VYKOURA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VYKOURA (VYKOURA).
VYKOURA (aP2-anti-miR-17 oligonucleotide) is a locked nucleic acid (LNA) antisense oligonucleotide that binds to and inhibits miR-17-5p, a microRNA that represses expression of the transcription factor aP2 (FABP4). By blocking miR-17-5p, VYKOURA increases aP2 levels, which promotes fatty acid uptake into adipose tissue, thereby reducing circulating free fatty acids and improving insulin sensitivity.
| Metabolism | Metabolized by 5' exonuclease-mediated hydrolysis to shorter oligonucleotides; not a substrate for CYP450 enzymes. |
| Excretion | Primarily renal (85% unchanged) and fecal (10%); 5% metabolized. Biliary excretion is minimal. |
| Half-life | 12-15 hours; clinical context: requires dose adjustment in renal impairment (CrCl <30 mL/min). |
| Protein binding | 95% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.2-0.3 L/kg; clinical meaning: low Vd indicates minimal tissue distribution, primarily stays in plasma. |
| Bioavailability | Oral: 70-85%; food increases to 90%; IV: 100%. |
| Onset of Action | Oral: 30-60 min; IV: 2-5 min. |
| Duration of Action | 6-8 hours; clinical notes: extended duration may occur with hepatic impairment or drug interactions. |
10 mg orally once daily.
| Dosage form | SOLUTION |
| Renal impairment | eGFR 30-59 mL/min: 5 mg once daily; eGFR <30 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 5 mg once daily; Child-Pugh C: contraindicated. |
| Pediatric use | Not established; safety and efficacy not studied in pediatric patients. |
| Geriatric use | No specific adjustment; monitor renal function due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VYKOURA (VYKOURA).
| Breastfeeding | Contraindicated during breastfeeding. VYKOURA is excreted in human milk; the M/P ratio is unknown but presumed high based on pharmacokinetics. Potential for serious adverse reactions in nursing infants, including bone marrow suppression and gastrointestinal toxicity. Discontinue breastfeeding or discontinue the drug. |
| Teratogenic Risk | Pregnancy Category X. VYKOURA is contraindicated in pregnancy due to teratogenicity. First trimester: high risk of major congenital malformations (neural tube defects, cardiovascular anomalies). Second and third trimesters: risk of fetal growth restriction, premature birth, and fetal death. There is no safe trimester for use. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to VYKOURA or any excipient","Severe hepatic impairment (Child-Pugh Class C)","Concurrent use with strong UGT1A1 inducers (e.g., rifampin)"]
| Precautions | ["Hepatotoxicity and elevated liver enzymes","Hypoglycemia risk when used with insulin secretagogues or insulin","Injection site reactions (pain, erythema, pruritus)","Thrombocytopenia (rare)"] |
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| Fetal Monitoring | Confirm negative pregnancy test before initiation and monthly during therapy. Perform ultrasound monitoring for fetal growth and anatomy at 12-14 weeks and again at 18-20 weeks. Monitor for fetal distress with non-stress testing or biophysical profile in the third trimester. Monitor maternal complete blood count, liver function, and renal function weekly. |
| Fertility Effects | VYKOURA impairs fertility in both males and females. In females, ovarian suppression, anovulation, and premature ovarian failure may occur. In males, oligospermia, azoospermia, and testicular atrophy have been reported; effects are likely irreversible with prolonged therapy. Contraception counseling is required for patients of reproductive potential. |