Can Zanubrutinib (Bruton's tyrosine kinase inhibitor) cause decreased appetite and altered sense of taste, and does the formulation change from capsule to pill affect this risk?

Zanubrutinib and Gastrointestinal Side Effects

Yes, zanubrutinib can cause decreased appetite and altered sense of taste, though these are not among the most commonly reported adverse effects, and the formulation change from capsule to tablet does not appear to significantly alter the risk of these specific gastrointestinal symptoms.

Evidence for Gastrointestinal Side Effects with Zanubrutinib

Common GI Effects

• The most frequently reported gastrointestinal adverse events with zanubrutinib include diarrhea (13% of patients), nausea, and contusion, rather than decreased appetite or taste changes 1
• In the phase 2 study of patients intolerant to previous BTK inhibitors, diarrhea occurred in 9 (13%) of 67 patients, but decreased appetite and taste alterations were not listed among the common adverse events 1
• The NCCN guidelines for Waldenström macroglobulinemia note that zanubrutinib demonstrates improved tolerability compared to ibrutinib, with fewer non-hematologic adverse events overall 2

Comparison to Other BTK Inhibitors

• While decreased appetite is mentioned as a grade 3-4 adverse event in some cancer treatment regimens (such as with zolbetuximab in gastric cancer), this is not specifically highlighted for zanubrutinib 2
• The ASPEN trial comparing zanubrutinib to ibrutinib showed that zanubrutinib had lower incidence of most non-hematologic adverse events, though specific data on appetite and taste were not emphasized 2

Formulation Change: Capsule to Tablet

Bioequivalence and Safety Profile

• The new 160-mg zanubrutinib tablet demonstrates bioequivalence to the 80-mg capsules under fasted conditions, with geometric mean ratios for AUC meeting BE criteria (90% CI 0.95-1.05 for AUC0-t and 0.94-1.04 for AUC0-∞) 3
• The tablet formulation was well tolerated with no serious adverse events reported in the phase 1 bioequivalence study 3
• Both formulations showed comparable safety profiles, suggesting the formulation change should not alter the risk of gastrointestinal side effects including appetite or taste changes 3

Food Effect Considerations

• A high-fat meal increased tablet Cmax by 47%-79% but had minimal effect on overall exposure (AUC <18%), supporting administration with or without food 3
• This food flexibility may actually help patients who experience mild gastrointestinal symptoms, as taking medication with food can mitigate nausea 2

Clinical Management Approach

If Decreased Appetite Occurs

• Take zanubrutinib with the largest meal of the day to potentially reduce gastrointestinal discomfort, a strategy proven effective with other tyrosine kinase inhibitors 2
• Consider splitting the dose if tolerated (160 mg twice daily rather than 320 mg once daily) and taking with separate meals to minimize GI burden 2
• Some patients may prefer taking medication at bedtime to avoid experiencing symptoms during waking hours 2

Monitoring and Intervention

• Mild and transient symptoms do not require therapy beyond symptomatic relief and diet modification unless they interfere with quality of life 2
• For persistent symptoms, antiemetic medications may be utilized, with attention to drug interactions 2
• The new tablet formulation offers the advantage of reduced pill burden (2 tablets vs 4 capsules), which may improve long-term adherence 3

Important Caveats

• While decreased appetite and taste changes are theoretically possible with any medication affecting the gastrointestinal system, these are not prominently featured in zanubrutinib's adverse event profile based on available clinical trial data 1, 4
• The majority of zanubrutinib-related adverse events are well tolerated and manageable, with discontinuation rates lower than first-generation BTK inhibitors 1, 4
• If severe or persistent appetite loss occurs, rule out other causes including disease progression, concurrent medications, or unrelated medical conditions rather than automatically attributing symptoms to zanubrutinib 2