VIIBRYD
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VIIBRYD (VIIBRYD).
Vilazodone is a selective serotonin reuptake inhibitor (SSRI) and a partial agonist at serotonin 5-HT1A receptors. It increases serotonin levels in the synaptic cleft by inhibiting its reuptake, and the 5-HT1A partial agonism may enhance serotonergic transmission and reduce side effects like sexual dysfunction.
| Metabolism | Primarily metabolized via CYP3A4 and to a lesser extent via CYP2C19 and other enzymes. |
| Excretion | Approximately 95% of the dose is excreted in feces (as unchanged drug and metabolites) and <1% in urine as unchanged drug. Renal elimination accounts for <3% of the dose as the active metabolite. |
| Half-life | Terminal elimination half-life of vilazodone is approximately 25 hours (range 22-30 hours). Steady state is achieved within 3-4 days. The half-life supports once-daily dosing. |
| Protein binding | Approximately 96-99% bound to serum albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 293 L (≈ 4.2 L/kg for a 70 kg individual), indicating extensive extravascular distribution. |
| Bioavailability | Absolute bioavailability of oral vilazodone is approximately 72% (range 60-80%) when taken with food. Food enhances absorption (Cmax increased by up to 147%, AUC by 64%) compared to fasting conditions. |
| Onset of Action | Oral: Clinical improvement (antidepressant effect) may be observed as early as 1-2 weeks, but full therapeutic benefit typically requires 4-8 weeks. No parenteral route is available. |
| Duration of Action | Duration of action for a single oral dose is approximately 24 hours, consistent with once-daily dosing. Steady-state concentrations are maintained with daily administration. |
| Molecular Weight | 441.5 |
10 mg orally once daily for 7 days, then 20 mg once daily for 7 days, then 40 mg once daily; target dose 40 mg once daily. Maximum dose 40 mg once daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl 30-89 mL/min). For severe renal impairment (CrCl 15-29 mL/min): maximum dose 20 mg once daily. Not recommended for end-stage renal disease (CrCl <15 mL/min). |
| Liver impairment | Mild to moderate hepatic impairment (Child-Pugh A or B): maximum dose 20 mg once daily. Severe hepatic impairment (Child-Pugh C): not recommended. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment recommended; clinical studies included patients aged >65 years. Use with caution due to potential increased sensitivity; maximum dose 40 mg once daily. |
| 1st trimester | Insufficient human data; animal studies show no teratogenicity but risk cannot be excluded. |
| 2nd trimester | Limited data; consider risk of serotonin syndrome and neonatal adaptation syndrome. |
| 3rd trimester | Risk of persistent pulmonary hypertension and neonatal withdrawal syndrome; avoid unless benefit clearly outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for VIIBRYD (VIIBRYD).
| Placental transfer | Vilazodone crosses the placenta in animal studies; human data limited but expected based on molecular weight and lipophilicity. |
| Breastfeeding | VIIBRYD (vilazodone) is excreted into breast milk in low amounts. Limited data show no adverse effects in breastfed infants. Caution is advised, especially in preterm or compromised infants. |
■ FDA Black Box Warning
Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies. Monitor for worsening and emergence of suicidal thoughts and behaviors.
| Serious Effects |
Hypersensitivity to vilazodone or any excipientsConcomitant use with MAOIs or within 14 days of MAOI discontinuation
| Precautions | Suicidal thoughts and behaviors in pediatric and young adult patients, Serotonin syndrome or neuroleptic malignant syndrome-like reactions, Activation of mania/hypomania in bipolar disorder patients, Seizures (discontinue if seizures occur), Abnormal bleeding (especially with NSAIDs, aspirin, or anticoagulants), Angle-closure glaucoma (myadriasis risk), SIADH and hyponatremia in elderly or volume-depleted, Sexual dysfunction, Discontinuation syndrome upon abrupt withdrawal |
| Food/Dietary | Administer with food to enhance bioavailability (by ~60%). Avoid grapefruit juice as it inhibits CYP3A4 and may increase vilazodone levels. No specific restrictions with other foods. |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy Category C. No adequate studies in pregnant women. In animal studies, vilazodone caused decreased fetal body weight and delayed ossification at doses ≥2 times the MRHD. First trimester: insufficient data to assess risk of major malformations. Second and third trimesters: neonatal adaptation syndrome including respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying may occur following late third trimester exposure due to serotonergic effects. |
| Fetal Monitoring | Monitor for neonatal adaptation syndrome in infants exposed during third trimester; assess for signs of respiratory distress, feeding difficulties, and autonomic instability. In mother, monitor for signs of serotonin syndrome, especially if co-administered with other serotonergic drugs. Assess for mood changes and suicidality during pregnancy and postpartum. |
| Fertility Effects | Animal studies: at doses up to 2 times MRHD, no impairment of male or female fertility observed. Human data: insufficient. Theoretical risk of hyperprolactinemia and sexual dysfunction with SSRIs may affect fertility. |
| Clinical Pearls | Initiate at 10 mg once daily for 7 days, then increase to 20 mg once daily; therapeutic dose range 20-40 mg once daily. Requires dose titration. Metabolized primarily via CYP3A4; avoid strong CYP3A4 inhibitors (e.g., ketoconazole) and inducers (e.g., carbamazepine). Max dose 40 mg/day due to QT prolongation risk. No significant effect on weight or sexual function compared to SSRIs. Avoid abrupt discontinuation; taper dose. Contraindicated with MAOIs or linezolid. |
| Patient Advice | Take once daily at the same time each day. Swallow tablet whole; do not crush or chew. · Benefit may take 4-6 weeks. Continue even if feeling no improvement initially. · Do not stop suddenly; withdrawal symptoms may occur. Consult provider for dose tapering. · May cause dizziness, dry mouth, diarrhea, or insomnia; report severe or persistent symptoms. · Avoid grapefruit juice as it increases vilazodone levels. · Inform all healthcare providers you are taking this medication. · If pregnant, planning to become pregnant, or breastfeeding, discuss risks with provider. |