In 2019, Pexidartinib (Turalio) was approved with the recommended dose of 400 mg orally taken twice daily on an empty stomach for at least 1 hour before and 2 hours after a meal or snack (1). The total daily dose of Turalio taken by patients was 800 mg. Turalio came in 200 mg capsules.
However, in 2023, a study was conducted to determine the optimal dosing for Turalio leading to the changed recommendations (2). As of Feb 2023, the current recommended dosing for Turalio is 250 mg orally taken twice daily with a low-fat meal (approximately 11-14 g of total fat).
No fast is required. The total daily dose of Turalio taken by patients is 500 mg. Turalio now comes in 125 mg capsules instead of 200 mg. Dose modifications are available similarly for those who are not at full dose (800 mg previously and now 500 mg daily). For example, if a patient was on 600 mg or 400 mg prior to the change, the modified dose equivalent is 375 mg (one capsules in the morning and two capsule in the evening) or 250 mg (one capsule in the morning and one capsule in the evening) with a low-fat snack, respectively. This change was made due to something called the Food Effect.
Medication taken orally must go through the gut/stomach. Medications are taken based on food conditions or on an empty stomach because food can influence the absorption of medicine. It is important to investigate the impact of food on the circulating medicine concentration (medication within the body capable of having an effect) to accordingly adapt the dose, frequency of administration, and food conditions to optimize the treatment effectiveness and safety.
Fat in food can increase the absorption of the drug, potentially leading to harmful side effects. Food can also be used to reduce side effects and improve safety (example: certain antibiotics). In the case of Turalio, taking it on an empty stomach requires more drug within the capsule to get into the body. Additionally, patients who eat too soon before or after taking Turalio (400mg twice daily) had potential for too much of the drug to be absorbed. Therefore, a study was conducted to determine the best condition for TGCT patients to take Turalio. Food conditions (low-fat meal, medium-fat meal, and high-fat meal) was tested to optimize the safety and effectiveness of Turalio. It was found that 250 mg of Turalio taken twice daily (total 500 mg daily) with a low-fat meal was safe while maintaining the maximal anti-tumor effect. However, when the same 250 mg of Turalio taken twice daily was consumed with a high-fat meal, potentially dangerous concentrations of the drug was in the blood. Therefore, Daiichi Sankyo, the drug company, determined that the best way to take Turalio is 250 mg twice daily (total 500 mg daily) with a low-fat meal. A low-fat meal is defined as 11-14 total grams of fat.
Discuss with your healthcare provider or pharmacy about these changes. A dietitian can provide additional assistance.
patient examples of low-fat Meal (11-14 G TOTAL FAT)
A spoonful of peanut butter
1.5 teaspoon of peanut butter and celery or banana (12 g)
1 teaspoon of peanut butter and 6 Ritz crackers (14 g)
Two hard-boil eggs (11 g)
1/3 cup of shredded cheese (12 g)
1/2 cup of hummus with veggies (12 g)
tortilla chips (approximately 10 chips) and salsa (11 g)
1/2 avocado and x2 toast (13 g)
1 Oz of cashews, pistachios, and/or almonds (24 almonds)
5 snack size Hershey bars with fruit
ranch dressing (< 2 teaspoons) and veggies (12 g)
1/2 cup of sunflower seeds (12 g)
1 teaspoon of butter melted on 1 piece of whole grain toast (13 g)
10 slices of pepperoni (11 g)
4 pieces of bacon (13 g)
1.5 cup of edamame (12 g)
7.25 oz of Mac and Cheese (12 g)
4 slices of salami (12 g)
1.25 slices of cheddar cheese (12 g)
2 peanut butter cookies (14 g)
2 slices of Swiss cheese (14 g)
16 Oz Soy milk (11 g)
1.5 cup of cottage cheese (13.5 g)
2 cups diced Turkey meat (light and dark meat) (14 g)
4 Oz of baked or broiled salmon (12 g)
6 Oz lean sirloin steak (12 g)
These examples of total grams of fat are approximate. Send in your examples to SStern@TGCTSupport.org
Patient Examples of Low-Fat Meals/Snacks (March 2023)
What are the dose modifications?
Patients who do not tolerate the maximum total daily dose (800 mg before Feb 2023 or 500 mg after Feb 2023) may receive dose modifications. These dose modifications are used to reduce side effects and improve tolerability.
For patients on Turalio before Feb 2023, the 400 mg and 600 mg dose modifications are equivalent to the 250 mg and 375mg, respectively, in the new label (see below). These modifications can be found on the packet insert or label.