Doxecitine-Doxribtimine

Doxecitine-Doxribtimine is a prescription medication indicated for the treatment of thymidine kinase 2 deficiency (TK2d) in adults and pediatric patients with an age of symptom onset on or before 12 years.

• Doxecitine-Doxribtimine is available under the following different brand names: Kygevvi

Common side effects of Doxecitine-Doxribtimine include:

• diarrhea
• abdominal pain 
• vomiting 
• increased alanine aminotransferase (ALT)
• increased aspartate aminotransferase (AST)

Serious side effects of Doxecitine-Doxribtimine include:

• elevated liver enzymes
• gastrointestinal adverse reactions (including diarrhea requiring hospitalization)

Rare side effects of Doxecitine-Doxribtimine include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Powder for oral solution

• 2 g doxecitine and 2 g doxribtimine per single-use packet

Thymidine Kinase Deficiency

Adult and pediatric dosage

Recommended dosage

• Administer total daily dose in 3 equally divided doses approximately 6 hours apart (+/- 2 hours) with food
• Initial dose: 260 mg/kg-Day orally (130 mg doxecitine and 130 mg doxribtimine)
• Intermediate dose: 520 mg/kg-Day orally (260 mg doxecitine and 260 mg doxribtimine)
• Maintenance dose: 800 mg/kg-Day orally (400 mg doxecitine and 400 mg doxribtimine)

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Visit the RxList Drug Interaction Checker for any drug interactions. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Visit the RxList Drug Interaction Checker for any drug interactions. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Doxecitine-Doxribtimine?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Doxecitine-Doxribtimine?”

Cautions

• Elevated liver transaminase levels
  • Elevated liver transaminase (i.e., ALT, AST) levels
  • Obtain baseline liver transaminase and total bilirubin (TB) levels in patients before treatment initiation
  • If signs or symptoms consistent with liver injury are observed, interrupt treatment until AST, ALT, and TB levels have either returned to baseline or stabilized at a new baseline value
  • Consider permanently discontinuing if signs or symptoms consistent with liver injury persist or worsen
  • Monitor AST, ALT, and TB levels yearly and as clinically indicated
• Gastrointestinal adverse reactions
  • Diarrhea and vomiting leading to hospitalization, dose reduction, and permanent discontinuation reported
  • Based on the severity of diarrhea and/or vomiting, reduce dosage or interrupt treatment until diarrhea and/or vomiting improve or return to baseline
  • Consider restarting the last tolerated dose, and increase the dose as tolerated
  • For persistent or recurring diarrhea and/or vomiting, consider discontinuing permanently and provide supportive care with electrolyte repletion as clinically indicated

Pregnancy and Lactation

There are no available data regarding use during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes

Endogenous pyrimidine nucleosides are transported across the placenta

Clinical considerations

• Disease-associated maternal and/or embryo/fetal risk
• Mitochondrial myopathies are associated with increased adverse perinatal outcomes, including preterm birth, pre-eclampsia, and gestational diabetes

Lactation

• There are no data on the presence of doxecitine and doxribtimine or their metabolites in either human or animal milk, effects on breastfed infants, or effects on milk production
• Data from published literature have documented the presence of nucleosides and nucleotides in human milk