Ketoconazole with Cinacalcet Interaction Details
Brand Names Associated with Ketoconazole
- Ketoconazole
- Nizoral®
Brand Names Associated with Cinacalcet
- Cinacalcet
- Sensipar®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 02, 2023
Interaction Effect
Increased bioavailability of cinacalcet and risk of hypocalcemia
Interaction Summary
Co-administration of cinacalcet and ketoconazole induced a 2.3-fold increase in cinacalcet bioavailability. Subjects treated for 7 days with ketoconazole 200 milligrams (mg) twice daily received a single dose of cinacalcet 90 mg on day 5. Compared with subjects receiving cinacalcet alone, co-treated subjects experienced 2.2 and 2.3-fold increases, respectively, in cinacalcet maximum serum concentration and area under the concentration-time curve. No pharmacodynamic effects were reported; increased bioavailability could reduce serum parathyroid hormone and/or calcium concentrations, leading to an increased risk of hypocalcemia and potentially lower seizure threshold. To treat clinical signs and symptoms of hypocalcemia, administer calcium-containing phosphate binders and/or vitamin D sterols; withhold cinacalcet for calcium serum concentrations less than 7.5 milligrams/deciliter .
Severity
Moderate
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Adjustments of cinacalcet dose may be required during co-administration of ketoconazole. Monitoring serum concentrations of parathyroid hormone and calcium is recommended whenever a potent CYP3A4 inhibitor such as ketoconazole is initiated or discontinued during cinacalcet therapy. Monitor for signs and symptoms of hypocalcemia (parethesias, myalgias, cramping, tetany, convulsions). Close scrutiny should be provided to patients with a history of seizure disorder. Administer calcium-containing phosphate binders and/or vitamin D sterols to treat clinical signs and symptoms of hypocalcemia, and withhold cinacalcet for calcium serum concentrations less than 7.5 milligrams/deciliter.
Mechanism Of Interaction
Inhibition of CYP3A4-mediated cinacalcet metabolism
Ketoconazole Overview
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Ketoconazole is used to treat fungal infections when other medications are not available or cannot be tolerated. Ketoconazole should not be used to treat fungal meningitis (infection of the membranes surrounding the brain and spinal cord caused by a fungus) or fungal nail infections. Ketoconazole is in a class of antifungals called imidazoles. It works by slowing the growth of fungi that cause infection.
Cinacalcet Overview
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Cinacalcet is used alone or with other medications to treat secondary hyperparathyroidism (a condition in which the body produces too much parathyroid hormone [a natural substance needed to control the amount of calcium in the blood] which can cause serious problems with the bones, heart, blood vessels, and lungs) in patients with chronic kidney disease (condition in which the kidneys stop working slowly and gradually) who are being treated with dialysis (medical treatment to clean the blood when the kidneys are not working properly). Cinacalcet is also used to treat high levels of calcium in the blood of patients who have parathyroid cancer (cancer of the glands in the neck that make parathyroid hormone). Cinacalcet is in a class of medications called calcimimetics. It works by signaling the body to produce less parathyroid hormone in order to decrease the amount of calcium in the blood.
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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:
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.