Tarceva

Active material: Erlotiniʙ
When ATH: L01XX34
CCF: Anticancer drug. An inhibitor of protein tyrosine kinase
ICD-10 codes (testimony): C25, C34
When CSF: 22.06
Manufacturer: F.Hoffmann-La Roche Ltd. (Switzerland)

Pharmaceutical form, composition and packaging

Pills, coated white or white with a yellowish tint, round, lenticular, inscribed on the surface “TARCEVA 25” orange color and logo.

Excipients: lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, sodium lauryl, magnesium stearate.

The composition of the shell: Opadry White Y-5-7068 (gipromelloza, hydroksypropyltsellyuloza, polyethylene glycol, Titanium dioxide (E171)).

10 PC. – blisters (3) – packs cardboard.

Pills, coated white or white with a yellowish tint, round, lenticular, inscribed on the surface “TARCEVA 100” gray and logo.

Excipients: lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, sodium lauryl, magnesium stearate.

The composition of the shell: Opadry White Y-5-7068 (gipromelloza, hydroksypropyltsellyuloza, polyethylene glycol, Titanium dioxide (E171)).

10 PC. – blisters (3) – packs cardboard.

Pills, coated white or white with a yellowish tint, round, lenticular, inscribed on the surface “TARCEVA 150” brown color and logo.

Excipients: lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, sodium lauryl, magnesium stearate.

The composition of the shell: Opadry White Y-5-7068 (gipromelloza, hydroksypropyltsellyuloza, polyethylene glycol, Titanium dioxide (E171)).

10 PC. – blisters (3) – packs cardboard.

Pharmacological action

Anticancer drug. Receptor tyrosine kinase inhibitor of epidermal growth factor HER1 / EGFR (HER1 – epidermal growth factor receptor of human 1 type, EGFR – epidermal growth factor receptor).

Tyrosine kinase is responsible for the intracellular phosphorylation of HER1 / EGFR. The expression of HER1 / EGFR is observed on the surface of both normal, and tumor cells. Inhibition of EGFR phosphotyrosine inhibits the growth of tumor cell lines and / or leads to their death.

Pharmacokinetics

Absorption

Erlotinib is well absorbed after oral administration. C_max Plasma is 1.995 ng / ml achieved after 4 no. Bioavailability of erlotinib – 59%, meal may increase the bioavailability.

Distribution

C_ss achieved at 7-8 day. Before taking the next dose average C_min erlotinib plasma 1.238 ng / ml. Mezhdozovogo AUC in the range when the C_ss – 41.3 mcg x h / ml.

In Кажущийся_d – 232 n distribution in the tumor tissue. In tumor tissue samples (lung cancer, cancer of the larynx) on 9 daily average concentration of erlotinib treatment is 1.185 ng / g, what is 63% from C_max in plasma at steady state. The concentration of the main active metabolite in tumor tissue is 160 ng / g, corresponding 113% C_max in plasma at steady state. C_max in tissue is about 73% plasma concentration, the time to reach C_max in tissue – 1 no. Plasma protein binding (albumin and acid α₁-glycoprotein) – 95%.

Metabolism

Erlotinib is metabolised in the liver with the participation of CYP3A4, to a lesser extent lung and CYP1A2 isoform CYP1A1. In vitro 80-95% erlotinib is metabolized by CYP3A4,. Metabolism occurs in three ways: 1) O-dimethylation one or both of the side chains followed by oxidation to carboxylic acid; 2) oxidation of the acetylene moiety followed by hydrolysis to the aryl carboxylic acids; and 3) aromatic hydroxylation phenyl-acetylene moiety. The main metabolites formed as a result of O-dimethylation one of the side chains and have activity, comparable with erlotinib. They are present in plasma concentrations, which constitute <10% concentrations of erlotinib, gee pharmacokinetics similar pharmacokinetics эrlotiniba.

Deduction

Average clearance – 4.47 l /. There was no relationship between age and clearance, body weight, sex, the patient's race. Average T_1/2 is 36.2 no. Metabolites and trace amounts derived erlotinib, predominantly, with stool (>90%), with a small amount of urine output of the administered dose.

Reduced clearance erlotinib observed with increasing concentration of total bilirubin and acid α₁-glycoproteins, a increase of its – smokers.

Pharmacokinetics in special clinical situations

Specific studies in children and elderly patients have not been conducted.

There is currently no data on the impact of the presence of metastases in the liver and / or hepatic dysfunction on the pharmacokinetics of erlotinib.

Erlotinib is metabolized and excreted through the liver. Erlotinib and its metabolites are excreted by the kidneys in small amounts – less 9% single dose. Clinical studies in patients with renal impairment have not been conducted.

Testimony

- Locally advanced or metastatic non-small cell lung cancer after failure of one or more chemotherapy regimens;

- Locally advanced unresectable or metastatic pancreatic cancer as first-line therapy in combination with gemcitabine.

Dosage regimen

The drug is taken orally, 1 time / day, no less, than 1 hours before or after 2 h postprandial.

At small cell lung cancer the drug is prescribed for 150 mg daily, protractedly.

At pancreatic cancer – by 100 mg daily, long, in combination with gemcitabine.

If signs of disease progression Tarceva therapy should be discontinued.

Precautions should be prescribed Tarceva patients impaired liver function. Safety and efficacy of Tarceva in patients with hepatic impairment have not been studied.

Safety and efficacy of Tarceva in patients with impaired renal function We have not been studied.

Safety and efficacy of Tarceva in patients Up to 18 years We have not been studied.

If necessary, dose adjustment is recommended to be reduced gradually, each time for 50 mg.

Side effect

The most frequent adverse events regardless of causality with the drug: rash (69-75%) and diarrhea (48-54%), most of which 1 and 2 severity and require no. Rash and diarrhea 3-4 severity observed in 9% and 6% patients with small cell lung cancer and 5% pancreatic cancer, receiving Tarceva. Each of these phenomena has demanded termination of therapy 1% patients and correction of the dose of erlotinib in 1-6% patients. The average period before the rash – 8-10 days, before diarrhea – 12-15 days.

Adverse reactions were distributed in frequency as follows: Often (≥10%); often (≥1%, <10%); infrequently (≥0.001%, <1%); rarely (≥0.0001, <0.001%); rarely (<0.0001%, including individual cases).

Adverse Reactions, observed in patients, receiving Tarceva 150 mg as monotherapy and Tarceva 100 mg 150 mg in combination with gemcitabine:

From the digestive system: Often – anorexia, diarrhea, vomiting, stomatitis, dyspepsia, stomach ache; often – gastrointestinal bleeding (some of which were associated with the concurrent use of NSAIDs or warfarin), abnormal liver function (including increased ALT, IS, bilirubin), primarily, transitory, mild or moderate or associated with liver metastases.

On the part of the organ of vision: Often – conjunctivitis, keratoconjunctivitis sicca; often – keratit, identified in the case of transition corneal ulcer.

The respiratory system: Often – cough, breathlessness; often – nose bleed; infrequently – interstitial lung disease (interstitial pneumonia, obliterating bronchiolitis, fibrosis lyegkikh, acute respiratory distress syndrome and pulmonary infiltration, including cases with fatal outcome).

From the central and peripheral nervous system: Often – headache, Neuropathy, depression.

Dermatological reactions: Often – rash, alopecia, xerosis, itch.

Other: Often – fever, fatigue, chills, severe infections (with or without neutropenia), pneumonia, sepsis, fibrous cellulitis, weight loss.

Contraindications

- Pregnancy;

- Lactation (breast-feeding);

- Hypersensitivity to erlotinib or to any component of the drug.

FROM caution should be prescribed with abnormal liver function, patients aged 18 years.

Pregnancy and lactation

Use of the drug Tarceva is contraindicated in pregnancy and lactation.

During treatment with Tarceva and, least, within 2 weeks after it should use reliable methods of contraception.

Cautions

Interstitial lung disease (OUT), ILD including fatal, rarely diagnosed in patients with small cell lung cancer, pancreatic cancer or other solid tumors, receiving Tarceva. In patients with small cell lung cancer, Tarceva or placebo, the frequency of serious ILD was 0.8% in each group. The incidence of ILD patients with pancreatic cancer, receiving Tarceva and gemcitabine, made 2.5% compared with 0.4% in Group, treated with gemcitabine and placebo. The overall incidence of ILD in patients, receiving Tarceva, including use in combination with chemotherapy, is 0.6%. ILD includes interstitial pneumonia, obliterating bronchiolitis, fibrosis lyegkikh, acute respiratory distress syndrome and pulmonary infiltration. Most cases of ILD was associated with receiving concomitant chemotherapy or previously conducted, radiation therapy, parenchymal lung disease in history, or metastatic lung infection. With the development of new and / or progression of pulmonary symptoms (breathlessness, cough and fever) receiving Tarceva must temporarily stop to determine the cause. In case you want to cancel the development of ILD Tarceva and conduct the necessary treatment.

In the event of severe or mild diarrhea to assign loperamide. In some cases, it may require dose reduction of Tarceva. In severe diarrhea, or Sustainable, toshnote, anorexia, or vomiting with dehydration Tarceva temporarily cancel and spend rehydration.

Use in Pediatrics

Safety and efficacy of Tarceva in patients aged 18 years We have not been studied.

Overdose

Single doses up to erlotinib 1600 mg orally well tolerated. When receiving erlotinib at a dose higher than the recommended may experience heavy adverse events: diarrhea, skin rashes, occasionally elevated liver transaminases.

In case of suspected overdose, treatment is suspended and symptomatic therapy.

Drug Interactions

Inhibitors of CYP3A4 (ketoconazole) reduce erlotinib metabolism and increase its concentration in plasma. Inhibition of CYP3A4 metabolism under the effect of ketoconazole (200 mg orally 2 times / day for 5 days) It leads to an increase in AUC on erlotinib 86% and C_max on 69%. Care should be taken when using Tarceva in combination with inhibitors of CYP3A4. In the case of toxicity is necessary to reduce the dose of Tarceva.

Индукторы изофермента CYP3А4 (rifampicin) metabolism increase erlotinib significantly reduce its concentration in plasma. Induction of metabolism involving CYP3A4 while taking rifampicin (600 mg orally 4 times / day for 7 days) It leads to a decrease in the median erlotinib AUC 69%. The clinical significance of this observation is unclear. If possible, it is necessary to provide an alternative method of treatment without induction of CYP3A4.

With simultaneous use of Tarceva with warfarin and other coumarin derivatives was an increase in INR and bleeding, including gastrointestinal bleeding, some of which have been associated with the administration of warfarin. Patients, taking warfarin or other coumarin derivatives, should regularly monitor the prothrombin time or INR.

Interactions with Tarceva plus gemcitabine were found.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored at a temperature no higher than 30 ° C, out of reach of children. Shelf life – 3 year. The drug should not be used after the expiration date.