What is the recommended preparation, dilution, storage, hydration, antiemetic prophylaxis, dosing, monitoring, and alternative therapy for cisplatin administration?

Cisplatin Preparation and Infusion Protocol

Preparation and Dilution

Cisplatin must be diluted in 2 liters of 5% Dextrose in 1/2 or 1/3 normal saline containing 37.5 g of mannitol and infused over 6-8 hours. 1

• Do not dilute cisplatin in 5% Dextrose Injection alone 1
• Never use needles or IV sets containing aluminum parts, as aluminum reacts with cisplatin causing precipitate formation and loss of potency 1
• If the diluted solution is not used within 6 hours, protect it from light 1
• Cisplatin should never be given by rapid intravenous injection 1
• Always wear impervious gloves when handling vials and IV sets to minimize dermal exposure risk 1

Storage

• Store unopened vials at 20-25°C (68-77°F); do not refrigerate 1
• Protect unopened containers from light 1
• After initial vial entry, cisplatin remains stable for 28 days when protected from light or 7 days under fluorescent room light 1

Pre-Hydration Protocol

Administer 1-2 liters of intravenous fluid over 8-12 hours prior to cisplatin infusion. 1

• Target urine output ≥100 mL/hour (or 3 mL/kg/hour in children <10 kg) during pre-hydration 2
• Adequate hydration and urinary output must be maintained for 24 hours following cisplatin administration 1
• Relative contraindications to aggressive saline hydration include congestive heart failure and significant urinary obstruction 2

Dosing Regimens

Standard Dosing by Indication

Testicular Cancer: 20 mg/m² IV daily for 5 days per cycle (in combination with other agents), repeated every 21 days 3, 1

Ovarian Cancer:

• 75-100 mg/m² IV once every 4 weeks in combination with cyclophosphamide 1
• 100 mg/m² IV as single agent every 4 weeks 1
• Intraperitoneal route: 75-100 mg/m² IP on day 2 after IV paclitaxel, repeated every 3 weeks 3

Bladder Cancer: 50-70 mg/m² IV every 3-4 weeks 1

• For heavily pretreated patients, use initial dose of 50 mg/m² every 4 weeks 1

Anal Cancer: 60 mg/m² IV on days 1 and 29 with maximum surface area of 2.0 m² (maximum single dose 120 mg) 3

• Alternative: 20 mg/m² IV weekly with continuous FU infusion 3

Antiemetic Prophylaxis

For cisplatin (high emetogenic risk), administer a three-drug combination: NK1-receptor antagonist + 5-HT3 receptor antagonist + dexamethasone + olanzapine. 3

Day 1 Dosing:

• NK1 antagonist options: Aprepitant 125 mg oral or 130 mg IV, OR fosaprepitant 150 mg IV, OR netupitant-palonosetron 300 mg/0.5 mg oral, OR rolapitant 180 mg oral 3
• 5-HT3 antagonist options: Ondansetron 24 mg oral or 8 mg/0.15 mg/kg IV, OR palonosetron 0.5 mg oral or 0.25 mg IV, OR granisetron 2 mg oral or 1 mg IV 3
• Dexamethasone: 12 mg oral or IV (if using aprepitant, fosaprepitant, or netupitant-palonosetron); 20 mg oral or IV (if using rolapitant) 3
• Olanzapine: 10 mg or 5 mg oral 3

Days 2-4:

• Aprepitant 80 mg oral on days 2-3 (if used on day 1) 3
• Dexamethasone 8 mg oral or IV once daily on days 2-4 3
• Olanzapine 10 mg or 5 mg oral on days 2-4 3

Monitoring Requirements

Pre-Treatment Assessment:

• Serum creatinine must be <1.5 mg/100 mL 1
• BUN must be <25 mg/100 mL 1
• Platelet count ≥100,000/mm³ 1
• WBC ≥4,000/mm³ 1
• Audiometric analysis confirming normal auditory acuity 1

During and Post-Treatment:

• Monitor electrolytes every 6 hours for the first 24 hours in high-risk patients 4, 2
• Continue daily electrolyte monitoring until levels stabilize 2
• Assess renal function (creatinine, BUN) at least every 24 hours during acute management 2
• Document urine output continuously; target ≥100 mL/hour during administration 4
• Monitor for hypomagnesemia, which exacerbates potassium wasting and requires aggressive correction 2

Post-Chemotherapy Hydration:

Many patients require 5-7 days of outpatient IV fluids after cisplatin to prevent or treat dehydration. 3, 4, 2

Special Considerations for High-Dose Cisplatin (≥60 mg/m²)

For doses ≥60 mg/m² (especially ≥100 mg/m²), add mannitol 12.5-25 g (0.25-0.5 g/kg) to hydration fluids and infuse over 20-30 minutes during or immediately after cisplatin to promote forced diuresis. 2

• Consider urinary catheter placement when using mannitol to accurately measure urine output 2
• Administer mannitol through an in-line filter 2
• Monitor serum osmolality periodically during diuresis 2
• Oral hydration alone is insufficient for cisplatin ≥60 mg/m² in curative-intent treatment 2

Contraindications and Drug Interactions

Cisplatin is contraindicated in patients with renal dysfunction, significant neuropathy, or hearing loss. 3

• Avoid concomitant nephrotoxic drugs (NSAIDs, aminoglycosides) during cisplatin administration 2
• Immunosuppressed patients should avoid mitomycin-based regimens due to increased myelosuppression risk; use cisplatin-FU instead 3
• Temporarily discontinue potentially nephrotoxic drugs in patients with GFR <60 mL/min/1.73 m² who have serious intercurrent illness 2

Alternative Platinum Agents (When Cisplatin Contraindicated)

• Carboplatin: AUC 5-6 IV every 3 weeks; less nephrotoxic but may have reduced efficacy 2, 5
• Oxaliplatin: 70 mg/m² weekly; markedly lower nephrotoxicity with distinct toxicity profile 2
• Nedaplatin: 100 mg/m² every 3 weeks; primarily used in Asian practice 2

Documentation Requirements

Document the specific clinical indication, exact medication concentration and dose, infusion rate, total volume administered, baseline and serial vital signs, urine output monitoring, and any adverse reactions. 4

• Record pre-hydration and post-hydration protocols for nephrotoxic agents 4
• Note target urine output ≥100 mL/hour during cisplatin administration 4
• Document use of aseptic technique when preparing and administering IV medications 4