Does Mavyret Interact With Methadone Or Metoprolol?
In our latest question and answer, the pharmacist discusses the potential drug interactions between Mavyret, methadone, and metoprolol.
I am taking methadone. I also take metoprolol tartrate 25 mg twice a day. I'm about to take Mavyret for my hepatitis C but I want to make sure it's okay with the methadone and metoprolol tartrate?
Metoprolol, Mavyret, and methadone are considered safe to take together, but there are a few potential interactions to be aware of.
Low Blood Pressure With Metoprolol and Methadone
Methadone can lower blood pressure in some individuals.
Since metoprolol also lowers blood pressure, there is a chance that taking methadone with it can have additive effects.
Methadone specifically is known to cause 'orthostatic hypotension', which is a significant drop in blood pressure when going from a sitting or lying down position to standing. This drop in blood pressure can cause dizziness, lightheadedness and can increase the risk of falls.
The prescribing information for methadone states the following:
The administration of methadone may result in severe hypotension in patients whose ability to maintain normal blood pressure is compromised (e.g., severe volume depletion).
Even though methadone and metoprolol can lower blood pressure, they can be used together safely.
It is just important to be aware of signs of symptoms of low blood pressure (e.g. lightheadedness, dizziness) and check it periodically. Take care especially when standing up and be sure to discuss anything you are experiencing with your doctor.
Mavyret isn't known to affect blood pressure, so the concern lies only with methadone and metoprolol in this regard.
Methadone With Mavyret
Although there is not a documented interaction between methadone and Mavyret (most online drug interaction checkers will produce no result), these drugs may affect each other based on their known pharmacokinetic profiles.
Mavyret is a known inhibitor of p-glycoprotein, which is also known as multidrug resistance protein 1 [MDR1]. It has many functions but essentially acts as a drug efflux pump. It pumps drugs out of cells into the GI tract, bile, and urine for excretion from the body.
Altering p-glycoprotein levels is a well-known mechanism by which drugs may cause interactions.
Numerous studies have reported that methadone is a substrate for p-glycoprotein, and altering levels of it could affect concentrations of the drug in the blood.
The prescribing information for Mavyret states that it is an inhibitor of p-glycoprotein:
Glecaprevir and pibrentasvir [Mavyret] are inhibitors of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transporting polypeptide (OATP) 1B1/3. Coadministration with MAVYRET may increase plasma concentration of drugs that are substrates of P-gp, BCRP, OATP1B1 or OATP1B3
Since Mavyret can inhibit p-glycoprotein, taking it with methadone could decrease methadone excretion, increasing concentrations of the drug. This could increase the risk of side effects.
As mentioned above, this potential interaction hasn't been documented in studies but is certainly something to be aware of. It likely isn't overly significant however, as methadone is primarily metabolized via other pathways (e.g. via CYP enzymes in the liver).
Answer SummaryMetoprolol and methadone can both lower blood pressure. Additionally, Mavyret can inhibit P-glycoprotein (P-gp), which could decrease methadone excretion, increasing drug concentrations in the body.
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