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.

Read More

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.

Read More

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.

Read More

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.

Read More

What is the difference between azivudine, monogravir and nematvir/ritonavir?💫💫💫

Azivudine, monogravir and nematvir/ritonavir are all clinical drugs used to treat the new coronavirus. What's the difference between them? 

What is the anti-coronavirus mechanism?

The new coronavirus is composed of RNA and protein. The raw material for RNA synthesis is cytosine nucleoside. Azivudine and monogravir are cytosine nucleoside analogs. They will synthesize poor RNA with the new coronavirus and inhibit the replication of the virus. Nematvir is a peptidomimetic substance. It will prevent the virus from synthesizing functional proteins by inhibiting 3C-like protease, and the replication of the virus will be inhibited. Although ritonavir has no effect against the new coronavirus, it will inhibit the elimination of nematvir and enhance its effect.

What are the properties of azivudine, monogravir and nematvir/ritonavir?

Due to their different chemical structures, they have different adverse reactions and metabolic processes in the body. 

Bone and Cartilage Toxicity: In trials, rats were repeatedly dosed with monogravir, which caused toxicity to the bones and cartilage of rats. Therefore, monogravir may affect bone and cartilage development in children.

Dosage in Patients with Hepatic or Renal Impairment: Monolavir is not eliminated primarily through the liver or kidneys, so no dose adjustment is required in patients with hepatic or renal impairment.

Drug interactions:

• Azivudine: Caution is required when combined with amiodarone, colchicine, dabigatran, digoxin, dronedarone, voriconazole, grapefruit juice, etc.
• Monolavir: Due to limited available data, no drug interactions have been found.
• Nematvir/ritonavir: These interact with many medicines.

What are the treatment differences between azivudine, monogravir, and nematvir/ritonavir?

Azivudine: It is mainly used to treat adult patients with characteristic pneumonia manifestations of new coronavirus infection visible on imaging (moderate infection). It is not intended for use in pregnant or breastfeeding women. If Azivudine is used, breastfeeding should be discontinued during treatment and for 4 days after treatment.

Monolavir: It is indicated for the treatment of adult patients with mild or moderate infections within five days of onset and who are at high risk for progression to severe disease. It has fetal toxicity similar to that of azivudine. If monogravir is used, breastfeeding should be discontinued during treatment and for 4 days after the end of treatment.

Nematrevir/ritonavir: Same indications as monogravir. However, it may still be used when the potential benefit to the mother outweighs the potential risk to the fetus. If nematvir/ritonavir is used, breastfeeding should be discontinued during treatment and for 7 days after the end of treatment.

What are the dosages of azivudine, monogravir, and nematvir/ritonavir?

Azivudine: If taken after meals, its absorption rate and total amount will be increased. Changes in drug concentration in the blood will also increase, thereby increasing the risk of adverse reactions. Its recommended usage is to take it orally once on an empty stomach before going to bed, 5mg each time (generally each tablet is 1mg, 5 pills taken orally each time), and the course of treatment should not exceed 14 days.

Monolavir: Take on an empty stomach or with food, once every 12 hours, 0.8g each time (usually 0.2g per tablet, 4 tablets taken orally each time) for 5 consecutive days.

Nematrevir/ritonavir: Take on an empty stomach or with food, once every 12 hours, 300 mg of nematvir (each tablet is 150 mg, 2 tablets taken orally each time) and 100 mg of ritonavir ( Each tablet is 100mg, 1 tablet taken orally at a time), taken continuously for 5 days.

What are the adverse reactions of azivudine, monogravir, and nematvir/ritonavir?

Azivudine: Common adverse reactions include diarrhea, increased transaminases, increased breathing, and occasionally increased the level of blood glucose. It may cause moderate to severe damage to the liver, so patients with moderate to severe liver damage should use it with caution.

Monolavir: Common adverse reactions include diarrhea, nausea, dizziness, and occasionally rash and urticaria.

Nematrevir/ritonavir: Common adverse reactions include diarrhea and taste problems, and occasionally elevated transaminases. It may cause severe liver damage and is therefore contraindicated in patients with severe hepatic impairment.

Additionally, they can affect fertility. Therefore, it recommends the use of effective contraception during and for 4 days after treatment with azivudine and monogravir, and the use of effective contraception during and for 7 days after treatment with nematvir/ritonavir.

Read More

What is the difference between acetaminophen and ibuprofen?👀👀👀

Acetaminophen and ibuprofen are very commonly used antipyretic and
analgesic drugs in clinical practice. However, their chemical structure, intensity of action and adverse reactions will differ. Will there be any difference in clinical use?

Difference in effectiveness of acetaminophen and ibuprofen.

The analgesic and antipyretic effect of ibuprofen is slightly stronger than that of acetaminophen, and its duration is also longer (ibuprofen <183 minutes, acetaminophen <134 minutes). However, ibuprofen takes a slightly slower onset of action. Patients will experience a more significant decrease in body temperature within 30 minutes of taking acetaminophen than ibuprofen. Both of them can be used to treat headaches, migraines, toothaches, muscle pain, dysmenorrhea (ibuprofen is more effective), and osteoarthritis (ibuprofen is more effective). However, acute attacks of gout and rheumatoid arthritis can only be treated with ibuprofen. Neither of them can be used to treat abdominal pain. In terms of effectiveness alone, ibuprofen is superior to acetaminophen.

Comparison of the safety of acetaminophen and ibuprofen.

Acetaminophen: Excessive doses of acetaminophen can cause life-threatening liver failure. Patients who are dehydrated or malnourished also have an increased risk of liver damage. It is less damaging to the gastrointestinal tract. It is contraindicated in patients with viral hepatitis and favismia. It should be used with caution in patients with renal insufficiency, active peptic ulcer, or aspirin allergy. Acetaminophen may also be used during pregnancy and in patients with severe heart failure.

Ibuprofen: It can cause irreversible damage to the kidneys. Overdose or use while dehydrated may increase a patient's risk of kidney damage. It also increases the risk of myocardial infarction and cerebral infarction. Although it can also cause gastrointestinal bleeding, ulceration, and perforation, the risk is lower than other NSAIDs. Ibuprofen is contraindicated in patients with renal insufficiency, active peptic ulcer, severe heart failure, pregnancy, and aspirin allergy. However, it can be used in patients with viral hepatitis and favismia.

Precautions when using acetaminophen and ibuprofen.

Acetaminophen: It can be used in children older than 3 months and can be taken before meals. The maximum daily dose for children is 15 mg/kg and for adults it is 2 g/day, once every 4 to 6 hours, and should not be taken more than 4 times a day. Alcohol and other hepatotoxic drugs can worsen liver damage when combined with acetaminophen. Acetaminophen is occasionally used concomitantly with coumarin anticoagulants without significant effects.

Ibuprofen: It can be used in children older than 6 months, with or after meals. The maximum daily dose for children is 10mg/kg and for adults it is 1.2g/day, once every 6 to 8 hours, and should not be taken more than 4 times a day. When ibuprofen is combined with alcohol, it can aggravate gastrointestinal damage. When used together with antihypertensive drugs, it will also reduce the antihypertensive effect. It may also reduce the effectiveness of low-dose aspirin in preventing cardiovascular disease and stroke. Other nephrotoxic drugs may worsen kidney damage when used with ibuprofen. When anticoagulant drugs such as heparin and dicoumarol are used together with it, it will prolong the prothrombin time and increase the risk of bleeding.

Conclusion.

For children, the elderly over 60 years old, and patients with multiple underlying diseases (except those with liver dysfunction), it is recommended to use acetaminophen first.

For patients who require long-term medication and those with arthritis, it is recommended to give priority to ibuprofen (because acetaminophen has no anti-inflammatory effect).

Read More

When should lipid-lowering drugs be taken?⌚⌚⌚

Dyslipidemia generally refers to elevated levels of cholesterol and/or
triglycerides (TG) in the blood. It is also called hyperlipidemia. At the same time, it also includes various dyslipidemias including low high-density lipoprotein cholesterol (HDL-C). The main clinical lipid-lowering drugs currently include cholesterol absorption inhibitors, HMG-CoA inhibitors (statins), fibrates, anti-lipid peroxidation drugs (probucol), niacin drugs, and PCSK9 inhibitors. , bile acid chelators, high-purity fish oil preparations and other lipid-lowering drugs, etc.

Lipid-lowering drugs can generally be divided into three categories.

1. Drugs that mainly lower cholesterol: Such drugs include statins, cholesterol absorption inhibitors, probucol, bile acid chelators. They reduce cholesterol levels by inhibiting cholesterol synthesis in liver cells, accelerating low-density lipoprotein cholesterol (LDL-C) catabolism, or reducing intestinal cholesterol absorption.
2. Drugs mainly aimed at lowering triglycerides: These drugs include fibrates, niacin and high-purity fish oil preparations. They can lower blood levels of triglycerides in patients.
3. PCSK9-inhibitors: such as evolocumab. It prevents the degradation of LDL-receptors by inhibiting PCSK9, thereby promoting the body's clearance of LDL-C. It reduces blood levels of LDL-C and has a powerful cholesterol-lowering effect.
4. Microsomal triglyceride transfer protein inhibitors: such as lomitapide. It lowers blood levels of LDL-C.
5. Apolipoprotein B-100 synthesis inhibitors: such as mipomexan. It reduces the production and secretion of VLDL. At the same time, it will also reduce the blood level of LDL-C.

The timing of taking lipid-lowering medications.

Drugs that mainly lower cholesterol:

1. Statins: Lovastatin, simvastatin, pravastatin, fluvastatin (tablets) and other statins with short half-lives are recommended to be taken before going to bed. While cholesterol will reach its synthesis peak at night, these drugs will also reach their concentration peak. Statins with long half-lives such as fluvastatin (sustained-release preparation), atorvastatin, rosuvastatin, and pitavastatin can be taken at any time, but it is recommended that patients take them at the same time every day to avoid missing doses. 
2. Cholesterol absorption inhibitors: such as ezetimibe. It inhibits the intestinal absorption of cholesterol. Statins will have a good synergistic effect when combined with it. At the same time, it will not affect the absorption of other drugs and fat-soluble vitamins. Food will not affect its absorption. Therefore, it is generally taken once daily, with or without food.
3. Probucol: It is mainly suitable for hypercholesterolemia. It will enter the core of LDL and affect lipoprotein metabolism. LDL becomes easily eliminated through non-receptor pathways. It can also reduce xanthomas on the skin. Food increases its absorption, so patients are advised to take it with a meal. Generally, it needs to be taken twice a day, with breakfast and dinner.

Drugs mainly aimed at lowering triglycerides: 

1. Fibrates: such as bezafibrate, fenofibrate, gemfibrozil. Bezafibrate generally needs to be taken with or after meals. To reduce stomach upset caused by fenofibrate, it is recommended to take it with food. Gemfibrozil is generally taken twice daily, and it is recommended to take it 30 minutes before breakfast and dinner. Additionally, when they are combined with statins, it is recommended to take fibrates in the morning and statins at bedtime. This reduces the occurrence of drug interactions.
2. Niacin drugs: This type of drugs includes acipimox and niacin extended-release tablets. The usual dose of acipimox is two or three times a day, taken with or after meals. Acipimox dispersible tablets need to be taken after meals. The usual dose of niacin extended-release tablets is once daily, taken before bed.

Read More

Basic knowledge about febuxostat.📃📃📃

Febuxostat is a xanthine oxidase inhibitor. It inhibits the production of uric acid. While allopurinol can only inhibit the reduced form of xanthine oxidase, febuxostat can inhibit both the reduced and oxidized forms of xanthine oxidase. Therefore, febuxostat's ability to lower uric acid is faster and stronger. 80% of blood uric acid is synthesized in the body, and only 20% is absorbed from food. Patients with gout need to control their blood uric acid within the target range (<360 μmol/mL) throughout their lives to reduce the frequency of gout attacks, prevent tophi formation, prevent bone destruction, and reduce the risk of death. Therefore, they may need to take long-term uric acid-lowering medications.

What are the indications for Febuxostat?

Allopurinol, febuxostat, and benzbromarone are recommended for patients with gout. However, febuxostat is not recommended for use in asymptomatic hyperuricemia. In patients with asymptomatic hyperuricemia in stages 3 and 4 chronic kidney disease, the dose of allopurinol needs to be adjusted and severe hypersensitivity reactions may occur. Therefore, febuxostat may be a better treatment. Febuxostat is indicated for the long-term treatment of hyperuricemia in patients with gout. However, it is not recommended for use in patients with asymptomatic hyperuricemia. Febuxostat has little effect on renal function. No dose adjustment is required in patients with renal insufficiency.

When should uric acid-lowering drugs be used?

Some guidelines recommend that patients with gout can start uric acid-lowering drug treatment after the acute gout attack is completely relieved for 2 to 4 weeks. This is because urate-lowering medications can worsen the symptoms of gouty arthritis. However, if gout attacks are frequent, uric acid-lowering medication can be started at the time of the gout attack. Therefore, they should not be used until the symptoms of acute inflammation of gouty arthritis have resolved. In addition, allopurinol is generally recommended as the first-choice uric acid-lowering drug, but HLA-B*5801 genotype monitoring should be performed before use. Allopurinol is contraindicated in patients with positive HLA-B*5801 genotype.

What is the dosage of Febuxostat?

Common tablet doses of febuxostat are 20mg, 40 mg and 80 mg. The recommended starting dose of febuxostat is 20 mg daily. Patients whose serum uric acid levels do not reach the target value after 2 to 4 weeks of treatment can be increased to 40 mg per day, with a maximum dose of 80 mg per day. Febuxostat tablets can usually be taken in split doses without affecting the effectiveness of the medicine. Its uric acid-lowering effect is not affected by food. 

What are the adverse effects of Febuxostat?

Common adverse reactions generally refer to adverse reactions that occur in at least 1% of patients and are at least 0.5% higher than those in the placebo group. Abnormal liver function, arthralgia, nausea, and rash are common adverse reactions of febuxostat. Abnormal liver function is the most common adverse reaction causing patients to discontinue febuxostat treatment. Therefore, patients should undergo a liver function test before doctors prescribe febuxostat. In addition, if patients experience fatigue, loss of appetite, right upper quadrant discomfort, soy sauce-colored urine or jaundice during the medication period, they should seek medical treatment in time.

Side effect	Placebo group	Allopurinol	Febuxostat
			40 mg/day	80 mg/day
Abnormal liver function	0.7%	4.2%	6.6%	4.6%
Arthralgia	0%	0.7%	1.1%	0.7%
Nausea	0.7%	0.8%	1.1%	1.3%
Rash	0.7%	1.6%	0.5%	1.6%

Febuxostat is more likely to increase the risk of cardiovascular death in patients with gout than allopurinol. Therefore, febuxostat should be used with caution in elderly patients with gout and cardiovascular and cerebrovascular diseases. Allopurinol is the first-line treatment for gout patients with severe cardiovascular disease (such as myocardial infarction, history of stroke, unstable angina). During the medication period, patients should seek medical attention immediately if they develop symptoms such as chest pain, shortness of breath, fast or irregular heartbeat, numbness or weakness on one side of the body, dizziness, difficulty speaking, or sudden severe headache.

Read More

What is the difference between allopurinol, benzbromarone and febuxostat?💫💫💫

Hyperuricemia is a very common metabolic disease today. It not only causes kidney stones, chronic kidney disease and gout in patients, but may also cause diabetes and cardiovascular and cerebrovascular diseases. Allopurinol, benzbromarone and febuxostat are the most commonly used urate-lowering drugs in clinical practice. What is the difference between the three of them?

How to choose uric acid-lowering drugs for treatment?

Febuxostat is approved only for the long-term treatment of hyperuricemia in patients with gout. In addition, due to the potential cardiovascular risks of febuxostat, it is not recommended for the treatment of patients with asymptomatic hyperuricemia. 

The first-line urate-lowering drugs for patients with asymptomatic hyperuricemia are allopurinol or benzbromarone. Patients start with the lowest dose and slowly increase to the highest available dose. If the patient's blood uric acid level does not reach the target range, allopurinol and benzbromarone can be used in combination.

First-line urate-lowering drugs for patients with diagnosed gout are allopurinol, benzbromarone and febuxostat. Patients start with the lowest dose and slowly increase to the highest available dose. If the patient's serum uric acid level fails to reach the target range, allopurinol or febuxostat is used in combination with benzbromarone. In order to reduce the frequency of gout attacks, prevent tophi formation, prevent bone destruction, and reduce the risk of death in gout patients, they need to control their blood uric acid levels to <360 μmol/ml throughout their lives. Therefore, they may need to take urate-lowering medications for life. 

What is the difference in the uric acid-lowering abilities of allopurinol, benzbromarone and febuxostat?

Increased blood uric acid levels are mainly due to increased uric acid synthesis or decreased uric acid excretion in the body. 

1. Allopurinol: It is a hypoxanthine analogue. Its active metabolites are xanthine analogs. Allopurinol inhibits the reduced form of xanthine oxidase and reduces uric acid synthesis.
2. Benzbromarone: It inhibits urate transporter-1 on the renal tubules and reduces uric acid reabsorption. The excretion of uric acid will increase and the patient's blood uric acid level will decrease.
3. Febuxostat: It is a non-purine analogue. It inhibits both the oxidized and reduced forms of xanthine oxidase. Therefore, its ability to inhibit uric acid synthesis will be stronger than that of allopurinol.

Uric acid-lowering intensity: febuxostat > allopurinol ≈ benzbromarone.

What are the advantages and risks of allopurinol?

Some studies have pointed out that allopurinol can improve vascular endothelial function and exercise tolerance in patients with angina pectoris. It can also reduce the morbidity and mortality of heart failure. Both systolic and diastolic blood pressure are lowered by allopurinol. Allopurinol may also increase creatinine clearance and decrease serum creatinine in patients with chronic kidney disease.

However, allopurinol can cause hypersensitivity syndromes such as fatal exfoliative dermatitis. HLA-B*5801 gene positivity is a risk factor for hypersensitivity reactions to allopurinol. Therefore, it is recommended that patients undergo HLA-B*5801 gene testing before using allopurinol. Allopurinol may cause renal damage, so the dose needs to be adjusted based on the patient's renal function.

What are the advantages and risks of febuxostat?

Febuxostat has the strongest uric acid-lowering ability among the three. Moreover, it is mainly cleared by the liver and has little impact on kidney function. Therefore, there is no need to adjust its dose for patients with CrCl ≥ 30ml/min.

However, febuxostat is associated with a greater risk of death from cardiovascular events than allopurinol. Therefore, allopurinol is a first-line treatment for gout patients with severe cardiovascular disease (such as myocardial infarction, history of stroke, or unstable angina).

What are the advantages and risks of benzbromarone?

Benzbromarone is a uricosuric drug. It is generally used as an alternative treatment to xanthine oxidase inhibitors. It is contraindicated in patients with CrCl <30 ml/min or in patients with kidney stones.

What are the drug interactions with uric acid-lowering drugs?

Allopurinol and febuxostat are xanthine oxidase inhibitors. Significant drug interactions may occur when they are combined with drugs that are metabolized by xanthine oxidase (such as aminophylline, azathioprine, mercaptopurine and theophylline). 

Allopurinol: It combined with amoxicillin may increase the incidence of rash. The combination of allopurinol and captopril may result in fatal Stevens-Johnson syndrome, especially in patients with chronic renal failure. Allergy and renal failure may occur when thiazide diuretics are used with it. Aluminum hydroxide may decrease the absorption of allopurinol. It will cause iron-containing hemoglobin deposition when combined with iron, so the two cannot be taken at the same time. It will also increase the bleeding risk of anticoagulant drugs, and it is recommended to monitor the patient's prothrombin time when used together.

Benzbromarone: Diuretics can increase uric acid and reduce the effectiveness of benzbromarone. It is also not suitable for use in combination with anticoagulant drugs.

What are the indications and dosages of uric acid-lowering drugs?

Allopurinol: It is indicated for primary and secondary gout, hyperuricemia secondary to malignancy, hyperuricemia after organ transplantation, and calcium oxalate stone disease. Its initial dose is 50 to 100 mg daily, taken in 1 to 3 divided doses. Its maximum dose is 600mg daily. To prevent the formation of xanthine stones, patients should drink plenty of water while taking medication. Patients need to alkalinize their urine if necessary.

Febuxostat: It is indicated for the long-term treatment of hyperuricemia in patients with gout. Its initial dose is 20 to 40 mg once daily. Its maximum dose is 80mg daily. To prevent the formation of xanthine stones, patients should drink plenty of water while taking medication. Patients need to alkalinize their urine if necessary.

Benzbromarone: It is indicated for primary and secondary hyperuricemia, gout caused by various causes, and gouty arthritis. Its initial dose is 25 to 50 mg once daily. Its maximum dose is 100mg daily. To prevent the formation of uric acid crystals, patients should drink no less than 1.5 to 2L of water per day while taking medication. Patients need to alkalinize their urine if necessary.

Read More

What is methotrexate?😵😵😵

Methotrexate is a drug that can be used to treat both cancer and non-cancer. It prevents cell division and the production of new cells. It can be used to prevent rejection in patients following bone marrow or stem cell transplants. It is also used to treat psoriasis and rheumatoid arthritis.

What are the indications and doses of methotrexate?

Methotrexate is a metabolic inhibitor of folic acid analogues. Dihydrofolate reductase will be inhibited by it and interfere with DNA synthesis, cell repair and replication. It is generally more sensitive to actively proliferating tissues such as malignant cells, bone marrow, fetal cells, oral cavity cells, intestinal mucosal cells, and bladder cells. It is mainly suitable for the treatment of hematological malignancies, solid tumors, psoriasis and various arthritis.

Treatment of adult hematological malignancies:

• Various acute leukemias (especially acute lymphoblastic leukemia), non-Hodgkin lymphoma, malignant lymphoma and mycosis fungoides, multiple myelopathy.
• Intrathecal methotrexate can be used to prevent and treat neural invasion of meningeal leukemias and malignant lymphomas.
• Methotrexate is used in combination with other chemotherapy drugs for the palliative treatment of acute leukemias, especially acute lymphoblastic leukemia. It is also used to treat Burkitt's lymphoma, coronal lymphosarcoma and mycosis fungoides.
• High-dose methotrexate is used to treat non-Hodgkin's disease subtypes but must be combined with rescue therapy with leucovorin.
• Oral administration: Adults take 1 to 2 days a week, once a day, 5 to 10 mg each time. The safe dosage for a course of treatment is 50 to 100 mg. Its maintenance dose for acute lymphoblastic leukemia is 15 to 20 mg/m² once a week.

Treatment of various solid tumors in adults including head and neck cancer, lung cancer, various soft tissue sarcomas, breast cancer, ovarian cancer, cervical cancer, malignant mole, chorioepithelial cancer, and testicular cancer. Commonly used oral tablet dosages are as follows:

• Adults take it orally 1 to 2 days a week, once a day, 5 to 10 mg each time. The safe dose for a course of treatment is 50 to 100 mg.

For the treatment of rheumatoid arthritis in adults. Common dosages are as follows:

• Rheumatoid Arthritis: 7.5 to 15 mg orally once weekly, with the highest dose being 25 mg once weekly. The dose of methotrexate should be reduced when used in combination with other immunosuppressants.
• Psoriatic Arthritis: 15 to 20 mg orally once weekly.
• Peripheral arthritis in ankylosing spondylitis: 7.5 to 10 mg orally once weekly.

Methotrexate is also used to treat severe, refractory and disabling psoriasis in adults who are unresponsive to conventional treatments. Commonly used injectable dosage forms.

What is the pharmacological mechanism of methotrexate?

Its main mechanism of action is to competitively inhibit folate reductase. Folic acid is reduced to tetrahydrofolate by folate reductase during DNA synthesis and cell replication. Folate reductase is inhibited by methotrexate, which interferes with cell replication. Methotrexate is a cell cycle-specific drug and acts primarily on cells during the DNA synthesis phase. 

Tissues and cells with active proliferation such as bladder cells, bone marrow, embryonic cells, intestinal mucosal cells, malignant tumor cells, oral cells, and skin epithelial cells are generally more sensitive to the effects of methotrexate. In addition, most normal tissues proliferate more slowly than malignant tumor tissues, so methotrexate will preferentially weaken the growth of malignant tumors. The skin epithelial cells of patients with psoriasis also have a greater ability to proliferate than normal skin cells, so methotrexate can also be used to control the progression of psoriasis. 

One of the important coenzymes in the synthesis of pyrimidine deoxynucleotides and purine nucleotides in the human body is tetrahydrofolate. Methotrexate is a folate reductase inhibitor. It inhibits dihydrofolate reductase and prevents dihydrofolate from being reduced to active tetrahydrofolate. This blocks the transfer of carbon groups during the biosynthesis of pyrimidine deoxynucleotides and purine nucleotides. DNA biosynthesis will be inhibited. In addition, although methotrexate also inhibits thymus nucleotide synthase, its inhibitory effect on protein and RNA synthesis is weak. It mainly acts in the S phase of the cell cycle. It is a cell cycle specific drug. It also delays cells in the G1/S phase, but the effect is weaker.

What are the common side effects of methotrexate?

Blood and Lymphatic System: Myelosuppression, pancytopenia, agranulocytosis, granulocytopenia, anemia, leukopenia, aplastic anemia, neutropenia, thrombocytopenia, lymphopenia.

Cardiovascular system: palpitations, tachycardia, increased blood pressure.

Gastrointestinal system: nausea, vomiting, oral ulcers, abdominal pain, diarrhea, oral mucositis, oropharyngeal pain, abdominal distension, acid reflux, gastrointestinal bleeding, lip ulcers, indigestion, blood in the stool, flatulence, dry mouth, oral bleeding, Belching, tongue ulcers, dysphagia, bleeding gums, peptic ulcers, melena, anal ulcers, and tongue pain.

Hepatobiliary system: abnormal liver function, liver cell damage, liver damage, hepatitis, jaundice, liver failure.

Immune system: Hypersensitivity reactions, anaphylactoid reactions, graft-versus-host disease.

Infections: infectious pneumonia, cytomegalovirus infection, fungal infection, herpes virus infection, sepsis, herpes zoster, Epstein-Barr virus infection.

Kidney and urinary system: renal damage, hematuria, hemorrhagic cystitis.

Nervous system: dizziness, headache, hypoesthesia, tremor.

Respiratory system: cough, dyspnea, pneumonia, pharyngitis, interstitial lung disease, pulmonary fibrosis, respiratory failure.

Skin and subcutaneous tissue: rash, pruritus, alopecia, erythema, skin ulcers, ecchymosis, erythema multiforme, maculopapular rash, vesicular rash, papules, erythematous eruption, urticaria, peeling, dermatitis, pruritic rash, purpura, Petechiae, exfoliative dermatitis, skin erosions.

Systemic reactions: fatigue, fever, mucosal ulcers, chest tightness, pain, chills, mucosal erosion, chills, facial edema, high fever, peripheral edema.

Others: loss of appetite, appetite disorder, joint pain, irregular menstruation, blurred vision, visual impairment, flushing, tinnitus.

Adverse effects of methotrexate can be prevented by using low-dose folic acid, but it should be used 24 hours after the patient takes the drug. It is recommended that patients supplement 5mg of folic acid every week to reduce gastrointestinal adverse reactions and liver function damage. Leucovorin and levofolinic acid are antidotes for methotrexate overdose. Patients with methotrexate overdose should be given an antidote as soon as possible and should undergo hydration and alkalinization of the urine.

Read More