Molindone

Unless your doctor tells you otherwise, continue your normal diet.

Taking molindone with other drugs that make you sleepy or slow your breathing can cause dangerous side effects or death. Ask your doctor before taking a sleeping pill, narcotic pain medicine, prescription cough medicine, a muscle relaxer, or medicine for anxiety, depression, or seizures.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• phenytoin; or

• an antibiotic such as demeclocycline, doxycycline, minocycline, or tetracycline.

This list is not complete. Other drugs may interact with molindone, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

For all patients taking this medicine:

• If you have an allergy to molindone or any other part of molindone.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are very sleepy.
• If you have recently drunk a lot of alcohol or taken a big amount of drugs that may slow your actions like phenobarbital or some pain drugs like oxycodone.

Children:

• If your child is younger than 12 years of age. Do not give this medicine to a child younger than 12 years of age.

This is not a list of all drugs or health problems that interact with molindone.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Protect from light.
• Keep lid tightly closed.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Molindone Hydrochloride has a pharmacological profile in laboratory animals which predominantly resembles that of other antipsychotic agents causing reduction of spontaneous locomotion and aggressiveness, suppression of a conditioned response and antagonism of the bizarre stereotyped behavior and hyperactivity induced by amphetamines. In addition, Molindone Hydrochloride antagonizes the depression caused by the tranquilizing agent tetrabenazine.

In human clinical studies an antipsychotic effect is achieved in the absence of muscle relaxing or incoordinating effects. Based on EEG studies, Molindone Hydrochloride exerts its effect on the ascending reticular activating system.

Human metabolic studies show Molindone Hydrochloride Tablets to be rapidly absorbed and metabolized when given orally. Unmetabolized drug reached a peak blood level at 1.5 hours. Pharmacological effect from a single oral dose persists for 24 to 36 hours. There are 36 recognized metabolites with less than 2 to 3% unmetabolized Molindone Hydrochloride Tablets being excreted in urine and feces.

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. Molindone Hydrochloride Tablets are 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.)

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.

Falls

Molindone Hydrochloride 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.

Symptomatic, supportive therapy should be the rule.

Gastric lavage is indicated for the reduction of absorption of Molindone Hydrochloride which is freely soluble in water.

Since the adsorption of Molindone Hydrochloride by activated charcoal has not been determined, the use of this antidote must be considered of theoretical value.

Emesis in a comatose patient is contraindicated. Additionally, while the emetic effect of apomorphine is blocked by Molindone Hydrochloride in animals, this blocking effect has not been determined in humans.

A significant increase in the rate of removal of unmetabolized Molindone Hydrochloride from the body by forced diuresis, peritoneal or renal dialysis would not be expected. (Only 2% of a single ingested dose of Molindone Hydrochloride is excreted unmetabolized in the urine). However, poor response of the patient may justify use of these procedures.

While the use of laxatives or enemas might be based on general principles, the amount of unmetabolized Molindone Hydrochloride in feces is less than 1%. Extrapyramidal symptoms have responded to the use of Diphenhydramine (Benadryl®)*, Amantadine HCl (Symmetrel®)† and the synthetic anticholinergic antiparkinson agents, (i.e., Artane®‡, Cogentin®§, Akineton®¶).

Initial and maintenance doses of Molindone Hydrochloride Tablets should be individualized.

Initial Dosage Schedule

The usual starting dosage is 50 to 75 mg/day.
Increase to 100 mg/day in 3 or 4 days.
Based on severity of symptomatology, dosage may be titrated up or down depending on individual patient response.
An increase to 225 mg/day may be required in patients with severe symptomatology.
    Elderly and debilitated patients should be started on lower dosage.

Maintenance Dosage Schedule

1.      Mild-5 mg to 15 mg three or four times a day.
2.      Moderate-10 mg to 25 mg three or four times a day.
3.      Severe-225 mg/day may be required.

Molindone Hydrochloride Tablets USP, 5 mg are light orange to orange, oval compressed tablets debossed with “cor” on one side and “228” on the other side.

They are supplied as follows:

Bottles of 100          NDC 64720-228-10

Molindone Hydrochloride Tablets USP, 10 mg are light blue to blue, oval compressed tablets debossed with “cor” on one side and “229” on the other side.

They are supplied as follows:

Bottles of 100          NDC 64720-229-10

Molindone Hydrochloride Tablets USP, 25 mg are light green to green, oval compressed tablets debossed with “cor 230” on one side and bisect on the other side. They are supplied as follows:

Bottles of 100          NDC 64720-230-10

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

KEEP TIGHTLY CLOSED

*Benadryl is a registered trademark of Warner-Lambert.
†Symmetrel is a registered trademark of Endo Pharmaceuticals Inc.
‡Artane is a registered trademark of Lederle Laboratories.
§Cogentin is a registered trademark of Merck & Co., Inc.
¶ Akineton is a registered trademark of Knoll Laboratories.

LB # 774-01

Rev. November, 2016

Manufactured and Distributed by:
CorePharma, LLC
Middlesex, NJ 08846

Molindone Hydrochloride Tablets, USP
5 mg - 100 Tablets
NDC 64720-228-10

24 to 36 hours

Half-Life Elimination

1.5 hours

Protein Binding

76% (Owen 1989)

Refer to adult dosing. Use lower initial doses.

Psychosis/agitation associated with dementia (off-label use): Oral: Initial: One-third to one-half the usual dose to treat psychosis in younger adults or the smallest available dosage. In patients without a clinically significant response after 4 weeks, taper and withdraw therapy. In patients with an adequate response, attempt to taper and withdraw therapy within 4 months, unless symptoms recurred with a previous taper attempt. Assess symptoms at least monthly during taper and for at least 4 months after withdrawal of therapy (APA [Reus 2016]).

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.
• Blurred eyesight.
• Upset stomach.
• Dry mouth.
• More saliva.
• Hard stools (constipation).

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.