Leyuan

Uses

Leyuan is used for Depressive illness, Obsessive-compulsive disorder, Post-traumatic stress disorder, Panic disorder

Leyuan is also used to associated treatment for these conditions: Binge Eating Disorder (BED), Bulimia Nervosa, Generalized Anxiety Disorder (GAD), Major Depressive Disorder (MDD), Obsessive Compulsive Disorder (OCD), Panic Disorder, Post Traumatic Stress Disorder (PTSD), Premenstrual Dysphoric Disorder, Social Anxiety Disorder (SAD)

How Leyuan works

Leyuan selectively inhibits the reuptake of serotonin (5-HT) at the presynaptic neuronal membrane, thereby increasing serotonergic activity. This results in an increased synaptic concentration of serotonin in the CNS, which leads to numerous functional changes associated with enhanced serotonergic neurotransmission. These changes are believed to be responsible for the antidepressant action and beneficial effects in obsessive-compulsive (and other anxiety related disorders). It has been hypothesized that obsessive-compulsive disorder, like depression, is also caused by the disregulation of serotonin.

In animal studies, chronic administration of sertraline results in down-regulation of brain norepinephrine receptors. Leyuan displays affinity for sigma-1 and 2 receptor binding sites, but binds with stronger affinity to sigma-1 binding sites. In vitro, sertraline shows little to no affinity for GABA, dopaminergic, serotonergic (5HT1A, 5HT1B, 5HT2), or benzodiazepine receptors. It exerts weak inhibitory actions on the neuronal uptake of norepinephrine and dopamine and exhibits no inhibitory effects on the monoamine oxidase enzyme.

Dosage

Leyuan dosage

Depressive illness:

• Adult: Initially 50 mg daily, increased if necessary by increments of 50 mg over several weeks to maximum 200 mg daily. Usual maintenance dose is 50 mg daily.
• Child and adolescent less than 18 years:Not recommended.

Obsessive-compulsive disorder:

• Adult and adolescent over 13 years: Initially 50 mg daily, increased if necessary in steps of 50 mg over several weeks. Usual dose range is 50-200 mg daily.
• Child (6-12 years): Initially 25 mg daily, increased to 50 mg daily after 1 week, further increased if necessary in steps of 50 mg at intervals of at least 1 week (maximum 200 mg daily).

Post-traumatic stress disorder:

• Adult: Initially 25 mg daily, increased after 1 week to 50 mg daily; if response is partial and if drug is tolerated, dose can be increased in steps of 50 mg over several weeks to maximum 200 mg daily.
• Child and adolescent less than 18 years: Not recommended.

Side Effects

Leyuan may cause side effects like upset stomach, diarrhoea, constipation, vomiting, dry mouth, loss of appetite, weight changes, drowsiness, dizziness, headache, pain, burning or tingling in the hands or feet, excitement, sore throat etc.

Toxicity

The LD50 of sertraline is >2000 mg/kg in rats according to the FDA label. One other references indicates an oral LD50 of in mice and rats of 419 - 548 mg/kg and 1327 - 1591mg/kg, respectively.

The most common signs and symptoms associated with a non-fatal sertraline overdose are somnolence, vomiting, tachycardia, nausea, dizziness, agitation, and tremor. No cases of fatal overdose with only sertraline have been reported. Most fatal cases are associated with the ingestion of sertraline with other drugs. Consequences of a sertraline overdose may include serotonin syndrome, hypertension, hypotension, syncope, stupor, coma, bradycardia, bundle branch block, QT-prolongation, torsade de pointes, delirium, hallucinations, and pancreatitis.

Precaution

Precaution should be taken in case of liver problems, kidney diseases, seizures, heart problems and any allergies. This drug may cause dizziness or drowsiness. Caution should be taken in activities requiring alertness such as driving or using machinery. Caution is advised while using this product in the elderly because they may be more sensitive to the effects of the drug. Do not take this drug if you have taken monoamine oxidase inhibitor in the last five weeks.

Interaction

Potential effects of co-administration of drugs that are highly bound to plasma proteins- As Leyuan is tightly bound to plasma protein, the administration of Leyuan to a patient taking another drug which is tightly bound to protein, (e.g. warfarin, digitoxin) may cause a shift in plasma concentrations potentially resulting in an adverse effect. Conversely adverse effects may result from displacement of protein bound Leyuan by other tightly bound drugs. Leyuan may interact with other drugs such as Cimetidine, CNS active drugs like Diazepam, Hypoglycemic drugs, Atenolol etc.

Food Interaction

• Avoid St. John's Wort.
• Take with or without food.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of sertraline.

Use in combination may result in additive central nervous system depression and

In addition, limited clinical data suggest that consumption of grapefruit juice during treatment with sertraline may result in increased plasma concentrations of sertraline.

The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruit.

An in-vitro study demonstrated that grapefruit juice dose-dependently inhibits the conversion of sertraline to its metabolite, desmethylsertraline.

In a study with eight Japanese subjects, mean plasma levels of sertraline increased by approximately 100% and maximum plasma concentrations increased by 66% after the ingestion of three 250 mL glasses of grapefruit juice per day for 5 days and administration of a single dose of sertraline 75 mg on the sixth day.

In another small study with 5 patients, mean sertraline trough levels increased by 47% after taking sertraline for at least 6 weeks, then taking sertraline with 240 mL grapefruit juice daily for 1 week.

The clinical significance is unknown; however, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

The possibility of significant interaction in some patients should be considered.

MANAGEMENT: Patients receiving sertraline should be advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how sertraline affects them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Some authorities recommend that consumption of grapefruit juice should be avoided during sertraline therapy.

Leyuan Drug Interaction

Major: amphetamine / dextroamphetamineModerate: aspirin, aspirin, diphenhydramine, pregabalin, metoprolol, metoprolol, albuterol, cetirizineMinor: alprazolamUnknown: rosuvastatin, omega-3 polyunsaturated fatty acids, atorvastatin, esomeprazole, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid, ergocalciferol, cholecalciferol

Leyuan Disease Interaction

Major: depressionModerate: hyponatremia, glaucoma, liver disease, mania, platelet function, seizure disorders, SIADHMinor: renal dysfunction, weight loss

Volume of Distribution

Leyuan is widely distributed, and its volume of distribution is estimated to be more than 20L/kg. Post-mortem studies in humans have measured liver tissue concentrations of 3.9–20 mg/kg for sertraline and between 1.4 to 11 mg/kg for its active metabolite, N-desmethyl-sertraline (DMS). Studies have also determined sertraline distributes into the brain, plasma, and serum.

Elimination Route

Following once-daily administration of 50 to 200 mg for two weeks, the mean peak plasma concentrations (Cmax) of sertraline occurred between 4.5 to 8.4 hours after administration, and measured at 20 to 55 μg/L. Steady-state concentrations are reached after 1 week following once-daily administration, and vary greatly depending on the patient. Bioavailability has been estimated to be above 44%. The area under the curve in healthy volunteers after a 100mg dose of sertraline was 456 μg × h/mL in one study.

Effects of food on absorption

The effects of food on the bioavailability of the sertraline tablet and oral concentrate were studied in subjects given a single dose with and without food. For the tablet, AUC was slightly increased when sertraline was administered with food, the Cmax was 25% greater, and the time to peak plasma concentration was shortened by about 2.5 hours. For the oral concentrate preparation of sertraline, peak concentration was prolonged by approximately 1 hour with the ingestion of food.

Half Life

The elimination half-life of sertraline is approximately 26 hours. One reference mentions an elimination half-life ranging from 22-36 hours.

Clearance

In pharmacokinetic studies, the clearance of a 200mg dose of sertraline in studies of both young and elderly patients ranged between 1.09 ± 0.38 L/h/kg - 1.35 ± 0.67 L/h/kg.

Elimination Route

Since sertraline is extensively metabolized, excretion of unchanged drug in the urine is a minor route of elimination, with 12-14% of unchanged sertraline excreted in the feces.

Pregnancy & Breastfeeding use

Pregnancy: Although animal studies did not provide any evidence of teratogenicity, the safety of Leyuan during human pregnancy has not been established.

Lactation: Leyuan is known to be excreted in breast milk. Its effects on the nursing infant have not yet been established. If treatment with Leyuan is considered necessary, discontinuation of breast-feeding should be considered.

Contraindication

Leyuan is contraindicated in patients with a known hypersensitivity to Leyuan or any of the excipients of drug.

Storage Condition

Store at 25° C.

Innovators Monograph

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