tirzepatide

General

Pronunciation:
tir-zep-a-tide

Trade Name(s)

  • Mounjaro
  • Zepbound

Ther. Class.

antidiabetics

Pharm. Class.

glucagon like peptide 1 glp 1 receptor agonists

glucose-dependent insulinotropic polypeptide (GIP) receptor agonists

Indications

  • Mounjaro: Type 2 diabetes mellitus (as adjunct to diet and exercise).
  • Zepbound: Chronic weight management in patients who are obese (body mass index [BMI] ≥30 kg/m2 )  OR  are overweight (BMI ≥27 kg/m2 ) with ≥1 weight-related comorbid condition (e.g., hypertension, dyslipidemia, type 2 diabetes, obstructive sleep apnea, or cardiovascular disease) (as adjunct to reduced-calorie diet and increased physical activity).

Action

Acts as a glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 (GLP-1) receptor agonist; increases insulin secretion and reduces glucagon secretion, both in a glucose-dependent manner. Also slows gastric emptying. Also helps to suppress appetite, leading to decreased caloric intake.

Therapeutic Effect(s):

  • Improved glycemic control.
  • Reduction in body weight.

Pharmacokinetics

Absorption: 80% absorbed following subcutaneous administration.

Distribution: Minimally distributed to tissues.

Protein Binding: 99%.

Metabolism and Excretion: Metabolized by proteolytic cleavage, beta-oxidation, and amide hydrolysis. Excreted in the urine and feces, with very little being eliminated as unchanged drug.

Half-life: 5 days.

TIME/ACTION PROFILE (plasma concentrations)

ROUTEONSETPEAKDURATION
SUBQunknown8–72 hrunknown

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity;
  • Personal or family history of medullary thyroid carcinoma;
  • Multiple endocrine neoplasia syndrome type 2;
  • Type 1 diabetes;
  • Severe gastroparesis.

Use Cautiously in:

  • History of pancreatitis;
  • Diabetic retinopathy (↑ risk of complications);
  • History of angioedema or anaphylaxis to another GLP-1 receptor agonist;
  • History of suicide or active suicidal ideation;
  • Rep:  Women of reproductive potential;
  • OB:  Use during pregnancy only if potential maternal benefit justifies potential fetal risk; insulin recommended for glucose management in pregnancy;
  • Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
  • Pedi:   Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

CV: hypotension, ↑ heart rate

Derm: hair loss

EENT: retinopathy complications

Endo: hypoglycemia, MEDULLARY THYROID CARCINOMA

GI: constipation, diarrhea, nausea, vomiting, ↑ amylase, ↑ lipase, abdominal distension, abdominal pain, cholecystitis, cholelithiasis, dyspepsia, flatulence, gastroesophageal reflux disease, PANCREATITIS

GU: acute kidney injury

Local: injection site reactions

Metabolic: ↓ appetite

Neuro: dizziness, fatigue, SUICIDAL THOUGHTS/BEHAVIOR

Misc: HYPERSENSITIVITY REACTIONS (including anaphylaxis and angioedema)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  • Concurrent use with  agents that increase insulin secretion, including  sulfonylureas  or  insulin, may ↑ the risk of serious hypoglycemia; use cautiously and consider dose ↓ of agent increasing insulin secretion.
  • May alter absorption of concomitantly administered  oral medications, including  oral hormonal contraceptives, due to delayed gastric emptying; advise patients taking oral hormonal contraceptive to switch to a nonoral contraceptive method or add a barrier contraceptive method for 4 wk after initiating therapy and for 4 wk after each dose escalation of tirzepatide.

Route/Dosage

Type 2 Diabetes

SUBQ (Adults): Mounjaro: 2.5 mg once weekly initially for 4 wk, then ↑ to 5 mg once weekly; may then ↑ dose in 2.5 mg/wk increments every 4 wk, if needed, to achieve glycemic goals (max weekly dose = 15 mg/wk).

Chronic Weight Management

SUBQ (Adults): Zepbound: 2.5 mg once weekly initially for 4 wk, then ↑ to 5 mg once weekly; may then ↑ dose in 2.5 mg/wk increments every 4 wk, if needed, to achieve weight loss goals. Recommended maintenance dose is 5 mg/wk, 10 mg/wk, or 15 mg/wk (max weekly dose = 15 mg/wk).

Availability

Solution for injection (prefilled pens): 2.5 mg/0.5 mL, 5 mg/0.5 mL, 7.5 mg/0.5 mL, 10 mg/0.5 mL, 12.5 mg/0.5 mL, 15 mg/0.5 mL

Assessment

  • Observe patient taking concurrent insulin for signs and symptoms of hypoglycemic reactions (sweating, hunger, weakness, dizziness, tremor, tachycardia, anxiety, headache, blurred vision, slurred speech, irritability).
  • If thyroid nodules or elevated serum calcitonin are noted, patient should be referred to an endocrinologist.
  • Monitor for pancreatitis (persistent severe abdominal pain, sometimes radiating to the back, with or without vomiting). If pancreatitis is suspected, discontinue tirzepatide; if confirmed, do not restart tirzepatide.
  • Monitor for signs and symptoms of hypersensitivity reactions (anaphylaxis, angioedema) during therapy.
  • Monitor for new or worsening depression, suicidal thoughts or behaviors, and/or any unusual changes in mood or behavior. If patient experiences suicidal thoughts or behaviors, discontinue tirzepatide.
  • Monitor weight before and periodically during therapy.

Lab Test Considerations:

Monitor serum A1c  periodically during therapy to evaluate effectiveness.

  • Zepbound:  In patients with type 2 diabetes, monitor blood glucose prior to starting and during therapy.
  • May ↑ lipase and pancreatic amylase.

Implementation

  • Patients stabilized on a diabetic regimen who are exposed to stress, fever, trauma, infection, or surgery may require administration of insulin.
  • SUBQ Administer once weekly at any time of the day, without regard to food. Day of wk may be changed as long as at least 72 hr before next dose. Inject into abdomen, thigh, or upper arm. Rotate injection sites with each dose. Solution is clear and colorless to slightly yellow; do not administer solutions that are cloudy, discolored, or contain particulate matter. Store pens in refrigerator; can also be stored at room temperature for up to 21 days; do not freeze. Store in the original carton to protect from light.
  • When using with insulin, administer as separate injections; never mix. If injecting tirzepatide and insulin in same body region, injections should not be close to each other.

Patient/Family Teaching

  • Instruct patient on use of pen and to use tirzepatide as directed. Advise patient to rotate injection sites with each dose. Follow manufacturer's instructions for pen use. Pen should never be shared between patients, even if needle is changed. Store pen in refrigerator; do not freeze. After initial use, pen may be stored at room temperature for up to 21 days. Advise patient to read the  Medication Guide  before starting tirzepatide and with each Rx refill in case of changes.
  • Take missed dose as soon as remembered within 4 days 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.
  • Advise patient taking insulin and tirzepatide to never mix insulin and tirzepatide together. Give as two separate injections. Both injections may be given in the same body area, but should not be given right next to each other.
  • Explain to patient that this medication controls hyperglycemia but does not cure diabetes. Therapy is long-term.
  • Review signs of hypoglycemia and hyperglycemia with patient. If hypoglycemia occurs, advise patient to take a glass of orange juice or 2–3 tsp of sugar, honey, or corn syrup dissolved in water and notify health care professional.
  • Encourage patient to follow prescribed diet, medication, and exercise regimen to prevent hypoglycemic or hyperglycemic episodes.
  • Instruct patient in proper testing of serum glucose and ketones. These tests should be closely monitored during periods of stress or illness, and health care professional should be notified if significant changes occur.
  • Advise patient to notify health care professional if changes in vision occur during therapy.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
  • Advise patient to notify health care professional immediately if signs of pancreatitis (nausea, vomiting, abdominal pain) or hypersensitivity (swelling of face, lips, tongue or throat, problems breathing or swallowing, severe rash or itching, fainting or feeling dizzy, very rapid heartbeat) occur.
  • Inform patient of risk of benign and malignant thyroid C-cell tumors. Advise patient to notify health care professional if symptoms of thyroid tumors (lump in neck, hoarseness, trouble swallowing, shortness of breath) occur.
  • Advise patient to inform health care professional of medication regimen before treatment or surgery.
  • Advise patient to carry a form of sugar (sugar packets, candy) and identification describing disease process and medication regimen at all times.
  • Rep:  Insulin is the preferred method of controlling blood glucose during pregnancy. Counsel females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Advise patients using oral hormonal contraceptives to switch to a nonoral contraceptive method, or add a barrier method of contraception for 4 wk after initiation and for 4 wk after each dose escalation.
  • Emphasize the importance of routine follow-up exams.

Evaluation/Desired Outcomes

Improved glycemic control.