What is the dose of Glutathione for intramuscular (IM) or subcutaneous (SC) administration?

Glutathione Dosing for Intramuscular or Subcutaneous Administration

Based on available clinical evidence, glutathione for IM administration is dosed at 600 mg daily (typically on days 2-5 following IV administration), though this route has limited supporting data and is not FDA-approved for any indication in the United States. 1

Evidence-Based Dosing from Clinical Trials

Intramuscular Administration

• 600 mg IM daily was used in a randomized controlled trial for prevention of cisplatin-induced neurotoxicity, administered on days 2-5 following initial IV dosing 1
• This represents the only well-documented IM dosing regimen in peer-reviewed literature 1
• The IM route was used as adjunctive therapy following primary IV administration at 1.5 g/m² 1

Subcutaneous Administration

• No established dosing protocols exist for SC administration of glutathione in clinical guidelines or high-quality research 2
• The evidence base does not support SC administration as a validated route 2

Critical Context: Intravenous Dosing (Primary Route)

Since IM/SC dosing is poorly established, understanding IV protocols is essential:

Chemotherapy-Induced Neuropathy Prevention

• 1,500 mg/m² IV over 15 minutes immediately before chemotherapy administration 2, 1
• Alternative dosing: 2.5 g IV over 15 minutes before cisplatin 2
• This represents the most robust evidence base for glutathione administration 2

Peripheral Artery Disease

• Dosing not specified in evidence, but administered IV twice daily for 5 days in clinical trials 3

Parkinson's Disease (Empirical Use)

• Dosing varies widely in case reports, with no standardized protocol 4
• This represents off-label, empirical use without guideline support 4

Pharmacokinetic Considerations

Glutathione has extremely rapid elimination kinetics that fundamentally limit the utility of IM/SC routes:

• Half-life: 11.4 to 52.4 minutes depending on dose, with higher doses eliminated faster 5
• Plasma clearance: 0.84 to 2.44 mL/min with dose-dependent increases 5
• Rapid oxidation in plasma is the primary elimination mechanism, not tissue extraction 5
• The body tightly regulates plasma GSH levels within narrow physiological limits 5

These pharmacokinetics explain why IV bolus administration is preferred - the rapid elimination makes sustained therapeutic levels from IM/SC injection highly unlikely 5

Critical Safety and Regulatory Warnings

Lack of FDA Approval

• Glutathione is NOT FDA-approved for any indication via any route of administration 2
• All clinical use represents off-label prescribing based on research protocols 2, 1

Route-Specific Concerns

• IM injection technique matters: Use 22-25 gauge, 1-1½ inch needle at 90-degree angle into deltoid, anterolateral thigh, or ventrogluteal area 6
• Site rotation is mandatory to prevent tissue damage and ensure proper absorption 6
• SC administration lacks any safety or efficacy data in peer-reviewed literature 2

Monitoring Requirements

• No established monitoring protocols exist for IM/SC glutathione administration 2
• IV protocols suggest monitoring for hypersensitivity reactions, though specific parameters are not defined 1

Common Pitfalls to Avoid

1. Assuming IM/SC routes are equivalent to IV administration - the pharmacokinetics strongly suggest they are not 5

2. Using glutathione without addressing the underlying condition - evidence supports its use as adjunctive therapy, not monotherapy 1

3. Failing to recognize this is entirely off-label use - there are no FDA-approved indications for glutathione by any route 2

4. Expecting sustained plasma levels from IM/SC injection - the 11-52 minute half-life makes this pharmacologically implausible 5

5. Not rotating injection sites - repeated IM injections at the same site cause tissue damage and unpredictable absorption 6

Clinical Decision Algorithm

If considering glutathione administration:

1. Verify the indication - only chemotherapy-induced neuropathy prevention has Level Ib evidence 2

2. Choose IV route preferentially - this is the only route with substantial clinical evidence 2, 1

3. If IM must be used (e.g., lack of IV access):

   • Dose: 600 mg IM daily 1
   • Technique: 22-25 gauge needle, 90-degree angle, rotate sites 6
   • Recognize this extrapolates from limited data 1

4. Avoid SC route entirely - no evidence base exists 2

5. Counsel patients that this represents off-label use without FDA approval 2