, Post-Market Adverse Reactions). Liver chemistry tests (ALT, AST, and bilirubin) should be performed prior to the initiation of treatment with ESBRIET, and subsequently at monthly intervals for the first 6 months and then every 3 months thereafter.
In addition, liver function tests should be promptly measured in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. In the event of elevations of ALT and/or AST, or clinical signs and symptoms of liver injury, the dose of ESBRIET may need to be reduced or treatment discontinued (see 7 WARNINGS AND PRECAUTIONS, Monitoring and Laboratory Tests and 4 DOSAGE AND ADMINISTRATION, Recommendations in Case of ALT, AST, Bilirubin Elevations).
, Child-Pugh Class B), ESBRIET exposure was increased by 60%. , Child-Pugh Class A and B) given the potential for increased ESBRIET exposure. Patients should be monitored closely for signs of toxicity especially if they are concomitantly taking a known CYP1A2 inhibitor (see 9 DRUG INTERACTIONSand10 CLINICAL PHARMACOLOGY).
ESBRIET has not been studied in individuals with severe hepatic impairment. ESBRIET should not be used in patients with severe hepatic impairment or end-stage liver disease (see 2 CONTRAINDICATIONS). Immune Angioedema Reports of angioedema (some serious) such as swelling of the face, lips and/or tongue which may be associated with difficulty breathing or wheezing have been received in association with use of ESBRIET in the post-marketing setting.
Therefore, patients who develop signs or symptoms of angioedema following administration of ESBRIET should immediately discontinue treatment. Patients with angioedema should be managed according to standard of care. ESBRIET should not be used in patients with a history of angioedema due to ESBRIET (see 2 CONTRAINDICATIONS).
Monitoring and Laboratory Tests Liver chemistry tests (ALT, AST and bilirubin) should be performed prior to the initiation of treatment with ESBRIET, and subsequently at monthly intervals for the first 6 months and then every 3 months thereafter.
In addition, liver function tests should be promptly measured in patients who report symptoms that may indicate livery injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. In the event of elevation in ALT, AST and/or bilirubin or clinical signs and symptoms of liver injury, the dose of ESBRIET may need to be reduced or treatment discontinued (see 4 DOSAGE AND ADMINISTRATION: Recommendations in case of elevations in ALT, AST, bilirubin).
If a patient exhibits any ALT and/or AST elevation accompanied by clinical signs and symptoms of liver injury or accompanied by hyperbilirubinaemia, ESBRIET should be discontinued promptly. The patient should be monitored closely until resolution of elevated ALT, AST and bilirubin and symptoms.
The patient should NOT be re-challenged with ESBRIET. If a patient exhibits ALT and/or AST elevation to ≥5 × ULN regardless of the level of serum bilirubin, ESBRIET should be discontinued promptly and the patient monitored closely until resolution of ALT and AST.
The patient should NOT be re-challenged with ESBRIET. Neurologic Dizziness Dizziness has been reported in patients treated with ESBRIET. , driving or using machinery). Patients who experience intolerance to therapy due to dizziness should be reminded to take ESBRIET with food to reduce dizziness.
If dizziness does not improve or worsens in severity, dose adjustment or discontinuation of ESBRIET may be warranted. Renal Page 11 of 42 ESBRIET should not be used in patients with severe renal impairment, or end-stage renal disease requiring dialysis (CrCl <30 mL/min, per Cockcroft-Gault equation) (see 2 CONTRAINDICATIONS).
ESBRIET should be used with caution in patients with mild (CrCl 51-80 mL/min) and moderate renal impairment (CrCl 30-50 mL/min) (see 10 CLINICAL PHARMACOLOGY- Renal Insufficiency).
Reproductive Health:
Female and Male Potential Fertility No adverse effects on fertility were observed in preclinical studies (see 16 NON-CLINICAL TOXICOLOGY). Skin Photosensitivity Reaction and Rash Photosensitivity reaction and rash have been reported in patients treated with ESBRIET.
Patients treated with ESBRIET should be advised to avoid or minimize exposure to direct and indirect sunlight, including through windows and from sunlamps, and to avoid other medicinal products known to cause photosensitivity. Patients should be instructed to use daily an effective sun block (at least SPF 50 against UVA and UVB), and to wear clothing that protects against sun exposure such as wide- brimmed hats and long sleeves.
Patients should be instructed to report promptly to their physician symptoms of photosensitivity reaction or rash. Severe photosensitivity reactions are uncommon. Dose reduction and temporary treatment discontinuation may be necessary in the event of photosensitivity reaction or rash.
ESBRIET may be reintroduced with re-escalation to the tolerated dose in the same manner as the dose-escalation period (see 4 DOSAGE AND ADMINISTRATION). Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported post-marketing in association with the use of ESBRIET.
If signs or symptoms of SCARs occur, ESBRIET should be withdrawn immediately. If the patient has developed SJS or TEN or DRESS with the use of ESBRIET, treatment with ESBRIET must not be restarted and should […]