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For concomitant use with strong CYP inducers, such as phenytoin and rifampin, which can decrease gefitinib levels Chhun et al. Gefitinib should not be used with proton pump inhibitors and, when concomitant use is necessary, dosing of gefitinib and the proton pump inhibitor should be spaced by 12 hours AstraZeneca Pharmaceuticals LP.
Similar to erlotinib, gefitinib use has been linked to adverse reactions, including hemorrhage and INR elevations, in patients using warfarin or other coumarin derivatives Onoda et al.
Weight, age, gender, race, and mild or moderate hepatic impairment do not have a significant effect on afatinib PK Freiwald et al.
Severe renal impairment has been shown to increase afatinib exposure; thus, according to the US prescribing information, these patients should receive a starting dose of 30 mg afatinib Boehringer Ingelheim Pharmaceuticals,.
No studies have examined the effects of afatinib on patients with severe hepatic impairment Child-Pugh C, although these patients should be closely monitored and have their dose adjusted for tolerability Boehringer Ingelheim Pharmaceuticals,.
If periodic liver testing shows worsening of liver function, gefitinib should be withheld; for those who develop severe hepatic impairment, treatment should be discontinued.
When concomitant use of afatinib with P-gp inhibitors is required, the afatinib dose should be reduced by 10 mg, as tolerated Boehringer Ingelheim Pharmaceuticals,; Table 2.
Patients taking afatinib with a P-gp inducer should increase their afatinib dose by 10 mg Boehringer Ingelheim Pharmaceuticals,; Table 2. There is also evidence for an inhibitory effect of afatinib on OATs, although this effect is less potent than that observed with erlotinib or gefitinib Johnston et al.
The recommended osimertinib dose is 80 mg once daily, taken orally with or without food AstraZeneca Pharmaceuticals LP.
There are limited PK and drug interaction data available for osimertinib, as its approval was recent and studies are ongoing.
Grade 1 is defined as an increase of less than 4 stools per day over baseline, grade 2 as 4 to 6 stools per day over baseline, grade 3 as more than 7 stools per day over baseline or incontinence, grade 4 includes life-threatening consequences, and grade 5 is death Cancer.
Management strategies for diarrhea include dietary modifications such as avoiding foods that are difficult to digest e.
For more severe diarrhea, diphenoxylate and atropine or octreotide can be considered. Reported rates for these AEs in clinical trials were between 40.
Rashes typically present in stages, with early erythema and edema observed in weeks 1 to 2 of treatment.
In week 2, papulopustular eruptions can occur in skin with a high density of sebaceous glands, followed by crusting of the skin in week 4 Lacouture et al.