Molindone Hydrochloride Tablets

MOBAN (molindone hydrochloride) is a dihydroindolone compound which is not structurally related to the phenothiazines, the butyrophenones or the thioxanthenes.

MOBAN is 3-ethyl-6, 7-dihydro-2-methyl-5-(morpholinomethyl) indol-4 (5H)-one hydrochloride. It is a white to off-white crystalline powder, freely soluble in water and alcohol.

MOBAN Tablets contain the following inactive ingredients:

Calcium sulfate, lactose, magnesium stearate, microcrystalline cellulose and povidone.

The 5 mg strength also contains alginic acid, colloidal silicon dioxide and FD&C Yellow 6.

The 10 mg strength also contains alginic acid, colloidal silicon dioxide, FD&C Blue 2 and FD&C Red 40.

The 25 mg strength also contains alginic acid, colloidal silicon dioxide, D&C Yellow 10, FD&C Blue 2, and FD&C Yellow 6.

The 50 mg strength also contains FD&C Blue 2 and sodium starch glycolate.

Molindone Hydrochloride is represented by the following structural formula:

The empirical formula is C16H24N2O2 • HCl representing a molecular weight of 312.83.

MOBAN is indicated for the management of schizophrenia. The efficacy of MOBAN in schizophrenia was established in clinical studies which enrolled newly hospitalized and chronically hospitalized, acutely ill, schizophrenic patients as subjects.

CNS Effects

The most frequently occurring effect is initial drowsiness that generally subsides with continued usage of the drug or lowering of the dose.

Noted less frequently were depression, hyperactivity and euphoria.

Neurological

Extrapyramidal symptoms noted below may occur in susceptible individuals and are usually reversible with appropriate management.

Motor restlessness may occur early.

Akinesia, characterized by rigidity, immobility and reduction of voluntary movements and tremor, have been observed. Occurrence is less frequent than akathisia.

Class effect: Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.

Antipsychotic drugs are known to cause a syndrome of dyskinetic movements commonly referred to as tardive dyskinesia. The movements may appear during treatment or upon withdrawal of treatment and may be either reversible or irreversible (i.e., persistent) upon cessation of further antipsychotic administration.

The syndrome is known to have a variable latency for development and the duration of the latency cannot be determined reliably. It is thus wise to assume that any antipsychotic agent has the capacity to induce the syndrome and act accordingly until sufficient data has been collected to settle the issue definitively for a specific drug product. In the case of antipsychotics known to produce the irreversible syndrome, the following has been observed.

Tardive dyskinesia has appeared in some patients on long-term therapy and has also appeared after drug therapy has been discontinued. The risk appears to be greater in elderly patients on high-dose therapy, especially females. The symptoms are persistent and in some patients appear to be irreversible. The syndrome is characterized by rhythmical involuntary movements of the tongue, face, mouth or jaw (e.g., protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements). There may be involuntary movements of extremities.

There is no known effective treatment of tardive dyskinesia; antiparkinsonism agents usually do not alleviate the symptoms of this syndrome. It is suggested that all antipsychotic agents be discontinued if these symptoms appear. Should it be necessary to reinstitute treatment, or increase the dosage of the agent, or switch to a different antipsychotic agent, the syndrome may be masked. It has been reported that fine vermicular movements of the tongue may be an early sign of the syndrome and if the medication is stopped at that time the syndrome may not develop (See WARNINGS).

Autonomic Nervous System

Occasionally blurring of vision, tachycardia, nausea, dry mouth and salivation have been reported. Urinary retention and constipation may occur particularly if anticholinergic drugs are used to treat extrapyramidal symptoms. One patient being treated with MOBAN experienced priapism which required surgical intervention, apparently resulting in residual impairment of erectile function.

Laboratory Tests

There have been rare reports of leucopenia and leucocytosis. If such reactions occur, treatment with MOBAN may continue if clinical symptoms are absent. Alterations of blood glucose, B.U.N., and red blood cells have not been considered clinically significant.

Metabolic And Endocrine Effects

Alteration of thyroid function has not been significant. Amenorrhea has been reported infrequently. Resumption of menses in previously amenorrheic women has been reported. Initially heavy menses may occur. Galactorrhea and gynecomastia have been reported infrequently. Increase in libido has been noted in some patients. Impotence has not been reported. Although both weight gain and weight loss have been in the direction of normal or ideal weight, excessive weight gain has not occurred with MOBAN.

Hepatic Effects

There have been rare reports of clinically significant alterations in liver function in association with MOBAN use.

Cardiovascular

Rare, transient, non-specific T wave changes have been reported on E.K.G. Association with a clinical syndrome has not been established. Rarely has significant hypotension been reported.

Ophthalmological

Lens opacities and pigmentary retinopathy have not been reported where patients have received MOBAN. In some patients, phenothiazine induced lenticular opacities have resolved following discontinuation of the phenothiazine while continuing therapy with MOBAN.

Skin

Early, non-specific skin rash, probably of allergic origin, has occasionally been reported. Skin pigmentation has not been seen with MOBAN usage alone.

MOBAN has certain pharmacological similarities to other antipsychotic agents. Because adverse reactions are often extensions of the pharmacological activity of a drug, all of the known pharmacological effects associated with other antipsychotic drugs should be kept in mind when MOBAN is used. Upon abrupt withdrawal after prolonged high dosage an abstinence syndrome has not been noted.

Increased Mortality in Elderly Patients with Dementia-Related Psychosis - Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. MOBAN is not approved for the treatment of patients with dementia-related psychosis (see BOXED WARNING).

Tardive Dyskinesia

Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown.

Both the risk of developing the syndrome and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses.

There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying disease process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.

Given these considerations, antipsychotics should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that, 1) is known to respond to antipsychotic drugs, and 2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.

If signs and symptoms of tardive dyskinesia appear in a patient on antipsychotics, drug discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome.

(For further information about the description of tardive dyskinesia and its clinical detection, please refer to the section on Adverse Reactions.)

Falls

MOBAN may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.

Neuroleptic Malignant Syndrome (NMS)

A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias).

The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology.

The management of NMS should include, 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.

If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported.

Molindone is not for use in psychotic conditions related to dementia. Molindone may cause heart failure, sudden death, or pneumonia in older adults with dementia-related conditions.

You should not use this medication if you are allergic to molindone, or if you have decreased alertness caused by taking certain medications or drinking alcohol.

Call your doctor at once if you have restless muscle movements in your eyes, tongue, jaw, or neck.

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

Avoid drinking alcohol. You should not take molindone if you are under the effects of alcohol.

Avoid becoming overheated or dehydrated during exercise and in hot weather. Molindone can decrease perspiration and you may be more prone to heat stroke.

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

Avoid drinking alcohol. You should not take molindone if you are under the effects of alcohol.

Avoid becoming overheated or dehydrated during exercise and in hot weather. Molindone can decrease perspiration and you may be more prone to heat stroke.