Diacomit
Diacomit
Generic Name
Diacomit
Mechanism
- Selective antagonism of 5‑HT₃ receptors in the central nervous system (nucleus tractus solitarius, dorsal vagal complex) and in the gastrointestinal tract.
- Blocks serotonin‑mediated transmission of emetic signals, thereby preventing the “vomiting reflex” triggered by chemotherapeutics and opioid analgesics.
Pharmacokinetics
| Property | Detail |
| Absorption | Rapid, >95 % oral bioavailability; IV bypasses first‑pass metabolism. |
| Distribution | Volume of distribution ~30 L; crosses the placenta and enters breast milk. |
| Metabolism | Predominantly hepatic via CYP3A4/2C19 → hydrolysis; minimal CYP involvement for IV route. |
| Elimination | Renal (≈70 %) and biliary. Half‑life ≈1 day (IV) and 3–6 h (oral). |
| Drug interactions | Inhibitors/inducers of CYP3A4 can alter levels; caution with CYP3A4‑substrates—no major clinically relevant interactions reported. |
Indications
- Acute (first 24 h) CINV in patients receiving moderately or highly emetogenic chemotherapy.
- Delayed CINV (24–120 h) for highly emetogenic regimens.
- Post‑operative nausea and vomiting prophylaxis in major surgeries.
- Opioid‑induced nausea as adjunct to multimodal antiemetic therapy.
Contraindications
- Hypersensitivity to granisetron or any excipients.
- QTc prolongation: cautious in patients with congenital long QT syndrome, electrolyte disturbances, or concurrent QT‑prolonging drugs (e.g., ondansetron, azithromycin).
- Severe hepatic dysfunction: Not recommended; dose adjustment may be necessary.
- Pregnancy: Category C; use only if benefits outweigh risks.
Dosing
| Route | Dosage | Timing | Notes |
| IV | 1 mg (1 mL solution) | 30 min before chemotherapy, repeat after 1st dose of chemo. | Followed by dexamethasone 4–8 mg PO for highly emetogenic agents. |
| Oral (capsule) | 3.3 mg | 30 min before chemo. | Light, non‑fatty meal optional. |
| Oral (tablet) | 0.5 mg | 30 min before chemo, repeat 12 h for delayed phase. | |
| Post‑operative | 1–2 mg IV or 0.1 mg/kg IV 15 min before incision |
*Note*: A 7‑day delayed‑phase regimen (e.g., 0.5 mg PO q11 h for 7 days) is sometimes used for highly emetogenic protocols.
Adverse Effects
- Common: headache, constipation, dizziness, fatigue, flushing, mild diarrhea.
- Serious: rare cases of serotonin syndrome (with other serotonergic agents), significant QTc prolongation leading to arrhythmias, Splenic rupture (extremely rare).
- Pregnancy: potential teratogenic effects not fully characterized; use with caution.
Monitoring
- Baseline: ECG (QTc interval) if at risk; electrolytes (K⁺, Mg²⁺, Ca²⁺); liver function tests if hepatic impairment.
- During therapy: Vitals, emesis frequency, and response to antiemetic.
- Post‑operative: Monitor for respiratory depression and arrhythmias in high‑dose cases.
Clinical Pearls
- Combination therapy: For highly emetogenic chemotherapy, combine granisetron + dexamethasone + an NK1 antagonist for optimal prophylaxis.
- Renal impairment: Since granisetron is primarily renally excreted, dose reduction is not usually required; still monitor drug accumulation in severe renal failure.
- Drug interactions: Be mindful of agents that prolong QT, such as some antiarrhythmics or antibiotics; consider baseline ECG.
- Pregnancy & lactation: Granisetron crosses the placenta; switch to a safer antiemetic if pregnancy is confirmed.
- Brand vs. generic: Equivalent efficacy; generic formulations may save costs without compromising therapeutic effect.
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• References:
1. *Hoffman R, Santus R. Granisetron: A Review of Its Use in Chemotherapy‑Induced Nausea and Vomiting*. J Clin Oncol. 2018.
2. *American Society of Clinical Oncology Guidelines for Antiemetic Therapy*. 2023.
3. *DrugBank: Granisetron* (latest pharmacology profile 2025).