Remeron

Remeron is a prescription medicine used to treat depression. 

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Remeron, there are no specific foods that you must exclude from your diet when receiving this medication. Do not drink alcohol while taking this medication.

Tell your healthcare provider if you are breastfeeding or plan to breastfeed. Some Remeron may pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby while taking Remeron.

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

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

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

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

• 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

Mirtazapine is used to treat depression. Mirtazapine belongs to a group of medicines called tetracyclic antidepressants. These medicines work in the central nervous system (CNS) to make certain chemicals in the brain stronger.

This medicine is available only with your doctor's prescription.

It is very important that your doctor check your progress at regular visits, to allow changes in your dose and help reduce any side effects. Blood tests may be needed to check for unwanted effects.

Do not take mirtazapine with a monoamine oxidase (MAO) inhibitor (eg, isocarboxazid [Marplan®], linezolid [Zyvox®], methylene blue injection, phenelzine [Nardil®], selegiline [Eldepryl®], tranylcypromine [Parnate®]). Do not start taking mirtazapine during the 2 weeks after you stop a MAO inhibitor and wait 2 weeks after stopping mirtazapine before you start taking a MAO inhibitor. If you take them together or do not wait 2 weeks, you may develop confusion, agitation, restlessness, stomach or intestinal symptoms, a sudden high body temperature, an extremely high blood pressure, or severe convulsions.

Mirtazapine may cause a serious condition called serotonin syndrome if taken together with some medicines. Do not use mirtazapine with buspirone (Buspar®), fentanyl (Abstral®, Duragesic®), lithium (Eskalith®, Lithobid®), tryptophan, St. John's wort, or some pain or migraine medicines (eg, rizatriptan, sumatriptan, tramadol, Frova®, Imitrex®, Maxalt®, Relpax®, Ultram®, Zomig®). Check with your doctor first before taking any other medicines with mirtazapine.

For some children, teenagers, and young adults, this medicine can increase thoughts of suicide. Tell your doctor right away if you start to feel more depressed and have thoughts of hurting yourself. Report any unusual thoughts or behaviors that trouble you, especially if they are new or getting worse quickly. Make sure the doctor knows if you have trouble sleeping, get upset easily, have a big increase in energy, or start to act reckless. Also tell the doctor if you have sudden or strong feelings, such as feeling nervous, angry, restless, violent, or scared. Let the doctor know if you or anyone in your family has bipolar disorder (manic-depressive) or has tried to commit suicide.

Using this medicine may cause a serious condition called serotonin syndrome. Check with your doctor right away if you are having agitation, convulsions, difficulty in breathing, a fast heartbeat, hallucinations, a high fever, high or low blood pressure, increased sweating, loss of bladder control, severe muscle stiffness, unusually pale skin, or tiredness while you are taking this medicine.

This medicine may add to the effects of alcohol and other CNS depressants (medicines that make you drowsy or less alert). Some examples of CNS depressants are antihistamines or medicine for allergies or colds, sedatives, tranquilizers, or sleeping medicines, prescription pain medicine or narcotics, medicine for seizures or barbiturates, muscle relaxants, or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are taking this medicine.

This medicine can temporarily lower the number of white blood cells in your blood, increasing your chance of getting an infection. If you can, avoid people with infections. Check with your doctor right away if you think you are getting an infection or if you have a fever or chills, sore throat, sores in the mouth, lower back or side pain, or painful or difficult urination.

Do not suddenly stop taking this medicine without first checking with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping completely. This may help prevent a possible worsening of your condition and reduce the possibility of withdrawal symptoms such as headache, nausea, or a general feeling of discomfort or illness.

This medicine may increase your weight. Your doctor may need to check your weight on a regular basis while you are using this medicine.

Mirtazapine may cause drowsiness, trouble with thinking, or trouble with controlling body movements. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that requires you to be alert, well-coordinated, and able to think well.

Dizziness, lightheadedness, or fainting may occur, especially when you get up suddenly from a lying or sitting position. Getting up slowly may help. If this problem continues or gets worse, check with your doctor.

This medicine may cause dry mouth. For temporary relief, use sugarless gum or candy, melt bits of ice in your mouth, or use a saliva substitute. However, if your mouth feels dry for more than 2 weeks, check with your medical doctor or dentist. Continuing dryness of the mouth may increase the chance of dental disease, including tooth decay, gum disease, and fungal infections.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Feeling sleepy.
• Dizziness.
• Hard stools (constipation).
• Dry mouth.
• More hungry.
• Weight gain.
• Feeling tired or weak.
• Strange or odd dreams.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

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

Clinical Worsening and Suicide Risk

Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18–24) with major depressive disorder (MDD) and other psychiatric disorders. 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.

The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across different indications, with the highest incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1.

No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.

It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.

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.

The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.

Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.

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. Prescriptions for Remeron (mirtazapine) Tablets should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that Remeron (mirtazapine) Tablets are not approved for use in treating bipolar depression.

Agranulocytosis

In premarketing clinical trials, 2 (1 with Sjögren's Syndrome) out of 2796 patients treated with Remeron (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 Remeron was stopped. These 3 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 1000. If a patient develops a sore throat, fever, stomatitis, or other signs of infection, along with a low WBC count, treatment with Remeron should be discontinued and the patient should be closely monitored.

Serotonin Syndrome

The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including Remeron, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's wort), and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome.

The concomitant use of Remeron with MAOIs intended to treat psychiatric disorders is contraindicated. Remeron should also not be started in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue. All reports with methylene blue that provided information on the route of administration involved intravenous administration in the dose range of 1 mg/kg to 8 mg/kg. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection) or at lower doses. There may be circumstances when it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking Remeron. Remeron should be discontinued before initiating treatment with the MAOI (see CONTRAINDICATIONS and DOSAGE AND ADMINISTRATION).

If concomitant use of Remeron with other serotonergic drugs, including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, and St. John's wort, is clinically warranted, be aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.

Treatment with Remeron and any concomitant serotonergic agents should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated.

Angle-Closure Glaucoma

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

NDC 0052-0109-30

Remeron®
(mirtazapine)Tablets

45 mg

Dispense the accompanying
Medication Guide to each patient.

Rx only

30 Tablets

Avoid drinking alcohol. It may increase certain side effects of Remeron.

Remeron may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Applies to mirtazapine: oral tablet, oral tablet disintegrating

Along with its needed effects, mirtazapine (the active ingredient contained in Remeron) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking mirtazapine:

• Decreased or increased movement
• mood or mental changes, including abnormal thinking, agitation, anxiety, confusion, and feelings of not caring
• shortness of breath
• skin rash
• swelling

• Change in menstrual cycle (periods)
• convulsions (seizures)
• decreased sexual ability
• menstrual pain
• mood or mental changes, including anger, feelings of being outside the body, hallucinations (seeing, hearing, or feeling things that are not there), mood swings, and unusual excitement
• mouth sores
• sore throat, chills, or fever

Some side effects of mirtazapine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Constipation
• dizziness
• drowsiness
• dry mouth
• increased appetite
• weight gain

• Abdominal or stomach pain
• abnormal dreams
• back pain
• dizziness or fainting when getting up suddenly from a lying or sitting position
• increased need to urinate
• increased sensitivity to touch
• increased thirst
• low blood pressure
• muscle pain
• nausea
• sense of constant movement of self or surroundings
• trembling or shaking
• vomiting
• weakness

• Used for the treatment of significant depression (Major Depressive Disorder).