Oksaliplatin-Promomed (Concentrate) Instructions for Use

Marketing Authorization Holder

Promomed Rus LLC (Russia)

Manufactured By

Biokhimik, JSC (Russia)

ATC Code

L01XX41 (Eribulin)

Active Substance

Oxaliplatin (Rec.INN WHO registered)

Dosage Forms

	Oxaliplatin-Promomed	Concentrate for solution for infusion 2 mg/ml: 25 ml or 50 ml vials, 1, 2, 5, 10 or 50 pcs.
		Concentrate for solution for infusion 5 mg/ml: 25 ml or 50 ml vials, 1, 2, 5, 10 or 50 pcs.

Dosage Form, Packaging, and Composition

Concentrate for solution for infusion is a transparent colorless or light yellow liquid; the prepared solution must be transparent and must not contain undissolved particles.

Excipients: water for injections.

25 ml – vials of colorless or light-protective glass of hydrolytic class I (1, 5 or 10) – cardboard packs.
25 ml – vials of colorless or light-protective glass of hydrolytic class I (50) – cardboard packs (for hospitals).
50 ml – vials of colorless glass (1, 5 or 10) – cardboard packs.
50 ml – vials of colorless glass (50) – cardboard packs (for hospitals).

Concentrate for solution for infusion is a transparent colorless or light yellow liquid; the prepared solution must be transparent and must not contain undissolved particles.

Excipients: water for injections.

10 ml, 20 ml or 30 ml – vials of colorless or light-protective glass of hydrolytic class I (1, 5 or 10) – cardboard packs.
10 ml, 20 ml or 30 ml – vials of colorless or light-protective glass of hydrolytic class I (50) – cardboard packs (for hospitals).
40 ml – vials of colorless glass (1, 5 or 10) – cardboard packs.
40 ml – vials of colorless glass (50) – cardboard packs (for hospitals).

Clinical-Pharmacological Group

Antineoplastic drug

Pharmacotherapeutic Group

Antineoplastic agent, other antineoplastic agents

Pharmacological Action

Antineoplastic agent, platinum derivative. Oxaliplatin is a stereoisomer in which the central platinum atom is surrounded by an oxalate ligand and a diaminocyclohexane ligand 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-DNA adducts is rapid and reaches a maximum within 15 minutes (this process is biphasic for cisplatin with a slow 4-8 hour phase). The 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 extensively metabolized and by the end of a 2-hour infusion at a dose of 130 mg/m² it is no longer detectable, with 15% of the administered dose remaining in the blood and the remaining 85% rapidly distributing into tissues (or excreted in urine). Platinum binds to plasma albumin.

It is excreted in urine within the first 48 hours.

By the fifth day, approximately 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 dosage individually based on the therapeutic regimen, disease stage, and patient hematological status.

Administer as an intravenous infusion over 2 to 6 hours. Do not administer as a bolus injection.

Use only 5% dextrose solution for dilution. Do not use sodium chloride solutions or other chloride-containing diluents.

Prepare the infusion solution immediately prior to administration. Discard any unused solution.

For metastatic colorectal cancer, the recommended dose in combination therapy is 85 mg/m² every 2 weeks.

Pre-medicate with effective antiemetic agents.

Monitor blood counts before each cycle. Postpone administration if neutrophils are below 1.5 x 10⁹/L or platelets are below 100 x 10⁹/L.

Conduct regular neurological examinations. Discontinue if persistent functional impairment occurs.

Reduce dosage or delay administration in cases of severe hematological, neurological, or gastrointestinal toxicity.

Avoid concomitant use of other potentially neurotoxic or nephrotoxic drugs.

Do not administer to patients with severe renal impairment.

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 triggered by exposure to cold. Paresthesia mainly regresses between treatment cycles, however, it can become persistent and cause functional impairments usually after exceeding a cumulative dose of 800 mg/m² (6 cycles).

Other: in some cases – fever, skin rash.

Contraindications

Myelosuppression prior to the first therapy cycle with neutrophil count less than 2×10⁹/L and/or platelet count less than 100×10⁹/L, peripheral sensory neuropathy prior to the first therapy cycle, 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 each subsequent administration of oxaliplatin, a peripheral blood test must be performed; in addition, regular neurological examination should be performed, especially when used concomitantly with drugs having 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 blood counts return 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.