Mirtazapine Tablets

• If you have an allergy to mirtazapine or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are taking any of these drugs: Diazepam, linezolid, or methylene blue.
• If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson's disease like selegiline or rasagiline in the last 14 days. Taking this medicine (mirtazapine tablets) within 14 days of those drugs can cause very bad high blood pressure.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine (mirtazapine tablets) with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take at bedtime if it causes sleepiness.
• Take with or without food. Take with food if it causes an upset stomach.
• Keep taking this medicine (mirtazapine tablets) as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Hypersensitivity

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

Monoamine Oxidase Inhibitors

The  use of monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders with Mirtazapine Tablets, USP or within 14 days of stopping treatment with Mirtazapine Tablets is contraindicated because of an increased risk of serotonin syndrome. The use of Mirtazapine Tablets within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated (see WARNINGS and DOSAGE AND ADMINISTRATION). 

Starting Mirtazapine Tablets in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome (see WARNINGS and DOSAGE AND ADMINISTRATION).

Human Experience

There is very limited experience with Mirtazapine Tablets overdose. In premarketing clinical studies, there were eight reports of Mirtazapine Tablets overdose alone or in combination with other pharmacological agents. The only drug overdose death reported while taking Mirtazapine Tablets was in combination with amitriptyline and chlorprothixene in a non-US clinical study. Based on plasma levels, the Mirtazapine Tablets dose taken was 30 to 45 mg, while plasma levels of amitriptyline and chlorprothixene were found to be at toxic levels. All other premarketing overdose cases resulted in full recovery. 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 Tablets 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 (see PRECAUTIONS, Drug Interactions and ADVERSE REACTIONS sections).

Overdose Management

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 overdosage. 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. Telephone numbers for certified poison control centers are listed in the Physicians’ Desk Reference (PDR). 

Initial Treatment

The recommended starting dose for Mirtazapine Tablets is 15 mg/day, administered in a single dose, preferably in the evening prior to sleep. In the controlled clinical trials establishing the efficacy of mirtazapine in the treatment of major depressive disorder, the effective dose range was generally 15 to 45 mg/day. While the relationship between dose and satisfactory response in the treatment of major depressive disorder for Mirtazapine Tablets has not been adequately explored, patients not responding to the initial 15-mg dose may benefit from dose increases up to a maximum of 45 mg/day.  Mirtazapine Tablets has an elimination half-life of approximately 20 to 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 (see PRECAUTIONS and CLINICAL PHARMACOLOGY).

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 to 12 weeks of initial treatment at a dose of 15 to 45 mg/day (see CLINICAL PHARMACOLOGY). Based on these limited data, it is unknown whether or not the dose of Mirtazapine Tablets 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 a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

  At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with Mirtazapine Tablets. Conversely,  at least 14 days should be allowed after stopping Mirtazapine Tablets before starting an MAOI intended to treat psychiatric disorders (see CONTRAINDICATIONS).

Use of Mirtazapine Tablets With Other MAOIs, Such as Linezolid or Methylene Blue

Do not start Mirtazapine Tablets in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered (see CONTRAINDICATIONS). 

In some cases, a patient already receiving therapy with mirtazapine may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, Mirtazapine Tablets should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with Mirtazapine Tablets may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue (see WARNINGS). 

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with Mirtazapine Tablets is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see WARNINGS).

Discontinuation of Mirtazapine Tablets, USP Treatment

Symptoms associated with the discontinuation or dose reduction of Mirtazapine Tablets have been reported. Patients should be monitored for these and other symptoms when discontinuing treatment or during dosage reduction. A gradual reduction in the dose over several weeks, rather than abrupt cessation, is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, dose titration should be managed on the basis of the patient’s clinical response (see PRECAUTIONS and ADVERSE REACTIONS).

Information for Patients

Patients should be advised that taking Mirtazapine Tablets can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle-closure glaucoma. Pre-existing glaucoma is almost always open-angle glaucoma because angle-closure glaucoma, when diagnosed, can be treated definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle-closure glaucoma. Patients may wish to be examined to determine whether they are susceptible to angle-closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible.