Flatiplat (Concentrate) Instructions for Use

Marketing Authorization Holder

Pharmasintez-Nord, JSC (Russia)

ATC Code

L01XA03 (Oxaliplatin)

Active Substance

Oxaliplatin (Rec.INN registered by WHO)

Dosage Form

Flatiplat

Concentrate for preparation of solution for infusion 2 mg/ml: bottle 25 ml or 50 ml 1 pc.

Dosage Form, Packaging, and Composition

Concentrate for preparation of solution for infusion transparent, colorless.

Excipients: water for injections.

25 ml – glass bottles (1) – cardboard packs.
50 ml – glass bottles (1) – cardboard packs.

Clinical-Pharmacological Group

Antineoplastic drug

Pharmacotherapeutic Group

Antineoplastic agent, alkylating compound

Pharmacological Action

Antineoplastic agent, platinum derivative. Oxaliplatin is a stereoisomer in which the central platinum atom is surrounded by oxalate and diaminocyclohexane located in trans positions.

Like other platinum derivatives, Oxaliplatin interacts with DNA, forming intra- and interstrand cross-links, which blocks its synthesis and subsequent replication.

The formation of oxaliplatin bonds with DNA is rapid and reaches a maximum within 15 minutes (in cisplatin this process is biphasic with a slow 4-8 hour phase).

Disruption of DNA synthesis leads to inhibition of RNA and cellular protein synthesis.

Oxaliplatin is effective against some cisplatin-resistant cell lines.

Pharmacokinetics

Oxaliplatin is intensively metabolized and by the end of a 2-hour infusion at a dose of 130 mg/m² is no longer detectable, with 15% of the administered dose remaining in the blood and the remaining 85% rapidly distributed in tissues (or excreted in urine).

Platinum binds to plasma albumin.

It is excreted in urine within the first 48 hours.

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

In renal impairment, a significant decrease in clearance from 17.55±2.18 L/h to 9.95±1.91 L/h and V_d from 330±40.9 to 241±36.1 L was observed.

The effect of severe renal impairment on platinum clearance has not been studied.

Indications

Metastatic colorectal cancer as monotherapy or as part of combination therapy with fluoropyrimidines.

Ovarian cancer.

ICD codes

Dosage Regimen

Determine the dose individually based on the therapeutic regimen, disease stage, and patient’s hematological status.

Calculate the dose using body surface area. Administer as an intravenous infusion over 2 to 6 hours.

For metastatic colorectal cancer, use a dose of 85 mg/m² every 2 weeks in combination therapy with fluoropyrimidines.

As monotherapy, use a dose of 130 mg/m² every 3 weeks.

For ovarian cancer, follow the specific regimen as established by clinical protocols.

Pre-medicate with effective antiemetics to prevent nausea and vomiting.

Do not administer as an intravenous bolus. Do not use aluminum-containing equipment for preparation or administration.

Reconstitute the concentrate only with Water for Injections or 5% Glucose solution.

Further dilute the reconstituted solution in 250-500 mL of 5% Glucose solution to a final concentration of 0.2 to 0.7 mg/mL.

Inspect the prepared solution visually for particulate matter and discoloration prior to administration. Discard if cloudy or precipitated.

Monitor blood counts before each cycle. Postpone administration if neutrophil count is below 1.5×10⁹/L or platelet count is below 100×10⁹/L.

Perform regular neurological assessments. Discontinue if severe or persistent peripheral sensory neuropathy occurs.

Adjust the dose for severe hematological toxicity, severe diarrhea, or grade 3 neurosensory events.

Reduce the dose in patients with moderate renal impairment. Do not use in patients with severe renal impairment (creatinine clearance less than 30 mL/min).

Adverse Reactions

From the hematopoietic system: anemia, leukopenia, granulocytopenia, thrombocytopenia.

From the digestive system: nausea, vomiting, diarrhea.

From the CNS and peripheral nervous system: frequently – peripheral neuropathies characterized by paresthesia of the extremities; may be accompanied by cramps, dysesthesia of the perioral area or upper respiratory tract (which may mimic the clinical picture of reversible laryngospasm) and gastrointestinal tract.

The appearance of such symptoms is often caused by exposure to cold.

Paresthesia mainly regresses between treatment courses, but can become permanent and cause functional impairments usually after exceeding a total dose of 800 mg/m² (6 courses).

Other: in some cases – fever, skin rash.

Contraindications

Myelosuppression before the start of the first course of therapy with neutrophil count less than 2×10⁹/L and/or platelet count less than 100×10⁹/L, peripheral sensory neuropathy before the start of the first course of therapy, severe renal impairment (creatinine clearance less than 30 ml/min), pregnancy, lactation (breastfeeding), hypersensitivity to oxaliplatin.

Use in Pregnancy and Lactation

Oxaliplatin is contraindicated for use during pregnancy and lactation.

Use in Renal Impairment

Contraindicated in severe renal impairment (creatinine clearance less than 30 ml/min).

Special Precautions

Oxaliplatin should be used only by a qualified physician experienced in anticancer chemotherapy.

Before starting treatment and before the next administration of oxaliplatin, a peripheral blood test must be performed; in addition, regular neurological examination should be performed, especially when used concomitantly with drugs that have potential neurotoxicity.

For the prevention and treatment of nausea and vomiting, the use of antiemetics is recommended.

In cases of hematological disorders (leukopenia less than 2×10⁹/L and/or thrombocytopenia less than 50×10⁹/L), the next administration should be postponed until the blood picture returns to normal.

Drug Interactions

When oxaliplatin is used in combination with 5-fluorouracil, a synergistic cytotoxic effect is observed in vitro and in vivo, and the severity of neutropenia and thrombocytopenia is increased.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.