ADDYI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ADDYI (ADDYI).
Selective agonist of melanocortin 4 receptor (MC4R), activating central pathways to regulate appetite and energy expenditure.
| Metabolism | Primarily metabolized by CYP3A4 to an active metabolite (M1) and other minor metabolites; also metabolized by CYP2C19 and CYP2C9 to a lesser extent. |
| Excretion | Renal: 88% (44% unchanged, 44% as metabolites); Fecal: 9%; Biliary: minimal |
| Half-life | Terminal half-life: 11 hours (range 9-13 h) in premenopausal women; 50% longer in hepatic impairment |
| Protein binding | 99% bound to serum albumin and α1-acid glycoprotein |
| Volume of Distribution | Vd: 7.5 L/kg (300-500 L total), indicating extensive tissue distribution |
| Bioavailability | Oral: Not reported (undetermined due to lack of IV formulation; estimated ~30-50% based on metabolism and first-pass effect) |
| Onset of Action | Oral: 30-60 minutes to subjective improvement in hypoactive sexual desire disorder (HSDD); peak effect ~2-4 hours |
| Duration of Action | Effects persist for 12-24 hours; dosing is daily in the morning; tolerance may develop with chronic use |
100 mg orally once daily, as needed, approximately 1 hour prior to sexual activity. Maximum dosing frequency: once daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl >30 mL/min). Not recommended for use in patients with severe renal impairment (CrCl ≤30 mL/min) due to lack of data. |
| Liver impairment | Contraindicated in patients with hepatic impairment (Child-Pugh class A, B, or C) due to increased risk of hypotension and syncope. Use is not recommended. |
| Pediatric use | Safety and efficacy in pediatric patients (<18 years) have not been established. Not indicated for use. |
| Geriatric use | Not indicated for use in females >65 years of age due to lack of safety and efficacy data. Limited clinical experience in elderly patients. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ADDYI (ADDYI).
| Breastfeeding | Unknown if excreted in human breast milk. M/P ratio not determined. Caution advised: avoid breastfeeding during therapy due to potential adverse effects in nursing infants. |
| Teratogenic Risk | Pregnancy category X. Addyi is contraindicated during all trimesters due to known teratogenic effects in animal studies showing fetal resorption, reduced fetal weight, and skeletal anomalies. No adequate human studies exist; risk of fetal harm outweighs any potential benefit. |
| Fetal Monitoring |
■ FDA Black Box Warning
WARNING: RISK OF SERIOUS HYPOTENSION AND SYNCOPE. Can cause severe hypotension and syncope, especially within the first 2 hours of dosing. Avoid use in patients at risk for hypotension or syncope. Not indicated in postmenopausal women or men.
| Serious Effects |
Uncontrolled hypertension; known cardiovascular disease (e.g., stroke, myocardial infarction, unstable angina); heart failure; hypotension risk; concurrent use of CYP3A4 inhibitors; end-stage renal disease; pregnancy; men; postmenopausal women; history of syncope.
| Precautions | Hypotension and syncope; increased risk with alcohol use, CYP3A4 inhibitors, or compromised blood pressure regulation. Not recommended in patients with uncontrolled hypertension, cardiovascular disease, or diabetes. Discontinue if hypotension occurs. Use lowest effective dose. |
| Food/Dietary | Avoid high-fat meals as they may delay absorption and onset of action. Grapefruit juice may increase drug levels; avoid concurrent consumption. |
Loading safety data…
| Pregnancy testing is recommended prior to initiation and monthly during therapy. Monitor for signs of hypotension or syncope during co-administration with moderate CYP3A4 inhibitors. Evaluate hepatic function if hepatic adverse events suspected. |
| Fertility Effects | No specific human fertility data. In animal studies, high doses caused irregular estrous cycles and reduced fertility in female rats. Relevance to humans is unknown but potential for reversible impairment exists. |
| Clinical Pearls | Onset of effect requires several weeks; monitor for hypotension, syncope, and CNS depression. Avoid concurrent use with alcohol or other CNS depressants. Contraindicated in patients with uncontrolled hypertension or cardiovascular disease. Discontinue if no improvement after 8 weeks. |
| Patient Advice | Do not drink alcohol while taking this medication. · May cause drowsiness or dizziness; avoid driving until you know how the drug affects you. · Take at least 30 minutes before anticipated sexual activity, but no more than once daily. · Inform your doctor if you have a history of low blood pressure, fainting, or heart problems. · Report any episodes of fainting or severe dizziness to your healthcare provider. |