Molindone

Name: Molindone

Uses of Molindone

Molindone is used in the treatment of:

  • Psychotic Disorders
  • Schizophrenia

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

What is molindone?

Molindone is an antipsychotic medicine that affects the actions of chemicals in your brain.

Molindone is used to treat schizophrenia.

Molindone may also be used for purposes not listed in this medication guide.

What should I discuss with my healthcare provider before taking molindone?

You should not use molindone if you are allergic to it, or:

  • if you have decreased alertness caused by taking certain medications or drinking alcohol.

Molindone is not approved for use in psychotic conditions related to dementia. Molindone may increase the risk of death in older adults with dementia-related conditions.

To make sure molindone is safe for you, tell your doctor if you have:

  • epilepsy or other seizure disorder;

  • a history of low white blood cell (WBC) counts;

  • urination problems; or

  • a history of breast cancer.

Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

Taking antipsychotic medication during the last 3 months of pregnancy may cause problems in the newborn, such as withdrawal symptoms, breathing problems, feeding problems, fussiness, tremors, and limp or stiff muscles. However, you may have withdrawal symptoms or other problems if you stop taking your medicine during pregnancy. If you become pregnant while taking molindone, do not stop taking it without your doctor's advice.

It is not known whether molindone passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

How should I take molindone?

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.

You may not start feeling better right away when you start taking molindone. For best results, keep using the medication as directed.

Call your doctor if your symptoms do not improve, or if they get worse.

Store at room temperature away from moisture, heat, and light.

What should I avoid while taking molindone?

Do not drink alcohol. Dangerous side effects or death could occur.

Molindone may impair your thinking or reactions. Avoid driving or operating machinery until you know how this medicine will affect you.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Dizziness or severe drowsiness can cause falls, fractures, or other injuries.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Shakiness, trouble moving around, or stiffness.
  • Seizures.
  • Nipple discharge.
  • For women, no period.
  • Enlarged breasts.
  • Change in sex ability.
  • Erection that lasts more than 4 hours.
  • Not able to sit still.
  • Mood changes.
  • Restlessness.
  • Trouble swallowing.
  • A fast heartbeat.
  • Trouble passing urine.
  • Some people who take this medicine may get a very bad muscle problem called tardive dyskinesia. This muscle problem may not go away even if molindone is stopped. Sometimes, signs may lessen or go away over time after this medicine is stopped. The risk of tardive dyskinesia may be greater in people with diabetes and in older adults, especially older women. The risk is also greater the longer you take molindone or with higher doses. Muscle problems may also occur after short-term use with low doses. Call your doctor right away if you have trouble controlling body movements or if you have muscle problems with your tongue, face, mouth, or jaw like tongue sticking out, puffing cheeks, mouth puckering, or chewing.
  • A very bad and sometimes deadly health problem called neuroleptic malignant syndrome (NMS) may happen. Call your doctor right away if you have any fever, muscle cramps or stiffness, dizziness, very bad headache, confusion, change in thinking, fast heartbeat, heartbeat that does not feel normal, or are sweating a lot.

If OVERDOSE is suspected

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.

Dosing Adult

Schizophrenia: Oral:

Initial: 50 to 75 mg/day, may increase based on response and tolerability to 100 mg/day in 3 to 4 days; may further increase dose gradually to maximum of 225 mg/day

Maintenance: 5 to15 mg (mild symptoms) or 10 to 25 mg (moderate symptoms) 3 to 4 times/day (up to 225 mg/day may be required in severe cases). Treatment guidelines recommend maintenance doses of 30 to 100 mg/day (APA [Lehman 2004]; Buchanan 2010).

Debilitated patients: Use lower starting doses.

Discontinuation of therapy: American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend gradually tapering antipsychotics to avoid withdrawal symptoms and minimize the risk of relapse (APA [Lehman 2004]; Cerovecki 2013; CPA [Addington 2005]; WFSBP [Hasan 2012]); risk for withdrawal symptoms may be highest with highly anti-cholinergic or dopaminergic antipsychotics (Cerovecki 2013). When stopping antipsychotic therapy in patients with schizophrenia, the CPA guidelines recommend a gradual taper over 6 to 24 months, and the APA guidelines recommend reducing the dose by 10% each month (APA [Lehman 2004]; CPA [Addington 2005]). Continuing anti-parkinsonism agents for a brief period after discontinuation may prevent withdrawal symptoms (Cerovecki 2013). When switching antipsychotics, 3 strategies have been suggested: Cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic), overlap and taper (maintaining the dose of the first antipsychotic while gradually increasing the new antipsychotic, then tapering the first antipsychotic), and abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose). Evidence supporting ideal switch strategies and taper rates is limited, and results are conflicting (Cerovecki 2013; Remington 2005).

Dosing Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Storage

Store at controlled room temperature of 20°C to 25°C (68°F to 77°F). Protect from light.

Warnings/Precautions

Concerns related to adverse effects:

• Altered cardiac conduction: May alter cardiac conduction (rare); life-threatening arrhythmias have occurred with therapeutic doses of antipsychotics.

• Anticholinergic effects: May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased gastrointestinal motility, paralytic ileus, urinary retention, benign prostatic hyperplasia, xerostomia, or visual problems. Relative to other neuroleptics, molindone has a low potency of cholinergic blockade (Owen 1989; Richelson 1999).

• Antiemetic effects: May mask toxicity of other drugs or conditions (eg, intestinal obstruction, Reye syndrome, brain tumor) due to antiemetic effects.

• Blood dyscrasias: Leukopenia, neutropenia, and agranulocytosis (sometimes fatal) have been reported in clinical trials and postmarketing reports with antipsychotic use; presence of risk factors (eg, preexisting low white blood cell count or history of drug-induced leuko-/neutropenia) should prompt periodic blood count assessment. Discontinue therapy at first signs of blood dyscrasias or if absolute neutrophil count <1,000/mm3.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving). Relative to other neuroleptics, molindone has a lower tendency for sedation (Owen 1989).

• Esophageal dysmotility/aspiration: Antipsychotic use has been associated with esophageal dysmotility and aspiration; use with caution in patients at risk of pneumonia (ie, Alzheimer disease) (Maddalena 2004).

• Extrapyramidal symptoms: May cause extrapyramidal symptoms (EPS), including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia. Risk of dystonia (and possibly other EPS) may be greater with increased doses, use of conventional antipsychotics, males, and younger patients (APA [Lehman 2004]). Factors associated with greater vulnerability to tardive dyskinesia include older in age, female gender combined with postmenopausal status, Parkinson disease, pseudoparkinsonism symptoms, affective disorders (particularly major depressive disorder), concurrent medical diseases such as diabetes, previous brain damage, alcoholism, poor treatment response, and use of high doses of antipsychotics (APA [Lehman 2004]; Soares-Weiser 2007). Consider therapy discontinuation with signs/symptoms of tardive dyskinesia.

• Falls: May increase the risk for falls due to somnolence, orthostatic hypotension, and motor or sensory instability. Complete fall risk assessments at baseline and periodically during treatment in patients with diseases or on medications that may also increase fall risk.

• Hyperprolactinemia: Use associated with increased prolactin levels; clinical significance of hyperprolactinemia in patients with breast cancer or other prolactin-dependent tumors is unknown.

• Neuroleptic malignant syndrome (NMS): Use may be associated with NMS; monitor for mental status changes, fever, muscle rigidity, and/or autonomic instability. Following recovery from NMS, reintroduction of drug therapy should be carefully considered; if an antipsychotic agent is resumed, monitor closely for NMS.

• Orthostatic hypotension: May rarely cause orthostatic hypotension; use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use that may predispose to hypotension/bradycardia).

• Temperature regulation: Impaired core body temperature regulation may occur with antipsychotics; caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects (Kwok 2005; Martinez 2002).

Disease-related concerns:

• Dementia: [US Boxed Warning]: Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo. Most deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Use with caution in patients with Lewy body dementia or Parkinson disease dementia due to greater risk of adverse effects, increased sensitivity to extrapyramidal effects, and association with irreversible cognitive decompensation or death. The APA recommends giving preference to second generation antipsychotics over first generation antipsychotics in elderly patients with dementia-related psychosis due to a potentially greater risk of harm relative to second generation antipsychotics (APA [Reus 2016]). Molindone is not approved for the treatment of dementia-related psychosis.

• Hepatic impairment: Use with caution in patients with hepatic impairment; transaminase alterations have been reported rarely.

• Parkinson disease: Use with caution in patients with Parkinson disease; antipsychotics may aggravate motor disturbances (APA [Lehman 2004]; APA [Reus 2016]).

• Seizure disorder: Use with caution in patients at risk of seizures.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Discontinuation of therapy: When discontinuing antipsychotic therapy, the American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend gradually tapering antipsychotics to avoid physical withdrawal symptoms, including anorexia, anxiety, diaphoresis, diarrhea, dizziness, dyskinesia, headache, myalgia, nausea, paresthesia, restlessness, tremulousness, and vomiting (APA [Lehman 2004]; CPA [Addington 2005]; Lambert 2007; WFSBP [Hasan 2012]). The risk of withdrawal symptoms is highest following abrupt discontinuation of highly anti-cholinergic or dopaminergic antipsychotics (Cerovecki 2013). Additional factors such as duration of antipsychotic exposure, the indication for use, medication half-life and risk for relapse should be considered. In schizophrenia, there is no reliable indicator to differentiate the minority who will not from the majority who will relapse with drug discontinuation. However, studies in which the medication of well-stabilized patients were discontinued indicate that 75% of patients relapse within 6 to 24 months. Indefinite maintenance antipsychotic medication is generally recommended, and especially for patients who have had multiple prior episodes or 2 episodes within 5 years (APA [Lehman 2004]).

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies. Antipsychotic use during the third trimester of pregnancy has a risk for abnormal muscle movements (extrapyramidal symptoms [EPS]) and withdrawal symptoms in newborns following delivery. Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor; these effects may be self-limiting or require hospitalization. If needed, the minimum effective maternal dose should be used in order to decrease the risk of EPS (ACOG 2008).

Usual Pediatric Dose for Schizophrenia

12 to 18 years:
Initial Dosage Schedule:
-Recommended dose: 50 to 75 mg orally per day, increasing the dose to 100 mg/day in 3 to 4 days
-Maximum dose: 225 mg/day

Maintenance Dosing Schedule:
-Mild symptomology: 5 to 15 mg orally 3 to 4 times a day
-Moderate symptomology: 10 to 25 mg orally 3 to 4 times a day
-Severe symptomology: Up to 225 mg/day

Comments:
-Patients with severe symptomology may require 225 mg/day.
-Debilitated patients should begin on the lower dosage.

Use: Management of schizophrenia

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