An introduction to Nivolumab (Opdivo®) and its common usage and dosage.(Part 1)👀👀👀

Nivolumab (Opdivo®) is a monoclonal antibody. It binds to the PD-1 receptor,
thereby blocking the interaction of the PD-1 receptor with PD-L1 and PD-L2. Immunosuppressive responses mediated by the PD-1 pathway will be blocked (such as tumor immune responses). Nivolumab can be used to treat a variety of malignant tumors in adults. Nivolumab is commonly used in the form of injection.

Common Adult Usage and Dosage of Nivolumab:

Recommended dose of nivolumab monotherapy:

Indications	Dosage	Duration
Non-small cell lung cancer (including metastatic) Head and Neck Squamous Cell Carcinoma Gastroesophageal junction adenocarcinoma	Once every two weeks, 240 mg each time, intravenous infusion over 30 minutes. or Once every four weeks, 480 mg each time, intravenous infusion over 30 minutes. or Once every two weeks, 3 mg/kg each time, intravenous infusion over 30 minutes.	Until disease progression or unacceptable toxicity.
Advanced renal cell carcinoma Classical Hodgkin's lymphoma Locally advanced or metastatic urothelial carcinoma Esophageal squamous cell carcinoma Unresectable or metastatic melanoma Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer	Once every two weeks, 240 mg each time, intravenous infusion over 30 minutes. or Once every four weeks, 480 mg each time, intravenous infusion over 30 minutes.	Until disease progression or unacceptable toxicity.
Adjuvant therapy for melanoma Adjuvant therapy for urothelial carcinoma (UC)	Once every two weeks, 240 mg each time, intravenous infusion over 30 minutes. or Once every four weeks, 480 mg each time, intravenous infusion over 30 minutes.	Until disease progression or unacceptable toxicity occurs, no longer than one year.
Adjuvant therapy after resection of esophageal or gastroesophageal junction cancer	Once every two weeks, 240 mg each time, intravenous infusion over 30 minutes. or Once every four weeks, 480 mg each time, intravenous infusion over 30 minutes. Continue for 16 weeks, then 480 mg every four weeks	Until disease progression or unacceptable toxicity. The total course of treatment is one year.

Recommended doses of nivolumab when used in combination with other drugs:

Indications	Dosage	Duration
Unresectable or metastatic melanoma	Once every three weeks, 1 mg/kg each time, intravenous infusion over 30 minutes, combined with ipilimumab 3 mg/kg intravenous injection.	Administer in combination with ipilimumab for up to four times or until unacceptable toxicity occurs, whichever occurs first.
	Once every two weeks, 240 mg each time, intravenous infusion over 30 minutes. or Once every four weeks, 480 mg each time, intravenous infusion over 30 minutes.	After completing four cycles of combination therapy, the drug was administered as a single agent until disease progression or unacceptable toxicity.
Neoadjuvant therapy for resectable non-small cell lung cancer	Nivolumab 360 mg combined with platinum-containing drugs were infused on the same day once every three weeks, intravenously over 30 minutes.	Combined with a platinum-containing doublet chemotherapy regimen for a total of three cycles.
Metastatic non-small cell lung cancer expressing PD-L1	360 mg once every three weeks, intravenous infusion over 30 minutes. Ipilimumab was administered as an intravenous infusion of 1 mg/kg over 30 minutes every 6 weeks.	Administer ipilimumab in combination until disease progression or unacceptable toxicity or up to two years in patients without disease progression.
Metastatic or recurrent non-small cell lung cancer	360 mg once every three weeks, intravenous infusion over 30 minutes. Ipilimumab was administered as an intravenous infusion of 1 mg/kg over 30 minutes every 6 weeks. Platinum-based doublet chemotherapy every three weeks	Administer ipilimumab in combination until disease progression or unacceptable toxicity or up to two years in patients without disease progression.
		Two cycles of histology-based platinum doublet chemotherapy.
Malignant pleural mesothelioma	Nivolumab 360 mg once every three weeks is administered as an intravenous infusion over 30 minutes. Ipilimumab was administered as an intravenous infusion of 1 mg/kg over 30 minutes every 6 weeks. Or Nivolumab 3 mg/kg every two weeks.	Administer ipilimumab in combination until disease progression or unacceptable toxicity or up to two years in patients without disease progression.
Advanced renal cell carcinoma	Nivolumab 3 mg/kg once every 3 weeks, with ipilimumab 1 mg/kg, was infused intravenously over 30 minutes.	Use in combination with ipilimumab for four doses.
	Once every two weeks, 240 mg each time, intravenous infusion over 30 minutes. or Once every four weeks, 480 mg each time, intravenous infusion over 30 minutes.	Nivolumab: Until disease progression, unacceptable toxicity or up to two years.
	Nivolumab and cabozantinib 40 mg are taken orally once daily without food.	Cabozantinib: until disease progression or unacceptable toxicity.
	Once every two weeks, 240 mg each time, intravenous infusion over 30 minutes. or Once every four weeks, 480 mg each time, intravenous infusion over 30 minutes.	After completing four doses of ipilimumab combination therapy, it was administered as a single agent until disease progression or unacceptable toxicity.
Microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer	Nivolumab 3 mg/kg once every 3 weeks, with ipilimumab 1 mg/kg, was infused intravenously over 30 minutes.	Combined with ipilimumab for four doses.
	Once every two weeks, 240 mg each time, intravenous infusion over 30 minutes. or Once every four weeks, 480 mg each time, intravenous infusion over 30 minutes.	After completing four doses of combination therapy, the drug was administered as a single agent until disease progression or unacceptable toxicity.
Hepatocellular carcinoma	Nivolumab 3 mg/kg once every 3 weeks, with ipilimumab 1 mg/kg, was infused intravenously over 30 minutes.	Combined with ipilimumab for four doses.
	Once every two weeks, 240 mg each time, intravenous infusion over 30 minutes. or Once every four weeks, 480 mg each time, intravenous infusion over 30 minutes.	After completing four doses of combination therapy, the drug was administered as a single agent until disease progression or unacceptable toxicity.
Esophageal squamous cell carcinoma	Once every two weeks, 240 mg each time, intravenous infusion over 30 minutes. or Once every four weeks, 480 mg each time, intravenous infusion over 30 minutes. Nivolumab administered in combination with fluoropyrimidine-containing and platinum-containing chemotherapy	Nivolumab: Until disease progression, unacceptable toxicity or up to two years.
		Chemotherapy: Until disease progression or unacceptable toxicity.
	3 mg/kg once every two weeks, intravenous infusion over 30 minutes. or 360 mg once every three weeks, intravenous infusion over 30 minutes. Combined with ipilimumab, 1 mg/kg per dose is administered intravenously over 30 minutes every six weeks.	Use in combination with ipilimumab until disease progression, unacceptable toxicity, or up to two years.
Gastric cancer, gastroesophageal junction cancer, esophageal adenocarcinoma	240mg once every two weeks, intravenous infusion for 30 minutes, fluoropyrimidine-containing and platinum-containing chemotherapy once every two weeks or 360 mg once every three weeks, intravenous infusion for 30 minutes, fluoropyrimidine-containing and platinum-containing chemotherapy once every three weeks	Until disease progression, unacceptable toxicity or up to two years.

Preparation method of Nivolumab injection.

Nivolumab is generally diluted with 0.9% sodium chloride injection or 5% glucose injection to prepare an infusion solution with a concentration of 1 mg/ml to 10 mg/ml.

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An introduction to Ipilimumab (Yervoy®) and its common usage and dosage.👀👀👀

Ipilimumab (Yervoy®) is a cytotoxic T lymphocyte-associated antigen-4
(CTLA-4) immune checkpoint inhibitor. It is a monoclonal antibody that binds to CTLA-4 and inhibits the interaction between CTLA-4 and its ligands CD80/CD86. It blocks T cell inhibitory signals induced by the CTLA-4 pathway, thereby increasing the number of active effector T cells. These T cells will directly launch a T cell immune attack against tumor cells. CTLA-4 can block and reduce the ability of regulatory T cells, thus helping to enhance the anti-tumor immune response function. Ipilimumab selectively depletes regulatory T cells in tumor locations, leading to an increase in effector T cells within the tumor. It causes tumor cell death.

Common Adult Usage and Dosage of Ipilimumab:

The common dosage form of Ipilimumab is an injection. It can only be given as an IV infusion and not as an IV push or bolus injection. When it is used with nivolumab, nivolumab should be infused first, followed by ipilimumab infusion on the same day.

The combination of Ipilimumab and nivolumab is indicated for the treatment of unresectable, previously untreated, non-epitheloid malignant pleural mesothelioma: Ipilimumab - 1 mg/kg once every six weeks, administered intravenously over 30 minutes. Nivolumab - 360 mg once every three weeks, intravenous infusion over 30 minutes; or 3 mg/kg once every two weeks, intravenous infusion over 30 minutes.

Unresectable or metastatic melanoma: Ipilimumab - 3 mg/kg once every three weeks, administered intravenously over 30 minutes, for a maximum of four doses. Ipilimumab (3 mg/kg, once every three weeks, as an intravenous infusion over 30 minutes) can be used in combination with nivolumab (1 mg/kg, once every three weeks, as an intravenous infusion over 30 minutes) for a maximum of four doses or unacceptable toxicity, whichever occurs first. After completing four doses of combination therapy, nivolumab was administered as a single agent until disease progression or unacceptable toxicity.

Adjuvant treatment of melanoma: Ipilimumab - 10 mg/kg once every three weeks for a maximum of four doses, followed by 10 mg/kg once every twelve weeks for a maximum of three years, administered as a 90-minute intravenous infusion.

Advanced renal cell carcinoma: Ipilimumab (1 mg/kg, once every three weeks, intravenous infusion over 30 minutes) can be combined with nivolumab (3 mg/kg, once every three weeks, intravenous infusion over 30 minutes). After completing four doses of combination therapy, nivolumab was administered as a single agent until disease progression or unacceptable toxicity.

Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer: Ipilimumab (1 mg/kg every three weeks as an intravenous infusion over 30 minutes) may be combined with nivolumab (3 mg/kg every three weeks as an intravenous infusion over 30 minutes). After completing four doses of combination therapy, nivolumab was administered as a single agent until disease progression or unacceptable toxicity.

Hepatocellular carcinoma: Ipilimumab (3 mg/kg every three weeks as an intravenous infusion over 30 minutes) may be combined with nivolumab (1 mg/kg every three weeks as an intravenous infusion over 30 minutes). After completing four doses of combination therapy, nivolumab was administered as a single agent until disease progression or unacceptable toxicity.

Metastatic non-small cell lung cancer with PD-L1 positive expression: Ipilimumab (1 mg/kg, once every six weeks) combined with Nivolumab (360 mg, once every three weeks, intravenous infusion over 30 minutes). Patients received combination therapy until disease progression or unacceptable toxicity. Alternatively, treatment was continued for two years in patients without disease progression.

Metastatic or recurrent non-small cell lung cancer: Ipilimumab (1 mg/kg, once every six weeks) combined with Nivolumab (360 mg, once every three weeks, intravenous infusion over 30 minutes). Platinum-doublet chemotherapy was administered every three weeks based on histology. Patients received combination therapy until disease progression or unacceptable toxicity. Alternatively, treatment was continued for two years in patients without disease progression. Two cycles of histology-based platinum-doublet chemotherapy.

Esophageal squamous cell carcinoma: Ipilimumab (1 mg/kg, once every six weeks, intravenous infusion over 30 minutes) combined with Nivolumab (3 mg/kg, once every two weeks. Or 360 mg, once every three weeks. Intravenous infusion over 30 minutes) treatment. Patients received the combination therapy until disease progression, unacceptable toxicity, or up to two years.

At the same time, ipilimumab can be used to treat unresectable or metastatic melanoma, MSI-H or dMMR metastatic colorectal cancer in pediatric patients 12 years of age and older. Injection is also a commonly used dosage form of ipilimumab for children. The dosage is generally the same as that for adults.

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An introduction to Atezolizumab (Tecentriq®) and its common usage and dosage.👀👀👀

Programmed death ligand 1 (PD-L1) may be expressed on tumor cells and/or tumor-infiltrating immune cells. It promotes the suppression of antitumor immune responses in the tumor microenvironment. PD-L1 binds to the PD-1 and B7.1 receptors on T cells and antigen-presenting cells. The activity, proliferation and cytokine production of cytotoxic T cells are thereby inhibited. Atezolizumab is a monoclonal antibody. It binds to PD-L1, blocking its interaction with PD-1 and B7.1 receptors. Therefore, PD-L1/PD-1-mediated suppression of immune responses is released. This includes activating anti-tumor immune responses without inducing antibody-dependent cellular cytotoxicity. Atezolizumab (Tecentriq®) inhibits tumor growth and improves tumor immunogenicity.

Common Usage and Dosage of Atezolizumab:

Small cell lung cancer (SCLC): Atezolizumab combined with carboplatin and etoposide as first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC). 

• Recommended Usage-1: On the first day of the induction phase, atezolizumab 1200 mg is administered intravenously, followed by carboplatin and finally etoposide. Etoposide was given intravenously on the second and third days. This regimen was administered once every three weeks for a total of four treatment cycles. The induction phase is followed by a chemotherapy-free maintenance phase. During the maintenance phase, atezolizumab was administered as an intravenous infusion of 1200 mg every three weeks.
• Recommended Usage-2: Atezolizumab is administered intravenously once every two weeks, 840 mg each time. Or once every three weeks, 1200 mg each time. Or once every four weeks, 1680 mg each time. If chemotherapy is needed on the same day as atezolizumab injection, it should be given before chemotherapy.
• Duration: Until disease progression or unacceptable toxicity.
• Delayed or missed medication: If a dose is missed on the scheduled day, the dose should be given as soon as possible. The dosing schedule should also be adjusted so that the two doses are separated by three weeks.
• The safety and effectiveness of atezolizumab for the treatment of small cell lung cancer in pediatric patients younger than 18 years of age have not been established.

Hepatocellular Carcinoma (HCC): Atezolizumab combined with bevacizumab for the treatment of patients with unresectable HCC who have not received prior systemic therapy.

• Recommended Usage-1: Atezolizumab (recommended dose 1200 mg) is first intravenously infused, followed by bevacizumab 15 mg/kg intravenously, once every three weeks.
• Recommended Usage-2: Once every two weeks, 840 mg each time. Or once every three weeks, 1200 mg each time. Or once every four weeks, 1680 mg each time. If patients need to receive bevacizumab on the same day, atezolizumab should be administered before bevacizumab. (Bevacizumab once every three weeks, 15 mg/kg each time)
• Duration: May continue until disease progression or unacceptable toxicity.
• Delayed or missed medication: If a dose is missed on the scheduled day, the dose should be given as soon as possible. The dosing schedule should also be adjusted so that the two doses are separated by three weeks.
• The safety and effectiveness of atezolizumab for the treatment of hepatocellular carcinoma in pediatric patients younger than 18 years of age have not been established.

Non-Small Cell Lung Cancer (NSCLC): Atezolizumab can be used alone or in combination with pemetrexed and platinum chemotherapy to treat metastatic non-squamous NSCLC that is negative for epidermal growth factor receptor (EGFR) gene mutations and negative for anaplastic lymphoma kinase (ALK). Patients with stage II to IIIA NSCLC were selected for atezolizumab monotherapy based on PD-L1 expression on tumor cells. Select patients with first-line metastatic NSCLC for atezolizumab as monotherapy based on PD-L1 expression on tumor cells or tumor-infiltrating immune cells.

• Monotherapy dosage: The recommended dose is 1200 mg of atezolizumab administered intravenously once every three weeks until clinical benefit disappears or unacceptable toxicity occurs.
• Combination dose: When atezolizumab is used in combination with carboplatin or cisplatin and pemetrexed, 1200 mg of atezolizumab is infused intravenously on the first day of the induction phase, followed by 500 mg/m2 of pemetrexed intravenously, and finally carboplatin 6 mg/ml/min or cisplatin 75 mg/m2, administered once every three weeks for a total of four or six treatment cycles. The patients were then treated with a maintenance phase of atezolizumab 1200 mg and pemetrexed 500 mg/m2 intravenously every three weeks. Treatment continued until loss of clinical benefit or unacceptable toxicity occurred.
• Delayed or missed medication: If a dose is missed on the scheduled day, the dose should be given as soon as possible. The dosing schedule should also be adjusted so that the two doses are separated by three weeks.
• The safety and effectiveness of atezolizumab for the treatment of NSCLC in pediatric patients younger than 18 years of age have not been established.

Melanoma: Atezolizumab in combination with cobimetinib and vemurafenib is used to treat adult patients with BRAF V600 mutation-positive unresectable or metastatic melanoma.

• Recommended dose: Atezolizumab is administered as an intravenous infusion of 840 mg once every two weeks, or 1200 mg once every three weeks, or 1680 mg once every four weeks. At the same time, take 60 mg of cobimetinib orally once a day (take the medicine for 21 days and rest for 7 days) and take 720 mg of vemurafenib orally twice a day. Treatment was until disease progression or unacceptable toxicity.
• Before starting atezolizumab treatment, patients should receive a 28-day oral treatment cycle of cobimetinib and vemurafenib: 60 mg of cobimetinib once daily (21 days of treatment followed by 7 days of rest). and 960 mg of vemurafenib twice daily (Days 1 to 21), followed by 720 mg of vemurafenib twice daily (Days 22 to 28).
• The safety and effectiveness of atezolizumab for the treatment of melanoma in pediatric patients younger than 18 years of age have not been established.

Alveolar soft part sarcoma (ASPS): Atezolizumab is indicated as a monotherapy for the treatment of unresectable or metastatic ASPS.

• Usual dosage for adults: Atezolizumab 840 mg once every two weeks, or 1200 mg once every three weeks, or 1680 mg once every four weeks. Treatment was until disease progression or unacceptable toxicity.
• Usual dose for children: Atezolizumab can also be used as a single agent to treat unresectable or metastatic ASPS in children 2 years and older. 15 mg/kg once every three weeks, maximum dose is 1200 mg. Treatment was until disease progression or unacceptable toxicity.

The initial intravenous infusion should last at least 60 minutes. If the patient tolerates the first infusion well, the duration of subsequent infusions can be shortened appropriately, but should continue for at least 30 minutes.

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An introduction to Avelumab (Bavencio®) and its common usage and dosage.👀👀👀

Avelumab (Bavencio®): It is a Programmed Death Ligand 1 (PD-L1) inhibitor that was first approved by the FDA in 2017. Programmed Death Ligand 1 is expressed on tumor cells and immune cells infiltrating tumors. It suppresses anti-tumor immunity in the tumor microenvironment. PD-1 and B7.1 receptors on T cells and antigen-presenting cells bind to PD-L1. They inhibit cytotoxic T-cell activity, T-cell proliferation, and cytokine production. The binding of avelumab to PD-L1 will prevent PD-L1 from interacting with PD-1 and B7.1 receptors. Therefore, it can restore immune responses, including anti-tumor immune responses. In in vitro studies, avelumab induced antibody-dependent cell-mediated cytotoxicity (ADCC). Blocking PD-L1 activity has also been shown to reduce tumor growth in mouse tumor models.

Common Usage and Dosage of Avelumab:

Metastatic Merkel cell carcinoma (MCC): Avelumab can be used in patients 12 years of age and older with metastatic Merkel cell carcinoma. It is recommended for intravenous infusion of 800 mg every two weeks (infusion time is 60 minutes) until disease progression or unacceptable toxicity occurred.

Locally advanced or metastatic urothelial carcinoma (UC): Avelumab is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have not progressed on first-line platinum-containing chemotherapy. It is also indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease has progressed during or after platinum-containing chemotherapy, and for patients with locally advanced or metastatic urothelial carcinoma whose disease has progressed within 12 months of neo-adjuvant or adjuvant treatment with platinum-containing chemotherapy. It is recommended for intravenous infusion of 800 mg every two weeks (infusion time is 60 minutes) until disease progression or unacceptable toxicity occurred.

Advanced Renal Cell Carcinoma (RCC): Avelumab can be used in combination with axitinib as a first-line treatment for patients with advanced RCC. It is recommended to be administered by intravenous infusion of 800 mg (infusion time is 60 minutes) every two weeks in combination with oral axitinib 5 mg (twice daily, 12 hours apart, with or without food) until disease progression or unacceptable toxicity occurred. When used in combination with axitinib, it may be considered to increase axitinib to above 5 mg every two weeks or longer intervals. However, before adjusting the dose, the relevant physiological indicators of axitinib should be reviewed. 

The recommended dose for children 12 years and older is the same as that for adults. However, the safety and efficacy of avelumab in patients younger than 12 years of age have not yet been established.

Administration of Avelumab:

Before the first four infusions of avelumab, patients were given antihistamines and acetaminophen. Subsequent Avelumab treatment requires prophylactic medication based on previous injection reactions, severity and clinical judgment.

Common adverse reactions:

• Gastrointestinal disorders: abdominal pain, constipation, diarrhea, nausea, vomiting.
• General disorders: fatigue, infusion-related reactions, peripheral edema.
• Metabolic and nutritional disorders: decreased appetite and weight loss.
• Musculoskeletal and Connective Tissue Disorders: arthralgia, musculoskeletal pain.
• Nervous system disorders: dizziness, headache.
• Respiratory, thoracic and mediastinal disorders: cough, dyspnea.
• Skin and subcutaneous tissue disorders: itching, rash.
• Vascular disease: hypertension.
• Laboratory index changes: anemia, hyperglycemia, increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), increased lipase, increased amylase, increased bilirubin, lymphocytopenia, neutropenia, thrombocytopenia.

Serious adverse reactions:

• Blood disorders: anemia.
• Cardiovascular disease: hypertension.
• Gastrointestinal diseases: abdominal pain, intestinal obstruction.
• Infections: cellulitis, sepsis.
• Kidney disease: acute kidney injury, hematuria, urinary tract infection.
• Respiratory disorders: difficulty breathing.

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An introduction to Durvalumab (Imfinzi®) and its common usage and dosage.👀👀👀

1. Durvalumab (Imfinzi®): It is a monoclonal antibody that inhibits programmed death ligand 1 (PD-L1). Durvalumab is a human immunoglobulin G1κ (IgG1κ) monoclonal antibody. It is produced by using recombinant DNA technology in Chinese hamster ovary (CHO) cells which cultured in suspension. The expression of PD-L1 may be induced by inflammatory signals (such as IFN-γ) and can be expressed on tumor cells and tumor-associated immune cells in the tumor microenvironment. T cell function and activation are blocked due to the interaction of PD-L1 with PD-1 and CD80. PD-L1 binds to its receptor and reduces activation, proliferation, and cytokine production of cytotoxic T cells. Durvalumab binds to PD-L1 and inhibits the interaction of PD-L1 with PD-1 and CD80. The effects of PD-L1/PD-1 and PD-L1/CD80 on suppressing the release of immune responses will therefore be blocked. In in vitro studies, blocking PD-L1 with durvalumab resulted in increased T cell activation. It reduces tumor size in both human tumor transplantation and immune cell allogeneic transplantation in mouse models.

Indications and dosage:

Locally advanced non-small cell lung cancer (NSCLC): durvalumab can be used to treat patients with locally advanced, unresectable non-small cell lung cancer who have not worsened after receiving radiation therapy and platinum-based chemotherapy.

• For patients with locally advanced non-small cell lung cancer over 30 kg, it is recommended to take 10 mg/kg once every two weeks or 1500 mg once every four weeks. 
• For patients less that 30 kg, it is recommended to take 10mg/kg once every two weeks.
• The duration of treatment with durvalumab is until disease progression, development of intolerable toxicity, or up to 12 months. 

Small cell lung cancer (SCLC): Durvalumab is used in combination with etoposide and either carboplatin or cisplatin as a first-line treatment for patients with extensive stage-small cell lung cancer (ES-SCLC).

• For patients with extensive stage-small cell lung cancer over 30 kg, it is recommended to take 1500 mg once every three weeks (21 days) in combination with chemotherapy for four cycles, and then 1500 mg once every four weeks as a monotherapy. 
• Patients weighing less that 30 kg should be treated with chemotherapy at 20 mg/kg once every three weeks (21 days) for four cycles, and then a monotherapy of 20 mg/kg once every four weeks until the weight increases to more than 30 kg.
• The duration of treatment with durvalumab is until the patient's condition worsens or until intolerable toxicity occurs.

Cholangiocarcinoma: Durvalumab is used in combination with cisplatin and gemcitabine to treat adult patients with locally advanced or metastatic cholangiocarcinoma.

• For patients weighing more than 30kg, it is recommended to receive 1500 mg once every three weeks (21 days) combined with chemotherapy for four cycles, followed by monotherapy of 1500 mg once every four weeks. 
• Patients weighing less than 30kg are recommended to receive 20 mg/kg once every three weeks (21 days) combined with chemotherapy for four cycles, followed by monotherapy of 20 mg/kg once every four weeks. 
• Durvalumab treatment is continued until the patient's condition worsens or until intolerable toxicity occurs.

Hepatocellular carcinoma: Durvalumab combined with tremelimumab is indicated for the treatment of adult patients with advanced or unresectable hepatocellular carcinoma (uHCC) who have not received systemic therapy.

• For patients weighing more than 30kg: A single dose of tremelimumab 300 mg was given on day 1 of cycle 1, followed by durvalumab 1500 mg, then every four weeks with a monotherapy of durvalumab 1500 mg.
• For patients weighing less than 30kg: A single dose of tremelimumab 4 mg/kg was given on day 1 of cycle 1, followed by durvalumab 20 mg/kg, then every four weeks with a monotherapy of durvalumab 20 mg/kg.
• The duration of treatment with durvalumab was after the first cycle of combination therapy, then durvalumab was administered as a monotherapy every four weeks until the patient's disease worsened or unacceptable toxicity occurred.

Administration method:

During the infusion, the intravenous infusion tube must be infused for 60 minutes with a 0.2 or 0.22 micron in-tube filter (sterile, low protein binding rate). Do not give other medications through the same infusion line at the same time. When durvalumab is combined with tremelimumab, administer tremelimumab for 60 minutes followed by observation for 60 minutes. Durvalumab is then infused for an additional 60 minutes on the same day. A separate infusion bag and filter must be used for each infusion. 

Adverse effects: 

Diarrhea, hepatitis, hypothyroidism, joint pain, loss of appetite, pneumonitis (sudden severe coughing, wheezing), rash/dry itchy skin.

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What are the functions of various B vitamins?🔢🔢🔢

There are many kinds of vitamin B, such as vitamin B1, B2, B6, and B12. They all work in different ways and can relieve many different symptoms. They will be introduced one by one below.

1. Vitamin B1：Alcoholics should supplement in appropriate amounts.

Vitamin B1 is also called thiamine. Long-term alcohol consumption can cause vitamin B1 deficiency. Beriberi is another name for vitamin B1 deficiency. Its early symptoms include fatigue, headache, loss of appetite, muscle aches, etc. As the condition worsens, patients may develop edema, heart failure, peripheral neuropathy, and Wernicke's encephalopathy. 

Recommended supplementary foods: cereals, egg yolks, lean meat, milk, tomatoes, etc.

Vitamin B1 supplement: Vitamin B1 tablets are used to prevent and treat vitamin B1 deficiency, such as beriberi complicated with neuritis or indigestion. Adults take it orally three times a day, 10 to 20 mg each time.

2. Vitamin B2: Patients with angular stomatitis or chapped lips can supplement it in appropriate amounts.

Vitamin B2 is also called riboflavin. It has a close relationship with protein metabolism. Lack of vitamin B2 reduces the activity of lysyl oxidase, which affects the formation of collagen cross-links. It is considered to be a major cause of skin damage. Symptoms of vitamin B2 deficiency will first appear on the skin. The most common clinical manifestations are pale mucous membranes and ulcers at the corners of the mouth (angular stomatitis), cinnabar-red lips (cheilosis), and scrotal inflammation.

Recommended supplementary foods: animal liver, animal kidney, eggs, milk, soybeans, etc.

Vitamin B2 supplement: Vitamin B2 tablets are used to prevent and treat vitamin B2 deficiency, such as angular stomatitis, chapped lips, conjunctivitis, glossitis, scrotumitis, seborrheic dermatitis, etc. Adults take it orally 3 times a day, 5 to 10 mg each time. It is recommended to be taken after meals. After taking vitamin B2 tablets, the urine will turn yellow, which is a normal reaction.

3. Vitamin B3: Patients with pellagra can supplement it in appropriate amounts.

Niacin plays an important role in maintaining normal tissue, especially the integrity of the digestive tract, nervous system, and skin. Niacin deficiency is also known as pellagra. The clinical manifestations of pellagra are dementia, dermatitis, diarrhea and death. Dermatitis is its most typical symptom, usually appearing on exposed parts of the limbs and appearing symmetrically. It is manifested as a diffuse pigmented rash.

Recommended supplementary foods: animal liver, animal kidney, fish, meat, peanuts, soybeans, etc.

Niacin supplement: Niacin tablets are used to prevent and treat niacin deficiency disorders such as pellagra. Adults take it orally 5 times a day, 50 to 100 mg each time. It is not advisable to take more than 500 mg a day. Common adverse reactions include headache, skin redness (especially on the face and neck) and other vasodilation reactions. Taking large doses of niacin may cause arrhythmia, hyperglycemia, hyperuricemia, and liver toxicity.

4. Vitamin B6: Patients with seborrheic dermatitis can supplement it in appropriate amounts.

Vitamin B6 is involved in the metabolism of neurotransmitters and all amino acids. Patients lacking vitamin B6 will mainly suffer from skin and mucosal inflammation, including glossitis, stomatitis, seborrheic dermatitis and desquamative dermatitis. In addition, some patients may develop mental and neurological symptoms such as peripheral neuritis and depression.

Recommended supplementary foods: lean meat, liver, vegetables, etc.

Vitamin B6 supplement: Vitamin B6 tablets can be used to prevent and treat vitamin B6 deficiency such as chapped lips and seborrheic dermatitis. It can also be used to relieve pregnancy vomiting. Adults take 10 to 20 mg orally daily for three weeks. Long-term or excessive use of vitamin B6 may cause severe peripheral neuritis. Patients may experience abnormal nerve sensations, unsteady gait, and numbness in their hands and feet. Therefore, patients must take the recommended dosage, do not take excessive amounts, and should stop taking the medicine after 3 weeks.

5. Folic acid: Women preparing for pregnancy can supplement it in appropriate amounts.

Folic acid is also called vitamin B9, vitamin M or vitamin B11. Folic acid is an essential component for the synthesis of DNA and RNA. It participates in various metabolic links in the human body. It is an essential substance for the growth and reproduction of body cells. It is also involved in the maturation of red blood cells. Folic acid is also required for the development of the fetal nervous system.

Recommended supplementary foods: Animal liver, fruits, green vegetables, etc.

Folic acid supplement: Folic acid tablets are mainly used as supplements for pregnant and lactating women. It prevents congenital neural tube defects in fetuses. Women of childbearing age should take 0.4 mg orally once a day from the time of planning pregnancy to the end of the third month after pregnancy. Folic acid can turn urine yellow when taken in large amounts.

6. Vitamin B12: Patients with peripheral neuropathy can supplement it in appropriate amounts.

Vitamin B12 is also called cobalamin. It is the only vitamin that contains metallic elements. Vitamin B12 can increase the bioavailability of folic acid, thereby promoting the synthesis of DNA and nucleic acids. It is also an essential component required for the synthesis of nerve myelin lipoproteins. Patients lacking vitamin B12 may develop megaloblastic anemia and peripheral neuropathy. Methylcobalamin is the active form of vitamin B12 in the body.

Recommended supplementary foods: Dairy products, meat, eggs, fish, etc.

Vitamin B12 supplement: Methylcobalamin tablets are used to treat peripheral neuropathy and megaloblastic anemia caused by vitamin B12 deficiency. Adults take 0.5 mg orally three times a day. Methylcobalamin is easily decomposed by light. Therefore, it should be used immediately after opening and should be protected from light. In addition, when used to treat peripheral neuropathy, if taking it for more than one month is ineffective, there is no need to continue taking it.

7. Other Vitamin B:

• Vitamin B4: It can be used to prevent and treat acute granulocytopenia and leukopenia caused by various causes (especially caused by tumor chemotherapy and radiotherapy and benzene poisoning).

• Vitamin B5: It is also called pantothenic acid. Pantothenic acid deficiency is rare in humans because pantothenic acid is widely present in food.

• Vitamin B7: It is also known as biotin or vitamin H. Biotin comes from a wide range of sources. Human intestinal bacteria can also synthesize it. Therefore, biotin deficiency rarely occurs. However, raw egg whites contain proteins that resist biotin, so long-term use of large amounts of raw egg whites may lead to biotin deficiency.

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What are the characteristics of pregabalin?📄📄📄

Pregabalin is a drug used to treat neuropathic pain. Clinically, it is widely used to treat post-herpetic neuralgia, neuralgia caused by diabetic neuropathy, etc.

What are the clinical indications for pregabalin?

Pregabalin is clinically approved for the treatment of diabetic peripheral neuropathy, fibromyalgia, neuralgia associated with spinal cord injury, partial seizures in certain adults with epilepsy, and postherpetic neuralgia. In addition, it will also be used to treat postoperative or post-traumatic neuropathic pain, tumor-related neuropathic pain, and chemotherapy-related neuropathic pain.

What is the mechanism of action of pregabalin?

Clinically, it is believed that changes in calcium ion channels in the nervous system are related to neuropathic pain. Calcium ion channels are composed of four subunits: α1, α2-δ, β, and γ. Pregabalin binds to the α2-δ subunit of calcium channels in the nervous system. It inhibits neuronal presynaptic membrane Ca2+ influx. This reduces the release of excitatory neurotransmitters (such as calcitonin, glutamate, substance P, etc.), thereby controlling pain. 

What is the dosage of pregabalin?

Oral pregabalin mainly comes in regular dosage forms and sustained-release dosage forms.

Common oral dosage forms of pregabalin: It is generally taken two to three times daily, with or without food.

Treatment of postherpetic neuralgia and diabetic peripheral neuropathic pain:

• Initial dose: 150 mg orally daily in two to three divided doses.
• Adjust the dose: According to the drug's efficacy and the patient's tolerance, it can be increased to 300 mg orally daily within one week, taken in two to three times. If the patient takes 300 mg daily, the pain symptoms cannot be fully relieved after two to four weeks and the patient can tolerate pregabalin. The dose can be increased to 600 mg orally daily in two to three divided doses.

Treating fibromyalgia:

• Initial dose: 75 mg orally twice daily.
• Adjust the dose: It can be increased to 150 mg twice daily (300 mg/d) within a week based on the efficacy of the drug and the patient's tolerance. If the patient does not have sufficient efficacy even if taking 300 mg daily, the dosage can be increased to 225 mg twice daily (450 mg/d). However, it is considered that the adverse effects of pregabalin are dose-dependent, so the dose exceeding 450 mg/d is not recommended.

Sustained-release preparation: Take once daily orally after dinner. 

Pregabalin is mainly absorbed in the upper small intestine and its sustained-release dosage forms generally use a material that floats in the stomach as a backbone. After dinner, the gastric pylorus closes better and the gastric emptying rate slows down. Therefore, taking the extended-release form of pregabalin after dinner may increase its retention and release time in the stomach. It promotes drug absorption and improves bioavailability. Additionally, patients often experience more severe pain symptoms at night. Therefore, patients will have better analgesic effects if they take the medicine at night. Drowsiness and dizziness are the most common adverse reactions of pregabalin. Therefore, by the time a patient takes pregabalin in the evening and its drug levels reach peak levels, the patient will already be less active or sleeping. This increases patient tolerance and compliance with the medication.

What are the adverse reactions of pregabalin?

The most common adverse reactions are drowsiness and dizziness. Common ones include increased appetite (weight gain), blurred vision, conjunctivitis, disorientation, ecchymosis, abnormal gait, loss of libido, joint pain, leg cramps, myalgia, nasopharyngitis, etc. Some patients with diabetes may need to adjust the dose of their antidiabetic medications because they gain weight while taking pregabalin. If the patient develops angioedema, he should stop taking the drug immediately and seek medical treatment promptly. Patients should inform their doctor as soon as possible if they develop unexplained muscle pain, tenderness, or weakness (especially if these muscle symptoms are accompanied by general malaise or fever) and visual changes.

After short-term or long-term treatment with pregabalin, some patients may experience withdrawal symptoms after stopping the drug. Therefore, if a patient needs to discontinue pregabalin, it is recommended that the dose be tapered over at least one week. Patients should abstain from alcohol while taking pregabalin.

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