Anlotinib

BRAND NAMES

ALUNBRIG – This is sometimes used internationally, though primarily for other TKIs; check regional approvals. 

Anlotinib (generic name) – In China, it is commonly sold simply under its generic name. 

AL3818 – Development code used in clinical trials before official approval.

MECHANISM OF ACTION

Anlotinib is a multi-targeted tyrosine kinase inhibitor that exerts its anticancer effects by blocking several key receptors involved in tumor growth and angiogenesis. It inhibits VEGFR1–3, PDGFRα/β, FGFR1–4, c-Kit, and Ret, thereby reducing the formation of new blood vessels that supply tumors and interfering with signaling pathways that promote cancer cell proliferation and survival. By simultaneously targeting both tumor angiogenesis and tumor cell growth, Anlotinib effectively slows tumor progression and has shown clinical activity in cancers such as non-small cell lung cancer and soft tissue sarcoma.

PHARMACOKINETICS

Absorption

Anlotinib is well absorbed orally, reaching peak plasma levels in 4–6 hours, and food does not significantly affect its bioavailability.

Distribution

Anlotinib is highly protein-bound (~93%) and distributes well into tissues, including tumors, supporting its anticancer activity.

Metabolism

Anlotinib is primarily metabolized in the liver, mainly by cytochrome P450 enzymes, especially CYP3A4. Its metabolism produces several inactive metabolites, which are then eliminated from the body. Hepatic function can influence its clearance, so dose adjustments may be needed in patients with liver impairment.

Elimination

Anlotinib is mainly eliminated through feces, with a smaller portion excreted in the urine. It has a half-life of approximately 96 hours, allowing once-daily dosing in clinical use. Clearance is primarily hepatic, and impaired liver function can affect drug elimination.

PHARMACODYNAMICS

Anlotinib is a multi-targeted tyrosine kinase inhibitor that suppresses tumor growth by inhibiting angiogenesis and cell proliferation. It blocks VEGFR1–3, PDGFRα/β, FGFR1–4, c-Kit, and Ret, preventing tumor blood vessel formation and disrupting growth signaling pathways in cancer cells. By targeting both the tumor vasculature and tumor cells directly, Anlotinib reduces tumor progression, delays metastasis, and has demonstrated clinical efficacy in cancers such as non-small cell lung cancer and soft tissue sarcoma. Its effects are dose-dependent, with higher plasma concentrations producing stronger inhibition of target receptors.

ADMINISTRATION

Anlotinib is administered orally, usually in the form of tablets. The standard dosing schedule in clinical use is once daily for 2 weeks followed by a 1-week break (a 2-weeks-on/1-week-off cycle), but the regimen may vary depending on the type of cancer and patient tolerance. It can be taken with or without food, and tablets should be swallowed whole with water. Dose adjustments may be required for patients with hepatic or renal impairment or those experiencing significant adverse effects.

DOSAGE AND STRENGTH

Anlotinib is usually given as 12 mg tablets once daily for 14 days, followed by 7 days off (2-weeks-on/1-week-off cycle). Depending on side effects or patient condition, the dose can be reduced to 10 mg or 8 mg daily.

DRUG INTERACTIONS

Anlotinib is metabolized by CYP3A4, so inhibitors can increase its levels and side effects, while inducers can reduce its effectiveness. Caution is needed with anticoagulants, antiplatelets, or blood pressure medications.

FOOD INTERACTIONS

Anlotinib can be taken with or without food, as meals do not significantly affect its absorption or overall bioavailability. No specific dietary restrictions are required, though patients should maintain a balanced diet to support overall treatment and health.

CONTRAINDICATIONS

Anlotinib should not be used in patients with known hypersensitivity to the drug, severe liver impairment, pregnancy, or breastfeeding. It is also contraindicated in those with uncontrolled hypertension or recent serious cardiovascular events, and caution is needed in patients with kidney problems or bleeding disorders.

SIDE EFFECTS

Common side effects of Anlotinib include hypertension, fatigue, hand-foot syndrome, diarrhea, and loss of appetite. Other possible adverse effects are proteinuria, thyroid dysfunction, bleeding, and liver enzyme elevations. Most side effects are manageable with dose adjustments or supportive care, but severe reactions such as cardiovascular events or gastrointestinal bleeding require immediate medical attention.

TOXICITY

Anlotinib’s toxicity is generally dose-dependent and primarily affects the cardiovascular, hepatic, and hematologic systems. Common toxicities include hypertension, hand-foot syndrome, fatigue, and diarrhea. Severe toxicities may involve cardiac events, bleeding complications, liver dysfunction, or proteinuria, which can require dose reduction or treatment interruption. Careful monitoring of blood pressure, liver function, and kidney function is recommended to minimize serious adverse effects.