Menelat 30

Mirtazapine (Menelat 30) 30 mg is a pink coloured, round, biconvex, film coated tablet plain on one side and break line on other side.
Mirtazapine has a tetracyclic chemical structure unrelated to selective serotonin reuptake inhibitors (MAOI). Mirtazapine belongs to the piperazanoazepine group of compounds and is an analogue of Mianserin. It is designated 1,2,3,4,10,14b-hexahydro-2-methylpyrazino [2,1-a] pyrido [2,3-c] benzazepine and has the empirical formula of C₁₇H₁₉Cl₃. Its molecular weight is 265.36.
Mirtazapine is a white to creamy white crystalline powder which is slightly soluble in water.
Each film-coated tablet contains: Mirtazapine, USP 30 mg.

Antidepressant.
Pharmacology: Pharmacodynamics: The mechanism of action of mirtazapine as with other drugs effective in the treatment of major depressive disorder, is unknown. Evidence gathered in preclinical studies suggests that mirtazapine enhances central noradrenergic and serotonergic activity. These studies have shown that mirtazapine acts as an antagonist at central presynaptic α2 adrenergic inhibitory auto receptors and heteroreceptors, an action that is postulated to result in an increase in central noradrenergic and serotonergic activity. Mirtazapine is a potent antagonist of 5-HT2 and 5-HT3 receptors. Mirtazapine has no significant affinity for the 5-HT1A and 5-HT1B receptors.
Mirtazapine is a potent antagonist of histamine (H1) receptors, a property that may explain its prominent sedative effects.
Mirtazapine is a moderate peripheral α1 adrenergic antagonist, a property that may explain the occasional orthostatic hypotension reported in association with its use. Mirtazapine is a moderate antagonist at muscarinic receptors, a property that may explain the relatively low incidence of anticholinergic side effects associated with its use.
Pharmacokinetics: Mirtazapine tablets are rapidly and completely absorbed following oral administration and have a half-life of about 20-40 hours. Peak plasma concentrations are reached within about 2 hours following an oral dose. The presence of food in the stomach has a minimal effect on both the rate and extent of absorption and does not require a dosage adjustment. Mirtazapine is extensively metabolized after oral administration. Major pathways of biotransformation are demethylation and hydroxylation followed by glucuronide conjugation. In vitro data from human liver microsomes indicate that cytochrome 2D6 and 1A2 are involved in the formation of the 8-hydroxy metabolite of mirtazapine, whereas cytochrome 3A is considered to be responsible for the formation of the N-desmethyl and N-oxide metabolite. Mirtazapine has an absolute bioavailability of about 50%. It is eliminated predominantly via urine (75%) with 15% in feces. Several unconjugated metabolites possess pharmacological activity but are present in the plasma at very low levels. The (-) enantiomer has an elimination half-life that is approximately twice as long as the (+) enantiomer and therefore achieves plasma levels that are about three times as high as that of the (+) enantiomer.
Plasma levels are linearly related to dose over a dose range of 15-80 mg. The mean elimination half-life of mirtazapine after oral administration ranges from approximately 20-40 hours across age and gender subgroups, with females of all ages exhibiting significantly longer elimination half-lives than males (mean half-life of 37 hours for females vs. 26 hours for males). Steady state plasma levels of mirtazapine are attained within 5 days, with about 50% accumulation (accumulation ratio = 1.5).
Mirtazapine is approximately 85% bound to plasma proteins over a concentration range of 0.01 - 10 µg/mL.

Mirtazapine is indicated for the treatment of major depressive disorder.

Initial Treatment: The initial dose is 15 or 30 mg, taken preferably in the evening. The maintenance dose is usually between 15 mg and 45 mg per day.
Mirtazapine has an elimination half-life of approximately 20-40 hours; therefore, dose changes should not be made at intervals of less than one to two weeks in order to allow sufficient time for evaluation of the therapeutic response to a given dose.
Elderly and Patients with Renal or Hepatic Impairment: The clearance of mirtazapine is reduced in elderly patients and in patients with moderate to severe renal or hepatic impairment. Consequently, the prescriber should be aware that plasma mirtazapine levels may be increased in these patient groups, compared to levels observed in younger adults without renal or hepatic impairment.
Maintenance/Extended Treatment: It is generally agreed that acute episodes of depression require several months or longer of sustained pharmacological therapy beyond response to the acute episode. Systematic evaluation of mirtazapine tablets has demonstrated that its efficacy in major depressive disorder is maintained for periods of up to 40 weeks following 8-12 weeks of initial treatment at a dose of 15-45 mg/day. Based on these limited data, it is unknown whether or not the dose of mirtazapine needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.
Switching Patients To or From a Monoamine Oxidase Inhibitor: At least 14 days should elapse between discontinuation of an MAOI and initiation of therapy with mirtazapine tablets. In addition, at least 14 days should be allowed after stopping mirtazapine before starting an MAOI.

Overdosage and Treatment: There is very limited experience with mirtazapine tablets overdose. The only drug overdose death reported while taking mirtazapine was in combination with amitriptyline and chlorprothixene in a non-clinical study. Based on plasma levels, the mirtazapine dose taken was 30-45 mg, while plasma levels of amitriptyline and chlorprothixene were found to be at toxic levels. Signs and symptoms reported in association with overdose included disorientation, drowsiness, impaired memory, and tachycardia. There were no reports of ECG abnormalities, coma or convulsions following overdose with mirtazapine alone.
However, based on postmarketing reports, there is a possibility of more serious outcomes (including fatalities) at dosages much higher than the therapeutic dose, especially with mixed overdoses. In these cases, QT prolongation and Torsades de Pointes have also been reported.
Treatment should consist of those general measures employed in the management of overdose with any drug effective in the treatment of major depressive disorder. Ensure an adequate airway, oxygenation, and ventilation. Monitor ECG parameters (including cardiac rhythm) and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion, or in symptomatic patients. Activated charcoal should be administered. There is no experience with the use of forced diuresis, dialysis, hemoperfusion, or exchange transfusion in the treatment of mirtazapine overdose. No specific antidotes for mirtazapine are known.
In managing overdosage, consider the possibility of multiple-drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose.

Mirtazapine tablets are contraindicated in patients with a known hypersensitivity to mirtazapine or any of the excipients.

Antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders and those considering use of these agents must balance risk with the clinical need.
Clinical Worsening and Suicide Risk: All pediatric patients being treated with antidepressants for any indication should be observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Such observation would generally include at least weekly face-to-face contact with patients or their family members or caregivers during the first 4 weeks of treatment, then every other week visit for the next 4 weeks, then at 12 weeks, and as clinically indicated beyond 12 weeks. Additional contact by telephone may be appropriate between face-to-face visits.
Adults with MDD or co-morbid depression in the setting of other psychiatric illness being treated with antidepressants should be observed similarly for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.
Screening Patients for Bipolar Disorder: Prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that mirtazapine tablets are not approved for use in treating bipolar depression.
Agranulocytosis: If a patient develops a sore throat, fever, stomatitis or other signs of infection, along with a low WBC count, treatment with mirtazapine should be discontinued and the patient should be closely monitored.
Serotonin Syndrome: The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including Mirtazapine, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's wort), and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome.
The concomitant use of Mirtazapine with MAOIs intended to treat psychiatric disorders is contraindicated. Mirtazapine should also not be started in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue. All reports with methylene blue that provided information on the route of administration involved intravenous administration in the dose range of 1 mg/kg to 8 mg/kg. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection) or at lower doses. There may be circumstances when it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking Mirtazapine. Mirtazapine should be discontinued before initiating treatment with the MAOI. If concomitant use of Mirtazapine with other serotonergic drugs, including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, and St. John's wort, is clinically warranted, be aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.
Treatment with Mirtazapine and any concomitant serotonergic agents should be discontinued immediately if the previously mentioned events occur and supportive symptomatic treatment should be initiated.
Angle-Closure Glaucoma: The pupillary dilation that occurs following use of many antidepressant drugs including Mirtazapine may trigger an angle-closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.
QT Prolongation and Torsades de Pointes: Caution should be exercised when Mirtazapine is prescribed in patients with known cardiovascular disease or family history of QT prolongation, and in concomitant use with other medicinal products thought to prolong the QTc interval.

Somnolence: In the clinical study, somnolence was reported in 54% of patients treated with mirtazapine tablets, compared to 18% for placebo and 60% for amitriptyline. In these studies, somnolence resulted in discontinuation for 10.4% of mirtazapine-treated patients, compared to 2.2% for placebo. It is unclear whether or not tolerance develops to the somnolent effects of mirtazapine. Because of mirtazapine's potentially significant effects on impairment of performance, patients should be cautioned about engaging in activities requiring alertness until they have been able to assess the drug's effect on their own psychomotor performance.
Dizziness: In the clinical studies, dizziness was reported in 7% of patients treated with mirtazapine, compared to 3% for placebo and 14% for amitriptyline. It is unclear whether or not tolerance develops to the dizziness observed in association with the use of mirtazapine.
Increased Appetite/Weight Gain: In the clinical studies, appetite increase was reported in 17% of patients treated with mirtazapine, compared to 2% for placebo and 6% for amitriptyline. In the same trials, weight gain of ≥ 7% of body weight was reported in 7.5% of patients treated with mirtazapine, compared to 0% for placebo and 5.9% for amitriptyline.
Cholesterol/Triglycerides: In the clinical studies, non-fasting cholesterol increases to ≥ 20% above the upper limits of normal were observed in 15% of patients treated with mirtazapine, compared to 7% for placebo and 8% for amitriptyline. In these same studies, non-fasting triglyceride increases to ≥ 500 mg/dL were observed in 6% of patients treated with mirtazapine, compared to 3% for placebo and 3% for amitriptyline.
Transaminase Elevations: Clinically significant ALT (SGPT) elevations (≥ 3 times the upper limit of the normal range) were observed in 2.0% of patients exposed to mirtazapine in the clinical trials, compared to 0.3% of placebo patients and 2.0% of amitriptyline patients. Most of these patients with ALT increases did not develop signs or symptoms associated with compromised liver function. While some patients were discontinued for the ALT increases, in other cases, the enzyme levels returned to normal despite continued mirtazapine treatment. Mirtazapine should be used with caution in patients with impaired hepatic function.
Activation of Mania/Hypomania: The incidence of mania/hypomania was very low during treatment with mirtazapine, it should be used carefully in patients with a history of mania/hypomania.
Seizure: Care should be taken when mirtazapine is used in these patients.
Use in Patients with Concomitant Illness: Mirtazapine should be used with caution in patients with known cardiovascular or cerebrovascular disease that could be exacerbated by hypotension (history of myocardial infarction, angina, or ischemic stroke) and conditions that would predispose patients to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medication).
Mirtazapine clearance is decreased in patients with moderate [glomerular filtration rate (GFR) = 11-39 mL/min/1.73 m²] and severe (GFR < 10 mL/min/1.73 m²) renal impairment, and also in patients with hepatic impairment. Caution is indicated in administering mirtazapine to such patients.
Interference with Cognitive and Motor Performance: Mirtazapine may impair judgement, thinking, and particularly, motor skills, because of its prominent sedative effect. The drowsiness associated with mirtazapine use may impair a patient's ability to drive, use machines or perform tasks that require alertness. Thus, patients should be cautioned about engaging in hazardous activities until they are reasonably certain that mirtazapine therapy does not adversely affect their ability to engage in such activities.
Concomitant Medication: Patients should be advised to inform their physician if they are taking, or intend to take, any prescription or over-the-counter drugs since there is a potential for mirtazapine to interact with other drugs.
Alcohol: Mirtazapine may increase the CNS depressant effect of alcohol. Patients should therefore be advised to avoid alcoholic beverages.

Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during mirtazapine therapy.
Because some Mirtazapine may be excreted into breast milk, caution should be exercised when Mirtazapine are administered to nursing women. Patients should be advised to notify their physician if they are breast-feeding an infant.

Significant: Akathisia, anticholinergic effects (e.g. blurred vision, constipation, xerostomia), arrhythmia, agranulocytosis, hyperlipidemia, hyponatremia, increased sedation, increased risk of suicidal ideation, angle closure glaucoma, orthostatic hypotension, increased transaminase levels, increased appetite, weight gain.
Blood and Lymphatic System Disorders: Anemia, leucopenia, lymphocytosis, pancytopenia and thrombocytopenia.
Cardiac Disorders: Angina pectoris, bradycardia, myocardial infarction.
Ear and Labyrinth Disorders: Deafness, hyperacusis, otitis media.
Endocrine Disorders: Goiter, hyperprolactinemia.
Eye Disorders: Abnormal accommodation, abnormal lacrimation, conjunctivitis, diplopia, blepharitis, eye pain.
Gastrointestinal Disorders: Abdominal pain, acute abdominal syndrome, colitis, constipation, diarrheas, dry mouth, abdomen enlarged, eructation, gastritis, glossitis, hiccup, intestinal obstruction, pancreatitis, salivary gland enlargement, stomatitis, tongue discoloration, nausea, vomiting and ulcer.
General Disorders and Administration Site: Abnormal healing, asthenia, ataxia, fatigue, fever, malaise, edema.
Hepatobiliary Disorders: Cholecystitis, jaundice, liver cirrhosis.
Injury, Poisoning and Procedural Complications: Asphyxia, bone fracture, phlebitis, tendon rupture.
Investigations: Increased acid phosphatase, increased creatine kinase.
Metabolism and Nutrition Disorders: Anorexia, frequent thirst, dehydration, peripheral edema.
Musculoskeletal and Connective Tissue Disorders: Arthralgia, arthritis, back pain, bursitis, gout, hypotonia, myalgia, myositis, neck rigidity, rhabdomyolysis, tenosynovitis.
Nervous System Disorders: Agitation, amnesia, cerebral ischemia, convulsions, dizziness, dyskinesia, dystonia, extrapyramidal syndrome, headache, hypokinesia, hypoesthesia, nystagmus, myasthenia, myoclonus, migraine, paralysis, paresthesia, restless legs syndrome, stupor, tremors, vertigo.
Psychiatric Disorders: Anxiety, apathy, aphasia, confusion, delirium, delusions, dementia, depersonalization, depression, dysarthria, emotional lability, euphoria, hallucination, hostility, insomnia, manic reaction, neurosis, paranoid reaction, somnolence, abnormal dreams or thinking.
Renal and Urinary Disorders: Cystitis, dysuria, polyuria, urinary frequency, urinary retention, UTI.
Reproductive System and Breast Disorders: Breast engorgement and enlargement, amenorrhea, dysmenorrhea, hematuria, increased libido, leucorrhea, metrorrhagia, impotence.
Respiratory, Thoracic and Mediastinal Disorders: Cough, dyspnea, bronchitis, asthma, laryngitis, flu syndrome, pneumonia, pneumothorax, pulmonary embolus, sinusitis.
Skin and Subcutaneous Tissue Disorders: Acne, alopecia, exanthema, erythema multiforme, exfoliative dermatitis, urticaria, herpes simplex, herpes zoster, petechiae, rash, seborrhea, skin hypertrophy, skin photosensitivity.
Vascular Disorders: Epistaxis, hypertension, hypotension, syncope, vasodilation.
Potentially Fatal: Serotonin syndrome, severe skin reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis).
Patient to seek medical attention immediately at the first sign of any adverse reaction.

Increased Sedative effects with benzodiazepines (e.g. Alprazolam, Clonazepam, Diazepam).
Increased risk of serotonin syndrome with SSRIs (e.g. escitalopram, fluoxetine, sertraline), serotonin-norepinephrine reuptake inhibitors (e.g. venlafaxine, duloxetine, sibutramine), TCAs (e.g. amitriptyline, clomipramine, imipramine), triptans (e.g. sumatriptan, zolmitriptan, almotriptan), amphetamine, buspirone, fentanyl, lithium, tramadol and tryptophan.
Increased serum plasma concentration with potent CYP3A4 inhibitors such as HIV-protease inhibitors (e.g. ritonavir), azole antifungals (e.g. itraconazole, ketoconazole), erythromycin and nefazodone.
Decreased serum plasma concentration with potent CYP3A4 inducers (e.g. carbamazepine, phenytoin, rifampin).
Increased serum plasma concentration when concurrently administered with cimetidine. Increased risk of QT prolongation with drugs concurrently administered with QTc interval prolonging drugs (e.g. azithromycin, fluconazole, chloroquine).
May diminish antihypertensive effect of α2-agonist (e.g. clonidine, methyldopa).
May enhance the anticoagulant of warfarin.
Potentially Fatal: Increased risk of serotonin syndrome when concurrently administered with or within 14 days of discontinuing MAOIs (e.g. isocarboxazid, linezolid, IV methylene blue, phenelzine, selegiline, tranylcypromine).
Food Interaction: Increased sedative effect with alcohol. Increased risk of serotonin syndrome with St. John's wort.

Store at temperatures not exceeding 30°C. Protect from light & moisture.

Antidepressants

N06AX11 - mirtazapine ; Belongs to the class of other antidepressants.

Rx