Anlotinib Hydrochloride Capsules is an antineoplastic agent belonging to the class of multi-targeted receptor tyrosine kinase inhibitors. It exerts its therapeutic effect by blocking multiple signaling pathways that promote tumor growth and angiogenesis.
Indications
1.Non-small cell lung cancer (NSCLC), the most common type of lung cancer.
2.Small cell lung cancer (SCLC), an aggressive type of lung cancer with rapid growth characteristics.
3.Soft tissue sarcoma, a malignant tumor arising from soft tissues such as muscles and fat.
4.Medullary thyroid carcinoma, a distinct subtype of thyroid cancer.
Specifications
Anlotinib Hydrochloride is available in three dosage strengths: 8 mg, 10 mg, and 12 mg.
Dosage and Administration
Recommended Dose
The recommended dosage of anlotinib hydrochloride is 12 mg once daily, administered orally before breakfast. The treatment schedule consists of continuous dosing for 2 weeks followed by a 1-week drug holiday, defining a 3-week (21-day) treatment cycle. Therapy should be continued until disease progression or the occurrence of intolerable adverse reactions.
Note: Package insert contents may vary for the same drug produced by different manufacturers. If such discrepancies are identified prior to medication use, healthcare providers or pharmacists must be consulted promptly.
Post-Administration Precautions
Close monitoring of patients' physical responses is essential during treatment.
Physicians will adjust treatment regimens based on individual tolerance. Common adverse reactions can be managed through dose adjustment, temporary treatment interruption, or symptomatic interventions.
Any dose modification must be performed under the guidance of a physician. In the event of sudden chest pain, dyspnea, severe bleeding, or other critical symptoms, immediate treatment discontinuation and medical attention are required.
Missed Dose Management
If a missed dose is identified and less than 12 hours remain until the next scheduled dose, the missed dose should not be taken. If patients are unable to determine the appropriate dose or dosing interval, they should consult a physician or pharmacist immediately.
Contraindications
Anlotinib Hydrochloride is contraindicated in the following patient populations:
1.Patients hypersensitive to any component of the drug (e.g., those experiencing skin rashes, dyspnea, or other allergic reactions after administration).
2.Patients diagnosed with central squamous cell lung cancer or those at high risk of massive hemoptysis (e.g., individuals with a history of expectorating large volumes of bright red blood).
3.Patients with severe hepatic impairment, characterized by significantly reduced liver metabolic function.
4.Patients with severe renal impairment, marked by severely compromised renal excretory function.
5.Pregnant or lactating women.
Adverse Reactions
General Disorders
Very common: Fatigue, weight loss
Common: Chest pain, pyrexia, influenza-like illness, edema, cancer-related pain
Uncommon: Hypersensitivity reaction, chills
Rare: Poor wound healing。
Cardiac Disorders
Very common: Hypertension, sinus tachycardia.
Common: Sinus bradycardia, palpitations, myocardial ischemia, sinus arrhythmia.
Uncommon: Heart failure, vena cava thrombosis, atrial fibrillation, pulmonary thrombosis, myocardial infarction, extremity venous thrombosis, flushing.
Rare: Hot flushes.
Hemorrhagic Events
Common: Hemoptysis, gastrointestinal bleeding, other hemorrhagic events.
Gastrointestinal Disorders
Very common: Diarrhea, abdominal pain, oropharyngeal pain, vomiting, nausea, toothache, oral mucositis.
Common: Abdominal distension, constipation, oral ulceration, xerostomia, oral pain, gastroesophageal reflux disease, intestinal obstruction.
Uncommon: Gastritis, pancreatitis, enteritis, melena.
Skin and Subcutaneous Tissue Disorders
Very common: Hand-foot syndrome.
Common: Rash, alopecia, pruritus, skin exfoliation, subungual hematoma, hyperhidrosis.
Uncommon: Skin pain, acneiform dermatitis, pigmentation disorders, xeroderma, erythema, pustulosis, seborrheic dermatitis.
Rare: Eczema, bullous dermatitis, generalized erythema, dermatitis herpetiformis, herpes simplex, blistering.
Renal and Urinary Disorders
Very common: Proteinuria.
Common: Urinary tract infection.
Metabolism and Nutrition Disorders
Very common: Hypertriglyceridemia, decreased appetite, hypercholesterolemia, hyperglycemia, hyponatremia, hypoalbuminemia.
Common: Hypokalemia, hypophosphatemia, hypocalcemia, hyperuricemia, hypomagnesemia.
Respiratory, Thoracic and Mediastinal Disorders
Very common: Dysphonia, cough.
Common: Dyspnea, upper respiratory tract infection, epistaxis, pulmonary infection, pneumothorax, pleural effusion.
Uncommon: Interstitial lung disease.
Blood and Lymphatic System Disorders
Very common: Leukopenia, thrombocytopenia, anemia, neutropenia.
Common: Lymphopenia.
Rare: Eosinophilia.
Musculoskeletal and Connective Tissue Disorders
Very common: Musculoskeletal pain.
Common: Arthralgia.
Endocrine Disorders.
Very common: Hypothyroidism.
Common: Hyperthyroidism.
Psychiatric and Nervous System Disorders
Common: Headache, dizziness, insomnia, hypoesthesia.
Uncommon: Paresthesia, somnolence, vertigo, oral hypoesthesia, epilepsy, dysgeusia.
Ocular Disorders
Uncommon: Visual disturbance, dry eye.
Hepatobiliary Disorders.
Common: Hyperbilirubinemia.
Uncommon: Cholecystitis, jaundice.
Rare: Hepatic failure.
Ear and Labyrinth Disorders
Common: Tinnitus.
Precautions
Medication Guidance
This drug must be prescribed and administered under the supervision of experienced oncologists. Treatment cycles should be completed in full unless disease progression or severe adverse reactions necessitate discontinuation.
Special Populations Requiring Caution
1.Patients with mild to moderate hepatic or renal impairment:
Treatment eligibility must be determined by physicians following comprehensive organ function assessment.
2.Patients with bleeding tendency or coagulation abnormalities (e.g., easy bruising, prolonged wound hemostasis)
Regular coagulation function monitoring, including prothrombin time (PT) and international normalized ratio (INR), is mandatory during treatment.
3.Patients with a history of epilepsy:
Close monitoring is required even in the absence of active seizures.
Special Population Dosing
1.Pregnant women
Animal studies have demonstrated potential teratogenic effects of the drug. Administration is strictly prohibited in pregnant patients. If pregnancy occurs during treatment, immediate drug discontinuation and obstetric consultation are required. Women of childbearing potential must use effective contraception during treatment and for at least 6 months following treatment cessation.
2.Lactating women
No data are available regarding the excretion of anlotinib into human breast milk. Given the potential risk of adverse effects in nursing infants, breastfeeding is contraindicated during treatment.
3.Elderly patients (≥ 65 years old)
Clinical trial data indicate comparable safety profiles between elderly and younger patients, with no dose adjustment required.
4.Pediatric and adolescent patients (< 18 years old)
Safety and efficacy data in this population are currently lacking.
5.Patients with hepatic/renal impairment
Treatment may cause elevations in transaminases or bilirubin. Regular monitoring of liver function parameters (e.g., alanine aminotransferase [ALT], aspartate aminotransferase [AST], bilirubin) is recommended. For patients with renal impairment, urinalysis should be performed every 6 weeks. Persistent urinary protein ≥ ++ on two consecutive tests warrants further evaluation and potential dose adjustment based on clinical findings.
6.Patients at high risk of bleeding
Strict physician supervision is required for patients with a history of severe bleeding within 4 weeks, unhealed wounds, or thromboembolic events (e.g., stroke, pulmonary embolism) within 6 months. Patients receiving warfarin require coagulation parameter monitoring every 1–2 weeks.
7.Patients with congenital long QT syndrome
This population is at increased risk of life-threatening arrhythmias, and treatment with anlotinib is contraindicated. Patients with heart failure or those receiving other QT-prolonging medications require electrocardiogram (ECG) and serum electrolyte monitoring every 3–6 weeks.
Treatment Monitoring
1.Very common monitoring parameter abnormalities
Elevated thyroid-stimulating hormone (TSH), elevated aspartate aminotransferase (AST), elevated gamma-glutamyl transferase (GGT), elevated blood bilirubin, elevated alanine aminotransferase (ALT), prolonged QT interval on ECG, elevated low-density lipoprotein (LDL), positive urinary red blood cells, elevated blood alkaline phosphatase, elevated conjugated bilirubin, positive occult blood.
2.Common monitoring parameter abnormalities
Elevated lipase, elevated amylase, elevated serum creatinine, prolonged activated partial thromboplastin time (APTT), elevated blood urea.
Criteria for Dose Adjustment
1.Severe adverse reactions (Grade 3–4 non-hemorrhagic events)
Immediate treatment interruption is required.
2.Hemorrhagic events
Temporary treatment suspension for mild bleeding (Grade 2); permanent discontinuation for severe bleeding (Grade ≥ 3).
3.Sudden chest pain or dyspnea
May indicate pneumothorax; immediate medical evaluation is required.
Dose adjustment decisions must be made by physicians based on comprehensive assessment of clinical findings and symptom severity.
Drug Interactions
1.Enzyme modulators affecting drug metabolism
Metabolism accelerators
Drugs including rifampicin, dexamethasone, and phenytoin sodium (acting via CYP3A4/5 enzymes), as well as omeprazole and moricizine (acting via CYP1A2 enzymes), may decrease anlotinib plasma concentrations.
Metabolism inhibitors
Drugs including ketoconazole and clarithromycin (inhibiting CYP3A4/5 enzymes), as well as ciprofloxacin and fluvoxamine (inhibiting CYP1A2 enzymes), may increase anlotinib plasma concentrations.
2.Drugs affected by anlotinib
Special attention is required for co-administration with the following drugs:the analgesic alfentanil, the antimigraine agent ergotamine, and the anticoagulant warfarin. These drugs have narrow therapeutic windows, and co-administration with anlotinib may alter their plasma concentrations. Concurrent use should be avoided or performed under close physician supervision.
Combination Therapy Information
Clinical trials are currently underway to evaluate the efficacy of anlotinib in combination with chemotherapy, targeted therapy, or immunotherapy. Such combination regimens may synergistically inhibit tumor progression through distinct mechanisms of action. However, specific administration protocols and efficacy outcomes are pending confirmation from ongoing clinical studies.
Drug Overdose
No specific antidote exists for anlotinib overdose. In cases of suspected overdose, immediate treatment discontinuation and prompt medical attention are essential. Physicians will initiate supportive care measures based on presenting symptoms.
Duration of Therapeutic Effect
The duration of therapeutic efficacy varies across different cancer types:
1.For patients with advanced non-small cell lung cancer
In the ALTER0303 clinical trial, the median tumor control duration was 5.4 months in patients who had failed two prior lines of chemotherapy and targeted therapy.
2.For patients with medullary thyroid carcinoma
The ALTER01031 trial demonstrated a median tumor control duration of 20.7 months in patients with locally advanced or metastatic disease.
