Guanfacine

Mechanism :

Inhibition of cAMP production by stimulation of the postsynaptic adrenergic alpha2A receptors. Also works by closing HCN channels, thus improving the effectiveness of pyramidal neurons’ signalling in the prefrontal cortex which enhances attention and working memory. It is a selective alpha2-adrenergic receptor agonist which leads to reduce sympathetic outflow and gradual decrease in vasomotor tone and heart rate. Its longtearm intake reduces heartrates without affecting cardiac output. It reduces left ventricular hypertrophy.

Indication :

• Hypertension
• Tourette Syndrome
• Attention Deficit Hyperactivity Disorder (ADHD)

Contraindications :

• Hypersensitivity

• Abrupt withdrawal/discontinuation to be avoided: abrupt discontinuation or dose reduction can result in rebound hypertension, hypertensive encephalopathy, confusion, nervousness, irritability, headache, agitation, tremor, somnolence, vomiting (common in pediatric patients), visual disturbances, seizures and anxiety. Blood pressure and pulse should be monitored while tapering the dose. Daily dose should be tapered in decrements of less than 1mg every 3 to 7 days

• Due to differences in the bioavailability of the immediate and extended release formulations, they are not interchangeable. Titrate the immediate release formulation with the extended release formulation in accordance with the recommended schedule

• Caution with cardiovascular disease, coronary artery disease, recent myocardial infarction, cerebrovascular disease

• Caution while using immediate release: elderly patients

• Caution while using extended release: heart conduction disturbances, hypotension, orthostatic hypotension, bradycardia, heart block, dehydration, syncope

• There is no identifiable drug related major birth defects risk, adverse fetal or maternal outcomes, or miscarriage as per the available data

• While there is no data available on whether guanfacine is present in breastmilk, its effects on breastfeeding infant, or its effects on the production of milk, guanfacine is present in rat’s milk and thus its presence in human milk is a possibility. Monitoring of a breastfeeding infant exposed to the it for symptoms like lethargy, poor feeding, sedation (symptoms of reduced blood pressure/heart rate) becomes necessary

Dosing :

Adverse Effect :

• Common IR: dry mouth, pain in the abdomen, constipation, fatigue, headache, dizziness, sleepiness

• Common ER: sleepiness, headache, dizziness, fatigue, pain in the abdomen, reduced appetite

• Uncommon IR: decreased BP, decreased HR, palpitations, asthenia, lethargy, dizziness, weakness, insomnia, irritability, confusion, depression, hypokinesia, alopecia, dermatitis, increased sweating, pruritis, cramps in the legs, impotence, difficulty swallowing, indigestion, nausea, reduced appetite, difficulty breathing

• Uncommon ER: decreased BP, decreased HR, insomnia, lethargy, irritability, postural dizziness, nightmares, enuresis, anxiety, increased weight, nausea, loose stools, constipation, xerostomia, rash

• Undefined frequency IR: pain in the joints, muscle pain, rash, exfoliation, orthostatic hypotension

• Undefined frequency ER: AV block, chest pain, increased BP, increased urinary frequency, asthenia, convulsions, hypersensitivity, increase alanine aminotransferase, pallor

Interaction :

• Strong/moderate CYPA3A4 inhibitors: increase guanfacine concentration in the plasma significantly. If starting therapy while already taking a CYP3A4 inhibitor or adding a CYP3A4 inhibitor, reduce the dose to half the recommended level. CYP3A4 inhibitor is stopped while continuing therapy, dose should be increased to recommended level

• Strong/moderate CYP3A4 inducers: decrease guanfacine concentration in the plasma significantly. If starting therapy with ER formulation while already taking a CYP3A4 inducer or adding a CYP3A4 inducer, increase the dose over 1-2 weeks to up to double the recommended level. CYP3A4 inducer is stopped while continuing therapy, dose should be decreased over 1-2 weeks to recommended level. More frequent dosing of IR formulation is necessitated if co-administered with a CYP3A4 inducer

Hepatic Dose :

Not defined for pediatric population. However, caution should be exercised in case of hepatic impairment