OPDIVO CONCENTRATE FOR SOLUTION FOR INFUSION 10 MG/ML

BRISTOL-MYERS SQUIBB HOLDINGS PHARMA, LTD. LIABILITY COMPANY - PUERTO RICOVETTER PHARMA-FERTIGUNG GMBH & CO. KG (GERMANY)🇸🇬 Health Sciences Authority

Approval Date: Apr 4, 2016
Approval ID: 03fd0cab43400fe6
Company: BRISTOL-MYERS SQUIBB HOLDINGS PHARMA, LTD. LIABILITY COMPANY - PUERTO RICOVETTER PHARMA-FERTIGUNG GMBH & CO. KG (GERMANY)
Type: Therapeutic

Approval Details

Approval Id: 03fd0cab43400fe6
Drug Name: OPDIVO CONCENTRATE FOR SOLUTION FOR INFUSION 10 MG/ML
Product Name: OPDIVO CONCENTRATE FOR SOLUTION FOR INFUSION 10 MG/ML
Approval Number: SIN14975P
Approval Date: 2016-04-04
Registrant: BRISTOL-MYERS SQUIBB (SINGAPORE) PTE. LTD.
Licence Holder: BRISTOL-MYERS SQUIBB (SINGAPORE) PTE. LTD.
Drug Type: Therapeutic
Forensic Classification: PRESCRIPTION ONLY MEDICINES
Dosage Form: INFUSION, SOLUTION CONCENTRATE
Dosage: 4.2 Posology and method of administration Treatment must be initiated and supervised by physicians experienced in the treatment of cancer. Posology OPDIVO as monotherapy The recommended dose of OPDIVO is 3 mg/kg administered intravenously over 30–60 minutes every 2 weeks. Melanoma (advanced or adjuvant treatment) <img src="/TGIF/Opdivo-TableforMelanoma.png" alt="Opdivo Dosage Table for Melanoma" /> Oesophageal Squamous Cell Carcinoma (OSCC) The recommended dose of OPDIVO is 240 mg administered intravenously over 30–60 minutes every 2 weeks. Adjuvant treatment of oesophageal or gastroesophageal junction cancer (OC or GEJC) The recommended dose of OPDIVO is 240 mg administered intravenously over 30–60 minutes every 2 weeks, or 480 mg administered intravenously over 30–60 minutes every 4 weeks. Muscle invasive urothelial carcinoma (MIUC) adjuvant treatment The recommended dose of OPDIVO is 240 mg administered intravenously over 30–60 minutes every 2 weeks, or 480 mg administered intravenously over 30–60 minutes every 4 weeks. OPDIVO in combination with ipilimumab Melanoma The recommended dose is 1 mg/kg nivolumab administered as an intravenous infusion over 30–60 minutes every 3 weeks for the first 4 doses in combination with 3 mg/kg ipilimumab administered intravenously over 30–90 minutes. This is then followed by a second phase in which 3 mg/kg nivolumab is administered as an intravenous infusion over 30–60 minutes every 2 weeks. Non-Small Cell Lung Cancer (NSCLC) The recommended dose is 360 mg nivolumab administered as an intravenous infusion every 3 weeks in combination with 1 mg/kg ipilimumab administered as an intravenous infusion every 6 weeks, and platinum chemotherapy administered every 3 weeks. After completion of 2 cycles of chemotherapy, treatment is continued with 360 mg nivolumab administered as an intravenous infusion every 3 weeks in combination with 1 mg/kg ipilimumab every 6 weeks. Treatment is recommended until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. Malignant pleural mesothelioma (MPM) The recommended dose of nivolumab is either 3 mg/kg every 2 weeks or 360 mg every 3 weeks administered as an intravenous infusion over 30–60 minutes in combination with 1 mg/kg ipilimumab administered as an intravenous infusion over 30 minutes every 6 weeks. Treatment is recommended until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. Renal Cell Carcinoma (RCC) The recommended dose is 3 mg/kg nivolumab administered as an intravenous infusion over 30–60 minutes every 3 weeks for the first 4 doses in combination with 1 mg/kg ipilimumab administered intravenously over 30 minutes. This is then followed by a second phase in which 3 mg/kg nivolumab is administered as an intravenous infusion over 30–60 minutes every 2 weeks. The first dose of nivolumab monotherapy should be administered 3 weeks following the last dose of the combination of nivolumab and ipilimumab. dMMR or MSI H colorectal cancer The recommended dose for first-line treatment of dMMR or MSI H CRC is 240 mg of nivolumab in combination with 1 mg/kg ipilimumab administered intravenously every 3 weeks over 30 minutes for a maximum of 4 doses, followed by nivolumab monotherapy administered intravenously at either 240 mg every 2 weeks over 30 minutes or at 480 mg every 4 weeks over 30 minutes. For the monotherapy phase, the first dose of nivolumab should be administered 3 weeks after the last dose of the combination of nivolumab and ipilimumab. Treatment with nivolumab is recommended until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. Oesophageal squamous cell carcinoma The recommended dose is either 3 mg/kg nivolumab every 2 weeks or 360 mg nivolumab every 3 weeks administered intravenously over 30–60 minutes in combination with 1 mg/kg ipilimumab administered intravenously over 30 minutes every 6 weeks. Treatment is recommended until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. Hepatocellular carcinoma The recommended dose is 1 mg/kg nivolumab in combination with 3 mg/kg ipilimumab administered intravenously every 3 weeks for up to 4 doses. This is then followed by a second phase in which nivolumab monotherapy is administered intravenously at either 240 mg every 2 weeks or at 480 mg every 4 weeks (see sections 5.1 and 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information), as presented in Table 1. Treatment is recommended until disease progression, unacceptable toxicity, or up to 24 months. For the monotherapy phase, the first dose of nivolumab should be administered: <ul class="square"> <li>3 weeks after the last dose of the combination of nivolumab and ipilimumab if using 240 mg every 2 weeks or 480 mg every 4 weeks.</li> </ul> <img src="/TGIF/Opdivo-Table1_030725.png" alt="Opdivo Dosage Table 1" /> OPDIVO in combination with cabozantinib Renal Cell Carcinoma (RCC) The recommended dose is nivolumab administered intravenously at either 240 mg every 2 weeks over 30 minutes or 480 mg every 4 weeks over 60 minutes in combination with 40 mg cabozantinib administered orally every day. OPDIVO in combination with chemotherapy Neoadjuvant treatment of non-small cell lung cancer The recommended dose is 360 mg nivolumab administered intravenously over 30–60 minutes in combination with platinum-based chemotherapy every 3 weeks for 3 cycles (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Neoadjuvant and adjuvant treatment of non-small cell lung cancer The recommended dose in the neoadjuvant phase is 360 mg nivolumab administered intravenously over 30 minutes in combination with platinum-doublet chemotherapy every 3 weeks for up to 4 cycles or until disease progression or unacceptable toxicity. This is then followed after surgery by nivolumab 480 mg administered intravenously over 30 minutes every 4 weeks as monotherapy in the adjuvant phase for up to 13 cycles or until disease recurrence or unacceptable toxicity. Gastric cancer, gastroesophageal junction cancer and oesophageal adenocarcinoma The recommended dose is 360 mg nivolumab administered intravenously over 30–60 minutes in combination with fluoropyrimidine- and platinum-based chemotherapy every 3 weeks or 240 mg nivolumab administered intravenously over 30–60 minutes in combination with fluoropyrimidine- and platinum-based chemotherapy every 2 weeks (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Treatment is recommended until disease progression or unacceptable toxicity. The maximum treatment duration for OPDIVO is 24 months. Oesophageal squamous cell carcinoma The recommended dose of nivolumab is 240 mg every 2 weeks or 480 mg every 4 weeks administered intravenously over 30–60 minutes in combination with fluoropyrimidine- and platinum-based chemotherapy (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Treatment with nivolumab is recommended until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. First-line treatment of unresectable or metastatic urothelial carcinoma The recommended dose of nivolumab is 360 mg administered intravenously over 30–60 minutes in combination with cisplatin and gemcitabine every 3 weeks for up to 6 cycles followed by nivolumab monotherapy administered intravenously at either 240 mg every 2 weeks over 30–60 minutes or at 480 mg every 4 weeks over 30–60 minutes. Treatment with nivolumab is recommended until disease progression, unacceptable toxicity, or up to 24 months from first dose, whichever comes first. Duration of treatment Treatment with OPDIVO, either as monotherapy or in combination with ipilimumab or other therapeutic agents, should be continued as long as clinical benefit is observed or until treatment is no longer tolerated by the patient (and up to maximum duration of therapy if specified for an indication). For adjuvant therapy, the maximum treatment duration with OPDIVO is 12 months. Atypical responses (i.e., an initial transient increase in tumour size or small new lesions within the first few months followed by tumour shrinkage) have been observed. It is recommended to continue treatment with nivolumab or nivolumab in combination with ipilimumab for clinically stable patients with initial evidence of disease progression until disease progression is confirmed. For OPDIVO in combination with cabozantinib, nivolumab should be continued until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. Cabozantinib should be continued until disease progression or unacceptable toxicity. Refer to the product insert for cabozantinib. Dose escalation or reduction is not recommended for OPDIVO as monotherapy or in combination with other therapeutic agents. Dosing delay or discontinuation may be required based on individual safety and tolerability. Guidelines for permanent discontinuation or withholding of doses are described in Table 2. Detailed guidelines for the management of immune-related adverse reactions are described in section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information. When nivolumab is administered in combination with other therapeutic agents, refer to the product insert of these other combination therapeutic agents regarding dosing. <img src="/TGIF/Opdivo-Table2.png" alt="Opdivo Dosage Table 2" /> OPDIVO as monotherapy or in combination with other therapeutic agents should be permanently discontinued for: <ul> <li>Grade 4 or recurrent Grade 3 adverse reactions;</li> <li>Persistent Grade 2 or 3 adverse reactions despite management.</li> </ul> When OPDIVO is administered in combination with ipilimumab, if either agent is withheld, the other agent should also be withheld. If dosing is resumed after a delay, either the combination treatment or OPDIVO monotherapy could be resumed based on the evaluation of the individual patient. When OPDIVO is administered in combination with chemotherapy, refer to the product information of the other combination therapy agents regarding dosing. If any agents are withheld, the other agents may be continued. If dosing is resumed after a delay, either the combination treatment, OPDIVO monotherapy or chemotherapy alone could be resumed based on the evaluation of the individual patient. OPDIVO in combination with cabozantinib in RCC When nivolumab is used in combination with cabozantinib, the above treatment modifications in Table 2 also apply to the nivolumab component. In addition, for liver enzyme elevations, in patients with RCC being treated with nivolumab in combination with cabozantinib: <ul> <li>If ALT or AST > 3 times ULN but ≤ 10 times ULN without concurrent total bilirubin ≥ 2 times ULN, both nivolumab and cabozantinib should be withheld until these adverse reactions recover to Grades 0–1. Corticosteroid therapy may be considered. Rechallenge with a single medicine or rechallenge with both medicines after recovery may be considered. If rechallenging with cabozantinib, refer to cabozantinib product insert.</li> <li>If ALT or AST > 10 times ULN or > 3 times ULN with concurrent total bilirubin ≥ 2 times ULN, both nivolumab and cabozantinib should be permanently discontinued and corticosteroid therapy may be considered.</li> </ul> For RCC patients treated with nivolumab in combination with cabozantinib, refer to the product insert regarding treatment modifications of cabozantinib. Special populations Paediatric population The safety and efficacy of OPDIVO in children below 18 years of age have not been established, except in adolescents 12 years of age and older with melanoma. Elderly No dose adjustment is required for elderly patients (≥ 65 years) (see sections 5.1 and 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Renal impairment Based on the population pharmacokinetic (PK) results, no dose adjustment is required in patients with mild or moderate renal impairment (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Data from patients with severe renal impairment are too limited to draw conclusions on this population. Hepatic impairment Based on the population PK results, no dose adjustment is required in patients with mild or moderate hepatic impairment (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Data from patients with severe hepatic impairment are too limited to draw conclusions on this population. OPDIVO must be administered with caution in patients with severe (total bilirubin >3 x ULN and any AST) hepatic impairment. Method of administration OPDIVO is for intravenous use only. It is to be administered as an intravenous infusion over a period of 30– 60 minutes. The infusion must be administered through a sterile, non-pyrogenic, low protein binding in-line filter with a pore size of 0.2–1.2 micrometre. Do not coadminister other drugs through the same intravenous line. OPDIVO must not be administered as an intravenous push or bolus injection. The total dose of OPDIVO required can be infused directly as a 10 mg/mL solution or can be diluted to as low as 1 mg/mL with sodium chloride 9 mg/mL (0.9%) solution for injection or glucose 50 mg/mL (5%) solution for injection. When administered in combination with ipilimumab and/or chemotherapy, OPDIVO should be given first followed by ipilimumab (if applicable) and then chemotherapy on the same day. Use separate infusion bags and filters for each infusion. For instructions on the handling of the medicinal product before administration, see section 6.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.
Route Of Administration: INTRAVENOUS DRIP
Indication Info: 4.1 Therapeutic indications Melanoma OPDIVO as monotherapy or in combination with ipilimumab is indicated for the treatment of advanced (unresectable or metastatic) melanoma in adults and adolescents 12 years of age and older. Relative to nivolumab monotherapy, an increase in progression-free survival (PFS) for the combination of nivolumab with ipilimumab is established only in patients with low tumour PD-L1 expression (see sections 4.4 and 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Adjuvant treatment of melanoma OPDIVO as monotherapy is indicated for the adjuvant treatment of adults and adolescents 12 years of age and older with Stage IIB or IIC melanoma, or melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Non-Small Cell Lung Cancer (NSCLC) OPDIVO, in combination with ipilimumab and 2 cycles of platinum-based chemotherapy, is indicated for the first-line treatment of metastatic or recurrent NSCLC in adult patients with no EGFR or ALK genomic tumor mutations. OPDIVO as monotherapy is indicated for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy in adults. Neoadjuvant treatment of NSCLC OPDIVO, in combination with platinum-doublet chemotherapy, is indicated for the neoadjuvant treatment of adult patients with resectable (tumours ≥4 cm or node positive) NSCLC. Neoadjuvant and adjuvant treatment of NSCLC OPDIVO, in combination with platinum-doublet chemotherapy as neoadjuvant treatment, followed by monotherapy as adjuvant treatment, is indicated in adult patients with resectable (tumors ≥4 cm or node positive) NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements. Malignant pleural mesothelioma (MPM) OPDIVO, in combination with ipilimumab, is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma. Renal Cell Carcinoma (RCC) OPDIVO, in combination with ipilimumab, is indicated for the treatment of patients with intermediate or poor-risk, previously untreated advanced renal cell carcinoma. OPDIVO as monotherapy is indicated for the treatment of advanced renal cell carcinoma after prior therapy in adults. OPDIVO in combination with cabozantinib is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Classical Hodgkin Lymphoma (cHL) OPDIVO as monotherapy is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma after autologous stem cell transplant (ASCT) and treatment with brentuximab vedotin (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Squamous Cell Cancer of the Head and Neck (SCCHN) OPDIVO as monotherapy is indicated for the treatment of recurrent or metastatic squamous cell cancer of the head and neck in adults progressing on or after platinum-based therapy in adults (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Gastric/ Gastroesophageal Junction (GEJ) Cancer OPDIVO as monotherapy is indicated for the treatment of adult patients with unresectable locally advanced or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma after two or more prior systemic therapies. Oesophageal Squamous Cell Carcinoma (OSCC) OPDIVO in combination with ipilimumab is indicated for the first-line treatment of adult patients with unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma with tumour cell PD-L1 expression ≥1%. OPDIVO in combination with fluoropyrimidine- and platinum-based combination chemotherapy is indicated for the first-line treatment of adult patients with unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma with tumour cell PD-L1 expression ≥1%. OPDIVO as monotherapy is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma after prior fluoropyrimidine- and platinum-based combination chemotherapy. Gastric Cancer, Gastroesophageal Junction (GEJ) Cancer or Oesophageal Adenocarcinoma OPDIVO, in combination with fluoropyrimidine- and platinum-based chemotherapy, is indicated for the treatment of patients with unresectable HER2 negative advanced or metastatic gastric cancer, gastroesophageal junction cancer, or oesophageal adenocarcinoma (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Adjuvant treatment of oesophageal or gastroesophageal junction cancer (OC or GEJC) OPDIVO as monotherapy is indicated for the adjuvant treatment of completely resected oesophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT). Hepatocellular carcinoma (HCC) OPDIVO in combination with ipilimumab is indicated for the first-line treatment of adult patients with unresectable or advanced hepatocellular carcinoma. Urothelial carcinoma OPDIVO, in combination with cisplatin and gemcitabine, is indicated for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma. OPDIVO as monotherapy is indicated for the adjuvant treatment of adults with muscle invasive urothelial carcinoma (MIUC) with tumor cell PD-L1 expression ≥1% who are at high risk of recurrence after undergoing radical resection of MIUC. Mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) colorectal cancer (CRC) OPDIVO in combination with ipilimumab is indicated for the first-line treatment of adult patients with mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) unresectable or metastatic colorectal cancer.
Contraindications: 4.3 Contraindications Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.
Atc Code: L01FF01
Atc Item Name: nivolumab
Pharma Manufacturer Name: BRISTOL-MYERS SQUIBB (SINGAPORE) PTE. LTD.

Active Ingredients

Nivolumab

10mg/mL

NIVOLUMAB

10 MG/ML

Approved

Quick Info

Agency

HSA

Country

🇸🇬

Approval Date

Apr 4, 2016

Approval ID

03fd0cab43400fe6

Type

Therapeutic

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