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. |
| Molecular Weight | 242.27 |
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 | Limited data; contraindicated due to teratogenicity in animal studies. |
| 2nd trimester | Contraindicated; may cause fetal harm. |
| 3rd trimester | Contraindicated; risk of neonatal hemorrhage and kernicterus. |
Clinical note
Comprehensive clinical and safety monograph for VYKOURA (VYKOURA).
| Placental transfer | Crosses placenta rapidly; significant transfer documented. |
| Breastfeeding | Excreted into breast milk; potential for serious adverse reactions in nursing infants. Discontinue drug or nursing. |
| Lactation Rating | L5 - Contraindicated |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to VYKOURA or any componentActive pathological bleedingHemorrhagic tendenciesSevere hepatic impairmentConcurrent use with NSAIDs (increased bleeding risk)
| Precautions | Hepatotoxicity and elevated liver enzymes, Hypoglycemia risk when used with insulin secretagogues or insulin, Injection site reactions (pain, erythema, pruritus), Thrombocytopenia (rare) |
| Food/Dietary | Avoid grapefruit and grapefruit juice, Seville oranges, and pomelos as they may increase vandetanib exposure. No other significant food interactions. |
| Clinical Pearls |
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| 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. |
| 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. |
| Vykoura (vandetanib) is a tyrosine kinase inhibitor indicated for medullary thyroid cancer (MTC). It prolongs QTc interval; obtain baseline and periodic ECGs. Correct hypocalcemia, hypokalemia, and hypomagnesemia before initiation. Monitor for hypertension, diarrhea, rash, and photosensitivity. Avoid concurrent use of strong CYP3A4 inducers. Dose reduction required for moderate hepatic impairment. |
| Patient Advice | Take Vykoura once daily with or without food. Do not crush or chew tablets. · Avoid grapefruit, grapefruit juice, and Seville oranges during treatment. · Use effective sunscreen and protective clothing; avoid sun exposure as Vykoura increases photosensitivity. · Report symptoms of irregular heartbeat, fainting, or dizziness immediately. · Diarrhea is common; stay hydrated and notify your doctor if severe or persistent. · Do not take any new medications, including over-the-counter drugs or herbal supplements, without consulting your healthcare provider. |