INTUNIV
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INTUNIV (INTUNIV).
Selective alpha-2A adrenergic receptor agonist, reducing sympathetic outflow from the central nervous system, leading to decreased peripheral vasomotor tone and improved attention and impulse control.
| Metabolism | Primarily metabolized by CYP3A4 to active metabolite; also minor pathways via CYP2D6. |
| Excretion | Renal (primarily as metabolites, <1% unchanged) and fecal (biliary); approximately 70% renal, 20% fecal. |
| Half-life | Terminal half-life approximately 18 hours; supports once-daily dosing. Steady-state reached in 4 days. |
| Protein binding | 70% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 2.3 L/kg; indicates extensive extravascular distribution. |
| Bioavailability | Oral: approximately 40% (range 20-60%); high-fat meal increases Cmax and AUC (up to 60%). |
| Onset of Action | Oral: 2-4 hours for initial effect; maximal effect by 4-8 weeks. |
| Duration of Action | 24 hours; sustained blood pressure reduction and symptom control with once-daily dosing. |
Initial: 1 mg orally once daily; may increase by 1 mg/week as needed; maximum 4 mg/day.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | GFR 30-89 mL/min: no adjustment; GFR <30 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: not recommended. |
| Pediatric use | Children 6-17 years: initial 1 mg orally once daily; adjust in 1 mg increments weekly; max 4 mg/day. |
| Geriatric use | No specific dose adjustment based on age; titrate cautiously due to potential orthostatic hypotension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for INTUNIV (INTUNIV).
| Breastfeeding | Present in human milk at low levels (relative infant dose approximately 1-2% of maternal weight-adjusted dose). M/P ratio not reported. Limited data suggest no adverse effects in breastfed infants. Caution in preterm infants or those with renal impairment. Use only if clearly needed. |
| Teratogenic Risk | Pregnancy Category C. Animal studies demonstrated reduced fetal weight and increased skeletal ossification delays at doses 5 times the maximum recommended human dose (MRHD). No adequate human studies. Risk cannot be ruled out. Use only if benefit outweighs risk. First trimester: avoid. Second/third trimester: caution; associated with increased risk of preeclampsia and preterm birth possibly due to alpha-2 agonist effects. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to guanfacine or any component of formulation","Concurrent use with strong CYP3A4 inhibitors (e.g., ketoconazole) or strong CYP3A4 inducers (e.g., rifampin) due to significant drug interactions"]
| Precautions | ["Hypotension, bradycardia, and syncope: monitor heart rate and blood pressure","Sedation and somnolence: caution with driving or hazardous activities","QT interval prolongation in overdose or with hepatic impairment","Rebound hypertension if abruptly discontinued","Not recommended in severe hepatic impairment"] |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate throughout pregnancy, especially during initiation or dose changes. Fetal monitoring: assess fetal growth via ultrasound if prolonged use; monitor for signs of preterm labor or preeclampsia. Neonatal: observe for hypotension, bradycardia, and sedation after delivery. |
| Fertility Effects | In animal studies, no adverse effects on fertility at doses up to 2 times MRHD. Human data insufficient. Possible hormonal alterations due to alpha-2 agonism may theoretically affect reproductive function, but clinical significance unknown. |