Granisetron

Intravenous
Nausea and vomiting associated with cancer chemotherapy

Intravenous
Prophylaxis of nausea and vomiting associated with radiation therapy

Intravenous
Postoperative nausea and vomiting

Oral
Nausea and vomiting associated with cancer chemotherapy

Oral
Prophylaxis of nausea and vomiting associated with radiation therapy

Subcutaneous
Prophylaxis of chemotherapy-induced nausea and vomiting

Transdermal
Prophylaxis of chemotherapy-induced nausea and vomiting

Subcutaneous
Prophylaxis of chemotherapy-induced nausea and vomiting:

CrCl (mL/min)	Dosage
<30	Avoid use.
30-59	10 mg on Day 1 of chemotherapy; do not administer more frequently than once every 14 days.

Granisetron May be taken with or without food.

IV infusion: Dilute with a compatible infusion fluid (e.g. NaCl 0.9%, dextrose 5% in water) to a total volume of 20-50 mL (adult) or 10-30 mL (child). 

Patient with cardiac co-morbidities or disease, congenital long QT syndrome or other predisposition for QT prolongation (e.g. electrolyte abnormalities, medications known to prolong QT interval, cardiotoxic chemotherapy), sub-acute intestinal obstruction. May mask progressive ileus and/or gastric distention (particularly after abdominal surgery). Patients receiving anticoagulant or antiplatelet agents are at higher risk of having severe inj site bruising or haematoma (SC). Renal impairment (SC). Children (IV). Pregnancy and lactation.

Significant: Constipation or faecal impaction; QT prolongation; hypersensitivity reactions (e.g. anaphylaxis); serotonin syndrome (e.g. altered mental status, autonomic instability, neuromuscular changes, seizures); inj site reactions associated with SC formulation (e.g. infection, severe bruising, haematomas, bleeding, nodules, pain, tenderness).
Blood and lymphatic system disorders: Anaemia, leucopenia, thrombocytopenia.
Cardiac disorders: Atrial fibrillation (IV).
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal pain, dyspepsia; dysgeusia (IV).
General disorders and administration site conditions: Fever, asthenia, fatigue; transdermal application site reactions (e.g. rash, pruritus, pain, erythema).
Investigations: Elevated hepatic transaminases.
Metabolism and nutrition disorders: Decreased appetite.
Nervous system disorders: Headache, dizziness, somnolence, extrapyramidal syndrome.
Psychiatric disorders: Insomnia, anxiety; agitation (IV).
Skin and subcutaneous tissue disorders: Rash, alopecia.
Vascular disorders: Hypertension; flushing, syncope (IV).

IV/Parenteral/PO/SC/Transdermal: B

Avoid excessive exposure to natural or artificial sunlight; cover the transdermal patch with protective clothing over treated areas when going outdoors and for 10 days following removal.

Monitor for signs and symptoms of constipation or decreased bowel activity development (specifically to those at risk for gastrointestinal obstruction); inj site reactions (SC); hypersensitivity reactions, and serotonin syndrome.

Symptom: Mild headache. Management: Symptomatic treatment.

Increased total plasma clearance with phenobarbital. May enhance the QT-prolonging effect when used concomitantly with QT-prolonging agents.
Potentially Fatal: Enhanced risk of serotonin syndrome with other serotonergic agents (e.g. SSRI, SNRI, MAOI, fentanyl, lithium, mirtazapine, IV methylthioninium chloride [methylene blue], tramadol).

Description:
Mechanism of Action: Granisetron, a potent anti-emetic, is a highly selective inhibitor of type 3 serotonin (5-HT₃) receptors. It blocks serotonin both centrally in the chemoreceptor trigger zone and peripherally on vagal nerve terminals. Granisetron binds to 5-HT₃-receptors and blocks the stimulation of serotonin hence preventing cytotoxic-induced emesis.
Onset: 1-3 minutes (IV).
Duration: Up to 24 hours (IV, oral).
Pharmacokinetics:
Absorption: Rapidly and completely absorbed from the gastrointestinal tract (oral); slowly absorbed and crosses intact skin into the systemic circulation via passive diffusion (transdermal). Bioavailability: Approx 60% (oral). Time to peak plasma concentration: Approx 2 hours (oral); approx 24 hours (SC); approx 48 hours with a range of 24-168 hours (transdermal).
Distribution: Widely distributed throughout the body. Volume of distribution: Approx 3 L/kg. Plasma protein binding: Approx 65%.
Metabolism: Primarily metabolised in the liver via N-demethylation and aromatic ring oxidation then conjugation by CYP1A1 and CYP3A4 enzymes.
Excretion: Via urine (11-12% as unchanged drug; 48-49% as metabolites); faeces (34-38% as metabolites). Elimination half-life: 6 hours (oral); 5-9 hours (IV); approx 24 hours (SC).

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5284566, Granisetron. https://pubchem.ncbi.nlm.nih.gov/compound/Granisetron. Accessed Sept. 24, 2024.

Tab/intact vial/transdermal patch: Store between 15-30°C. Protect from light. Do not freeze the vial. Diluted solution for IV infusion: May be stored at room temperature for up to 24 hours. SC inj: Store between 2-8°C. Do not freeze. May return to the refrigerator after being kept at room temperature and may store at room temperature for up to 7 days. Protect from light.

Antiemetics / Supportive Care Therapy

A04AA02 - granisetron ; Belongs to the class of serotonin (5HT3) antagonists. Used for the prevention of nausea and vomiting.

Anon. Granisetron. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 31/07/2024.

Buckingham R (ed). Granisetron. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 24/01/2024.

Granisetron 1 mg/1 mL Concentrate for Solution for Infusion or Injection (Torrent Pharma [UK] Ltd.). MHRA. https://products.mhra.gov.uk. Accessed 24/01/2024.

Granisetron 2 mg Film-coated Tablets (Crescent Pharma Limited). MHRA. https://products.mhra.gov.uk. Accessed 24/01/2024.

Granisetron Hydrochloride Injection (Hikma Pharmaceuticals USA Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 31/07/2024.

Granisetron Hydrochloride Tablet (Breckenridge Pharmaceutical, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 24/01/2024.

Granisetron. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 31/07/2024.

Granisetron. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 31/07/2024.

Joint Formulary Committee. Granisetron. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 24/01/2024.

Kytril Ampoules (DKSH Malaysia Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 24/01/2024.

Kytril Tablet (DKSH Malaysia Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 24/01/2024.

Paediatric Formulary Committee. Granisetron. BNF for Children [online]. London. BMJ Group, Pharmaceutical Press, and RCPCH Publications. https://www.medicinescomplete.com. Accessed 24/01/2024.

Rex Medical Limited. Granirex Injection data sheet 31 January 2022. Medsafe. http://www.medsafe.govt.nz. Accessed 24/01/2024.

Sancuso 3.1 mg/24 hours Transdermal Patch (Kyowa Kirin Holdings B.V.). MHRA. https://products.mhra.gov.uk. Accessed 24/01/2024.

Sancuso Patch (Cumberland Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 31/07/2024.

Sustol Injection (Heron Therapeutics, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 24/01/2024.