Valrubicin; Uses, Dosage, Side Effects, Interactions

Valrubicin

Valrubicin is a semisynthetic derivative of the antineoplastic anthracycline antibiotic doxorubicin. With a mechanism of action that appears to differ from doxorubicin, valrubicin is converted intracytoplasmically into N-trifluoroacetyladriamycin, which interacts with topoisomerase II, stabilizing the complex between the enzyme and DNA; consequently, DNA replication and repair and RNA and protein synthesis are inhibited and the cell cycle is arrested in the G2 phase. In addition, this agent accumulates in the cell cytoplasm where it inhibits protein kinase C (PKC). Valrubicin is less cardiotoxic than doxorubicin when administered systemically; applied topically, this agent shows excellent tissue penetration. Structurally, the trifluoro-acetyl moiety on the amino group of the glycoside and the valerate moiety appears to result in lipophilicity that is greater than of doxorubicin, resulting in increased intracytoplasmic concentrations.

Mechanism of Action of Valrubicin

Valrubicin is an anthracycline that affects a variety of inter-related biological functions, most of which involve nucleic acid metabolism. It readily penetrates into cells, where after DNA intercalation, it inhibits the incorporation of nucleosides into nucleic acids, causes extensive chromosomal damage, and arrests cell cycle in G2. Although valrubicin does not bind strongly to DNA, a principal mechanism of its action, mediated by valrubicin metabolites, is interference with the normal DNA breaking-resealing action of DNA topoisomerase II.
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Valrubicin is an anthracycline glycoside that affects a number of biological functions involving nucleic acid metabolism. After penetration into cells, it inhibits incorporation of nucleosides into nucleic acids, causes extensive chromosomal damage, and arrests cells in the G2 phase of cell division. Although it does not bind strongly to DNA, its metabolites interfere with the normal DNA breaking-resealing action of DNA topoisomerase II.

Indications of Valrubicin

  • For the treatment of cancer of the bladder.
  • Antineoplastic
  • Urinary Tumor
  • Intravesical valrubicin is indicated for the treatment of carcinoma in situ of the urinary bladder that is refractory to Bacillus Calmette-Guerin (BCG), in patients for whom immediate cystectomy would be associated with unacceptable morbidity or mortality.

Contra-Indications of Valrubicin

  • Severe infection
  • Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
  • Decreased function of bone marrow
  • Anemia
  • Decreased Blood Platelets
  • Decreased Neutrophils a Type of White Blood Cell
  • heart attack within the last 30 days
  • Disease of the Muscle of the Heart with Enlargement
  • Atrioventricular Heart Block
  • Bundle Branch Block
  • Abnormal heart rhythm
  • Heart Failure
  • Inflammation of the Middle Tissue Heart Muscle
  • liver problems
  • High Amount of Bilirubin in the Blood
  • Tingling
  • Pain
  • Redness and Edema of Hands and Feet
  • Pregnancy
  • A mother who is producing milk and breastfeeding
  • Dysfunction of Left Ventricle of Heart Without Symptoms
  • Anemia from Pyruvate Kinase and G6PD Deficiencies
  • Allergies to Anthracyclines

Dosage of Valrubicin

Strengths: 40 mg/mL

Urinary Tumor

  • Usual Adult Dose: 800 mg administered intravesically once a week for six weeks.

Side Effects of Valrubicin

Most Common

  • Pain, redness, swelling at the place of injection
  • Painful swallowing
  • Signs of anemia (e.g., feeling weak, dizzy, or short of breath)
  • Signs of bleeding (e.g., bloody nose, blood in urine, coughing blood, cuts that don’t stop bleeding)
  • Signs of a blood clot in blood vessels, such as sudden vision change or dizziness, chest pain, pain and swelling in one leg muscle
  • Signs of an infection (e.g., fever over 38°C, chills or sweating, sore throat, coughing, redness or swelling around a cut, wound or catheter site, painful or difficult urination, unusual vaginal itching or discharge)

More Common

  • Hair loss, thinning of hair
  • Nausea and vomiting
  • Sores in the mouth and on the lips
  • Darkening of the soles, palms, or nails
  • Diarrhea
  • Fast or irregular heartbeat
  • Shortness of breath
  • Swelling of the feet and lower legs

Less Common

  • Cough or hoarseness accompanied by fever or chills
  • Darkening or redness of the skin (if you recently had radiation treatment)
  • Fast or irregular heartbeat
  • Fever or chills
  • Joint pain
  • Lower back or side pain accompanied by fever or chills
  • Pain at the injection site
  • Painful or difficult urination accompanied by fever or chills
  • Red streaks along the injected vein

Drug Interactions of Valrubicin

Valrubicin may interact with following drugs, supplements & may change the efficacy of drugs

  • antipsychotics (e.g., chlorpromazine, clozapine)
  • atorvastatin
  • “azole” antifungals (e.g., fluconazole, itraconazole, voriconazole)
  • bevacizumab
  • calcium channel blockers (e.g., diltiazem, verapamil)
  • carbamazepine
  • carvedilol
  • celecoxib
  • ciprofloxacin
  • cyclosporine
  • dasatinib
  • macrolide antibiotics (e.g., clarithromycin, erythromycin)
  • mercaptopurine
  • metronidazole
  • non-drowsy” antihistamines (e.g., cetirizine, desloratadine, loratadine)
  • norfloxacin
  • other anthracycline cancer medications (e.g., daunorubicin, idarubicin)
  • other cancer medications (e.g., cyclophosphamide, doxetaxel, irinotecan, paclitaxel)
  • oxcarbazepine
  • propranolol
  • protease inhibitors (e.g., lopinavir, ritonavir, stavudine)
  • selegiline
  • SSRI antidepressants (e.g., fluoxetine, paroxetine, sertraline)
  • tetracycline

Pregnancy Category

FDA Pregnancy Category: C

Pregnancy

This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.

Lactation

This medication passes into breast milk. If you are a breastfeeding mother and are taking doxorubicin, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. Children who receive doxorubicin are at an increased risk of developing leukemia. Children may also be more susceptible to the effects of this medication on the heart

References

Valrubicin