Skytrofa
Skytrofa
Generic Name
Skytrofa
Mechanism
- Elvitegravir – Binds the active site of viral integrase and its essential Mg²⁺ co‑factor, blocking the 3′‑processing and strand‑transfer steps needed for proviral DNA integration into host genome.
- Cobicistat – A selective CYP3A inhibitor that suppresses hepatic metabolism of elvitegravir, thus maintaining therapeutic plasma concentrations.
- Emtricitabine and tenofovir alafenamide – Nucleoside/nucleotide reverse‑transcriptase inhibitors that get incorporated into viral DNA, causing chain termination and inhibition of reverse transcription.
The quartet synergistically shuts down viral replication at multiple stages.
Pharmacokinetics
| Parameter | Elvitegravir | Cobicistat | Emtricitabine | Tenofovir alafenamide |
| Absorption | Oral, bioavailability ~54 % | Oral, bioavailability ~90 % | Oral, >90 % | Oral, >70 % |
| Peak plasma | T₍max₎ 1–2 h (±) | T₍max₎ 2–4 h | T₍max₎ 2 h | T₍max₎ 3–4 h |
| Distribution | Vd ≈ 224 L | Vd ≈ 137 L | Vd ≈ 37 L | Vd ≈ 8 L |
| Metabolism | CYP3A‑mediated → inhibited by cobicistat | Primarily CYP3A | Not metabolized | Hydrolyzed to tenofovir by carboxylesterases |
| Elimination | Renal (≈30 %) | Renal | Renal (≈90 %) | Renal (≈90 %) |
| Half‑life | ~14 h (stabilized by cobicistat) | 4–5 h | ~10 h | ~17 h |
Steady‑state achieved within 2–3 days; dose adjustments are needed in renal impairment (see contraindications).
Indications
- First‑line or subsequent HIV‑1 therapy in adults and adolescents > 12 yr when combined with at least two other antiretrovirals (preferably non‑NRTI backbone).
- CDC category B and C efficacy.
Key phrase for SEO: *Skytrofa HIV treatment*, *fixed‑dose HIV regimen*.
Contraindications
- Contraindications
- Known hypersensitivity to any component.
- Severe renal impairment (CrCl < 30 mL/min) – dosage reduction not licensed; consider alternative.
- Severe hepatic impairment (Child‑Pugh C).
- Warnings
- Renal dysfunction – tenofovir alafenamide is safer than TDF but still 90 % renally excreted; monitor CrCl.
- Fibrosis/Steatosis – Cobicistat may worsen liver enzymes; baseline and periodic ALT/AST checks.
- Drug‑drug interactions – Cobicistat inhibits CYP3A; avoid concomitant strong CYP3A inducers or inhibitors unless dose adjusted.
- Pediatric – Use only in clinical trials; not approved for younger kids.
Dosing
- Adult/Adolescent: 1 tablet once daily (30 mg elvitegravir/150 mg cobicistat/200 mg emtricitabine/25 mg tenofovir alafenamide) with or without food.
- Renal adjustment (CrCl 30–50 mL/min): Reduce dose of emtricitabine to 150 mg/time (elvitegravir/cobicistat unchanged) or use alternate regimen per guidelines.
- Discontinuation: Taper rather than abrupt cessation to avoid rebound viremia.
Takeaway for physicians: Keep dosage simple; a single pill plus co‑administered NRTIs simplifies adherence.
Adverse Effects
| System | Common (≤10 %) | Serious (≤1 %) |
| GI | Nausea, diarrhea, dyspepsia | Vomiting (requiring hydration) |
| CNS | Headache, insomnia, dizziness | Confusion, rare seizures |
| Hepatic | Mild transaminase rise | Elevated ALT/AST > 5× ULN, structural liver injury |
| Renal | Rare creatinine rise | Acute kidney injury (possibly due to tenofovir) |
| Haematologic | Anemia (rare) | Lymphopenia |
| Metabolic | Lipid ↑ (in some) | Hyperglycemia, rare pancreatitis |
| Skin | Rash, pruritus | Stevens–Johnson syndrome (very rare) |
Best practice: Monitor liver enzymes at baseline, month 1, month 3, then every 6 months. Watch for signs of renal dysfunction and counsel patients on adequate hydration.
Monitoring
- Virologic – HIV‑1 RNA at weeks 4, 12, then every 3 months.
- Immunologic – CD4⁺ T‑cell count at baseline, week 12, then every 6 months.
- Renal – Serum creatinine & CrCl at baseline, week 4, then quarterly.
- Liver – ALT/AST at baseline, month 1, month 3, every 6 months.
- Blood pressure – Baseline and annually; minimal impact but check for any hypertension.
- Drug interactions – Review concomitant meds each visit; adjust as needed.
Clinical Pearls
- Cobicistat, not ritonavir – It lacks antiretroviral activity, so monitor for bleeding and other coagulation effects (unlike ritonavir).
- Fixed‑dose synergy – One pill simplifies adherence; reduce pill burden by >10 % compared to separate NRTIs.
- Renal monitoring is crucial – Even though tenofovir alafenamide is less nephrotoxic, >80 % is renally cleared.
- Pregnancy – Skytrofa is category B; use only if benefits outweigh risks; avoid in women of childbearing potential unless using effective contraception.
- Drug–drug interaction rail – Use of strong CYP3A inducers (e.g., rifampin, carbamazepine) greatly diminishes elvitegravir levels; not recommended without dose adjustment or alternative.
- Lifestyle – Encourage adequate fluids, avoid excessive alcohol (may increase liver strain).
SEO highlight: *Skytrofa pharmacology review for healthcare professionals*, *Elvitegravir dosing guidelines*, *HIV first‑line therapy insights*.
--
• References
1. Centers for Disease Control and Prevention (CDC) HIV Treatment Guidelines, 2024.
2. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13th ed.
3. FDA Prescribing Information – Skytrofa (2018–2024).