Does Tenofovir Disoproxil Fumarate (TDF) interfere with the efficacy of Provenge (Sipuleucel-T)?

No Clinically Significant Interaction Between Tenofovir Disoproxil Fumarate and Provenge

Tenofovir Disoproxil Fumarate (TDF) does not interfere with the efficacy of Provenge (Sipuleucel-T), and these medications can be safely co-administered without dose adjustments.

Mechanism and Pharmacology

TDF is a nucleotide reverse transcriptase inhibitor used for HIV treatment and prevention, as well as hepatitis B management 1. The drug has a well-characterized pharmacokinetic profile:

• TDF is not a substrate, inducer, or inhibitor of cytochrome P450 enzymes in vitro or in vivo 2
• The drug is primarily eliminated through renal excretion (70-80% unchanged in urine) with minimal hepatic metabolism 2, 3
• TDF has minimal protein binding (7.2%) and does not significantly interact with most concomitant medications 2

Provenge (Sipuleucel-T) is an autologous cellular immunotherapy for metastatic castration-resistant prostate cancer. As a cell-based therapy, it does not undergo traditional drug metabolism and has no known drug-drug interactions through cytochrome P450 pathways or other metabolic routes.

Evidence for Lack of Interaction

The absence of interaction is supported by multiple lines of evidence:

• TDF has been studied with 15 other antiretroviral and concomitant medications frequently used in HIV-infected populations, with only didanosine and atazanavir requiring dosage modifications 2
• No clinically significant drug interactions have been observed with TDF outside of these two specific agents 2
• The mechanism of action of TDF (intracellular phosphorylation to tenofovir diphosphate, which inhibits reverse transcriptase) does not overlap with or affect cellular immunotherapy mechanisms 2, 3

Clinical Considerations for Co-Administration

Monitoring Requirements

When using TDF in cancer patients receiving Provenge, standard TDF monitoring applies 1, 4:

• Monitor renal function (serum creatinine, estimated GFR) as TDF can cause proximal renal tubular dysfunction 4
• Assess serum phosphate levels to detect tubular dysfunction, particularly in patients with risk factors 4
• Consider switching to tenofovir alafenamide (TAF) if eGFR declines to <60 mL/min/1.73m² or shows rapid decline (>3-5 mL/min/1.73m² per year) 4

Special Populations

For patients with cancer receiving both therapies 1:

• Immediate ART initiation is recommended for HIV-positive cancer patients, with attention to drug-drug interactions with chemotherapy agents (not Provenge specifically) 1
• TDF dose adjustment is necessary only in patients with significant renal impairment (creatinine clearance <50 mL/min), not due to Provenge interaction 2
• No hepatic dose adjustment is needed for TDF 2

Common Pitfalls to Avoid

• Do not confuse TDF interactions with boosted regimens: When TDF is combined with ritonavir or cobicistat, tenofovir levels increase by 25-37%, raising nephrotoxicity risk 5. However, this is unrelated to Provenge co-administration 1
• Do not assume all antiretrovirals behave similarly: While TDF has minimal interactions, other antiretrovirals (particularly protease inhibitors with ritonavir/cobicistat boosting) may have different interaction profiles 6
• Do not overlook baseline renal function: The primary concern with TDF is renal toxicity, not drug interactions, so baseline and ongoing renal monitoring is essential regardless of Provenge use 4