Generic Name

Pexidartinib Hydrochloride

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Classification

FDA Approved Indications

• Turalio is indicated for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe functional limitations or exacerbation of symptoms not suitable for surgery.

Mechanism of Action

Pexidartinib inhibits colony stimulating factor-1 receptor (CSF1R), c-KIT, and FLT3, reducing tumor-associated macrophages and tumor growth.

Dosage and Administration

Adult: 800 mg once daily for 2 weeks, then 800 mg daily (divided doses if needed), with dose modifications based on response and tolerability.

Pediatric: Not approved for pediatric use.

Geriatric: No specific adjustments documented; use with caution due to age-related comorbidities.

Renal Impairment: No specific dosage adjustment, but monitor closely.

Hepatic Impairment: Contraindicated in patients with pre-existing hepatic impairment; dose adjustments may be necessary in hepatic impairment.

Pharmacokinetics

Absorption: Rapid absorption, peak levels in approximately 2 hours.

Distribution: Extensively bound to plasma proteins (~79%).

Metabolism: Primarily hepatic via CYP3A4; also via UGT1A9.

Excretion: Excreted mainly in feces (~53%) and urine (~31%).

Half Life: Approximate half-life is 27 hours.

Contraindications

• Known hypersensitivity to pexidartinib or excipients.

Precautions

• Hepatotoxicity risk; monitor liver function closely.
• Risks of QT prolongation; perform baseline and periodic ECGs.
• Potential for embryo-fetal toxicity; effective contraception required during treatment.
• Use with caution in patients with hepatic impairment or on other hepatotoxic drugs.

Adverse Reactions - Common

• Hepatotoxicity (elevated liver enzymes, bilirubin) (Very common)
• An edema (Common)
• Nausea (Common)
• Fatigue (Common)

Adverse Reactions - Serious

• Hepatic failure, including cases leading to liver transplantation or death (Uncommon)
• QT prolongation, arrhythmias (Uncommon)
• Hypersensitivity reactions (Rare)

Drug-Drug Interactions

• CYP3A4 inducers/inhibitors affecting metabolism of pexidartinib.
• QT prolonging agents.

Drug-Food Interactions

• Limited data, avoid grapefruit juice and other CYP3A4-modulating foods.

Drug-Herb Interactions

• Lack of data; use caution with herbal supplements affecting liver or QT interval.

Nursing Implications

Patient/Family Teaching

• Report immediately any signs of liver dysfunction (jaundice, dark urine).
• Avoid alcohol and hepatotoxic medications.
• Follow contraception guidelines during and after treatment due to teratogenic risk.
• Attend regular monitoring appointments.

Special Considerations

Black Box Warnings:

• Hepatotoxicity leading to potential liver failure.

Genetic Factors: None identified.

Lab Test Interference: May alter liver function tests; interpret with caution.

Overdose Management

Signs/Symptoms: Signs of hepatotoxicity, arrhythmias, or other adverse effects.

Treatment: Supportive care, discontinue the medication, monitor liver function, and manage symptoms as needed.

Storage and Handling

Storage: Store at room temperature, away from light and moisture.

Stability: Stable according to manufacturer; use before expiration date.