Oxaliplatin - instructions for use, dose, side effects, contraindications

Contains platinum, interacts with DNA, resulting in the formation of inter- and intra-helical cross-links. This blocks the synthesis and replication of DNA, which causes cytotoxicity and antitumor effect.

Pharmacokinetics:

The connection with plasma proteins is irreversible, is 90%, excreted by the kidneys within 48 hours.

Oxaliplatin intensively biotransformed with the formation of active metabolites and by the end of a 2-hour administration at a dose of 130 mg / m² already can not be determined, with 15% of the administered dose in the blood, and the remaining 85% are quickly distributed in the tissues (or excreted in the urine).

By the fifth day, about 54% of the total dose is found in the urine and less than 3% in the stool.

Indications:

Adjuvant therapy for colorectal cancer of Stage III (C Duke) after radical resection of the primary tumor, in combination with fluorouracil / folinic acid.
Disseminated colorectal cancer as monotherapy or combination therapy in combination with fluorouracil / folinic acid.
Ovarian cancer as the 2nd line of therapy.

ICD-10

II.C15-C26.C18 Malignant neoplasm of colon

II.C15-C26.C19 Malignant neoplasm of rectosigmoidal joint

II.C15-C26.C20 Malignant neoplasm of rectum

II.C51-C58.C56 Malignant neoplasm of ovary

Contraindications:

Myelosuppression before the first course of therapy.
Pregnancy and lactation.
Hypersensitivity.
Peripheral sensory neuropathy with functional impairment before the start of the first course of treatment.
Severe renal impairment (creatinine clearance <30 mL / min).
Children under 18 years.

Carefully:

In patients with moderate impairment of renal function before oxaliplatin, the benefit / risk ratio should be weighed (due to the limited data on safety and tolerability of the drug).

Pregnancy and lactation:

Category FDA - D. In animal studies, reproductive toxicity was observed. To date, there is no available information on the safety of the drug in pregnant women.Therefore, the use of the drug is contraindicated in women during pregnancy.

Excretion into breast milk has not been studied. During treatment should stop breastfeeding.

Dosing and Administration:

The dosage regimen is set individually by the attending physician, depending on the individual clinical parameters of the patient.

Intravenously. With monotherapy or combined chemotherapy: usually 85 mg / m² 1 time in 2 weeks in the form of 2-6 h infusion into 250-500 ml of 5% dextrose solution - without additional hydration therapy. The dose is selected individually, adjusted based on the clinical effect and the severity of the neurological symptoms. Repeated administration of oxaliplatin is performed only at a neutrophil count of more than 1.5 × 10⁹/ l and platelets more than 50 · 10⁹/ l.

The safety profile in patients older than 65 years was consistent with the profile observed in patients under 65 years of age.

Side effects:

From the side nervous system: paresthesia, peripheral sensory neuropathy (paresthesia of upper and lower extremities), convulsions, dysesthesia of the perioral region, upper respiratory tract.

From the side gastrointestinal tract: vomiting, diarrhea, nausea.

From the side circulatory system: leukopenia, anemia, granulocytopenia, thrombocytopenia.

Other: skin rash, fever, development of infections, facial hyperemia, pneumosclerosis, lung infiltration, sexual dysfunction, teratogenicity, embryotoxicity, allergic reactions, including anaphylactoid.

Overdose:

Increased side effects, treatment is symptomatic. If necessary, transfusion of blood components, the appointment of broad-spectrum antibiotics; monitoring of vital functions.

Interaction:

Pharmaceutically incompatible with aluminum salts (a precipitate is formed and effectiveness is reduced). Incompatible with solutions of salts (alkaline) containing chlorides, and other drugs in the same infusion system (especially with 5-fluorouracil and folic acid). Reduces the effectiveness of immunization with inactivated vaccines; when using vaccines containing live viruses, enhances the replication of the virus and the side effects of vaccination. Potentiates neurotoxic action other antineoplastic agents, myelosuppression, induced by myelotoxic drugs and radiation therapy. Compatible in combination with other antitumor drugs, including 5-fluorouracil (synergistic cytotoxic action).

Special instructions:

Treatment should be conducted by a doctor who has experience in carrying out anti-tumor chemotherapy. Do not use undiluted solutions. A solution with signs of precipitation is not suitable for use and must be destroyed. The infusion system after oxaliplatin administration should be washed before use for administration of other drugs.

Prior to and during treatment (at short intervals), it is necessary to determine the level of blood cells, complete a neurological examination. The number of platelets before the subsequent course should be more than 50 · 10⁹/ l, leukocytes 2 · 10⁹/ l, with more severe bone marrow suppression treatment should be discontinued until symptoms of hematotoxicity are eliminated.

The impact on the ability to drive and engage in other activities that require increased concentration and speed of psychomotor reactions has not been studied.

However, the use of oxaliplatin increases the risk of dizziness, nausea and vomiting, as well as other neurological symptoms affecting gait and balance, which affects the ability to drive or move vehicles lightly or to medium degree.

Instructions

Oxaliplatin (Oxaliplatinum)