What are the management strategies for side effects occurring 9-10 days after a 4-hour infusion of Pluvicto (Lutetium 177 vipivotide tetraxetan) for prostate cancer?

Management of Side Effects 9-10 Days After Pluvicto Infusion

For side effects occurring 9-10 days after Pluvicto infusion, the primary concern is myelosuppression and delayed organ toxicity, which should be managed according to FDA-approved dosage modifications including withholding treatment until improvement and potentially reducing the dose by 20% to 5.9 GBq (160 mCi). 1

Timeline and Expected Side Effects

The 9-10 day post-infusion window is a critical period for monitoring delayed toxicities from Pluvicto:

• Myelosuppression typically manifests during this timeframe, as hematologic nadirs generally occur within the first 2-4 weeks after radiopharmaceutical administration 1
• Renal toxicity may become apparent through rising creatinine or declining creatinine clearance 1
• Hepatotoxicity can present with transaminase elevations, with onset typically 5-10 days post-infusion and resolution by 15-21 days 2

Specific Management by Toxicity Type

Myelosuppression (Anemia, Thrombocytopenia, Leukopenia, Neutropenia)

Grade 2 (moderate):

• Withhold the next scheduled Pluvicto dose until improvement to Grade 1 or baseline 1
• Monitor complete blood counts at least weekly 1

Grade ≥3 (severe):

• Withhold Pluvicto until improvement to Grade 1 or baseline 1
• Reduce subsequent dose by 20% to 5.9 GBq (160 mCi) 1
• If Grade ≥3 myelosuppression recurs after one dose reduction, permanently discontinue Pluvicto 1

Renal Toxicity

Monitor for:

• Confirmed serum creatinine increase (Grade ≥2) 1
• Confirmed creatinine clearance <30 mL/min (calculate using Cockcroft-Gault with actual body weight) 1
• ≥40% increase from baseline serum creatinine AND >40% decrease from baseline creatinine clearance 1

Management:

• Withhold Pluvicto until improvement or return to baseline 1
• Reduce dose by 20% to 5.9 GBq (160 mCi) for confirmed ≥40% changes 1
• Permanently discontinue for Grade ≥3 renal toxicity or recurrent toxicity after one dose reduction 1

Gastrointestinal Toxicity

For nausea, vomiting, diarrhea, or constipation:

• Grade ≥3 symptoms not amenable to medical intervention: withhold Pluvicto until improvement to Grade 2 or baseline, then reduce dose by 20% 1
• Nausea can be managed with 5-HT3 antagonists such as ondansetron 4-8 mg IV 2
• Permanently discontinue if Grade ≥3 gastrointestinal toxicity recurs after one dose reduction 1

Dry Mouth (Xerostomia)

This is a common side effect occurring in >20% of patients 3:

Grade 2:

• Withhold Pluvicto until improvement or return to baseline 1
• Consider reducing dose by 20% to 5.9 GBq (160 mCi) 1

Grade 3:

• Withhold Pluvicto until improvement or return to baseline 1
• Reduce dose by 20% to 5.9 GBq (160 mCi) 1
• Permanently discontinue if Grade 3 dry mouth recurs after one dose reduction 1

Fatigue

Grade ≥3:

• Withhold Pluvicto until improvement to Grade 2 or baseline 1
• Fatigue occurs in >20% of patients and is one of the most common adverse reactions 3

Electrolyte and Metabolic Abnormalities

Grade ≥2:

• Withhold Pluvicto until improvement to Grade 1 or baseline 1
• Common abnormalities include decreased calcium and sodium (occurring in ≥30% of patients) 3

Hepatotoxicity

AST or ALT >5 times upper limit of normal in the absence of liver metastases:

• Permanently discontinue Pluvicto 1
• Note that transaminitis without hyperbilirubinemia typically has onset 5-10 days post-infusion with full resolution by 15-21 days 2

Neurologic Symptoms

While less common, neurologic symptoms can occur:

• Dysgeusia (altered taste) is the most common neurologic symptom, occurring in 11.9% of patients 4
• Dizziness occurs in approximately 6% of patients, with some requiring emergency department evaluation 4
• Headaches occur in 2.7% of patients, with severe cases requiring emergency evaluation 4
• Paresthesias occur in 3.2% of patients 4
• Severe neurologic problems are rare and unlikely to require treatment discontinuation 4

Critical Pitfalls to Avoid

Do not delay dose modifications:

• If a treatment delay due to an adverse reaction persists for >4 weeks, treatment with Pluvicto must be permanently discontinued 1
• The dosing interval can be extended from every 6 weeks up to every 10 weeks, but not beyond 1

Do not re-escalate dose:

• Once the dose is reduced by 20% to 5.9 GBq (160 mCi), do not re-escalate 1
• If a patient requires an additional dose reduction beyond the single 20% reduction, permanently discontinue Pluvicto 1

Avoid inappropriate use of antihistamines and vasopressors:

• First-generation antihistamines (diphenhydramine) and vasopressors should be avoided for infusion-related reactions, as they can convert minor reactions into hemodynamically significant events 2
• Second-generation antihistamines (loratadine 10 mg orally or cetirizine 10 mg IV/orally) are preferred if antihistamines are needed 2

Monitoring Requirements

Weekly complete blood counts should be performed starting 2 weeks after Pluvicto administration until recovery from cytopenias 2

Renal function monitoring should include serial creatinine and calculated creatinine clearance using Cockcroft-Gault formula with actual body weight 1

Liver function tests should be monitored, particularly in patients without liver metastases, as AST/ALT >5 times ULN mandates permanent discontinuation 1