12 avril 2014

À propos de l'Intuniv (guanfacine) pour le TDAH

Information tiré de 
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935643/

Pharmacy and Therapeutics, august 2010. vol. 35 no. 8

Used in children and adolescents 6 to 17 years of age, but it is not approved for adults with ADHD. Combination therapy comprising both atomoxetine and guanfacine, along with behavioral and psychological interventions, is often beneficial in ADHD.

This selective alpha2A-adrenergic receptor agonist is not a central nervous system (CNS) stimulant. The mechanism of action in ADHD is not known, but the drug appears to work on certain receptors in the prefrontal cortex, a part of the brain where behaviors related to ADHD, such as inattention and impulsiveness, are thought to be controlled.

 It should NOT be taken with high-fat meals.

This product has an affinity that is 15 to 20 times higher for the alpha2A receptor subtype than for the alpha2B or alpha2C subtypes. As an antihypertensive agent, guanfacine stimulates alpha2A-adrenergic receptors, thereby reducing sympathetic nerve impulses from the vasomotor center to the heart and blood vessels. The result is a decrease in peripheral vascular resistance and a reduced heart rate.

During the clinical trials, the highest mean systolic and diastolic blood pressure (BP) changes from baseline, respectively, were as follows:
  • guanfacine 2 mg/day: −7 and −3.8 mm Hg
  • guanfacine 3 mg/day: −7 and −4.7 mm Hg
  • guanfacine 4 mg/day: −10.1 and −7.1 mm Hg
The highest mean pulse rate changes from baseline were −5.7, −8.1, and −8 beats/minute with guanfacine 2 mg/day, 3 mg/day, and 4 mg/day, respectively. Common adverse effects reported in the study were somnolence, fatigue, upper abdominal pain, and sedation. There were no significant changes in mean height or weight in patients receiving guanfacine ER.

Interactions:
There was a three-fold increase in the area-under-the-curve (AUC) concentration of guanfacine when it was given with ketoconazole (Nizoral, Janssen). Caution should be used when guanfacine ER is given with other CYP 3A4 and 3A5 inhibitors such as ketoconazole. Patients should be monitored for hypotension, bradycardia, and sedation. Dose adjustments may be needed if guanfacine ER is taken with a CYP 3A4 inducer because the AUC concentration of guanfacine ER is decreased by 70%.
Patients should be monitored for potential CNS side effects when guanfacine ER is given with valproic acid because of increased concentrations of valproic acid with coadministration. Potential additive pharmacodynamic effects (e.g., hypotension and syncope) must be monitored when guanfacine ER is taken with other antihypertensive agents. Sedation and somnolence may be experienced if guanfacine ER is taken with alcohol, sedatives, hypnotics, benzodiazepines, barbiturates, or antipsychotic agents.

Monitoring:
In most cases, the American Academy of Pediatrics (AAP) does not recommend the routine use of electrocardiograms or routine subspecialty cardiology evaluations before initiating stimulant therapy to treat ADHD, even though the American Heart Association (AHA) had previously recommended this step to detect cardiac conditions that might put children at risk for sudden cardiac death. The following cardiac monitoring recommendations:
  1. A thorough examination should be conducted before patients begin taking guanfacine for ADHD. Special attention should be given to symptoms that suggest a cardiac condition (e.g., palpitations, near syncope, or syncope).
  2. A complete family and patient history should be obtained to check for conditions associated with sudden cardiac death.
  3. Clinicians should determine whether patients are currently using other prescribed or over-the-counter agents.
  4. Patients should be evaluated for cardiac murmurs, hypertension, physical findings associated with Marfan syndrome, and signs of arrhythmias.
  5. Further evaluation is indicated if the family history, patient history or physical findings suggest cardiac disease during the initial visit or at follow-up visits. If indicated, a pediatric cardiologist should be consulted.
  6. Patients should continue to be assessed for cardiac symptoms and any changes in family history at follow-up visits.
  7. BP and heart rate should be evaluated at the baseline assessment, during routine follow-up visits within one to three months, and at follow-up appointments every six to 12 months.

Dosage:

For children 6 to 17 years of age with ADHD, the starting dose of guanfacine ER is 1 mg once daily; this amount may be increased in increments of 1 mg/week, up to 4 mg, the recommended maximum daily dose. A maintenance dose of 0.05 to 0.08 mg/kg once daily, up to 0.12 mg/kg, may be considered. For patients discontinuing guanfacine ER, the dose should be tapered in decrements of no more than 1 mg every three to seven days. 

Precautions:

Precautions are advised for those with a history of bradycardia, cardiovascular disease, heart block, hypotension, and syncope.
To avoid the risk of rebound hypertension, patients should not stop therapy abruptly. The concomitant use of alcohol and other known depressants, as well as other guanfacine-containing drugs (e.g., Tenex) should be avoided.
Patients should not drive or operate heavy equipment until they know how they respond to guanfacine ER. The safety and efficacy of the drug have not been established in children younger than six years of age. It is unknown whether the drug is effective if used for longer than nine weeks.

Adverse Reactions:

Most common and dose-related adverse reactions include somnolence, sedation, abdominal pain, dizziness, hypotension or decreased BP, dry mouth, irritability, nausea, decreased appetite, and constipation.

The drug may be considered a possible alternative for treating ADHD, but it is not expected to replace any agents currently indicated for this condition.

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