奥沙利铂（eloxatin）

【Function and indications】
Combined with 5-fluorouracil and folinic acid (leucovorin): first-line treatment of metastatic colorectal cancer; adjuvant treatment of stage III (Duke’s C) colon cancer after complete resection of the primary tumor. This indication is based on the results of foreign clinical studies.

【Model and specification】
This product is a white or off-white freeze-dried loose block or powder. Molecular formula: C8H14N2O4Pt, molecular weight: 397.29CAS: 61825-94-3, 50mg, 100mg powder injection

【Usage and dosage】
For adult use only.

For adjuvant treatment, the recommended dose of oxaliplatin is 85mg/m, intravenous drip, repeated once every 2 weeks. A total of 12 cycles (6 months).

For the treatment of metastatic colorectal cancer, the recommended dose of oxaliplatin is 85mg/m, intravenous drip, repeated once every 2 weeks.

The dose should be adjusted according to the patient’s tolerance (see “Special Warnings and Special Precautions for Use” in [Precautions]).

Oxaliplatin should be administered before infusion of fluorouracil.

Dissolve oxaliplatin in 250-500mL of 5% glucose solution (in order to reach a concentration of more than 0.2mg/mL) and infuse continuously for 2-6 hours.

Oxaliplatin is mainly used in combination regimens based on continuous infusion of 5-fluorouracil. In the biweekly regimen, 5-fluorouracil is administered by a combination of push injection and continuous infusion.

[Clinical Studies]
This product has general toxic reactions of platinum compounds. Species-specific cardiac toxicity occurs. This product does not have the renal toxicity of cisplatin or the bone marrow toxicity of carboplatin. This product is a new platinum derivative that acts on DNA by producing alkylated conjugates to form intra-chain and inter-chain crosslinks, thereby inhibiting DNA synthesis and replication. The product binds to DNA rapidly, taking up to 15 minutes, and the binding of cisplatin to DNA is divided into two phases, including a delayed phase after 48 hours. One hour after administration in the human body, its presence can be shown by measuring the adducts in white blood cells. DNA synthesis during replication, subsequent DNA separation, RNA and cell protein synthesis are all inhibited. This product is effective in treating certain cell lines resistant to cisplatin.

[Precautions]
Doctors should explain to patients that patients should not be exposed to cold stimulation during medication, and try to wash their hands and feet with warm water, drink warm water, etc., to prevent cold stimulation from stimulating peripheral nerves, causing numbness and desquamation of hands and feet, glove sign, sock sign, and even loss of sensation in hands and feet.

Do not use injection materials containing aluminum;

Do not use without dilution;

Do not prepare or dilute this product with saline solution;

Do not mix with any other drugs or use them simultaneously through the same infusion channel (especially 5-fluorouracil, alkaline solution, tromethamine, and folinic acid drugs containing excipient tromethamine). The infusion line needs to be flushed after the infusion of oxaliplatin.

Oxaliplatin and folinic acid can be given simultaneously by using a Y-type infusion tube connector before the injection site, and the Y-type tube is placed close to the venous puncture end, but the two drugs cannot be mixed in the same infusion bag.

Folinic acid must be prepared with an isotonic solution, such as 5% glucose, and do not use saline or alkaline solutions.

After the infusion of oxaliplatin, the infusion line needs to be flushed.

Only recommended solvents can be used (see below).

If there is any precipitate in the prepared solution, it cannot be used again and should be destroyed in accordance with the handling principles of hazardous materials required by regulations.

[Use in pregnant and lactating women] There is currently no data to determine the safety of oxaliplatin in pregnant women. Based on preclinical experience, clinically recommended doses of oxaliplatin can be lethal and/or teratogenic. Therefore, oxaliplatin is not recommended in pregnant women. Oxaliplatin should only be considered after a full evaluation of the risk to the fetus and with the patient’s consent.

It has not been studied whether the drug is excreted through breast milk. Breastfeeding should be avoided during the use of oxaliplatin.

[Adverse Reactions and Contraindications]
During the combined use of oxaliplatin and 5-fluorouracil/folinic acid, the most common adverse reactions observed are gastrointestinal (diarrhea, nausea, vomiting, and mucositis), hematological (neutropenia, thrombocytopenia), and nervous system reactions (acute, dose-accumulated, peripheral sensory neuropathy). In general, these adverse reactions are more common and more severe when oxaliplatin is used in combination with 5-fluorouracil/folinic acid than when 5-fluorouracil/folinic acid is used alone.

The adverse reaction rates shown in the following table are from clinical studies conducted in the treatment of metastatic cancer and adjuvant therapy (oxaliplatin and 5-fluorouracil/leucovorin combination therapy included 416 and 1108 patients, respectively), as well as from post-marketing experience.

The adverse reaction rates shown in the table are defined using the following criteria: very common (>1/10), common (>1/100, ≤1/10), uncommon (>1/1000, ≤1/100), rare (>1/10000, ≤1/1000), and very rare (≤1/10000), including individual cases.

More detailed information is given after the table.

Administration site conditions: injection site reactions are very common (* leakage may cause local pain and inflammation, the latter of which may be severe and cause complications, especially when oxaliplatin is infused via a peripheral intravenous route (see “Special Warnings and Special Precautions for Use” in [Precautions]).

Autonomic nervous system disorders: facial flushing is common.

Systemic disorders*: fever is very common (fever is very common, including infectious-neutropenia with or without fever, or immunogenic), fatigue, allergic/anaphylactic reactions (common allergic reactions such as rash, especially urticaria, conjunctivitis, rhinitis. Common allergic reactions include bronchospasm, angioedema, hypotension and anaphylactic shock), weakness, pain, weight gain (adjuvant therapy); common chest pain, weight loss (metastatic cancer treatment); rare immune allergic reactions, thrombocytopenia, hemolytic anemia Blood.

Central and peripheral nervous system disorders*: Peripheral sensory neuropathy, headache, paresthesia are very common; dizziness, motor neuritis, meningitis are common; dysarthria is rare.

Gastrointestinal disorders: Diarrhea, nausea, vomiting, stomatitis/mucositis, abdominal pain, constipation, anorexia are very common; dyspepsia, gastroesophageal reflux, hiccups are common; intestinal obstruction, small bowel obstruction are uncommon; colitis, including diarrhea caused by Clostridium difficile, is rare.

Metabolic and nutritional disorders: Dehydration is common; metabolic acidosis is uncommon.

Musculoskeletal disorders: Back pain is very common; joint pain, bone pain are common.

Platelet, bleeding and coagulation disorders: Epistaxis is very common; bleeding, hematuria, thrombophlebitis, pulmonary embolism, rectal bleeding are common.

Psychiatric disorders: Depression, insomnia are very common; tension is common.

Abnormal defense mechanisms: Infection is very common .

Respiratory system disorders: Very common dyspnea, cough; Common rhinitis, upper respiratory tract infection; Rare interstitial lung disease, pulmonary fibrosis**.

Skin and subcutaneous tissue disorders: Very common skin disorders, alopecia; Common skin peeling (e.g., hand-foot syndrome), erythematous rash, rash, excessive sweating, skin appendage disorders.

Abnormalities affecting other sensory organs: Very common taste abnormalities; Uncommon ototoxicity; Rare deafness.

Kidney and urinary system disorders: Common urination difficulties, frequent urination and abnormal urination.

Eye disorders: Common conjunctivitis, abnormal eye function; Uncommon transient decrease in visual acuity, abnormalities affecting the visual field, optic neuritis.

Abnormal laboratory parameters:

Hematologic system* – Very common anemia, neutropenia, thrombocytopenia, leukopenia, lymphopenia; Common neutrophils Reduce fever/neutropenia combined with sepsis (e.g., grade 3/4 neutropenia and clear infection).

Biochemistry-very common elevated alkaline phosphatase levels, elevated bilirubin, abnormal blood glucose, elevated LDH, hypokalemia, elevated liver enzyme levels (SGPT/ALAT, SGOT/ASAT), abnormal serum sodium; common elevated blood creatinine levels.

[Contraindications]
Oxaliplatin is contraindicated in the following patients:

Those with known allergy to oxaliplatin;

Lactating women; Those with bone marrow suppression before the start of the first course of treatment, such as neutrophil count <2×10/L and/or platelet count <100×10/L;

Those with peripheral sensory neuropathy and dysfunction before the start of the first course of treatment;

Those with severe renal insufficiency (creatinine clearance less than 30mL/min).

[Pregnant women]
Use with caution during pregnancy and lactation.

【Drug Interactions】
⒈Due to the incompatibility with sodium chloride and alkaline solutions (especially 5-FU), oxaliplatin must not be mixed with the above preparations or administered through the same vein.
⒉In vivo studies in animals and humans have shown that the combination of oxaliplatin and 5-FU has a synergistic anti-cancer effect.
3. Oxaliplatin is widely used in the treatment of colorectal cancer and metastatic colorectal cancer, but due to the existence of relatively serious bone marrow suppression, gastrointestinal reactions and liver and kidney damage, it can be taken with ginsenoside rh2 at the same time. As a BRM drug, it can be taken with oxaliplatin to effectively enhance the activity of lymphokine il-12 and other factors, enhance immunity, stimulate the bone marrow, restore the hematopoietic function of the bone marrow, and enhance the tolerance of cells to the toxicity of chemical drugs, reduce side effects, and enhance the effect of drugs.

【Storage】
Shade, seal, and store below 25°C.

【Manufacturer】
Belgium