Decitana (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Pharmasintez-Nord, JSC (Russia)

ATC Code

L01BC08 (Decitabine)

Active Substance

Decitabine (Rec.INN WHO registered)

Dosage Form

Decitana

Lyophilizate for preparation of concentrate for preparation of solution for infusion 50 mg: vial 1 pc.

Dosage Form, Packaging, and Composition

Lyophilizate for the preparation of a concentrate for the preparation of a solution for infusion in the form of a lyophilized mass or powder of white or almost white color.

Excipients: potassium dihydrogen phosphate – 37.65 mg, sodium phosphate dibasic dodecahydrate – 81.75 mg.

50 mg – vials (1) – cardboard packs.
50 mg – vials from 2 to 100 pcs. – cardboard boxes (for hospitals).

Clinical-Pharmacological Group

Antitumor drug. Antimetabolite

Pharmacotherapeutic Group

Antineoplastic agent, antimetabolite

Pharmacological Action

Antitumor agent, antimetabolite. Decitabine is an analog of the natural nucleoside 2′-deoxycytidine and is a specific and potent inhibitor of the enzyme DNA methyltransferase. Methylation and demethylation are associated with the control of gene expression. It has been shown that methylation of a gene’s promoter region or a region close to it inhibits transcription. DNA demethylation restores gene expression. Gene activation by DNA methylation inhibitors, particularly decitabine, may be expressed in the induction of differentiation, a desired effect in the therapy of myelodysplastic syndromes and other malignant blood neoplasms, activation of tumor suppressor genes and other genes, the effect of which may extend to many types of tumors.

Fixed complexes of the DNA methyltransferase enzyme and 5-aza-deoxycytidine can induce apoptosis when the cell exits the DNA synthesis cycle and a cycle of cell isolation and mitotic blockade is induced.

Alternative mechanisms, such as overcoming drug resistance, facilitating immune responses, and inducing apoptosis, may also result from the effects of decitabine.

Decitabine acts in the S-phase of the cell cycle. Cells must independently reach the S-phase for the effect of decitabine to be maximally manifested.

Pharmacokinetics

In patients with advanced solid tumors receiving a 1-hour infusion of decitabine at a dose of 100 mg/m², the plasma concentration of the drug increased during the infusion and then decreased in a biphasic manner; the mean C_max in plasma was 0.459±0.100 µg/ml, and the mean AUC was 408±88 ng × h/ml. In patients with advanced solid tumors receiving a 72-hour infusion of decitabine at doses of 20, 25, or 30 mg/m²/day, the AUC was 543±158, 743±98, and 743±124 ng × h/ml, respectively.

The V_d of decitabine at steady state is approximately 4.59±1.42 L/kg. Plasma protein binding is negligible (<1%).

The main pathway of decitabine metabolism is deamination by cytidine deaminase, which is present mainly in the liver, as well as in granulocytes, intestinal epithelium, and plasma. In vitro metabolism studies suggest that Decitabine is not a substrate for human liver cytochrome P450 isoenzymes.

Less than 1% of the decitabine dose is excreted unchanged in the urine. This suggests that the drug is eliminated primarily as metabolites. In patients with advanced solid tumors receiving a 1-hour infusion of decitabine at a dose of 100 mg/m², the total clearance of the drug is 126±21 ml/min/kg, which exceeds hepatic blood flow. This indicates the contribution of extrahepatic metabolism to the elimination of decitabine from the body. The mean T_1/2 in the terminal elimination phase is approximately 35±5 min.

Indications

Myelodysplastic syndrome of all types.

ICD codes

Dosage Regimen

In the first treatment cycle, the recommended dose is 15 mg/m² by continuous 3-hour IV infusion every 8 hours for 3 days. Premedication with antiemetics in standard doses should be administered.

Cycles are repeated every 6 weeks. A minimum of 4 treatment cycles is recommended, but longer treatment may be required to achieve a partial or complete effect. Treatment can be continued as long as the therapeutic effect persists.

Dose adjustment or delay of the next administration is carried out based on the results of a complete blood count.

Adverse Reactions

From the hematopoietic system: neutropenia, thrombocytopenia, anemia, febrile neutropenia, leukopenia, lymphadenopathy, leukemia.

From the digestive system: nausea, vomiting, constipation, unspecified diarrhea, unspecified vomiting, abdominal pain, oral mucosal rash, stomatitis, dyspepsia, ascites, hyperbilirubinemia.

From the body as a whole: fever, peripheral edema, chills, unspecified edema, unspecified pain, lethargy, tenderness.

Infections: pneumonia, cellulitis, unspecified candidiasis, herpes simplex.

From the metabolism: increased blood urea, hypoalbuminemia, hypomagnesemia, hypokalemia, hyperkalemia, anorexia, increased blood urea.

From the musculoskeletal system: arthralgia, limb pain, back pain.

From the CNS and peripheral nervous system: headache, dizziness, hypoesthesia, insomnia, confusion.

From the respiratory system: cough, pharyngitis, pulmonary wheezing, hypoxia.

Dermatological reactions: ecchymoses, unspecified rash, erythema, unspecified skin lesions, skin itching, petechiae, skin pallor.

Contraindications

Pregnancy, lactation period, hypersensitivity to decitabine.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

Decitabine has a teratogenic effect.

Use in Hepatic Impairment

Use with caution in patients with impaired liver function.

Use in Renal Impairment

Use with caution in patients with impaired renal function.

Pediatric Use

The safety and efficacy of the drug in children have not been established.

Special Precautions

Use with caution in patients with impaired liver and kidney function.

After the first treatment cycle at the recommended dose, the dose for subsequent cycles should be adjusted or the start of the cycle delayed depending on the minimum recorded blood cell count (nadir) and the impact on hematological parameters.

The need for early use of growth factors and/or antibacterial, antifungal, or antiviral drugs for the treatment of suspected infection in patients showing signs of it during myelosuppression should be considered.

A complete blood count should be performed with the frequency necessary to monitor therapeutic and toxic effects, but as infrequently as possible, for example, before each treatment cycle. Liver function and serum creatinine levels should be assessed before starting treatment.

The safety and efficacy of the drug in children have not been established.

Drug Interactions

It can be expected that the myelosuppression caused by decitabine will be enhanced under the influence of other antitumor drugs. It is known that monotherapy with tamoxifen is accompanied by thrombocytopenia (platelet count <100,000/µl) and thromboembolic complications, and this effect is enhanced with the simultaneous use of other antitumor drugs. One patient receiving Decitabine in combination with tamoxifen experienced severe thrombocytopenia (40,000/µl) with bleeding and subdural hematoma. The benefit and risk of combined use of decitabine and tamoxifen should be weighed. Patients receiving combination therapy should be monitored for bleeding and/or symptoms of thromboembolism.

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.