Label: MIRTAZAPINE tablet, film coated

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Updated February 23, 2021

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  • HIGHLIGHTS OF PRESCRIBING INFORMATION
    HIGHLIGHTS OF PRESCRIBING INFORMATION
    These highlights do not include all the information needed to use MIRTAZAPINE TABLETS
    safely and effectively. See full prescribing information for MIRTAZAPINE TABLETS.
    MIRTAZAPINE TABLETS, for oral use
    Initial U.S. Approval: 1996

    INDICATIONS AND USAGE

    Mirtazapine Tablets is indicated for the treatment of major depressive disorder (MDD) in adults. (1) (2)

    DOSAGE AND ADMINISTRATION

    • Starting dose: 15-mg once daily; may increase up to maximum recommended dose of 45 mg
    once daily. (2.1)
    • Administer orally once daily, preferably in the evening prior to sleep. (2.1)
    • Reduce dose gradually when discontinuing mirtazapine tablets. (2.6, 5.13) (3)

    DOSAGE FORMS AND STRENGTHS

    • Tablets: 15 mg scored and 30 mg scored. (3) (4)

    CONTRAINDICATIONS

    • Concomitant use of monoamine oxidase inhibitors (MAOIs) or use within 14 days of stopping
    MAOIs. (2.4, 4,7)
    • Known hypersensitivity to mirtazapine or any of the excipients in mirtazapine tablets. (4) (5)

    WARNINGS AND PRECAUTIONS

    • Agranulocytosis: If sore throat, fever, stomatitis or signs of infection occur, along with a low
    white blood cell count, treatment with mirtazapine tablets should be discontinued and the
    patient should be closely monitored. (5.2)
    • Serotonin Syndrome: Increased risk when co-administered with other serotonergic drugs (e.g.,
    SSRI, SNRI, triptans), but also when taken alone. If it occurs, discontinue mirtazapine tablets and
    initiate supportive treatment. (2.4, 4, 5.3, 7)
    • Angle-Closure Glaucoma: Angle closure glaucoma has occurred in patients with untreated
    anatomically narrow angles treated with antidepressants. (5.4) (6)

    • QT Prolongation: Use mirtazapine tablets with caution in patients with risk factors for QT
    prolongation. (5.5, 7)
    • Increased Appetite/Weight Gain: Mirtazapine tablets have been associated with increased
    appetite and weight gain. (5.6)
    • Somnolence: May impair judgment, thinking and/or motor skills. Use with caution when
    engaging in activities requiring alertness, such as driving or operating machinery. (5.7, 7)
    • Activation of Mania/Hypomania: Screen patients for bipolar disorder prior to initiating treatment.
    (2.3, 5.8)
    • Seizures: Use with caution in patients with a seizure disorder. (5.9)
    • Elevated Cholesterol/Triglycerides: Has been reported with mirtazapine tablet use. (5.10)
    • Hyponatremia: May occur as a result of treatment with serotonergic antidepressants, including
    mirtazapine tablets. (5.11)
    • Transaminase Elevations: Clinically significant elevations have occurred. Use with caution in
    patients with impaired hepatic function. (5.12) (6)

    ADVERSE REACTIONS

    Most common adverse reactions ((≥5% or greater and twice placebo) were somnolence, increased
    appetite, weight gain, and dizziness. (6.1)
    To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at, at 1-800-706-5575 or
    FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
    (7)

    DRUG INTERACTIONS

    • Strong CYP3A inducers: Dosage increase may be needed for mirtazapine tablets with
    concomitant use of strong CYP3A inducers. (2.5, 7)
    • Strong CYP3A inhibitors: Dosage decrease may be needed when mirtazapine tablets are
    coadministered with strong CYP3A inhibitors. (2.5, 7)
    • Cimetidine: Dosage decrease may be needed when mirtazapine tablets are coadministered with
    cimetidine. (2.5, 7)
    • Warfarin: Monitor INR during concomitant use. (7) (8)

    USE IN SPECIFIC POPULATIONS

    • Geriatric Use: Use with caution in elderly patients. (5.11, 5.14, 8.5)
    • Renal impairment: Dosage decrease may be needed in patients with moderate to severe renal
    impairment. (8.6)
    • Hepatic impairment: Dosage decrease may be needed in patients with hepatic impairment. (8.6) (9)


    See 17 for PATIENT COUNSELING INFORMATION and Medication Guide (9)


    Revised: 11/2020 (9)

    See 17 for Medication Guide.

    Revised: 3/2021

  • Table of Contents

    FULL PRESCRIBING INFORMATION: CONTENTS*

    1 INDICATIONS AND USAGE

    2 DOSAGE AND ADMINISTRATION

    2.1 Recommended Dosage

    2.3 Screen for Bipolar Disorder Prior to Starting Mirtazapine Tablets

    2.4 Switching Patients to or from a Monoamine Oxidase Inhibitor Antidepressant

    2.5 Dosage Modifications Due to Drug Interactions

    2.6 Discontinuation of Mirtazapine Tablets Treatment

    3 DOSAGE FORMS AND STRENGTHS

    4 CONTRAINDICATIONS

    5 WARNINGS AND PRECAUTIONS

    5.1 Suicidal Thoughts and Behaviors in Adolescents and Young Adults

    5.2 Agranulocytosis

    5.3 Serotonin Syndrome

    5.4 Angle-closure Glaucoma

    5.5 QT Prolongation and Torsades de Pointes

    5.6 Increased Appetite and Weight Gain

    5.7 Somnolence

    5.8 Activation of Mania or Hypomania

    5.9 Seizures

    5.10 Elevated Cholesterol and Triglycerides

    5.11 Hyponatremia

    5.12 Transaminase Elevations

    5.13 Discontinuation Syndrome

    5.14 Use in Patients with Concomitant Illness

    6 ADVERSE REACTIONS

    6.1 Clinical Trial Experience

    ECG Changes

    Other Adverse Events Observed During the Premarketing Evaluation of Mirtazapine Tablets

    6.2 Postmarketing Experience

    7 DRUG INTERACTIONS

    8 USE IN SPECIFIC POPULATIONS

    8.1 Pregnancy

    8.2 Lactation

    8.4 Pediatric Use

    8.5 Geriatric Use

    8.6 Renal or Hepatic Impairment

    10 OVERDOSAGE

    Human Experience

    Overdose Management

    11 DESCRIPTION

    12 CLINICAL PHARMACOLOGY

    12.1 Mechanism of Action

    12.2 Pharmacodynamics

    12.3 Pharmacokinetics

    13 NONCLINICAL TOXICOLOGY

    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

    14 CLINICAL STUDIES

    16 HOW SUPPLIED/STORAGE AND HANDLING

    *
    Sections or subsections omitted from the full prescribing information are not listed.
  • SPL UNCLASSIFIED SECTION

    WARNING: SUICIDAL THOUGHTS AND BEHAVIORS
    Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and
    young adult patients in short-term studies. Closely monitor all antidepressant-treated
    patients for clinical worsening, and for emergence of suicidal thoughts and behaviors [see
    Warnings and Precautions (5.1)]. Mirtazapine tablets are not approved for use in pediatric
    patients [see Use in Specific Populations (8.4)].

  • 1 INDICATIONS AND USAGE

    Mirtazapine Tablets are indicated for the treatment of major depressive disorder (MDD) in adults
    [see Clinical Studies (14)].

  • 2 DOSAGE AND ADMINISTRATION

    2.1 Recommended Dosage

    The recommended starting dose for mirtazapine tablets is 15 mg once daily, administered orally,
    preferably in the evening prior to sleep. If patients do not have an adequate response to the initial
    15 mg dose, increase the dose up to a maximum of 45 mg per day. Dose changes should not be
    made in intervals of less than 1 to 2 weeks to allow sufficient time for evaluation of response to a
    given dose [see Clinical Pharmacology (12.3)].

    2.3 Screen for Bipolar Disorder Prior to Starting Mirtazapine Tablets

    Prior to initiating treatment with mirtazapine tablets or another antidepressant, screen patients for a
    personal or family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions
    (5.8)].

    2.4 Switching Patients to or from a Monoamine Oxidase Inhibitor Antidepressant

    At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI)
    antidepressant and initiation of mirtazapine tablets. In addition, at least 14 days must elapse after
    stopping mirtazapine tablets before starting an MAOI antidepressant [see Contraindications (4) and
    Warnings and Precautions (5.3)].

    2.5 Dosage Modifications Due to Drug Interactions

    Strong CYP3A Inducers
    An increase in dosage of mirtazapine tablets may be needed with concomitant strong CYP3A
    inducer (e.g., carbamazepine, phenytoin, rifampin) use. Conversely, a decrease in dosage of
    mirtazapine tablets may be needed if the CYP3A inducer is discontinued [see Drug Interactions (7)].
    Strong CYP3A Inhibitors
    A decrease in dosage of mirtazapine tablets may be needed with concomitant use of strong
    CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin). Conversely, an increase in dosage of
    mirtazapine tablets may be needed if the CYP3A inhibitor is discontinued [see Drug Interactions (7)].
    Cimetidine
    A decrease in dosage of mirtazapine tablets may be needed with concomitant use of cimetidine.
    Conversely, an increase in dosage of mirtazapine tablets may be needed if cimetidine is
    discontinued [see Drug Interactions (7)].

    2.6 Discontinuation of Mirtazapine Tablets Treatment

    Adverse reactions may occur upon discontinuation or dose reduction of mirtazapine tablets [see
    Warnings and Precautions (5.13)]. Gradually reduce the dosage of mirtazapine tablets rather than
    stopping abruptly whenever possible.

  • 3 DOSAGE FORMS AND STRENGTHS

    Mirtazapine Tablets, USP 15 mg are available for oral administration as pale yellow, oval-shaped,
    scored, film-coated tablets imprinted "APO" on one side and "MI" bisect "15" on the other side.
    Mirtazapine Tablets, USP 30 mg are available for oral administration as light pink, oval-shaped,
    scored, film-coated tablets imprinted "APO" on one side and "MI" bisect "30" on the other side.

  • 4 CONTRAINDICATIONS

    Mirtazapine tablets are contraindicated in patients:
    • Taking, or within 14 days of stopping, MAOIs (including the MAOIs linezolid and intravenous
    methylene blue) because of an increased risk of serotonin syndrome [see Warnings and
    Precautions (5.3), Drug Interactions (7)].
    • With a known hypersensitivity to mirtazapine or to any of the excipients in mirtazapine tablets.
    Severe skin reactions, including Stevens-Johnson syndrome, bullous dermatitis, erythema
    multiforme and toxic epidermal necrolysis have been reported following the use of mirtazapine
    tablets [see Adverse Reactions (6.2)].

  • 5 WARNINGS AND PRECAUTIONS

    5.1 Suicidal Thoughts and Behaviors in Adolescents and Young Adults

    In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other
    antidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatric
    patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24
    years and younger was greater than in placebo-treated patients. There was considerable variation
    in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in
    young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts
    and behaviors across the different indications, with the highest incidence in patients with MDD. The
    drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1000
    patients treated are provided in Table 1.

    Table 1: Risk Differences of the Number of Patients with Suicidal Thoughts and Behavior in
    the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients
    Age RangeDrug-placebo Difference in Number of Patients with Suicidal Thoughts and Behaviour in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients
    Increases Compared to Placebo
    <18 years old14 additional patients
    18 to 24 years old5 additional patients
    Decreases Compared to Placebo
    25 to 64 years old1 fewer patients
    ≥65 years old6 fewer patients

    It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and young
    adults extends to longer-term use, i.e., beyond four months. However, there is substantial evidence
    from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the
    recurrence of depression and that depression itself is a risk factor for suicidal thoughts and behaviors.

    Monitor all antidepressant-treated patients for any indication of clinical worsening and emergence
    of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, and at

    times of dosage changes. Counsel family members or caregivers of patients to monitor for changes
    in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen,
    including possibly discontinuing mirtazapine tablets, in patients whose depression is persistently
    worse, or who are experiencing emergent suicidal thoughts or behaviors.

    5.2 Agranulocytosis

    In premarketing clinical trials, 2 (1 with Sjögren’s Syndrome) out of 2796 patients treated with
    mirtazapine tablets developed agranulocytosis [absolute neutrophil count (ANC) <500/mm3 with
    associated signs and symptoms, e.g., fever, infection, etc.] and a third patient developed severe
    neutropenia (ANC <500/mm3 without any associated symptoms). For these 3 patients, onset of
    severe neutropenia was detected on days 61, 9, and 14 of treatment, respectively. All 3 patients
    recovered after mirtazapine tablets were stopped. If a patient develops a sore throat, fever,
    stomatitis, or other signs of infection, along with a low white blood cell (WBC) count, treatment with
    mirtazapine tablets should be discontinued and the patient should be closely monitored.

    5.3 Serotonin Syndrome

    Serotonergic antidepressants, including mirtazapine tablets, can precipitate serotonin syndrome, a
    potentially life-threatening condition. The risk is increased with concomitant use of other
    serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol,
    tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism
    of serotonin, i.e., MAOIs [see Contraindications (4), Drug Interactions (7)]. Serotonin syndrome can
    also occur when these drugs are used alone.
    Serotonin syndrome signs and 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 gastrointestinal symptoms (e.g., nausea,
    vomiting, diarrhea).
    The concomitant use of mirtazapine tablets with MAOIs is contraindicated. In addition, do not
    initiate mirtazapine tablets in a patient being treated with MAOIs such as linezolid or intravenous
    methylene blue. No reports involved the administration of methylene blue by other routes (such as
    oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as
    linezolid or intravenous methylene blue in a patient taking mirtazapine tablets, discontinue
    mirtazapine tablets before initiating treatment with the MAOI [see Contraindications (4), Drug
    Interactions (7)].
    Monitor all patients taking mirtazapine tablets for the emergence of serotonin syndrome.
    Discontinue treatment with mirtazapine tablets and any concomitant serotonergic agents
    immediately if the above symptoms occur and initiate supportive symptomatic treatment. If
    concomitant use of mirtazapine tablets with other serotonergic drugs is clinically warranted, inform
    patients of the increased risk for serotonin syndrome and monitor for symptoms.

    5.4 Angle-closure Glaucoma

    The pupillary dilation that occurs following use of many antidepressant drugs, including mirtazapine
    tablets, may trigger an angle-closure attack in a patient with anatomically narrow angles who does
    not have a patent iridectomy.

    5.5 QT Prolongation and Torsades de Pointes

    The effect of mirtazapine tablets on QTc interval was assessed in a clinical randomized trial with
    placebo and positive (moxifloxacin) controls involving 54 healthy volunteers using exposure
    response analysis. This trial showed a positive relationship between mirtazapine concentrations and
    prolongation of the QTc interval. However, the degree of QT prolongation observed with both 45 mg
    and 75 mg (1.67 times the maximum recommended daily dose) doses of mirtazapine was not at a
    level generally considered to be clinically meaningful. During postmarketing use of mirtazapine,
    cases of QT prolongation, Torsades de Pointes, ventricular tachycardia, and sudden death, have
    been reported [see Adverse Reactions (6.1, 6.2)]. The majority of reports occurred in association
    with overdose or in patients with other risk factors for QT prolongation, including concomitant use
    of QTc-prolonging medicines [see Drug Interactions (7) and Overdosage (10)]. Exercise caution
    when mirtazapine tablets is prescribed in patients with known cardiovascular disease or family
    history of QT prolongation, and in concomitant use with other drugs thought to prolong the QTc
    interval.

    5.6 Increased Appetite and Weight Gain

    In U.S. controlled clinical studies, appetite increase was reported in 17% of patients treated with
    mirtazapine tablets, compared to 2% for placebo. In these same trials, weight gain of ≥7% of body
    weight was reported in 7.5% of patients treated with mirtazapine, compared to 0% for placebo. In a
    pool of premarketing U.S. clinical studies, including many patients for long-term, open-label
    treatment, 8% of patients receiving mirtazapine tablets discontinued for weight gain.
    In an 8-week-long pediatric clinical trial of doses between 15 to 45 mg/day, 49% of mirtazapine
    tablets-treated pediatric patients had a weight gain of at least 7%, compared to 5.7% of
    placebo-treated patients. The safety and effectiveness of mirtazapine tablets in pediatric patients
    with MDD have not been established [see Use in Specific Populations (8.4)].

    5.7 Somnolence

    In U.S. controlled studies, somnolence was reported in 54% of patients treated with mirtazapine
    tablets, compared to 18% for placebo. In these studies, somnolence resulted in discontinuation for
    10.4% of mirtazapine tablets-treated patients, compared to 2.2% for placebo. It is unclear whether
    tolerance develops to the somnolent effects of mirtazapine tablets. Because of the potentially
    significant effects of mirtazapine tablets on impairment of performance, caution patients about
    engaging in activities that require alertness, including operating hazardous machinery and motor
    vehicles, until they are reasonably certain that mirtazapine does not affect them adversely. The
    concomitant use of benzodiazepines and alcohol with mirtazapine tablets should be avoided [see
    Drug Interactions (7)].

    5.8 Activation of Mania or Hypomania

    In patients with bipolar disorder, treating a depressive episode with mirtazapine tablets or another
    antidepressant may precipitate a mixed/manic episode. In controlled clinical trials, patients with
    bipolar disorder were generally excluded; however, symptoms of mania or hypomania were
    reported in 0.2% of patients treated with mirtazapine tablets. Prior to initiating treatment with
    mirtazapine tablets, screen patients for any personal or family history of bipolar disorder, mania, or
    hypomania.

    5.9 Seizures

    Mirtazapine tablets have not been systematically evaluated in patients with seizure disorders. In
    premarketing clinical trials, 1 seizure was reported among the 2796 U.S. and non-U.S. patients
    treated with mirtazapine tablets. Mirtazapine tablets should be prescribed with caution in patients
    with a seizure disorder.

    5.10 Elevated Cholesterol and Triglycerides

    In U.S. controlled studies, nonfasting cholesterol increases to ≥20% above the upper limits of
    normal were observed in 15% of patients treated with mirtazapine tablets, compared to 7% for
    placebo. In these same studies, nonfasting triglyceride increases to ≥500 mg/dL were observed in
    6% of patients treated with mirtazapine tablets, compared to 3% for placebo.

    5.11 Hyponatremia

    Hyponatremia may occur as a result of treatment with serotonergic antidepressants, including
    mirtazapine tablets. Cases with serum sodium lower than 110 mmol/L have been reported.


    Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory
    impairment, confusion, weakness, and unsteadiness, which may lead to falls. Signs and symptoms
    associated with more severe or acute cases have included hallucination, syncope, seizure, coma,
    respiratory arrest, and death. In many cases, this hyponatremia appears to be the result of the
    syndrome of inappropriate antidiuretic hormone secretion (SIADH).


    In patients with symptomatic hyponatremia, discontinue mirtazapine tablets and institute
    appropriate medical intervention. Elderly patients, patients taking diuretics, and those who are
    volume- depleted may be at greater risk of developing hyponatremia [see Use in Specific
    Populations (8.5)].

    5.12 Transaminase Elevations

    Clinically significant ALT (SGPT) elevations ((≥3 times the upper limit of the normal range) were
    observed in 2.0% (8/424) of patients treated with mirtazapine tablets in a pool of short-term, U.S.
    controlled trials, compared to 0.3% (1/328) of placebo patients. While some patients were
    discontinued for the ALT increases, in other cases, the enzyme levels returned to normal despite
    continued mirtazapine treatment. Mirtazapine tablets should be used with caution in patients with
    impaired hepatic function [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

    5.13 Discontinuation Syndrome

    There have been reports of adverse reactions upon the discontinuation of mirtazapine tablets
    (particularly when abrupt), including but not limited to the following: dizziness, abnormal dreams,
    sensory disturbances (including paresthesia and electric shock sensations), agitation, anxiety,
    fatigue, confusion, headache, tremor, nausea, vomiting, and sweating, or other symptoms which
    may be of clinical significance.
    A gradual reduction in the dosage, rather than an abrupt cessation, is recommended [see Dosage
    and Administration (2.6)].

    5.14 Use in Patients with Concomitant Illness

    Mirtazapine tablets have not been systematically evaluated or used to any appreciable extent in
    patients with a recent history of myocardial infarction or other significant heart disease. Mirtazapine
    tablets were associated with significant orthostatic hypotension in early clinical pharmacology trials
    with normal volunteers. Orthostatic hypotension was infrequently observed in clinical trials with
    depressed patients [see Adverse Reactions (6.1)]. Mirtazapine tablets 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).

  • 6 ADVERSE REACTIONS

    The following adverse reactions are described in more detail in other sections of the prescribing
    information:
    • Hypersensitivity [see Contraindications (4)]
    • Suicidal Thoughts and Behaviors [see Warnings and Precautions (5.1)]
    • Agranulocytosis [see Warnings and Precautions (5.2)]
    • Serotonin Syndrome [see Contraindications (4), Warnings and Precautions (5.3), Drug
    Interactions (7)]
    • Angle-Closure Glaucoma [see Warnings and Precautions (5.4)]
    • QT Prolongation and Torsades de Pointes [see Warnings and Precautions (5.5)]
    • Increased Appetite and Weight Gain [see Warnings and Precautions (5.6)]
    • Somnolence [see Warnings and Precautions (5.7)]
    • Activation of Mania or Hypomania [see Warnings and Precautions (5.8)]
    • Seizures [see Warnings and Precautions (5.9)]
    • Elevated Cholesterol and Triglycerides [see Warnings and Precautions (5.10)]
    • Hyponatremia [see Warnings and Precautions (5.11)]
    • Transaminase Elevations [see Warnings and Precautions (5.12)]
    • Discontinuation Syndrome [see Warnings and Precautions (5.13)]
    • Use in Patients with Concomitant Illness [see Warnings and Precautions (5.14)]

    6.1 Clinical Trial Experience

    Because clinical trials are conducted under widely varying conditions, adverse reaction rates
    observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of
    another drug and may not reflect the rates observed in practice.
    The data described below are from clinical trials in which mirtazapine tablets were administered to
    2796 patients in phase 2 and 3 clinical studies. The trials consisted of double-blind controlled and
    open-label studies, inpatient and outpatient studies, fixed dose, and titration studies.
    Adverse Reactions Leading to Discontinuation of Treatment
    Approximately 16% of the 453 patients who received mirtazapine tablets in US 6-week
    placebo-controlled clinical trials discontinued treatment due to an adverse reaction, compared to
    7% of the 361 placebo-treated patients in those studies. The most common reactions leading to
    discontinuation (>= and at a rate at least twice that of placebo) are included in Table 2.

    Table 2 : Adverse Reactions (≥1% and at least twice placebo) Leading to Discontinuation of Mirtazapine in 6-Week Clinical Trials in Patients with MDD

    Mirtazapine Tablets
    (n=453
    )
    Placebo
    (n=3
    61)
    Somnolence10.4%2.2%
    Nausea1.5%0%

    Common Adverse Reactions

    The most common adverse reactions (≥5% and twice placebo) associated with the use of
    mirtazapine tablets are listed in Table 3.

    Table 3: Adverse Reactions (≥5% and twice placebo) in 6-Week U.S. Clinical Trials of
    Mirtazapine in Patients with MDD

    Mirtazapine Tablets
    (n=453)
    Placebo
    (n=3 61)
    Somnolence54%18%
    Increased Appetite17%2%
    Weight Gain12%2%
    Dizziness7%3%

    Table 4 enumerates adverse reactions that occurred in ≥1% of mirtazapine tablets-treated patients
    and were more frequent than the placebo-treated patients, who participated in 6-week, U.S.
    placebo-controlled trials in which patients were dosed in a range of 5 to 60 mg/day. This table
    shows the percentage of patients in each group who had at least 1 episode of an adverse reaction
    at some time during their treatment.

    Table 4:Adverse Reactions (≥1% and greater than placebo) in 6-Week U.S. Clinical Studies
    of Mirtazapine in Patients with MDD
    Mirtazapine Tablets
    (n=453)
    Placebo
    (n=361)
    Body as a Whole
    Asthenia8%5%
    Flu Syndrome5%3%
    Back Pain2%1%
    Digestive System
    Dry Mouth25%15%
    Increased Appetite17%2%
    Constipation13%7%
    Metabolic and Nutritional Disorders
    Weight Gain12%2%
    Peripheral Edema2%1%
    Edema1%0%
    Musculoskeletal System
    Myalgia2%1%
    Nervous System
    Somnolence54%18%
    Dizziness7%3%
    Abnormal Dreams4%1%
    Thinking Abnormal3%1%
    Tremor2%1%
    Confusion2%0%
    Respiratory System
    Dyspnea1%0%
    Urogenital System
    Urinary Frequency2%1%

    ECG Changes

    The electrocardiograms for 338 patients who received mirtazapine tablets and 261 patients who
    received placebo in 6-week, placebo-controlled trials were analyzed. Mirtazapine tablets was
    associated with a mean increase in heart rate of 3.4 bpm, compared to 0.8 bpm for placebo. The
    clinical significance of these changes is unknown.

    Other Adverse Events Observed During the Premarketing Evaluation of Mirtazapine Tablets

    The following list does not include reactions: 1) already listed in previous tables or elsewhere in
    labeling, 2) for which a drug cause was remote, 3) which were so general or excessively specific so
    as to be uninformative, 4) which were not considered to have significant clinical implications, or 5)
    which occurred at a rate equal to or less than placebo.
    Adverse reactions are categorized by body system according to the following definitions: frequent
    adverse reactions are those occurring in at least 1/100 patients; infrequent adverse reactions are
    those occurring in 1/100 to 1/1000 patients; rare adverse reactions are those occurring in fewer
    than 1/1000 patient.

    Body as a Whole

    Frequent: malaise, abdominal pain, abdominal syndrome acute; infrequent: chills, fever, face edema, ulcer, photosensitivity reaction, neck rigidity, neck pain, abdomen enlarged; rare: cellulitis, chest pain substernal.

    Cardiovascular System

    Frequent: hypertension, vasodilatation; infrequent: angina pectoris, myocardial infarction, bradycardia, ventricular extrasystoles, syncope, migraine, hypotension; rare: atrial arrhythmia, bigeminy, vascular headache, pulmonary embolus, cerebral ischemia, cardiomegaly, phlebitis, left heart failure.

    Digestive System

    Frequent: vomiting, anorexia; infrequent: eructation, glossitis, cholecystitis, nausea and vomiting, gum hemorrhage, stomatitis, colitis, liver function tests abnormal; rare: tongue discoloration, ulcerative stomatitis, salivary gland enlargement, increased salivation, intestinal obstruction, pancreatitis, aphthous stomatitis, cirrhosis of liver, gastritis, gastroenteritis, oral moniliasis, tongue edema.

    Endocrine System

    Rare: goiter, hypothyroidism.

    Hemic and Lymphatic System

    Rare: lymphadenopathy, leukopenia, petechia, anemia, thrombocytopenia, lymphocytosis, pancytopenia.

    Metabolic and Nutritional Disorders

    Frequent: thirst; infrequent: dehydration, weight loss; rare: gout, SGOT increased, healing abnormal, acid phosphatase increased, SGPT increased, diabetes mellitus, hyponatremia.

    Musculoskeletal System

    Frequent: myasthenia, arthralgia; infrequent: arthritis, tenosynovitis; rare: pathologic fracture, osteoporosis fracture, bone pain, myositis, tendon rupture, arthrosis, bursitis.

    Nervous System

    Frequent: hypesthesia, apathy, depression, hypokinesia, vertigo, twitching, agitation, anxiety, amnesia, hyperkinesia, paresthesia; infrequent: ataxia, delirium, delusions, depersonalization, dyskinesia, extrapyramidal syndrome, libido increased, coordination abnormal, dysarthria, hallucinations, manic reaction, neurosis, dystonia, hostility, reflexes increased, emotional lability, euphoria, paranoid reaction; rare: aphasia, nystagmus, akathisia (psychomotor restlessness), stupor, dementia, diplopia, drug dependence, paralysis, grand mal convulsion, hypotonia, myoclonus, psychotic depression, withdrawal syndrome, serotonin syndrome.

    Respiratory System

    Frequent: cough increased, sinusitis; infrequent: epistaxis, bronchitis, asthma, pneumonia; rare: asphyxia, laryngitis, pneumothorax, hiccup.

    Skin and Appendages

    Frequent: pruritus, rash; infrequent: acne, exfoliative dermatitis, dry skin, herpes simplex, alopecia; rare: urticaria, herpes zoster, skin hypertrophy, seborrhea, skin ulcer.

    Special Senses

    Infrequent: eye pain, abnormality of accommodation, conjunctivitis, deafness, keratoconjunctivitis, lacrimation disorder, angle-closure glaucoma, hyperacusis, ear pain; rare: blepharitis, partial transitory deafness, otitis media, taste loss, parosmia.

    Urogenital System

    Frequent: urinary tract infection; infrequent: kidney calculus, cystitis, dysuria, urinary incontinence, urinary retention, vaginitis, hematuria, breast pain, amenorrhea, dysmenorrhea, leukorrhea, impotence; rare: polyuria, urethritis, metrorrhagia, menorrhagia, abnormal ejaculation, breast engorgement, breast enlargement, urinary urgency.

    6.2 Postmarketing Experience

    The following adverse reactions have been identified during post-approval use of mirtazapine
    tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is
    not always possible to reliably estimate their frequency or establish a causal relationship to drug
    exposure.
    Cardiac disorders: ventricular arrhythmia (Torsades de Pointes)
    Endocrine disorders: hyperprolactinemia (and related symptoms, e.g., galactorrhea and
    gynecomastia)
    Musculoskeletal and connective tissue disorders: increased creatine kinase blood levels and
    rhabdomyolysis
    Psychiatric disorders: somnambulism (ambulation and other complex behaviors out of bed)
    Reproductive system and breast disorder: priapism
    Skin and subcutaneous tissue disorders: severe skin reactions, including Stevens-Johnson
    syndrome, bullous dermatitis, erythema multiforme and toxic epidermal necrolysis

  • 7 DRUG INTERACTIONS

    Table 5 includes clinically important drug interactions with Mirtazapine Tablets [see Clinical

    Pharmacology (12.3)].

    Table 5: Clinically Important Drug Interactions with Mirtazapine Tablets
    Monoamine Oxidase Inhibitors (MAOIs)
    Clinical ImpactThe concomitant use of serotonergic drugs, including Mirtazapine Tablets, and
    MAOIs increases the risk of serotonin syndrome.
    InterventionMirtazapine tablets are contraindicated in patients taking MAOIs, including
    MAOIs such as linezolid or intravenous methylene blue [see Dosage and
    Administration (2.4), Contraindications (4), Warnings and Precautions (5.3)]
    Examplesselegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue
    Other Serotonergic Drugs
    Clinical ImpactThe concomitant use of serotonergic drugs with mirtazapine tablets increases
    the risk of serotonin syndrome.
    InterventionMonitor patients for signs and symptoms of serotonin syndrome, particularly
    during treatment initiation and dosage increases. If serotonin syndrome occurs,
    consider discontinuation of mirtazapine tablets and/or concomitant serotonergic
    drugs [see Warnings and Precautions (5.3)]
    ExamplesSSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, amphetamines,
    St. John’s Wort, tramadol, tryptophan, buspirone
    Strong CYP3A Inducers
    Clinical ImpactThe concomitant use of strong CYP3A inducers with mirtazapine tablets
    decreases the plasma concentration of mirtazapine [see Clinical Pharmacology
    (12.3)].
    InterventionIncrease the dose of mirtazapine tablets if needed with concomitant CYP3A
    inducer use. Conversely, a decrease in dosage of Mirtazapine Tablets may be
    needed if the CYP3A inducer is discontinued [see Dosage and Administration
    (2.5)].
    Examplesphenytoin, carbamazepine, rifampin
    Strong CYP3A Inhibitors
    Clinical ImpactThe concomitant use of strong CYP3A inhibitors with mirtazapine tablets may
    increase the plasma concentration of mirtazapine [see Clinical Pharmacology
    (12.3)].
    InterventionDecrease the dose of mirtazapine tablets if needed with concomitant strong
    CYP3A inhibitor use. Conversely, an increase in dosage of mirtazapine tablets
    may be needed if the CYP3A inhibitor is discontinued [see Dosage and
    Administration (2.5)].
    Examplesitraconazole, ritonavir, nefazodone
    Cimetidine
    Clinical ImpactThe concomitant use of cimetidine, a CYP1A2, CYP2D6, and CYP3A inhibitor, with
    mirtazapine tablets may increase the plasma concentration of mirtazapine [see
    Clinical Pharmacology (12.3)]
    InterventionDecrease the dose of mirtazapine tablets if needed with concomitant cimetidine
    use. Conversely, an increase in dosage of mirtazapine tablets may be needed if
    cimetidine is discontinued [see Dosage and Administration (2.5)].
    Benzodiazepines and Alcohol
    Clinical ImpactThe concomitant use of benzodiazepines or alcohol with mirtazapine tablets
    increases the impairment of cognitive and motor skills produced by mirtazapine
    tablets alone.
    InterventionAvoid concomitant use of benzodiazepines and alcohol with mirtazapine tablets
    [see Warnings and Precautions (5.7), Clinical Pharmacology (12.3)].
    Examplesdiazepam, alprazolam, alcohol
    Drugs that Prolong QTc Interval
    Clinical ImpactThe concomitant use of other drugs which prolong the QTc interval with
    mirtazapine tablets, increase the risk of QT prolongation and/or ventricular
    arrhythmias (e.g., Torsades de Pointes).
    InterventionUse caution when using mirtazapine tablets concomitantly with drugs that
    prolong the QTc interval [see Warnings and Precautions (5.5), Clinical
    Pharmacology (12.3)].
    Warfarin
    Clinical ImpactThe concomitant use of warfarin with mirtazapine tablets may result in an
    increase in INR [see Clinical Pharmacology (12.3)].
    InterventionMonitor INR during concomitant use of warfarin with mirtazapine tablets

  • 8 USE IN SPECIFIC POPULATIONS

    8.1 Pregnancy

    Pregnancy Exposure Registry
    There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to
    antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling
    the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at
    https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/.
    Risk Summary
    Prolonged experience with mirtazapine in pregnant women, based on published observational
    studies and postmarketing reports, has not reliably identified a drug-associated risk of major birth
    defects, miscarriage or adverse maternal or fetal outcomes. There are risks associated with
    untreated depression in pregnancy (see Clinical Considerations).
    In animal reproduction studies, oral administration of mirtazapine to pregnant rats and rabbits
    during the period of organogenesis revealed no evidence of teratogenic effects up to 20 and 17
    times the maximum recommended human dose (MRHD) of 45 mg, respectively, based on mg/m2
    body surface area. However, in rats, there was an increase in post implantation loss at 20 times the
    MRHD based on mg/m2 body surface area. Oral administration of mirtazapine to pregnant rats
    during pregnancy and lactation resulted in an increase in pup deaths and a decrease in pup birth
    weights at doses 20 times the MRHD based on mg/m2 body surface area (see Data).
    The estimated background risk of major birth defects and miscarriage for the indicated population
    is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse
    outcomes. In the U.S. general population, the estimated background risk of major birth defects and
    miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

    Clinical Considerations
    Disease-Associated Maternal and/or Embryo/Fetal Risk
    Women who discontinue antidepressants during pregnancy are more likely to experience a relapse
    of major depression than women who continue antidepressants. This finding is from a prospective,
    longitudinal study that followed 201 pregnant women with a history of major depressive disorder
    who were euthymic and taking antidepressants at the beginning of pregnancy. Consider the risk of
    untreated depression when discontinuing or changing treatment with antidepressant medication
    during pregnancy and postpartum.

    Data
    Animal Data
    Mirtazapine was administered orally to pregnant rats and rabbits during the period of
    organogenesis at doses of 2.5, 15, and 100 mg/kg/day and 2.5, 10, and 40 mg/kg/day,
    respectively, which are up to 20 and 17 times the maximum recommended human dose (MRHD) of
    45 mg based on mg/m2 body surface area, respectively. No evidence of teratogenic effects was
    observed. However, in rats, there was an increase in post implantation loss in dams treated with
    mirtazapine at 100 mg/kg/day which is 20 times the MRHD based on mg/m2 body surface area.
    Oral administration of mirtazapine at doses of 2.5, 15, and 100mg/kg/day to pregnant rats during
    pregnancy and lactation resulted in an increase in pup deaths during the first 3 days of lactation
    and a decrease in pup birth weights at 20 times the MRHD based on mg/m2 body surface area. The
    cause of these deaths is not known. The no effect dose level is 3 times the MRHD based on mg/m2
    body surface area.

    8.2 Lactation

    Risk Summary
    Data from published literature report the presence of mirtazapine in human milk at low levels with
    relative infant doses for mirtazapine ranging between 0.6 and 2.8% of the maternal
    weight-adjusted dose (see Data). No adverse effects on the breastfed infant have been reported in
    most cases of maternal use of mirtazapine. There are no data on the effects of mirtazapine on milk
    production.
    The developmental and health benefits of breastfeeding should be considered along with the
    mother’s clinical need for mirtazapine and any potential adverse effects on the breastfed infant
    from mirtazapine or from the underlying maternal condition.
    Data
    In a published pooled analysis of 8 breastfeeding mother-infant pairs, the mean (min, max) total
    relative infant doses for mirtazapine and its desmethyl metabolite were 1.5% (0.6%, 2.8%) and
    0.4% (0.1%, 0.7%) of the maternal weight-adjusted dose (median (min, max) dose of 38 mg
    (30 mg, 120 mg), respectively). No adverse drug effects were reported for any of the infants.

    8.4 Pediatric Use

    The safety and effectiveness of mirtazapine tablets have not been established in pediatric patients
    with MDD. Two placebo-controlled trials in 258 pediatric patients with MDD have been conducted
    with mirtazapine tablets, and the data were insufficient to establish the safety and effectiveness of
    mirtazapine tablets in pediatric patients with MDD.
    Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients [see
    Boxed Warning and Warnings and Precautions (5.1)].
    In an 8-week-long clinical trial in pediatric patients receiving doses between 15 to 45 mg per day,
    49% of mirtazapine tablets-treated patients had a weight gain of at least 7%, compared to 5.7% of
    placebo- treated patients. The mean increase in weight was 4 kg (2 kg SD) for mirtazapine
    tablets-treated patients versus 1 kg (2 kg SD) for placebo-treated patients [see Warnings and
    Precautions (5.6)].

    8.5 Geriatric Use

    Approximately 190 patients≥ 65 years of age participated in clinical studies with mirtazapine
    tablets. Mirtazapine tablets are known to be substantially excreted by the kidney (75%), and the
    risk of decreased clearance of this drug is greater in patients with impaired renal function.
    Pharmacokinetic studies revealed a decreased clearance of mirtazapine in the elderly [see Clinical
    Pharmacology (12.3)]
    Sedating drugs, including mirtazapine tablets, may cause confusion and over-sedation in the
    elderly. Elderly patients may be at greater risk of developing hyponatremia. Caution is indicated
    when administering mirtazapine tablets to elderly patients [see Warnings and Precautions (5.11),
    (5.14) and Clinical Pharmacology (12.3)]. In general, dose selection for an elderly patient should be
    conservative, usually starting at the low end of the dosing range, reflecting the greater frequency of
    decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

    8.6 Renal or Hepatic Impairment

    The clearance of mirtazapine is reduced in patients with moderate to severe renal or hepatic
    impairment. Consequently, plasma mirtazapine levels may be increased in these patient groups,
    compared to levels observed in patients without renal or hepatic impairment. Dosage decrease may
    be necessary when administering mirtazapine tablets to patients with moderate to severe renal or
    hepatic impairment [see Warnings and Precautions (5.12), Use in Specific Populations (8.5), and
    Clinical Pharmacology (12.3)].

  • 10 OVERDOSAGE

    Human Experience

    In premarketing clinical studies, there were reports of mirtazapine tablets overdose alone or in
    combination with other pharmacological agents. Signs and symptoms reported in association with
    overdose included disorientation, drowsiness, impaired memory, and tachycardia.
    Based on postmarketing reports, serious outcomes (including fatalities) may occur at dosages
    higher than the recommended doses, especially with mixed overdoses. In these cases, QT
    prolongation and Torsades de Pointes have also been reported [see Warnings and Precautions (5.5),
    Adverse Reactions (6.2), and Drug Interactions (7)].

    Overdose Management

    No specific antidotes for mirtazapine are known.
    Contact Poison Control (1-800-222-1222) for the latest recommendations.

  • 11 DESCRIPTION

    Mirtazapine tablets contain mirtazapine. Mirtazapine has a tetracyclic chemical structure and
    belongs to the piperazino-azepine group of compounds. It is designated
    1,2,3,4,10,14b-hexahydro-2-methylpyrazino [2,1-a] pyrido [2,3-c][2] benzazepine and has the
    empirical formula of C17H19N3. Its molecular weight is 265.35. The structural formula is the
    following and it is the racemic mixture:

    11 DESCRIPTION

    Mirtazapine is a white to creamy white crystalline powder which is practically insoluble in water.
    Mirtazapine tablets are available for oral administration as scored film-coated tablets containing 15
    or 30 mg of mirtazapine. Each tablet contains the following inactive ingredients: croscarmellose
    sodium, hydroxypropyl cellulose, hypromellose, lactose monohydrate, magnesium stearate,
    microcrystalline cellulose, polyethylene glycol and titanium dioxide. In addition, mirtazapine tablets,
    USP 15 mg and 30 mg contains iron oxide yellow and mirtazapine tablets, USP 30 mg contains iron
    oxide red

  • 12 CLINICAL PHARMACOLOGY

    12.1 Mechanism of Action

    The mechanism of action of mirtazapine for the treatment of major depressive disorder, is unclear.
    However, its efficacy could be mediated through its activity as an antagonist at central presynaptic
    α2-adrenergic inhibitory auto-receptors and heteroreceptors and enhancing central noradrenergic
    and serotonergic activity.

    12.2 Pharmacodynamics

    In preclinical studies, mirtazapine acts as an antagonist at α2-adrenergic inhibitory auto-receptors
    and heteroreceptors and as an antagonist at serotonin 5-HT2 and 5-HT3 receptors. Mirtazapine has
    no significant affinity for the 5-HT1A and 5-HT1B receptors.
    Mirtazapine also acts as an antagonist of histamine (H1) receptors, peripheral α1-adrenergic
    receptors, and muscarinic receptors. Actions at these receptors may explain some of the other
    clinical effects of mirtazapine (e.g., its prominent somnolent effects and orthostatic hypotension
    may be explained by its inhibition of histamine (H1) receptors and peripheral α1-adrenergic
    receptors, respectively).
    Cardiac Electrophysiology
    The effect of mirtazapine tablets on QTc interval was assessed in healthy subjects. At a dose of
    75 mg (1.67 times the maximum recommended dosage), mirtazapine tablets do not prolong the
    QTc interval to a clinically meaningful extent.

    12.3 Pharmacokinetics

    Plasma levels of mirtazapine are linearly related to dose over a dose range of 15 to 80 mg (1.78
    times the maximum recommended dose). Steady state plasma levels of mirtazapine are attained
    within 5 days, with about 50% accumulation (accumulation ratio=1.5). The (–) enantiomer has an
    elimination half-life that is approximately twice as long as the (+) enantiomer and therefore
    achieves plasma levels that are about 3 times as high as that of the (+) enantiomer.
    Absorption
    Mirtazapine has an absolute bioavailability of about 50% following oral administration. Peak plasma
    concentrations of mirtazapine are reached within about 2 hours post dose.
    Food Effect
    The presence of food in the stomach has a minimal effect on both the rate and extent of absorption.
    Distribution
    Mirtazapine is approximately 85% bound to plasma proteins over a concentration range of 0.01 to
    10 mcg/mL.
    Elimination
    Mirtazapine has a half-life of about 20 to 40 hours following oral administration of mirtazapine
    tablets

    Metabolism
    Mirtazapine is extensively metabolized after oral administration. Major pathways of
    bio-transformation are demethylation and hydroxylation followed by glucuronide conjugation. In
    vitro data from human liver microsomes indicate that CYP2D6 and CYP1A2 are involved in the
    formation of the 8-hydroxy metabolite of mirtazapine, whereas CYP3A is considered to be
    responsible for the formation of the N-desmethyl and N-oxide metabolite. Several unconjugated
    metabolites possess pharmacological activity but are present in the plasma at very low levels.
    Excretion
    Mirtazapine and its metabolites are eliminated predominantly (75%) via urine with 15% in feces.
    Specific Populations
    Geriatric Patients
    Following oral administration of mirtazapine tablets 20 mg/day for 7 days to subjects of varying
    ages (range 25 to 74 years old), oral clearance of mirtazapine was reduced in the elderly compared
    to the younger subjects. The clearance in elderly males was 40% lower compared to younger
    males, while the clearance was 10% lower in elderly females compared to younger females [see
    Warnings and Precautions (5.14), Use in Specific Populations (8.5)]

    Male and Female Patients
    The mean elimination half-life of mirtazapine after oral administration ranges from approximately
    20 to 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).
    Race
    There have been no clinical studies to evaluate the effect of race on the pharmacokinetics of
    mirtazapine tablets.
    Patients with Renal Impairment
    When compared to subjects with normal renal function, total body clearance of mirtazapine was
    reduced approximately 30% in renal impaired patients with GFR=11–39 mL/min/1.73 m2 and
    approximately 50% in renal impaired patients with GFR=<10 mL/min/1.73 m2) [see Warnings and
    Precautions (5.14), Use in Specific Populations (8.6)].
    Patients with Hepatic Impairment
    Following a single 15-mg oral dose of mirtazapine tablets, the oral clearance of mirtazapine in
    patients with hepatic impairment was decreased by approximately 30%, compared to subjects with
    normal hepatic function [see Warnings and Precautions (5.12, 5.14), Use in Specific Populations
    (8.6)].

    Drug Interactions Studies
    Warfarin
    Mirtazapine (30 mg daily) at steady state caused a statistically significant increase (0.2) in the
    International Normalized Ratio (INR) in subjects treated with warfarin [see Drug Interactions (7)].
    QTc-Prolonging Drugs
    The risk of QT prolongation and/or ventricular arrhythmias (e.g., Torsades de Pointes) may be
    increased with concomitant use of medicines which prolong the QTc interval (e.g., some
    antipsychotics and antibiotics) and in mirtazapine overdose [see Warnings and Precautions (5.5),
    Adverse Reactions (6.1,6.2), Drug Interactions (7), and Overdosage (10)].
    Phenytoin
    In healthy male subjects (n=18), phenytoin (200 mg daily, at steady state) increased mirtazapine
    (30 mg daily, at steady state) clearance about 2-fold, resulting in a decrease in average plasma
    mirtazapine concentrations of 45% [see Drug Interactions (7)]. Mirtazapine did not significantly
    affect the pharmacokinetics of phenytoin.
    Carbamazepine
    In healthy male subjects (n=24), carbamazepine (400 mg twice a day, at steady state) increased
    mirtazapine (15 mg twice a day, at steady state) clearance about 2-fold, resulting in a decrease in
    average plasma mirtazapine concentrations of 60% [see Drug Interactions (7)].

    Cimetidine
    In healthy male subjects (n=12), when cimetidine, a weak inhibitor of CYP1A2, CYP2D6, and
    CYP3A4, given at 800 mg b.i.d. at steady state was coadministered with mirtazapine (30 mg daily)
    at steady state, the Area Under the Curve (AUC) of mirtazapine increased more than 50% [see Drug
    Interactions (7)]. Mirtazapine did not cause relevant changes in the pharmacokinetics of cimetidine.
    Ketoconazole
    In healthy male Caucasian subjects (n=24), coadministration of the strong CYP3A4 inhibitor
    ketoconazole (200 mg b.i.d. for 6.5 days) increased the peak plasma levels and the AUC of a single
    30 mg dose of mirtazapine by approximately 40% and 50%, respectively [see Drug Interactions (7)].
    Amitriptyline
    In healthy, CYP2D6 extensive metabolizer patients (n=32), amitriptyline (75 mg daily), at steady
    state, did not cause relevant changes to the pharmacokinetics of steady state mirtazapine (30 mg
    daily); mirtazapine also did not cause relevant changes to the pharmacokinetics of amitriptyline.
    Paroxetine
    In healthy CYP2D6 extensive metabolizer subjects (n=24), mirtazapine (30 mg/day), at steady state,
    did not cause relevant changes in the pharmacokinetics of steady state paroxetine (40 mg/day), a
    CYP2D6 inhibitor.

    Lithium
    No relevant clinical effects or significant changes in pharmacokinetics have been observed in
    healthy male subjects on concurrent treatment with lithium 600 mg/day for 10 days at steady state
    and a single 30 mg dose of mirtazapine. The effects of higher doses of lithium on the
    pharmacokinetics of mirtazapine are unknown.
    Risperidone
    Mirtazapine (30 mg daily) at steady state did not influence the pharmacokinetics of risperidone (up
    to 3 mg twice a day) in subjects (n=6) in need of treatment with an antipsychotic and
    antidepressant drug.
    Alcohol
    Concomitant administration of alcohol (equivalent to 60 g) had a minimal effect on plasma levels of
    mirtazapine (15 mg) in 6 healthy male subjects. However, the impairment of cognitive and motor
    skills produced by mirtazapine tablets were shown to be additive with those produced by alcohol.
    Diazepam
    Concomitant administration of diazepam (15 mg) had a minimal effect on plasma levels of
    mirtazapine (15 mg) in 12 healthy subjects. However, the impairment of motor skills produced by
    mirtazapine tablets has been shown to be additive with those caused by diazepam.

  • 13 NONCLINICAL TOXICOLOGY

    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

    Carcinogenesis
    Carcinogenicity studies were conducted with mirtazapine given in the diet at doses of 2, 20, and
    200 mg/kg/day to mice and 2, 20, and 60 mg/kg/day to rats. The highest doses used are
    approximately 20 and 12 times the maximum recommended human dose (MRHD) of 45 mg/day,
    based on body surface area (mg/m2) in mice and rats, respectively. There was an increased
    incidence of hepatocellular adenoma and carcinoma in male mice at the high dose. In rats, there
    was an increase in hepatocellular adenoma in females at the mid and high doses and in
    hepatocellular tumors and thyroid follicular adenoma/cystadenoma and carcinoma in males at the
    high dose.
    Mutagenesis
    Mirtazapine was not mutagenic or clastogenic and did not induce general DNA damage as
    determined in several genotoxicity tests: Ames test, in vitro gene mutation assay in Chinese
    hamster V 79 cells, in vitro sister chromatid exchange assay in cultured rabbit lymphocytes, in vivo
    bone marrow micronucleus test in rats, and unscheduled DNA synthesis assay in HeLa cells.
    Impairment of Fertility
    In a fertility study in rats, mirtazapine was given at doses up to 100 mg/kg [20 times the maximum
    recommended human dose (MRHD), based on body surface area (mg/m2)]. Mating and conception
    were not affected by the drug, but estrous cycling was disrupted at doses that were 3 or more
    times the MRHD, and pre-implantation losses occurred at 20 times the MRHD.

  • 14 CLINICAL STUDIES

    The efficacy of mirtazapine tablets as a treatment for major depressive disorder was established in
    4 placebo- controlled, 6-week trials in adult outpatients meeting DSM-III criteria for major
    depressive disorder. Patients were titrated with mirtazapine tablets from a dose range of 5 mg to
    35 mg/day. The mean mirtazapine dose for patients who completed these 4 studies ranged from 21
    to 32 mg/day. Overall, these studies demonstrated mirtazapine tablets to be superior to placebo on
    at least 3 of the following 4 measures: 21-Item Hamilton Depression Rating Scale (HDRS) total
    score; HDRS Depressed Mood Item; CGI Severity score; and Montgomery and Asberg Depression
    Rating Scale (MADRS). Superiority of mirtazapine tablets over placebo was also found for certain
    factors of the HDRS, including anxiety/somatization factor and sleep disturbance factor.
    Examination of age and gender subsets of the population did not reveal any differential
    responsiveness on the basis of these subgroupings.
    In a longer-term study, patients meeting (DSM-IV) criteria for major depressive disorder who had
    responded during an initial 8 to 12 weeks of acute treatment on mirtazapine tablets were
    randomized to continuation of mirtazapine tablets or placebo for up to 40 weeks of observation for
    relapse. Response during the open phase was defined as having achieved a HAM-D 17 total score
    of
    ≤8 and a CGI-Improvement score of 1 or 2 at 2 consecutive visits beginning with week 6 of the 8
    to 12 weeks in the open-label phase of the study. Relapse during the double-blind phase was
    determined by the individual investigators. Patients receiving continued mirtazapine tablets
    treatment experienced significantly lower relapse rates over the subsequent 40 weeks compared to
    those receiving placebo. This pattern was demonstrated in both male and female patients.

  • 16 HOW SUPPLIED/STORAGE AND HANDLING

    Mirtazapine tablets are supplied as:
    Mirtazapine Tablets, USP 15 mg are available for oral administration as pale yellow, oval-shaped,
    scored, film-coated tablets imprinted “APO” on one side and “MI” bisect “15” on the other side.
    They are supplied as follows:
    Boxes of 10x10 UD 100 count NDC 63739-098-10
    Mirtazapine Tablets, USP 30 mg are available for oral administration as light pink, oval-shaped,
    scored, film-coated tablets imprinted “APO” on one side and “MI” bisect “30” on the other side.
    They are supplied as follows:
    Boxes of 10x10 UD 100 count NDC 63739-099-10
    Storage
    Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see
    USP Controlled Room Temperature]. Protect from light and moisture. Use immediately upon opening
    individual tablet blister.

  • 17 PATIENT COUNSELING INFORMATION

    Advise the patient to read the FDA-approved patient labeling (Medication Guide).
    Suicidal Thoughts and Behaviors
    Advise patients and caregivers to look for the emergence of suicidality, especially early during
    treatment and when the dosage is adjusted up or down, and instruct them to report such symptoms
    to the healthcare provider [see Boxed Warning and Warnings and Precautions (5.1)].
    Agranulocytosis
    Advise patients to contact their physician if they experience fever, chills, sore throat, mucous
    membrane ulceration, flu-like complaints, or other symptoms that might suggest infection [see
    Warnings and Precautions (5.2)].
    Serotonin Syndrome
    Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of
    mirtazapine tablets with other serotonergic drugs including triptans, tricyclic antidepressants,
    fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, 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). Advise patients to contact their healthcare provider or
    report to the emergency room if they experience signs or symptoms of serotonin syndrome [see
    Dosage and Administration (2.4), Contraindications (4), Warnings and Precautions (5.3), Drug
    Interactions (7)].

    QT Prolongation and Torsades de Pointes
    Inform patients to consult their physician immediately if they feel faint, lose consciousness, or have
    heart palpitations [see Warnings and Precautions (5.5), Drug Interactions (7), Overdosage (10)].
    Advise patients to inform physicians that they are taking mirtazapine tablets before any new drug is
    taken.
    Somnolence
    Advise patients that mirtazapine tablets may impair judgment, thinking, and particularly, motor
    skills, because of its prominent sedative effect. Caution patients about performing activities
    requiring mental alertness, such as operating hazardous machinery or operating a motor vehicle,
    until they are reasonably certain that mirtazapine tablets therapy does not adversely affect their
    ability to engage in such activities. [see Warnings and Precautions (5.7)].
    Alcohol
    Advise patients to avoid alcohol while taking mirtazapine tablets [see Warnings and Precautions
    (5.7), Drug Interactions (7)].
    Activation of Mania/Hypomania
    Advise patients and their caregivers to observe for signs of activation of mania/hypomania and
    instruct them to report such symptoms to the healthcare provider [see Warnings and Precautions
    (5.8)].

    Discontinuation Syndrome
    Advise patients not to abruptly discontinue mirtazapine tablets and to discuss any tapering regimen
    with their healthcare provider. Adverse reactions can occur when mirtazapine tablets are
    discontinued [see Dosage and Administration (2.6), Warnings and Precautions (5.13)].
    Allergic Reactions
    Advise patients to notify their healthcare provider if they develop an allergic reaction such as rash,
    hives, swelling, or difficulty breathing [see Contraindications (4), Adverse Reactions (6.2)].
    Pregnancy
    • Advise patients to notify their physician if they become pregnant or intend to become pregnant
    during mirtazapine tablets therapy.
    • Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes
    in women exposed to mirtazapine tablets during pregnancy [see Use in Specific Populations
    (8.2)].
    Lactation
    Advise patients to notify their physician if they are breastfeeding an infant [see Use in Specific
    Populations (8.2)].

    Angle-Closure Glaucoma
    Patients should be advised that taking mirtazapine 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 [see
    Warnings and Precautions (5.4).]


    Manufactured by:
    Apotex Inc
    Toronto, Ontario
    Canada M9l 1T9
    Distributed by:
    McKesson Corporation
    4971 Southridge Blvd, Suite 101
    Memphis, TN 38141
    21495
    January 2021

  • MEDICATION GUIDE

    Mirtazapine Tablets, USP

    (mir taz’ a peen)

    What is the most important information I should know

    about mirtazapine tablets?

    Mirtazapine tablets may cause serious side effects, including:

    • Increased risk of suicidal thoughts or actions in
    some children and young adults.
    Mirtazapine tablets,
    and other antidepressant medicines may increase
    suicidal thoughts or actions in some people 24 years of
    age and younger, especially within the first few
    months of treatment or when the dose is changed.
    Mirtazapine tablets are not for use in children.
    ° Depression or other serious mental illnesses are
    the most important causes of suicidal thoughts or

    How can I watch for and try to prevent suicidal
    thoughts and actions?

    ° Pay close attention to any changes, especially sudden
    changes in mood, behavior, thoughts, or feelings, or if
    you develop suicidal thoughts or actions. This is very
    important when an antidepressant medicine is started
    or when the dose is changed.
    ° Call your healthcare provider right away to report new
    or sudden changes in mood, behavior, thoughts, or
    feelings.
    ° Keep all follow-up visits with your healthcare provider
    as scheduled. Call your healthcare provider between
    visits as needed, especially if you have concerns
    about symptoms.

    Call your healthcare provider or get emergency medical
    help right away if you or your family member have any
    of the following symptoms, especially if they are new,
    worse, or worry you:

    • attempts to commit suicide
    • acting aggressive, being angry or violent
    • new or worse depression
    • panic attacks
    • new or worse irritability
    • an extreme increase in activity or talking (mania)
    • acting on dangerous impulses
    • thoughts about suicide or dying
    • new or worse anxiety
    • feeling very agitated or restless
    • trouble sleeping
    • other unusual changes in behavior or mood

    What are mirtazapine tablets?

    Mirtazapine tablets are prescription medicines used to treat
    a certain type of depression called Major Depressive
    Disorder (MDD) in adults.
    It is not known if mirtazapine tablets are safe and effective
    for use to treat MDD in children.

    Who should not take mirtazapine tablets? Do not take
    mirtazapine tablets if you:

    • take a Monoamine Oxidase Inhibitor (MAOI)
    • have stopped taking an MAOI in the last 14 days
    • are being treated with the antibiotic linezolid or
    intravenous methylene blue
    • if you are allergic to mirtazapine or any of the ingredients
    in mirtazapine tablets. See the end of this Medication
    Guide for a complete list of ingredients in mirtazapine
    tablets

    Ask your healthcare provider or pharmacist if you are not
    sure if you take an MAOI, including the antibiotic linezolid or
    intravenous methylene blue.

    Do not start taking an MAOI for at least 14 days after
    you stop treatment with mirtazapine tablets.
    Before taking mirtazapine tablets, tell your healthcare
    provider about all your medical conditions, including if you:​

    • have a history of suicide or depression
    • have a history or family history of bipolar disorder, mania
    or hypomania
    • have a low white blood cell count
    • have glaucoma (high pressure in the eye)
    • have or had heart problems or stroke
    • have an abnormal heart beat called QT prolongation or a
    family history of QT prolongation
    • have seizures
    • have high cholesterol or triglyceride levels
    • have low sodium levels in your blood
    • have or had kidney or liver problems
    • have low blood pressure
    • are pregnant or plan to become pregnant. It is not known
    if mirtazapine tablets will harm your unborn baby.

    • Talk to your healthcare provider if you become pregnant
    or think you may be pregnant during treatment with
    mirtazapine tablets.
    • If you become pregnant while taking mirtazapine tablets,
    talk to your healthcare provider about registering with
    the National Pregnancy Registry for Antidepressants. You
    can register by calling 1-844-405-6185 or visiting online
    at http://womensmentalhealth.org/clinical-and-researchprograms/
    pregnancyregistry/antidepressants/. The
    purpose of this registry is to monitor the pregnancy
    outcomes in women who have been treated with
    mirtazapine tablets at any time during pregnancy.
    • are breastfeeding or plan to breastfeed. Mirtazapine may
    pass into your breast milk. Talk to your healthcare
    provider about the best way to feed your baby during
    treatment with mirtazapine tablets.

    Tell your healthcare provider about all the medicines
    you take,
    including prescription and over-the-counter
    medicines, vitamins, and herbal supplements.
    Mirtazapine tablets and other medicines may affect each
    other causing possible serious side effects.
    Mirtazapine tablets may affect the way other medicines
    work and other medicines may affect the way mirtazapine
    tablets work.

    Especially tell your healthcare provider if you take:
    • MAOIs
    • medicines to treat migraine headaches known as
    triptans
    • tricyclic antidepressants
    • fentanyl
    • lithium
    • tramadol
    • tryptophan
    • buspirone
    • amphetamines
    • benzodiazepines
    • St. John’s Wort

    • medicines used to treat mood, anxiety, psychotic or
    thought disorders, including selective serotonin reuptake
    inhibitors (SSRIs) and serotonin norepinephrine reuptake
    inhibitors (SNRIs)
    • medicines that may affect your heart rhythm (such as
    certain antibiotics and some antipsychotics)
    Ask your healthcare provider if you are not sure if you are
    taking any of these medicines. Your healthcare provider can
    tell you if it is safe to take mirtazapine tablets with your
    other medicines.

    Do not start or stop any other medicines during treatment
    with mirtazapine tablets without talking to your healthcare
    provider first. Stopping mirtazapine tablets suddenly may
    cause you to have serious side effects. See, "What are the
    possible side effects of mirtazapine tablets?"

    Know the medicines you take. Keep a list of them to show
    to your healthcare provider and pharmacist when you get a
    new medicine.

    How should I take mirtazapine tablets?
    • Take mirtazapine tablets exactly as your healthcare
    provider tells you to. Do not change your dose or stop
    taking mirtazapine tablets without first talking to your
    healthcare provider.
    • Your healthcare provider may need to change the dose of
    mirtazapine tablets until it is the right dose for you
    • Take mirtazapine tablets 1 time each day, preferably in
    the evening at bedtime
    • If you take too much mirtazapine tablets call your
    healthcare provider or poison control center at
    1-800-222-1222 right away or go to the nearest hospital
    emergency room.

    What should I avoid while taking mirtazapine tablets?
    • Do not drive, operate heavy machinery, or do other
    dangerous activities until you know how mirtazapine
    tablets affects you. Mirtazapine tablets can cause
    sleepiness or may affect your ability to make decisions,
    think clearly, or react quickly.
    • Avoid drinking alcohol during treatment with mirtazapine
    tablets.
    • Avoid taking medicines used to treat anxiety, insomnia,
    and seizures, called benzodiazepines, during treatment
    with mirtazapine tablets. Ask your healthcare provider if
    you are not sure if you take one of these medicines.

    What are the possible side effects of mirtazapine tablets?
    Mirtazapine tablets may cause serious side effects,
    including:

    • See, "What is the most important information I
    should know about mirtazapine?"

    Low white blood cell count. Tell your healthcare
    provider right away if you develop any signs or
    symptoms of a low white blood cell count, including:
    ° fever
    ° sore Throat
    ° flu-like symptoms
    ° chills
    ° mouth and nose sores
    ° infections

    • Serotonin syndrome.A potentially life A potentially
    life-threatening problem called serotonin syndrome can
    happen when you take mirtazapine tablets with certain
    other medicines. See, "Who should not take
    mirtazapine tablets?"
    Stop taking mirtazapine tablets
    and call your healthcare provider or go to the nearest
    hospital emergency room right away if you have any of
    the following signs and symptoms of serotonin
    syndrome:

    ° agitation
    ° confusion
    ° fast heart beat
    ° dizziness
    ° flushing
    ° tremors, stiff muscles, or muscle twitching
    ° seizures
    ° seeing or hearing things that are not real
    (hallucinations)
    ° coma
    ° blood pressure changes
    ° sweating
    ° high body temperature (hyperthermia)
    ° loss of coordination nausea,
    ° vomiting, diarrhea

    • Eye problems (angle-closure glaucoma). Mirtazapine
    tablets may cause a certain type of eye problem called
    angle-closure glaucoma. Call your healthcare provider if
    you have eye pain, changes in your vision, or swelling or
    redness in or around the eye. Only some people are at
    risk for these problems. You may want to undergo an eye
    examination to see if you are at risk and receive
    preventative treatment if you are.

    • Heart rhythm problems.
    • Increased appetite and weight gain.
    • Sleepiness.
    See, "What should I avoid while taking
    mirtazapine tablets?"

    • Mania or hypomania (manic episodes) in people who
    have a history of bipolar disorder. Symptoms may
    include:

    ° greatly increased energy
    ° racing thoughts
    ° unusually grand ideas
    ° talking more or faster than usual
    ° severe trouble sleeping
    ° reckless behavior
    ° excessive happiness or irritability

    • Seizures (convulsions).
    • Increased fat levels (cholesterol and triglycerides) in
    your blood.
    • Low sodium levels in your blood (hyponatremia).
    Low
    sodium levels in your blood may be serious and may
    cause death. Elderly people may be at greater risk for
    this. Signs and Symptoms of low sodium levels in your
    blood may include:
    ° headache
    ° memory changes
    ° weakness and unsteadiness on your feet which can
    lead to falls
    ° difficulty concentrating
    ° confusion

    In severe or more sudden cases, signs and symptoms
    include:

    ° hallucinations (seeing or hearing things that are not
    real)
    ° seizures
    ° respiratory arrest
    ° fainting
    ° coma
    ° death

    • Changes in liver function tests.
    • Discontinuation syndrome.
    Suddenly stopping
    mirtazapine tablets may cause you to have serious side
    effects. Your healthcare provider may want to decrease
    your dose slowly. Symptoms may include:
    ° dizziness
    ° irritability and agitation
    ° anxiety
    ° sweating
    ° seizures
    ° ringing in your ears (tinnitus)
    ° nausea and vomiting
    ° problems sleeping
    ° tiredness
    ° confusion

    ° electric shock sensation (paresthesia)
    ° shaking (tremor)
    ° headache
    ° abnormal dreams
    ° changes in your mood
    ° hypomania

    The most common side effects of mirtazapine tablets
    include:

    • sleepiness
    • increased appetite
    • weight gain
    • dizziness
    These are not all the possible side effects of mirtazapine
    tablets.
    Call your doctor for medical advice about side effects. You
    may report side effects to FDA at 1-800-FDA-1088.
    How should I store mirtazapine tablets?
    • Store mirtazapine tablets at room temperature between
    68°F to 77°F (20°C to 25°C).
    • Keep mirtazapine tablets away from light and moisture.

    Keep mirtazapine tablets, and all medicines out of the
    reach of children.
    General information about the safe and effective use of
    mirtazapine tablets.

    Medicines are sometimes prescribed for purposes other
    than those listed in a Medication Guide. Do not use
    mirtazapine tablets for a condition for which it was not
    prescribed. Do not give mirtazapine tablets to other people,
    even if they have the same symptoms that you have. It may
    harm them. You can ask your healthcare provider or
    pharmacist for information about mirtazapine tablets that is
    written for healthcare professionals.

    What are the ingredients in mirtazapine tablets?
    Active ingredient:
    mirtazapine
    Inactive ingredients: Colloidal silicon dioxide anhydrous,
    corn starch, ferric oxide (yellow), hydroxypropyl cellulose,
    hypromellose, polyethylene glycol 8000, lactose
    monohydrate, magnesium stearate, and titanium dioxide.
    The 30 mg tablets also contain ferric oxide (red).

    Manufactured by
    Apotex Inc.
    Toronto, Ontario
    Canada M9L 1T9


    Distributed by:
    McKesson Corporation
    4971 Southridge Blvd, Suite 101
    Memphis, TN 38141


    21495
    January 2021

  • Mirtazapine

    Mirtazapine

  • Mirtazapine

    MirtazapineMirtazapine

  • INGREDIENTS AND APPEARANCE
    MIRTAZAPINE 
    mirtazapine tablet, film coated
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:63739-098(NDC:60505-0247)
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    MIRTAZAPINE (UNII: A051Q2099Q) (MIRTAZAPINE - UNII:A051Q2099Q) MIRTAZAPINE15 mg
    Inactive Ingredients
    Ingredient NameStrength
    CROSCARMELLOSE SODIUM (UNII: M28OL1HH48)  
    HYDROXYPROPYL CELLULOSE (1600000 WAMW) (UNII: RFW2ET671P)  
    HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO)  
    LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)  
    MAGNESIUM STEARATE (UNII: 70097M6I30)  
    MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)  
    POLYETHYLENE GLYCOL 8000 (UNII: Q662QK8M3B)  
    TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
    FERRIC OXIDE RED (UNII: 1K09F3G675)  
    FERRIC OXIDE YELLOW (UNII: EX438O2MRT)  
    Product Characteristics
    ColoryellowScore2 pieces
    ShapeOVALSize9mm
    FlavorImprint Code APO;MI;15
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:63739-098-1010 in 1 BOX11/15/2019
    110 in 1 BLISTER PACK; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA07766608/22/2007
    MIRTAZAPINE 
    mirtazapine tablet, film coated
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:63739-099(NDC:60505-0248)
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    MIRTAZAPINE (UNII: A051Q2099Q) (MIRTAZAPINE - UNII:A051Q2099Q) MIRTAZAPINE30 mg
    Inactive Ingredients
    Ingredient NameStrength
    CROSCARMELLOSE SODIUM (UNII: M28OL1HH48)  
    HYDROXYPROPYL CELLULOSE (1600000 WAMW) (UNII: RFW2ET671P)  
    HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO)  
    LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)  
    MAGNESIUM STEARATE (UNII: 70097M6I30)  
    MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)  
    POLYETHYLENE GLYCOL 8000 (UNII: Q662QK8M3B)  
    TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
    FERRIC OXIDE RED (UNII: 1K09F3G675)  
    FERRIC OXIDE YELLOW (UNII: EX438O2MRT)  
    Product Characteristics
    ColorpinkScore2 pieces
    ShapeOVALSize11mm
    FlavorImprint Code APO;MI;30
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:63739-099-1010 in 1 BOX11/15/2019
    110 in 1 BLISTER PACK; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA07766608/22/2007
    Labeler - McKesson Corporation dba SKY Packaging (140529962)
    Establishment
    NameAddressID/FEIBusiness Operations
    Legacy Pharmaceutical Packaging, LLC143213275repack(63739-098, 63739-099) , relabel(63739-098, 63739-099)