Mirtazapine
State of Florida DOH Central Pharmacy
Mirtazapine Tablets, USP
FULL PRESCRIBING INFORMATION: CONTENTS*
- Suicidality and Antidepressant Drugs
- MIRTAZAPINE DESCRIPTION
- CLINICAL PHARMACOLOGY
- MIRTAZAPINE INDICATIONS AND USAGE
- MIRTAZAPINE CONTRAINDICATIONS
- WARNINGS
- PRECAUTIONS
- General
- Somnolence
- Dizziness
- Increased Appetite/Weight Gain
- Cholesterol/Triglycerides
- Transaminase Elevations
- Activation of Mania/Hypomania
- Seizure
- Use in Patients with Concomitant Illness
- Information for Patients
- Clinical Worsening and Suicide Risk
- Agranulocytosis
- Interference with Cognitive and Motor Performance
- Completing Course of Therapy
- Concomitant Medication
- Alcohol
- Pregnancy
- Nursing
- Laboratory Tests
- Drug Interactions
- MIRTAZAPINE ADVERSE REACTIONS
- Associated with Discontinuation of Treatment
- Commonly Observed Adverse Events in US Controlled Clinical Trials
- Adverse Events Occurring at an Incidence of 1% or More Among Mirtazapine-Treated Patients
- ECG Changes
- Other Adverse Events Observed During the Premarketing Evaluation of Mirtazapine
- Other Adverse Events Observed During Postmarketing Evaluation of Mirtazapine
- DRUG ABUSE AND DEPENDENCE
- OVERDOSAGE
- MIRTAZAPINE DOSAGE AND ADMINISTRATION
- HOW SUPPLIED
- Medication Guide
- 15mg Label
- 30mg Label
- 45mg Label
FULL PRESCRIBING INFORMATION
Suicidality and Antidepressant Drugs
Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of mirtazapine tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Mirtazapine is not approved for use in pediatric patients. (See Warnings: Clinical Worsening and Suicide Risk, Precautions: Information for Patients, and Precautions: Pediatric Use)
MIRTAZAPINE DESCRIPTION
17193
CLINICAL PHARMACOLOGY
Pharmacodynamics
2
2 31A1B
1
1
Pharmacokinetics
In vitro
Special Populations
Geriatric
PRECAUTIONSDOSAGE AND ADMINISTRATION
Pediatrics
PRECAUTIONS
Gender
Pharmacokinetics
Race
Renal Insufficiency
22PRECAUTIONSDOSAGE AND ADMINISTRATION
Hepatic Insufficiency
PRECAUTIONSDOSAGE AND ADMINISTRATION
Clinical Trials Showing Effectiveness
MIRTAZAPINE INDICATIONS AND USAGE
CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY
MIRTAZAPINE CONTRAINDICATIONS
WARNINGS
Clinical Worsening and Suicide Risk
| Table 1 |
|
| Age Range |
Drug-Placebo Difference in Number of Cases of Suicidality per 1000 Patients Treated |
| |
Increases Compared to Placebo |
| <18 |
14 additional cases |
| 18-24 |
5 additional cases |
| |
Decreases Compared to Placebo |
| 25-64 |
1 fewer case |
|
>65 |
6 fewer cases |
All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.
Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers.Such monitoring should include daily observation by families and caregivers.
Screening Patients for Bipolar Disorder
Agranulocytosis
In premarketing clinical trials, two (one with Sjögren’s Syndrome) out of 2,796 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 three patients, onset of severe neutropenia was detected on days 61, 9, and 14 of treatment, respectively. All three patients recovered after mirtazapine was stopped. These three cases yield a crude incidence of severe neutropenia (with or without associated infection) of approximately 1.1 per thousand patients exposed, with a very wide 95% confidence interval i.e., 2.2 cases per 10,000 to 3.1 cases per 1,000. If a patient develops a sore throat, fever, stomatitis or other signs of infection, along with a low WBC count, treatment with mirtazapine should be discontinued and the patient should be closely monitored.
MAO Inhibitors
In patients receiving other drugs for major depressive disorder in combination with a monoamine oxidase inhibitor (MAOI) and in patients who have recently discontinued a drug for major depressive disorder and then are started on an MAOI, there have been reports of serious, and sometimes fatal, reactions, e.g., including nausea, vomiting, flushing, dizziness, tremor, myoclonus, rigidity, diaphoresis, hyperthermia, autonomic instability with rapid fluctuations of vital signs, seizures, and mental status changes ranging from agitation to coma. Although there are no human data pertinent to such an interaction with mirtazapine tablets, it is recommended that mirtazapine not be used in combination with an MAOI, or within 14 days of initiating or discontinuing therapy with an MAOI.
PRECAUTIONS
General
Somnolence
Information for Patients
Dizziness
Increased Appetite/Weight Gain
PRECAUTIONS: Pediatric Use
Cholesterol/Triglycerides
Transaminase Elevations
CLINICAL PHARMACOLOGYDOSAGE AND ADMINISTRATION
Activation of Mania/Hypomania
Seizure
Use in Patients with Concomitant Illness
22CLINICAL PHARMACOLOGYDOSAGE AND ADMINISTRATION
Information for Patients
Clinical Worsening and Suicide Risk
Agranulocytosis
Interference with Cognitive and Motor Performance
Completing Course of Therapy
Concomitant Medication
Alcohol
Pregnancy
Nursing
Laboratory Tests
Drug Interactions
CLINICAL PHARMACOLOGY
Drugs Affecting Hepatic Metabolism
Drugs that are Metabolized by and/or Inhibit Cytochrome P450 Enzymes
In vitroin vitro
Alcohol
Diazepam
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
2
Mutagenesis
in vitro in vitro in vivo
Impairment of Fertility
2
Pregnancy
Teratogenic effects
Pregnancy Category C.
22
Nursing Mothers
Pediatric Use
BOX WARNINGWARNINGS—Clinical Worsening and Suicide Risk
PRECAUTIONS-Increased Appetite/Weight Gain
Geriatric Use
CLINICAL PHARMACOLOGYDOSAGE AND ADMINISTRATION
MIRTAZAPINE ADVERSE REACTIONS
Associated with Discontinuation of Treatment
| Common Adverse Events Associated with Discontinuation of Treatment in 6-Week US Mirtazapine Trials |
||
| Adverse Event |
Percentage of Patients Discontinuing with Adverse Event |
|
| Mirtazapine (n=453) |
Placebo (n=361) |
|
| Somnolence |
10.4% |
2.2% |
| Nausea |
1.5% |
0% |
Commonly Observed Adverse Events in US Controlled Clinical Trials
| Common Treatment–Emergent Adverse Events Associated with the Use of Mirtazapine in 6-Week US Trials |
||
| Adverse Event |
Percentage of Patients Reporting Adverse Event |
|
| Mirtazapine (n=453) |
Placebo (n=361) |
|
| Somnolence |
54% |
18% |
| Increased Appetite |
17% |
2% |
| Weight Gain |
12% |
2% |
| Dizziness |
7% |
3% |
Adverse Events Occurring at an Incidence of 1% or More Among Mirtazapine-Treated Patients
|
1 Events reported by at least 1% of patients treated with mirtazapine are included, except the following events which had an incidence on placebo ≥ mirtazapine: headache, infection, pain, chest pain, palpitation, tachycardia, postural hypotension, nausea, dyspepsia, diarrhea, flatulence, insomnia, nervousness, libido decreased, hypertonia, pharyngitis, rhinitis, sweating, amblyopia, tinnitus, taste perversion. |
||
| Body System Adverse Clinical Experience |
Mirtazapine (n=453) |
Placebo (n=361) |
|
Body as a Whole
|
||
| Asthenia |
8% |
5% |
| Flu Syndrome |
5% |
3% |
| Back Pain |
2% |
1% |
|
Digestive System
|
||
| Dry Mouth |
25% |
15% |
| Increased Appetite |
17% |
2% |
| Constipation |
13% |
7% |
|
Metabolic and Nutritional Disorders
|
||
| Weight Gain |
12% |
2% |
| Peripheral Edema |
2% |
1% |
| Edema |
1% |
0% |
|
Musculoskeletal System
|
||
| Myalgia |
2% |
1% |
|
Nervous System
|
||
| Somnolence |
54% |
18% |
| Dizziness |
7% |
3% |
| Abnormal Dreams |
4% |
1% |
| Thinking Abnormal |
3% |
1% |
| Tremor |
2% |
1% |
| Confusion |
2% |
0% |
|
Respiratory System
|
||
| Dyspnea |
1% |
0% |
|
Urogenital System
|
||
| Urinary Frequency |
2% |
1% |
ECG Changes
Other Adverse Events Observed During the Premarketing Evaluation of Mirtazapine
WARNINGSPRECAUTIONS
Body as a Whole:frequent:infrequent: rare:
Cardiovascular System:frequent: infrequent:rare:
Digestive System:frequent: infrequent: rare:
Endocrine System:rare:
Hemic and Lymphatic System: rare:
Metabolic and Nutritional Disorders:frequent: infrequent: rare:
Musculoskeletal System:frequent: infrequent: rare:
Nervous System:frequent: infrequent: rare:
Respiratory System:frequent: infrequent: rare:
Skin and Appendages: frequent: infrequent: rare:
Special Senses:infrequent: rare:
Urogenital System:frequent:infrequent: rare:
Other Adverse Events Observed During Postmarketing Evaluation of Mirtazapine
DRUG ABUSE AND DEPENDENCE
Controlled Substance Class
Physical and Psychological Dependence
OVERDOSAGE
Human Experience
Overdose Management
Physicians’ Desk Reference (
MIRTAZAPINE DOSAGE AND ADMINISTRATION
Initial Treatment
Elderly and Patients with Renal or Hepatic Impairment
PRECAUTIONSCLINICAL PHARMACOLOGY
Maintenance/Extended Treatment
CLINICAL PHARMACOLOGY
Switching Patients To or From a Monoamine Oxidase Inhibitor
HOW SUPPLIED
15 mg Tablets
30 mg Tablets
45 mg Tablets
They are supplied by State of Florida DOH Central Pharmacy as follows:
| NDC | Strength | Quantity/Form | Color | Source Prod. Code |
| 53808-0482-1 | 15 mg | 30 Tablets in a Blister Pack | YELLOW | 60505-0247 |
| 53808-0483-1 | 30 mg | 30 Tablets in a Blister Pack | PINK | 60505-0248 |
| 53808-0484-1 | 45 mg | 30 Tablets in a Blister Pack | WHITE | 60505-0249 |
Apotex Inc.
This Product was Repackaged By:
State of Florida DOH Central Pharmacy
104-2 Hamilton Park Drive
Tallahassee, FL 32304
United States
Medication Guide
Antidepressant Medicines, Depression and other Serious Mental Illnesses, and Suicidal Thoughts or Actions
Talk to your, or your family member’s, healthcare provider about:
- all risks and benefits of treatment with antidepressant medicines
- all treatment choices for depression or other serious mental illness
What is the most important information I should know about antidepressant medicines, depression and other serious mental illnesses, and suicidal thoughts or actions?
- Antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment.
- Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have a particularly high risk of having suicidal thoughts or actions. These include people who have (or have a family history of) bipolar illness (also called manic-depressive illness) or suicidal thoughts or actions.
- How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member?
- Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant medicine is started or when the dose is changed.
- Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings.
- Keep all follow-up visits with the healthcare provider as scheduled. Call the healthcare provider between visits as needed, especially if you have concerns about symptoms.
Call a healthcare provider right away if you or your family member has any of the following symptoms, especially if they are new, worse, or worry you:
- thoughts about suicide or dying
- attempts to commit suicide
- new or worse depression
- new or worse anxiety
- feeling very agitated or restless
- panic attacks
- trouble sleeping (insomnia)
- new or worse irritability
- acting aggressive, being angry, or violent
- acting on dangerous impulses
- an extreme increase in activity and talking (mania)
- other unusual changes in behavior or mood
What else do I need to know about antidepressant medicines?
- Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an antidepressant medicine suddenly can cause other symptoms.
- Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. Patients and their families or other caregivers should discuss all treatment choices with the healthcare provider, not just the use of antidepressants.
- Antidepressant medicines have other side effects. Talk to the healthcare provider about the side effects of the medicine prescribed for you or your family member.
- Antidepressant medicines can interact with other medicines. Know all of the medicines that you or your family member takes. Keep a list of all medicines to show the healthcare provider. Do not start new medicines without first checking with your healthcare provider.
- Not all antidepressant medicines prescribed for children are FDA approved for use in children. Talk to your child’s healthcare provider for more information.
15mg Label
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30mg Label
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45mg Label
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PLEASE, BE CAREFUL!
Be sure to consult your doctor before taking any medication!
