Generic Name: Mirtazapine
Class: Antidepressants, Miscellaneous
VA Class: CN609
Chemical Name: 1,2,3,4,10,14b-Hexahydro-2-methylpyrazino[2,1-a]pyrido [2,3-c][2]benzazepine
Molecular Formula: C17H19N3
CAS Number: 61337-67-5

Warning(s)

  • Suicidality in Children and Adolescents
  • Antidepressants may increase risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder and other psychiatric disorders (See Pediatric Use under Cautions); balance this risk with clinical need.a b Mirtazapine is not approved for use in pediatric patients.a b

  • Closely monitor pediatric patients who are started on mirtazapine therapy for clinical worsening, suicidality, or unusual changes in behavior; involve family members and/or caregivers in this process. (See Worsening of Depression and Suicidality Risk under Cautions.)a b

Introduction

Tetracyclic antidepressant;1 2 3 4 5 6 7 8 9 10 a piperazinoazepine-derivative.1 4

Uses for Remeron

Major Depressive Disorder

Treatment of major depressive disorder.13 5 6 10 11 a

Slideshow: Can Prescription Drugs Lead to Weight Gain?

Remeron Dosage and Administration

General

  • Allow at least 2 weeks to elapse between discontinuance of an MAO inhibitor and initiation of mirtazapine, and vice versa.a b

  • Monitor for possible worsening of depression or suicidality, especially at the beginning of therapy or during periods of dosage adjustments.19 b (See Worsening of Depression and Suicidality Risk under Cautions.)

  • Sustained therapy may be required; monitor periodically for need for continued therapy.a b

  • Maximum antidepressant effects of therapy may not be evident until ≥4 weeks of treatment.1 b

Administration

Oral Administration

Administer orally as conventional tablets and orally disintegrating tablets once daily (at bedtime) without regard to meals.1 11

Do not break orally disintegrating tablets.11

Just prior to administration of orally disintegrating tablet, remove tablet from blister package; peel open blister package, place tablet on tongue to dissolve, and swallow with saliva; administration with liquid is not necessary.11

Dosage

Adults

Major Depressive Disorder
Oral

Initially, 15 mg daily.1 11 If no improvement, dosage may be increased up to a maximum of 45 mg daily at intervals of not less than 1–2 weeks.1 11 a b

Prescribing Limits

Adults

Major Depressive Disorder
Oral

Maximum 45 mg daily.1 11 a b

Special Populations

Hepatic Impairment

Decreased clearance; however, no special population dosage recommendations at this time.1 11 (See Hepatic Impairment under Cautions.)

Renal Impairment

Decreased clearance in patients with moderate to severe renal impairment; however, no special population dosage recommendations at this time.1 11 (See Renal Impairment under Cautions.)

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.a b

Cautions for Remeron

Contraindications

  • Known hypersensitivity to mirtazapine or any ingredient in the formulation.a b

Warnings/Precautions

Warnings

Worsening of Depression and Suicidality Risk

Possible worsening of depression and/or emergence of suicidal ideation and behavior (suicidality); may persist until clinically important remission occurs with therapy.19 a b Closely supervise patients with major depressive disorder or other psychiatric illness with comorbid depression during initiation of therapy and during periods of dosage adjustments.19 a b (See Boxed Warning.)

If anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and/or mania occur, consider changing or discontinuing therapy, particularly if severe, abrupt in onset, or not a part of patient’s presenting symptoms.19 a b

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.1 19 b

Observe these precautions for patients with psychiatric (e.g., major depressive disorder, obsessive-compulsive disorder) or nonpsychiatric disorders.19 a b

Bipolar Disorder

May unmask bipolar disorder.19 a b (See Activation of Mania or Hypomania under Cautions.)

Screen for risk of bipolar disorder by obtaining detailed psychiatric history (e.g., family history of suicide, bipolar disorder, depression) prior to initiating therapy.19 a b

Hematologic Effects

Agranulocytosis or severe neutropenia (with or without infection) reported rarely.a b If signs of infection (e.g., sore throat, fever, stomatitis) and low WBC counts occur, discontinue therapy and monitor patient closely.a b

Drug Interactions

Concomitant use with an MAO inhibitor associated with serious, sometimes fatal reactions, including manifestations resembling serotonin syndrome (e.g., hyperthermia, rigidity, myoclonus, autonomic instability, mental status changes) or neuroleptic malignant syndrome. (See Specific Drugs under Interactions.)a b

General Precautions

CNS Effects

Risk of impaired mental alertness or physical coordination required for performing hazardous tasks (e.g., driving, operating machinery).a b

Possible dizziness.a b

Altered Appetite and Weight

Possible increased appetite and weight gain.a b

Hyperlipidemia

Clinically important increases in serum cholesterol (e.g., >20% ULN) and serum triglyceride (e.g., 500 mg/dL) concentrations reported.a b

Hepatic Effects

Potentially clinically important elevations (e.g., 3 times ULN) in serum ALT concentrations; not usually associated with impaired hepatic function.a b

Activation of Mania or Hypomania

Possible activation of mania or hypomania; use with caution in patients with a history of mania or hypomania.a b (See Bipolar Disorder under Cautions.)

Seizures

Risk of seizures; use with caution in patients with a history of seizures.a b

Concomitant Illnesses

Experience in patients with concomitant diseases is limited.a b

Use with caution in patients with concomitant illnesses affecting metabolism or hemodynamic response.a b

Cardiovascular Effects

Safety in patients with recent history of MI or those with unstable heart disease not established.a b

Orthostatic hypotension reported infrequently.a b Use with caution in patients with known cardiovascular or cerebrovascular disease and in patients with conditions that predispose them to hypotension (e.g., dehydration, hypovolemia, concurrent antihypertensive therapy).a b

Possible increased heart rate and changes in ECG; clinical significance not known.a b

Phenylketonuria

Remeron SolTab orally disintegrating tablets contain aspartame (e.g., NutraSweet), which is metabolized in the GI tract to provide 2.6, 5.2, and 7.8 mg of phenylalanine per 15, 30, and 45 mg tablet, respectively.b

Specific Populations

Pregnancy

Category C.b

Lactation

Not known whether mirtazapine is distributed into milk.a b Caution if used in nursing women.a b

Pediatric Use

Safety and efficacy not established.1 a b

Geriatric Use

No substantial differences in adverse effects relative to younger adults; however, increased sensitivity to sedative effects possible in some geriatric individuals.a b

Use with caution in patients >65 years of age.a b

Hepatic Impairment

Decreased clearance; use with caution.a b

Renal Impairment

Decreased clearance in patients with moderate to severe renal impairment; use with caution.a b

Common Adverse Effects

Somnolence, increased appetite, weight gain, dizziness.a b

Interactions for Remeron

Metabolized by CYP2D6, CYP3A4, and CYP1A2; a b not a potent inhibitor of CYP2D6, CYP3A4, and CYP1A2.a b

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction (decreased mirtazapine metabolism) with inhibitors of CYP2D6, CYP3A4, or CYP1A2.a b

Potential pharmacokinetic interaction (increased mirtazapine metabolism) with inducers of CYP2D6, CYP3A4, or CYP1A2.a b

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP2D6, CYP3A4, or CYP1A2: potential pharmacokinetic interaction (decreased plasma substrate concentrations).a b However, mirtazapine is not a potent inhibitor of these enzymes and clinically important interaction is unlikely.a b

Specific Drugs

Drug

Interaction

Comments

Alcohol

Potentiates cognitive and motor effects of alcohola b

Concomitant use is not recommendeda b

Benzodiazepines (diazepam)

Additive sedative effectsa b

Concomitant use is not recommendeda b

MAO inhibitors

Possible serotonin or neuroleptic malignant syndromea b

Concomitant use is not recommendeda b

Allow at least 2 weeks to elapse between discontinuance of an MAO inhibitor and initiation of mirtazapine, or vice versaa b

Remeron Pharmacokinetics

Absorption

Bioavailability

Well absorbed from the GI tract following oral administration, with peak plasma concentration usually attained within 2 hours.a b

Bioavailability is approximately 50%.a

Food

Food does not appear to affect absorption.1 11

Distribution

Extent

Not known whether distributed into milk.a

Plasma Protein Binding

Approximately 85%.a b

Elimination

Metabolism

Extensively metabolized in the liver, via CYP2D6 and CYP1A2 to the 8-hydroxy metabolite, and via CYP3A4 to the N-desmethyl and N-oxide metabolitea .b

Elimination Route

Excreted in urine (75%) and feces (15%).a b

Half-life

20–40 hours.a b

Special Populations

Renal impairment may reduce clearance.1 11 a b

Hepatic impairment may reduce clearance.1 11 a b

Stability

Storage

Oral

Tablets and Orally Disintegrating Tablets

25°C in the original container;a protect from light and moisture.b

Actions

  • Mechanism of action as an antidepressant is unclear, but is presumed to be linked to potentiation of noradrenergic and serotonergic activity in the CNS resulting from its antagonism at central presynaptic α2-adrenergic autoreceptors and heteroreceptors.1 2 7 8 9 10 11

  • Exhibits potent antagonism of serotonin type 2 (5-HT2) and type 3 (5-HT3) receptors;1 2 7 10 11 does not exhibit high affinity for serotonin type 1A (5-HT1A) or type 1B (5-HT1B) receptors.1 2 7 11

  • Exhibits potent antagonism of histamine H1 receptors.1 11

  • Exhibits moderate peripheral α1-adrenergic blocking activity and moderate antagonism at muscarinic receptors.1 11

Advice to Patients

  • Risks of suicidality; importance of patients, caregivers, and families immediately reporting emergence of suicidality, worsening depression, or other manifestations associated with increased risk of worsening depression or suicidality.19 25 b

  • Importance of considering possible impaired ability to perform hazardous activities (e.g., operating machinery, driving a motor vehicle); avoid driving or operating machinery until effects on individual are known.a b

  • Importance of avoiding alcohol-containing beverages or products.a b

  • Importance of continuing therapy even if improvement is evident within 1–4 weeks, unless directed otherwise.1 11 b Importance of patients not discontinuing therapy without first consulting clinician.17 18

  • Importance of not breaking orally disintegrating tablets.11

  • Importance of informing patients with phenylketonuria that orally disintegrating tablets contain aspartame.b

  • Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.b

  • Importance of women notifying clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Mirtazapine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

15 mg*

Remeron (scored)

Organon

30 mg*

Remeron (scored)

Organon

45 mg*

Remeron

Organon

Tablets, orally disintegrating

15 mg

Remeron SolTab (with aspartame)

Organon

30 mg

Remeron SolTab (with aspartame)

Organon

45 mg

Remeron SolTab (with aspartame)

Organon

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Mirtazapine 15MG Dispersible Tablets (PRASCO LABORATORIES): 30/$72.99 or 90/$207.97

Mirtazapine 15MG Tablets (AUROBINDO PHARMA USA): 30/$55.99 or 90/$149.98

Mirtazapine 30MG Dispersible Tablets (PRASCO LABORATORIES): 30/$79.99 or 90/$219.98

Mirtazapine 30MG Tablets (AUROBINDO PHARMA USA): 30/$49.99 or 90/$145.96

Mirtazapine 45MG Dispersible Tablets (PRASCO LABORATORIES): 30/$74.99 or 90/$214.97

Mirtazapine 45MG Tablets (AUROBINDO PHARMA USA): 30/$46.99 or 90/$118.96

Mirtazapine 7.5MG Tablets (GREENSTONE): 30/$49.99 or 90/$139.97

Remeron 30MG Tablets (ORGANON): 30/$134.98 or 90/$383.95

Remeron 45MG Tablets (ORGANON): 30/$139.99 or 90/$403.43

Remeron SolTab 15MG Dispersible Tablets (ORGANON): 30/$105.99 or 90/$317.97

Remeron SolTab 30MG Dispersible Tablets (ORGANON): 30/$109.99 or 90/$295.98

Remeron SolTab 45MG Dispersible Tablets (ORGANON): 30/$119.99 or 90/$319.96

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions May 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Organon Inc. Remeron (mirtazapine) tablets prescribing information. West Orange, NJ; 1999 Mar.

2. de Boer T, Ruigt GSF. The selectiveα2-adrenoceptor antagonist mirtazapine (Org 3770) enhances noradrenergic and 5-HT1A-mediated serotonergic neurotransmission. CNS Drugs. 1995; 4(Suppl 1):29-38.

3. Bremner JD. A double-blind comparison of Org 3770, amitriptyline, and placebo in major depression. J Clin Psychiatry. 1995; 56:519-25. [IDIS 358479] [PubMed 7592505]

4. Smith WT, Glaudin V, Panagides J et al. Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder. Psychopharmacol Bull. 1990; 26:191-6. [PubMed 2236455]

5. Claghorn JL, Lesem MD. A double-blind placebo-controlled study of Org 3770 in depressed outpatients. J Affect Disord. 1995; 34:165-71. [PubMed 7560544]

6. Halikas JA. Org 3770 (mirtazapine) versus trazodone: a placebo controlled trial in depressed elderly patients. Hum Psychopharmacol. 1995; 10:S125-33.

7. De Boer T, Ruigt GSF, Berendsen HHG. The α2-selective adrenoceptor antagonist Org 3770 (mirtazapine, Remeron) enhances noradrenergic and serotonergic transmission. Hum Psychopharmacol. 1995; 10(Suppl 2):S107-18.

8. de Montigny C, Haddjeri N, Mongeau R et al. The effects of mirtazapine on the interactions between central noradrenergic and serotonergic systems. CNS Drugs. 1995; 4(Suppl 1):13-7.

9. Frazer A. Pharmacology of antidepressants. J Clin Psychopharmacol. 1997; 17(Suppl 1):2-18S.

10. Burrows GD, Kremer CME. Mirtazapine: clinical advantages in the treatment of depression. J Clin Psychopharmacol. 1997; 17(Suppl 1):34-9S. [PubMed 9004055]

11. Organon Inc. Remeron SolTab (mirtazapine) orally disintegrating tablets prescribing information. West Orange, NJ; 2001 Feb.

12. American Medical Association Council on Scientific Affairs. Aspartame: review of safety issues. JAMA. 1985; 254:400-2. [IDIS 202002] [PubMed 2861297]

13. Gossel TA. A review of aspartame: characteristics, safety and uses. US Pharm. 1984; 9:26,28-30.

14. Food and Drug Administration. Aspartame as an inactive ingredient in human drug products; labeling requirements. Proposed rule. [21 CFR Part 201] Fed Regist. 1983; 48:54993-5. (lDIS 178728)

15. Food and Drug Administration. Food additives permitted for direct addition to food for human consumption; aspartame. Final rule. [21 CFR Part 172] Fed Regist. 1983; 48:31376-82. (IDIS 172957)

16. Anon. Aspartame and other sweeteners. Med Lett Drugs Ther. 1982; 24:1-2. [PubMed 7054648]

17. Anon. FDA issues public health advisory entitled: Reports of suicidality in pediatric patients being treated with antidepressant medications for major depressive disorder (MDD). FDA Talk Paper. Rockville, MD: Food and Drug Administration; 2003 Oct 27. From the FDA website:

18. Anon. Reports of suicidality in pediatric patients being treated with antidepressant medications for major depressive disorder (MDD). FDA Public Health Advisory. Rockville, MD: Food and Drug Administration; 2003 Oct 27. From the FDA website: ().

19. Food and Drug Administration. Class suicidality labeling language for antidepressants. From the FDA website: ().

20. Food and Drug Administration. Public health advisory: suicidality in children and adolescents being treated with antidepressant medications. Rockville, MD; 2004 Oct 15. From the FDA website: ().

25. Food and Drug Administration. Medication guide: about using antidepressants in children or teenagers. Rockville, MD; 2005 Jan 16. From the FDA website: ().

a. Organon Inc. Remeron (mirtazapine) tablets prescribing information. West Orange, NJ; 2005 Jun

b. Organon Inc. Remeron SolTab (mirtazapine) orally disintegrating tablets prescribing information. West Orange, NJ; 2005 Jun

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