TROSPIUM/ XANOMELINE CAP,ORAL
Clinical Criteria Summary
Document 685
Indication
- • Treatment of schizophrenia
Patient Selection & Clinical Criteria
- • Adults aged 18–65 years with a diagnosis of schizophrenia
- • Recent worsening of psychosis warranting hospital admission
- • Positive and Negative Syndrome Scale (PANSS) score of 80 or higher
- • Clinical Global Impression-Severity (CGI-S) score of 4 or higher
Dosing & Administration
- • Capsules available in strengths: 50mg/20mg, 100mg/20mg, 125mg/30mg
- • Days 1–2: 50 mg xanomeline and 20 mg trospium twice daily
- • Days 3–7: 100 mg xanomeline and 20 mg trospium twice daily
- • Beginning on day 8: Flexible dosing with optional increase to 125 mg xanomeline and 30 mg trospium twice daily or return to 100 mg/20 mg based on tolerability
Contraindications
- • Urinary retention
- • Moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment
- • Gastric retention
- • History or hypersensitivity to KarXT or trospium
- • Untreated narrow-angle glaucoma
Warnings & Precautions
- • Risk of urinary retention
- • Not recommended in patients with mild hepatic impairment (Child-Pugh Class A)
- • Risk of use in patients with biliary disease
- • Decreased gastrointestinal motility
- • Risk of angioedema
- • Risk of use in patients with narrow-angle glaucoma
- • Increases in heart rate
- • Anticholinergic adverse reaction in patients with renal impairment (not recommended for use in moderate and severe renal impairment, eGFR <60ml/min)
- • Central nervous system effects
Required Pre-prescribing Assessments
- • Assess liver enzymes and bilirubin prior to initiation
- • Assess heart rate at baseline
Formulary & Clinical Considerations
- • Formulary status: NF/TBD
- • Considerations include GI side effects and hypertension/increased heart rate
- • Note that efficacy trials were limited to 5 weeks; long-term efficacy and safety beyond controlled inpatient settings are not fully characterized
Document 686
Exclusion Criteria
- Moderate or severe renal impairment (eGFR < 60 ml/min)
- Mild (Child-Pugh Class A), moderate (Child-Pugh Class B), or severe (Child-Pugh Class C) hepatic impairment
- Untreated narrow-angle glaucoma
- Active biliary disease (e.g., symptomatic gallstones)
- Uncontrolled hypertension
- Concomitant condition with risk of urinary retention (e.g., neurogenic bladder, benign prostatic hyperplasia, bladder outlet obstruction, diabetic cystopathy)
- Concomitant condition with risk of bowel obstruction (e.g., gastric retention, inflammatory bowel disease, intestinal atony, neurogenic bowel)
Inclusion Criteria
- Diagnosis of schizophrenia
- Prescriber is a VA/VA Community Care psychiatrist
- Insufficient response or intolerance to trials of three of the following antipsychotics categories: partial dopamine agonism (e.g., aripiprazole), low dopamine affinity (e.g., olanzapine) and moderate to high dopamine affinity (e.g., risperidone)
- Inadequate response, intolerance, or patient determined not to be a candidate for clozapine
Monitoring & Prerequisites
- Liver enzymes, bilirubin, and heart rate should be assessed prior to initiation and as clinically indicated during treatment
- Adherent to, and achieved a target dose consistent with the effective doses specified in the FDA label for at least 6 weeks
- If intolerance is due to metabolic effects, efforts to mitigate these effects have been attempted with an adequate trial of at least 2 of the following: MOVE program participation, Metformin, Topiramate