What Factors Affect a Sufficient Carboplatin Dose?

Carboplatin injection, the indication is suitable for the treatment of advanced epithelial ovarian cancer: 1. First-line treatment. 2. Second-line treatment after other treatment failures; This product is also suitable for the treatment of small cell lung cancer and squamous cell carcinoma of the head and neck.

Drug Name: Carboplatin injection

Drug type: Prescription drugs, medicines for medical workers' injuries
Use classification: Cytotoxic drugs

Carboplatin injection composition

The main ingredients and chemical name of this product are: cis-diamino-1,1-cyclobutanedicarboxylic acid platinum and its structural formula is:

Molecular formula: C ₆ H ₁₂ N ₂ O ₄ Pt
Molecular weight: 371.3
The auxiliary material is water for injection.

Carboplatin injection properties

This product is colorless or pale yellow clear liquid.

Carboplatin injection indications

This product is suitable for the treatment of ovarian cancer of advanced epithelial origin: First-line treatment.
2. Second-line treatment after other treatment failures;
This product is also suitable for the treatment of small cell lung cancer and squamous cell carcinoma of the head and neck.

Carboplatin injection specifications

150mg / 15mg / piece

Carboplatin injection dosage

This medicine is for intravenous use only. For adult patients with normal renal function, the recommended dose is 400 mg / , and a single dose of intravenous infusion is 15-60 minutes. The interval between the two administrations is 4 weeks and / or the neutrophil count is 2000 / mm ³ ; the platelet count is 100,000 / mm ³ before the next course of treatment can be performed.
Patients with risk factors, such as patients with a previous history of bone marrow suppression treatment and poor general conditions (ECOG-Zubrod 2-4, Karst score [80), it is recommended to reduce the initial dose of this drug by 20-25%. For patients over 65 years of age, the initial dose and subsequent doses should be adjusted according to the physical condition of the patient.
It is recommended that during the initial course of treatment, the peripheral blood cell count be measured weekly to determine the lowest point of blood cell reduction in order to adjust the dose for the next course of treatment.
Patients with impaired renal function have an increased risk of severe bone marrow suppression in patients with creatinine clearance <60ml / min. When using the following recommended doses of Burdine, severe leukopenia, neutropenia or thrombocytopenia generally occur in 25% about:

Patients with creatinine clearance <15ml / min do not have sufficient data to allow the recommended dose.
The above recommended doses are used for the initial course of treatment, and the subsequent doses should be adjusted according to the patient's tolerance and the acceptable degree of bone marrow suppression.
Combination therapy When combined with other bone marrow inhibitors, the dose should be adjusted according to the treatment plan and plan.
Formula calculation method to calculate the initial dose of Berd. Another method is to calculate the initial dose of Berd according to the mathematical formula of the patient's renal function before the treatment of Berd. To avoid changes due to differences in renal function, avoid underdose (patient's renal function is higher than normal) or excessive (renal function is lower than normal).
The following is the formula proposed by Calvert, which is based on the glomerular filtration rate (GFR, ml / min) of the patient and the set AUC (mg / ml min) of the Belden. The GFR was measured by the ₅₁ Cr-EDTA method.
Calvert calculates the total dose of Burr formula (mg) = set AUC × (GFR + 25)
Note: The dose calculated by the formula is the total dose, not the dose per square meter.

Medication is prescribed by a physician.
The preparation guideline can be further diluted with 5% glucose or 0.9% sodium chloride to a concentration of 0.5mg / ml.
This product should not come into contact with aluminum-containing needles or other devices during dilution or administration. Aluminum will react with this product and / or reduce its titer.

Carboplatin injection adverse reactions

The incidence of the following adverse reactions is based on the case data of 1893 different prognostic factors. Hematological toxicity Myelosuppression is a dose-limiting toxicity of this drug. Patients with normal haematology before treatment had a 25% incidence of thrombocytopenia (less than 50000 / mm ³ ); 18% of neutropenia (less than 1000 / mm ³ ) and leukopenia (leukocyte count below 2000 / mm ³ ) is 14%. Generally, the lowest point is 21 days after treatment (15 days for patients receiving combined chemotherapy). By day 28, 90% of patients have platelet recovery> 100000 / mm ³ ; 74% of patients have neutrophils] 2000 / mm ³ ; white blood cells in 67% of patients] 4000 / mm ³ .
Patients with renal insufficiency are generally in poor condition. Myelosuppression may be longer and more severe in patients over 65 years of age who have received intense chemotherapy or who have received cisplatin therapy.
In general, myeloid suppression is reversible and not cumulative if the regimen recommended by Baldien is single-agent chemotherapy. The incidence of infection and bleeding complications was 4% and 5%, respectively. <1% of patients can die from this hematological toxicity. In patients with normal hemoglobin before treatment, 71% of patients with this drug experienced hemoglobin reduction (less than 11g / dL), and the incidence of anemia increased with the increase of medication.
Renal toxicity In general, nephrotoxicity is not dose-limiting and does not require precautions such as hydration or diuresis. Increases in blood urea nitrogen or serum creatinine occur in 6-15% of patients, and increases in uric acid occur in 5% of patients. 27% of patients with creatinine clearance greater than 60ml / min will have a lower incidence. Patients with impaired renal function before treatment may have increased incidence and severity of renal toxicity. It is unclear whether sufficient hydration therapy can prevent or reduce this toxicity. When renal function is severely impaired, the dose must be reduced or treatment stopped. Serum electrolytes (magnesium, potassium, sodium, and rare calcium) have been reported to decrease with the use of burdine.
Gastrointestinal toxicity 15% of patients have nausea without vomiting, 65% of patients have nausea, and about 1/3 of patients have severe vomiting. Retreated patients (especially those who have used cisplatin) are more likely to vomit. Nausea and / or vomiting often stop within 24 hours after administration. Antiemetics are effective and preventable. Prolonged administration of the drug (continuous instillation for 5 consecutive days) has a lower incidence of vomiting than single-dose intermittent medication. When this drug is combined with other vomiting drugs to form a combined chemotherapy regimen, vomiting increases. Other gastrointestinal side effects include abdominal pain (17%), diarrhea (6%), and constipation (6%). The exact effect of this product on these side effects is unclear.
Allergic reactions Allergic reactions such as rash, urticaria, erythema, purpura, rarely bronchospasm, and hypotension occur in less than 2% of patients treated with belding. These reactions are similar to other platinum-based drugs and generally occur within minutes of the injection of burdine.
In 15% of patients with ototoxicity, hearing loss may occur in the subclinical high-frequency region (4000-8000Hz) after receiving the Bernard therapy, but only 1% of patients have clinical symptoms, most of which are tinnitus. If hearing impairment occurred during previous cisplatin treatment, it may persist or worsen after the treatment with burdine.
After treatment with this drug, the incidence of peripheral neuropathy was 4%. Most cases were limited to paresthesia and reduced deep tendon reflexes. These side effects have increased in the incidence and severity of patients who have previously used cisplatin; and patients who have been treated with this product for a long time.
Paresthesias that previously existed, especially after treatment with cisplatin, may persist or worsen after treatment with beldine. Central symptoms were observed in 5% of patients, and most were related to antiemetic use. In combination with other drugs and / or prolonged treatment, the potential for cumulative neurotoxicity may increase.
One-third of patients with hepatic toxicity with normal baseline liver function showed mild and moderate changes in liver function after receiving beldine. Alkaline phosphatase (24%) was higher than SGPT, SGOT (15%), and total Changes in bilirubin (5%) are common. Usually, these changes can be reversed automatically. Severe liver impairment is seen in high-dose patients.
Other patients who responded to berdine treatment reported a decrease in serum sodium, potassium, calcium, and magnesium of 29%, 20%, 22%, and 29%, respectively. Hyponatremia is occasionally reported.
Other toxicities related to beldine treatment include altered taste (rare), hair loss (3%), weakness (8%), fever due to non-infection or allergies, chills. Hair loss and weakness are more common when combined with other drugs.
Respiratory, cardiovascular, mucosal, urogenital, skin, muscle, and bone side effects occurred <5%.
The incidence of cardiovascular disease death (heart failure, embolism, cerebrovascular accident) was <1%. Whether this death is related to chemotherapy or general conditions is unclear. Hypotension has also been reported since it was placed on the market.
Hemolytic uremic syndrome is rarely reported.
Patients who report undesired side effects should promptly report to a physician and pharmacist.

Carboplatin injection contraindications

This product is contraindicated in patients with severe renal insufficiency and patients with severe bone marrow depression;
It is also contraindicated in patients with a history of allergies to this product and other platinum-containing compounds;
In addition, this product is contraindicated in patients with bleeding tumors.
This product is contraindicated in pregnant and nursing women, and is generally contraindicated in children.

Carboplatin injection precautions

The treatment course of this product must be separated from the previous treatment course by 4 weeks and / or at least 2000 / mm3 neutrophils and at least 100,000 / mm3 platelets.
This product must be used under the guidance of an experienced physician, and must be treated in a hospital with appropriate treatment facilities and experience. Blood cell counts and renal and liver function tests must be performed regularly. Nervous system tests must also be performed regularly. If bone marrow suppression or abnormal renal or liver function is observed, the drug should be discontinued.
The bone marrow suppression caused by the use of this product is closely related to the glomerular clearance of the kidney. Severe and persistent bone marrow suppression often occurs in patients with impaired renal function or in combination with other renal toxic drugs.
Renal function must be carefully evaluated before and during treatment.
The normal use frequency of this product should not be more than once a month.
Injection of this product may lead to thrombocytopenia, granulocytopenia, and anemia. Therefore, regular blood tests should be performed before and after treatment.
Once severe bone marrow suppression occurs, transfusion therapy may be necessary.
This product can cause nausea and vomiting. These reactions are more serious in patients who have been treated in the past, especially those who have been treated with cisplatin in the past. Prophylactic administration of antiemetics and prolonged administration of this product by continuous infusion or 5 consecutive days of medication can reduce the frequency and severity of nausea and vomiting.
This product may change renal function. Although it has not yet been confirmed whether renal toxicity has increased when used in combination with aminoglycosides and other nephrotoxic drugs, it is recommended to avoid combination with these drugs.
Similar to other platinum compounds, this product may cause allergic reactions. Allergic reactions occur within a few minutes after the start of administration, and appropriate treatment should be given.
Carcinogenicity tests have not been performed for this product, but compounds that have similar mechanisms of action and mutagenicity as this product have been reported to be carcinogenic. This product has mutagenic effect in in vitro and in vivo tests.
Use of this product in patients with impaired renal function in excess of the recommended dose may cause visual impairment, including vision loss, but it is extremely rare. After several weeks of stopping the injection of this product, vision can be completely restored or significantly restored.
High doses of this product (5 times higher than the recommended single dose) can cause severe liver and kidney damage.
Increased severity of bone marrow suppression in patients previously treated (especially cisplatin) and / or renal impairment. The initial dose of this product should be appropriately reduced in these patients, and these effects should be carefully monitored by repeated blood counts between doses. The combination of this product with other bone marrow inhibitor treatments should be planned very carefully, taking into account the dose and timing choices to reduce side effects.
The relationship between hyponatremia and this product is unknown, but the possibility of hyponatremia should be considered, especially for patients with other risk factors such as concomitant diuretic therapy. Sodium supplementation or water restriction can generally correct hyponatremia.
Specifications for proper handling and disposal of anticancer drugs should be implemented. To reduce the risk of skin exposure to drugs, be sure to wear isolation gloves during handling. These operations include everything that takes place in clinical wards, pharmacies, drug stores, and home medical settings: the process of unpacking inspections, device-to-device transfers, dose preparation, and administration. Care must be taken at all times when using anticancer drugs. Measures must be taken to prevent operators from being exposed to the drug. Appropriate equipment such as wearing gloves and washing hands with soap and water after operation must be taken during operation.
This product should not come into contact with aluminum-containing needles or other devices during dilution or administration. Aluminum will react with this product to precipitate, or reduce the titer.

Carboplatin injection for pregnant and lactating women

This product has fetal toxicity when administered to pregnant women. Similar to most anticancer and immunosuppressive drugs, this product is carcinogenic to experimental animals under specific test conditions. This product has been confirmed to have embryotoxicity and potential mutagenic effects in many non-clinical experiments.
No clinical trials have been conducted in pregnant women. Because carboplatin may harm the fetus, women who are likely to become pregnant must be informed of this danger. Women of childbearing age should be advised to avoid pregnancy when starting carboplatin treatment.
It is not clear whether this product is excreted from human milk in lactating women. Since many drugs are excreted from breast milk, and this product may have serious toxic side effects on lactating infants, it should be based on the importance of the drug to the mother Decide whether to stop breastfeeding or stop using this product.

Carboplatin injection for children

Insufficient data are available to determine recommended dosages and methods for pediatric use. This product has not undergone systematic safety and effectiveness clinical trials in children.

Carboplatin injection for the elderly

In clinical trials of carboplatin and cyclophosphamide, elderly patients receiving carboplatin were more likely to leave school for severe thrombocytopenia than younger patients. In clinical trials of carboplatin for different types of tumors, the incidence of adverse events in young patients and elderly patients is similar, but it cannot be ruled out that some elderly patients are more sensitive.
Renal function is common in elderly patients, so renal function status should be considered when determining metering.

Carboplatin injection drug interactions

This product is usually used in combination with other drugs, so you must be alert to the addition of toxicity, especially when combined with drugs that have bone marrow suppression or renal toxicity.
When this product is used in combination with other myelosuppressive drugs, the dosage and cycle must be carefully designed.
When this product is used in combination with aminoglycosides, it can cause increased ototoxicity and renal toxicity.
When this product is combined with other vomiting drugs, vomiting increases.
This product should be avoided in combination with other nephrotoxic drugs.

Carboplatin injection overdose

There is no antidote for this product. The complications caused by overdose are related to bone marrow suppression and liver and kidney damage. When the dose exceeds the recommended dose, it may cause vision loss. The dose must be accurately calculated. If poisoned nephrotoxicity, leukocytopenia and / or thrombocytopenia occur, it is necessary to stop medication and take appropriate treatment measures.

Carboplatin injection pharmacology and toxicology

Pharmacological effect: This product is a periodic non-specific anti-tumor drug, which has the same biochemical properties as cisplatin, and mainly causes cross-linking and binding between DNA chains to affect its synthesis to inhibit cancer cells.
Toxicology study: This product has not been tested for carcinogenesis, but compounds with the same effect and carcinogenic mutation mechanism have been reported to be carcinogenic. This product has mutagenic effects in vitro and in vivo. Organogenesis rats have embryo toxicity and carcinogenicity after using this product.

Carboplatin injection pharmacokinetics

After using this product, there is a linear relationship between the dosage of the drug and the plasma platinum concentration and free (ultrafiltration) platinum concentration in the human body. There was a similar linear relationship between dose and AUC / total platinum time course. The same dose was repeated for 4 consecutive days without accumulation of platinum in the plasma. The terminal half-lives of free (ultrafiltration) platinum and carboplatin are approximately 6 hours and 1.5 hours, respectively. In the initial stage, most exist as free (ultrafiltration) platinum. The terminal half-life of total platinum in plasma is 24 hours. Carboplatin showed a dose-independent, linear pharmacokinetic profile in patients with creatinine clearance 60 ml / min over the dose range studied. Approximately 87% of plasma platinum binds to plasma proteins 24 hours after administration. The systemic clearance and renal clearance of filterable free platinum are related to the glomerular filtration rate and have nothing to do with renal tubular secretion. Carboplatin clearance is reported to be 3-4 times higher in pediatric patients. For adult patients, data in the literature suggest that renal function may cause changes in carboplatin clearance.
When given to patients (creatinine clearance 60 mL / min), the product was 300-500 mg / m ² , and the plasma concentration decayed in a biphasic mode. The and half-lives (average) were 1.6 hours and 3 hours, respectively. The total clearance, apparent volume of distribution, and average residence time were 73 mL / min, 16 L, and 3.5 hours, respectively. Cmax and AUC _0- increased linearly with dose. Therefore, those with normal or slightly reduced creatinine clearance exhibit linear pharmacokinetics in the dose range studied (300-500 mg / m ² ). Except carboplatin, there are not many platinum-containing analogs in free and ultrafiltration state. Carboplatin binds to plasma proteins and releases slowly. The shortest half-life is 5 days. This product is mainly cleared by the kidneys. Those with a creatinine clearance of 60mL / min will excrete 70% of the dose of this product within 12-16 hours after administration. The platinum in urine is derived from this product within 24 hours and only excreted within 24 to 96 hours. -5% platinum. In patients with creatinine clearance <60 mL / min, renal and overall clearance decreased with decreasing creatinine clearance. Therefore, patients with mild renal failure should reduce the amount of this product. There is no sufficient data to determine whether this product is excreted through the biliary or intestinal tract.

Carboplatin injection storage

Store at room temperature (15 ° C-30 ° C) away from light.
Use within the expiration date printed on the box.
Note during storage: Because the preparation has no antibacterial ingredients, the diluted solution should be stable at room temperature for 8 hours.

Carboplatin injection packaging

20ml colorless transparent glass bottle, 1 pc / box.

Carboplatin injection validity period

24 months

Carboplatin injection standard

JX20080255 ^[1]