Triheptanoin

FDA Drug Information • Also known as: Dojolvi

Brand Names: Dojolvi
Dosage Form: OIL
Product Type: BULK INGREDIENT

Description

11 DESCRIPTION DOJOLVI (triheptanoin) is a synthetic medium odd-chain (C7) triglyceride supplied as a colorless to light yellow clear oral liquid. The chemical name of triheptanoin is heptanoic acid, 1,1',1''-(1,2,3-propanetriyl) ester. The empirical formula is C 24 H 44 O 6 and its molecular weight is 428.6 g/mol. The chemical structure is: The caloric value of triheptanoin is 8.3 kcal/mL. The fat content is 0.96 g/mL. Chemical Structure

What Is Triheptanoin Used For?

1 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

2 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...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS Most common adverse reactions are (≥10%): abdominal pain, diarrhea, vomiting, and nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ultragenyx Pharmaceutical Inc. at 1-888-756-8657 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety population included 79 patients with LC-FAOD exposed to DOJOLVI in two studies: one open-label 78-week study of DOJOLVI in 29 patients (Study 1) followed by an open-label extension study (Study 2). Twenty-four patients from Study 1 continued into Study 2. Patients ranged from 4 months to 63 years of age and the population was 52% male. Of the 79 patients, 87% were White, 5% were Black or African-American, 4% were Asian, and 4% other. The daily dosage of DOJOLVI ranged between 12% and 41% DCI (which corresponds to 0.7 g/kg/day to 6.0 g/kg/day for pediatric patients and 0.5 g/kg/day to 1.3 g/kg/day for adult patients) for a mean duration of 23 months. The most common adverse reactions to DOJOLVI reported in the pooled safety population of Study 1 and Study 2 were gastrointestinal (GI)-related, and included abdominal pain (abdominal discomfort, abdominal distension, abdominal pain, abdominal pain upper, GI pain) [60%], diarrhea [44%], vomiting [44%], and nausea [14%]. Gastrointestinal (GI) Adverse Reactions In Study 1 and Study 2, median time to onset of a first occurrence of a GI adverse reaction was 7.3 weeks. GI adverse reactions led to dose reductions in 35% and 12% of patients in Study 1 and Study 2, respectively. In Study 3, a 4-month double-blind randomized controlled study, commonly reported adverse reactions with triheptanoin were similar to those reported in Study 1 and Study 2.

Drug Interactions

7 DRUG INTERACTIONS Pancreatic Lipase Inhibitors : Avoid co-administration due to potential for reduced clinical effect of DOJOLVI. ( 7.1 ) 7.1 Pancreatic Lipase Inhibitors Co-administration of triheptanoin with a pancreatic lipase inhibitor (e.g., orlistat) may reduce exposure to the triheptanoin metabolite, heptanoate, and reduce the clinical effect of triheptanoin [see Clinical Pharmacology (12.3) ] . Avoid co-administration of DOJOLVI with pancreatic lipase inhibitors.

Contraindications

4 CONTRAINDICATIONS None. None.

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no available data on triheptanoin use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies conducted in pregnant rats and rabbits administered triheptanoin during the period of organogenesis, the primary toxicological effect (reduced body weight gain) was considered to be specific to decreased food consumption related to taste aversion in animals, and therefore is not relevant to clinical use in the intended populations. There is a pregnancy safety study for DOJOLVI. If a patient becomes pregnant while receiving DOJOLVI, healthcare providers should report DOJOLVI exposure by calling Ultragenyx Pharmaceutical Inc. at 1-888-756-8657. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Embryofetal developmental studies have been conducted with triheptanoin in rats and rabbits following oral administration of 10% (3.2 g/kg), 30% (9.7 g/kg) and 50% (16 g/kg) DCI in rats and 10% (1.2 g/kg), 20% (2.3 g/kg) and 30% (3.5 g/kg) DCI in rabbits during the period of organogenesis. Reduced body weight gain, associated with decreased food consumption, was observed in pregnant rats and rabbits following administration of triheptanoin food mixture and was attributed to taste aversion. The NOAEL for this maternal toxicity (lack of body weight gain) was 10% DCI for both rats and rabbits. Administration of dietary triheptanoin to pregnant rats at doses approximately 2 times above, and pregnant rabbits approximately equal to the targeted clinical dose of 35% DCI resulted in increased incidence of skeletal...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING DOJOLVI (triheptanoin) oral liquid is supplied in a glass bottle as follows: 500 mL bottle NDC 69794-050-50 Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) (see USP Controlled Room Temperature). Do not freeze. DOJOLVI can be used for up to 9 months after opening but not beyond the expiration date on the bottle. Do not dose or store using materials made of polystyrene or polyvinyl chloride (PVC) containers [see Dosage and Administration (2.4) ] . Pharmacist : Dispense only in glass or HDPE bottles.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.