Mechanism of effect
Alkylating agent that produces crosslinking of DNA strands by reacting with phosphate groups to inhibit protein synthesis, DNA, and RNA
Pharmacodynamic
The unstable nitrogen-carbon groups alkylate with DNA causing irrepairable DNA damage. They stop tumor growth by crosslinking guanine nucleobases in DNA double-helix strands, directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. These drugs act nonspecifically.
Pharmacokinetics
Half-life elimination: 2.4 hour (parent drug), 17.6 hr (metabolite)
Metabolism: Liver
Total body clearance: 446-419 mL/min
Excretion: Urine
Dialyzable: Yes
Dosage
Bladder Cancer
Intravesical (superficial bladder cancer): 30-60 mg in 30-60 mL NS qWeek for 4 weeks; retain for 2 hours; if patient can not retain for 2 hr, dilute and use successive doses in 30 mL of sodium chloride 0.9% instead of 60 mL
Ovarian Cancer
0.3-0.4 mg/kg q1-4Weeks OR 0.2 mg/kg for 4-5 days q2-4Weeks
Effusions
Intracavitary: 0.6-0.8 mg/kg or 30-60 mg weekly
Leptomeningeal Metastases
1-10 mg/m² intrathecal in qWeek to 2 times/week as 1 mg/mL in sterile water for injection
High-dose IV Therapy for Bone Marrow Transplant
500 mg/m², up to 1,125 mg/m²
Side effects
Diarrhea , nausea , vomiting , Seizures , allergic reaction , asthenia , fever , tiredness , RashInteractions
Melphalan , Vitamin A , Vitamin E , Chlorambucil , Streptozocin , Ifosfamide , Busulfan , Trastuzumab , Dacarbazine , Deferiprone , Carmustine , Siponimod , Influenza vaccine , denosumab , Tofacitinib , Palifermin , Bendamustine , Meningococcal Vaccines , Cisplatin , Cyclophosphamide , Fingolimod , Lomustine , Hydroxy urea , Zidovudine , Adenovirus types 4 and 7 live, oral , Naltrexone and Bupropion , Meningococcal conjugate vaccineAlerts
Avoid pregnancy
May be mutagenic and teratogenic
Myelosuppression may occur
Secondary malignancies may develop (potentially carcinogenic)
Caution in hepatic impairment (may require dose reduction; use may also be contraindicated depending on type of hepatic impairment)
Caution in renal impairment (may require dose reduction; use may also be contraindicated depending on type of hepatic impairment)
Use appropriate precautions for handling and disposal
Points of recommendation
IV Incompatibilities
Additive: cisplatin
Y-site: cisplatin, filgrastim, minocycline, vinorelbine
IV Compatibilities
Solution: D5W(?), NS(?)
Y-site (partial list): acyclovir, allopurinol, ampicillin/sulbactam, bleomycin, carboplatin, clindamycin, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, dopamine, etoposide, etoposide phosphate, filgrastim, fluconazole, fluorouracil, gemcitabine, heparin, idarubicin, lorazepam, MgSO4, metronidazole, mitomycin, morphine, ondansetron, KCl, prochlorperazine, teniposide, tobramycin, vancomycin, vinblastine, vincristine
IV Preparation
Reconstitute in 1.5 mL SWI to 10 mg/mL which is stable for 8 hr at refrigeration; further dilution in NS, D5W, or LR should be used immediately (within 1 hr of preparation)
Standard IV dilution
- IVP: use 10 mg/mL solution
- IVPB: dose/250 mL D5W; further dilution in NS, D5W, or LR should be used immediately (within 1 hr of preparation)
- Continuous 24 hr IV infusion Dose >250 mg: QS to 50 mL (total volume) in NSDose 230-250 mg: QS to 45 mL (total volume) in NSDose 200-230 mg: QS to 40 mL (total volume) in NS
IV Administration
Administer over 1 min
Solutions should be filtered through a 0.22 micron filter prior to administration
1 mg/mL solution is considered isotonic
Storage
Store intact vials under refrigeration (2-8°C)
Protect from light
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