Cobenfy(KarXT)中文说明书

Author: Medicalhalo

Release time: 2025-10-19 11:44:20

Cobenfy (KarXT) is a compound preparation developed by Karuna Therapeutics, which was later acquired and integrated by Bristol-Myers Squibb (BMS).

Indications for Cobenfy (KarXT)

It is suitable for the treatment of schizophrenia in adults.

Cobenfy (KarXT) usage and dosage

1. Recommended testing and monitoring before starting Cobenfy treatment and during treatment

Evaluate liver enzymes and bilirubin before starting Cobenfy treatment and during treatment as clinically necessary.

Assess heart rate at baseline and as clinically necessary during treatment.

2. Recommended dose

The recommended starting dose is to take one 50mg/20mg capsule (containing 50mg xanomeline and 20mg trospium chloride) orally twice a day for at least two days.

Increase the dose to one 100 mg/20 mg capsule (containing 100 mg xanomeline and 20 mg trospium chloride) orally twice daily for at least five days.

Based on the patient's tolerance and response, the dose can be increased to one 125 mg/30 mg capsule (containing 125 mg xanomeline and 30 mg trospium chloride) orally twice daily.

The maximum recommended dose is 125mg/30mg, taken orally twice daily.

3. Medication time

Cobenfy should be taken orally at least one hour before or two hours after a meal.

4. Dosage recommendation for elderly patients

The recommended starting dose of Cobenfy for elderly patients is one 50mg/20mg capsule, taken orally twice a day. Consider slower dose titration in elderly patients. The maximum recommended dose for elderly patients is one 100 mg/20 mg capsule twice daily.

5. Overdose

Cobenfy overdose may produce cholinergic, anticholinergic, or mixed cholinergic and anticholinergic signs and symptoms:

Cholinergic signs and symptoms: seizures, vomiting, diarrhea, abdominal pain, hyperhidrosis, hypersalivation, hypotension (may be preceded by hypertension).

Anticholinergic signs and symptoms (elderly patients may be more susceptible): delirium, agitation, slurred speech, dizziness, hypertension, tachycardia, dry mouth and eyes, ileus, blurred vision, and urinary retention.

The pictures come from public channels (such as the official website of the FDA, the official website of the original drug manufacturer, etc.) and are for reference only.

Contraindications of Cobenfy (KarXT)

Cobenfy is contraindicated in the following patients:

1. Patients with urinary retention.

2. Patients with moderate (Child-Pugh class B) or severe (Child-Pugh class C) liver dysfunction.

3. Patients with gastric retention.

4. Patients with a history of allergies to Cobenfy or trospium chloride have reported angioedema when using Cobenfy and trospium chloride.

5. Patients with untreated angle-closure glaucoma.

Cobenfy (KarXT) Precautions

1. Risk of urinary retention

Cobenfy can cause urinary retention. Elderly patients and patients with clinically significant bladder outlet obstruction and incomplete bladder emptying (e.g., patients with benign prostatic hyperplasia, diabetic cystopathy) may be at increased risk of urinary retention.

Cobenfy is contraindicated in patients with pre-existing urinary retention and is not recommended in patients with moderate or severe renal impairment.

Patients taking Cobenfy should be monitored for symptoms of urinary retention, including hesitation to urinate, weak urinary flow, incomplete bladder emptying, and difficulty urinating. Instruct patients to understand the risks and promptly report symptoms of urinary retention to their healthcare provider.

Urine retention is a known risk factor for urinary tract infections. For patients who develop symptoms of urinary retention, consider reducing the Cobenfy dose, discontinuing Cobenfy, or referring for urological evaluation as clinically indicated.

2. Risks of use in patients with hepatic insufficiency

Cobenfy is contraindicated in patients with moderate or severe hepatic insufficiency, and the use of Cobenfy in patients with mild hepatic insufficiency is not recommended.

Assess liver enzymes before initiating treatment with Cobenfy and as clinically necessary during treatment.

3. Risks of use in patients with biliary tract disease

Cobenfy is not recommended for patients with active biliary tract disease, such as patients with symptomatic gallstones. Assess liver enzymes and bilirubin before initiating treatment with Cobenfy and as clinically necessary during treatment. In the presence of symptoms such as dyspepsia, nausea, vomiting, or epigastric pain, gallbladder disease, biliary tract disease, and pancreatitis should be evaluated as clinically indicated.

Cobenfy should be discontinued if signs or symptoms of overt liver injury occur, such as jaundice, pruritus, or alanine aminotransferase levels greater than five times the upper limit of normal or five times the baseline value.

4. Decreased gastrointestinal motility

Cobenfy contains trospium chloride. Like other antimuscarinics, trospium chloride may decrease gastrointestinal motility. Cobenfy should be administered with caution to patients with obstructive gastrointestinal disease due to the risk of gastric retention.

Cobenfy should be used with caution in patients with conditions such as ulcerative colitis, intestinal atony, and myasthenia gravis.

5. Risk of angioedema

There have been reports of angioedema of the face, lips, tongue and/or throat using Cobenfy and its component trospium chloride.

If the tongue, hypopharynx, or larynx is involved, Cobenfy should be discontinued and appropriate treatment initiated and/or necessary measures taken to ensure a patent airway. Cobenfy is contraindicated in patients with a history of allergy to trospium chloride.

6. Risks of use in patients with narrow-angle glaucoma

For patients with known anatomical narrow angles, Cobenfy should only be used when the potential benefits outweigh the risks and are monitored closely.

7. Increased heart rate

Cobenfy can increase heart rate, and heart rate should be assessed at baseline and during Cobenfy treatment based on clinical needs.

8. Anticholinergic adverse reactions in patients with renal insufficiency

Trospium chloride, one of the components of Cobenfy, is mainly excreted through the kidneys. Cobenfy is not recommended for use in patients with moderate or severe renal impairment (estimated glomerular filtration rate (eGFR) <60 mL/min).

Systemic exposure to trospium chloride is higher in patients with moderate and severe renal impairment. Therefore, anticholinergic adverse reactions, including dry mouth, constipation, dyspepsia, urinary tract infection, and urinary retention, are expected to be more severe in patients with moderate and severe renal impairment.

9. Central Nervous System Effects

Patients should be monitored for signs of anticholinergic CNS effects, especially after initiating treatment or increasing the dose.

Patients are advised not to drive or operate heavy machinery until they know how Cobenfy affects them. If a patient develops anticholinergic CNS effects, consider reducing the dose or discontinuing the medication.

Cobenfy (KarXT) adverse reactions/side effects

1. Cardiovascular: chest pain, hypertensive crisis, palpitations, supraventricular tachycardia, syncope.

2. Gastrointestinal tract: gastritis.

3. Whole body: rash.

4. Musculoskeletal: rhabdomyolysis.

5. Nervous system: confusion, delirium, dizziness, hallucinations, drowsiness, and abnormal vision.

6. Skin and subcutaneous tissue diseases: angioedema, allergic reactions, Stevens-Johnson syndrome.

Cobenfy (KarXT) use in special populations

1. Pregnancy

There are currently no available data on the use of Cobenfy in pregnant women to assess drug-related risks of major birth defects, miscarriage or other adverse maternal and infant outcomes. Untreated schizophrenia presents risks to the mother (see Clinical Considerations).

In animal reproduction studies, administration of Cobenfy during organogenesis or during pregnancy and lactation resulted in maternal toxicity including adverse clinical symptoms, weight loss, weight gain and food consumption, and/or maternal death.

Embryofetal and developmental toxicity at these maternally toxic doses includes fetal and neonatal weight loss, stillbirth, and/or neonatal death.

2. Lactation period

There is no data on whether Cobenfy (KarXT) is present in human milk, its effects on breastfed infants, or its effects on milk production. Cobenfy (KarXT) is present in animal milk, and when the drug is present in animal milk, it is likely that it will also be present in human milk.

The developmental and health benefits of breastfeeding should be considered, as well as the mother's clinical need for Cobenfy and any potential adverse effects of Cobenfy or the underlying maternal condition on the breastfed infant.

3. Pediatric use

The safety and effectiveness of Cobenfy in pediatric patients have not been determined.

4. Geriatric use

Controlled clinical studies of Cobenfy did not include patients over the age of 65, and it is impossible to determine whether their responses are different from those of younger adult patients.

Because Cobenfy may increase the risk of urinary retention in older patients, including older men with bladder outlet obstruction due to benign prostatic hyperplasia, slower dose titration and lower maximum doses are recommended in older patients.

5. Renal insufficiency

Patients with mild renal insufficiency (eGFR60 to <90mL/min) had higher systemic exposure to Cobenfy ingredients trospium chloride and xanomeline compared with subjects with normal renal function.

The use of Cobenfy is not recommended in patients with moderate or severe renal impairment (eGFR<60mL/min).

6. Hepatic insufficiency

Patients with mild to moderate hepatic insufficiency (Child-Pugh class A and B, respectively) have a higher exposure to xanomeline than patients with normal liver function.

The pharmacokinetics of Cobenfy have not been studied in patients with severe hepatic impairment (Child-Pugh class C).

Cobenfy is contraindicated in patients with moderate or severe hepatic impairment and is not recommended for use in patients with mild hepatic impairment.

Cobenfy (KarXT) mechanism of action

Cobenfy (KarXT) is a muscarinic antagonist that mainly antagonizes muscarinic receptors in peripheral tissues. The mechanism of action of Cobenfy (KarXT) in treating schizophrenia is unclear, but its efficacy is thought to be due to its agonist activity at M1 and M4 muscarinic acetylcholine receptors in the central nervous system.

Cobenfy (KarXT) Pharmacokinetics

After taking Cobenfy, the area under the plasma concentration-time curve and maximum concentration of xanomeline increased by 50% during the 12-hour dosing interval at steady state when the dose was increased from 100 mg/20 mg twice daily to 125 mg/30 mg twice daily. Trospium chloride exposure increased in a dose-proportional manner over the Cobenfy dose range from 100 mg/20 mg twice daily to 125 mg/30 mg twice daily.