Kygevvi (doxecitine/doxribtimine)
Oral Powder In Packet (Ea)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Doxecitine and doxribtimine (doxecitine/doxribtimine) is a fixed combination of 2 pyrimidine nucleosides.
Doxecitine and doxribtimine (doxecitine/doxribtimine) is a fixed combination preparation containing 2 pyrimidine nucleosides. Administration of doxecitine/doxribtimine incorporates the pyrimidine nucleosides doxecitine and doxribtimine into skeletal muscle mitochondrial DNA, restoring mitochondrial DNA copy number in thymidine kinase 2 deficiency (TK2d) mutant mice.
The absolute bioavailability of doxecitine and doxribtimine have not been determined. The median time to peak plasma concentrations was approximately 2 hours for doxecitine and 4 hours for doxribtimine. Following oral administration of 133 mg/kg doxecitine and 133 mg/kg doxribtimine with a high-fat, high calorie meal in healthy adult subjects, peak plasma concentration and AUC increased by 79% and 137%, respectively, for doxecitine; and increased by 27% and 74%, respectively, for doxribtimine, compared to fasted conditions.
Plasma protein binding of doxecitine and doxribtimine was <10% over the concentration 0.23-23 mcg/mL. The mean half-life was approximately 1 hour for doxecitine and 5 hours for doxribtimine following a single oral administration of 133 mg/kg doxecitine and 133 mg/kg doxribtimine under fed conditions in healthy adult subjects. Doxecitine and doxribtimine are primarily degraded by cytidine deaminase and thymidine phosphorylase, respectively, to their nucleobases and the 2-deoxy-alpha-D-ribose 1-phosphate moiety.
Intermediate products of doxecitine catabolism are deoxyuridine, uracil, and dihydrouracil with the end products beta-alanine, ammonia, and carbon dioxide. Thymine, the pyrimidine nucleobase of doxribtimine, is subsequently catabolized to dihydrothymine and ultimately to gamma-amino-isobutyric acid and carbon dioxide. Doxecitine and doxribtimine are not metabolized by cytochrome P450 (CYP) isoforms.
Following oral administration, urinary excretion of doxecitine and doxribtimine was <1% of the administered dose in healthy subjects.
Generic name: doxecitine/doxribtimine
Therapeutic class: Locomotor System
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Kygevvi
Indications
The following indications are listed for Kygevvi:
- Thymidine Kinase 2 Deficiency
Dosing
No dosing information is available for this tab.
Doxecitine and doxribtimine (doxecitine/doxribtimine) is administered orally (as an oral solution) with food. The drug is supplied in a single-use packet containing 2 g doxecitine and 2 g doxribtimine that must be reconstituted prior to administration. Use the manufacturer-supplied administration kit (ZX2000) to prepare and administer the prescribed dose. The solution should be prepared and administered by adults only.
Obtain the required number of doxecitine/doxribtimine packets to prepare a one-day supply of solution each morning. Use 40 mL of water to reconstitute each packet; do not use any other liquids. To prepare the solution, add the appropriate amount of room temperature water (20-25degreesC) to the mixing bottle. Next, add the powder from the required number of doxecitine/doxribtimine packets to the mixing bottle. Attach the dosing cup tightly onto the mixing bottle and gently mix the solution by inverting the bottle at least 20 times; repeat this process until the powder is completely dissolved. The mixed solution may appear cloudy and have some residual powder remaining at the bottom or top. See full prescribing information for additional administration and preparation instructions.
Store doxecitine/doxribtimine packets at 20-25degreesC (excursion permitted 15-30degreesC). Store the reconstituted doxecitine/doxribtimine solution at room temperature (20-25degreesC) or in the refrigerator (2-8degreesC). Discard any remaining solution 16 hours after reconstitution or after taking or giving the 3 equally divided daily doses, whichever comes first.
If a dose is missed, take it as soon as possible. If it is within 2 hours of the next scheduled dose, skip the missed dose and resume the regular dosing schedule.
| Drug label | Dosing type | Instructions |
|---|---|---|
| Kygevvi 4 Gm (2Gm-2Gm) Powd Pk | Maintenance | Take 266.667 mg/kg (round to the nearest 500 mg) by oral route 3 times per day approximately 6 hours apart. |
No dosing information is available for this tab.
Drug interactions
Doxecitine and doxribtimine are not inducers, inhibitors, or substrates of cytochrome P-450 (CYP) isoenzymes at clinically relevant concentrations.
Doxecitine and doxribtimine do not inhibit P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), bile salt export pump (BSEP), organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 1, OCT2, multidrug and toxin extrusion transporter (MATE) 1, or MATE2-K at clinically relevant concentrations. Doxribtimine may be a substrate of BCRP, but its clinical significance is unknown.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*None.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
- No disease contraindications
Adverse reactions
The most common adverse reactions (>=5%) reported with doxecitine/doxribtimine in clinical trials were diarrhea, abdominal pain (including upper abdominal pain), vomiting, increased ALT, and increased AST.
There are no severe adverse reactions for this drug.
More Frequent
- Acute abdominal pain
- Diarrhea
- Increased alanine transaminase
- Increased aspartate transaminase
- Upper abdominal pain
- Vomiting
Precautions
No enhanced messaging available.
The safety and effectiveness of doxecitine/doxribtimine have been established in pediatric patients with thymidine kinase 2 deficiency with an age of symptom onset on or before 12 years. Use of doxecitine/doxribtimine for this indication is supported by evidence from 2 retrospective studies, an open-label study, and an expanded access program in which a total of 68 patients 0.7 to <17 years of age were treated. In one study, a higher percentage of pediatric patients experienced adverse reactions of vomiting and elevated liver transaminases compared to adults. Serious adverse reactions in pediatric patients included hospitalization due to diarrhea in 2 patients.
There are no adequate data regarding use of doxecitine/doxribtimine in pregnant women. In animal reproduction studies, oral administration of doxecitine/doxribtimine during organogenesis resulted in maternal and fetal toxicity in rabbits at exposures 1233- and 811-fold the maximum recommended human dose (MRHD) of 400 mg/kg/day for doxecitine and doxribtimine, respectively, based on plasma exposures; these effects were not observed in rats.
It is not known whether doxecitine or doxribtimine is distributed into human milk, or if the combination drug has any effects on the breastfed infant or on milk production. Published literature reports the presence of nucleosides and nucleotides in human milk.
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for doxecitine/doxribtimine and any potential adverse effects on the breastfed infant from the drugs or from the underlying maternal condition.
The manufacturer makes no specific dosage recommendations for geriatric patients.
Clinical studies of doxecitine/doxribtimine did not include a sufficient number of patients >=65 years of age to determine whether they respond differently from younger adult patients.
ICD codes
| Code | Type | Description |
|---|---|---|
| Thymidine kinase 2 deficiency | ||
| E88.40 | ICD10CM | Mitochondrial metabolism disorder, unspecified |
ICD code information from First Databank (FDB).
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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