Drug Interactions between acetaminophen / butalbital / caffeine / codeine and encorafenib

Using narcotic pain or cough medications together with other medications that also cause central nervous system depression can lead to serious side effects including profound sedation, respiratory distress, coma, and even death. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. Do not drink alcohol or self-medicate with these medications without your doctor's approval, and do not exceed the doses or frequency and duration of use prescribed by your doctor. Also, because these medications may cause dizziness, drowsiness, difficulty concentrating, and impairment in judgment, reaction speed and motor coordination, you should avoid driving or operating hazardous machinery until you know how they affect you. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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Using acetaminophen together with butalbital may alter the effects of acetaminophen and cause serious side effects that may affect your liver. Call your doctor immediately if you experience a fever, chills, joint pain or swelling, excessive tiredness or weakness, unusual bleeding or bruising, skin rash or itching, loss of appetite, nausea, vomiting, or yellowing of the skin or the whites of your eyes. If your doctor does prescribe these medications together, you may need a dose adjustment or special tests to safely take both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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Consumer information for this interaction is not currently available.

MONITOR: Coadministration of codeine with potent or moderate CYP450 3A4 inducers may result in lower codeine plasma concentrations, higher levels of the inactive metabolite norcodeine, and less metabolism via CYP450 2D6, resulting in lower morphine levels. This interaction may lead to reduced codeine efficacy and potentially initiate the onset of withdrawal symptoms in patients who are physically dependent. In addition, patients may be at an increased risk of CNS and/or respiratory-depressant effects from increased levels of codeine once concomitant therapy with the CYP450 3A4 inducer is ceased. This is particularly worrisome if the CYP450 3A4 inducer also possesses CNS- and/or respiratory-depressant effects. This interaction has also been reported with dihydrocodeine.

MANAGEMENT: The potential loss of efficacy of codeine or dihydrocodeine and onset of opioid withdrawal symptoms should be considered when used in combination with a potent or moderate CYP450 3A4 inducer. Alternative agents with no or minimal CYP450 3A4 induction potential are recommended whenever possible. Some manufacturers of products containing codeine advise against the concomitant use of codeine with CYP450 3A4 inducers. If concomitant use is considered necessary, caution and close clinical and laboratory monitoring are recommended. Dosage adjustments may also be required whenever a CYP450 3A4 inducer is added to or withdrawn from therapy. Following discontinuation of a CYP450 3A4 inducer, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression.

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with encorafenib may increase the plasma concentrations of drugs that are substrates of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic cation transporter (OCT2), organic anion transporter (OAT1, OAT3), organic anion transporting polypeptide (OATP1B1, OATP1B3), or uridine diphosphate glucuronosyltransferase (UGT) 1A1. In in vivo studies, encorafenib has been shown to be an inhibitor of OATP1B1, 1B3, and BCRP. In vitro studies have demonstrated it to be an inhibitor of OCT2, OAT1, OAT3, and P-gp at expected clinical concentrations as well as a potent, reversible inhibitor of UGT1A1. Administration of a single dose of rosuvastatin, an OATP1B1, OATP1B3 and BCRP substrate, after repeated administration of encorafenib 450 mg once daily and binimetinib 45 mg twice daily, resulted in increased systemic exposure (AUC) and peak plasma concentration (Cmax) of rosuvastatin by approximately 1.6 fold and 2.7 fold respectively.

MANAGEMENT: Caution is advised if encorafenib must be used concomitantly with drugs that are substrates of the affected transporters or UGT1A1, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever encorafenib is added to or withdrawn from therapy.

Butalbital may reduce the blood levels of encorafenib in some patients, which may make the medication less effective. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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