Vincristine

[Drug Name]

Common name: Vincristine Sulfate for Injection

English name: Vincristine Sulfate for Injection

Chinese Pinyin: Zhusheyong Liusuan Changchunxinjian

[Ingredients]

The main ingredient of this product is vincristine sulfate

Chemical structural formula:

Molecular formula: C46H56N4O10· H2SO4

Molecular weight: 923.04

The excipients are: lactose, hydrochloric acid or sodium hydroxide solution.

[Character]

This product is a white or off-white loose substance or amorphous solid; it has hygroscopicity and will easily turn yellow when exposed to light or heat.

[Indications]

It is used to treat acute leukemia, Hodgkin's disease, malignant lymphoma, breast cancer, bronchial lung cancer, soft tissue sarcoma, neuroblastoma, etc.

[Specifications]

1mg

[Usage and Dosage]

This medicine is for intravenous use only. Add appropriate amount of sodium chloride injection to dissolve before use.

1. Commonly used dosage for adults

Intravenous injection, one time based on body surface area 1-1.4mg/m2, or one time based on body weight 0.02-0.04mg/Kg, one time dose does not exceed 2mg, once a week, a total course of treatment is 20mg;

2. Commonly used dosage in children

Intravenous injection, one time based on body weight 0.05-0.075mg/Kg, once a week.

[Adverse reactions]

1. Dose-limiting toxicity is nervous system toxicity, which mainly causes peripheral nerve symptoms, such as fingers, neurotoxicity, etc., and is related to the cumulative amount. Numbness of toes, slow or absent tendon reflexes, and peripheral neuritis. Abdominal pain, constipation, and paralytic intestinal obstruction are occasionally seen. Motor nerves, sensory nerves and cranial nerves can also be damaged and produce corresponding symptoms. Neurotoxicity often occurs in people over 40 years old. Children are better tolerated than adults. Patients with malignant lymphoma are more prone to neurotoxicity than patients with other tumors.

2. Myelosuppression and gastrointestinal reactions are mild.

3. Repeated intravenous injection can cause thrombophlebitis. Leakage outside the blood vessels during injection can cause local tissue necrosis.

4. This product has carcinogenic effects in animals. Long-term use can inhibit testicular or ovarian function, causing amenorrhea or lack of sperm.

5. Hair loss and occasional changes in blood pressure may be seen.

[Contraindications]

This product cannot be used for intramuscular, subcutaneous or intrathecal injection. Vincristine sulfate should not be used in patients with demyelinating progressive neurocervical muscular atrophy syndrome.

[Precautions]

1. Interference with diagnosis: This product can increase serum potassium, blood and urine uric acid.

2. It should be used with caution in the following situations: patients with a history of gout, liver damage, infection, leukopenia, neuromuscular disease, a history of urate kidney stones, and patients who have recently been treated with radiotherapy or anti-cancer drugs.

3. Peripheral blood, liver and kidney functions should be checked regularly during medication. Pay attention to heart rate, bowel sounds, tendon reflexes, etc.

4. During the course of medication, if severe numbness of limbs, loss of knee reflexes, paralytic intestinal obstruction, abdominal cramps, tachycardia, cranial nerve palsy, low white blood cells, or liver function damage occur, the medication should be discontinued or the dose should be reduced.

5. When the liquid leaks out of the blood vessel during injection, the injection should be stopped immediately, dilute the local area with sodium chloride injection, or seal it locally with 1% procaine injection, and apply warm, wet or cold compresses. If the skin breaks out, treat it as an ulcer.

6. Prevent the liquid from splashing into the eyes. If this happens, flush the eyes with plenty of saline immediately, and then use dexamethasone eye ointment for protection.

7. Avoid direct sunlight when injecting into the vein.

8. Reduce the dosage when liver function is abnormal.

[Drugs for pregnant and lactating women]

Anti-cancer drugs can affect cell dynamics and cause mutagenesis and malformation, so they should be used with caution by pregnant and lactating women.

【Children's Medication】

The myelination of peripheral nerves in children under 2 years old is not yet complete and should be used with caution.

[Drug use in the elderly]

It is not clear yet.

[Drug Interactions]

1. Pyrrole series antifungal agents (itraconazole) increase side effects on the muscle and nervous system. If side effects are found, appropriate treatment such as dose reduction, suspension or discontinuation of medication should be carried out. Itraconazole has the effect of blocking hepatic cytochrome P-450 3A, and vincristine is metabolized by hepatic cytochrome P-450 3A. Combined use can inhibit the metabolism of vincristine.

2. Combined use with phenytoin may reduce the absorption of phenytoin or cause hypermetabolism.

3． Combined use with platinum-containing anti-sub and malignant tumor agents may enhance the eighth pair of cranial nerve disorders.

4． Combined use with L-asparaginase may enhance neurological and blood system disorders. To minimize toxicity, vincristine sulfate can be used 12 to 24 hours before L-asparaginase administration.

5. This product can prevent methotrexate from leaking out of cells and increase the intracellular concentration of the latter. Therefore, this product is often injected first, and then methotrexate is used.

6. Combined use with isoniazid and spinal cord radiotherapy can aggravate nervous system toxicity.

[Drug overdose]

Unclear.

[Pharmacology and Toxicology]

Vincristine is an active ingredient extracted from Catharanthus roseus, a plant of the Apocynaceae family. The target of anti-tumor effect is microtubules, which mainly inhibits the polymerization of tubulin and affects the formation of spindle microtubules. Stop mitosis in metaphase. It can also interfere with protein metabolism and inhibit the activity of RNA polymerase, and inhibit the synthesis of cell membrane lipids and the transport of amino acids on the cell membrane. Vincristine has greater inhibitory effect on transplanted tumors than vinblastine and has a broad anti-tumor spectrum. In addition to being effective against vinblastine-sensitive tumor strains, it is also effective against mouse Ridgeway osteosarcoma, Mecca lymphosarcoma, and X-5563 myeloma. There is no cross-resistance among vincristine, vinblastine and vindesine, and vincristine is the most neurotoxic among the three.

[Pharmacokinetics]

Vincristine is rapidly distributed in various tissues after intravenous injection. The concentration in nerve cells is high and rarely penetrates the blood-brain barrier. The cerebrospinal fluid concentration is 1/30 to 1/20 of the plasma concentration. Protein binding rate is 75%. In adults, T1/2α is less than 5 minutes, T1/2β is 50 to 155 minutes, and the terminal elimination phase T1/2γ is as long as 85 hours. It is metabolized in the liver and has the highest concentration in bile. It is mainly excreted with bile, with 70% excreted in feces and 5% to 16% excreted in urine. Vincristine can selectively concentrate in cancer tissues, synchronize proliferating cells, and thereby enhance the effectiveness of anti-tumor drugs.

[Storage]

Shade, seal, and store in a cold place (2-10℃).