Giotrif 30mg Boehringer medicine for lung cancer treatment (4 blisters x 7 tablets)

Dosage form Box of 4 blisters x 7 tablets
Specifications Afatinib

Ingredient

Composition information	Content
Afatinib	30mg

Uses

Indications

Giotrif drug used in single therapy is indicated for treatment of non -small cell lung cancer in the spot or metastases with receptor mutations for epidermal growth factors (EGFR) for adult patients who have not been previously treated with EGFR Tyrosine Kinase.

Pharmacokinatus

Pharmacological treatment group: other anti -cancer drugs - inhibit protein kinase, ATC code: L01xe13.

Mechanism of action

Afatinib is an ErBB inhibitor that has a strong, selective and non -recovery effect. Afatinib binds covalent and inhibited non -recovery signals from Homo - and Heterodimer formed by members of the ERBB group: EGFR (ERBB1), Her2 (ERBB2), ERBB3 and ERB4.

Pharmacological effects

Erbb signal may be triggered by mutations and/or amplifiers of EGFR, amplifier or mutations Her2 and/or increase the expression of Ligand ERBB contributes to creating abnormal characteristics in patients subgroups with many different types of cancer.

In the preclinical pathological models that have lost control of the ERBB route, Afatinib uses a single substance that effectively inhibits the signal transmission of the ERBB receptor that inhibits tumor growth or degrees of tumor. The NSCLC model with L858R or Del 19 EGFR mutations is particularly sensitive when treated with Afatinib. Afatinib maintains a significant tumor resistance in NSCLC in vitro cell lines and in vivo tumor models (transplanted with genetically transferred models) determined by the mutant EGFR -like similarity such as T790M which is determined to be resistant to EGFR inhibitors with Ellotinib and Gefitinib.

pharmacokinetics

absorption and distribution

After taking Giotrif, the maximum concentration (cmax) of Afatinib is observed about 2 to 5 hours after taking the drug. The average average CMAX and AUC0-Avple value increases than the ratio in the afatinib dose range from 20 mg to 50 mg. Afatinib's systemic concentration decreased by 50% (CMAX) and 39% (AUC0-fit), when taken with food rich in fat compared to when drinking hungry. Based on the dynamic dynamic data obtained from clinical trials with different types of tumors, saw AUCτ, S decreased on average 26% when eating within 3 hours before or 1 hour after using Afatinib. Therefore, do not eat for at least 3 hours ago and within 1 hour after taking Afatinib. After using Afatinib, relatively average bioavailability is 92% (the average ratio of the correction of AUC0 -∞) when compared to the oral solution.

In vitro afatinib is connected to protein in human plasma about 95%.

Metabolism and elimination

The metabolic reactions by catalytic enzymes play a negligible role for Afatinib In Vivo. Products that connect covalent with protein are the main metabolites of Afatinib.

After taking 15 mg of Afatinib in the form of solution, 85.4% of the dose is found in feces and 4.3% in urine. The initial Afatinib compound accounts for 88% of the detected dose. The last elimination selling time is 37 hours. The plasma concentration in the stable state of Afatinib is achieved within 8 days after taking multiple doses of Afatinib causing AUC accumulation 2.77 times and CMAX is 2.11 times.

Before taking Giotrif 30mg Boehringer medicine for lung cancer treatment (4 blisters x 7 tablets)

How to use

Giotrif drugs for oral use.

If you cannot take the whole pill, you can mix Giotrif in about 100 ml of carbonate -free drinks. Do not use other solutions. Put the tablet into the water and not be crushed, occasionally stir for 15 minutes until the pill is disintegrated into very small particles and drink immediately. Should rinse with 100 ml of water and drink it afterwards. This solution can be used through the gastric catheter.

Dosage

Small cell lung cancer (NSCLC)

Giotrif dose recommends that 40 mg oral once a day for step one or for patients who have not been treated earlier with EGFR Tyrosine Kinase inhibitors (patients have never used EGFR TKI).

Should be treated with Giotrif continuously until the disease progresses or the patient is no longer tolerated.

Dose increase

It is possible to consider increasing the maximum dose of 50 mg daily in patients who have never used EGFR TKI and tolerated 40 mg daily (i.e. without diarrhea, rash, stomatitis and other drug -related events with a level of> 1 according to CTCAE) for the first 3 weeks. Do not increase the dose in patients who have reduced the previous dose.

In any case, the maximum daily dose is 50 mg.

Adjust the dose due to adverse reactions

The adverse reaction that causes symptoms related to the drug (such as severe/prolonged diarrhea or adverse reactions on the skin) can be well treated by suspension of treatment and reduced giootrif dose.

Information about the dose due to adverse reactions

Adultery events due to ctcaea drugs Load) or level> 3 stopped the drug until the level of 0/1b continues to treat but reduced the dose of 10 mg

B: In the case of diarrhea, should take anti -diarrhea drugs (such as looperamid) and if there is still diarrhea, continue to drink until the stool is over.

c: diarrhea> 48 hours and/or rash> 7 days.

D: If the patient is not tolerated by a dose of 20 mg per day, permanent giotrif should be considered.

Think of interstitial lung disease (ILD) if a patient has acute or deteriorated respiratory symptoms, this case should temporarily suspend Giotrif while waiting for the assessment. If it is diagnosed with iLD, it is advisable to stop giotrif and conduct appropriate treatment.

Patients with renal failure

The observed giotrif concentration is increased in patients with medium or severe renal impairment. It is not necessary to adjust the starting dose in patients with mild renal impairment (EGFR 60 - 89 ml/min/1.73m2), average (EGFR 30 - 59 ml/min/1.73m2) or heavy (EGFR 15 - 29 ml/min/1.73m2). Monitor patients with severe renal impairment (EGFR 15 - 29 ml/min/1.73m2) and adjust the giotrif dose if not tolerated.

Do not recommend giotrif treatment in patients with EGFR

Patients with liver failure:

Giotrif's time concentration does not change significantly in mild hepatic impairment patients (Child Pugh A) or medium (Child Pugh B). There is no need to adjust the starting dose in patients with mild or medium liver failure. Giotrif has not been studied in patients with severe liver failure (Child Pugh C). Do not recommend using Giotrif for this group of patients.

Age, race, gender: No need to adjust the dose according to age, race or gender.

Children:

Giotrif's safety and effectiveness has not been studied in children. Therefore, it is not recommended to use Afatinib for children or adolescents.

Use P-Glycoprotein inhibitors (P-GP):

If you need to use P-GP inhibitors, it is recommended to be staggered with Giotrif, for example, the P-GP inhibitors are the most possible way to the time compared to the Giotrif dose. This means that P-GP inhibitors should be used 6 hours (for P-GP inhibitors twice a day) or 12 hours (for P-GP inhibitors used once a day) compared to Giotrif.

Note: The above dose is for reference only. Specific dosage depends on the condition and level of progression of the disease. For a suitable dose, you need to consult a doctor or medical specialist.

What to do when overdose? The adverse reactions observed when using these doses are mainly skin events (rash/acne) and on the digestive tract (especially diarrhea). Overdose in 2 healthy young people when each person takes 360 mg of Giotrif (is part of the oral mixture), causing adverse adverse reactions related to the drug: nausea, vomiting, weakness, dizziness, headache, abdominal pain and amylase increase (

Treatment: There is no specific antidote when giotrif overdose. In case of overdose, giotrif should be stopped and supported. If indicated, it is possible to eliminate the unused Afatinib by causing vomiting or gastric lavage.

In an emergency, call the 115 emergency center immediately or go to the nearest local health station.

What to do when you forget a dose? However, skip the forgotten dose if the next dose will be taken within 8 hours.

Side Effects

Unwanted effects (ADR) generally related to EGFR inhibitors in Afanitib activity. All unwanted effects are summarized below. The most unwanted effect is diarrhea and adultery events on the skin and stomatitis, inflammation around the nail.

In general, reducing the dose leads to reduced frequency of common side effects.

In patients treated with Giotrif 40 mg once a day, reducing the dose due to unwanted effects occurs in 57% of patients in Lux-Lung 3 clinical trial. Stop drugs due to unwanted effects of diarrhea and acne rashes are 1.3% and 0% in Lux-Lung 3 test.

Reactions like interstitial lung disease are reported in 0.7% of patients treated with Afatinib. There has been a report on the case of water glossy, blistering, scales, including rare cases suggesting Stevens-Johnson syndrome and poisoned epidermal necrosis although these cases may be due to other causes.

Summary of the frequency of unwanted effects from NSCLC tests and from experience used after Giotrif drugs circulate at a dose of 40 mg or 50 mg of monochromatic therapy. The following terms are used to classify unwanted effects by frequency: Very common (≥ 1/10); popular (≥ 1/100 to

Summary of unwanted effects of frequency classification

system 1/1000) Blood Mac Vomiting

indigestion

Pancreatitis

Skin disorders and subcutaneous skin rash 3
Actroccity dermatitis 4
Itching 5
Dry DA6 Mechanical spasms Drugs

Fever Nails. use after circulation.

Describe unwanted effects: Unwanted frequency effects are very common when treating with Giotrif occurring in at least 10% of patients in Lux-Lung 3 clinical trials synthesized according to the criteria of toxicity-National Cancer Institute (NCI-CTC).

Unwanted effects are very popular in Lux-Lung 3 test

NC-CTC

giotrif (40 mg/day)

n = 229

pemetrexed/cisplatin
n = 111 Come on 3 4 coincide with

surround inflammation 1 57,6
11,4

0 0 0 0 mouth 20.5 3,1 0 53.2 2.7 0 CAM 13.1 0 0 0.9 0.9 0

stomatitis 2

lip inflammation

95,2

69,9

12,2

14,4

8.3

0.4

15,3

13.5

0.9

Caviar dermatitis 4

Dry skin

itchy 6

70.3

34,9

29,7

19,2

2.6

0.4

6.3

1.8

0.9

patient evaluation Hail bed inflammation. After circulating the drug.

Abnormalities in liver function test:

The abnormalities in liver function tests (including ALT and AST increases) are observed in patients using Giotrif 40 mg. This increase is largely fleeting and does not lead to stopping the drug. Increase ALT level 2 (> 2.5 to 5.0 times on normal) occurs at less than 8% of patients treated with this drug. Increasing ALT level 3 (> 5.0 to 20.0 times on normal) occurs at less than 4% of patients treated with giotrif.

Warnings

Before using the drug you need to read the instructions carefully and refer to the information below.

contraindicated

Giotrif drugs contraindicated in the following cases:

Contraindicated Giotrif for patients with hypersensitivity to Afatinib or any excipients.

Be cautious when using

evaluate the situation of EGFR mutations

When assessing the condition of EGFR mutations in a patient, it is important to choose an accurate method and have been carefully evaluated to avoid fake or false negative results.

diarrhea

diarrhea, including severe diarrhea, has been reported during treatment with Giotrif. Diarrhea can lead to dehydration or no renal failure, in rare cases that can lead to death. Diarrhea usually appears in the first 2 weeks of treatment. Level 3 diarrhea usually appears in the first 6 weeks of treatment. It is important to proactively treat diarrhea including enough water to combine with anti -diarrhea drugs for the first 6 weeks of treatment and start as soon as there are first signs of diarrhea. Anti -diarrhea should be used (such as Loperamid) and if necessary, the highest recommended dose should be approved. An anti -diarrhea should be available so that patients can be treated when they have the first sign of diarrhea and should be treated continuously until it is gone to a loose stool for 12 hours. Patients with severe diarrhea may need to suspend the drug and reduce the dose or permanently stop treatment with Giotrif. Patients dehydration may need intravenous and electrolyte infusion.

Skin adultery

There has been a report on acne/acne in patients treated with giotrif. In general, the board manifests itself in the form of a light or medium erythema and an acne -like rash that may appear or get worse in areas exposure to the sun. Patients who are exposed to sunlight should be advised to use covered clothes, and/or sunscreen. Early intervention of skin reactions (such as skin softening cream, antibiotics) can facilitate continuous treatment with giotrif.

Patients with prolonged or serious skin reactions may also need to be temporarily stopped, dose, additional treatment, and examination of dermatologists to treat skin effects. There have been reports of water glossy, blistering, flaking, including rare cases suggesting Stevens-Johnson syndrome and poisoned epidermal necrosis. Giotrif should be suspended or permanently stopped permanently if the patient shows signs of water, blistering or severe peeling.

Women's patients, mild weight and renal failure: Observed the concentration of the high time of Afatinib in female patients, mild weight and patients with renal failure. This may increase the risk of adverse events through EGFR intermediaries such as diarrhea, rash/acne and stomatitis. Should closely monitor patients with these risk factors.

Interstitial lung disease (ILD)

There have been ILD reports or ILD -like events (such as pulmonary infection, pneumonia, acute respiratory insufficiency syndrome, allergic alveoli), including deaths in patients using Giotrif to treat NSCLC. ILD -like events related to drugs are reported at 0.7% of more than 3800 patients treated. ILD -like events are ≥3 according to CTCAE, regardless of cause and effect, reported in 1% of patients. No research in patients with a history of ILD. Careful evaluation of all patients with symptoms in the lungs (shortness of breath, cough, fever) manifest acute and/or bad progression for unknown reasons to eliminate iLD. Giotrif treatment should be suspended while waiting to evaluate symptoms. Giotrif should be stopped permanently if diagnosis is ILD and appropriate treatment when needed.

Severe liver failure

Hepatic failure, including death, has been reported during Giotrif treatment at less than 1% of patients. In these patients, jamming factors include liver disease that has existed before and/or diseases that come with the progression of malignant tumors. Liver function should be checked periodically for patients who have had liver disease in advance. Giotrif may be suspended in patients with liver function. Giotrif should be stopped permanently if the patient appears serious liver failure during medication.

Cerematitis

Need to see an eye specialist immediately if there are symptoms of acute or bad inflammation, watery, light sensitivity, blurred vision, eye pain and/or red eye. If diagnosed with corneal ulcers, it is recommended to suspend or permanently stop treatment with giotrif. If diagnosis of keratitis should be careful between the benefits and risks of continuing treatment. Be cautious when using Giotrif for patients with a history of keratitis, corneal ulcers or severe dry eyes. Using contact lenses is also a risk factor for keratitis and ulcer.

Left ventricular function

left ventricular dysfunction is associated with HER2 inhibition. Based on the existing clinical data, there is no suggestion showing that Giotrif has a disadvantageous effect on heart contractions. However, there is no study of Giotrif in patients with abnormal LVEF blood vessels (LVEF) or a history of severe heart disease. In patients with heart risk factors and patients who may affect LVEF, cardiovascular monitoring should be considered, including LVEF evaluation at the beginning and during Giotrif treatment. If the patient appears the signs/symptoms related to the heart during treatment, cardiovascular monitoring includes LVEF reviews. In patients with lower hematoma than the lower limit of the normal level as prescribed, the cardiovascular specialist should be examined as well as the temporary suspension or permanent suspension of giotrif.

Interaction with P-Glycoprotein inhibitors (P-GP)

Using strong P-GP inhibitors before using Giotrif may cause an increase in concentration over time of afatinib and thus use caution. If you need to use P-GP inhibitors, you should use it at the same time or after giotrif. Simultaneous treatment with strong P-GP induction drugs can reduce the concentration over time of Afatinib.

Combined with Vinorelbin in metastatic breast cancer with her2 positive

In a mid -term analysis of the entire survival during the first time of a phase III study in metastatic breast cancer with a positive Her2 showed an increase in the mortality rate in patients using Giotrif in combination with Vinorelbin compared to using Trastuzumab and Vinorelbin. Combining Giotrif with Vinorelbin also increases the adverse effect rate (such as diarrhea, rash) and fatal events associated with progressive bacterial infections and cancer. Giotrif should not be used in combination with vinorelbin for patients with metastatic breast cancer with a positive Her2.

lactose

Giotrif contains lactose. Patients with rare genetic diseases are galactose intolerance, such as Lapp Lactase deficiency or Glucose-Galactose, which should not be taken.

The effect of the drug on driving and operating machinery

There is no study on the ability to drive and operate machinery.

Use drugs for women during pregnancy and lactation

Pregnant women:

Clinical studies with Afatinib show that there is no sign of teratogenicity when using the mother's death. The adverse changes only appear at clearly toxic doses. There is no study in pregnant women using Giotrif. Therefore, the potential risk in people is unknown. Women who have the ability to give birth should be advised to avoid getting pregnant during giotrif treatment. Appropriate contraceptive measures should be used during the medication period and at least 2 weeks after the last dose of the drug. If Giotrif is used during pregnancy or if the patient is pregnant during giotrif, it is advisable to notify the patient the potential dangers for the fetus.

breastfeeding women:

Based on non -clinical data, capable of Afatinib is excluded into breast milk. Can not exclude the risk of breastfeeding. Mothers should not breastfeed when using giotrif.

Reproduction:

There is no Giotrif research on human fertility. Clinical non -clinical toxic data has been shown to affect the reproductive organs when high doses. Therefore, it is not possible to eliminate adverse effects on fertility in humans when treated with giotrif.

Drug interaction

The effect of P-GP inhibitors and anti-drug protein inhibitors in breast cancer (BCRP) on Afatinib: In vitro studies have shown that Afatinib is the substrate of P-GP and BCRP. When using a strong P-GP and BCRP inhibitor is Ritonavir (200 mg twice a day for three days) an hour before using a single dose of 20 mg of Giotrif, Afatinib concentration increases 48% (the area under the curve (AUC0 -∞)) and 39% (cmax peak concentration (CMAX)). On the other hand, when using Ritonavir simultaneously or 6 hours after using 40 mg of Giotrif, the relative bioavailability of Afatinib is 119% (AUC0 -∞), 104% (cmax) and 111% (AUC0-fit), 105% (cmax). Therefore, it is recommended to use strong P-GP inhibitors (including but not only limited to ritonavir, cyclosporine A, ketoconazole, iTraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquavir, and amiodarone) SO LE Compared to giotrif (see the dosage and usage).

The effect of P-GP induction drugs on Afatinib: previous treatment with Rifampicin (600 mg once a day for 7 days) is a strong stimulant P-GP that reduces Afatinib levels 34% (AUC0 -∞) and 22% (CMAX) after the single dose of Giotrif 40 mg. Strong P-GP induction drugs (including but not only limited to rifampicin, carbamazepine, phenytoin, phenobarbital or St. John’s (Hypericum Perforatum) herbs that can reduce Afatinib levels.

The influence of Afatinib on the substrates of P-GP: Based on in vitro, Afatinib data is the average P-GP inhibitor, however, based on clinical data, treatment with Giotrif is considered not to change the plasma concentration of the substrates of P-GP.

Interaction with BCRP: In vitro studies show that Afatinib is a substrate and a BCRP transportation inhibitor. Afatinib may increase the bioavailability of oral BCRP substrates (including but not only limited to rosuvastatin and sulfasalazine).

Effects of food on Afatinib: taking Giotrif with a fat-rich meal that significantly reduces the concentration over time of Afatinib, specifically CMAX decreased by 50% and AUC0-∞ decreased by about 39%. Therefore, Giotrif should therefore be with food.

Storage

Leave a cool place, avoid light, temperatures below 30⁰C.

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