes patients taking Iressa, noted interstitial lung disease, in some cases fatal. With an increase in symptoms such as shortness of breath, cough, fever, use of the drug should be discontinued immediately and surveyed. If the patient has confirmed the presence of interstitial lung disease, receiving press is stopped and the patient following treatment.
Most often develop interstitial lung lesions were observed in Japan (approximately 2% of the cases at 27,000 patients taking Iressa) as compared to other countries (in 0.3% of cases among 39000 patients).
Among the factors that increase the risk of interstitial lung disease have been noted: smoking, severe general condition (PS> 2), normal lung tissue according to CT <50%, the duration of the disease (NSCLC) <6 months, interstitial pneumonia history, older age (> 55 years), concomitant cardiovascular disease.
Against reception Press noted asymptomatic increase in activity of “liver” transaminases, in this connection, it is recommended to periodically assess liver function. In marked increase in transaminases taking the drug should be discontinued.
Patients taking warfarin, you should regularly monitor the prothrombin time.
In case of any symptoms of the eyes or in the development of severe or prolonged diarrhea, nausea, vomiting or anorexia, the patient should seek immediate medical attention.
In the application of Iressa in combination with radiation therapy as first-line therapy in children with glioma brain stem glioma or incompletely removed supratentorial localization reported 4 cases (one fatal) bleeding into the brain. Another case of bleeding in the brain was observed in a child with ependymoma with Iressa monotherapy. In adult patients with NSCLC in the treatment of Iressa such side effects are not fixed in any way.
Men and women of childbearing age during treatment trenbolone enanthate 200 with Iressa and, at least for 3 months after you should use reliable methods of contraception. Because during therapy with Iressa may develop side effects such as the fatigue, nausea and vomiting, you must be careful when driving and busy with other potentially hazardous activities that require high concentration and psychomotor speed reactions.
Patients with rare hereditary conditions such as lactose intolerance, lactase deficiency or malabsorption syndrome Iressa ® should be administered with caution, due to the presence of lactose.
Coated tablets of 250 mg. 10 tablets in a blister of PVC and aluminum. 3 in the blister package of aluminum foil. The package is placed in a cardboard box with the instructions for medical use.
In original packaging at a temperature not higher than 30 ° C, out of reach of children.
Do not use beyond the expiration date printed on the package.