Naurif1 mg

Chemotherapy-Induced Nausea and Vomiting (CINV)

Naurif is FDA-approved for the prevention of nausea and/or vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including high-dose cisplatin.

Radiation-Induced Nausea and Vomiting

Naurif is FDA-approved (oral tablet formulation) for the prevention of nausea and vomiting associated with radiation, including total body irradiation and fractionated abdominal radiation.

Postoperative Nausea and Vomiting (PONV)

Naurif (injection) is FDA-approved for the prevention and treatment of postoperative nausea and vomiting in adults. Routine prophylaxis is not recommended when there is little expectation of nausea and/or vomiting after surgery.

Not Indicated For

Naurif has not been shown to be effective for nausea and vomiting from causes other than its approved indications above (for example, ordinary motion sickness), and should not be used for such purposes.

Each dose contains Granisetron (as Granisetron hydrochloride) as the active ingredient. Granisetron is available as film-coated tablets (1 mg) and as an injectable solution (1 mg/mL, in single-dose and multiple-dose vials) for intravenous use; in Bangladesh it is marketed as 1 mg tablets and 1 mg/mL injection.

Naurif is a selective serotonin 5-HT3 receptor antagonist used as an antiemetic to prevent and, for the injectable form, treat nausea and vomiting caused by cancer chemotherapy, radiation therapy, and surgery. It works by blocking serotonin at 5-HT3 receptors both in the gastrointestinal tract and in the central nervous system, interrupting the signals that trigger the vomiting reflex. Naurif does not stimulate gastrointestinal motility and is not used for general nausea unrelated to its approved indications. It is available as an oral tablet and as an intravenous injection, and is typically given as a single dose timed around chemotherapy, radiation, or surgery rather than as ongoing daily therapy.

Antiemetic - Selective 5-HT3 (serotonin) receptor antagonist

Granisetron is a potent, highly selective antagonist of 5-HT3 receptors, with little or no affinity for other receptor types including dopamine receptors. Serotonin release from cells in the small intestine triggers vagal afferent activation of the vomiting reflex; Granisetron blocks this action both peripherally, on vagal nerve terminals, and centrally, in the chemoreceptor trigger zone.

After oral administration, Granisetron is well absorbed, undergoes hepatic first-pass metabolism, and reaches peak plasma concentration within a few hours. Following intravenous administration, the elimination half-life is approximately 5-9 hours in cancer patients (somewhat shorter in healthy subjects). Granisetron is extensively metabolized in the liver, primarily via the cytochrome P450 3A subfamily, through N-demethylation and aromatic ring oxidation; metabolites are not thought to contribute significantly to activity. Elimination occurs through both hepatic metabolism and renal excretion, with roughly 12% of a dose excreted unchanged in the urine within 48 hours and the remainder recovered as metabolites in urine and feces. Total clearance is reduced (approximately halved) in patients with hepatic impairment, but is not significantly affected by severe renal impairment.

• Oral Naurif tablets should be swallowed with water; they may be taken with or without food.
• Naurif injection is given intravenously by a healthcare professional, either undiluted over 30 seconds or diluted in 0.9% sodium chloride or 5% dextrose and infused over up to 5 minutes.
• Timing relative to chemotherapy, radiation, or surgery is important: doses are generally given shortly before the triggering event (see Dosage), not after symptoms have already started, except where specifically indicated for treatment of established postoperative nausea/vomiting.
• Naurif should not be relied upon as a substitute for nasogastric suction and does not stimulate gastric or intestinal motility.
• Do not adjust the dose or timing of Naurif without medical advice.

• Serotonergic drugs (SSRIs, SNRIs, MAOIs, mirtazapine, fentanyl, lithium, tramadol, intravenous methylene blue): concurrent use with Naurif carries a risk of serotonin syndrome; monitor for mental status changes, autonomic instability, and neuromuscular symptoms if these are combined with Naurif.
• Apomorphine: concurrent use with Naurif is contraindicated because of reports of profound hypotension and loss of consciousness when apomorphine has been co-administered with 5-HT3 antagonists such as Naurif (see Contraindications).
• QT-prolonging drugs (e.g., certain antiarrhythmics, antipsychotics, some antibiotics): combining these with Naurif may increase the risk of clinically significant QT prolongation, particularly with intravenous Naurif and in patients with electrolyte abnormalities.
• Hepatic enzyme inducers or inhibitors (e.g., ketoconazole, phenobarbital): because Naurif is metabolized by hepatic cytochrome P450 3A enzymes, strong inducers or inhibitors could alter its clearance and half-life; phenobarbital has been shown to increase plasma clearance of Naurif, and ketoconazole may inhibit its metabolism in vitro, though the clinical significance is not fully established.
• Benzodiazepines, neuroleptics, and anti-ulcer medications: no clinically significant interaction has been demonstrated with Naurif when these are used concurrently.

Common Side Effects

• Headache
• Constipation
• Weakness (asthenia) or somnolence
• Diarrhea
• Dizziness

Less Common but Important Side Effects

• Hepatic enzyme elevation
• Abdominal pain, fever (reported with postoperative use)
• Insomnia, agitation, or anxiety

Serious Side Effects (Seek Medical Attention)

• Signs of a severe allergic/hypersensitivity reaction: hives, facial or throat swelling, difficulty breathing, or a sudden drop in blood pressure
• Signs of an abnormal heart rhythm related to QT prolongation: fainting, palpitations, or irregular heartbeat (see Precautions and Warnings)
• Signs of serotonin syndrome when Naurif is combined with other serotonergic drugs: agitation, hallucination, rapid heartbeat, fever, muscle rigidity or twitching, loss of coordination (see Precautions and Warnings)

Pregnancy

Naurif is classified under the older FDA pregnancy category system as Category B: animal reproduction studies in rats and rabbits have not shown evidence of impaired fertility or harm to the fetus, but there are no adequate and well-controlled studies in pregnant women. Naurif should be used during pregnancy only if clearly needed, after the treating physician has weighed the potential benefit against the potential, though unconfirmed, risk to the fetus.

Breastfeeding

It is not known whether Naurif is excreted in human breast milk. Because many drugs are excreted in human milk and the effect on a nursing infant is unknown, caution should be exercised, and a decision should be made whether to discontinue nursing or discontinue Naurif, taking into account the importance of the drug to the mother; a physician should be consulted before using Naurif while breastfeeding.

• QT interval prolongation: Naurif has been associated with QT prolongation, which can be more pronounced with intravenous administration; use with caution in patients with pre-existing arrhythmias, cardiac conduction disorders, electrolyte abnormalities (hypokalemia, hypomagnesemia), or in those taking other QT-prolonging drugs.
• Serotonin syndrome: there is a risk of serotonin syndrome when Naurif is used together with other serotonergic drugs (see Interaction); patients should be monitored for the characteristic mental status, autonomic, and neuromuscular changes.
• Hypersensitivity reactions: Naurif should be used with caution in patients known to be hypersensitive to other 5-HT3 receptor antagonists, as hypersensitivity reactions, including rare cases of anaphylaxis, have been reported.
• Masking of underlying gastrointestinal conditions: Naurif does not stimulate gastric or intestinal peristalsis and should not be used as a substitute for nasogastric suction; it may mask a progressive ileus or gastric distention following abdominal surgery or in patients with chemotherapy-induced nausea and vomiting.
• Limited indication: Naurif is not effective for nausea and vomiting due to causes other than its approved indications (for example, motion sickness) and should not be used for that purpose.
• Hepatic impairment: clearance of Naurif is reduced (approximately halved) in patients with hepatic impairment; use with appropriate clinical caution (see Use in Special Populations).

There is no specific antidote for Naurif overdose; treatment should be symptomatic and supportive. In reported cases, doses of up to 38.5 mg have been given without symptoms, or with only a slight headache. If overdose of Naurif is suspected, contact a poison control center or seek immediate emergency medical attention; the patient's cardiac status (including QT interval) and overall clinical condition should be monitored, and general supportive measures should be provided as clinically indicated.

Store Naurif tablets and injection at controlled room temperature, between 20°C and 25°C (68°F to 77°F); protect from light and do not freeze the injection. Keep Naurif out of reach of children, and discard any unused portion of single-dose injection vials after use.

• Pediatric use: for chemotherapy-induced nausea and vomiting, intravenous Naurif at 10 mcg/kg has been studied and used in children 2 to 16 years of age; it has not been studied in children under 2 years. Safety and effectiveness of oral Naurif tablets, and of Naurif for prevention of postoperative nausea/vomiting in children, have not been established; QT prolongation was observed in a pediatric postoperative trial, so Naurif is not recommended for postoperative nausea/vomiting prevention in children. See Pediatric Uses for details.
• Elderly (geriatric) patients: the safety and effectiveness of Naurif in patients 65 years of age and older are similar to those in younger adults, and no dosage adjustment is necessary.
• Renal impairment: total clearance of Naurif was not significantly affected in patients with severe renal failure; no dosage adjustment is required.
• Hepatic impairment: total clearance of Naurif is approximately halved in patients with hepatic impairment; because of wide individual variability in pharmacokinetics, routine dosage adjustment is not considered necessary, but Naurif should be used with caution.
• Pregnancy and breastfeeding: see Pregnancy and Lactation for detailed guidance.

Naurif is used for short, defined periods tied to the triggering event rather than as continuous long-term therapy. For chemotherapy-induced nausea and vomiting, Naurif is given only on the day(s) chemotherapy is administered. For radiation-induced nausea and vomiting, it is given once daily on treatment days. For postoperative nausea and vomiting, Naurif is typically given as a single intravenous dose around the time of surgery. Naurif is not intended for ongoing daily use outside of these specific treatment periods.

Antiemetics; Selective 5-HT3 (serotonin) receptor antagonists

Granisetron selectively blocks serotonin (5-HT3) receptors located on vagal nerve terminals in the gastrointestinal tract and in the chemoreceptor trigger zone of the central nervous system. Chemotherapy, radiation, and surgery can cause release of serotonin from enterochromaffin cells in the small intestine, which activates 5-HT3 receptors on vagal afferents and initiates the vomiting reflex. By blocking these 5-HT3 receptors both peripherally and centrally, Granisetron interrupts this signaling pathway and prevents the nausea and vomiting reflex from being triggered, without affecting dopamine receptors or gastrointestinal motility.

B

Naurif injection is approved for the prevention of chemotherapy-induced nausea and vomiting in children 2 to 16 years of age, at a dose of 10 mcg/kg given intravenously before chemotherapy; it has not been studied in children younger than 2 years for this use. The safety and effectiveness of oral Naurif tablets have not been established in pediatric patients. Naurif is also not recommended for the prevention of postoperative nausea and vomiting in children, because a pediatric postoperative study showed QT interval prolongation with Naurif use in this setting and safety and efficacy for this indication have not been established. A pediatrician or pediatric oncologist should determine whether and how Naurif is used in a child, based on the specific indication and the child's age and weight.