Cabozantinib and Ivermectin Drug Interaction
There are no documented pharmacokinetic or pharmacodynamic interactions between cabozantinib (Cabometyx) and ivermectin, and concurrent use appears safe from a drug-drug interaction perspective.
Metabolic Pathways and Interaction Risk
Cabozantinib is primarily metabolized by CYP3A4 and is a substrate of P-glycoprotein (P-gp), making it susceptible to interactions with strong CYP3A4 inhibitors or inducers 1, 2.
Ivermectin is also a CYP3A4 substrate and P-gp substrate, but it does not significantly inhibit or induce these pathways at therapeutic doses 3, 4.
Neither agent is a strong inhibitor or inducer of the other's metabolic pathway, suggesting minimal risk of clinically significant pharmacokinetic interaction.
Clinical Considerations for Concurrent Use
Cabozantinib Monitoring Requirements
Patients on cabozantinib require continuous monitoring of thyroid function (TSH levels), particularly those who have undergone total thyroidectomy, as TSH elevation occurs in 57% of patients 5.
Common adverse events with cabozantinib include diarrhea (15.9% grade 3+), hand-foot syndrome (12.6%), fatigue (9.3%), and hypertension 5, 1, 6.
Dose reductions are frequently required, with 56-79% of patients requiring initial dose reduction across clinical trials 5, 7, 1.
Ivermectin Administration Guidelines
Ivermectin should be taken with food to increase bioavailability for most parasitic infections, which is the standard recommendation 3.
Standard dosing is 200 mcg/kg orally, with specific timing depending on the indication (single dose for cutaneous larva migrans, repeated in 2 weeks for scabies) 3.
Hepatic impairment requires extreme caution with ivermectin, and this is particularly relevant since cabozantinib can cause hepatotoxicity 3, 4.
Practical Management Algorithm
Before Prescribing Ivermectin to a Patient on Cabozantinib:
Verify hepatic function - Check liver enzymes, as both agents can affect hepatic function and ivermectin safety is not established in severe liver disease 4, 6.
Review current cabozantinib dose and tolerability - If the patient has already required dose reductions or is experiencing significant adverse events, consider timing ivermectin administration during a cabozantinib dose interruption if clinically feasible 5, 1.
Assess for overlapping toxicities - Both agents can cause gastrointestinal symptoms (diarrhea, nausea), so prophylactic antidiarrheals may be warranted 5, 3, 1.
During Concurrent Therapy:
Monitor for additive gastrointestinal toxicity - Diarrhea is common with cabozantinib (occurring in >30% of patients) and can occur with ivermectin 5, 1.
Ensure adequate hydration and electrolyte monitoring - Particularly important given cabozantinib's association with diarrhea and potential for dehydration 1, 6.
Continue standard cabozantinib monitoring - Do not alter the established monitoring schedule for thyroid function, blood pressure, and other cabozantinib-related parameters 5, 7.
Critical Caveats
The absence of documented interactions does not guarantee absolute safety - Post-marketing surveillance data for this specific combination is limited.
Ivermectin's neurotoxicity risk in specific populations (children <15 kg, patients with severe liver disease) remains a concern independent of cabozantinib use 3, 4.
Cabozantinib formulations are not interchangeable - Tablets (60 mg daily for DTC) versus capsules (140 mg daily for MTC) have different bioavailability 7.
If the patient is on other CYP3A4 inhibitors or inducers concurrently, the interaction risk profile changes and requires reassessment 1, 2.