Zepbound interactions to avoid

In this article:

• Zepbound drug interactions
• How to minimize Zepbound interactions
• When to talk to a healthcare provider

In this article

• Zepbound drug interactions
• How to minimize Zepbound interactions
• When to talk to a healthcare provider

Zepbound (tirzepatide) is a prescription medication used for weight loss, weight management, and obstructive sleep apnea. The weekly injection belongs to the drug class of dual glucose-dependent insulinotropic (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists. Like any medication, the Zepbound treatment can interact with other drugs, such as oral birth control and antidiabetic drugs. The weight loss medication isn’t known to interact with certain foods, but alcohol and caffeine could increase your chances of side effects. Knowing Zepbound’s interactions can prevent unwanted and potentially serious side effects while using this drug.

Zepbound drug interactions

Here’s a look at known drug interactions with Zepbound and potential side effects that may occur:

Drug class or group name	Drug name	Interactions/side effects
Sulfonylureas	Diabeta, Glynasen (glyburide) Amaryl (glimepiride) Glucotrol XL (glipizide)	Can lower blood sugar
Oral contraceptives	Aurovela, Blisovi, Hailey Fe, etc. (ethinyl estradiol/norethindrone acetate) Yasmin, Yaz, and Syeda (ethinyl estradiol/drospirenone) Estaylla, Vylibra, Tri-Mili, etc. (ethinyl estradiol/norgestimate)	Decreased efficacy
Insulin	Fiasp, NovoLog (insulin aspart) Levemir (insulin detemir) Lantus, Toujeo (insulin glargine)	Can lower blood sugar
Meglitinides	Repaglinide Starlix (nateglinide)	Can lower blood sugar
Any oral medications	Jantoven (warfarin) Gengraf, Neoral, and Sandimmune (cyclosporine)	Decreased efficacy

Sulfonylureas

Sulfonylureas are a class of medications used to manage blood sugar levels in people with Type 2 diabetes. Taking the antidiabetic drug with Zepbound may lower blood sugar (known as hypoglycemia). “This doesn’t necessarily mean that Zepbound is off the table for these patients, but it does mean that it’ll need to be added under close medical supervision,” says Marlee Bruno, MMS, PA-C, a board-certified physician assistant and founder of Mind Body & Soul Medical in Pensacola, Florida. “I’ve had patients try to white-knuckle their way through hypoglycemia episodes because no one explained that the combination could hit that hard.”

The types of sulfonylureas healthcare providers may prescribe include the following:

• Chlorpropamide (Diabinese)
• Tolbutamide (Orinase, Tol-Tab)
• Glyburide (DiaBeta, Micronase, Glynase, Glynase PresTab, Glycron)
• Glipizide (Glucotrol, Glucotrol XL)
• Gliclazide (Diamicron, Diaprel, Glydex, Zircon)

If your healthcare provider prescribes Zepbound while you’re taking sulfonylureas, they should prescribe a lower dosage of the antidiabetic drug to reduce your risk of adverse side effects. 

Oral contraceptives

Oral contraceptives, also known as hormonal contraceptives, are prescription or over-the-counter medications used to prevent pregnancy. Taking oral birth control pills with Zepbound can make the medication less effective. “Zepbound significantly reduces the absorption of birth control pills,” says John La Puma, MD, FACP, a board-certified internist, weight management expert, best-selling author of REFUEL, and founder of The Ozempic Blueprint: A Simple Guide to Boost GLP-1 Naturally of Santa Barbara, California. 

Below are some oral contraceptives that can interact with Zepbound:

• Aurovela, Blisovi, Hailey Fe, etc. (ethinyl estradiol/norethindrone acetate)
• Yasmin, Yaz, and Syeda (ethinyl estradiol/drospirenone)
• Estaylla, Vylibra, Tri-Mili, etc. (ethinyl estradiol/norgestimate)

Your healthcare provider may recommend a backup birth control method in the early weeks of taking Zepbound. “I suggest patients use a barrier as an added precaution or switch to a non-oral form of birth control for four weeks with the start of Zepbound and for four weeks each time the dose is increased,” Dr. Puma explains.

Insulin

Insulin is a natural hormone in the body, but it is also prescribed (known as human insulin) as an injectable medication to manage blood sugar levels in people with Type 1 or 2 diabetes. “Taking insulin itself greatly increases the risk of hypoglycemia if you’re on Zepbound,” Dr. Puma explains.

The types of human insulin available include:

• Insulin aspart (Fiasp, NovoLog)
• Insulin detemir (Levemir)
• Insulin glargine (Lantus, Toujeo)

If you start taking Zepbound, your healthcare provider will adjust the dosage of your insulin injections to reduce the risk of low blood sugar.

Meglitinides

Meglinitides are oral antidiabetic drugs prescribed to control high blood sugar levels in people with Type 2 diabetes. Like sulfonylureas and human insulin, Zepbound can mess with the effectiveness of meglinitides, potentially increasing the risk of hypoglycemia. 

Below are the types of meglitinides that can interact with Zepbound:

• Repaglinide 
• Nateglinide (Starlix)

If you need to take Zepbound along with meglinitides, your healthcare provider will make the appropriate adjustments to the dosage of the antidiabetic drug to reduce the risk of hypoglycemia. 

Other Zepbound interactions

Having a family history of certain health conditions could increase the risk of adverse reactions while taking Zepbound. “Zepbound does have a black box warning due to findings in rodent studies concerning thyroid tumors,” Bruno says. “While this hasn’t been seen in humans, anyone with a personal or family history of medullary thyroid carcinoma or MEN2 should steer clear.”

Zepbound and alcohol

While alcohol doesn’t directly interact with Zepbound, Dr. Puma says that the substance could worsen the weight loss drug’s GI side effects. “There is also an increased risk of hypoglycemia, particularly if taken on an empty stomach or in diabetic patients,” he says. 

Zepbound and caffeine 

Similar to alcohol, caffeine doesn’t interact with Zepbound. However, because of the medication’s effects on the GI system, drinking caffeine in the early weeks of starting Zepbound could cause some mild side effects. “Adding in caffeine, especially on an empty stomach, can cause some jitteriness, nausea, or just generally feeling unwell,” Bruno explains. “If a patient is sensitive to reflux or gets the anxious jitters, I usually recommend scaling back their caffeine or at least pairing it with food.”

How to minimize Zepbound interactions

There are several ways to reduce your risk of Zepbound interactions. A good starting point is making sure that you don’t have any medical conditions or situations that could increase the risk of interactions.

According to the FDA, these interactions include:

• Digestive problems: Zepbound is known to cause several digestive problems, such as nausea, vomiting, diarrhea, constipation, abdominal pain, and indigestion.
• Kidney problems: Because Zepbound may cause GI problems, it might lead to dehydration due to severe fluid loss. If you already have an existing kidney condition, this could worsen it.
• Type 2 diabetes and diabetic retinopathy: If you have diabetic retinopathy caused by Type 2 diabetes, Zepbound may cause temporary vision changes. 
• Mood disorders: Taking the weight loss drug while managing depression or similar mood disorders could lead to suicidal thoughts, ideation, or behavior.
• Severe allergic reaction: If you’re allergic to any of the ingredients in Zepbound, your healthcare provider likely won’t prescribe the medication, as there’s a risk you could experience another allergic reaction.
• Upcoming surgery: Due to the weight loss drug’s mechanism of action, it can slow down how quickly food leaves your stomach. This could lead to pulmonary aspiration (or aspiration pneumonia), which is when food or other stomach contents are inhaled into your airways and lungs while under general anesthesia. If you have a scheduled surgery involving sedation, notify your healthcare provider before starting Zepbound. If you’re already taking the injectable medicine, ensure that your healthcare team is aware. 

There’s no research to determine whether Zepbound is safe to inject during pregnancy or while breastfeeding. If you are pregnant, plan to become pregnant, or are breastfeeding or plan to, please consult your healthcare provider before starting Zepbound.

Aside from certain medical conditions and situations, you can lower your risk of adverse side effects from Zepbound with the following tips:

• Consult your healthcare provider: Before starting Zepbound, notify your healthcare provider of any medications, supplements, or substances you’re currently taking, family history of medical conditions, and any plans for pregnancy or breastfeeding. Doing so can help them determine if taking the weight loss medication is safe for your health.
• Keep a medication list on hand: You can use the FDA’s downloadable medication list to record any prescription or over-the-counter medications you’re taking and share it with your healthcare provider or pharmacist. 
• Know the warning signs: Be aware of any side effects that could indicate a Zepbound drug interaction, such as dizziness, sweating, confusion, rapid heartbeat, vision changes, or GI issues. Please reach out to your healthcare provider if you’re experiencing abnormal symptoms or seek immediate medical attention in emergencies. 

When to talk to a healthcare provider about Zepbound interactions

Please note that this is not an exhaustive list of all the potential Zepbound interactions. If you have any questions or concerns about taking the weight loss drug with other medications, supplements, or medical conditions, please consult your healthcare provider.