Rubisandin

Uses

Rubisandin Injection is an anthracycline topoisomerase II inhibitor used as a component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast cancer

Rubisandin is also used to associated treatment for these conditions: Breast Cancer, Breast Cancer Stage II, Breast Cancer Stage III, Colorectal Cancers, Hormone Refractory Prostate Cancer, Non-Small Cell Lung Carcinoma (NSCLC), Ovarian Cancer, Papillary transitional cell carcinoma of bladder, Recurrent Superficial Bladder Cancer, Small Cell Lung Cancer (SCLC), Soft Tissue Sarcoma (STS), Stomach Tumor, Carcinoma in situ of urinary bladder

How Rubisandin works

Rubisandin has antimitotic and cytotoxic activity. It inhibits nucleic acid (DNA and RNA) and protein synthesis through a number of proposed mechanisms of action: Rubisandin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes. It also interferes with DNA replication and transcription by inhibiting DNA helicase activity.

Dosage

Rubisandin dosage

Acute leukaemias; Lymphoma; Multiple myeloma; Solid tumours:

• As a single agent: 60-90 mg/m2 3-4 wkly.
• Max (total cumulative dose): 0.9-1 g/m2.
• Palliative care: 12.5-25 mg/m2 once wkly.

Adjuvant treatment in axillary-node positive breast cancer: Recommended starting doses: 100-120 mg/m2 as a single dose on day 1 or as 2 divided doses on days 1 and 8 of each 28-day cycle. Repeat for 6 cycles.

Intravesical Local treatment of bladder carcinoma: As 0.1% soln: 50 mg/wk for 8 wk; reduce dose if chemical cystitis develops.

For carcinoma in-situ: 80 mg in 50 mL wkly.

For prevention of recurrence in patients who have undergone transurethral resection: 50 mg/wk for 4 wk, followed by 50 mg/mth for 11 mth; retain soln in the bladder for 1 hr during each administration.

Side Effects

In early breast cancer, acute adverse events occurring in ≥10% of patients are leucopenia, neutropenia, anemia, thrombocytopenia, amenhorrhea, lethargy, nausea/vomiting, mucositis, diarrhea, infection, conjunctivitis/keratitis, alopecia, local toxicity and rash/itch.

Long term adverse events occurring at a frequency of 1-2% are asymptomatic drops in LVEF and CHF and secondary leukemia.

Toxicity

bone marrow aplasia, grade 4 mucositis, and gastrointestinal bleeding

Precaution

Previous extensive radiotherapy, bone infiltration by tumour, severe renal and hepatic dysfunction. May cause tumor lysis syndrome or radiation recall. Elderly women >70 yr. CV disease, hypertensive cardiomyopathy; monitor hematological and cardiac function regularly. Extravasation during IV admin may result in severe local tissue necrosis. Do not give via IM/SC routes as extravasation can lead to severe local necrosis

Interaction

Paclitaxel and other anthracyclines. Cimetidine, heparin. Antineoplastic drugs, cardiotoxic drugs, radiation, hepatoactive drugs.

Food Interaction

• Drink plenty of fluids. Increased fluid intake increases urine output and the excretion of uric acid.

Rubisandin Alcohol interaction

[Moderate]

The concomitant or sequential use of epirubicin with agents known to induce hepatotoxicity may potentiate the risk of liver injury.

Rubisandin undergoes elimination through the hepatobiliary system.

Caution and clinical and laboratory monitoring for signs of liver injury are advisable before, during, or after use of epirubicin with other agents that are potentially hepatotoxic.

Rubisandin Drug Interaction

Moderate: amoxicillin / clavulanate, amoxicillin / clavulanate, ethanol, ethanol, acetaminophen, acetaminophen, tramadol, tramadol, valproic acid, valproic acidUnknown: paclitaxel protein-bound, paclitaxel protein-bound, aspirin, aspirin, amoxicillin, amoxicillin, aprepitant, aprepitant, esomeprazole, esomeprazole

Rubisandin Disease Interaction

Major: heart disease/toxicity, liver disease, neutropeniaModerate: myelosuppression/infection, renal impairment

Volume of Distribution

• 21 ± 2 L/kg [60 mg/m2 Dose]
• 27 ± 11 L/kg [75 mg/m2 Dose]
• 23 ± 7 L/kg [120 mg/m2 Dose]
• 21 ± 7 L/kg [150 mg/m2 Dose]

Elimination Route

100%

Half Life

Half-lives for the alpha, beta, and gamma phases of about 3 minutes, 2.5 hours and 33 hours, respectively

Clearance

• 65 +/- 8 L/hour [Patients1 with Solid Tumors Receiving Intravenous Rubisandin 60 mg/m2]
• 83 +/- 14 L/hour [Patients1 with Solid Tumors Receiving Intravenous Rubisandin 75 mg/m2]
• 65 +/- 13 L/hour [Patients1 with Solid Tumors Receiving Intravenous Rubisandin 120 mg/m2]
• 69 +/- 13 L/hour [Patients1 with Solid Tumors Receiving Intravenous Rubisandin 150 mg/m2]

Elimination Route

Rubisandin and its major metabolites are eliminated through biliary excretion and, to a lesser extent, by urinary excretion.

Pregnancy & Breastfeeding use

Discontinue nursing prior to taking Rubisandin. Not known if excreted in breast milk

Contraindication

Cardiac impairment, severe or recent Ml; previous full cumulative doses of anthracyclines. Hypersensitivity; severe hepatic dysfunction. Not for intravesical use where invasive tumours have penetrated the bladder wall; urinary infections, bladder inflammation or catheterisation problems. Pregnancy, lactation.

Innovators Monograph

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