Iressa
Iressa: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Iressa
ATX code: L01XE02
Active ingredient: gefitinib (Gefitinib)
Manufacturer: AstraZeneca Yu-Kay, Ltd. (AstraZeneca UK, Ltd.) (UK)
Description and photo updated: 30.11.2018
Prices in pharmacies: from 73,000 rubles.
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Iressa is an antineoplastic drug.
Release form and composition
The drug is produced in the form of film-coated tablets: biconvex, round, brown, engraved on one side with "IRESSA" and "250"; the core at the break of the tablet is white (10 pcs. in a blister, in a bag of aluminum foil 3 blisters, in a cardboard box with first opening control 1 bag and instructions for use of Iressa).
Composition of 1 film-coated tablet:
- active substance: gefitinib - 250 mg;
- additional components: croscarmellose sodium, lactose monohydrate, povidone (K29-32), sodium lauryl sulfate, microcrystalline cellulose, magnesium stearate;
- film shell: macrogol 300, hypromellose, titanium dioxide (E171), iron oxide yellow (E172) and iron oxide red (E172).
Pharmacological properties
Pharmacodynamics
Gefitinib is an antineoplastic agent related to selective inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase, the expression of which has been found in many solid tumors. The active substance slows down tumor growth, its angiogenesis and metastasis, and also initiates the death of cancer cells. It inhibits the development of different lines of cancer cells in humans and enhances the antitumor effect of chemotherapeutic agents, as well as radiation and hormonal therapy. According to clinical data, Iressa exhibits an objective antitumor effect, increases the period until progression of non-small cell lung cancer (NSCLC) in patients with metastatic or locally advanced form of this disease.
Gefitinib, when compared with docetaxel, shows similar overall survival rates, a better tolerance profile, and a better quality of life in previously treated patients with advanced NSCLC. Clinical characteristics such as the established morphological variation of adenocarcinoma tumor, no smoking history, female sex, and Asian race are associated with a high frequency of tumor EGFR mutations and are predictive factors for effective drug therapy.
Conducted studies of the efficacy of Iressa and the combination of carboplatin and paclitaxel in the first line of therapy for advanced NSCLC (stage IIIB / IV) in representatives of the Asian race who do not have a history of smokers (who quit smoking more than 15 years ago and smoked less than 10 packs per year), with histological type adenocarcinoma tumors demonstrated statistically significant advantages of gefitinib in terms of symptom-free survival and objective response both in the entire group and in the group of patients with the identified EGFR mutation.
There was no statistically significant difference in overall survival between the gefitinib group and the carboplatin + paclitaxel group.
In the presence of frequently noted EGFR mutations (deletions in exon 19; L858R), gefitinib sensitivity has been convincingly demonstrated in clinical trials. Some data have been reported on the response to gefitinib therapy in the presence of less common mutations. Revealed sensitivity to the active substance with rare mutations L861Q, G719X and S7681, but with isolated insertions of exon 20 or isolated mutation T790M, resistance to the drug was found.
Pharmacokinetics
After oral administration of Iressa, there is a rather slow absorption of gefitinib. The maximum concentration (C max) of the substance in the plasma is observed after 3–7 hours. The average absolute bioavailability is 59%. The bioavailability of the drug does not depend on the time of food intake and decreases by 47% when the pH of the gastric juice is more than 5. Against the background of regular use of the drug once a day, the concentration increases 2–8 times compared with a single dose.
The equilibrium concentration (C ss) is determined after taking 7-10 doses. When C ss is reached, the volume of distribution of gefitinib (V d) is 1400 l, which is evidence of the extensive distribution of the substance in the tissues. With plasma proteins (α 1 -glycoprotein and serum albumin), the agent binds to almost 90%.
The CYP3A4 isoenzyme of the cytochrome P 450 system bears the greatest responsibility for the oxidative metabolism of gefitinib. The metabolic transformation of a substance proceeds through the transformation of the N-propylmorpholine group, demethylation of the methoxyl group, and oxidative dephosphorylation of the halogenated phenyl group. Based on in vitro studies, it has been established that gefitinib is able to slightly inhibit the CYP2D6 enzyme. Taking gefitinib in combination with metoprolol, which is a substrate for CYP2D6, resulted in a slight increase in metoprolol concentration (by 35%), which is not clinically significant.
The main metabolite of gefitinib, O-desmethylgefitinib, detected in blood plasma, exhibits 14 times lower pharmacological activity compared to that of the main substance in relation to cell growth, activated by epidermal growth factor. As a result, it is assumed that a significant contribution of O-desmethylgefitinib to the clinical activity of gefitinib is unlikely. The total plasma clearance of the active substance is approximately 500 ml / min, the half-life (T ½) is an average of 41 hours. The drug is excreted mainly in the feces, less than 4% of the dose taken - in the urine.
No association was found between body weight, age, sex, ethnicity, or creatinine clearance (CC) and the lower C ss level of the drug.
In the case of daily use of Iressa at a dose of 250 mg, the period of reaching C ss, total plasma clearance and C ss values were similar for groups of patients with normal liver function and moderate hepatic insufficiency.
Data on 4 patients with severely impaired liver function due to liver metastases indicate that C ss agents in these patients are similar to those in those with normal liver function.
Indications for use
- metastatic or locally advanced form of NSCLC with activating mutations of the EGFR tyrosine kinase domain in the first line of therapy;
- a metastatic or locally advanced form of NSCLC refractory to chemotherapy regimens containing platinum preparations.
Contraindications
Absolute:
- age up to 18 years;
- pregnancy and lactation;
- hypersensitivity to any of the constituents of the drug.
Relative (it is required to use Iressa tablets with extreme caution due to the marked increased mortality rate from these diseases during drug therapy):
- interstitial pneumonia;
- idiopathic pulmonary fibrosis;
- post-radiation pneumonia;
- pneumoconiosis;
- drug pneumonia.
You should also take Iressa with caution in case of a slight / moderate increase in the concentration of bilirubin and the activity of hepatic transaminases.
Iressa, instructions for use: method and dosage
Iressa tablets are taken orally, regardless of food intake, 1 time per day, 1 pc. (250 mg).
If the patient has forgotten to take the next dose, it should be used only if the period before taking the next dose is at least 12 hours. In order to compensate for the missed dose, you should not take a double dose of the drug.
Before taking, you can dissolve the tablet in 100 ml (½ glass) of drinking still water; other liquids cannot be used for this purpose. The tablet should be immersed in water without crushing and stirring for about 15 minutes until it is completely dissolved. The prepared solution must be drunk immediately, and then pour another ½ glass of water, rinsing the walls, and also immediately drink the resulting suspension. Administration of the solution through a nasogastric tube is allowed.
In the presence of undesirable effects on the part of the skin or diarrhea that is difficult to treat, you can stop taking Iressa, and then resume it no later than 14 days later at a daily dose of 250 mg.
Side effects
As a rule, the undesirable effects that occurred during the use of Iressa were observed during the first month of the course of therapy and were reversible. Approximately 10% of patients developed serious impairment (according to general criteria for toxicity grade 3-4). At the same time, only 3% of patients refused to continue treatment with the drug due to the occurrence of side effects. The most common disorders, noted in more than 20% of cases, were dry skin, itching, acne, skin rash, diarrhea.
Adverse reactions from systems and organs (classified as follows: very often - more than 10%, often - more than 1% and less than 10%, infrequently - more than 0.1% and less than 1%, rarely - more than 0.01% and less 0.1%):
- digestive organs: very often - diarrhea (sometimes severe), stomatitis, nausea (mostly mild), vomiting, anorexia, increased activity of alanine aminotransferase (mostly mild / moderate); often - dehydration (as a result of vomiting, diarrhea, anorexia and nausea), dry mouth (mild), increased bilirubin levels, increased aspartate aminotransferase activity (mostly mild / moderate); infrequently - hepatitis (isolated cases of liver failure were recorded, including with a fatal outcome), pancreatitis, perforation of the digestive tract;
- blood coagulation system: often - nosebleeds, hematuria; infrequently - hypocoagulation and / or an increase in the frequency of bleeding with concomitant use of warfarin;
- respiratory organs: often - interstitial pneumonia (3-4 degrees of toxicity, up to death);
- organ of vision: often - blepharitis, conjunctivitis, xerophthalmia (generally mild); infrequently - impaired growth of eyelashes, reversible corneal erosion, keratitis;
- urinary system: often - an asymptomatic increase in the concentration of creatinine in the blood, cystitis, proteinuria; rarely - hemorrhagic cystitis;
- allergic reactions: infrequently - urticaria, angioedema;
- skin: very often - dry skin (including the appearance of skin cracks against the background of erythema), itching, pustular rash; often - alopecia, nail changes; rarely - bullous skin disorders, including toxic epidermal necrolysis, exudative erythema multiforme, Stevens-Johnson syndrome, cutaneous vasculitis;
- others: very often - asthenia (usually mild); often pyrexia.
Overdose
Possible symptoms of Iressa overdose are an increase in the frequency and severity of some adverse reactions, mainly skin rash and diarrhea. Treatment for these violations is recommended symptomatic, there is no antidote.
special instructions
Before Iressa is prescribed in the first line of therapy for locally advanced or metastatic NSCLC, it is extremely important to establish the presence of an EGFR mutation in the tumor tissue in all patients, since the drug cannot be used instead of chemotherapy in the absence of an EGFR mutation. The choice of a validated and reliable technique that minimizes the risk of both false-negative and false-positive results is of great importance in identifying this mutation.
In some cases, during the period of therapy, the development of interstitial lung lesions was recorded, sometimes with a fatal outcome. If there is an aggravation of the manifestation of symptoms such as fever, shortness of breath, cough, it is required to stop taking the drug and urgently conduct an examination. Upon confirmation of the diagnosis of interstitial pulmonary disease, the use of Iressa is discontinued and the necessary treatment is carried out. Most often, this complication was noted in Japan (on average, 2% of cases in 27,000 patients receiving the drug) compared with other countries (in 0.3% of cases among 39,000 patients).
Factors that increase the risk of interstitial lung damage include: the presence of less than 50% of normal lung tissue (according to computed tomography), smoking, a severe general condition, a history of interstitial pneumonia, duration of NSCLC less than 6 months, age over 55 years, concomitant cardiac diseases.
Patients receiving warfarin require regular monitoring of prothrombin time.
In the event of severe / prolonged diarrhea, vomiting, nausea or anorexia, or any visual impairment, the patient should immediately seek medical advice.
During the therapy period, isolated cases of gastrointestinal perforation were recorded, usually with the following risk factors: history of peptic ulcer disease, smoking, advanced age, combined use with non-steroidal anti-inflammatory drugs (NSAIDs), steroids, metastases to the colon at the site of perforation. At the same time, a causal relationship between these phenomena and the use of Iressa has not been established.
Due to the lactose included in the drug, Iressa should be taken with caution in the presence of lactose intolerance, malabsorption syndrome or lactase deficiency.
Influence on the ability to drive vehicles and complex mechanisms
Patients managing complex and potentially dangerous mechanisms (including vehicles) should be careful during the treatment period, since Iressa can provoke the development of undesirable reactions in the form of vomiting, nausea and asthenia.
Application during pregnancy and lactation
Iressa is contraindicated during pregnancy and lactation. Men and women of reproductive age need to use reliable contraception during therapy and for at least 3 months after its completion.
Pediatric use
For patients under 18 years of age, Iressa is contraindicated, since the efficacy and safety of drug therapy in children and adolescents has not been evaluated.
With impaired renal function
There is no need to adjust the doses of Iressa depending on the activity of the kidneys.
For violations of liver function
Patients with moderate / severe hepatic impairment associated with metastatic liver damage do not require individual selection of doses of the drug. Iressa should be used with caution if there is an increase in the activity of hepatic transaminases. In the case of a significant increase in the level of bilirubin and the activity of transaminases, drug treatment should be discontinued.
The features of the action of gefitinib in patients with liver functional impairment as a result of cirrhosis or hepatitis have not been studied. During therapy, it is recommended to periodically assess liver function.
Use in the elderly
Elderly patients do not need Iressa dose adjustment.
Drug interactions
- itraconazole (an inhibitor of the isoenzyme CYP3A4) - the values of the area under the pharmacokinetic curve (AUC) of gefitinib increase by 80%, which can lead to an increase in the severity and frequency of side effects, since the latter depend on the concentration and dose of the agent;
- rifampicin (a powerful inducer of the isoenzyme CYP3A4) - the average AUC of gefitinib may decrease by 83%;
- vinorelbine - there may be an increase in the neutropenic effect of this cytostatic substance;
- drugs that provide a prolonged and significant (≥ 5) increase in the pH of gastric juice, - the AUC of gefitinib decreases by 47%;
- barbiturates, carbamazepine, phenytoin, St. John's wort tincture (drugs that stimulate the activity of the isoenzyme CYP3A4) - metabolism increases, and the plasma concentration of gefitinib decreases, thereby weakening the effect of the latter.
Analogs
Iressa's analogues are Gefitinib, Gefitinib-native.
Terms and conditions of storage
Store out of the reach of children at a temperature not exceeding 30 ° C.
Shelf life is 4 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Iresa
Reviews about Iresa are few, since the drug has a narrow therapeutic effect and a rather high cost. In the available reviews, many patients generally note a positive dynamics of the disease when using Iressa in combination with other drugs. However, quite often they also indicate the development of side effects, such as dry skin, skin rashes, nausea, vomiting, weakness and drowsiness.
Iressa price in pharmacies
The price for Iressa can be 99,500-104,500 rubles. per package containing 30 film-coated tablets.
Iressa: prices in online pharmacies
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Drug name Price Pharmacy |
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Iressa 250 mg film-coated tablets 30 pcs. RUB 73,000 Buy |
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
