What are the contraindications for using Phentermine (phentermine) with Mounjaro (tirzepatide) injections in a patient with obesity and type 2 diabetes, particularly those with a history of cardiovascular disease, severe hypertension, or impaired renal function?

Contraindications for Combining Phentermine with Mounjaro (Tirzepatide)

There are no absolute contraindications to combining phentermine with tirzepatide (Mounjaro) based on direct drug-drug interactions, but phentermine itself carries multiple absolute contraindications that must be screened before prescribing this combination, particularly cardiovascular disease, uncontrolled hypertension, and hyperthyroidism. 1

Absolute Contraindications to Phentermine (Apply Regardless of Tirzepatide Use)

Cardiovascular Disease

• Avoid phentermine entirely in patients with any history of cardiovascular disease, including coronary artery disease, stroke, arrhythmias, or congestive heart failure, due to lack of long-term cardiovascular outcome trial data 1
• This is critical because phentermine activates the sympathetic nervous system and can increase heart rate and blood pressure 2, 3

Uncontrolled Hypertension

• Phentermine is contraindicated in patients with uncontrolled hypertension as it may further elevate blood pressure 1
• Blood pressure must be controlled before initiating phentermine 3

Hyperthyroidism

• Untreated hyperthyroidism is an absolute contraindication due to concerns for arrhythmias and seizures 1
• Thyroid function must be assessed before starting phentermine 3

MAOI Use

• Phentermine must not be used concurrently with or within 14 days of monoamine oxidase inhibitors (MAOIs) due to risk of hypertensive crisis 1, 3, 4

Substance Abuse History

• Phentermine is contraindicated in patients with a history of drug abuse, as it is a Schedule IV controlled substance with abuse and dependence potential 1

Pregnancy and Lactation

• Phentermine is absolutely contraindicated in pregnancy 1, 3
• Women of childbearing potential require contraception counseling and potentially monthly pregnancy testing when taking phentermine 3

Additional High-Risk Situations Requiring Caution

Glaucoma

• Untreated closed-angle glaucoma is a contraindication to phentermine, particularly when combined with topiramate 2, 3

Seizure Disorders

• Exercise caution when prescribing phentermine to patients with seizure disorders, especially when combined with other medications 1

Renal Impairment

• While not an absolute contraindication, renal function should be evaluated before prescribing phentermine 3
• Tirzepatide (exenatide formulations) is contraindicated if eGFR is <30 mL/min/1.73 m², and renal function should be monitored with all GLP-1 RAs, especially in patients with nausea and possible dehydration 2

Tirzepatide-Specific Contraindications (Apply Regardless of Phentermine Use)

• Tirzepatide is contraindicated in persons with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 2
• Exercise caution in persons with a history of acute pancreatitis when using tirzepatide 2

Critical Pre-Treatment Screening Algorithm

Before prescribing this combination, you must:

1. Obtain complete cardiovascular history, including remote history of arrhythmias or structural heart disease 1
2. Measure baseline blood pressure and heart rate 3
3. Assess thyroid function to exclude hyperthyroidism 1, 3
4. Screen for glaucoma, particularly closed-angle glaucoma 3
5. Evaluate renal function (eGFR) 3
6. Assess pregnancy status in all women of reproductive potential 3
7. Screen for substance abuse history 1
8. Review all current medications for MAOI use or other sympathomimetic amines 1, 4
9. Screen for personal or family history of medullary thyroid carcinoma 2

Monitoring Requirements When Combining These Medications

• Monitor blood pressure and heart rate at every visit throughout treatment 3, 5
• Monitor for gastrointestinal side effects (nausea, vomiting, diarrhea), which are common with tirzepatide and can lead to dehydration 2
• Monitor renal function, especially if gastrointestinal side effects occur with tirzepatide 2
• Discontinue phentermine if patient has not lost at least 5% of body weight after 12 weeks on maximum dose 3

Common Pitfalls to Avoid

• Do not confuse phentermine monotherapy with the discontinued "fen-phen" combination (phentermine-fenfluramine), which was associated with valvular heart disease—these risks were attributed to fenfluramine, not phentermine 3
• Failing to obtain a complete cardiovascular history is a critical screening error 1
• Inadequate assessment of thyroid function before initiation is a critical screening error 1
• Do not prescribe phentermine to patients requiring general anesthesia without special management considerations 1