Doxecitine and doxribtimine
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From MedlinePlus, U.S. National Library of Medicine
Specialty pharmacy: therapy management checklist, storage and cold chain, dosing calendar, Medicare Part D coverage.
Dosing in kidney impairment
Renal Impairment Plasma concentrations of doxecitine and doxribtimine increased in patients with moderate or severe renal impairment. The pharmacokinetics (PK) of doxecitine and doxribtimine have not been evaluated in patients with mild renal impairment. An appropriate dosage adjustment of KYGEVVI in patients with renal impairment could not be determined because renal impairment had distinct effects on the PK of doxecitine and PK of doxribtimine, and it is not feasible to separately adjust the dosage for doxecitine or doxribtimine contained in KYGEVVI [see Clinical Pharmacology ] .
Dosing in liver impairment
Important Recommendation Prior to KYGEVVI Treatment Initiation Obtain baseline liver transaminase (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and total bilirubin levels in patients prior to treatment initiation with KYGEVVI [see Dosage and Administration and Warnings and Precautions ] .
Dosage and Administration Modifications and Monitoring Liver Test Abnormalities If signs or symptoms consistent with liver injury are observed, interrupt treatment with KYGEVVI until liver transaminase (ALT, AST) and total bilirubin levels have either returned to baseline or stabilized at a new baseline value. Consider re-starting KYGEVVI at the last tolerated dose and increase the dose based on tolerability [see Dosage and Administration ] .
Consider permanently discontinuing KYGEVVI if signs or symptoms consistent with liver injury persist or worsen. Monitor liver transaminases and total bilirubin levels yearly and as clinically indicated [see Warnings and Precautions ] . Gastrointestinal Based on the severity of the diarrhea and/or vomiting, reduce the dose of KYGEVVI or interrupt treatment until diarrhea and/or vomiting improves or returns to baseline.
Consider re-starting KYGEVVI at the last tolerated dose and increase the dose based on tolerability [see Dosage and Administration ] . For persistent or recurring diarrhea and/or vomiting, consider discontinuing KYGEVVI permanently. Monitor for dehydration and treat promptly with electrolyte replacement [see Warnings and Precautions ] .
Preparation and administration
Preparation and Administration Instructions Use Table 2 for preparation and administration information. [See table below.] Use the ZX2000 administration kit provided separately to prepare and administer the prescribed dose [see How Supplied/Storage and Handling ] . Refer to the Instructions for Use for full preparation and administration information on use of KYGEVVI with the ZX2000 administration kit.
Household devices such as measuring cups or spoons are not adequate measuring devices. KYGEVVI should be prepared and administered by adults only. Preparation Instructions Preparation of KYGEVVI with a liquid other than water has not been studied clinically and is not recommended. Obtain the required number of KYGEVVI packets to prepare a one-day supply of solution each morning.
Use 40 mL of water per packet. Pour the prescribed volume of room temperature water (between 20°C - 25°C or 68°F - 77°F) into the mixing bottle. Add the powder from the required number of KYGEVVI packets into the mixing bottle. Screw the dosing cup tightly onto the mixing bottle and gently invert the mixing bottle back and forth at least 20 times.
If powder remains, repeat until the powder dissolves. The mixed solution may appear cloudy and have some residual powder (inactive ingredients) remaining at the bottom or top. Administration Instructions Oral Administration Before each administration, gently invert the tightly closed mixing bottle slowly back and forth at least 3 times.
Use 1 of 2 methods (dosing cup or oral syringe) to administer KYGEVVI solution. Choose the method based on the volume of solution to be administered per dose. Take KYGEVVI solution in 3 equally divided doses approximately 6 hours apart (plus or minus 2 hours) with food. Do not administer another dose if the dose is spit out or if a complete dose is not taken.
Take the next dose at the next scheduled time. Discard any remaining KYGEVVI solution 16 hours after reconstitution or after taking or giving the 3 doses, whichever comes first. Feeding Tube Administration KYGEVVI is compatible with most commonly available feeding tubes. KYGEVVI is compatible with feeding tubes made with polyvinylchloride (PVC) free from DEHP (Phthalates), polyurethane (PUR), and silicone (SIL) material.
Follow the instructions of the feeding tube manufacturer to administer KYGEVVI. Draw up the KYGEVVI solution using a syringe compatible with the feeding tube. Administer the solution immediately through the feeding tube. Flush any residual solution in the syringe or feeding tube until no solution is left. To flush the tube, a single flushing step with a volume of water equivalent to the tube's priming volume is sufficient.
Discard any remaining KYGEVVI solution 16 hours after reconstitution or after taking or giving the 3 doses, whichever comes first.
Storage Instructions for Prepared KYGEVVI Solution Store reconstituted KYGEVVI solution at controlled room temperature between 20°C to 25°C (68°F to 77°F) or in the refrigerator between 2°C to 8°C (36°F to 46°F). Discard KYGEVVI solution 16 hours after reconstitution or after taking or giving the 3 doses, whichever comes first.
| Total Daily Dose (mg/day) | Volume of Solution (mL) (administered 3 times per day) | Total mL of Water for Reconstitution | Total Number of KYGEVVI Packets for Reconstitution |
|---|---|---|---|
| 750 – 824 | 2.5 | 40 | 1 |
| 825 – 974 | 3 | ||
| 975 – 1,124 | 3.5 | ||
| 1,125 – 1,299 | 4 | ||
| 1,300 – 1,449 | 4.5 | ||
| 1,450 – 1,649 | 5 | ||
| 1,650 – 1,949 | 6 | ||
| 1,950 – 2,249 | 7 | ||
| 2,250 – 2,549 | 8 | ||
| 2,550 – 2,849 | 9 | ||
| 2,850 – 3,149 | 10 | ||
| 3,150 – 3,449 | 11 | ||
| 3,450 – 3,749 | 12 | ||
| 3,750 – 4,049 | 13 | ||
| 4,050 – 4,349 | 14 | 80 | 2 |
| 4,350 – 4,649 | 15 | ||
| 4,650 – 4,949 | 16 | ||
| 4,950 – 5,249 | 17 | ||
| 5,250 – 5,549 | 18 | ||
| 5,550 – 5,849 | 19 | ||
| 5,850 – 6,149 | 20 | ||
| 6,150 – 6,449 | 21 | ||
| 6,450 – 6,749 | 22 | ||
| 6,750 – 7,049 | 23 | ||
| 7,050 – 7,349 | 24 | ||
| 7,350 – 7,649 | 25 | ||
| 7,650 – 7,949 | 26 | ||
| 7,950 – 8,249 | 27 The volume of each individual dose, when multiplied by 3, may not match the corresponding water volume used in the preparation of the oral solution as the final volume of the reconstituted oral solution will increase after the powder from the packets is added to the water volume. | ||
| 8,250 – 8,549 | 28 | 120 | 3 |
| 8,550 – 8,849 | 29 | ||
| 8,850 – 9,749 | 30 | ||
| 9,750 – 11,249 | 35 | ||
| 11,250 – 12,749 | 40 | ||
| 12,750 – 14,249 | 45 | 160 | 4 |
| 14,250 – 15,749 | 50 | ||
| 15,750 – 17,249 | 55 | ||
| 17,250 – 18,749 | 60 | 200 | 5 |
| 18,750 – 20,249 | 65 | ||
| 20,250 – 21,749 | 70 | ||
| 21,750 – 23,249 | 75 | 240 | 6 |
| 23,250 – 24,749 | 80 | ||
| 24,750 – 26,249 | 85 | 280 | 7 |
| 26,250 – 27,749 | 90 | ||
| 27,750 – 29,249 | 95 | ||
| 29,250 – 30,749 | 100 | 320 | 8 |
| 30,750 – 32,249 | 105 | ||
| 32,250 – 33,749 | 110 | ||
| 33,750 – 35,249 | 115 | 360 | 9 |
| 35,250 – 36,749 | 120 | ||
| 36,750 – 38,249 | 125 | ||
| 38,250 – 39,749 | 130 | 400 | 10 |
| 39,750 – 41,249 | 135 | ||
| 41,250 – 42,749 | 140 | ||
| 42,750 – 44,249 | 145 | 440 | 11 |
| 44,250 – 45,749 | 150 | ||
| 45,750 – 47,249 | 155 | ||
| 47,250 – 48,749 | 160 | 480 | 12 |
| 48,750 – 50,249 | 165 | ||
| 50,250 – 51,749 | 170 | ||
| 51,750 – 53,249 | 175 | 520 | 13 |
| 53,250 – 54,749 | 180 | ||
| 54,750 – 56,249 | 185 | 560 | 14 |
| 56,250 – 57,749 | 190 | ||
| 57,750 – 59,249 | 195 | ||
| 59,250 – 60,749 | 200 | 600 | 15 |
| 60,750 – 62,249 | 205 | ||
| 62,250 – 63,749 | 210 | ||
| 63,750 – 65,249 | 215 | 640 | 16 |
| 65,250 – 66,749 | 220 | ||
| 66,750 – 68,249 | 225 |
Drug interactions
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- Doxecitine and doxribtimine
Contraindications
None. None. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
LiverTox has no chapter for doxecitine and doxribtimine. Check the label's hepatic warnings.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary There are no available data on KYGEVVI 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. There are risks for adverse maternal and fetal outcomes during pregnancy with mitochondrial myopathies, including TK2 deficiency ( see Clinical Considerations ).
In animal reproduction studies, oral administration of doxecitine and doxribtimine to pregnant rats and rabbits during organogenesis resulted in maternal and fetal toxicities in the rabbit at dose exposures 1233 and 811 times the maximum recommended human dose (MRHD) of 400 mg/kg/day doxecitine and 400 mg/kg/day doxribtimine, respectively, based on plasma exposure, but were not observed in the rat ( see Data ). 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. 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. Data Animal Data In an embryofetal development study in pregnant rats, once daily oral doses of 200, 600, and 2000 mg/kg/day doxecitine and doxribtimine were administered throughout organogenesis between gestation day (GD) 7 to 17.
No maternal or embryofetal toxicity was observed up to 2000 mg/kg/day (1223 times and 425 times the MRHD of doxecitine and doxribtimine, respectively, based on plasma exposure). In an embryofetal development study in pregnant rabbits, once daily oral doses of 200, 600, and 2000 mg/kg/day doxecitine and doxribtimine were administered throughout organogenesis between GD 7 and GD 19. Marked maternal toxicity and fetal malformations (dilated aorta with an associated narrow pulmonary trunk) were observed at the highest dose (1233 times and 811 times the MRHD of doxecitine and doxribtimine, respectively, based on plasma exposure).
The maternal and fetal no observed adverse effect level (NOAEL) in rabbits (600 mg/kg/day) was associated with maternal plasma exposures 729 times and 126 times the MRHD of 400 mg/kg/day doxecitine and 400 mg/kg/day doxribtimine, respectively.
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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