Tucatinib with Nifedipine Interaction Details

Brand Names Associated with Tucatinib

Brand Names Associated with Nifedipine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Dec 20, 2023

Interaction Effect

Increased risk of hypotension, bradycardia, or acute renal injury

Interaction Summary

Coadministration of NIFEdipine and strong CYP3A inhibitors has been reported to increase the risk of NIFEdipine related side effects, including hypotension, bradycardia, and acute renal injury. Additionally, coadministration of clarithromycin (strong CYP3A inhibitor) with a calcium channel blocker (including NIFEdipine) was associated with significantly increased short-term risk of hospital admission within 7 days for hypotension or shock in a cohort study of geriatric patients . If concomitant use is required, NIFEdipine dose adjustment and careful monitoring of heart rate and blood pressure may be necessary . In a case report, a 50% reduction of the NIFEdipine dose was necessary .

Severity

Major

Onset

Delayed

Evidence

Established

How To Manage Interaction

Coadministration of NIFEdipine and strong CYP3A inhibitors has been reported to increase the risk of NIFEdipine side effects (hypotension, acute kidney injury). If concomitant use is required, NIFEdipine dosage adjustment and careful monitoring of heart rate and blood pressure may be necessary. In a case report, a 50% reduction of the NIFEdipine dose was necessary .

Mechanism Of Interaction

Inhibition of CYP3A4-mediated NIFEdipine metabolism

Literature Reports

A) Severe hypotension, dizziness, orthostasis, and complete heart block developed in a 51-year-old man with a history of coronary artery disease, HIV, and hypertension after 3 days of concomitant treatment with NIFEdipine and antiretroviral therapy consisting of zidovudine, lamivudine, and nelfinavir. After evaluation, antiretroviral therapy was held, but the patient continued his other medications (NIFEdipine, losartan, aspirin, and atenolol). Upon restarting his antiretroviral therapy, the patient noticed similar symptoms of weakness and fatigue within 2 days, with resolution several days after discontinuing antiretroviral therapy. The patient eventually tolerated an alternate antiretroviral regimen that did not contain a protease inhibitor (stavudine/didanosine/efavirenz), but then developed symptoms of hypotension, weakness, fatigue, and bradycardia when switched to zidovudine, abacavir, ritonavir and indinavir. Subsequent dosage reduction of NIFEdipine (by 50%) and atenolol led to symptom resolution .

B) In a large retrospective cohort study of elderly adults, initiation of clarithromycin (a strong CYP3A inhibitor) in patients receiving NIFEdipine was associated with a significant 5-fold increase in the risk of hospitalization for acute kidney injury compared with initiation of azithromycin .

C) In a case report, hypotension and acute kidney injury were observed within 2 days of oral voriconazole therapy in a 69-year-old woman who was concurrently receiving NIFEdipine, arotinolol, and terazosin for hypertension. The patient's medical history included antineutrophil cytoplasm antibody (ANCA) associated vasculitis (AAV) and she was hospitalized for fibrocellular crescent nephritis and coexistence of membranous nephropathy. Voriconazole therapy was initiated for the treatment of aspergillus flavus on day 10 of admission. On day 12, fatigue was noted and blood pressure was 120/70 mmHg (baseline 140/80 mm Hg on antihypertensive therapy). By day 15, the patient had gained 6 kg in weight, serum potassium was 6.08 mcmol/L, urine output was decreased, serum creatinine (SCr) was 340 mcmol/L, the calculated nitrogen:SCr ratio was 22, and blood pressure was 90/40 mmHg; all hypertensive drugs and voriconazole were discontinued due to acute kidney injury, hypotension, hyperkalemia, and sinus arrest with junctional escape rhythm. Upon rechallenge of NIFEdipine and voriconazole, the patient experienced hypotension and anuria again. Voriconazole was discontinued and gradually the urine output increased. A drug interaction between voriconazole (a strong CYP3A4 inhibitor) and NIFEdipine (a CYP3A4 substrate) was suspected which may have caused NIFEdipine toxicity, therefore an antihypertensive not metabolized through CYP3A4 (terazosin) was utilized instead of NIFEdipine once her blood pressure rose again to 170/90 mmHg. Voriconazole treatment was resumed with concomitant terazosin without incident. She remained stable for the next 3 days prior to discharge, and 2 months after discharge, her SCr was 220 mcmol/L with normal urine output and serum potassium .

D) Coadministration of macrolide antibiotics erythromycin or clarithromycin with a calcium channel blocker was associated with significantly increased short-term risk of hospital admission within 7 days for hypotension or shock ([OR, 5.8; 95% CI, 2.25 to 14.98] or [OR, 3.7; 95% CI, 2.26 to 6.06]) in a case-crossover cohort study of geriatric patients (N=7100); there was no significant risk associated with azithromycin. In a stratified analysis of dihydropyridine calcium channel blockers (amlodipine, felodipine, NIFEdipine), the results remained significant for coadministration of erythromycin or clarithromycin. Calcium channel blocker treatment included diltiazem (40%), amlodipine (29.6%), NIFEdipine (19.4%), verapamil (8%), or felodipine (3%). The findings suggest that erythromycin and clarithromycin potentiate calcium channel blockers (CYP3A4 substrates) by inhibiting CYP3A4; azithromycin does not inhibit CYP3A4 .

Tucatinib Overview

• Tucatinib is used with trastuzumab (Herceptin) and capecitabine (Xeloda) to treat a certain type of hormone receptor–positive breast cancer that has spread to other parts of the body and cannot be treated with surgery in adults who have already been treated with at least one other chemotherapy medication. Tucatinib is also used with trastuzumab to treat a certain type of colorectal cancer (cancer that begins in the large intestine) that has spread to other parts of the body and cannot be treated with surgery in adults who have already been treated with other chemotherapy medications and have not improved or worsened. Tucatinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop or slow the spread of cancer cells.

Nifedipine Overview

• Nifedipine is used to treat high blood pressure and to control angina (chest pain). Nifedipine is in a class of medications called calcium-channel blockers. It lowers blood pressure by relaxing the blood vessels so the heart does not have to pump as hard. It controls chest pain by increasing the supply of blood and oxygen to the heart.

• High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.