SERENTIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SERENTIL (SERENTIL).
SERENTIL (mesoridazine) is a phenothiazine antipsychotic that blocks postsynaptic dopamine D2 receptors in the mesolimbic system, and also exhibits alpha-adrenergic blocking, anticholinergic, and antihistaminic effects. It has high affinity for D2, 5-HT2A, and alpha-1 receptors.
| Metabolism | Extensively metabolized in the liver via CYP2D6 and, to a lesser extent, CYP3A4. The major active metabolites include sulforidazine and mesoridazine sulfoxide. Excretion primarily via urine and feces. |
| Excretion | Primarily renal (70-80% as conjugated and unconjugated metabolites) and fecal (15-20%). Biliary excretion contributes to enterohepatic circulation. |
| Half-life | Terminal elimination half-life is approximately 24-30 hours in adults. Does not correlate well with duration of antipsychotic effect due to active metabolite formation. |
| Protein binding | Approximately 95% bound to plasma proteins, primarily albumin and α1-acid glycoprotein. |
| Volume of Distribution | Vd is 10-17 L/kg, indicating extensive tissue distribution and accumulation in brain and other tissues. |
| Bioavailability | Oral bioavailability is approximately 65% due to first-pass hepatic metabolism. Intramuscular bioavailability is near 100%. |
| Onset of Action | Oral: 30-60 minutes. Intramuscular: 10-30 minutes. Peak effect for psychosis may require 2-4 weeks of regular dosing. |
| Duration of Action | Antipsychotic effects last 4-6 hours after single oral dose; steady-state therapeutic effects maintained with divided daily dosing. Sedation may persist longer. |
| Molecular Weight | 386.56 |
Oral: 50–100 mg 3 times daily; maximum 400 mg/day. IM: 25 mg every 4–6 hours.
| Dosage form | TABLET |
| Renal impairment | GFR 30–59 mL/min: 50–75% of usual dose. GFR 15–29 mL/min: 25–50% of usual dose. GFR <15 mL/min: avoid use. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50%. Child-Pugh Class C: reduce dose by 75% or avoid. |
| Pediatric use | Not recommended for children <12 years; >12 years: 0.5–1 mg/kg/day divided q6–8h, not to exceed 3 mg/kg/day. |
| Geriatric use | Start at 25 mg once daily; increase slowly; monitor for QT prolongation, hypotension, sedation; maximum 300 mg/day. |
| 1st trimester | Avoid due to lack of safety data; mesoridazine is not recommended in pregnancy, especially first trimester, as animal studies suggest potential teratogenicity. |
| 2nd trimester | Use only if potential benefit justifies risk; may be considered for severe psychosis where alternative therapies are ineffective. |
| 3rd trimester | Avoid near term due to risk of extrapyramidal symptoms and neonatal withdrawal (e.g., agitation, feeding disorders) in newborns exposed during the third trimester. |
Clinical note
Comprehensive clinical and safety monograph for SERENTIL (SERENTIL).
| Placental transfer | Mesoridazine crosses the placenta based on animal studies and its lipophilic nature; human data limited but placental transfer is expected due to moderate molecular weight and high lipid solubility. |
| Breastfeeding | Mesoridazine is excreted into breast milk. Due to potential for serious adverse reactions such as sedation, extrapyramidal symptoms, and neuroleptic malignant syndrome in nursing infants, breastfeeding is not recommended during therapy. Consider alternative antipsychotics with better safety profiles (e.g., haloperidol, olanzapine). |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis. SERENTIL is not approved for this condition. Additionally, it can cause QT interval prolongation, which may lead to torsades de pointes and sudden death; contraindicated in patients with certain conditions or concurrent use of QT-prolonging drugs.
| Serious Effects |
Hypersensitivity to mesoridazine or phenothiazinesComatose states or severe CNS depressionHistory of blood dyscrasias (e.g., agranulocytosis)Prolonged QTc interval or congenital long QT syndromeConcurrent use with drugs known to prolong QTc interval
| Precautions | QT prolongation and risk of torsades de pointes; neuroleptic malignant syndrome; tardive dyskinesia; orthostatic hypotension; anticholinergic effects; seizure threshold lowering; leukopenia/agranulocytosis; risk of falls; impaired core body temperature regulation; hepatic and renal impairment; interactions with QT-prolonging drugs, CNS depressants, anticholinergics, and CYP2D6 inhibitors. |
| Food/Dietary | Avoid alcohol and grapefruit juice as they may alter drug metabolism. Limit caffeine intake due to potential additive CNS stimulation. Take with food if gastrointestinal upset occurs; avoid high-fat meals that may increase absorption. |
Loading safety data…
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | First trimester: Limited data; phenothiazines are not major teratogens but risk of fetal malformations cannot be excluded. Second/third trimester: Potential for neonatal extrapyramidal symptoms, withdrawal, and respiratory depression with chronic use near term. |
| Fetal Monitoring | Monitor maternal blood pressure, ECG, hepatic function, and signs of neuroleptic malignant syndrome. Fetal monitoring for growth and movement; neonatal observation for extrapyramidal symptoms and withdrawal after delivery. |
| Fertility Effects | May cause hyperprolactinemia leading to galactorrhea, amenorrhea, and reduced libido; potentially reversible upon discontinuation. Effects on spermatogenesis not well studied; may impair fertility in both sexes. |
| Clinical Pearls | SERENTIL (mesoridazine) is a phenothiazine antipsychotic primarily used for schizophrenia. Monitor for QT prolongation, torsades de pointes, and anticholinergic effects. Avoid in patients with pre-existing cardiac conditions or electrolyte imbalances. Dose titration should be slow to minimize orthostatic hypotension. Extrapyramidal symptoms may occur; consider benztropine for management. Discontinue if signs of neuroleptic malignant syndrome appear. |
| Patient Advice | Take exactly as prescribed; do not stop abruptly as withdrawal symptoms may occur. · Rise slowly from sitting or lying to prevent dizziness. · Avoid alcohol and CNS depressants. · Report symptoms like irregular heartbeat, fainting, muscle stiffness, or fever. · May cause drowsiness; avoid driving until you know how the drug affects you. · Use sun protection as photosensitivity may occur. |