Drug Name: Biolot

Common name: Escitalopram Oxalate Tablets

Biolot Specifications: 10mg*7 tablets/box

Bilot unit: box

Bilot approval number: National Drug Approval No. H20080788

Bilot manufacturer: Sichuan Kelun Pharmaceutical Co., Ltd. Results from short-term clinical trials of depressive disorder (MDD) and other psychiatric disorders show that antidepressants increase the risk of suicidal thoughts and suicidal behaviors (suicidal tendencies) in children, adolescents, and young adults (<24 years) compared with placebo. risk. Anyone considering the use of escitalopram oxalate or other antidepressants in children, adolescents, or young adults (<24 years of age) must weigh the risks against the clinical needs. Short-term clinical trials did not show an increased risk of suicidality compared with placebo when using antidepressants in adults aged 24 years and older, and increased risk of suicide after using antidepressants in adults 65 years and older. The risk of tendencies is reduced. Depression and certain mental disorders themselves are associated with an increased risk of suicide, and patients of all ages must be closely observed for worsening of clinical symptoms, suicidal tendencies, and abnormal changes in behavior after the initiation of antidepressant treatment. Families and caregivers should be advised to monitor closely and communicate with doctors. Escitalopram oxalate is not approved for use in pediatric patients (see Biolot Precautions - Warnings, Clinical Worsening and Risk of Suicide).

Bilot Ingredients Main ingredients of Biolot: Escitalopram oxalate Chemical name: (S)-1-[3-(dimethylamino)propyl]-1-(4-fluoro) Phenyl)-1,3-dihydro-5-cyanoisobenzofuran oxalate. Molecular formula: C20H21FN2O·C2H2O4 Molecular weight: 414.43 Biolot Properties Biolot is a film-coated tablet, which appears white after the film coating is removed. Bailot Indications: Suitable for the treatment of depression. Biolot Specification: 10 mg (based on escitalopram). Bailot Usage and Dosage Usage: Oral, can be taken with food. Dosage: 1 time per day. The usual dose is 10 mg daily, and the maximum daily dose can be increased to 20 mg based on individual patient response. Antidepressant effects are usually achieved in 2-4 weeks. After symptoms are relieved, treatment should be continued for at least 6 months to consolidate the effect. Elderly patients (>65 years old) It is recommended to start treatment with half of the conventional starting dose mentioned above, and the maximum dose should be reduced accordingly. Children and Adolescents (<18 years old): Efficacy and safety studies have not been conducted in this population, and use in this population is not currently recommended. Patients with reduced renal function: Patients with mild to moderate renal function reduction (CLCR<30ml/minute) do not need to adjust the dose. Patients with severe renal function reduction should use with caution. For patients with reduced liver function, the recommended starting dose is 5 mg per day and continued treatment for 2 weeks. Depending on the patient's individual response, the dose may be increased to 10 mg daily. CYP2C19 slow metabolizers: For patients known to be CYP2C19 slow metabolizers, the recommended starting dose is 5 mg daily for 2 weeks. The dose can be increased to 10 mg daily based on the patient's individual response. Withdrawal symptoms When it is necessary to stop treatment with Biolot, the dose should be gradually reduced within 1 to 2 weeks to avoid withdrawal symptoms. The safety of doses above 20 mg daily has not been proven. Bilot Adverse Reactions Foreign literature reports that adverse reactions mostly occur in the first 1-2 weeks of treatment, and the severity and incidence of adverse reactions will decrease after continued treatment. After long-term use of SSRI drugs and sudden discontinuation of treatment, some patients will develop withdrawal symptoms. Although withdrawal symptoms may occur after stopping treatment, the existing preclinical and clinical evidence does not show that SSRI drugs can cause dependence. There has not been a systematic review of the withdrawal reactions of Biolot. Citalopram withdrawal reactions have been observed, manifesting as: dizziness, headache and nausea, most of which are mild and self-limiting. In double-blind placebo-controlled studies conducted abroad, the following adverse reactions occurred significantly more with Biolot than with placebo, and the listed incidence rates have not been corrected for placebo.

Metabolic and nutritional disorders are common (>1/100, <1/10); Psychiatric disorders with decreased appetite are common (>1/100, <1/10); Reduced sexual desire and anorgasmia (females); Nervous system disorders are common (> 1/100, <1/10); Insomnia, drowsiness, and dizziness are rare (>1/1000, <1/100); Abnormal taste, sleep disorders, respiratory system, chest and diaphragm abnormalities are common (>1/100, <1 /10); Sinusitis, yawning, gastrointestinal system abnormalities are common (>1/10); Nausea is common (>1/100, <1/10); Diarrhea, constipation, skin and subcutaneous tissue abnormalities are common (>1/100 , <1/10); Hyperhidrosis, reproductive system and breast abnormalities are common (>1/100, <1/10); Ejaculation disorders, systemic symptoms of impotence and local abnormal manifestations of medication are common (>1/100, <1/10) ; Fatigue, fever. The following are adverse reactions of SSRI drugs: Metabolic and nutritional disorders: hyponatremia, abnormal antidiuretic hormone secretion; Psychiatric disorders: hallucinations, mania, confusion, agitation, anxiety, personality changes, panic attacks , Neuroticism; Nervous system disorders: seizures, tremors, movement disorders, serotonin syndrome; Eyes: visual abnormalities; Cardiovascular system: orthostatic hypotension; Gastrointestinal system: nausea, vomiting, dry mouth, diarrhea, Lack of appetite; Hepatobiliary system: abnormal liver function tests; Skin and subcutaneous tissue: rash, ecchymosis, pruritus, angioedema, and hyperhidrosis; Musculoskeletal system: arthralgia and myalgia; Kidney and urinary system: urinary retention; Reproductive system : Galactorrhea, sexual function includes: impotence, ejaculation disorder, anorgasmia; Systemic symptoms: insomnia, dizziness, fatigue, drowsiness and allergic reactions. Biolot Contraindications: It is contraindicated for use by those who are allergic to escitalopram oxalate or any of the excipients. Concomitant use with non-selective, irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated. Biolot Precautions: Antidepressants are not suitable for children and adolescents under 18 years of age. In clinical trials in children and adolescents under 18 years of age, suicide-related behaviors (suicide attempts and suicidal ideation) and hostility (aggression, confrontational behavior, and irritability) were found to occur more frequently in the Biolot group than in the placebo group. . Even for clinical trials, patients still need to be closely monitored for suicidal manifestations. The following special warnings and cautions apply to all SSRI drugs. Paradoxical Anxiety Some patients with panic disorder may experience worsening of their anxiety symptoms during the initial stages of treatment with antidepressants. This paradoxical reaction usually diminishes within two weeks of starting treatment. It is recommended that lower starting doses may reduce this anxiogenic effect of the drug. Seizures Patients who experience seizures should discontinue medication. SSRIs should be avoided in patients with unstable seizures, and patients with controlled seizures should be monitored during treatment. If seizure frequency increases, SSRIs should be discontinued. Mania SSRIs should be used with caution in patients with a history of manic or hypomanic episodes. Patients who develop a manic episode should discontinue SSRIs. Diabetes For patients with diabetes, treatment with SSRI drugs may affect blood sugar regulation. Patients taking insulin and/or oral hypoglycemic agents may require dosage adjustments of these medications. Suicide: The inherent symptoms of depression may lead to suicide attempts, which will continue until significant improvement occurs spontaneously or with treatment. Patients taking antidepressants should be monitored closely, especially early in treatment, to prevent worsening of symptoms and/or the development of suicidality (suicidal ideation and behavior). Such prevention should also be taken when treating other mental disorders associated with depression. Hyponatremia Hyponatremia (possibly due to abnormal secretion of antidiuretic hormone) has been reported rarely with SSRIs and usually resolves after discontinuation of drug therapy. Caution should be exercised in patients at risk such as the elderly, patients with cirrhosis, or when taking medications known to cause hyponatremia. Bleeding Subcutaneous bleeding, such as ecchymoses and purpura, have been reported with SSRI use.

It is recommended that SSRIs should be used with caution in the following groups, including: patients who are concurrently taking oral anticoagulants, or who are concurrently taking drugs known to have an impact on platelet function (such as atypical antipsychotics and phenothiazines, large Some tricyclic antidepressants, acetylsalicylic acid and nonsteroidal anti-inflammatory drugs, ticlopidine and dipyridamole) and patients with a known bleeding tendency. Electroconvulsive therapy (ECT) There is currently limited clinical experience with the combined use of SSRIs and electroconvulsive therapy, so caution is advised. Reversible, Selective MAO-A Inhibitors The combined use of Biolot and MAO-A inhibitors is generally not recommended due to the possible risk of serotonin syndrome. For concomitant use with non-selective, irreversible MAO inhibitors, see Drug Interactions. Serotonin Syndrome: Caution is recommended when administering Belotin with serotonergic drugs such as sumatriptan or other triptans, tramadol, and tryptophan. Serotonin syndrome has been reported in rare cases during concomitant treatment with SSRIs and serotonergic agents. If the following symptoms appear after the combination, such as agitation, tremor, myoclonus and high fever, it indicates that serotonin syndrome may have occurred. If this problem occurs, SSRIs and serotonergic drugs should be discontinued immediately and symptomatic treatment should be given. St. John's Wort: The combined use of SSRI drugs and Chinese herbal medicines containing St. John's wort (hyperin) may increase the occurrence of adverse reactions. Withdrawal symptoms: When stopping treatment with Biolot, it is recommended to gradually stop the drug within 1-2 weeks to avoid withdrawal symptoms. Effects on Ability to Drive and Operate Machinery Although studies have shown that Biolot does not affect intelligence or psychomotor performance, any psychoactive drug may affect judgment and skills. Patients should be aware of potential hazards that may affect their ability to drive a vehicle and operate machinery. Please keep it out of reach of children. Biolot: Medication for Pregnant and Lactating Women Pregnant Women: There is currently no clinical data on the use of Biolot for pregnant women. Its teratogenic effects were observed in reproductive toxicology studies in rats, and no increase in the incidence of malformations was found. The risk to the human body is unknown, so Biolot should not be used in pregnant women. If clinically necessary, it can only be used after careful consideration of its risks/benefits. Breastfeeding women: Escitalopram oxalate can be secreted in breast milk. Breastfeeding women should not receive Biolot treatment or stop breastfeeding while taking the drug. Biolot Children's Medication Please refer to Biolot usage and dosage. Biolot Elderly Medication Please refer to Biolot Usage and Dosage. Biolot Drug Interactions Pharmacodynamic Interactions Contraindicated Concomitant Use: Non-selective MAOIs Patients who are receiving SSRI drug therapy combined with selective monoamine oxidase inhibitors (MAOI) and those who have recently stopped taking SSRI drug therapy and started MAOI therapy Serious adverse reactions have been reported in patients. Some patients develop serotonin syndrome. Escitalopram oxalate is contraindicated in combination with non-selective MAOIs. Treatment with Biofloxacin can be initiated at least 14 days after discontinuation of treatment with irreversible MAOIs and at least 1 day after discontinuation of treatment with reversible MAOIs (e.g., moclobemide). Treatment with a non-selective MAOI can be started at least 7 days after discontinuing treatment with Biolot. Concomitant therapy not recommended: Reversible, selective MAO-A inhibitor (moclobemide). Due to the risk of serotonin syndrome, concomitant use of Bioflot with MAO-A inhibitors is not recommended. If combined treatment is indeed necessary, it should be started at the minimum recommended starting dose and clinical monitoring should be strengthened. Co-administration of selegiline with selegiline, an irreversible MAO-B inhibitor, requires caution due to the possible risk of serotonin syndrome. Selegiline is safe when combined with citalopram at doses below 10 mg per day. Serotonergic Drugs Concomitant use of serotonergic drugs (such as tramadol, sumatriptan, and other triptans) may result in serotonin syndrome. Drugs that lower the seizure threshold SSRI drugs can lower the seizure threshold. It is recommended that caution be used when combined with other drugs that can lower the seizure threshold. Lithium salts and tryptophan There are reports of synergistic effects from the combined use of SSRI drugs and lithium salts or tryptophan, so SSRI drugs and these drugs should be used with caution. St. John's Wort: The combined use of SSRI drugs and Chinese herbal medicines containing St. John's wort (hyperin) may increase the occurrence of adverse reactions.

Bleeding: The anticoagulant effect of oral anticoagulants may be altered when Bioflot is used concomitantly. Patients receiving oral anticoagulants should pay special attention to monitoring for anticoagulant effects when initiating or discontinuing treatment with Bioflot. Alcohol: There are no pharmacokinetic or pharmacodynamic interactions between Biolot and alcohol. However, like other psychoactive drugs, it is not recommended to use it with alcohol. Pharmacokinetic interactions Other drugs that affect the pharmacokinetics of Belotate The metabolism of Belotate in the body is mainly mediated by CYP2C19. CYP3A4 and CYP2D6 are also involved in its metabolism, but have a smaller impact. Escitalopram, desmethyl oxalate, the main metabolite of Biolot, may also be partially catalyzed by CYP2D6. Concomitant use of omeprazole (a CYP2C19 enzyme inhibitor) may result in a moderate increase (approximately 50%) in the plasma concentration of Belotate. Coadministration of escitalopram with cimetidine, a moderate inhibitor of multiple enzymes, may moderately increase escitalopram plasma concentrations (approximately 70%). Therefore, when the upper limit of the therapeutic dose of Bioflot is reached, CYP2C19 enzyme inhibitors (such as omeprazole, fluoxetine, fluvoxamine, lansoprazole, ticlopidine) and cimetidine should be used with caution . Strategies to lower Biolot may be necessary based on clinical judgment. Effects of Belot on the pharmacokinetics of other drugs. Belot is an inhibitor of CYP2D6. Caution should be used when combined with the following drugs, including drugs mainly metabolized by CYP2D6 and drugs with a narrow therapeutic index, such as: flecainide, propafenone and metoprolol (when treating heart failure), or some drugs that act on the central nervous system that are primarily metabolized by CYP2D6 (the antidepressants desipramine, clomipramine, nortriptyline, etc.) or The antipsychotics risperidone, thioridazine, and cloperidol), the dose should be adjusted when used together. Coadministration with normipramine or metoprolol may result in a more than twofold increase in plasma concentrations of these two drugs, both of which are CYP2D6 substrates. In vitro studies have shown that Biolot may also cause mild inhibition of CYP2C19. It is recommended that caution be used when combined with drugs metabolized by CYP2C19. Biolotel Overdose Toxicity Clinical data on Biolota overdose are very limited, but there have been reports of overdose of Biolota 190mg without any serious adverse reactions. Symptoms after citalopram overdose (>600mg) are: dizziness, tremor, agitation, drowsiness, unconsciousness, epileptic seizures, tachycardia, ECG changes, ST-T segment changes, QRS complex widening, QT interval Prolongation, cardiac arrhythmias, respiratory depression, vomiting, rhabdomyolysis, metabolic acidosis, hypokalemia. The same symptoms may occur after an overdose of escitalopram oxalate. Treatment: There is no specific rescue drug. It is critical to maintain a clear airway and ensure adequate oxygen uptake and respiratory function. Gastric lavage should be performed as soon as possible after oral administration of drugs. It is recommended to monitor heart and vital signs and provide systemic supportive treatment. Pharmacological effects Escitalopram oxalate is a selective serotonin reuptake inhibitor (SSRI). The possible mechanism of the pharmacological effects and clinical efficacy of Biolot is the inhibition of serotonin reuptake. Escitalopram oxalate affects 5-HT1A receptors, 5-HT2, dopamine D1 and D2 receptors, α1-, α2-, and β-adrenergic receptors, histamine H1, and muscarinic cholinergic receptors. In the body, benzodiazepines and opioid receptors have no or very low affinity. Toxicological studies Genotoxicity: In the racemic citalopram Ames test, in the absence of metabolic activators, 2 of the 5 test strains (TA98 and TA1537) had positive results. Racemic citalopram tested positive for CHL chromosomal aberrations in the presence or absence of metabolic activators. The results of racemic citalopram mouse lymphoma human lymphocyte chromosome aberration test (HPRT), rat liver cell unprogrammed DNA synthesis test (UDS), human lymphocyte chromosome aberration test, and mouse micronucleus test were all negative. Reproductive toxicity: In the fertility test, rats were orally administered racemic citalopram at 32, 48, and 72 mg/kg/day. It can be seen that the odds of survival in each dose group were reduced. Fertility was reduced when the dose was ≥32 mg/kg/day. The dose was Pregnancy events were prolonged at 48 mg/kg/day.

In the rat embryo-fetal developmental toxicity test, rats were orally administered escitalopram at 56, 112, and 150 mg/kg/day, medium and high doses (calculated based on mg/m2, equivalent to the maximum recommended human dose [MRHD] At 20mg/day ≥56 times, maternal toxicity (clinical abnormal symptoms, reduced weight gain, reduced food intake) was seen in all dose groups, and no teratogenic effect was found at the dose. It is 56 mg/kg/day, which is equivalent to about 28 times the MRHD. Pregnant rats were given escitalopram 6, 12, 24, and 48 mg/kg/day during the perinatal period, and the highest dose group (equivalent to about 24 times the MRHD). There was a slight increase in offspring mortality and slight growth retardation, and slight maternal toxicity (clinical abnormal symptoms, reduced weight gain, and reduced food intake) was seen in the 24 mg/kg/day dose group. The no-effect dose was 12 mg. /kg/day, equivalent to approximately 6 times the MRHD. In animal reproductive toxicity tests, racemic citalopram has shown adverse effects on embryonic/fetal development and postnatal development, including teratogenicity at doses higher than human therapeutic doses. Sex. In the rat embryo/fetal toxicity test, rats were orally administered 32, 56, and 112 mg/kg/day of racemic citalopram. At high doses, embryo/fetal growth inhibition, fetal survival rate decreased, and fetal abnormality rate increased. (including cardiovascular and skeletal defects) and maternal toxicity (clinical abnormal growth, reduced weight gain), with a no-effect dose on development of 56 mg/kg/day in rabbits administered oral racemic citalopram at doses up to 16 mg/mg/day. No abnormality was found for days. In the perinatal toxicity test, rats were orally administered 4.8, 12.8, and 32 mg/kg/day of racemic citalopram. In the high-dose group, the mortality rate of young rats increased within 4 days after birth, and the growth of young rats stagnated. No effect at 12.8 mg/kg/day. Carcinogenicity: NMRI/BOM mice and COBS WI rats were dosed orally with racemic citalopram for 18 to 24 months, respectively. No carcinogenicity was found at doses of 8 or 24 mg/kg/day. The relevance of this phenomenon to humans is unclear.