Spevigo | Pharmacology Mentor

Generic Name

Spevigo

Selective KOR activation in the area postrema, nucleus tractus solitarius, and vestibular nuclei → ↓ emetic signaling.
Lacks μ‑ or δ‑opioid receptor affinity → minimal respiratory depression, sedation, or GI motility slowing.
Modulates dorsal vagal complex and central vomition pathways, augmenting standard anti‑emetic regimens.

Parameter	Typical Value
Formulation	IV infusion, 15 µg/kg over 30 min (single dose)
Absorption	Immediate (IV)
Distribution	Low systemic exposure; plasma protein binding < 10 %
Metabolism	Peptidase‑mediated hydrolysis to inactive metabolites
Elimination	Renal (≈ 85 % unchanged)
Half‑life	~0.5–1 h (steady‑state trough ~15 min post‑infusion)
Clearance	CL ≈ 0.8 L/h/kg (dose‑proportional)
Drug‑Drug Interactions	Limited; avoid co‑administration with other CNS depressants that may potentiate sedation.

Prophylaxis of CINV in patients receiving moderately‑ or highly‑emetic‑risk chemotherapy regimens.
Administered IV 30 min prior to chemotherapy infusion.
Usually combined with a 5‑HT3 receptor antagonist and an NK‑1 receptor antagonist for maximal anti‑emetic synergy.

Hypersensitivity to difelikefalin or any excipients (tartrazine, poloxamer 407).
Pregnancy: Animal studies show no teratogenicity, but none of sufficient human data; use only if benefits outweigh risks.
Lactation: Excretion in breast milk not fully characterized; discontinue breastfeeding if administered.
Renal impairment: Clearance is renal; caution in CrCl < 30 mL/min; dose adjustment may be required.
CNS depressants: Avoid concomitant use with benzodiazepines or opioids that can enhance sedation.
PIPAT: No evidence of respiratory depression; monitoring still advised in high‑dose or repeated‑dose scenarios.

Adult dosing: 15 µg/kg IV over 30 min, prior to chemotherapy.
Repeated dosing: Same regimen on days 2–5 of chemotherapy (optional based on clinician discretion).
Infusion rate: 0.5 mg/kg/h; use a dedicated IV line to monitor for infusion reactions.
Route: IV only (no oral or topical formulations).
Special populations: Adjust dose in severe renal insufficiency; pediatric pharmacokinetics still under evaluation.

Common (≥ 5 %)	Serious (≤ 1 %)
Pruritus	Severe hypersensitivity reaction
Dizziness	Hypotension
Nausea	Arrhythmias (rare)
Somnolence	CNS depression (rare)
Headache	Anaphylaxis
Fatigue	Severe respiratory depression (none reported)

• Adverse event profile is favorable compared to μ‑opioid analgesics, with negligible GI motility impairment and no opioid‑related euphoria.

Vital signs: BP, HR, RR before, during, and 30 min post‑infusion.
Efficacy: Nausea/vomiting scale (0–10) and rescue anti‑emetic use.
Renal function: Serum creatinine and eGFR at baseline and periodically in patients with kidney disease.
Allergy signs: Watch for rash, angioedema, or bronchospasm during infusion.
Laboratory: Not routinely required unless patient has organ dysfunction.

Additive benefit: Spevigo’s KOR agonism provides anti‑emetic coverage distinct from 5‑HT3 and NK‑1 antagonists, reducing the need for corticosteroids.
Minimal respiratory depression allows its use in patients with compromised pulmonary reserve (e.g., COPD) where μ‑opioids would be contraindicated.
Rapid clearance: Difelikefalin’s short half‑life limits drug accumulation, making it attractive for multi‑day chemotherapy schedules.
Patient education: Counsel patients about the rare pruritic reaction and advise reporting any rash or breathing difficulty immediately.
Storage: 2–8 °C refrigerated; protect from light; keep unopened for up to 12 months.
Infusion compatibility: Compatible with glucose 5 % and normal saline; avoid mixing with incompatible parenteral solutions.
Cost–benefit: While initially higher than traditional anti‑emetics, Spevigo’s efficacy in high‑risk groups can reduce ICU admissions for refractory CINV, thereby lowering overall hospitalization costs.

*For detailed prescribing information, consult the latest FDA approval label and relevant clinical guidelines.*