Agorest25 mg

Agorest is indicated for the following condition:

Established/Approved Use

• Major Depressive Disorder (MDD) in adults - Agorest is approved (in regulatory jurisdictions where it is marketed, e.g. the European Union) for the treatment of major depressive episodes in adults, based on placebo-controlled trials demonstrating antidepressant efficacy along with a favorable profile regarding sexual dysfunction and weight gain compared with many other antidepressants.

Uses With Limited/Emerging Evidence (Not a Primary Approved Indication)

• Generalized anxiety disorder and sleep-disturbance symptoms associated with depression - some clinical trial data exists, but this is not a formally approved indication in most markets; use for this purpose should only be under a physician's direction.

Agorest is not approved or recommended for use in children or adolescents, and it is not a first-line treatment for bipolar depression or psychotic depression.

Each film-coated tablet contains 25 mg of Agomelatine as the active pharmaceutical ingredient, along with pharmaceutical excipients (including diluents, binders, and coating agents) that ensure tablet stability and appropriate release of the drug.

Agorest is an oral antidepressant with a mechanism of action that is distinct from the more commonly used selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs). It is a melatonergic agent, chemically classified as a naphthalene derivative, that acts as an agonist at melatonin MT1 and MT2 receptors and as an antagonist at serotonin 5-HT2C receptors.

Agorest is used primarily for major depressive disorder in adults and is notable for helping to resynchronize disrupted circadian (sleep-wake) rhythms that are commonly associated with depression, while carrying a distinctive risk of liver toxicity that requires monitoring during treatment.

Agorest belongs to the therapeutic class of melatonergic antidepressants, a distinct category separate from SSRIs, SNRIs, tricyclic antidepressants, and MAOIs.

Mechanism of Action

Agomelatine acts as an agonist at melatonin MT1 and MT2 receptors, which helps resynchronize disturbed circadian rhythms (sleep-wake cycles) frequently disrupted in major depressive disorder. It simultaneously acts as an antagonist at serotonin 5-HT2C receptors, which increases the release of noradrenaline and dopamine specifically in the frontal cortex without affecting extracellular serotonin levels. Agomelatine has no significant affinity for monoamine receptors (including serotonin, noradrenaline, or dopamine receptors), no effect on monoamine reuptake, and does not act as a monoamine oxidase inhibitor.

Pharmacokinetics

• Absorption: Rapidly and almost completely absorbed after oral administration, but undergoes extensive first-pass hepatic metabolism, resulting in low and highly variable absolute bioavailability (under 5% in men, somewhat higher in women).
• Metabolism: Extensively metabolized in the liver, mainly by the CYP1A2 enzyme (~90%) and to a lesser extent CYP2C9/19, into inactive metabolites.
• Half-life: Short elimination half-life of approximately 1-2 hours.
• Excretion: Metabolites are eliminated predominantly via urine.

Agorest tablets should be taken orally, swallowed whole with water, once daily at bedtime, with or without food. Do not crush or chew the tablet unless otherwise advised by a physician.

Contraindicated Combinations

• Potent CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin) - markedly increase Agorest exposure (fluvoxamine has been shown to increase exposure by as much as 60-fold), substantially raising the risk of hepatotoxicity. Concomitant use is contraindicated (see Contraindications).

Clinically Significant Interactions Requiring Caution

• Moderate CYP1A2 inhibitors (e.g., propranolol, enoxacin) - may increase Agorest plasma levels; use with caution and physician monitoring.
• Heavy smoking (more than 15 cigarettes/day) - induces CYP1A2 and can substantially reduce Agorest exposure, potentially reducing efficacy.
• Alcohol - concomitant heavy alcohol use should be avoided due to additive risk to the liver.
• Other antidepressants/CNS-active drugs - combination with other antidepressants (including MAOIs) should only be done under close physician supervision due to limited safety data.

Common Side Effects

• Headache
• Dizziness
• Somnolence or, alternatively, insomnia
• Nausea, diarrhea, constipation, or abdominal pain
• Back pain
• Fatigue
• Anxiety

Less Common but Serious Side Effects

• Elevated liver enzymes and, rarely, serious liver injury (see Precautions and Warnings for required monitoring).
• Worsening depression or emergence of suicidal thoughts/behavior, particularly in young adults (an antidepressant class warning).
• Skin reactions, including rash.

Pregnancy: Data on the use of Agorest in pregnant women are limited. Agorest should be used during pregnancy only if clearly needed and if the potential benefit to the mother justifies the potential risk to the fetus; a physician should always be consulted before use during pregnancy.

Lactation: It is not known whether Agorest is excreted in human breast milk. Because the risk to a nursing infant cannot be excluded, breastfeeding is generally not recommended during treatment; a physician should be consulted to weigh the benefits of treatment against the benefits of breastfeeding.

Hepatotoxicity (Important Warning)

Agorest has been associated with cases of liver injury, including rare cases of severe hepatotoxicity. Liver function tests should be performed in all patients before starting treatment, and periodically during treatment (typically at approximately 3, 6, 12, and 24 weeks, and thereafter as clinically indicated, particularly if the dose is increased). Agorest should be discontinued immediately if serum transaminases rise significantly above normal (generally more than 3 times the upper limit of normal) or if signs or symptoms of liver injury develop, such as dark urine, yellowing of the skin or eyes, right upper abdominal pain, or unexplained fatigue. Agorest should be used with added caution in patients with risk factors for liver disease, such as obesity/fatty liver disease or significant alcohol use.

Suicidality

As with other antidepressants, Agorest carries a class warning regarding the possible emergence or worsening of suicidal thoughts and behavior, particularly in children, adolescents, and young adults, especially during the early weeks of treatment or after dose changes. Patients and caregivers should be advised to monitor for worsening mood or unusual behavior changes and to seek medical advice promptly if these occur.

Elderly Patients

Use in patients with dementia is not recommended due to limited safety and efficacy data. Use in patients above 75 years of age is generally not recommended.

Other Precautions

Use with caution in patients with severe renal impairment (limited data available). Avoid combination with potent or moderate CYP1A2 inhibitors as described under Interactions.

Reported symptoms of Agorest overdose include epigastric pain, somnolence, fatigue, agitation, anxiety, tension, dizziness, and general malaise. There is no specific antidote for Agorest overdose.

In case of suspected overdose, seek immediate medical attention or contact emergency services/a poison control center right away. Management is supportive, including monitoring of vital signs and liver function; gastric decontamination may be considered by medical personnel if presentation is early, in line with standard overdose management protocols.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Elderly

Use of Agorest in patients over 75 years of age is generally not recommended due to limited data. Use in elderly patients with dementia is not recommended.

Hepatic Impairment

Agorest is contraindicated in patients with hepatic impairment (see Contraindications).

Renal Impairment

Data are limited; use with caution and close medical supervision in patients with severe renal impairment.

Pediatric Patients

Agorest is not recommended for use in children or adolescents under 18 years of age; safety and efficacy have not been established in this population.

Smokers

Heavy smokers (more than 15 cigarettes/day) may have reduced Agorest exposure and may require closer monitoring for treatment response.

A minimum treatment duration of approximately 6 months is generally recommended for an acute depressive episode treated with Agorest, in order to ensure the depressive episode has fully resolved. Response should be reassessed after about 3 months and then periodically. The need for continued treatment beyond the acute phase should be re-evaluated regularly by the prescribing physician, and any decision to stop treatment should be made under medical guidance.

Agomelatine belongs to the drug class of melatonergic antidepressants, acting as an MT1/MT2 melatonin receptor agonist and a 5-HT2C serotonin receptor antagonist.

Agomelatine works by acting as an agonist at melatonin MT1 and MT2 receptors, helping to resynchronize disrupted circadian rhythms, and as an antagonist at 5-HT2C serotonin receptors, which increases noradrenaline and dopamine release in the frontal cortex. This dual mechanism underlies its antidepressant effect without the direct serotonergic reuptake inhibition seen in SSRIs/SNRIs.

Agorest is not recommended for use in children or adolescents under 18 years of age. Safety and efficacy in this population have not been established, and clinical trial data in pediatric patients are insufficient to support use.