MOUNJARO (AUTOINJECTOR)

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MOUNJARO (AUTOINJECTOR) (MOUNJARO (AUTOINJECTOR)).

How it works

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. It increases glucose-dependent insulin secretion, decreases glucagon secretion, slows gastric emptying, and promotes satiety.

What the body does with it

Metabolism	Metabolized by proteolytic cleavage of the peptide backbone, followed by beta-oxidation of the fatty diacid moiety and amide hydrolysis. CYP enzymes and esterases are not involved.
Excretion	Renal: negligible; Fecal: primarily via biliary elimination as intact peptide; total clearance ~0.056 L/h.
Half-life	Terminal elimination half-life ~5 days (117 hours), supporting once-weekly dosing.
Protein binding	~99% bound to albumin.
Volume of Distribution	3.3 L (not weight-based), indicating limited tissue distribution.
Bioavailability	Subcutaneous: ~75–80%.
Onset of Action	Subcutaneous: glycemic effects observed within 2–4 weeks; maximal glucose lowering by 8–12 weeks.
Duration of Action	Subcutaneous: pharmacodynamic effects persist for at least 1 week; steady-state achieved after 4 weeks.

Classification & Brands

Dosing & administration

Subcutaneously once weekly; initial dose 2.5 mg for 4 weeks, then increase to 5 mg for 4 weeks, then 7.5 mg, 10 mg, 12.5 mg, and 15 mg as tolerated; maximum 15 mg weekly.

Dosage form	SOLUTION
Renal impairment	No dose adjustment required for mild to moderate renal impairment (eGFR 30-89 mL/min/1.73 m²). Not recommended for use in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease.
Liver impairment	No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not recommended for use in moderate to severe hepatic impairment (Child-Pugh B or C).
Pediatric use	Safety and efficacy not established in pediatric patients under 18 years of age.
Geriatric use	No dose adjustment recommended based on age alone; consider renal function as older patients may have reduced renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for MOUNJARO (AUTOINJECTOR) (MOUNJARO (AUTOINJECTOR)).

Breastfeeding	No data on presence in human milk, effects on breastfed infant, or milk production. M/P ratio unknown. Consider benefits of breastfeeding vs maternal need for drug and potential infant effects.
Teratogenic Risk	First trimester: No adequate human data; animal studies show fetal harm at clinically relevant exposures. Second and third trimesters: Potential for fetal harm due to maternal weight loss and metabolic changes; avoid use as pregnancy advances.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

WARNING: RISK OF THYROID C-CELL TUMORS. Tirzepatide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors in rats. It is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

Side Effect Profile

Serious Effects

Absolute Contraindications

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

Clinical Precautions

Precautions

["Risk of thyroid C-cell tumors","Acute pancreatitis","Hypoglycemia (especially with insulin secretagogues or insulin)","Hypersensitivity reactions","Acute kidney injury","Severe gastrointestinal disease","Diabetic retinopathy complications","Cholelithiasis and cholecystitis","Suicidal behavior or ideation"]

Clinical Tips & Counseling

Drug interactions

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MOUNJARO (AUTOINJECTOR)

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MOUNJARO (AUTOINJECTOR) (MOUNJARO (AUTOINJECTOR)).

How it works

What the body does with it

Metabolism	Metabolized by proteolytic cleavage of the peptide backbone, followed by beta-oxidation of the fatty diacid moiety and amide hydrolysis. CYP enzymes and esterases are not involved.
Excretion	Renal: negligible; Fecal: primarily via biliary elimination as intact peptide; total clearance ~0.056 L/h.
Half-life	Terminal elimination half-life ~5 days (117 hours), supporting once-weekly dosing.
Protein binding	~99% bound to albumin.
Volume of Distribution	3.3 L (not weight-based), indicating limited tissue distribution.
Bioavailability	Subcutaneous: ~75–80%.
Onset of Action	Subcutaneous: glycemic effects observed within 2–4 weeks; maximal glucose lowering by 8–12 weeks.
Duration of Action	Subcutaneous: pharmacodynamic effects persist for at least 1 week; steady-state achieved after 4 weeks.

Classification & Brands

Dosing & administration

Subcutaneously once weekly; initial dose 2.5 mg for 4 weeks, then increase to 5 mg for 4 weeks, then 7.5 mg, 10 mg, 12.5 mg, and 15 mg as tolerated; maximum 15 mg weekly.

Dosage form	SOLUTION
Renal impairment	No dose adjustment required for mild to moderate renal impairment (eGFR 30-89 mL/min/1.73 m²). Not recommended for use in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease.
Liver impairment	No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not recommended for use in moderate to severe hepatic impairment (Child-Pugh B or C).
Pediatric use	Safety and efficacy not established in pediatric patients under 18 years of age.
Geriatric use	No dose adjustment recommended based on age alone; consider renal function as older patients may have reduced renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for MOUNJARO (AUTOINJECTOR) (MOUNJARO (AUTOINJECTOR)).

Breastfeeding	No data on presence in human milk, effects on breastfed infant, or milk production. M/P ratio unknown. Consider benefits of breastfeeding vs maternal need for drug and potential infant effects.
Teratogenic Risk	First trimester: No adequate human data; animal studies show fetal harm at clinically relevant exposures. Second and third trimesters: Potential for fetal harm due to maternal weight loss and metabolic changes; avoid use as pregnancy advances.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

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