MOLINDONE HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MOLINDONE HYDROCHLORIDE (MOLINDONE HYDROCHLORIDE).
Dopamine D2 receptor antagonist; also blocks serotonin 5-HT2A receptors and alpha-adrenergic receptors.
| Metabolism | Hepatic via oxidation and conjugation; CYP450 enzymes involved (specific isoenzymes not well characterized). |
| Excretion | Renal: 65-70% as metabolites and unchanged drug; Fecal: 20-25%; Biliary: minor. |
| Half-life | 1.5-2 hours; shorter than typical antipsychotics, requiring multiple daily dosing. |
| Protein binding | 76% bound; primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 1.6-2.0 L/kg; extensive tissue distribution with high lipophilicity. |
| Bioavailability | Oral: 55-60% due to first-pass metabolism; IM: near 100%. |
| Onset of Action | Oral: 30-60 minutes; IM: 15-30 minutes. |
| Duration of Action | Oral: 4-6 hours; IM: 4-6 hours; clinical context: short duration necessitates TID or QID dosing. |
50-225 mg/day orally in 3-4 divided doses; usual effective dose 50-75 mg/day; maximum 225 mg/day.
| Dosage form | TABLET |
| Renal impairment | No specific dosage adjustment guidelines available; use with caution in severe renal impairment (CrCl <10 mL/min) as drug accumulation may occur. |
| Liver impairment | No specific dosage adjustment guidelines available; use with caution in severe hepatic impairment due to potential for increased exposure. |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established; not recommended for use in children. |
| Geriatric use | Initiate at lower doses (e.g., 25-50 mg/day) with gradual titration; monitor for orthostatic hypotension, sedation, and extrapyramidal symptoms due to increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MOLINDONE HYDROCHLORIDE (MOLINDONE HYDROCHLORIDE).
| Breastfeeding | Excreted into human breast milk; milk-to-plasma ratio not established. Data limited; observe infant for sedation, irritability, and poor feeding. Weigh benefits of breastfeeding against potential infant exposure. |
| Teratogenic Risk | Pregnancy category C. First trimester: Limited human data; animal studies show embryocidal effects and increased resorptions at high doses; risk cannot be excluded. Second and third trimesters: Antipsychotic exposure may cause extrapyramidal symptoms and/or withdrawal symptoms in neonates; fluoxetine-like neonatal adaptation syndrome possible. Overall, use only if potential benefit justifies potential risk. |
■ FDA Black Box Warning
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Molindone is not approved for the treatment of dementia-related psychosis.
| Serious Effects |
["Hypersensitivity to molindone","Severe CNS depression","Comatose states"]
| Precautions | ["Neuroleptic Malignant Syndrome (NMS)","Tardive Dyskinesia","QT Prolongation","Hyperprolactinemia","Sedation","Orthostatic Hypotension"] |
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| Fetal Monitoring | Monitor maternal blood pressure, weight gain, and glycemic control; fetal growth via ultrasound if prolonged exposure; neonatal monitoring for extrapyramidal symptoms, sedation, and withdrawal after birth. |
| Fertility Effects | Hyperprolactinemia may occur via dopamine D2 receptor blockade, leading to menstrual irregularities, anovulation, and impaired fertility; reversible upon discontinuation. Also may cause sexual dysfunction and galactorrhea. |