Zenpep
Zenpep
Generic Name
Zenpep
Mechanism
- Competitive antagonist at central and peripheral 5‑HT₃ receptors, inhibiting serotonin‑mediated activation of the vomiting center in the brainstem.
- Blocks neurotransmission in the enteric nervous system, reducing delayed‑phase emesis.
- Minimal effect on other serotonergic or dopaminergic systems, leading to a low incidence of extrapyramidal or hormonal side effects.
Pharmacokinetics
| Parameter | Value | Comment |
| Absorption | Rapid; peak plasma concentration (Tₘₐₓ) ~0.5 h | Oral bioavailability ~70% |
| Distribution | Vd ≈ 0.3 L/kg; extensive protein binding (~70%) | Penetrates the CNS to exert anti‑emetic effects |
| Metabolism | Primarily CYP3A4 (hepatically) with minor CYP2D6 contribution | Induction or inhibition of CYP3A4 significantly alters plasma levels |
| Elimination | Renal excretion of unchanged drug ~30% | Half‑life ~3–4 h in healthy adults |
| Special Populations | Clearance reduced in severe hepatic impairment; dose adjustment may be required |
Indications
- Acute and delayed CINV following moderately to highly emetogenic chemotherapy regimens
- Post‑operative nausea and vomiting (PONV) when pharmacologic options are preferred
- Nausea associated with radiotherapy for head and neck cancers
- Antiemetic prophylaxis in patients with history of motion sickness or vestibular disorders when pharmacologic treatment is warranted
Contraindications
- Hypersensitivity to the drug or any excipient
- Severe hepatic impairment (Child‑Pugh B/C) – dose reduction or avoidance
- Concurrent use with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) or inducers (e.g., rifampin, carbamazepine)
- New York Heart Association (NYHA) Class III/IV heart failure – monitor cardiovascular status
- Pregnancy – category B (limited data), but avoid if unnecessary
- Breastfeeding – excretion into milk; advise caution
Dosing
- Adult: 4 mg PO or IV, 30 min before chemotherapy; repeat dose 12 h later for highly emetogenic regimens
- Pediatric: 0.04 mg/kg (max 4 mg), PO or IV
- Renal Impairment: No adjustment needed for CrCl > 30 mL/min; consider dose reduction for CrCl < 30 mL/min
- Hepatic Impairment: Reduce dose by 25–50% if Child‑Pugh B; avoid in Child‑Pugh C
Adverse Effects
| Category | Examples |
| Common | Headache, constipation, diarrhea, fatigue, dizziness, mild QT prolongation |
| Serious | Severe hypersensitivity reactions (rash, anaphylaxis), significant QT interval prolongation (>500 ms), hepatotoxicity (rare), serotonin syndrome when combined with SSRIs/SNRIs |
Monitoring
- Electrocardiogram (ECG) pre‑ and post‑dose if baseline QT is prolonged or if combined with other QT‑prolonging agents
- Liver function tests (LFTs) at baseline and periodically in patients on long‑term therapy
- Renal function if dose adjustment is needed
- Patient diary for nausea intensity (0–10 scale) to assess therapeutic efficacy
Clinical Pearls
- Combination Therapy: Zenpep is most effective when paired with a glucocorticoid (e.g., dexamethasone) and an NK1‑receptor antagonist for highly emetogenic chemotherapy.
- Timing Is Crucial: Administer 30 min before chemotherapy for optimal anti‑emetic coverage of the acute phase; a second dose at 12 h improves delayed‑phase control.
- Drug‑Drug Interactions: Avoid co‑administration with strong CYP3A4 inhibitors; if unavoidable, monitor plasma levels and watch for increased toxicity.
- Pediatric Use: Weight‑based dosing is key; maximum dose is 4 mg irrespective of weight.
- Pregnancy & Lactation: While animal studies show low risk, human data remain limited – use only if benefits outweigh potential risks.
- QT Prolongation Alert: Screen patients with baseline QT > 460 ms; in patients requiring additional QT‑prolonging agents, consider ECG monitoring or use an alternative anti‑emetic.
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• Zenpep is a reliable, low‑risk anti‑emetic in the 5‑HT₃ antagonist class, offering both efficacy and convenience for patients undergoing challenging chemotherapy regimens.