EXSERVAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EXSERVAN (EXSERVAN).
Exservan (riluzole) is a benzothiazole derivative that modulates glutamatergic neurotransmission. Its mechanism of action involves inhibition of glutamate release, inactivation of voltage-dependent sodium channels, and interference with neurotransmitter binding to excitatory amino acid receptors.
| Metabolism | Riluzole is extensively metabolized in the liver via N-hydroxylation (CYP1A2) and glucuronidation (UGT1A1, UGT1A3, UGT1A8, UGT1A9, UGT2B7). |
| Excretion | Primarily renal excretion as unchanged drug: 80% excreted unchanged in urine; approximately 20% as metabolites; biliary/fecal <5%. |
| Half-life | Terminal elimination half-life is approximately 3–4 hours in patients with normal renal function; prolonged in renal impairment (up to 8–10 hours in ESRD). |
| Protein binding | Approximately 40% bound to plasma proteins (mainly albumin). |
| Volume of Distribution | Volume of distribution (Vd) is approximately 1.0 L/kg; moderate distribution suggests limited tissue binding. |
| Bioavailability | Sublingual film (EXSERVAN): bioavailability is 100% relative to oral disintegrating tablet; oral tablets exhibit approximately 30% bioavailability due to extensive first-pass metabolism. |
| Onset of Action | Oral: onset occurs within 15–30 minutes; sublingual film (EXSERVAN): onset within 5–15 minutes due to rapid absorption via oral mucosa. |
| Duration of Action | Duration of clinical effect is 3–5 hours for sublingual film; may be shorter with oral tablets (2–4 hours). Individual variability exists; careful titration required. |
Adults: 15 mg orally once daily in the morning; increase to 30 mg after 2 weeks if needed. Maximum 30 mg/day.
| Dosage form | FILM |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (eGFR<30 mL/min/1.73 m²). |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): 15 mg once daily. Moderate to severe hepatic impairment (Child-Pugh B or C): not recommended. |
| Pediatric use | Not approved for use in pediatric patients. |
| Geriatric use | No specific dose adjustment; use with caution due to increased sensitivity and potential for adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EXSERVAN (EXSERVAN).
| Breastfeeding | Not recommended due to potential for infant sedation and respiratory depression. M/P ratio: oxycodone 3.2:1 (based on milk-to-plasma ratio). |
| Teratogenic Risk | Pregnancy Category C. No adequate studies in pregnant women. In animal studies, oxycodone (active metabolite) caused fetal harm at high doses. First trimester: risk of neural tube defects (?). Second/third trimesters: risk of neonatal opioid withdrawal syndrome, respiratory depression, low birth weight, preterm birth. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
["Severe hypersensitivity to riluzole or any excipient","Severe hepatic impairment (e.g., Child-Pugh class C)","Concomitant use with strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin) is not recommended due to increased exposure."]
| Precautions | ["Hepatotoxicity: Elevation of serum aminotransferases; monitor LFTs regularly. Discontinue if ALT > 5x ULN or clinical jaundice develops.","Neutropenia: Rare; monitor CBC with differential.","Interstitial lung disease: Discontinue if respiratory symptoms develop.","Embryo-fetal toxicity: May cause fetal harm; advise females of reproductive potential to use effective contraception.","Renal impairment: Not recommended if CrCl < 30 mL/min."] |
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| Monitor for fetal growth restriction via ultrasound; assess for neonatal abstinence syndrome after delivery; monitor maternal respiratory status and sedation. |
| Fertility Effects | Opioids may impair fertility by disrupting hypothalamic-pituitary-gonadal axis, causing irregular menstruation and decreased libido. Reversible upon discontinuation. |