3.
Elsevier ClinicalKey Drug Monograph
Content last updated: April 4, 2024.
Administration
* Withdraw 0.5 mL of solution making sure to eliminate any air bubbles in the syringe.
* Inject subcutaneously into the thigh, abdomen, or upper arm.
* Rotate administration sites with each injection to prevent lipodystrophy; do not inject into areas of lipodystrophy or localized cutaneous amyloidosis. Do not inject where the skin is tender, bruised, scaly or hard, or into scars or damaged skin.
* Dispose of the used needle and syringe in an appropriate sharps container after each injection.
**Zepbound
**
General information
* Zepbound Pen is available in 6 pre-filled, disposable, single-dose pens and vials (2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg strengths). Ensure the correct dose of the pen or vial is chosen for the dose to be administered.
* Never mix tirzepatide with other medications or inject in the same injection site as other medications.
* Instruct patients/caregivers on proper injection technique. Adequate oral and written instructions on the use should be supplied before a patient or caregiver administers a dose. Instruct patients using the single-dose vials to use a syringe appropriate for dose administration (e.g., a 1 mL syringe capable of measuring a 0.5 mL dose). Patients/caregivers should review the "Instructions for Use" in their package. People who are blind or have vision problems should not use the pen without help from a person trained to use the pen.
* Administer once every 7 days (once weekly) on the same day each week; the dose can be administered at any time of day, with or without meals.
* Missed dose: If 1 dose is missed, instruct patients to administer tirzepatide as soon as possible within 4 days (96 hours) after the missed dose. If more than 4 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule. The day of weekly administration can be changed, if necessary, as long as the time between the two doses is at least 3 days (72 hours).
Administration
* ### **General Administration Information**
For storage information, see the specific product information within the How Supplied section.
* ### **Route-Specific Administration**
* Injectable Administration
* * Administer by subcutaneous injection only. Do not administer by intravenous or intramuscular injection.
* Visually inspect for particulate matter and discoloration prior to administration whenever solution and container permit.
* Injection pens should never be shared among patients. Even if the disposable needle is changed, sharing may result in transmission of hepatitis viruses, HIV, or other blood-borne pathogens. Do not share pens among multiple patients in an inpatient setting; reserve the use of any pen to 1 patient only.
* Subcutaneous Administration
* **Mounjaro
**
General information
* Mounjaro is available in pre-filled disposable, single-dose pens and vials (2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg strengths). Ensure the correct dose of the pen or vial is chosen for the dose to be administered.
* Never mix tirzepatide with other medications or inject in the same injection site as other medications. When used concomitantly with insulin therapy, the 2 injections may be injected in the same body region, but the injections should not be adjacent to each other.
* Instruct patients/caregivers on proper injection technique. Adequate oral and written instructions on the use should be supplied before a patient or caregiver administers a dose. Instruct patients using the single-dose vials to use a syringe appropriate for dose administration (e.g., a 1 mL syringe capable of measuring a 0.5 mL dose). Patients/caregivers should review the "Instructions for Use" in their package. People who are blind or have vision problems should not use the pen without help from a person trained to use the pen.
* Administer every 7 days (once weekly) on the same day each week; the dose can be administered at any time of day, with or without meals.
* Missed dose: If a dose is missed, give as soon as possible within 4 days (96 hours) after the missed dose.
Contraindications And Precautions
Hypoglycemia should be monitored by the patient and clinician when tirzepatide treatment is initiated and continued for type 2 diabetes mellitus (T2DM) and when used for weight reduction and maintenance. The risk of hypoglycemia, including severe hypoglycemia, is increased when tirzepatide is used in combination with insulin secretagogues (e.g., sulfonylureas, "glinides") or with insulin. Although specific dose recommendations are not available for most agents, the clinician should consider a dose reduction of the insulin secretagogue or insulin when used in combination with tirzepatide. In a trial of tirzepatide in adults with obesity/overweight without type 2 diabetes mellitus, there was no systematic capturing of hypoglycemia, but plasma glucose less than 54 mg/dL was reported in 0.3% of tirzepatide-treated patients versus no placebo-treated patients. Adequate blood glucose monitoring should be continued and followed. Patient and family education regarding hypoglycemia management is crucial; the patient and patient's family should be instructed on how to recognize and manage the symptoms of hypoglycemia. Early warning signs of hypoglycemia may be less obvious in patients with hypoglycemia unawareness which can be due to a long history of diabetes (where deficiencies in the release or response to counter-regulatory hormones exist), with autonomic neuropathy, intensified diabetes control, or taking medications such as beta-blockers, guanethidine, or reserpine. Patients should be aware of the need to have a readily available source of glucose (dextrose, d-glucose) or another carbohydrate to treat hypoglycemic episodes. In severe hypoglycemia, intravenous dextrose or glucagon injections may be needed. Because hypoglycemic events may be difficult to recognize in some elderly patients, antidiabetic agent regimens should be carefully managed to prevent an increased risk of severe hypoglycemia.
Adverse Reactions
Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists. In clinical studies, 14 events of acute pancreatitis were confirmed by adjudication in 13 patients treated with tirzepatide (0.23 patients per 100 years of exposure) versus 3 events in 3 comparator-treated patients (0.11 patients per 100 years of exposure). In the pool of placebo-controlled clinical trials, treatment with tirzepatide resulted in hyperamylasemia, with mean increases from baseline in serum pancreatic amylase concentrations of 33% to 38% and serum lipase concentrations of 31% to 42%. Placebo treated patients had a mean increase from baseline in pancreatic amylase of 4% and no changes were observed in lipase. The clinical significance of elevations in lipase or amylase with tirzepatide is unknown in the absence of other signs and symptoms of pancreatitis. Treatment with tirzepatide for weight management resulted in mean increases from baseline in serum pancreatic amylase concentrations of 20% to 25% and serum lipase concentrations of 28% to 35%, compared to mean increases from baseline in pancreatic amylase of 2.1% and serum lipase of 5.8% in placebo-treated patients. The clinical significance of elevations in amylase or lipase with tirzepatide is unknown in the absence of other signs and symptoms of pancreatitis. Patients should be instructed to seek prompt medical attention if they experience unexplained persistent severe abdominal pain, which may or may not be accompanied by vomiting. If pancreatitis is suspected, tirzepatide should be discontinued. If pancreatitis is confirmed, tirzepatide should not be restarted unless an alternative etiology is identified.
Interactions
Cyclafem 7/7/7: (Major) Advise patients receiving tirzepatide and oral contraceptives to switch to a non-oral contraceptive method or to add a barrier method of contraception for 4 weeks after initiation and for 4 weeks after each dose escalation of tirzepatide. Tirzepatide delays gastric emptying and may reduce the rate and extent of estrogen and progestin absorption which may reduce efficacy. Gastric emptying delays are greatest after the first dose of tirzepatide and diminish over time. Hormonal contraceptives that are not administered orally should not be affected. Additionally, estrogens can impair glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day.
