Important Safety Information — Tirzepatide

SHED Protocol

WARNING: RISK OF THYROID C-CELL TUMORS

In rats, tirzepatide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether tirzepatide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of tirzepatide-induced rodent thyroid C-cell tumors has not been determined.

Tirzepatide is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

Indications

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with obesity (BMI of 30 kg/m2 or greater) or overweight (BMI of 27 kg/m2 or greater) with at least one weight-related comorbid condition.

Contraindications

Personal or family history of medullary thyroid carcinoma (MTC)
Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
Known serious hypersensitivity to tirzepatide or any of the excipients

Warnings and Precautions

Thyroid C-cell tumors: Counsel patients regarding the potential risk and symptoms of thyroid tumors (a lump or swelling in the neck, hoarseness, difficulty swallowing, shortness of breath).
Acute pancreatitis: Has been reported. Discontinue promptly if suspected. Do not restart if confirmed.
Hypoglycemia: Risk is increased when used with insulin or insulin secretagogues (e.g., sulfonylureas). Consider reducing the dose of the concomitant agent.
Hypersensitivity reactions: Serious reactions including anaphylaxis and angioedema have been reported. Discontinue if suspected.
Diabetic retinopathy complications: Rapid improvement in glucose control may temporarily worsen diabetic retinopathy.
Acute gallbladder disease: Cholelithiasis and cholecystitis have been reported.
Acute kidney injury: Monitor renal function in patients with renal impairment who experience severe gastrointestinal reactions, as dehydration can lead to acute kidney injury.
Suicidal behavior and ideation: Monitor for depression or suicidal thoughts. Discontinue if symptoms develop.
Pulmonary aspiration: Tirzepatide delays gastric emptying, increasing the risk of pulmonary aspiration during procedures requiring general anesthesia or deep sedation.

Common Side Effects

Nausea
Diarrhea
Vomiting
Constipation
Abdominal pain
Dyspepsia (indigestion)
Injection site reactions
Fatigue
Decreased appetite
Hypersensitivity reactions
Eructation (belching)
Hair loss (alopecia)
Gastroesophageal reflux disease

Serious Side Effects

Seek medical attention immediately if you experience any of the following:

Severe, persistent abdominal pain, with or without vomiting (possible pancreatitis)
A lump or swelling in the neck, hoarseness, difficulty swallowing, or shortness of breath (possible thyroid tumor)
Signs of allergic reaction: rash, itching, swelling of the face, lips, tongue, or throat, difficulty breathing or swallowing
Severe pain in the upper right abdomen (possible gallbladder problems)
Decreased urination or dark-colored urine (possible kidney problems)
Changes in vision (in patients with diabetes)
Depression or thoughts of self-harm

Drug Interactions

Oral hormonal contraceptives: Tirzepatide may reduce the efficacy of oral contraceptives due to delayed gastric emptying. Patients should switch to a non-oral contraceptive method or add a barrier method of contraception for 4 weeks after initiation and for 4 weeks after each dose escalation.
Insulin and insulin secretagogues: Increased risk of hypoglycemia. Consider dose reduction.
Oral medications: Tirzepatide delays gastric emptying and may impact absorption of orally administered medications. Use caution when administering oral medications with tirzepatide.
Warfarin: Monitor INR when initiating or altering tirzepatide therapy.

Use in Specific Populations

Pregnancy: Contraindicated. Discontinue tirzepatide at least 2 months before a planned pregnancy. May cause fetal harm based on animal data.
Lactation: It is not known whether tirzepatide is present in human breast milk. Breastfeeding is not recommended during treatment.
Pediatric use: Safety and effectiveness have not been established in patients under 12 years of age.
Geriatric use: No overall differences in safety or efficacy observed, though greater sensitivity of some older individuals cannot be ruled out.
Renal impairment: Monitor renal function in patients reporting severe gastrointestinal reactions.
Hepatic impairment: No dose adjustment is required.