Estulic^® (Tablets) Instructions for Use

Marketing Authorization Holder

Egis Pharmaceuticals PLC (Hungary)

ATC Code

C02AC02 (Guanfacine)

Active Substance

Guanfacine (Rec.INN registered by WHO)

Dosage Form

Estulic®

Tablets 1 mg: 20 pcs.

Dosage Form, Packaging, and Composition

Tablets white or yellowish-white, round, flat, with a bevel, with a score on one side and with an engraved stylized letter “E” on the other side; odorless or almost odorless.

Excipients : lactose monohydrate, microcrystalline cellulose, povidone, stearic acid.

10 pcs. – blisters (2) – cartons.

Clinical-Pharmacological Group

Stimulator of central alpha₂-adrenergic receptors. Antihypertensive drug

Pharmacotherapeutic Group

Centrally acting antihypertensive agent

Pharmacological Action

Centrally acting antihypertensive agent. It stimulates postsynaptic α₂-adrenergic receptors of the inhibitory structures of the brainstem and reduces the flow of sympathetic impulses to the vessels and heart. The hypotensive effect is associated with a decrease in total peripheral vascular resistance, a decrease in heart rate and cardiac output. Guanfacine does not affect cardiac activity. The decrease in heart rate is compensated by an increase in stroke volume. It does not affect the mechanisms of blood pressure regulation either at rest or during physical exertion, and does not cause changes in kidney function. It reduces plasma renin activity.

It has sedative and analgesic properties. It inhibits somatovegetative manifestations of opioid and alcohol withdrawal.

Pharmacokinetics

Guanfacine is highly absorbed (80%) after oral administration, C_max is reached within 1-4 hours. Plasma protein binding is 70% (50% – with erythrocytes). C_ss in plasma is reached within 4 days after the start of treatment. Guanfacine penetrates the placental barrier and is excreted in breast milk. It is metabolized in the liver. T_1/2 – on average 17 hours (from 10 to 30 hours). 80% is excreted by the kidneys (40% – unchanged).

Indications

Arterial hypertension (as monotherapy or as part of combination therapy), including primary and renovascular.

Opioid withdrawal syndrome.

ICD codes

Dosage Regimen

Determine the dosage regimen individually for each patient.

Initiate therapy with a single daily dose of 0.5 mg to 1 mg, administered at bedtime to mitigate sedative effects.

If adequate blood pressure control is not achieved, increase the dose in increments of 0.5 mg to 1 mg at weekly intervals.

The average effective maintenance dose typically ranges from 2 mg to 3 mg per day, given as a single administration.

Do not exceed the maximum recommended daily dose without specialist consultation.

For patients with severe renal impairment, reduce the daily dose and titrate more cautiously; monitor blood pressure and renal function closely.

To discontinue therapy, gradually reduce the dose over a period of several days to prevent a potential withdrawal syndrome characterized by rebound hypertension and tachycardia.

Adhere to a consistent dosing schedule. If a dose is missed, take it as soon as remembered unless it is almost time for the next dose; in that case, continue with the regular schedule and do not double the dose.

Adverse Reactions

From the digestive system dry mouth (especially with high initial doses or with a sharp increase in dose); in some cases – loss of appetite, nausea, vomiting, stomach cramps, constipation, decreased gastric secretion.

From the CNS in some cases – drowsiness or insomnia, dizziness, headache, fainting, slowing of the speed of mental and motor reactions, weakness, depression, anxiety, tension, nervousness, psychomotor agitation, tremor of the hands and fingers, confusion.

From the cardiovascular system orthostatic hypotension, bradycardia.

From the organ of vision conjunctivitis (dryness, itching, burning in the eyes).

Other sweating, nasal congestion, decreased potency, decreased libido.

Contraindications

Recently suffered myocardial infarction, pregnancy, lactation, old age, hypersensitivity to guanfacine.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and during lactation (breastfeeding).

Use in Hepatic Impairment

Use with caution and under constant medical supervision in patients with chronic hepatic insufficiency.

Geriatric Use

Contraindicated in old age.

Special Precautions

Use with caution and under constant medical supervision in patients with AV block of II and III degree, history of depression, chronic hepatic insufficiency, severe cerebral atherosclerosis, coronary insufficiency, obliterating arterial diseases, sinus bradycardia.

After sudden discontinuation of therapy (after 2-7 days), withdrawal syndrome may develop (signs and symptoms of sympathetic hyperreactivity).

During treatment, blood pressure should be constantly monitored at certain intervals. During treatment, the concentrations of catecholamines and vanillylmandelic acid in the urine may be decreased, but may increase upon sudden withdrawal of guanfacine. The plasma growth hormone content may temporarily increase due to stimulation of its secretion, but with prolonged use of guanfacine, the growth hormone concentration normalizes.

During the use of guanfacine, control of body weight and diet (especially the consumption of table salt) may be required. Alcohol consumption should be avoided.

Influence on the ability to drive vehicles and mechanisms

Guanfacine may cause a decrease in the speed of the patient’s psychomotor reactions. In this regard, it is not recommended to drive vehicles and work with potentially dangerous equipment for some time at the initial stage of treatment or in case of dose increase (this period depends on the individual patient’s response to treatment).

Drug Interactions

With simultaneous use with α₂-adrenergic receptor antagonists (phentolamine, yohimbine), a decrease in the antihypertensive effect of guanfacine is possible.

With simultaneous use with beta-blockers, an excessive decrease in heart rate is possible.

With simultaneous use with diuretics, beta-blockers, peripheral vasodilators, an increase in the antihypertensive effect is possible.

With simultaneous use with neuroleptics, an increase in the sedative effect is possible.

With simultaneous use with sympathomimetics, a decrease in the antihypertensive effect of guanfacine is possible.

With simultaneous use with amitriptyline, imipramine, a case of a decrease in the antihypertensive effect of guanfacine has been described.

The hypotensive effect is reduced by NSAIDs (as a result of suppression of prostaglandin synthesis in the kidneys and retention of sodium ions and fluid in the body), estrogens (due to fluid retention in the body).

Storage Conditions

Store at 15°C (59°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.