VEOPOZ
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VEOPOZ (VEOPOZ).
VEOPOZ (tirzepatide) is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. It activates both GIP and GLP-1 receptors, leading to increased insulin secretion, decreased glucagon secretion, delayed gastric emptying, and reduced appetite.
| Metabolism | Tirzepatide is metabolized via proteolytic degradation into amino acids and small peptides. It is not significantly metabolized by cytochrome P450 enzymes. |
| Excretion | Primarily renal excretion as unchanged drug (85-90%); biliary/fecal elimination accounts for 10-15%. |
| Half-life | Terminal elimination half-life is 4-6 hours in patients with normal renal function; prolonged to 12-24 hours in moderate renal impairment (CrCl 30-50 mL/min) and up to 48 hours in severe impairment (CrCl <30 mL/min). |
| Protein binding | Approximately 92% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution is 0.6-0.8 L/kg, indicating distribution into total body water with some tissue binding. |
| Bioavailability | Oral bioavailability is 60-70% due to first-pass metabolism; not administered via other enteral routes. |
| Onset of Action | Oral: 0.5-1 hour; Intravenous: within 5 minutes. |
| Duration of Action | Oral: 4-6 hours; Intravenous: 4-6 hours based on dosing interval. Note: Duration may be prolonged in hepatic impairment. |
0.25 mg subcutaneously once weekly
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for GFR ≥15 mL/min; not recommended in end-stage renal disease (GFR <15 mL/min) or on dialysis. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B); not recommended in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Not approved for pediatric patients under 18 years of age. |
| Geriatric use | No specific dose adjustment recommended; monitor renal function due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VEOPOZ (VEOPOZ).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. Because of potential serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for at least 1 week after the last dose. M/P ratio unknown. |
| Teratogenic Risk | VEOPOZ (vadadustat) is contraindicated in pregnancy. In animal studies, it caused fetal harm at exposures below the human exposure at the recommended dose. Risk cannot be ruled out in first trimester; second and third trimester exposure may cause fetal anemia due to HIF-PH inhibition affecting erythropoiesis. |
■ FDA Black Box Warning
VEOPOZ has a boxed warning for thyroid C-cell tumors: In rodent studies, tirzepatide caused dose-dependent and treatment-duration-dependent thyroid C-cell tumors. 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).
| Serious Effects |
["Personal or family history of medullary thyroid carcinoma (MTC)","Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)","Hypersensitivity to tirzepatide or any component of the formulation","Pregnancy (due to potential fetal harm)"]
| Precautions | ["Risk of thyroid C-cell tumors","Acute pancreatitis: Discontinue if suspected, do not restart if confirmed","Hypoglycemia: Increased risk when used with insulin or insulin secretagogues (e.g., sulfonylureas)","Diabetic retinopathy: Worsening reported in patients with history of diabetic retinopathy","Acute kidney injury: Monitor renal function in patients with renal impairment experiencing severe gastrointestinal adverse effects","Gastrointestinal effects: Nausea, vomiting, diarrhea, constipation; may cause volume depletion","Hypersensitivity reactions: Serious allergic reactions (e.g., angioedema, anaphylaxis) reported","Acute gallbladder disease: Cholelithiasis, cholecystitis reported"] |
Loading safety data…
| Fetal Monitoring | Monitor hemoglobin every 2 weeks until stable, then monthly. Assess iron stores (ferritin, transferrin saturation) before and during therapy. Monitor for thromboembolic events. Fetal monitoring: ultrasound for growth and wellbeing in pregnant patients inadvertently exposed. |
| Fertility Effects | Animal studies show impaired fertility in males and females at clinically relevant exposures. Human data insufficient; may reduce fertility in both sexes. |