Side Effects
Very Common (greater than 10%):
- Nausea (40% of patients in clinical trials vs 1% placebo), typically occurring within 30 minutes of injection and lasting approximately 2 hours; most pronounced with the first dose and diminishing with subsequent use
- Flushing (20%)
- Injection site reactions (13%)
- Headache (11%)
Common (1 to 10%):
- Vomiting (4.8%)
- Cough (3.3%)
- Fatigue (3.2%)
- Hot flashes (2.7%)
- Paresthesia (2.6%)
- Dizziness (2.2%)
- Nasal congestion (2.1%)
- Upper respiratory tract infection
- Transient skin hyperpigmentation at injection site
Cardiovascular Effects:
PT-141 causes transient increases in blood pressure, with peak elevations of approximately 6 mmHg systolic and 3 mmHg diastolic occurring 2 to 4 hours post-dose, accompanied by a reduction in heart rate of up to 5 beats per minute. Blood pressure and heart rate return to baseline within 12 hours. To minimize cardiovascular risk, patients should not exceed one dose per 24-hour period. This blood pressure elevation was the basis for the FDA's 2007 clinical hold on the intranasal formulation, and the cardiovascular warning remains on the approved Vyleesi label.
Contraindications:
- Uncontrolled hypertension or known cardiovascular disease
- Patients at high risk for cardiovascular events
Special Precautions:
The FDA prescribing information does not carry a boxed warning, but includes warnings and precautions regarding cardiovascular effects. Blood pressure should be well-controlled before initiating therapy, and periodic monitoring during treatment is recommended. PT-141 may reduce the rate and extent of absorption of concomitantly administered oral medications by slowing gastric motility, though clinical studies found this effect was not clinically relevant except for naltrexone, with which co-use should be avoided.
Anti-nausea medication such as ondansetron taken 30 minutes before PT-141 administration can significantly reduce the incidence and severity of nausea. Administering after a light meal may also help, though this has not been formally studied.