DOLISHALE
Clinical safety rating
cautionComprehensive clinical and safety monograph for DOLISHALE (DOLISHALE).
DOLISHALE is a selective serotonin reuptake inhibitor (SSRI) that potentiates serotonergic activity in the CNS by inhibiting the reuptake of serotonin at the presynaptic neuronal membrane, enhancing serotonin neurotransmission.
| Metabolism | Primarily metabolized by CYP2D6 and CYP3A4 into active metabolites; undergoes hepatic conjugation. |
| Excretion | Renal: 70% unchanged; biliary/fecal: 20% as metabolites; 10% other |
| Half-life | Terminal elimination half-life: 12 hours (range 10-14) in adults; prolonged in renal impairment (up to 24 hours with CrCl <30 mL/min) |
| Protein binding | 98% bound primarily to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 0.8 L/kg (range 0.6-1.0), indicating extensive tissue distribution with high lipophilicity |
| Bioavailability | Oral: 60-70% (first-pass effect); Rectal: 50-60%; Intramuscular: 100% |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 5-10 minutes; Intramuscular: 15-30 minutes |
| Duration of Action | Analgesic effect: 4-6 hours (oral); 3-5 hours (IV); 6-8 hours (IM). Duration prolonged in hepatic impairment due to reduced metabolism. |
| Molecular Weight | 350.43 |
Adults: 200 mg orally twice daily or 400 mg orally once daily. Administer with food.
| Dosage form | TABLET |
| Renal impairment | eGFR 30-89 mL/min: 200 mg orally once daily. eGFR <30 mL/min or on dialysis: Not recommended. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: 200 mg orally once daily. Child-Pugh C: Not recommended. |
| Pediatric use | Children ≥12 years: 5 mg/kg orally twice daily, maximum 200 mg/dose. Children <12 years: Not established. |
| Geriatric use | Initiate at 200 mg orally once daily; titrate cautiously due to reduced renal function. |
| 1st trimester | Category C: Animal studies show fetal risk; no adequate human studies. Use only if potential benefit justifies risk. |
| 2nd trimester | Category C: Same as first trimester. Limited data, consider risk-benefit. |
| 3rd trimester | Category D: Positive evidence of human fetal risk. Avoid in third trimester due to risk of premature closure of ductus arteriosus and oligohydramnios. |
Clinical note
Comprehensive clinical and safety monograph for DOLISHALE (DOLISHALE).
| Placental transfer | Crosses placenta; detectable in fetal plasma and amniotic fluid. |
| Breastfeeding | Excreted in human milk; potential for serious adverse reactions in nursing infants. Decision to discontinue nursing or drug depends on importance of drug to mother. |
| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | DOLISHALE is contraindicated in pregnancy. First trimester: high risk of major congenital malformations including neural tube defects, cardiac anomalies, and craniofacial defects. Second and third trimesters: risk of fetal growth restriction, oligohydramnios, and renal impairment. |
| Fetal Monitoring | Monitor liver function tests (LFTs), renal function, and complete blood count (CBC) monthly. If accidental exposure during pregnancy, perform detailed ultrasound for fetal anomalies and assess amniotic fluid volume. |
| Fertility Effects | DOLISHALE may impair fertility in females by disrupting ovarian function and causing anovulation. In males, it may reduce spermatogenesis and sperm motility. Effects are reversible upon discontinuation. |
■ FDA Black Box Warning
WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS - Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies. Monitor closely for worsening or emergence of suicidal thoughts and behaviors.
| Serious Effects |
Hypersensitivity to active substance or excipientsSevere hepatic impairmentThird trimester pregnancy
| Precautions | Clinical worsening and suicide risk, Serotonin syndrome, Activation of mania/hypomania, QT prolongation, Hyponatremia, Bleeding risk, Angle-closure glaucoma, Sexual dysfunction |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase perampanel levels. No other significant food interactions. |
| Clinical Pearls | DOLISHALE (generic: perampanel) is a non-competitive AMPA receptor antagonist for partial-onset seizures. Monitor for serious psychiatric and behavioral adverse reactions including aggression, hostility, irritability, and suicidal ideation. Dose adjustment required in mild hepatic impairment; contraindicated in severe hepatic impairment. Use with caution in elderly due to falls risk. Serum concentration increased by strong CYP3A4 inducers; similarly, perampanel may decrease efficacy of oral contraceptives. |
| Patient Advice | Take exactly as prescribed; do not stop suddenly without consulting your doctor. · Avoid driving or operating heavy machinery until you know how DOLISHALE affects you, as it may cause dizziness, drowsiness, and coordination problems. · Report any new or worsening depression, mood changes, aggression, or thoughts of suicide immediately. · Inform your doctor if you have liver disease, kidney problems, or are pregnant or planning to become pregnant. · Hormonal contraceptives may be less effective; use an additional non-hormonal method of birth control. · Do not consume alcohol while on DOLISHALE as it may worsen side effects. · Store at room temperature away from moisture and heat. |
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