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. |
| Molecular Weight | 472.6 |
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 | No human data; animal studies show reproductive toxicity; avoid use unless no safer alternative. |
| 2nd trimester | No human data; potential fetal harm based on animal studies; use only if benefit outweighs risk. |
| 3rd trimester | May cause fetal harm and neonatal adverse effects; avoid use during third trimester if possible. |
Clinical note
Comprehensive clinical and safety monograph for VEOPOZ (VEOPOZ).
| Placental transfer | Crosses placenta extensively in animal studies; human data absent. |
| Breastfeeding | Excreted into breast milk in animal studies; no human data; consider discontinuing breastfeeding or drug based on importance to mother. |
| Lactation Rating |
■ 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 |
Hypersensitivity to VEOPOZ or any componentSevere hepatic impairmentConcomitant use with strong CYP3A4 inducers
| 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 |
| Food/Dietary |
Loading safety data…
| Avoid |
| 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. |
| 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. |
| No specific food interactions. However, patients should maintain adequate hydration and nutritional intake; report any significant appetite loss or weight changes. Avoid grapefruit juice as it may affect liver enzymes that metabolize some medications, though not specifically documented for necitumumab. |
| Clinical Pearls | VEOPOZ (necitumumab) is an EGFR antagonist approved for first-line treatment of metastatic squamous non-small cell lung cancer in combination with gemcitabine and cisplatin. Monitor for infusion reactions (premedicate with diphenhydramine and acetaminophen), electrolyte disturbances (hypomagnesemia, hypocalcemia, hypokalemia), and thromboembolic events. Hold for Grade 3 or 4 infusion reactions; permanently discontinue for severe or life-threatening reactions. Assess serum magnesium, calcium, and potassium before each dose and replete as needed. Advise patients to use effective contraception during and for 3 months after treatment. |
| Patient Advice | VEOPOZ is given by intravenous infusion and may cause infusion reactions; you will receive premedication to reduce this risk. · Report any signs of infusion reaction (fever, chills, difficulty breathing, rash) during or after the infusion. · Blood tests will be done regularly to check magnesium, calcium, and potassium levels; you may need supplements. · VEOPOZ can increase the risk of blood clots; notify your doctor if you experience leg pain, swelling, chest pain, or sudden shortness of breath. · Avoid pregnancy during treatment and for 3 months after the last dose; effective contraception is required. |