triheptanoin 1000 MG/ML Oral Solution [Dojolvi]

INDICATIONS AND USAGE DOJOLVI is indicated as a source of calories and fatty acids for the treatment of adult and pediatric patients with molecularly confirmed long-chain fatty acid oxidation disorders (LC-FAOD). DOJOLVI is a medium-chain triglyceride indicated as a source of calories and fatty acids for the treatment of adult and pediatric patients with molecularly confirmed long-chain fatty acid oxidation disorders (LC-FAOD).

DOSAGE AND ADMINISTRATION Assess metabolic requirements by determining daily caloric intake (DCI) prior to calculating the dose of DOJOLVI. ( 2.1 ) For patients receiving another medium-chain triglyceride product, discontinue prior to the first dose of DOJOLVI. ( 2.3 ) The recommended target daily dosage of DOJOLVI is up to 35% of the patient's total prescribed DCI divided into at least four doses and mixed thoroughly into semi-solid food/liquid or medical food/formula at mealtimes or with snacks. ( 2.2 ) See the full prescribing information for instructions on how to calculate the volume per dose; initiate and titrate the dosage to achieve the target; and prepare and administer DOJOLVI. ( 2.2 , 2.3 , 2.4 ) 2.1 Important Recommendations Prior to DOJOLVI Treatment All patients treated with DOJOLVI should be under the care of a clinical specialist knowledgeable in appropriate disease-related dietary management based upon current nutritional recommendations. Assess the metabolic requirements of the patient by determining their daily caloric intake (DCI) prior to calculating the dose of DOJOLVI. For patients receiving another medium-chain triglyceride (MCT) product, discontinue prior to the first dose of DOJOLVI. 2.2 Recommended Dosage The recommended target daily dosage of DOJOLVI is up to 35% of the patient's total prescribed DCI divided into at least four doses and administered by mixing thoroughly into semi-solid food/liquid or medical food/formula at mealtimes or with snacks. In order to reach a target daily dosage, patients may require an increase in their total fat intake. The neonatal population may require higher fat intake and therefore an increased amount of DOJOLVI. Consider current nutritional recommendations when dosing the neonatal population. Total Daily Dosage Calculation The target daily dosage from DOJOLVI (%) is converted to a volume of DOJOLVI (mL) to be administered using the following calculation: Caloric value of DOJOLVI = 8.3 kcal/mL Round the total daily dosage to the nearest whole milliliter. Divide the total daily dosage into at least four approximately equal individual doses. Image Missed Doses If a dose is missed, take the next dose as soon as possible with subsequent doses taken at 3 to 4-hour intervals. Skip the missed dose if it will not be possible to take all doses in a day. 2.3 Dosage Initiation and Titration For patients not currently taking an MCT product Initiate DOJOLVI at a total daily dosage of approximately 10% DCI divided into at least four times per day. Increase to the recommended total daily dosage by approximately 5% DCI every 2 to 3 days until the target dosage of up to 35% DCI is achieved. For patients switching from another MCT product Discontinue use of MCT products before starting DOJOLVI. Initiate DOJOLVI at the last tolerated daily dosage (mL) of MCT divided into at least four times per day. Increase the total daily dosage by approximately 5% DCI every 2 to 3 days until the target dosage of up to 35% DCI is achieved. Tolerability Consider more frequent smaller doses if a patient has difficulty tolerating 1/4 of the total daily dosage at one time based on gastrointestinal adverse reactions [see Adverse Reactions (6.1) ] . Monitor the patient's total caloric intake during dosage titration, especially in a patient with gastrointestinal adverse reactions, and adjust all components of the diet as needed. If a patient experiences gastrointestinal adverse reaction(s), consider dosage reduction until the gastrointestinal symptoms resolve [see Adverse Reactions (6.1) ] . If a patient is unable to achieve the target daily dosage of up to 35% DCI during dosage titration, maintain the patient at the maximum tolerated dosage. 2.4 Preparation and Administration Instructions Administer DOJOLVI by mixing thoroughly with semi-solid food/liquid (oral administration) or medical food/formula (feeding tube administration). Do not administer DOJOLVI alone to avoid gastrointestinal upset and feeding tube degradation [see Adverse Reactions (6.1) ] . Prepare or administer DOJOLVI using containers, oral syringes, or measuring cups made of compatible materials such as stainless steel, glass, high density polyethylene (HDPE), polypropylene, low density polyethylene, polyurethane, and silicone. Do not prepare or administer DOJOLVI using containers, oral syringes, or measuring cups made of polystyrene or polyvinyl chloride (PVC) plastics. Regularly monitor the containers, dosing components, or utensils that are in contact with DOJOLVI to ensure proper functioning and integrity. Oral Preparation and Administration Use an oral syringe or measuring cup made of compatible materials as listed above to withdraw the prescribed volume of DOJOLVI from the bottle. DOJOLVI can be mixed with soft food or liquid such as: plain or artificially sweetened fat free yogurt fat free milk, formula, or cottage cheese whole grain hot cereal fat free low carbohydrate pudding, smoothies, applesauce, or baby food Add the prescribed amount of DOJOLVI to a clean bowl, cup, or container, made of the compatible materials as listed above, which contains an appropriate amount of semi-solid food or liquid that takes into consideration the age, size, and fluid needs of the patient to ensure administration of the full dose. Mix DOJOLVI thoroughly into the food or liquid. Any unused mixture may be stored for up to 24 hours in refrigerated conditions. If not used within 24 hours, discard DOJOLVI mixture in the trash. Do not pour down the sink. Do not save for later . Feeding Tube Preparation and Administration DOJOLVI is administered as an oral or enteral bolus medication. Do not add DOJOLVI to the feeding bag, as the feeding equipment may degrade over time. DOJOLVI can be administered via oral or enteral feeding tubes manufactured of silicone or polyurethane. Do not use feeding tubes manufactured of polyvinyl chloride (PVC). Feeding device performance and functionality can degrade over time depending on usage and environmental conditions. Regularly monitor the feeding tube to ensure proper functioning and integrity [see Warnings and Precautions (5.1) ] . Use an oral syringe or measuring cup made of compatible materials as listed above to withdraw the prescribed volume of DOJOLVI from the bottle. Add the prescribed amount of DOJOLVI to a clean bowl, cup, or container, made of compatible materials as listed above, which contains an amount of medical food or formula that takes into consideration the age, size, and fluid needs of the patient in order to ensure administration of the full dose. Mix DOJOLVI thoroughly into the medical food or formula prior to administering via feeding tube, y-connector, or feeding tube extension set made of silicone or polyurethane. Draw up the entire amount of the DOJOLVI mixture into a slip tip syringe. Remove the residual air from the syringe and connect the syringe directly into the feeding tube port. Push the syringe contents into the feeding tube port using steady pressure until empty. Flush the feeding tubes with between 5 mL to 30 mL of water. Flush volume should be modified based on specific patient needs and in cases of fluid restriction. Discard any unused DOJOLVI mixture in the trash. Do not pour down the sink. Do not save for later use.

WARNINGS AND PRECAUTIONS Feeding Tube Dysfunction : Regularly monitor the feeding tube to ensure proper functioning and integrity. ( 5.1 ) Intestinal Malabsorption in Patients with Pancreatic Insufficiency : Low or absent pancreatic enzymes may reduce absorption of DOJOLVI. Avoid administration of DOJOLVI in patients with pancreatic insufficiency. ( 5.2 ) 5.1 Feeding Tube Dysfunction Feeding tube performance and functionality can degrade over time depending on usage and environmental conditions. In clinical trials, feeding tube dysfunction was reported in patients receiving triheptanoin. The contribution of DOJOLVI cannot be ruled out. Do not administer DOJOLVI in feeding tubes manufactured of polyvinyl chloride (PVC) [see Dosage and Administration (2.4 ] . Regularly monitor the feeding tube to ensure proper functioning and integrity. 5.2 Intestinal Malabsorption in Patients with Pancreatic Insufficiency Pancreatic enzymes hydrolyze triheptanoin and release heptanoate as medium-chain fatty acids in the small intestine. Low or absent pancreatic enzymes may result in reduced absorption of heptanoate subsequently leading to insufficient supplementation of medium-chain fatty acids. Avoid administration of DOJOLVI in patients with pancreatic insufficiency.

CONTRAINDICATIONS None. None.

Mechanism of Action Triheptanoin is a medium-chain triglyceride consisting of three odd-chain 7-carbon length fatty acids (heptanoate) that provide a source of calories and fatty acids to bypass the long-chain FAOD enzyme deficiencies for energy production and replacement.