Estulic
Estulic Uses, Dosage, Side Effects, Food Interaction and all others data.
Estulic, or BS 100-141, is a selective alpha-A2 adrenergic receptor agonist initially indicated for the treatment of hypertension but is now indicated as an extended release tablet for the treatment of ADHD. Estulic was first described in the literature in 1974.
Estulic was granted FDA approval on 27 October 1986.
Estulic is a selective alpha-2A adrenergic receptor agonist but it is unclear how this translates to the treatment of ADHD. It has a long duration of action as it is given once daily and a wide therapeutic window as fatal overdoses have not been described in literature. Patients should be counselled regarding the risk of hypotension, bradycardia, and syncope.
| Trade Name | Estulic |
| Availability | Prescription only |
| Generic | Guanfacine |
| Guanfacine Other Names | Guanfacina, Guanfacine, Guanfacinum |
| Related Drugs | amlodipine, lisinopril, metoprolol, losartan, furosemide, hydrochlorothiazide, Adderall, Vyvanse, methylphenidate, Concerta |
| Type | |
| Formula | C9H9Cl2N3O |
| Weight | Average: 246.093 Monoisotopic: 245.012267339 |
| Protein binding | Guanfacine is approximately 70% protein bound in serum. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Estulic is an alpha-2A adrenergic receptor agonist used to treat ADHD.
Estulic is indicated alone or as an adjunct with stimulants to treat ADHD.
Estulic is also used to associated treatment for these conditions: Attention Deficit Hyperactivity Disorder (ADHD), Gilles de la Tourette's Syndrome, High Blood Pressure (Hypertension), Migraine
How Estulic works
Estulic is a selective alpha-2A adrenergic receptor agonist, which reduces the effects of the sympathetic nervous system on the heart and circulatory system. The link between guanfacine’s molecular mechanism and it’s effect on the treatment of ADHD has not been determined.
Toxicity
The oral LD50 in rats is 142mg/kg and 15.3mg/kg in mice. The subcutaneous LD50 in rats is 114mg/kg and 46mg/kg in mice.
Patients experiencing and overdose may present with hypotension, drowsiness, lethargy, and bradycardia. Overdose should be managed by first calling local poison control. Patients may require intravenous saline to maintain blood pressure.
Food Interaction
- Avoid alcohol.
- Do not take with or immediately after a high-fat meal. High fat meals increase drug exposure.
[Major] GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of guanfacine.
The risk of adverse reactions such as hypotension, bradycardia, and sedation may increase.
The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.
Ketoconazole, a potent CYP450 3A4 inhibitor, has been reported to increase guanfacine peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 2- and 3-fold, respectively.
A computer simulation suggests that fluconazole, a moderate CYP450 3A4 inhibitor, would increase guanfacine Cmax and AUC by about 1.5- and 2-fold, respectively.
In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands.
Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.
GENERALLY AVOID: Alcohol may enhance the sedative and hypotensive effects of guanfacine.
GENERALLY AVOID: Administration of extended-release guanfacine with a high-fat meal may increase the bioavailability of guanfacine.
When a single 4 mg dose of extended-release guanfacine was administered to adult volunteers with a high-fat breakfast, mean guanfacine peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 75% and 40%, respectively, compared to dosing in a fasted state.
MANAGEMENT: Patients treated with guanfacine should avoid consumption of grapefruit and grapefruit juice.
In addition, it is preferable to avoid or limit the use of alcohol during treatment.
Patients should be advised against driving or operating hazardous machinery until they know how the medication affects them.
The extended-release formulation of guanfacine should not be taken together with a high-fat meal.
Estulic Drug Interaction
Moderate: aripiprazole, aripiprazole, methylphenidate, methylphenidate, quetiapine, quetiapineMinor: lisdexamfetamine, lisdexamfetamineUnknown: amphetamine / dextroamphetamine, amphetamine / dextroamphetamine, amphetamine / dextroamphetamine, amphetamine / dextroamphetamine, escitalopram, escitalopram, fluoxetine, fluoxetine, cholecalciferol, cholecalciferol, cetirizine, cetirizine
Estulic Disease Interaction
Moderate: bradyarrhythmia, depression, hypotension, ADHD, renal/liver disease
Volume of Distribution
Estulic has a volume of distribution of 6.3L/kg.
Elimination Route
Estulic is 80% orally bioavailable.
1mg immediate release oral guanfacine reaches a Cmax of 2.5±0.6ng/mL with a Tmax of 3.0h and an AUC of 56±15ng*h/mL. 1mg extended release oral guanfacine reaches a Cmax of 1.0±0.3ng/mL with a Tmax of 6.0h and an AUC of 32±9ng*h/mL.
In adults, a 4mg oral extended release dose reaches a Cmax of 3.58±1.39ng/mL with a Tmax of 5.5h; in children, a 2mg oral extended relsease dose reaches a Cmax of 2.6±1.03ng/mL with a Tmax of 4.98h; in adolescents, a 2mg oral extended release dose reaches a Cmax of 1.7±0.43ng/mL with a Tmax of 4.96h.
Half Life
Estulic has a half life of 17 hours, but this may range from 10-30 hours. The half life is largely independant of renal function.
Clearance
Estulic has a total body cleraance of 360±262mL/min and a renal clearance of 233±245mL/min in patients with normal renal function. Patients with a glomerular filtration rate (GFR) of 10-30mL/min had a total body clearance of 308±274mL/min and a renal clearance of 34±22mL/min. Patients with a GFR of 2
Elimination Route
Estulic is 57.0±32.0% eliminated in the urine in patients with normal renal function. Patients with a glomerular filtration rate (GFR) of 10-30mL/min eliminate 14.0±9.0% of a dose in the urine, while patients with a GFR of 2
Innovators Monograph
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