Idelalisib is an oral drug targeting PI3Kδ kinase that offers a new treatment option for patients with relapsed chronic lymphocytic leukemia (CLL). Its unique mechanism of action and strict medication specifications need to be fully understood in combination with clinical practice.

Presentation of the drug Idelalisib

By selectively inhibiting the PI3Kδ signaling pathway, Idelalisib blocks the survival and proliferation of malignant B cells, and is suitable for second-line combination therapy in selected patients.

Basic information and indications of the drug

Developed by Gilead in the United States, Idelalisib is available in 150mg×60 tablets at a price of about $6,530 per box. It is approved in combination with rituximab for the treatment of relapsed CLL who cannot receive other therapies due to comorbidities. It is not clearly indicated for follicular lymphoma, small lymphocytic lymphoma, or first-line therapy, and concomitant with bendamustine is contraindicated.

Targets of action and pharmacokinetics

Idelalisib primarily targets PI3Kδ kinase, which inhibits survival signaling in the tumor microenvironment. The drug is metabolized by aldehyde oxidase and CYP3A, the protein binding rate is ≥84%, and the half-life is independent of the dose. It should be used with caution in patients with abnormal liver function, and data on patients with abnormal liver enzymes at baseline are limited.

Idelalisib is not yet available in China, has no generic drugs or medical insurance coverage, and patients need to obtain it through formal channels and strictly follow the storage conditions (15-30°C).

Recommended dosage of Zydelig

The dosage regimen of Idelalisib needs to be dynamically adjusted in combination with patient tolerance and toxicity to ensure maximum benefit from treatment.

Standard dose versus missed dose

The recommended dose is 150mg orally, swallowed whole, twice daily. If you miss a dose, you can make up for it within 6 hours, and skip if you exceed it. Treatment is continued until disease progression or intolerable toxicity. Elderly patients (≥ 65 years old) account for 55% of the clinical trial population, and their risk of adverse reactions is high, and monitoring needs to be strengthened.

Dose adjustment and special population norms

In the event of severe hepatotoxicity, infection, or skin reactions, the drug should be discontinued and reduced to 100 mg twice daily. Recurrent toxicity is permanently discontinued. Pregnant and lactating females are contraindicated, and those of childbearing potential should take contraceptive measures during treatment and 1-3 months after discontinuation. Safety is not established and is not recommended for pediatric patients.

Before treatment, liver function and infection status should be assessed, and patients with abnormal liver enzymes at baseline should be closely monitored to avoid concomitant use of hepatotoxic drugs.

Management of adverse effects of Idelalisib

The side effects of Idelalisib involve multiple systems, and early identification and standardized treatment are the key to reducing the risk.

Hepatotoxicity and infection management

Severe hepatotoxicity occurred in 16% of patients, and ALT/AST elevated more than 5 times normal required discontinuation. Liver enzymes were monitored every 2 weeks for the first 3 months, and weekly if abnormal. Forty-eight percent of patients developed severe infection, and Pneumocystis jirovecii pneumonia (PJP) should be prevented before treatment, and CMV-positive patients should be monitored monthly. Medication should be suspended for infections above grade 3, and whether to restart treatment should be evaluated after control.

Diarrhea and skin reactions to deal with

In 20% of patients with severe diarrhoea or colitis, antidiarrheal drugs are contraindicated, treatment is suspended, and corticosteroids are suspended, with a median duration of remission of 1 week to 1 month. Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) requires permanent discontinuation. Grade 3-4 neutropenia occurred in 58% of patients, and routine blood tests were monitored weekly, and dosing was suspended when the count was below 1.0 Gi/L.

Intestinal perforation is rare but fatal, and new abdominal pain requires immediate evaluation. Patients with hypersensitivity reactions are contraindicated, and the drug is permanently discontinued and emergency is given in the event of anaphylactic shock. Record the changes in symptoms during treatment and communicate with the hematologist in a timely manner.

Idelalisib should be kept in its original packaging away from light and moisture. Patients should be regularly reviewed for growth indexes and toxicity, and the dosage guidelines should be strictly followed. If you miss a dose, follow the rules to make up the medication and avoid adjusting the regimen by yourself. Proper management of drug characteristics and risks can improve treatment adherence and clinical outcomes.