What is the protocol and sequence for administering doxorubicin (chemotherapy medication), ifosfamide (alkylating agent), and mesna (uroprotectant)?

Administration Protocol for Doxorubicin, Ifosfamide, and Mesna

Administer mesna as an IV bolus at 20% of the ifosfamide dose simultaneously with ifosfamide, followed by oral mesna tablets at 40% of the ifosfamide dose at 2 and 6 hours after each ifosfamide dose, for a total daily mesna dose equal to 100% of the ifosfamide dose. 1

Standard Dosing Protocol

For Short Infusion Ifosfamide (Standard-Dose)

Three-Dose IV Regimen:

• Calculate total daily mesna dose as 60% of total daily ifosfamide dose 1
• Administer mesna in three equal bolus doses (20% each):
  • First dose: 15 minutes before ifosfamide 1
  • Second dose: 4 hours after ifosfamide 1
  • Third dose: 8 hours after ifosfamide 1
• This applies when ifosfamide dose is less than 2.5 g/m²/day 1

FDA-Approved IV/Oral Combination Regimen (Preferred):

• First dose: IV mesna bolus at 20% of ifosfamide dose, given simultaneously with ifosfamide 1, 2
• Second dose: Oral mesna tablets at 40% of ifosfamide dose at 2 hours post-ifosfamide 1, 2
• Third dose: Oral mesna tablets at 40% of ifosfamide dose at 6 hours post-ifosfamide 1, 2
• Total daily mesna equals 100% of ifosfamide dose 1, 2
• This regimen is appropriate when total ifosfamide daily dose is less than 2.0 g/m² 1

For Continuous Infusion Ifosfamide

• Initial bolus: 20% of total ifosfamide dose 1
• Continuous infusion: 40% of ifosfamide dose, continuing for 12-24 hours after completion of ifosfamide infusion 1

Doxorubicin Administration Sequence

• Doxorubicin is typically administered first in combination regimens 3
• Standard dose: 60-75 mg/m² per cycle 3
• Can be given as continuous infusion over 72 hours when combined with ifosfamide and dacarbazine 3
• Doxorubicin should be administered through a long IV line extending to the axilla to minimize extravasation risk 3

Typical AID Regimen Sequence (Doxorubicin, Ifosfamide, Dacarbazine)

Day 1-3 or 1-5:

• Doxorubicin: 60 mg/m² (can be given as continuous infusion) 3
• Ifosfamide: 1.2 g/m²/day for 5 days (total 6 g/m² per cycle) or 7.5 g/m² total dose over 3-5 days 3, 4
• Mesna: Follow protocol above based on ifosfamide schedule 1, 5
• Repeat cycle every 3 weeks 3, 4

Critical Safety Measures

Vomiting Protocol

If patient vomits within 2 hours of taking oral mesna, immediately repeat the oral dose or switch to IV mesna 1, 5, 2

Hydration Requirements

• Maintain sufficient urinary output as required for ifosfamide treatment 2
• Ensure adequate hydration (2-3 L in 24 hours) to dilute toxic metabolites 6
• Instruct patients to urinate frequently, especially immediately upon waking in the morning, to prevent acrolein accumulation overnight 6, 5

Monitoring Requirements

• Monitor urine for presence of hematuria throughout treatment 2
• Check vital signs, hemoglobin, hematocrit, and coagulation parameters 6
• Assess renal function regularly, especially in patients with pre-existing renal impairment 6
• Monitor for signs of infection, as hemorrhagic cystitis predisposes to urinary tract infections 6

High-Dose Ifosfamide Considerations

• For very high-dose ifosfamide (>12 g/m²), more frequent and prolonged mesna dosing regimens may be necessary 1
• Maximum tolerated dose is approximately 16 g/m² per cycle 7
• Dose-limiting toxicity at 18 g/m² includes renal tubular acidosis 7

Common Pitfalls to Avoid

Contraindications

• Do not use in patients with known hypersensitivity to mesna or benzyl alcohol 2
• Avoid mesna injection containing benzyl alcohol in premature neonates and low-birth weight infants due to risk of serious and fatal adverse reactions 1, 2

Dosing Errors

• When ifosfamide dose is adjusted, maintain the same ratio of mesna to ifosfamide 2
• Repeat the mesna dosing schedule on each day that ifosfamide is administered 1, 2

Monitoring Failures

• Do not assume mesna prevents all urotoxicity—continue monitoring for hematuria 2
• Hematuria was significantly associated with lack of uroprotection in clinical studies 7

Hypersensitivity Recognition

• Monitor for anaphylactic reactions, which have been reported with mesna 2
• Watch for dermatologic toxicity including Stevens-Johnson syndrome, toxic epidermal necrolysis, skin rash with eosinophilia and systemic symptoms 2
• If hypersensitivity reaction occurs, discontinue mesna and provide supportive care 2

Laboratory Test Interference

• Mesna can cause false positive tests for urinary ketones 2
• Mesna may interfere with enzymatic CPK activity tests 2