xanomelene/trospium

Xanomelene: Acts as an agonist at M1 and M4 muscarinic acetylcholine receptors in the CNS. Trospium:Acts as a muscarinic antagonist. The mechanism of both xanomelene and trospium in treatment of schizophrenia is unclear.

Therapeutic effects:

Decreased manifestations of schizophrenia.

Pharmacokinetics ⬆ ⬇

Xanomelene

Absorption: High-fat meals ↑ absorption by 30%.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP2B6 isoenzymes. 78% excreted in urine; 12% excreted in feces.

Half-Life: 5 hr.

Trospium

Absorption: Low- or high-fat meals ↓ absorption by 85–90%.

Distribution: Well distributed to tissues.

Metabolism/Excretion: Primarily metabolized via ester hydrolysis and glucuronic acid conjugation. Primarily excreted in urine (85–90% as unchanged drug).

Half-Life: 6 hr.

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1–2 hr	12 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Urinary retention;
Moderate to severe renal impairment;
Hepatic impairment;
Active biliary disease (including symptomatic gallstones);
Gastric retention;
Untreated, narrow-angle glaucoma.

Use Cautiously in:

GI obstructive disorders;
Ulcerative colitis, intestinal atony, or myasthenia gravis;
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Safety and effectiveness not established in children;
Geri: Older adults may be at ↑ risk of adverse reactions.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, orthostatic hypotension, tachycardia

EENT: blurred vision

GI: constipation, dyspepsia, nausea, vomiting, ↑liver enzymes, ↑salivation, abdominal pain, diarrhea, dry mouth, gastroesophageal reflux disease

GU: dysuria, urinary hesitancy, urinary retention, urinary tract infection

Neuro: confusion, dizziness, hallucinations, sedation

Resp: cough

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

Strong CYP2D6 inhibitors may ↑ xanomelene levels and risk of toxicity.
Drugs eliminated by active tubular secretion may ↑ trospium levels and risk of toxicity.
May ↑ levels and risk of toxicity of CYP3A4 substrates or P-glycoprotein substrates.
May ↑ risk of anticholinergic effects when used with other anticholinergic drugs.
May alter absorption of concurrently administered drugs.

Route/Dosage ⬆ ⬇

PO (Adults ): One xanomelene 50 mg/trospium 20 mg capsule twice daily for ≥2 days, then ↑ to one xanomelene 100 mg/trospium 20 mg capsule twice daily for ≥5 days, then ↑ to one xanomelene 125 mg/trospium 30 mg capsule twice daily.
PO Geriatric Patients ): Start with one xanomelene 50 mg/trospium 20 mg capsule twice daily. Consider slower titration process. Max dose = one xanomelene 100 mg/trospium 20 mg twice daily.

Availability ⬆ ⬇

Capsules: xanomelene 50 mg/trospium 20 mg; xanomelene 100 mg/trospium 20 mg; xanomelene 125 mg/trospium 30 mg

Assessment ⬆ ⬇

Assess HR at baseline and as clinically indicated during therapy.
Monitor for signs/symptoms of urinary retention. If urinary retention occurs, consider discontinuing xanomelene/trospium, ↓ dose, and/or referring for urologic evaluation.
Monitor for signs/symptoms of anticholinergic CNS effects upon initiation and dose ↑. If CNS effects occur, consider ↓ dose or discontinuing xanomelene/trospium.

Lab Test Considerations:

Assess liver enzymes and bilirubin at baseline and as clinically indicated during therapy. If clinical signs of liver injury, or ALT levels >5 times upper limit of normal or baseline values occur, discontinue xanomelene/trospium.

Implementation ⬆ ⬇

PO: Administer 1 hr before or ≥2 hr after food. Do not open capsules.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Instruct patients to notify health care professional for symptoms of urinary retention (urinary hesitancy, weak stream, incomplete bladder emptying, painful urination).
Advise patient to immediately notify health care professional for signs/symptoms of angioedema (swelling of face, lips, tongue, larynx).
Advise patient to notify health care professional for signs/symptoms of ↓ GI motility or hepatic injury (dyspepsia, nausea, vomiting, upper abdominal pain, jaundice, itching), or anticholinergic CNS effects (dizziness, confusion, hallucinations, somnolence).
Advise patient not to drive or operate heavy machinery until they know how therapy affects them.
Rep: Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breastfeeding. Encourage pregnant patient to enroll in registry that monitors outcomes in patients who become pregnant while taking xanomelene/trospium by calling 1-866-961-2388 or visiting https://womensmentalhealth.org/research/pregnancyregistry/atypicalantipsychotic/.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇