Elunate Special Precautions

Haemorrhage: It was observed in clinical studies that this product may increase the risk of haemorrhage. The haemorrhage mainly includes gastrointestinal haemorrhage, haematuria, epistaxis, haemoptysis, and gingival haemorrhage, etc.; there were case reports of fatal outcomes which involved haemorrhage of the digestive tract and respiratory tract (refer to Adverse Reactions).
Clinicians should pay close attention to the risk of haemorrhage when using the drug and monitor the complete blood count and coagulation indicators of patients; especially for patients who take anticoagulants (such as warfarin) during the treatment period, increase the monitoring frequency of coagulation indicators such as the international normalized ratio (INR). Once signs of haemorrhage requiring urgent medical intervention occur, permanent discontinuation of this product should be considered (refer to Dosage & Administration).
Patients with potential risk of haemorrhage before the administration of this product, such as activated partial thromboplastin time (aPTT) or prothrombin time (PT) more than 1.5 times the upper limit of normal, within one month after major surgery, etc., should use this product with caution. Patients with severe active haemorrhage and active gastrointestinal ulcers are not advised to use this product.
Infection: It was observed in clinical studies that this product may increase the risk of infection, and the most common infections were upper respiratory tract infection and urinary tract infection. Among them, there were case reports on pulmonary infection with fatal outcomes (refer to Adverse Reactions).
For patients with severe infections prior the administration of this product, fruquintinib should be used only after the infection is effectively controlled. This product must be interrupted for patients who experience Grade 3 or above infection during the treatment period until the infection is well under controlled.
Transaminases increased and hepatic function abnormal: It was observed in clinical studies that this product may cause transaminases increased, blood bilirubin increased and hepatic function abnormal, and the majority were Grade 1-2. There were no reports on drug-induced liver injury (refer to Adverse Reactions).
Liver function tests (transaminase and bilirubin) must be conducted before administering this product, and routine monitoring of liver function must be conducted during the treatment period. If a patient experiences Grade ≥3 transaminases increased or clinically indicated during the treatment period, this product should be promptly interrupted, reduced dose or permanently discontinued based on the situation, hepatoprotective treatment should be actively applied and the liver function should be closely monitored. The monitoring frequency can be increased to once a week or every two weeks until the transaminase level resolves to Grade 1 or the level before drug administration (refer to Dosage & Administration).
As there is no clinical data on patients with hepatic impairment for this product, patients with hepatic impairment should use this product with caution.
Hypertension: It was observed in clinical studies that this product may increase the risk of hypertension, and majority were Grade 1-2; there were no occurrences of Grade 4 hypertension or hypertensive crisis (refer to Adverse Reactions).
In the clinical studies, hypertension usually occurred approximately 10 days after drug administration, and good control could usually be achieved through conventional antihypertensive treatment. Grade 3 hypertension can basically resolve to Grade 1 or the level before drug administration through active antihypertensive treatment or dose adjustment.
It is necessary to control the patient's blood pressure at the optimum level (<140/90 mmHg) before administration of this product; the blood pressure should be routinely monitored during the treatment period, once a week in the first three cycles and once per cycle thereafter. The monitoring frequency of blood pressure can be increased if clinically indicated.
Hand-foot skin reaction: It was observed in clinical studies that this product may increase the risk of hand-foot skin reaction, and majority were Grade 1-2 (refer to Adverse Reactions).
In clinical studies, hand-foot skin reactions usually occurred in the first cycle after drug administration. Grade 3 hand-foot skin reactions can basically be relieved or alleviated through symptomatic treatment and dose adjustment. Refer to Dosage & Administration for details on dose adjustment related to hand and foot skin reactions.
Proteinuria: It was observed in clinical studies that this product may increase the risk of proteinuria, which was mainly Grade 1-2. No nephrotic syndrome occurred (refer to Adverse Reactions).
In clinical studies, proteinuria occurred approximately 20 days after drug administration, and Grade 3 proteinuria can basically resolve to Grade 1 or the level before drug administration through dose adjustment and active symptomatic treatment.
During the treatment of this product, patients must undergo routine urine test regularly and should seek medical treatment promptly if proteinuria is observed. Urinary protein should be closely monitored in patients with renal impairment while receiving this product.
Gastrointestinal perforation or fistula formation: Gastrointestinal perforation or fistula formation are common disease-related complications in patients with peritoneal cancer. It was observed in clinical studies that the incidence of gastrointestinal perforation and fistula formation after administration of this product was both 0.8%, of which the incidence of Grade ≥3 gastrointestinal perforation and gastrointestinal fistula was 0.8% and 0.5%, respectively. The incidence of gastrointestinal perforation in the placebo arm was 0.5%; there were no case reports of gastrointestinal fistula. There were no case reports of fatal outcome in both arms.
During the treatment of this product, patients with gastrointestinal infiltration or previous history of gastrointestinal perforation must be closely monitored. If a patient has gastrointestinal perforation, this product must be permanently discontinued immediately, and the patient must be promptly treated. Gastrointestinal perforation is often accompanied by characteristic symptoms, such as sudden severe pain in the upper abdomen, persistent discomfort or burning pain that rapidly spreads to the entire abdomen.
Patients with unhealed gastrointestinal perforation or gastrointestinal fistula are not recommended to use this product.
Arterial thrombosis: It was observed in clinical studies that the incidence of arterial thrombosis caused by the administration of this product was 0.5%, which included 1 case report of cerebral infarction with fatal outcome.
During the treatment of this product, patients with high-risk factors of arterial thrombosis (including elderly, hypertension, diabetes, myocardial ischemia and infarction, cerebral ischemia and infarction) must be closely monitored. Discontinue this product immediately in patients who develop arterial thrombosis or stroke.
Patients with pre-existing arterial thrombosis or stroke must use this product with caution.
Reversible posterior leukoencephalopathy syndrome (RPLS): Reversible posterior leukoencephalopathy syndrome (RPLS) was not observed in clinical studies, but there are relevant reports for similar products. The signs and symptoms of RPLS include seizure, headache, altered mental status, visual impairment or cortical blindness, with or without associated hypertension. The diagnosis of RPLS must be verified using brain magnetic resonance imaging (MRI). Patients with suspected RPLS are recommended to permanently discontinue this product, along with control of hypertension and supportive medical measures for other medical symptoms.
Delayed wound healing: Antiangiogenic drugs may suppress or interfere wound healing. In order to prevent such situation, it is recommended for patients who require major surgery during the treatment period to interrupt the use of this product. The decision to resume treatment following major surgical intervention with this product should be based on clinical judgment of confirmed complete wound healing.
Effects on driving and machine operation: At present, there is still no study about the effects of this product on driving or machine operation. If the patient experiences symptoms that affect his/her attention and response during the treatment with this product, it is recommended to drive or operate machines after the symptoms have subsided.
Use in Children: At present, there is no clinical data on the use of this product on children or adolescent patients under the age of 18, hence paediatric patients are not recommended to take this product.
Use in the Elderly: In the Phase 1 clinical study of fruquintinib, there was no significant difference in the plasma drug concentration between elderly patients aged 65 years and above and patients aged below 65 years. In the Phase 3 FRESCO clinical study, there were a total of 78 elderly patients, accounting for 18.8%; among whom 50 patients came from the fruquintinib arm. In comparison to patients aged below 65 years, the efficacy was basically consistent. However, the incidence of Grade 3 or 4 adverse events and dose adjustment in elderly patients was slightly higher than patients aged below 65 years. Therefore, it is recommended for elderly patients to use this product with caution under the guidance of the physician. It is not required to adjust the initial dose for elderly patients.