Overview
11 DESCRIPTION Valrubicin Intravesical Solution, USP contains valrubicin (N-trifluoroacetyladriamycin-14-valerate), which is a semisynthetic analog of the anthracycline doxorubicin as a cytotoxic agent. The chemical name of valrubicin is (2 S - cis )-2-[1,2,3,4,6,11-hexahydro-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-4-[[2,3,6-trideoxy-3-[(trifluoroacetyl)amino]-α-L- lyxo...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Valrubicin is an anthracycline that affects a variety of interrelated biological functions, most of which involve nucleic acid metabolism. In cells, it inhibits the incorporation of nucleosides into nucleic acids, causes chromosomal damage, and arrests the cell cycle in G 2 . Although valrubicin does not bind strongly to DNA, valrubicin metabolites interfere with the normal DNA breaking-resealing action of DNA topoisomerase II. 12.3 Pharmacokinetics When 800 mg valrubicin intravesical solution was administered intravesically to patients with carcinoma in situ , valrubicin intravesical solution penetrated into the bladder wall.
Indications
- 1 INDICATIONS AND USAGE Valrubicin intravesical solution is an anthracycline topoisomerase inhibitor indicated for intravesical therapy of BCG-refractory carcinoma in situ (CIS) of the urinary bladder in patients for whom immediate cystectomy would be associated with unacceptable morbidity or mortality. • Valrubicin intravesical solution is an anthracycline topoisomerase inhibitor indicated for intravesical therapy of BCG-refractory carcinoma in situ (CIS) of the urinary bladder in patients for whom immediate cystectomy would be associated with unacceptable morbidity or mortality. ( 1 )
Common Doses
- 800 mg
- 5 mL
- 200 mg
- 20 mL
Dosage
2 DOSAGE AND ADMINISTRATION • For Intravesical Use Only. ( 2.1 ) • Valrubicin intravesical solution is recommended at a dose of 800 mg administered intravesically once a week for six weeks. ( 2.1 ) • Delay administration at least two weeks after transurethral resection and/or fulguration. ( 2.1 ) • Warm valrubicin intravesical solution slowly to room temperature, but do not heat. ( 2.1 ) • Use caution when handling and preparing the solution of valrubicin intravesical solution. ( 2.2 ) 2.1 Recommended Dosing For Intravesical Use Only. Do NOT administer by intravenous or intramuscular routes.
Contraindications
- 4 CONTRAINDICATIONS Valrubicin intravesical solution is contraindicated in patients with: • Perforated bladder [see Warnings and Precautions ( 5.2 )] • Known hypersensitivity to anthracyclines or polyoxyl castor oil • Active urinary tract infection • Small bladder capacity and unable to tolerate a 75 mL instillation • Perforated bladder or compromised bladder mucosa ( 4 , 5.2 ) • Hypersensitivity to anthracyclines or polyoxyl castor oil. ( 4 ) • Concurrent urinary tract infections. ( 4 ) • Patients with a small bladder capacity unable to tolerate a 75 mL instillation. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The most frequently reported adverse reactions ( > 5%) after administration of valrubicin intravesical solution are urinary frequency, dysuria, urinary urgency, bladder spasm, hematuria, bladder pain, urinary incontinence, cystitis, urinary tract infection, nocturia, local burning symptoms, abdominal pain, and nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hikma at us.hikma@primevigilance.com or call 1-877-845-0689 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.
Interactions
- 7 DRUG INTERACTIONS No drug interaction studies were conducted.