Sevabertinib

Sevabertinib is a prescription medication indicated for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-approved test, and who have received prior systemic therapy

• Sevabertinib is available under the following different brand names: Hyrnuo

Common side effects of Sevabertinib include:

• diarrhea
• rash
• paronychia
• stomatitis 
• nausea
• decreased potassium
• increased lipase
• decreased lymphocytes
• decreased sodium 
• increased amylase
• increased alanine transaminase 
• increased aspartate transaminase 

Serious side effects of Sevabertinib include:

• diarrhea
• hepatotoxicity
• interstitial lung disease (ILD)/pneumonitis
• ocular toxicity
• pancreatic enzyme elevation

Rare side effects of Sevabertinib 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, loss of coordination, feeling 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, light-headedness, or passing out

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result 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

• 10 mg

Non-small Cell Lung Cancer

Adult dosage

• 20 mg orally two times a day with food
• Continue 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 without first checking with your doctor, healthcare provider, or pharmacist.

Drug interaction overview

• CYP3A4 substrate (moderately sensitive)
• CYP3A4 moderate inhibitor
• CYP1A1 inhibitor (in vitro)
• P-gp weak-to-moderate inhibitor
• Strong CYP3A inhibitors
  • Avoid
  • Increases sevabertinib systemic exposure
  • If unavoidable, reduce the sevabertinib dose
• Moderate CYP3A inhibitors
  • Caution/monitor
  • Monitor for increased sevabertinib-associated adverse effects
• Strong or moderate CYP3A inducers
  • Avoid
  • May decrease sevabertinib plasma concentrations, which may reduce efficacy
• Sensitive CYP3A substrates
  • Avoid coadministration with CYP3A substrates, where minimal increases in concentration may lead to serious adverse reactions unless otherwise recommended in the substrate
  • Sevabertinib is a moderate CYP3A inhibitor
• Certain P-gp substrates
  • Refer to the prescribing information of the P-gp substrate
  • Sevabertinib may increase exposure of P-gp substrates (eg, dabigatran, digoxin, edoxaban)
• Sensitive CYP1A1 substrates
  • Refer to the prescribing information of the CYP1A1 substrate
  • Sevabertinib may increase exposure of CYP1A1 substrates (eg, riociguat)

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Sevabertinib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Sevabertinib?”

Cautions

• Diarrhea
  • Can cause severe diarrhea that can lead to dehydration and electrolyte imbalances
  • Median time to first onset of any grade diarrhea: 4 days
  • At the first sign of diarrhea or increased bowel movement frequency, instruct patients to start an antidiarrheal treatment (e.g., loperamide) and to increase their fluid and electrolyte intake
  • Interrupt, reduce dose, or permanently discontinue based on severity
• Hepatotoxicity
  • Can cause severe hepatotoxicity characterized by elevations of liver function tests
  • Median time to first onset of AST or ALT elevation was 1.4 months (range 0.2-14.5 months)
  • Monitor liver function tests, including ALT, AST, and total bilirubin at baseline before initiating, every 2 weeks for the first month, and then monthly thereafter as clinically indicated
  • More frequent testing may be needed in patients who develop transaminase elevations
  • Interrupt, reduce dose, or permanently discontinue based on the severity of hepatotoxicity
• Interstitial lung disease/pneumonitis
  • Can cause severe interstitial lung disease (ILD)/pneumonitis
  • Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever)
  • Discontinue upon confirmation of ILD/pneumonitis
• Ocular toxicity
  • Can cause ocular toxicity
  • Promptly refer patients presenting with new or worsening eye symptoms to an ophthalmologist
  • Interrupt, reduce dose, or permanently discontinue based on severity
• Pancreatic enzyme elevation
  • Can cause elevations of amylase and lipase levels
  • Median time to onset of increased amylase/lipase was 1.4 months (range 0.2-17 months)
  • Monitor amylase and lipase regularly during treatment
  • Interrupt, reduce dose, or permanently discontinue based on severity
• Embryofetal toxicity
  • Based on findings from animal studies and its mechanism of action, it can cause fetal harm when administered during pregnancy
  • Advise pregnant women and females of reproductive potential of potential fetal risk

Pregnancy and Lactation

Can cause fetal harm based on animal studies and its mechanism of action

There are no data in pregnant women to determine drug-associated risk

Advise pregnant women of the potential fetal risk

Verify pregnancy status in females of reproductive potential before initiating

Contraception

• Advise females of reproductive potential to use effective contraception during treatment and for 1 week after the last dose
• Males with female partners of reproductive potential should also use effective contraception during treatment and for 1 week after the last dose

Lactation

• There are no human data on the presence of sevabertinib in breast milk, its effects on breastfed infants, or milk production
• Because of the potential for serious adverse reactions in breastfed infants, women should not breastfeed during treatment and for 1 week after the last dose