Look at it with a patient! What drugs can't be taken with osimertinib? Other drugs affecting osimertinib on osimertinib on other drugs affecting pharmacokinetics in special populations

Oscitinib is a third-generation, irreversible oral EGFR TKI that effectively and selectively inhibits EGFR-sensitive mutations and EGFR T790M-resistant mutations and has been shown to be effective in patients with NSCLC brain metastases.

Trade name: Tagrisso

Common name: Osimertinib [Ossi (hysteretinib) ]

R&D code: AZD9291

Target: EGFR

Manufacturer: AstraZeneca

First approval in the United States: November 2015

First approval in China: March 2017

Specification: 80mg*30, 40mg*30

Approved indications: Non-small cell lung cancer with EGFR mutation

Recommended dose: 80 mg once daily, with or without meals

Price: 80mg * 30: 15300 yuan (has been enrolled in medical insurance)

<h1 class= "pgc-h-arrow-right" > the effects of other drugs on osetinib</h1>

Strong CYP3A4 inducer

The combined use of osimertinib and strong CYP3A4 inducers reduces the exposure of osimertinib compared with the use of osimertinib alone, thereby reducing the efficacy of osimitinib.

Strong CYP3A inducers include: enzalutamide, apalutamide, phenytoin, carbamazepine, oxcarbazepine, topiramate, phenobarbital, butabital, St. John's wort, rifampicin, rifabutin, efaviren, nevirapine, pioglitazone, trogiglitazone and the like.

Avoid combining with strong CYP3A inducers with oscitinib. If the simultaneous use of CYP3A4 inducers cannot be avoided, the dose of osimtinib is increased when combined with the strong CYP3A4 inducer (the dose of oscitinib is adjusted to 160 mg each time), and the dose of osimertinib is restored to 80 mg each time after 3 weeks of discontinuation of the strong CYP3A4 inducer. When oscitinib is used with moderate and / or weak CYP3A inducers, dose adjustment is not required.

< h1 class= "pgc-h-arrow-right" > the effects of oscitinib on other drugs</h1>

BCRP or P-gp substrate

The substrates of BCRP include pravastatin and a variety of phytoestrogens, and the substrates of P-gp are mostly hydrophobic cations.

The combination of oscitinib and breast cancer resistant protein (BCRP) or P-glycoprotein (P-gp) substrates increases substrate exposure compared to substrates alone. Increased exposure to BCRP or P-gp substrates may increase the risk of exposure-related toxicity. Adverse reactions when BCRP or P-gp substrates are combined with osetinib should be monitored.

Drugs that prolong the QTc interval

Drugs that cause QT interval prolongation include quinidine, disopyramide, procainamide, amiodarone, sotalol, ibutilide, dofetilide, cisapride, erythromycin, clarithromycin, methiopyridazine, chlorpromazine, misodrazine, haloperidol, loperamide, etc.

The effect of combining with osimertinib to prolong the QTc interval is unknown. Where feasible, simultaneous administration of drugs known to prolong the QTc interval should be avoided, as well as a known risk of thrombosis. If simultaneous administration of such drugs cannot be avoided, ecG monitoring should be performed regularly.

<h1 class = "pgc-h-arrow-right" > pharmacokinetics</h1>

absorb

The median time for oscitinib to reach Cmax is 6 hours (range 3 to 24 hours).

Taking 20 mg of osetinib after receiving a high-fat, high-calorie diet (containing about 58 grams of fat and 1000 calories), the Cmax and AUC of osimertinib are comparable to those of fasting conditions.

Peak concentration (Cmax) and peak time (Tmax): refers to the maximum concentration value and time of occurrence of the drug in the blood plasma after extravascular administration, representing the degree and speed of drug absorption, respectively

Area under the curve (AUC): Represents the bioavailability of the drug (the degree to which the drug is absorbed and utilized in the human body), and the AUC is large and the bioavailability is high, and vice versa

Vd: Apparent distribution volume, after the drug reaches homeostasis in vivo, the ratio of the amount of drug in vivo to the blood drug concentration is called the apparent distribution volume

CL: Clearance, the apparent volume of the drug cleared from the body per unit time

F: Bioavailability refers to the degree to which the drug is actually utilized, that is, the ratio of the amount of medicine entering the blood to the amount of drug administered

distribution

The steady-state mean apparent volume of distribution (Vd=Vz/F) of oscitinib was 918L, and the plasma protein binding rate was 95%.

purge

The blood concentration of osetinib decreased over time, with an overall estimated average half-life of 48 hours and a steady-state mean apparent clearance-bioavailability ratio (CL/F) of 14.3 (L/h).

metabolism

The main metabolic pathways of osetinib are oxidation (mainly CYP3A) and dealkyl action. After oral administration of osimertinib, two pharmacologically active metabolites (AZ7550 and AZ5104) are found in the blood plasma.

excretion

About 68% of the administered doses are found in the feces and 14% in the urine.

<h1 class= "pgc-h-arrow-right" > pharmacokinetics in special populations</h1>

The pharmacokinetics of oscitinib do not differ clinically well in the following population characteristics: age, sex, ethnicity, body weight, baseline albumin level, duration of treatment, smoking status, renal or hepatic impairment.

【Important】This public number [Global Good Medicine Information] All article information is for reference only, and the specific treatment is in accordance with the doctor's advice!