Remeron

Remeron Information

Generic Name: Mirtazapine

Remeron (mirtazapine) Tablets are indicated for the treatment of depression.

How Does Remeron Work?

The mechanism of action of Remeron (mirtazapine) Tablets, as with other antidepressants, is unknown.

Evidence gathered in preclinical studies suggests that Remeron (mirtazapine) enhances central noradrenergic and serotonergic activity. These studies have shown that mirtazapine acts as an antagonist at central presynaptic a2 adrenergic inhibitory autoreceptors and heteroreceptors, an action that is postulated to result in an increase in central noradrenergic and serotonergic activity.

Remeron (mirtazapine) is a potent antagonist of 5-HT2 and 5-HT3 receptors. Mirtazapine has no significant affinity for the 5-HT1A and 5-HT1B receptors. Mirtazapine is a potent antagonist of histamine (Hi) receptors, a property that may explain its prominent sedative effects.

Remeron (mirtazapine) is a moderate peripheral a1 adrenergic antagonist, a property that may explain the occasional orthostatic hypotension reported in association with its use.

Remeron (mirtazapine) is a moderate antagonist at muscarinic receptors, a property that may explain the relatively low incidence of anticholinergic side effects associated with its use.

Remeron Ingredients and Composition

How To Take Remeron and Remeron Dosage and Administration

Initial Treatment

The recommended starting dose for Remeron (mirtazapine) Tablets is 15 mg/day, administered in a single dose, preferably in the evening prior to sleep. In the controlled clinical trials establishing the antidepressant efficacy of Remeron, the effective dose range was generally 15-45 mg/day. While the relationship between dose and antidepressant response for Remeron has not been adequately explored, patients not responding to the initial 15 mg dose may benefit from dose increases up to a maximum of 45 mg/day. Remeron has an elimination half-life of approximately 20-40 hours; therefore, dose changes should not be made at intervals of less than one to two weeks in order to allow sufficient time for evaluation of the therapeutic response to a given dose.

Elderly and Patients with Renal or Hepatic Impairment

The clearance of the active ingredient of Remeron, mirtazapine, is reduced in elderly patients and in patients with moderate to severe renal or hepatic impairment. Consequently, the prescriber should be aware that plasma mirtazapine levels may be increased in these patient groups, compared to levels observed in younger adults without renal or hepatic impairment.

Maintenance Extended Treatment

There is no body of evidence available from controlled trials to indicate how long the depressed patient should be treated with Remeron (mirtazapine) Tablets. It is generally agreed, however, that pharmacological treatment for acute episodes of depression should continue for up to six months or longer. Whether the dose of antidepressant needed to induce remission is identical to the dose needed to maintain euthymia is unknown.

Switching Patients To or From a Monoamine Oxidase Inhibitor

At least 14 days should elapse between discontinuation of an M.O. and initiation of therapy with Remeron (mirtazapine) Tablets. In addition, at least 14 days should be allowed after stopping Remeron before starting an MAOI.

If you suspect a Remeron Overdose

Human Experience

There is very limited experience with Remeron (mirtazapine) Tablets overdose. In premarketing clinical studies, there were eight reports of Remeron overdose alone or in combination with other pharmacological agents. The only drug overdose death reported while taking Remeron was in combination with amitriptyline and chlorprothixene in a non- U.S. clinical study. Based on plasma levels, the Remeron dose taken was 30-45 mg, while plasma levels of amitriptyline and chlorprothixene were found to be at toxic levels. All other premarketing overdose cases resulted in full recovery. Signs and symptoms reported in association with overdose included disorientation, drowsiness, impaired memory, and tachycardia. There were no reports of ECG abnormalities, coma or convulsions following overdose with Remeron alone.

Overdose Management

Treatment should consist of those general measures employed in the management of overdose with any antidepressant. There are no specific antidotes for Remeron (mirtazapine) Tablets. If the patient is unconscious, establish and maintain an airway to ensure adequate oxygenation and ventilation. Gastric evacuation either by the induction of emesis or lavage or both should be considered. Activated charcoal should also be considered in treatment of overdose. Cardiac and vital signs monitoring is recommended along with general symptomatic and supportive measures.

In managing Remeron overdosage, consider the possibility of multiple-drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of Remeron overdose.

Remeron Side Effects

Remeron Precautions and Contraindications

Agranulocytosis

Patients who are to receive Remeron should be warned about the risk of developing agranulocytosis. Patients should be advised to contact their physician if they experience any indication of infection such as fever, chills, sore throat, mucous membrane ulceration or other possible signs of infection. Particular attention should be paid to any flu-like complaints or other symptoms that might suggest infection.

Interference with Cognitive and Motor Performance

Remeron may impair judgement, thinking, and particularly, motor skills, because of its prominent sedative effect. The drowsiness associated with Remeron (mirtazapine) use may impair a patient's ability to drive, use machines or perform tasks that require alertness. Thus, patients should be cautioned about engaging in hazardous activities until they are reasonably certain that Remeron therapy does not adversely affect their ability to engage in such activities.

Somnolence:

In U. S. controlled studies, somnolence was reported in 54% of patients treated with Remeron (mirtazapine) Tablets, compared to 18% for placebo and 60% for amitriptyline. In these studies, somnolence resulted in discontinuation for 10.4% of Remeron treated patients, compared to 2.2% for placebo. It is unclear whether or not tolerance develops to the somnolent effects of Remeron. Because of Remeron's potentially significant effects on impairment of performance, patients should be cautioned about engaging in activities requiring alertness until they have been able to assess the drug's effect on their own psychomotor performance.

Dizziness:

In U.S. controlled studies, dizziness was reported in 7% of patients treated with Remeron, compared to 3% for placebo and 14% for amitriptyline. It is unclear whether or not tolerance develops to the dizziness observed in association with the use of Remeron.

Increased Appetite/Weight Gain:

In U. S. controlled studies, appetite increase was reported in 17% of patients treated with Remeron, compared to 2% for placebo and 6% for amitriptyline. 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 and 5.9% for amitriptyline. In a p.o. of premarketing U.S. studies, including many patients for long-term, open label treatment, 8% of patients receiving Remeron discontinued for weight gain. In an 8-week long pediatric clinical trial of doses between 15- 45 mg/day, 49% of mirtazapine-treated patients had a weight gain of at least 7%, compared to 5.7% of placebo treated patients.

Cholesterol/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 Remeron, compared to 7% for placebo and 8% for amitriptyline. In these same studies, nonfasting triglyceride increases to 500 mg/dL were observed in 6% of patients treated with mirtazapine, compared to 3% for placebo and 3% for amitriptyline.

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 exposed to Remeron in a p.o. of short-term U.S. controlled trials, compared to 0.3% (1/328) of placebo patients and 2.0% (3/181) of amitriptyline patients. Most of these patients with ALT increases did not develop signs or symptoms associated with compromised liver function. While some patients were discontinued for the ALT increases, in other cases, the enzyme levels returned to normal despite continued Remeron treatment. Remeron should be used with caution in patients with impaired hepatic function.

Activation of Mania/Hypomania:

Mania/hypomania occurred in approximately 0.2% (3/1,299 patients) of Remeron treated patients in U.S. studies. Although the incidence of mania/hypomania was very low during treatment with mirtazapine, it should be used carefully in patients with a history of mania/hypomania.

Seizure:

In premarketing clinical trials only one seizure was reported among the 2,796 U.S. and non- U.S. patients treated with Remeron. However, no controlled studies have been carried out in patients with a history of seizures. Therefore, care should be exercised when mirtazapine is used in these patients.

Suicide:

Suicidal ideation is inherent in depression and may persist until significant remission occurs. As with any patient receiving antidepressants, high-risk patients should be closely supervised during initial drug therapy. Prescriptions of Remeron should be written for the smallest quantity consistent with good patient management, in order to reduce the risk of overdose.

Use in Patients with Concomitant Illness:

Clinical experience with Remeron in patients with concomitant systemic illness is limited. Accordingly, care is advisable in prescribing mirtazapine for patients with diseases or conditions that affect metabolism or hemodynamic responses.

Remeron has not been systematically evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or other significant heart disease. Remeron was not associated with clinically significant ECG abnormalities in U. S. and non- U.S. placebo controlled trials. Remeron was associated with significant orthostatic hypotension in early clinical pharmacology trials with normal volunteers. Orthostatic hypotension was infrequently observed in clinical trials with depressed patients. Remeron 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).

Mirtazapine clearance is decreased in patients with moderate [glomerular filtration rate (GFR) = 11-39 mL/min/1.73 m2] and severe [GFR < 10 mL/min/1.73 m2] renal impairment, and also in patients with hepatic impairment.

Remeron and Alcohol Interaction

The impairment of cognitive and motor skills produced by Remeron has been shown to be additive with those produced by alcohol. Accordingly, patients should be advised to avoid alcohol while taking mirtazapine.

Taking Remeron during Pregnancy or Breast-feeding

Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during Remeron therapy.

Patients should be advised to notify their physician if they are breast-feeding an infant while on Remeron therapy.