Agorest 25 mg

Indication:

Agorest 25 mg is indicated for the acute and maintenance management of specific psychiatric disorders:

1. Treatment of Major Depressive Disorder (MDD) in Adults: Management of moderate-to-severe major depressive episodes. It is particularly effective for patients presenting with pronounced circadian disruption, sleep disturbances, severe anhedonia, and daytime fatigue.
2. Prevention of Depressive Relapse: Long-term maintenance therapy (typically 6 months or longer) to stabilize clinical remission and prevent the recurrence of depressive episodes in adult patients who showed an initial response to acute treatment.

”রেজিস্ট্রার চিকিৎসকের পরামর্শ অনুযায়ী ঔষধ সেবন করুন”

Dogase & Adminstration:

Adult Dosage (Age 18 to 64 Years):

• Standard Starting Dose: 25 mg orally once daily, taken at bedtime.
• Dose Escalation: If there is no clinical improvement after two weeks of therapy, the dose may be increased to a maximum of 50 mg once daily (taken as two 25 mg tablets together at bedtime).
• Mandatory Liver Function Monitoring (LFTs): Due to the risk of hepatic transaminase elevations, liver function tests (ALT and AST) must be performed for every patient:
  • At the initiation of treatment (baseline).
  • At 3 weeks, 6 weeks, 12 weeks, and 24 weeks of therapy.
  • Periodically thereafter when clinically indicated.
  • If a patient’s transaminases exceed 3 times the upper limit of normal (ULN), agomelatine must be discontinued immediately.

Elderly Dosage (Age 65 Years and Older):

• Efficacy and Caution: The efficacy of agomelatine has not been clearly demonstrated in patients aged 75 years and older. Therefore, agomelatine is not recommended for use in patients aged 75 years or older. Caution and close monitoring are advised in patients aged 65 to 74 years.

Pediatric Dosage (Under 18 Years):

• Contraindicated / Not Recommended: The safety and efficacy of agomelatine have not been established in children and adolescents. Its use is not recommended in patients under 18 years of age due to lack of clinical data.

Administration Instructions:

• Timing: Agomelatine must be taken at bedtime. This aligns the drug’s peak concentrations with the body’s natural circadian phase shift, maximizing its sleep-restoring and antidepressant properties.
• Food Intake: Tablets can be taken with or without food.
• Missed Dose: If a dose is missed at bedtime, the patient should skip that dose entirely and take the next scheduled dose the following evening at bedtime. Do not take a double dose to make up for a missed one.

”রেজিস্ট্রার চিকিৎসকের পরামর্শ অনুযায়ী ঔষধ সেবন করুন”

Pharmacology:

• Mechanism of Action: Agomelatine is a novel, atypical antidepressant with a unique dual-action synergistic profile. It operates as a melatonergic receptor agonist (highly selective for MT1​ and MT2​ receptors) and a 5-HT2C​ receptor antagonist.
  • Melatonergic Agonism (MT1​ & MT2​): By binding directly to MT1​ and MT2​ receptors located in the suprachiasmatic nucleus (SCN) of the hypothalamus, agomelatine resynchronizes disrupted circadian rhythms. It restores normal sleep architecture (increasing slow-wave sleep) and regulates body temperature fluctuations without daytime sedation.
  • Serotonergic Antagonism (5-HT2C​): By blocking the inhibitory 5-HT2C​ receptors in the prefrontal cortex, agomelatine selectively disinhibits and increases the local release of dopamine and noradrenaline. This action specifically addresses core depressive symptoms, such as anhedonia, fatigue, and cognitive dullness, while avoiding the typical side effects of selective serotonin reuptake inhibitors (SSRIs), such as sexual dysfunction, weight gain, or emotional blunting.
• Pharmacokinetics:
  • Absorption: Rapidly and well absorbed (>80%) after oral administration. However, due to a highly pronounced hepatic first-pass metabolism, its absolute bioavailability is low (~3% at the therapeutic dose of 25 mg), which exhibits significant inter-individual variation.
  • Distribution: Highly bound to plasma proteins (~95%), primarily albumin. It is extensively distributed throughout body tissues.
  • Metabolism & Elimination: Agomelatine is rapidly and extensively metabolized in the liver, primarily via the CYP1A2 isoenzyme (~90%), with minor contributions from CYP2C9 and CYP2C19. The metabolites are pharmacologically inactive and are rapidly excreted, mostly in the urine (~80%) as conjugates. The elimination half-life (t1/2​) is extremely short, ranging from 1 to 2 hours

Side Effects:

• Common: Headache, dizziness, somnolence, insomnia, nausea, diarrhea, abdominal pain, back pain, fatigue, and anxiety.
• Serious: Hepatotoxicity (severe elevation of transaminases, hepatitis, jaundice, liver failure), suicidal ideation or behavior (especially in young adults initiating therapy), and severe skin reactions (e.g., eczema, pruritus).

Drug Interaction:

• Strong CYP1A2 Inhibitors (e.g., Fluvoxamine, Ciprofloxacin): Co-administration is strictly contraindicated. These drugs profoundly inhibit agomelatine’s primary metabolic pathway, leading to a massive (up to 100-fold) increase in agomelatine exposure and a high risk of hepatotoxicity.
• Moderate CYP1A2 Inhibitors (e.g., Estrogens, Propanolol, Enoxacin): Use with extreme caution. These may increase agomelatine blood levels and elevate the risk of adverse reactions.
• Rifampicin (CYP1A2 Inducer): May decrease plasma concentrations of agomelatine, potentially reducing its clinical efficacy.
• Alcohol: Concomitant use of alcohol during agomelatine treatment is strongly discouraged due to the added risk of liver toxicity and central nervous system effects.

Pregnancy & Lactation:

• Pregnancy: Category B/C. As a precautionary measure, it is preferable to avoid the use of agomelatine during pregnancy unless the clinical benefit clearly outweighs the potential risks to the fetus.
• Lactation: Animal studies show that agomelatine and its metabolites are excreted in breast milk. It is unknown whether it is excreted in human milk. A decision must be made whether to discontinue breastfeeding or discontinue the drug, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother.

Over Dosage:

• Symptoms: Experience with agomelatine overdose is limited. Reported symptoms include epigastric pain, somnolence, fatigue, dizziness, tension, anxiety, and agitation.
• Treatment: There is no specific antidote. Treatment should consist of gastric lavage if appropriate, followed by general symptomatic and supportive care in a specialized clinical setting. Continuous monitoring of liver function is highly recommended.

Therapeutic Class:

Antidepressant; Melatonergic Receptor Agonist and 5-HT2C​ Receptor Antagonist.

Storage Conditions:

Store below at 30°C  temperature in a dry place. Away from light and out of reach of children. Do not use the medication after its expiration date.