Everolimus - Warnings and Precautions

WARNINGS AND PRECAUTIONS Non-Infectious Pneumonitis: Monitor for clinical symptoms or radiological changes.

Withhold or permanently discontinue based on severity. ( 2.9 , 5.1 ) Infections: Monitor for signs and symptoms of infection.

Withhold or permanently discontinue based on severity. ( 2.9 , 5.2 ) Severe Hypersensitivity Reactions: Permanently discontinue for clinically significant hypersensitivity.

Angioedema: Patients taking concomitant angiotensin-converting-enzyme (ACE) inhibitors may be at increased risk for angioedema.

Permanently discontinue for angioedema. ( 5.4 , 7.2 ) Stomatitis: Initiate dexamethasone alcohol-free mouthwash when starting treatment. ( 5.5 , 6.1 ) Renal Failure: Monitor renal function prior to treatment and periodically thereafter.

Risk of Impaired Wound Healing: Withhold for at least 1 week prior to elective surgery.

Do not administer for at least 2 weeks following major surgery and until adequate wound healing.

The safety of resumption of treatment after resolution of wound healing complications has not been established.

Geriatric Patients: Monitor and adjust dose for adverse reactions.

Metabolic Disorders: Monitor serum glucose and lipids prior to treatment and periodically thereafter.

Withhold or permanently discontinue based on severity. ( 2.9 , 5.9 ) Myelosuppression: Monitor hematologic parameters prior to treatment and periodically thereafter.

Withhold or permanently discontinue based on severity. ( 2.9 , 5.10 ) Risk of Infection or Reduced Immune Response with Vaccination: Avoid live vaccines and close contact with those who have received live vaccines.

Complete recommended childhood vaccinations prior to starting treatment.

Radiation Sensitization and Radiation Recall: Severe radiation reactions may occur. ( 5.12 , 6.2 ) Embryo-Fetal Toxicity: Can cause fetal harm.

Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.13 , 8.1 , 8.3 ) 5.1 Non-infectious Pneumonitis Non-infectious pneumonitis is a class effect of rapamycin derivatives.

Non-infectious pneumonitis was reported in up to 19% of patients treated with everolimus tablets/everolimus tablets for oral suspension in clinical trials, some cases were reported with pulmonary hypertension (including pulmonary arterial hypertension) as a secondary event.

The incidence of Grade 3 and 4 non-infectious pneumonitis was up to 4% and up to 0.2%, respectively [see Adverse Reactions ].

Fatal outcomes have been observed.

Consider a diagnosis of non-infectious pneumonitis in patients presenting with non-specific respiratory signs and symptoms.

Consider opportunistic infections, such as pneumocystis jiroveci pneumonia (PJP) in the differential diagnosis.

Advise patients to report promptly any new or worsening respiratory symptoms.

Continue everolimus tablets/everolimus tablets for oral suspension without dose alteration in patients who develop radiological changes suggestive of non-infectious pneumonitis and have few or no symptoms.

Imaging appears to overestimate the incidence of clinical pneumonitis.

For Grade 2 to 4 non-infectious pneumonitis, withhold or permanently discontinue everolimus tablets/everolimus tablets for oral suspension based on severity [see Dosage and Administration ].

Corticosteroids may be indicated until clinical symptoms resolve.