Sunvozertinib

Sunvozertinib is a prescription medication indicated for treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy

• Sunvozertinib is available under the following different brand names: Zegfrovy

Common side effects of Sunvozertinib include:

• diarrhea
• nausea 
• itchy skin
• rash
• infected skin around the nail 
• dry skin
• decreased appetite 
• vomiting 
• urinary tract infection
• mouth sores 
• constipation
• abdominal pain
• feeling very tired 
• muscle or joint pain 
• decreased weight
• decreased white blood cell and red blood cell counts 
• decreased potassium and sodium levels
• increased pancreas enzyme levels 
• increase liver enzyme levels
• increased creatine kinase levels
• increased magnesium levels

Serious side effects of Sunvozertinib include:

• lung problems may cause symptoms like shortness of breath, trouble breathing, cough or fever
• gastrointestinal problems may cause symptoms like diarrhea, nausea, and vomiting
• severe skin rashes
• eye problems may cause symptoms like eye pain, increased tears, eye crusting, eye redness, discharge from the eyes,  blurred vision, light sensitivity, eye irritation,  loss of vision feeling like something is in the eye, dry eyes, or vision problems

Rare side effects of Sunvozertinib include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 150 mg
• 200 mg

Non-small Cell Lung Cancer (NSCLC)

Adult dosage

• 200 mg orally daily until disease progression or unacceptable toxicity

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

Sunvozertinib is a CYP3A4 substrate and weak CYP3A4 inducer; it also inhibits P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP)

Strong CYP3A inhibitors

• Avoid coadministration; sunvozertinib systemic exposure increased, which may increase adverse effects
• If concomitant use cannot be avoided, reduce the sunvozertinib dosage and monitor for adverse effects
• Resume at original dosage at 3-5 half-lives after CYP3A inhibitor is discontinued

Strong and moderate CYP3A inducers

• Avoid coadministration; sunvozertinib systemic exposure reduced, which may decrease efficacy
• If concomitant use cannot be avoided, increase the sunvozertinib dosage
• Resume at original dosage 7-14 days after CYP3A inducer is discontinued

Hormonal contraceptives

• Avoid coadministration
• Concomitant use may result in contraceptive failure
• Advise females of reproductive potential to use effective non-hormonal contraception during and after therapy

P-gp substrates

• Follow substrate recommendations for use with P-gp inhibitors
• Concomitant use may result in increased systemic exposure of P-gp substrates, which may increase adverse effects

BCRP substrates

• Follow substrate recommendations for use with BCRP inhibitors
• Concomitant use may result in increased systemic exposure of BCRP substrates, which may increase adverse effects

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

See “What Are Side Effects Associated with Using Sunvozertinib?”

Long-Term Effects

See “What Are Side Effects Associated with Using Sunvozertinib?”

Cautions

• Interstitial lung disease (ILD)/pneumonitis
  • Can cause severe and life-threatening ILD/pneumonitis
  • Median time to ILD/pneumonitis onset: 61 days (range, 35-86)
  • Monitor for new or worsening pulmonary symptoms (eg, dyspnea, cough, fever)
  • Hold therapy for suspected ILD/pneumonitis; permanently discontinue if ILD/pneumonitis confirmed
• Gastrointestinal (GI) adverse reactions
  • Can cause severe GI adverse reactions (eg, diarrhea, nausea, vomiting)
  • Administer with food to reduce GI adverse reactions
  • Monitor for GI toxicity; provide supportive care as indicated (eg, antidiarrheals, anti-emetics, fluid replacement)
  • Hold, dose reduce, or permanently discontinue based on severity
• Dermatologic adverse reactions
  • Can cause severe rash (eg, acneiform dermatitis) and pruritus
  • Advise patients to use alcohol-free (eg, isopropanol-free, ethanol-free) emollient cream during treatment and to avoid use of irritating skin products (eg, retinol/retinoic acid- or benzoyl peroxide-containing products)
  • Hold, dose reduce, or permanently discontinue based on severity
• Ocular toxicity
  • Can cause ocular toxicity (eg, keratitis, dry eye symptoms, blurred vision, visual impairment)
  • Promptly refer patients with new or worsening eye symptoms to an ophthalmologist
  • Advise discontinuation of contact lenses until ocular symptoms are evaluated
  • Hold, dose reduce, or permanently discontinue based on severity
• Embryo-fetal toxicity
  • May cause fetal harm when administered during pregnancy
  • Advise pregnant patients and females of reproductive potential of fetal risk
  • Effective contraception recommended for females of reproductive potential and male patients with female partners of reproductive potential

Pregnancy and Lactation

• May cause fetal harm when administered during pregnancy, based on findings from animal studies and its mechanism of action
• There are no available data on use in pregnant patients to inform the drug-associated risk
• Advise pregnant patients and females of reproductive potential of fetal risk
• Verify pregnancy status before starting therapy in females of reproductive potential
• Contraception requirements
  • Females of reproductive potential: Use effective non-hormonal contraception during therapy and for 2 weeks after the last dose; hormonal contraceptives may be ineffective
  • Males patients with female partners of reproductive potential: Use effective contraception during therapy and for 2 weeks after the last dose
• Infertility
  • May impair fertility in females, based on data from animal studies
  • Reversibility of effects on female fertility not assessed
• Lactation
  • No data on the presence of sunvozertinib or its metabolites in human milk or their effects on breastfed children or milk production
  • Due to potential for serious adverse reactions in breastfed children, avoid breastfeeding during therapy and for 2 weeks after the last dose