What is the recommended dose of glutathione for intravenous (IV) push administration?

IV Glutathione Dosing for Chemotherapy-Induced Peripheral Neuropathy Prevention

For chemotherapy-induced peripheral neuropathy prevention, administer 1,500 mg/m² IV over 15 minutes immediately before each chemotherapy infusion. 1, 2

Evidence-Based Dosing by Chemotherapy Agent

Oxaliplatin-Based Regimens

• Administer 1,500 mg/m² IV over 15 minutes immediately before each oxaliplatin infusion 1, 2
• This regimen reduced grade 3-4 neurotoxicity from 26% to 0% (P=0.01) 1, 2
• After 8 cycles, any neuropathy occurred in 43% of glutathione patients versus 79% of placebo patients (P=0.045) 1
• After 15 weeks, neuropathy incidence decreased from 88% to 17% (P<0.001) 1, 2

Cisplatin-Based Regimens

• Standard dose: 1,500 mg/m² IV over 15 minutes before each cisplatin infusion 1, 2
• Alternative higher dose studied: 2.5 g IV over 15 minutes, which reduced sensory neuropathy amplitude decline from 50% to 26% (relative risk 0.53,95% CI 0.21-1.29) 1
• A 3 g/m² dose over 20 minutes showed improved symptom scores (P=0.05), though evidence strength is moderate 2

Carboplatin/Paclitaxel Regimens

• Do not use glutathione for paclitaxel-induced neuropathy prevention 1, 2
• Glutathione showed no significant advantage (P=0.449) 1, 2
• Weekly paclitaxel schedules actually favored placebo over glutathione (P=0.002) 1, 2

Administration Protocol

Timing

• Administer within 15-20 minutes immediately before chemotherapy infusion 1, 2
• For cisplatin: give glutathione 30 minutes before cisplatin infusion 1
• For carboplatin/paclitaxel combinations: give 30 minutes before paclitaxel and 30 minutes before carboplatin 1

Infusion Rate

• Infuse over 15 minutes for the 1,500 mg/m² dose 1, 2
• Dilute in 100 mL of normal saline 1
• For higher doses (2.5 g), maintain the 15-minute infusion time 1

Monitoring Requirements

Baseline Assessment

• Obtain baseline neuropathy assessment using NCI-CTC or EORTC-QLQ-CIPN20 scales before initiating chemotherapy 1, 2
• Document baseline vibration perception threshold and vibration detection threshold if available 1

Serial Monitoring

• Reassess neuropathy symptoms before each chemotherapy cycle using validated scales 1, 2
• Monitor for sensory symptoms (numbness, tingling, pain) and motor symptoms (weakness, difficulty with fine motor tasks) 1
• Track cumulative chemotherapy dose, as neuropathy risk increases with higher cumulative exposure 1

Safety and Tolerability

Adverse Effects

• Glutathione is generally well-tolerated with minimal adverse effects reported in clinical trials 1, 3
• No safety concerns were identified in controlled trials for chemotherapy-induced neuropathy prevention 1
• In a Parkinson's disease trial using 1,400 mg IV three times weekly, adverse events were similar between glutathione and placebo groups 3

Contraindications and Precautions

• Do not confuse glutathione with glutamine - high-dose parenteral glutamine is contraindicated in critically ill patients with kidney failure 2
• No specific contraindications to glutathione have been established in the chemotherapy setting 1
• Long-term safety data for chronic IV glutathione use beyond chemotherapy cycles is lacking 4

Alternative Dosing for Non-Chemotherapy Indications

Acute Myocardial Infarction (Research Context)

• 2,500 mg IV over 10 minutes immediately before primary angioplasty, followed by the same dose at 24,48, and 72 hours reduced inflammatory markers and improved left ventricular function 5

Contrast-Induced Nephropathy Prevention (Research Context)

• 100 mg/min for 30 minutes before coronary angiography completely abolished urinary lipid peroxide increases (P<0.01 vs control) 6

COVID-19 Dyspnea (Case Reports Only)

• 2,000 mg IV or oral glutathione improved dyspnea within 1 hour in two case reports, but this lacks controlled trial evidence 7

Critical Pitfalls to Avoid

• Never use glutathione for taxane-based chemotherapy - evidence shows no benefit and potential harm with weekly paclitaxel schedules 1, 2
• Do not delay chemotherapy administration - glutathione must be given immediately before chemotherapy, not hours in advance 1, 2
• Do not use glutathione as monotherapy for established neuropathy - evidence supports prevention only, not treatment of existing symptoms 1, 2
• Avoid confusion with glutamine - these are different compounds with different indications and safety profiles 1, 2
• Do not use for cosmetic skin lightening - no safety data exists for chronic IV use for this indication, and regulatory assessment is needed 4