Zepbound side effects: what the Canadian product monograph says

Most common side effects

The product monograph says that, in a pool of 3 placebo-controlled trials for weight management, the most frequently reported adverse reactions were gastrointestinal disorders. They included nausea, diarrhea, constipation and vomiting. In general, these reactions were mild or moderate in severity.

The majority of nausea, vomiting and/or diarrhea events occurred during dose escalation and decreased over time.

All hair loss events reported with Zepbound in clinical trials were mild or moderate in severity.

The patient information also lists belching, bloating of the stomach, change in taste, decreased appetite, dizziness, dry mouth and gas. It lists increased heart rate, low blood pressure, reflux or heart burn, and unusual skin sensations.

The monograph says that the adverse reactions in the obstructive sleep apnea trials were similar to those in the two pooled weight reduction trials.

The numbers below are from two 72-week placebo-controlled studies in adults with obesity or overweight. Each line gives the share of patients on Zepbound 5 mg, 10 mg and 15 mg, then on placebo.

• Nausea: 24.6%, 29.0% and 28.0%. Placebo: 8.5%.
• Diarrhea: 18.7%, 20.8% and 22.5%. Placebo: 7.8%.
• Constipation: 16.8%, 14.1% and 10.8%. Placebo: 5.2%.
• Vomiting: 8.3%, 10.8% and 12.5%. Placebo: 2.2%.
• Abdominal pain: 8.9%, 9.3% and 10.4%. Placebo: 5.1%.
• Dyspepsia: 8.9%, 9.0% and 9.9%. Placebo: 3.9%.
• Injection site reactions: 5.7%, 8.1% and 8.2%. Placebo: 1.8%.
• Fatigue: 4.6%, 5.7% and 6.8%. Placebo: 3.1%.
• Hair loss: 5.1%, 4.2% and 4.9%. Placebo: 0.8%.

Serious warnings and precautions box

The box in the product monograph is about the risk of thyroid C-cell tumors. Tirzepatide, the medicinal ingredient in Zepbound, increased the risk of thyroid C-cell tumors in rats. It is not known if the risk seen in rats applies to humans.

The box says that it is uncertain if Zepbound may increase your risk of thyroid C-cell tumors, including medullary thyroid carcinoma.

The box says: do not use Zepbound if you have a personal or family history of medullary thyroid cancer (MTC). It says the same for Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

The patient information gives these symptoms of thyroid cancer: lump or swelling in the neck, voice changes, trouble swallowing.

Who must not use Zepbound

Zepbound is not indicated for pediatric use. The patient information says that it is not recommended in children and adolescents under 18 years.

The monograph does not recommend Zepbound in patients with severe gastrointestinal disease, including severe gastroparesis. It does not recommend use with other tirzepatide-containing products or with any GLP-1 receptor agonist.

The monograph says to avoid Zepbound in patients with a history of suicidal attempts or active suicidal ideation.

If you wish to become pregnant, the patient information says to stop Zepbound at least 1 month before you try to get pregnant.

The patient information says not to use Zepbound in these cases:

• You are allergic to tirzepatide, to any ingredient in Zepbound or to a component of its container. This includes benzyl alcohol, which is used as a preservative.
• You or a member of your family has ever had medullary thyroid cancer (MTC).
• You have Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
• You are pregnant. The patient information says that Zepbound may harm your unborn baby.

Other warnings in the monograph

The monograph also describes these risks:

• Pancreatitis: if pancreatitis is suspected, Zepbound should be discontinued. If pancreatitis is confirmed, Zepbound should not be restarted.
• Gallbladder disease: treatment with Zepbound is associated with an increased occurrence of acute gallbladder disease.
• Low blood sugar: the use of Zepbound with a sulfonylurea or insulin might increase the risk of low blood sugar.
• Kidney problems: nausea, vomiting and diarrhea can cause dehydration. Dehydration can lead to kidney problems, such as sudden kidney failure.
• Malnutrition: events related to malnutrition, including severe events, have been reported in patients who receive Zepbound.
• Heart rate: Zepbound causes an increase in heart rate.
• Low blood pressure: in 2 placebo-controlled trials, hypotension occurred in 1.1%, 1.4% and 2.1% of patients on Zepbound 5 mg, 10 mg and 15 mg. It occurred in 0.1% of patients on placebo.
• Mood: the monograph says to discontinue Zepbound in patients who experience suicidal thoughts or behaviours.
• Oral birth control: the patient information says that birth control taken by mouth may not work as well while you use Zepbound.
• Oral birth control: it says to switch to a different type of birth control or to add a barrier method. The barrier method is for 4 weeks after the start and for 4 weeks after each dose increase.
• Eye disease: in patients with type 2 diabetes, quick improvements in blood sugar control may cause a temporary worsening of diabetic eye disease.
• Anesthesia: the patient information says to tell your healthcare professional that you use Zepbound before a procedure with general anesthesia or deep sedation.
• Benzyl alcohol: the Zepbound pen contains 5.4 mg benzyl alcohol in each 0.6 mL dose. Benzyl alcohol may cause allergic reactions.

When to stop and get medical help

The patient information says to stop Zepbound and get medical help right away if you have any symptoms of a serious allergic reaction. This can include itching, rash or difficulty breathing.

It says to urgently contact your healthcare professional if you have a sudden loss of vision or rapidly worsening eyesight. It says to seek immediate medical attention for severe abdominal pain, yellowing of your skin, or high fever with chills. It says to speak to your healthcare professional immediately if you have severe pain in the stomach area or back which does not go away. It says to call your healthcare professional right away if you have thoughts or behaviours of harming or killing yourself.

For a suspected overdose, it says to contact a healthcare professional, a hospital emergency department or a regional poison control centre immediately. This applies even if there are no signs or symptoms. The monograph also gives the toll-free number of Health Canada: 1-844-764-7669.

The table of serious side effects lists gastrointestinal problems as very common and diabetic retinopathy as common. It lists severe low blood sugar as uncommon. The frequency of malnutrition, thyroid cancer and pulmonary aspiration during anesthesia is unknown. For these six, the table says to talk to your healthcare professional in all cases.

For the side effects below, the table says to stop using Zepbound and get immediate medical help:

• Rare: acute pancreatitis (sudden inflammation of the pancreas). Symptom: prolonged severe abdominal pain with or without vomiting.
• Rare: dehydration that can cause sudden kidney failure. Symptoms: dark yellow and strong-smelling pee, feeling extremely thirsty, feeling dizzy or lightheaded.
• Rare: sudden gallbladder problems. Symptoms: severe abdominal pain, yellowing of your skin, or high fever with chills.
• Frequency unknown: anaphylactic reaction or angioedema (serious allergic reaction). Symptoms: breathing problems, swelling of the throat and face, fast heartbeat.
• Frequency unknown: gastroparesis (slow stomach emptying). Symptoms: pain, severe nausea and vomiting, prolonged belching and prolonged bloating.
• Frequency unknown: suicidal ideation (thoughts of suicide). Symptoms: worsening depression, suicidal thoughts and behaviours, unusual changes in mood.
• Frequency unknown: ileus (loss of muscle contraction in the intestine). Symptoms: bloating, abdominal pain and cramping, gas, nausea, vomiting, constipation, loss of appetite.
• Frequency unknown: non-arteritic anterior ischemic optic neuropathy (NAION, an eye condition). Symptoms: sudden decreased vision (blurring or cloudiness) or permanent loss of vision.

Ask a health professional

This page repeats what the Canadian product monograph says. It is not medical advice. Ask your pharmacist or your prescriber what applies to you.