Exorum (Lyophilisate) Instructions for Use

ATC Code

L01XA03 (Oxaliplatin)

Active Substance

Oxaliplatin (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antineoplastic drug

Pharmacotherapeutic Group

Antineoplastic agents; other antineoplastic agents; platinum compounds

Pharmacological Action

Antineoplastic agent, platinum derivative. Oxaliplatin is a stereoisomer in which the central platinum atom is surrounded by oxalate and diaminocyclohexane 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 synthesis of oxaliplatin bonds with DNA is rapid and reaches a maximum of 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 the urine within the first 48 hours.

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

Establish the dosage individually based on the therapeutic regimen, disease stage, and patient hematological status.

Administer as a 2- to 6-hour intravenous infusion in 250-500 mL of 5% glucose solution.

Use only the specified diluent; do not use sodium chloride solution or other chloride-containing solutions for reconstitution or dilution.

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

When used in combination therapy with fluorouracil and leucovorin, the recommended dose is 85 mg/m² every 2 weeks.

For advanced ovarian cancer, the recommended dose is 100 mg/m² every 3 weeks or 130 mg/m² every 3 weeks in combination with cyclophosphamide.

Calculate the dose based on body surface area prior to each administration.

Premedicate with effective antiemetics to reduce the incidence and severity of nausea and vomiting.

Monitor peripheral blood count before initiation and prior to each subsequent cycle.

Perform regular neurological examinations, particularly when co-administered with other neurotoxic drugs.

Delay the next dose if hematological toxicity occurs: neutrophils less than 1.5×10⁹/L or platelets less than 100×10⁹/L.

Reduce the dose or discontinue therapy in case of severe or persistent peripheral sensory neuropathy.

Adjust the dose for patients with moderate renal impairment (creatinine clearance 30-59 mL/min); contraindicated in severe renal impairment.

Do not administer subsequent cycles until recovery of adverse reactions to Grade 0-1.

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 prior to 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 prior to 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 may only be used 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 with 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 count 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.