Granisetron

Granisetron is approved across multiple products and formulations for the prevention — and in some cases treatment — of nausea and vomiting in several settings.

• Prevention of nausea and vomiting from emetogenic (nausea-causing) cancer chemotherapy, including high-dose cisplatin — supported by granisetron hydrochloride tablets, Granisol oral solution, granisetron hydrochloride intravenous injection, and Sancuso skin patch
• Prevention of nausea and vomiting from radiation therapy, including total body irradiation and fractionated abdominal radiation — supported by granisetron hydrochloride tablets and Granisol oral solution
• Prevention and treatment of postoperative nausea and vomiting in adults — supported by granisetron hydrochloride intravenous injection
• Sancuso skin patch: prevention of nausea and vomiting in adults receiving moderately and/or highly emetogenic chemotherapy regimens of up to 5 consecutive days
• Sustol subcutaneous injection: prevention of acute and delayed nausea and vomiting associated with moderately emetogenic chemotherapy or anthracycline and cyclophosphamide combination regimens in adults, used alongside other antiemetics

Granisetron blocks a specific type of serotonin receptor called the 5-HT3 receptor. When chemotherapy or radiation damages cells in the gut lining, those cells release serotonin — a chemical messenger — which activates 5-HT3 receptors on nearby nerves and in a vomiting center in the brain called the chemoreceptor trigger zone. Granisetron selectively binds to these receptors and blocks that signal, preventing the chain reaction that leads to nausea and vomiting.

Granisetron comes in several forms, and the timing and frequency depend entirely on which product you've been prescribed and why. Tablets and oral solution are taken by mouth on the days chemotherapy or radiation is given — generally within an hour before treatment. The Sancuso skin patch is applied to the upper outer arm before chemotherapy begins and worn for the duration, up to 7 days. Intravenous and subcutaneous injections are given by a healthcare provider before treatment or surgery.

• Tablets and oral solution: taken only on treatment days; continued use on non-treatment days is not recommended
• Sancuso patch: applied at least 24 hours before chemotherapy; do not cut the patch or wear more than one at a time
• Sustol injection: given no more than once every 7 days (less frequently if you have kidney impairment)

Always follow your prescriber's specific instructions — do not adjust the timing or frequency on your own.

The most common side effects reported with granisetron include:

• Headache
• Constipation
• Fever
• Abdominal pain
• Elevated liver enzymes (seen on blood tests)
• Taste changes
• Skin rash
• Weakness or fatigue

Serious reactions are less common but require prompt medical attention: these include signs of serotonin syndrome (confusion, rapid heartbeat, high fever, muscle stiffness), severe allergic reactions (trouble breathing, hives, sudden low blood pressure), and heart rhythm abnormalities. Contact your care team or seek emergency help right away if any of these occur.

• Serotonin syndrome: A potentially life-threatening build-up of serotonin activity can occur, especially when granisetron is combined with other serotonin-affecting drugs such as SSRIs, SNRIs, MAO inhibitors, fentanyl, tramadol, or lithium. Some reported cases have been fatal. Watch for agitation, hallucinations, rapid heartbeat, high fever, sweating, muscle twitching, or loss of coordination — and seek emergency care immediately.
• Heart rhythm effects (QT prolongation): Granisetron has been associated with changes in heart electrical activity. People with pre-existing arrhythmias, heart disease, abnormal electrolyte levels, or who take other QT-prolonging drugs are at greatest risk.
• Bowel masking: Granisetron does not stimulate the digestive tract. After abdominal surgery or during chemotherapy, it may hide the signs of a serious bowel blockage (ileus). It is not a substitute for nasogastric suction.
• Allergic reactions: Severe hypersensitivity reactions — including anaphylaxis — can occur, particularly in people who have previously reacted to other 5-HT3 antagonists.

Tell your prescriber and pharmacist about all medications you take before starting granisetron — several drug combinations carry important risks.

• Serotonergic drugs (SSRIs, SNRIs, MAO inhibitors, mirtazapine, fentanyl, lithium, tramadol, IV methylene blue): combined use raises the risk of serotonin syndrome, a potentially life-threatening reaction
• QT-prolonging drugs (some antibiotics, antifungals, antipsychotics, antiarrhythmics): using these together with granisetron may increase the risk of serious heart rhythm problems
• CYP450 enzyme inducers (such as phenobarbital): can speed up the breakdown of granisetron, reducing how long it stays in your body
• CYP450 enzyme inhibitors (such as ketoconazole): may slow granisetron's metabolism, potentially increasing its effects

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Do not take granisetron if you have a known allergy to granisetron or any other 5-HT3 receptor antagonist (such as ondansetron or dolasetron)
• Tell your doctor if you have a heart rhythm disorder, heart disease, or abnormal blood electrolyte levels (such as low potassium or magnesium)
• Tell your doctor about all prescription and over-the-counter medications, especially antidepressants, opioid pain medicines, or any drug that affects heart rhythm
• Sustol: avoid if you have severe kidney impairment; use with reduced frequency in moderate kidney impairment
• Pregnancy: limited human safety data are available; animal studies showed no harm, but discuss the risks and benefits with your doctor
• Breastfeeding: it is not known whether granisetron passes into breast milk; weigh the benefits of breastfeeding against potential risks with your doctor
• Children: Sustol is not recommended under age 18; tablets and Granisol oral solution have not been established as safe and effective in children; intravenous granisetron hydrochloride has been studied in children aged 2–16 for chemotherapy-related nausea
• Older adults: no dose adjustment is typically required, but older adults may be more sensitive; clearance may be slower with intravenous granisetron in elderly patients

There is no specific antidote for a granisetron overdose. If too much is taken, treatment focuses on managing any symptoms that arise. Overdoses of up to very large single intravenous doses have been reported with no symptoms or only headache, but any suspected overdose should be reported to a healthcare provider or poison control immediately.

Granisetron is highly selective — it blocks 5-HT3 serotonin receptors with little to no effect on other receptor types, including dopamine, histamine, or opioid receptors. Studies show granisetron generally has little effect on blood pressure, heart rate, or heart electrical activity (ECG) in most people, though QT prolongation has been reported. It does not stimulate movement in the stomach or intestines, and oral doses have been shown to slow movement in the colon.

Granisetron is broken down primarily by the liver, through a process involving the CYP3A enzyme family, and is cleared mainly as metabolites — about half through the urine and about a third through the feces, with only a small fraction excreted unchanged. The Sancuso patch delivers granisetron slowly through the skin over up to 7 days, reaching peak blood levels around 48 hours after application; heat applied over the patch can increase absorption. In people with liver disease, clearance is significantly reduced. People with severe kidney disease do not appear to have significantly altered clearance of granisetron itself, though Sustol has additional kidney-related cautions due to its polymer vehicle.

Store single-dose vials and multiple-dose vials at 20º to 25°C (68º to 77°F) . Protect from light. Do not freeze.