Diarrhea is a common side effect of Nerlynx (neratinib) and diarrhea was experienced by 95% of women in clinical trials that did not receive anti-diarrhea medications while taking Nerlynx. 93% experienced diarrhea within the first month of treatment and the average time to the onset of diarrhea was 8 days.

However, the risk of this side effect can be greatly reduced if loperamide (brand names include Imodium, Kaopectate 1-D) is started on the same day as Nerlynx is started, instead of just waiting to see if you develop diarrhea or not.

The usual starting dose of Nerlynx is 240mg once daily. Loperamide should be started on the same day Nerlynx is started and the recommended dose is:

• Days 1 to 14: loperamide 4mg by mouth 3 times per day
• Days 15 to 56: loperamide 4mg by mouth 2 times per day
• Days 57 to 365 (or until Nerlynx is stopped): loperamide 4mg when needed so that only one or two bowel motions per day are experienced, but do not take more than 16mg per day.

To minimize your risk of diarrhea:

• Always take loperamide exactly as your health care provider has told you to take it
• If you have more than two bowel movements in one day, or you have diarrhea that doesn’t go away, tell your health care provider
• Call your health care provider immediately if you have severe diarrhea or experience weakness, dizziness, or fever at the same time as diarrhea
• If you develop severe diarrhea, fluid and electrolytes will also be needed. Ensure you drink about 2 liters of fluid a day anyway, to avoid dehydration.
• You may be able to decrease the dose of your loperamide after two weeks of Nerlynx treatment, and then again after 56 days of Nerlynx treatment
• If you develop diarrhea but your diarrhea resolves to Grade 0-1 in one week or less, your doctor may resume Nerlynx treatment at the same dose
• If you develop diarrhea, but it takes longer than one week for diarrhea to resolve, then Nerlynx should be resumed at a reduced dose
• With Grade 4 diarrhea, Nerlynx should be permanently discontinued.

Why does Nerlynx cause diarrhea?

It is not known exactly why Nerlynx causes diarrhea; however, experts have suggested it may be due to epidermal growth factor receptor inhibition in cells lining the intestinal tract, which may disrupt the protective mucosal lining. In addition, Nerlynx use may also result in some inflammation within the GI tract as well as reducing the reabsorption of bile acids in the small part of the intestine.

93% of patients taking Nerlynx who were not prescribed anti-diarrhea medication experienced diarrhea within the first month of Nerlynx treatment. Grade 3 diarrhea occurred in 40% and Grade 4 diarrhea occurred in 0.1% of patients.

The average time to the first onset of Grade 3 or greater diarrhea was 8 days (range was one day to 350 days) and the average length of time the grade 3 or greater diarrhea persisted for was 5 days (range one day to 139 days).