Medicinal Products

PARAPLATIN 10 mg / ml Solution for infusion Box of 1 bottle of 45 ml

Generic drug of the therapeutic class: Oncology and Hematology
active ingredients: Carboplatin
laboratory: Bristol Myers Squibb

Injection solution for IV infusion
All forms

Indication

- Carcinoma of the ovary of epithelial origin.
- Small cell lung carcinoma.
Squamous cell carcinoma of the upper aerodigestive tract.

Dosage PARAPLATIN 10 mg / ml Solution for infusion Box of 1 bottle of 45 ml

Dosage:
MONOCHIMIOTHERAPY:
- The recommended dosage of carboplatin in patients who have not previously been pre-treated with cytotoxic chemotherapy and whose renal function is normal is 400 mg / m² injected by short intravenous infusion (15 to 60 min). Treatment should not be repeated until 3-4 weeks after previous administration of carboplatin and / or as long as the number of neutrophils is not greater than or equal to 2000 / mm3 and the number of platelets to 100000 / mm3.
- A 20 to 25% decrease in this initial dose may be recommended for patients with risk factors such as previous chemotherapy or poor general condition. Any changes in dosage will be determined by regular monitoring of hematological parameters.
POLYCHIMIOTHERAPY:
The doses of carboplatin will be modified according to the toxicities, in particular renal and hematological, of the other products used.
RENAL FAILURE :
Determination of optimal carboplatin dosage in monochemotherapy requires regular monitoring of haematological and renal parameters. The recommended dosages for renally impaired patients are as follows:
Monochemotherapy:
- clearance of creatinine 41-60 ml / min: 250 mg / m².
- clearance of creatinine 20-40 ml / min: 200 mg / m².
- Creatinine clearance <20 ml / min: insufficient data to recommend a dosage.
OTHER METHODS OF DETERMINING DOSAGE (MONO OR POLYCHIMIOTHERAPY, INCLUDING IN THE CASE OF RENAL FAILURE):
Individual adaptation of carboplatin dosages can also be approximated using the Calvert formula or the Egorin formula.
- The Calvert formula takes into account the glomerular filtration rate (GFR in ml / min) and the area under the curve (AUC in mg / ml x min):
Dose (mg) = AUC x (GFR + 25) (Calvert's formula calculates total dose in mg, not mg / m²).
The reference method for determining glomerular filtration rate (GFR) is the measurement of chromium 51-labeled EDTA clearance that involves the handling of radioactive products. In practice, it is estimated that the flow rate is correctly assessed by the creatinine clearance (Clcr), which is itself estimated by Jeliffe's predictive method, which takes into account age, gender and plasma creatinine levels (Pcr). :
GFR (female) = 0.9 x GFR (male).
GFR (male) Clcr = [98 - 16 (Age - 20) / 20] / [Pcr (mg / 100 ml)].
The target ASCs are based on possible previous treatments and the therapeutic protocol depending on whether carboplatin is used alone or in combination:
AUC target: Anticipated chemotherapy / Previous treatment:
6-8 mg / ml x min: Carboplatin monotherapy / untreated patient.
4-6 mg / ml x min: Carboplatin monotherapy / pre-treated patient.
4-6 mg / ml x min: Carboplatin in combination / patient not pretreated.
Note: AUC values ​​have been validated for carboplatin in combination with cyclophosphamide in untreated patients and with etoposide in pretreated and untreated patients.
- The formula of Egorincalculates the total dose in mg / m²:
. Patient not pre-treated with chemotherapy :
Dose (mg / m²) = 0.091 x [Clcr (ml / min) / surf. corpor. (m²)] x [(pre-plaqued - nadir plaq.) x 100 / ready plaq.] + 86.
Monochemotherapy: in practice, to set a platelet nadir at 50000 / mm3 or adapt it according to the therapeutic objective (curative versus palliative).
. Patient pre-treated with chemotherapy :
Dose (mg / m²) = 0.091 x [Clcr (ml / min) / surf. corpor. (m²)] x [(pre-plaqued - nadir plaq.) x 100 - 17] / [flat tally] + 86.
Monochemotherapy: in practice, to set a platelet nadir at 50000 / mm3 or adapt it according to the therapeutic objective (curative versus palliative).
CHILD:
In the current state of knowledge, it is not possible to recommend a particular dosage for the pediatric use of carboplatin.
Administration mode :
- Route of administration: intravenous infusion.
The various carboplatin dosages can be administered as such at a concentration of 10 mg / ml as a by-product of a 5% glucose solution infusion. They can also be diluted before administration with a 5% glucose solution to a minimum concentration of 0.5 mg / ml. In all cases, it is recommended after infusion of Carboplatin to flush the vein with a 5% glucose solution.
- Note :
None of the components required for intravenous infusion of Carboplatin may contain aluminum in whole or in part. Indeed, an interaction between aluminum and platinum would be responsible for a black precipitate that could be observed after reconstitution of the solution.

Against indications

CONTRAINDICATED:
This medicine is contraindicated in the following situations:
- history of allergy to Carboplatin or other products containing platinum or mannitol.
- severe renal insufficiency (creatinine clearance <20 ml / min).
Pregnancy: Mutagenic, embryotoxic and teratogenic properties found in animal species and / or in vitro contraindicate the use of Carboplatin during pregnancy.
- breastfeeding: contraindicated the use of Carboplatin.
- in association with :
. the vaccine against yellow fever,
. phenytoin for prophylaxis (introduced as prophylaxis of the convulsant effect of certain anticancer drugs) (see interactions).
NOT RECOMMENDED :
This drug is generally not recommended in the following situations:
- severe medullary hypoplasia and / or haemorrhagic tumors.
- in combination with live attenuated vaccines (except yellow fever).

Paraplatin side effects

The frequency of adverse reactions reported below was based on data from 1893 patients who received Carboplatin monotherapy at the recommended doses. Of these, 20% had been pretreated with cisplatin and 30% with chemotherapy that did not include platinum salts.
MYELOTOXICITY:
- Thrombocytopenia: platelets less than 50000 / mm3 in 25% of patients with a nadir at day 21. Normalization occurred within an average of 35 days after the start of treatment.
- Leukopenia: leukocytes less than 2000 / mm3 in 14% of patients with a nadir at day 21. Normalization occurred within an average of 42 days after the start of treatment.
- Neutropenia: neutrophils less than 1000 / mm3 in 18% of patients with a nadir at day 21.
- Anemia: Hemoglobin level less than or equal to 8 g / dl observed in 15% of patients. This reversible cumulative anemia was more severe in pretreated patients.
Infectious or haemorrhagic complications have been reported in 4% and 5% of patients, respectively. They caused a death in 1% of cases.
Myelotoxicity may be more severe in the following cases:
. pretreated patients,
. renal failure,
. low performance index,
. over age 65,
. combination with treatments themselves myelotoxic.
Myelotoxicity is usually reversible.
NEPHROTOXICITY:
An increase in blood urea, serum uric acid and serum creatinine was observed in 14%, 5% and 6% of patients, respectively. A decrease in creatinine clearance of less than 60 ml / min is observed in 27% of patients who received previous treatment. These abnormalities may be greater and more frequent when renal function is already disturbed before treatment with Carboplatin but they are usually rapidly reversible.
A reduction (<lower limit of normal) of serum sodium, potassium, calcium, and magnesium levels was observed in 29%, 20%, 22%, and 29%, respectively, with, in particular, a few cases of early hyponatremia. ; however, these abnormalities have never been sufficiently marked to be responsible for clinical manifestations.
GASTROINTESTINAL TOXICITY:
- Digestive disorders such as nausea and vomiting, all grades combined, were observed in 80% of patients. In 22% of cases, these were grades III-IV.
Nausea and vomiting can be controlled or prevented by appropriate anti-emetic therapy. Finally, these phenomena usually disappear within 24 hours of treatment.
- Other reported gastrointestinal effects were pain in less than 8% of patients, diarrhea, constipation in 6% of patients.
OTOTOXICITY:
- At the audiogram, we find abnormalities in the range of high frequencies (4000 to 8000 Hz) in 15% of patients. Very rare cases of hearing loss have been reported.
- Such abnormalities, when they are the result of previous treatment with cisplatin, may persist or worsen in patients who have received Carboplatin in the second line.
NEUROTOXICITY:
Peripheral neuropathies are observed in 4% of patients; however, in a very large number of cases they only result in paresthesia and a decrease in osteotendinous reflexes. The frequency and intensity of these abnormalities increase in patients previously treated with carboplatin and in patients older than 65 years.
Sensory disturbances, visual disturbances, taste disorders (dysgeusia) have been reported in 1% of patients.
ALLERGIC REACTIONS:
Carboplatin is responsible for allergic reactions in less than 2% of patients. These reactions are identical to those observed after administration of other platinum derivatives: erythematous rash, fever without apparent cause, pruritus, rash, urticaria, more rarely bronchospasm and hypotension.
OTHER ADVERSE EFFECTS:
Moderate abnormalities (normal x 1.25) of liver function parameters were observed.
These are elevations of alkaline phosphatase in 24% of patients, and more rarely, SGOT, SGPT (15%) and total bilirubin (5% of patients). For the most part, they regressed spontaneously despite continued treatment with Carboplatin.
Finally, in less than 2% of patients in total, we observed: alopecia, fever and chills.

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