Savolitinib is a protein kinase inhibitor. It exerts dual therapeutic effects by precisely inhibiting the activity of c-Met protein kinase, a key "switch" that regulates cell growth.
I. Indications
Savolitinib is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring mutations in exon 14 of the mesenchymal-epithelial transition factor (c-Met) gene.
II. Dosage and Administration
(1) Dosage Form and Strength
Tablets, each containing 50 mg of savolitinib (active ingredient).
(2) Administration Method
Dosing Regimen: For oral use. The recommended dose is 300 mg (equivalent to 6 tablets) once daily. Continuous administration is required for a long term until disease progression or intolerable adverse reactions occur.
Administration Requirements: Must be taken on an empty stomach. No food shall be consumed for at least 2 hours before administration or within 1 hour after administration. Normal water intake is allowed during the medication period.
Medication Guidance: Savolitinib shall be used under the guidance of an oncologist. The administration method, dosage, and treatment duration shall be strictly adjusted in accordance with the doctor’s advice. Self-medication based on the package insert is strictly prohibited.
III. Contraindications
Savolitinib is strictly contraindicated in the following populations:
Patients with severe hypersensitivity to savolitinib or any inactive ingredient in the formulation;
Pregnant women;
Lactating women.
IV. Precautions for Special Populations and Populations Requiring Caution
(1) Populations Requiring Caution
Patients with severe hepatic impairment;
Patients with severe renal impairment.
If the use of savolitinib in the above populations is deemed necessary by the physician, close monitoring of the patient’s physical reactions is required. The physician shall formulate an emergency plan in advance, and discontinue the drug immediately and intervene if any discomfort occurs.
(2) Other Special Populations
Pediatric Population: Clinical data are currently lacking, and the safety and efficacy of savolitinib in this population have not been established.
Geriatric Population: Clinical data are currently lacking. Savolitinib should be used with caution under the doctor’s guidance based on the patient’s physical condition.
Patients who are planning pregnancy, pregnant, or lactating must actively inform their doctor before taking the drug, and the doctor will formulate an alternative treatment plan.
V. Drug Interactions
Savolitinib can inhibit the activity of MATE1 and MATE2-K transporters, with inhibitory concentrations of 1.48 μM and 1.85 μM, respectively. This may interfere with the metabolism of other drugs dependent on these two proteins, leading to elevated plasma drug concentrations and increased risk of side effects. The following precautions should be noted:
Combination use with drugs metabolized by MATE1/MATE2-K should be avoided as much as possible;
If combination use is unavoidable, for drugs whose slight changes in plasma concentration may trigger severe reactions, the dosage should be reduced in accordance with the corresponding drug package insert;
Continuous monitoring of drug safety is required during combination therapy, and the treatment plan should be adjusted in a timely manner.
Before taking savolitinib, patients must inform their doctor of all medications they are currently taking (including prescription drugs, over-the-counter drugs, and health supplements) to avoid the risk of drug interactions.
VI. Adverse Reactions
(1) Severe Adverse Reactions
Including but not limited to: edema, hepatic function impairment, neutropenia, hypoalbuminemia, hypokalemia, leukopenia, dyspnea complicated with pleural effusion, interstitial lung disease (inflammation of lung tissue), and QT interval prolongation (abnormal cardiac electrical activity).
(2) Mild Adverse Reactions
Including but not limited to: vomiting, headache, malaise, skin rash, fatigue, anorexia, nausea, dizziness, and back pain.
The occurrence of adverse reactions is related to individual constitution, dosage, and disease conditions. Patients should closely observe physical changes during medication. If any discomfort occurs, contact the doctor immediately. If necessary, monitor indicators such as blood pressure, heart rate, and respiratory rate, and intervene in a timely manner.
VII. Precautions for Medication
(1) Pre-administration Precautions
Clarify the allergy history; savolitinib is contraindicated in patients allergic to its ingredients;
Use with caution in patients with severe hepatic or renal impairment; hepatic and renal function tests should be completed before medication;
Savolitinib may cause dizziness, headache, and fatigue. Driving or operating machinery is prohibited during the medication period.
(2) Monitoring During Administration
Hepatic Function Monitoring: Baseline examination should be performed before medication. Re-examination should be conducted every two weeks during the first 3 months of treatment, and then once a month thereafter. The test items include alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin. If the indicators increase to grade 2 or above, the frequency of re-examination should be increased, and drug discontinuation, dosage reduction, or permanent drug withdrawal should be considered if necessary.
Pulmonary Symptom Monitoring: Pay close attention to symptoms such as shortness of breath, persistent dry cough, and dyspnea. If interstitial lung disease or non-infectious pneumonia is suspected, discontinue the drug immediately and conduct examinations. Permanent drug withdrawal is required for confirmed severe cases.
Cardiac Function Monitoring: Regular electrocardiograms should be performed to monitor changes in the QT interval, and medication should be adjusted as required (see "Discontinuation Indications" in this section for details).
(3) Post-administration Precautions
Follow the doctor’s advice for medication; do not arbitrarily increase or decrease the dosage, discontinue the drug, or change the administration frequency;
Adopt a light diet, avoid irritating foods such as chili and Chinese prickly ash to prevent affecting the efficacy or exacerbating discomfort;
Store the drug properly in a place out of the reach of children. Do not use the drug if there are any abnormalities in its color, shape, or odor;
Return for regular follow-up visits during the medication period, and timely feedback physical conditions and adverse reactions to the doctor.
(4) Discontinuation Indications
QT Interval Abnormality: If the corrected QT interval (QTc) exceeds 500 ms in two consecutive electrocardiograms, suspend the medication. After the QTc interval returns to ≤ 480 ms or the baseline level, the drug may be resumed at a reduced dose under the doctor’s guidance. If QT interval prolongation is accompanied by severe arrhythmia symptoms such as torsades de pointes, polymorphic ventricular tachycardia, syncope, or palpitations, permanent drug withdrawal is required and the patient should be transferred to the cardiovascular department for treatment.
Pulmonary Adverse Reactions: Permanent drug withdrawal is required for confirmed severe interstitial lung disease or non-infectious pneumonia.
Other Conditions: If intolerable severe adverse reactions occur, drug withdrawal and symptomatic treatment should be carried out after evaluation by the doctor.
VIII. Management of Missed Dose and Overdose
(1) Missed Dose
If a dose is missed on the same day, take the missed dose immediately once remembered. If the missed dose is remembered on the next day, do not take the missed dose, and do not double the dose on the next day. Take the next scheduled dose as usual. Taking a double dose at one time is strictly prohibited.
(2) Overdose
Strictly follow the prescribed dose by the doctor. In case of accidental overdose, closely monitor the physical reactions. If any discomfort occurs, contact the doctor immediately, and go to the hospital for symptomatic treatment if necessary.
IX. Instructions for Combination Therapy
As a precision-targeted drug, the combination therapy regimen of savolitinib requires rigorous evaluation. Whether to combine it with chemotherapy, immunotherapy, or other targeted drugs shall be comprehensively determined by the oncologist based on the patient’s genetic test results, disease progression stage, physical condition, etc., to formulate an individualized treatment plan. Patients are not allowed to combine savolitinib with other drugs without authorization.
