Generic Name

Biotin

Mechanism

Biotin (vitamin H, vitamin B₇) is a water‑soluble B‑vitamin that acts as a covalent cofactor (prosthetic group) for five key carboxylase enzymes:
• Pyruvate carboxylase
• Acetyl‑CoA carboxylase (fatty‑acid synthesis)
• Propionyl‑CoA carboxylase (odd‑chain fatty‑acid catabolism)
• β‑hydroxy‑β‑methylglutaryl (HMG)‑CoA carboxylase (cholesterol synthesis)
• Methylcrotonyl‑CoA carboxylase (leucine catabolism)

By forming biotinyl‑dihydrouridine on these enzymes, it stabilizes the carboxylated intermediate, enabling efficient carboxylation reactions vital for gluconeogenesis, fatty‑acid synthesis, ketone body formation, and amino‑acid catabolism. Deficiency impairs these metabolic pathways, leading to dermatitis, alopecia, and neurologic symptoms.

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Pharmacokinetics

• Absorption: Rapid oral absorption; peak plasma concentrations within 1–2 h. Follows first‑order kinetics up to ~10 mg; saturation occurs >100 mg/d.
• Distribution: Widely distributed in body tissues; crosses the blood–brain barrier and placenta. Plasma protein binding <10 %.
• Metabolism: Minimal hepatic biotransformation. Excreted unchanged.
• Excretion: Primarily renal; half‑life 3–4 h in healthy adults. Renal dose adjustment not routinely required, but consider in severe renal impairment.
• Interaction potential: No significant CYP inhibition/induction; may interfere with laboratory assays (e.g., immuno‑enzymatic biotin‑avidin tests) leading to false results.

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Indications

• Biotinidase deficiency (congenital or acquired) – replacement therapy.
• Impaired Biotin-dependent Carboxylase Disorders – adjunctive therapy in metabolic panel abnormalities.
• Therapeutic Dermatologic Use – off‑label high‑dose biotin (5–20 mg/d) for hair, nail, and skin disorders; evidence is largely anecdotal.
• Pre‑operative supplementation in patients with chronic alcoholism or malnutrition to mitigate neurocognitive decline.

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Contraindications

• Contraindications: None formally listed; avoid in patients with hypersensitivity to biotin (rare).
• Warnings:
• Laboratory Interference: High-dose biotin (>10 mg/d) can cause false‑negative or false‑positive results in assays using streptavidin/avidin reagents (e.g., TSH, NT‑proBNP, Troponin). Notify clinicians and labs when prescribing >10 mg/d.
• Pregnancy/Lactation: Generally regarded as safe; no controlled studies but no evidence of teratogenicity.
• Renal Impairment: Dose adjustment not required, but monitor if extreme renal failure.

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Dosing

• Administration: Standard tablet or oral solution; take with food to improve tolerance. For high‑dose (≥5 mg), recommend capsule with a soft‑gel to reduce gastrointestinal irritation.

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Adverse Effects

• Mitigation: Reduce dose if GI upset occurs; discontinue if hypersensitivity symptoms arise.

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Monitoring

• Serum biotin concentration (if in deficiency management) – target 10–30 nmol/L.
• Plasma carboxylase activity (e.g., plasma carboxylase for carboxylase disorders).
• Routine labs: CBC, CMP – minimal changes expected; monitor renal function if dosing >500 mg/d.
• Laboratory interference awareness: Verify biotin levels before important assays when dose >10 mg/d.
• Clinical assessment: Hair, nail, and skin changes; neurocognitive status in deficient patients.

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Clinical Pearls

• Lab Trapkeeper – Because biotin is a key component in streptavidin‑based immuno‑assays, patients on >10 mg/d should discontinue biotin ≥48 h before critical diagnostics (e.g., TSH, troponin). Discuss alternatives or schedule tests prior to high‑dose therapy.
• Biotinidase Check – Even in adult patients with unexplained hair loss or neuropathy, screen for biotinidase deficiency; early replacement can halt progression.
• Dose Scaling – The classic “half‑dose” rule works: doubling the dose (e.g., from 2.5 µg/kg to 5 µg/kg) often increases plasma levels by ~100 % but may cause GI side effect threshold; titrate gradually.
• Pregnancy – While considered safe, the obstetric literature recommends 400 µg/d (USDA RDA) for pregnant women on chronic medical conditions, not the high therapeutic 5–20 mg/d.
• Drug–Drug Interaction – Biotin competes for the same transporter as vitamin B12 in renal tubules; high-dose biotin may transiently reduce vitamin B12 serum concentration. Monitor B12 if on high‑dose therapy for extended periods.

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