Osimertinib

Osimertinib is used for first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. Osimertinib is also used for metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, in patients who have progressed on or after EGFR TKI therapy.

Osimertinib is available under the following different brand names: Tagrisso.

Common side effects of osimertinib include:

• Low white blood cell count (lymphopenia, neutropenia)
• Low platelets (thrombocytopenia)
• Anemia
• Diarrhea
• Rash
• High blood magnesium (hypermagnesemia)
• Low blood sodium (hyponatremia)
• Dry skin
• Nail toxicity
• Fatigue
• Low blood sugar (hypoglycemia)
• Eye disorders
• Decreased appetite
• Cough
• Nausea
• Inflammation of mouth and lips
• Constipation
• Itching
• Vomiting
• Back pain
• Headache
• Low blood potassium (hypokalemia)
• Venous thromboembolism
• Pneumonia
• Interstitial lung disease/pneumonitis
• QTc increased from a baseline greater than 60 milliseconds
• Low blood magnesium (hypomagnesemia)
• Cardiomyopathy

Less common side effects of osimertinib include:

• Keratitis

Postmarketing side effects of osimertinib reported include:

• Erythema multiforme and Stevens-Johnson syndrome

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

Adult dosage

Tablet

• 40 mg
• 80 mg

Non-small cell lung cancer

Adult dosage

Adjuvant therapy

• 80 mg orally once a day
• Continue until disease recurrence, or unacceptable toxicity, or for up to 3 years
• First-line treatment for metastatic NSCLC

Monotherapy

• 80 mg orally once a day
• Continue until disease progression or unacceptable toxicity
• Combination with pemetrexed and platinum-based chemotherapy
• Cycles 1-4: Osimertinib 80 mg orally once a day plus pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 or carboplatin AUC5 IV on Day 1 of 21-day cycles
• Cycle 5 and thereafter: Osimertinib 80 mg orally once a day plus pemetrexed 500 mg/m2 IV on Day 1 of 21-day cycles
• Continue until disease progression or unacceptable toxicity due to Osimertinib

Previously treated metastatic NSCLC

• 80 mg orally once a day
• Continue until disease progression or unacceptable toxicity

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, 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.

• Osimertinib has severe interactions with the following drug:
  • lefamulin
• Osimertinib has serious interactions with at least 105 other drugs
• Osimertinib has moderate interactions with at least 153 other drugs
• Osimertinib has minor interactions with the following drugs:
  • acetazolamide
  • anastrozole
  • cyclophosphamide
  • danazol
  • drospirenone
  • ketoconazole
  • larotrectinib
  • levoketoconazole
  • ribociclib

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

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

Long-Term Effects

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

Cautions

• Interstitial lung disease/pneumonitis
  • Interstitial lung disease (ILD)/pneumonitis reported
  • Permanently discontinue if diagnosed with ILD/pneumonitis
  • Withhold therapy and promptly investigate for ILD in patients who present with worsening respiratory symptoms which may be indicative of ILD (eg, dyspnea, cough, and fever)
  • Permanently discontinue therapy if ILD/pneumonitis is confirmed
• QTc interval prolongation
  • May prolong QTc interval
  • Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval
  • Permanently discontinue in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia
• Cardiomyopathy
• Cardiomyopathy (defined as cardiac failure, chronic cardiac failure, congestive heart failure, pulmonary edema, or decreased ejection fraction) occurred, including rare fatalities
• For patients who will be receiving monotherapy, conduct cardiac monitoring, including assessment of LVEF at baseline and during treatment, in patients with cardiac risk factors
• For patients who will be receiving this drug in combination with pemetrexed and platinum-based chemotherapy, conduct cardiac monitoring, including assessment of LVEF at baseline and during treatment, in all patients
• Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment
• For symptomatic congestive heart failure, permanently discontinue therapy
• Keratitis
  • Keratitis reported
  • Promptly refer patients with signs and symptoms suggestive of keratitis (eg, eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain, red eye) to an ophthalmologist
• Severe dermatologic reactions
  • Postmarketing cases consistent with toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), and erythema multiforme major (EMM) reported
  • Withhold therapy if EEM, SJS, or TEN is suspected and permanently discontinue if confirmed
• Cutaneous vasculitis
  • Postmarketing cases of cutaneous vasculitis including leukocytoclastic vasculitis, urticarial vasculitis, and IgA vasculitis reported
  • Withhold therapy if cutaneous vasculitis suspected
  • Evaluate for systemic involvement, and consider dermatology consultation
  • If no other etiology is identified, consider permanent discontinuation of therapy based on the severity
• Aplastic anemia
  • Aplastic anemia was reported; some cases had a fatal outcome
  • Inform patients of signs and symptoms of aplastic anemia including but not limited to, new or persistent fevers, bruising, bleeding, and pallor
  • If aplastic anemia is suspected, withhold therapy, and obtain a hematology consultation
  • If confirmed, permanently discontinue therapy
  • Perform complete blood count with differential before starting therapy, periodically throughout treatment, and more frequently if indicated
• Embryo-fetal toxicity
  • Based on data from animal studies and its mechanism of action, can cause fetal harm when administered to females
  • Verify the pregnancy status of women of reproductive potential before initiating
  • Advise pregnant women of potential risk to the fetus

Drug interaction overview

• Osimertinib is a CYP3A4 substrate; a P-gp and BCRP inhibitor
• CYP3A4 inducers
  • Avoid use; if concurrent use is unavoidable, increase the Osimertinib dose
  • Coadministration with a strong CYP3A4 inducer decreased Osimertinib systemic exposure
• BCRP and P-gp substrates
  • Monitor for adverse effects of BCRP and P-gp substrates
  • Coadministration with a BCRP or P-gp substrate increased exposure and risk of toxicities of BCRP or P-gp substrate
• Drugs that prolong QTC interval
  • Avoid use; if unavoidable, monitor ECG periodically
  • The effects of coadministration with QT-prolonging drugs are unknown

Pregnancy and Lactation

• Based on data from animal studies and its mechanism of action, fetal harm may occur when administered to pregnant women
• No data available on humans
• Infertility
  • Based on animal studies, may impair fertility in women and men of reproductive potential
• Contraception
  • Females of reproductive potential: Use effective contraception during treatment and for 6 weeks after the final dose
  • Males with female partners of reproductive potential: Use effective contraception during and for 4 months following the final dose
• Lactation
  • Unknown if distributed in human breast milk
  • Administration to rats during gestation and early lactation was associated with adverse effects, including reduced growth rates and neonatal death
  • Advise lactating women not to breastfeed during treatment and for 2 weeks after the final dose