What is the interaction between Kisqali (ribociclib) and Robitussin (dextromethorphan)?

Kisqali (Ribociclib) and Robitussin (Dextromethorphan) Interaction

There is no direct drug-drug interaction between ribociclib (Kisqali) and dextromethorphan (Robitussin), but caution is warranted due to ribociclib's CYP3A inhibition properties and the need to monitor for potential serotonergic effects if dextromethorphan is combined with other serotonergic medications.

Mechanism and Clinical Considerations

Ribociclib's Drug Interaction Profile

• Ribociclib is primarily metabolized by CYP3A4 and acts as an inhibitor of CYP3A and CYP1A2 enzymes 1
• Multiple 400 mg ribociclib doses increased midazolam (a CYP3A substrate) exposure by 3.8-fold in healthy volunteers 1
• At the 600 mg dose used in cancer patients, ribociclib increased midazolam exposure by 5.85-fold based on physiologically-based pharmacokinetic modeling 1
• The FDA labeling recommends caution when using CYP3A substrates with narrow therapeutic indices concurrently with ribociclib 1

Dextromethorphan Metabolism and Interactions

• Dextromethorphan is not primarily metabolized by CYP3A4 (it's mainly metabolized by CYP2D6), so the major metabolic pathway interaction with ribociclib is unlikely 2
• Dextromethorphan is a serotonergic medication that requires careful monitoring when combined with other serotonergic agents to avoid serotonin syndrome 3
• The dextromethorphan/quinidine combination specifically requires caution in older adults due to increased fall risk and drug interactions 3, 4

Practical Management Algorithm

Step 1: Assess the Clinical Need

• Determine if dextromethorphan is truly necessary for cough suppression
• Consider non-pharmacological alternatives (honey and lemon) for benign viral cough before using dextromethorphan 4
• Standard over-the-counter doses of dextromethorphan are typically subtherapeutic for optimal cough suppression 2

Step 2: Review Complete Medication List

• Screen for other serotonergic medications (antidepressants, other serotonergic agents) that could interact with dextromethorphan 3
• Assess for strong CYP3A inhibitors or inducers that could affect ribociclib levels 1
• Evaluate for medications with narrow therapeutic indices that are CYP3A substrates 1

Step 3: If Dextromethorphan is Necessary

• Use appropriate therapeutic doses (30-60 mg) for short-term relief only 4
• Avoid the dextromethorphan/quinidine combination entirely in patients on ribociclib, particularly in older adults 3, 4
• Monitor for signs of serotonin syndrome if patient is on other serotonergic medications 3

Step 4: Special Considerations for Cancer Patients on Ribociclib

• Ribociclib is approved for hormone receptor-positive, HER2-negative advanced or metastatic breast cancer in combination with endocrine therapy 5, 6
• Common grade 3-4 adverse events with ribociclib include neutropenia (61-66.5%), leukopenia (14-24.8%), and hepatobiliary toxicity (5-11%) 5
• Any additional medication should be carefully evaluated in the context of existing ribociclib toxicities and the patient's overall clinical status 5

Critical Pitfalls to Avoid

• Do not assume all cough medications are safe simply because they are over-the-counter 3
• Do not use dextromethorphan/quinidine combinations in patients on ribociclib due to multiple interaction concerns 3, 4
• Do not overlook the cumulative serotonergic burden when adding dextromethorphan to complex medication regimens 3
• Avoid concurrent use of strong CYP3A inhibitors or inducers with ribociclib, as these significantly alter ribociclib exposure 1

Monitoring Recommendations

• If dextromethorphan is used concurrently with ribociclib, monitor for:
  • Signs of serotonin syndrome (agitation, confusion, tremor, hyperthermia) if other serotonergic agents are present 3
  • Baseline ribociclib-related toxicities (neutropenia, hepatotoxicity) that may complicate clinical assessment 5
  • Fall risk, particularly in older adults 3