Carboplatin initial metabolic products may be mono and dihydrated diaminplatiny compound. These metabolites are highly reactive and bind firmly with sulfide groups blood plasma proteins.
Carboplatin is excreted mainly by the kidneys. Most platinum excreted within the first 6 hours. After 24 hours, carboplatin excretion is reduced to 2% or less doses per day. About 50% of carboplatin are eliminated in unchanged form. Cumulative urinary excretion is not dependent buy halotestin on the dose, but decreased with increasing severity of renal dysfunction. Patients with creatinine clearance less than 60 mL / min the dose should be reduced.
The pharmacokinetic parameters in children carboplatin are similar to those in adults. Since elderly patients may impair renal function, it is recommended to reduce the dose of carboplatin.
Contraindications for use
- Hypersensitivity to carboplatin or other platinum-compounds;
- pronounced renal dysfunction (creatinine clearance less than 15 mL / min);
- severe myelosuppression;
- heavy bleeding;
- pregnancy and lactation;
- Children’s age (safety and efficacy has been insufficiently studied). Carefully
To use caution in patients with depression function of bone marrow hematopoiesis (including on the background of concomitant radiotherapy and chemotherapy), impaired renal function; impaired function of the hearing aid; treated nephrotoxic drugs (eg cisplatin), acute infectious diseases, viral, fungal or bacterial origin, following immunization.
Application of pregnancy and lactation
controlled trial of carboplatin in pregnant women have been conducted. Animal studies have shown embryotoxic, teratogenic and mutagenic effects of carboplatin. Therefore, pregnant women should not use carboplatin.
It is not known whether carboplatin passes into breast milk penetrates, so to avoid the toxic effect of platinum on the baby during the period of treatment should stop breastfeeding.
Dosing and Administration
Carboplatin can be used both as a monotherapy and in combination with other anticancer drugs. The dose and regimen of medication is chosen individually.
Kapelno Carboplatin is administered within 15-60 min by one of the schemes:
- 1) 300-400 mg / m 2 1 every 4 weeks;
- 2) 100 mg / m 2 daily for 5 days with a repetition rate every 4-5 weeks.
Introduction Carboplatin is repeated at intervals of not less than 4 weeks at rates platelet least 100,000 cells / mm3 blood neutrophils and at least 2,000 cells / mm of blood.
Patients with risk factors, for example, after the mielosupressivnoi therapy or with low functional status (ECOG / WHO / Zubrod – 2-4 score or index below 80% on buy halotestin the Karnofsky scale), the initial dose should be reduced by 20-25%.
The frequency of side effects is set out in accordance with the following gradation: very common -> 10%, frequent -> 1% <10%, infrequent -> 0.1% <1%, rare -> 0.01% <0, 1%, very rare – <0.01%.
From the side of hematopoiesis very frequent: the suppression of the function of bone marrow hematopoiesis (dose-dependent). The maximum low platelet count and leukocyte / granulocyte usually achieved within 2-3 weeks from the start of dosing, with thrombocytopenia is more common. Adequate recovery to a level that allows reception of another dose of carboplatin, usually takes at least 4 weeks.
Anemia (hemoglobin less than 11 g / dl). There may be a need for transfusion therapy, particularly in patients undergoing long-term treatment (for example, more than six cycles of dosing). Leukopenia, neutropenia typically occurs at day 42 after initiation of therapy.
On the part of the gastro-intestinal tract Very common: nausea, vomiting, increased activity of “liver” transaminases, frequent: an inflammation of the oral mucosa, diarrhea, constipation, abdominal pain, increased bilirubin concentration and alkaline phosphatase in the blood serum; Rare – Colitis, including pseudomembranous colitis.
On the part of the central nervous system Frequent: peripheral neuropathy (paraesthesia, decreased deep tendon reflexes, it is more likely for patients older than 65 years), headache, dizziness, meningismus, depression, insomnia Uncommon: increased buy halotestin anxiety; very rare: stroke.
Neurotoxicity is the dose-limiting side effect. sensory neuropathy symptoms are often triggered by the cold. The duration of these symptoms, which are typically dealt with in between courses is increased depending on the total dose of carboplatin. Functional disorders, which are expressed in the difficulty of making precise movements are possible consequences of damage to the sensor.
From the hearing and sight are very frequent: ototoxicity (tinnitus, hearing impairment); rare: temporary blurred vision (possible loss of the ability to distinguish color and visible light). Improvement and / or total recovery of vision usually occurs within a few weeks after the drug is discontinued. Very rare: complete loss of vision, loss of hearing.
With the genitourinary system is very frequent: a temporary increase in the concentration of creatinine and urea in serum; rare: acute renal failure, hemolytic-uremic syndrome (Gasser syndrome – acute renal failure with oliguria, haemolytic anemia and thrombocytopenia).
From the electrolyte balance rare: hypokalemia, hypocalcemia, hyponatremia, hypomagnesemia. Allergic reactions are frequent: erythematous rash, fever, pruritus, urticaria, bronchospasm, hypotension, anaphylactic reactions, conjunctivitis, rhinitis very rare: exfoliative dermatitis.
Other frequent: alopecia, fatigue, arthralgia, intermittent fever; infrequent: infectious complications, taste disturbances, allergic reactions directly to the injection site, pain, redness, swelling. Very rare:necrosis.
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Symptoms: marked manifestation of the above side effects.
Treatment: The antidote is not known. Treatment is symptomatic. During the first 3 hours after drug administration is possible to use dialysis. how much to inject for weight loss
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