What Zofran really is

Hi everyone, sorry to open a thread again out of nowhere.

I just want to make something clear, as some people seem to be confused. In reality, Zofran is actually a medicine I used to take. That's exactly why I choosed that name. It's not something that is good to discuss, as mostly cancer people take the medication. But, I was just curious to know if you actually knew what it really is. If anyone wanted to come close - Narfoz is the name used for the medicine in Southeast asia, which is Zofran backwards. The non-brand name is Ondansetron, too.

Pic -

 

Oh wise one, bestowing your higher knowledge upon us petty mortals

 

yeah..i can see why
Stay safe brother

 

I saw this medicine in your signature before, so I googled it and found out it's used in cancer cases. So I wanted to ask, at that time, but I hesitated. I'll ask now instead: Have you had cancer? Are you still fighting cancer?

Did you know Otarez is a medicine too?
Nah, I'm just kidding. It's not. It would be cool if it was, however.

 

Sorry to know you're not feeling well, speedy recovery, we will pray for you right @Don @eden @Nessi?

 

Well, I'll explain. No, I luckily never had Cancer. But, this medicine was originally made as prescription only in extreme cancer related cases. Therefore, in my country, its not given to non-cancer people without a special permission. I went to the hospital and received a special permission for a prescription of this medicine - and it helped me. The point is, even if you have a prescription, you can't purchase it in pharmacies without the special permission I mentioned, unless you have Cancer. I had a very rare case of Gastro-enteritis, which is a problem in the intestines. I have recovered about 3 months ago, so all is good now. I'm glad you care about me and my health!

 

It's used pretty much anytime they dont want you to throw up/you're nauseous because of drugs, etc. Cancer is common, but it's also huge in patients going under for surgery (especially those who are in emergency surgery and might have food in their stomach, etc)

To whoever is curious I put everything from lexicomp in the spoiler, pharmacists use the database for info.
It's a lot of info, lol.

Spoiler: Lexicomp Zofran Database Entry

Ondansetron (Lexi-Drugs)
Drug Shortages
One or more forms of this drug may be in short supply or unavailable. Refer to the following for additional information:

ASHP: http://www.ashp.org/menu/DrugShortages

FDA: https://www-accessdata-fda-gov.une.idm.oclc.org/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Ondansetron Hydrochloride Injection&st=c&tab=tabs-1

Pronunciation
(on DAN se tron)

Brand Names: US
Zofran; Zofran ODT [DSC]; Zuplenz

Brand Names: Canada
Ondissolve ODF; Zofran ODT

Pharmacologic Category
Antiemetic; Selective 5-HT3 Receptor Antagonist

Dosing: Adult
Note: Single IV doses >16 mg are no longer recommended due to the potential for QT prolongation (FDA 2012).

Carcinoid syndrome-associated diarrhea, severe, refractory (alternative agent) (off-label use): Based on limited data (case reports):

Oral: 8 mg 3 times daily (Wymenga 1998) or 8 mg twice daily for 3 days, followed by a maintenance dose of 4 to 8 mg/day for 4 to 12 weeks (Kiesewetter 2013)

IV: 4 to 8 mg every 8 hours (Schwörer 1995)

Chemotherapy-induced nausea and vomiting, prevention: Single-day IV chemotherapy regimens:

Highly emetogenic chemotherapy (>90% risk of emesis [eg, cisplatin, breast cancer regimens that include an anthracycline combined with cyclophosphamide]):

Day of chemotherapy: Administer prior to chemotherapy and in combination with a neurokinin 1 (NK1) receptor antagonist, dexamethasone, with or without olanzapine (ASCO [Hesketh 2017]; MASCC/ESMO [Roila 2016]).

IV: 8 mg or 0.15 mg/kg (maximum: 16 mg/dose) as a single dose (manufacturer's labeling)

Oral:

All oral formulations except for the oral soluble film: 8 mg twice daily for 2 doses with the first dose administered prior to chemotherapy administration

Manufacturer’s labeling: Dosing in the prescribing information may not reflect current clinical practice: 24 mg as a single dose

Oral soluble film: 24 mg (three 8 mg doses given together) as a single dose

Post-chemotherapy days: 5-HT3 receptor antagonist use is not recommended (alternative agents are recommended) (ASCO [Hesketh 2017]; MASCC/ESMO [Roila 2016])

Moderately emetogenic chemotherapy (30% to 90% risk of emesis): Carboplatin-based regimens:

Day of chemotherapy: Administer prior to chemotherapy and in combination with an NK1 receptor antagonist and dexamethasone (ASCO [Hesketh 2017]; MASCC/ESMO [Roila 2016])

IV: 8 mg or 0.15 mg/kg (maximum: 16 mg/dose) as a single dose (manufacturer's labeling)

Oral: 8 mg twice daily for 2 doses with the first dose administered prior to chemotherapy administration (manufacturer's labeling)

Post-chemotherapy days: Antiemetic use is not necessary (ASCO [Hesketh 2017]; MASCC/ESMO [Roila 2016]).

Moderately emetogenic chemotherapy (30% to 90% risk of emesis): Non-carboplatin-based regimens (alternative agent):

Note: ASCO guidelines and MASCC/ESMO guidelines do not state a preference for which 5-HT3 receptor antagonist should be used in this setting; however, some experts recommend palonosetron as the preferred 5-HT3 receptor antagonist (Celio 2015; Hesketh 2018; Popovic 2014).

Day of chemotherapy: Administer prior to chemotherapy and in combination with dexamethasone (ASCO [Hesketh 2017]; MASCC/ESMO [Roila 2016])

IV: 8 mg or 0.15 mg/kg (maximum: 16 mg/dose) as a single dose (manufacturer's labeling)

Oral: 8 mg twice daily for 2 doses with the first dose administered prior to chemotherapy administration (manufacturer’s labeling)

Post-chemotherapy days: 5-HT3 receptor antagonist use is not recommended (alternative agents, depending on the chemotherapy regimen administered, may be recommended) (ASCO [Hesketh 2017]; MASCC/ESMO [Roila 2016]); however, if a first-generation 5-HT3 receptor antagonist (eg, ondansetron, granisetron) was used on day 1 of chemotherapy rather than palonosetron, some experts suggest the first-generation 5-HT3 receptor antagonist be continued for post-chemotherapy emetic prophylaxis on days 2 and 3 (Hesketh 2018).

Low emetogenic risk (10% to 30% risk of emesis):

Note: Single-agent ondansetron is one of many options for prophylaxis (ASCO [Hesketh 2017; MASCC/ESMO [Roila 2016]).

Day of chemotherapy: Administer as a single dose prior to chemotherapy (ASCO [Hesketh 2017])

IV: 8 mg or 0.15 mg/kg (maximum: 16 mg/dose) (ASCO [Hesketh 2017]; manufacturer's labeling)

Oral (off-label): 8 mg (ASCO [Hesketh 2017])

Post-chemotherapy days: Prophylaxis is not necessary on subsequent days (ASCO [Hesketh 2017]; MASCC/ESMO [Roila 2016])

Chemotherapy-induced nausea and vomiting, prevention: Oral chemotherapy agents: Limited data; based on expert opinion:

High/moderate emetogenic risk oral agent: Oral: 8 to 16 mg/day administered before chemotherapy and continued daily (Hesketh 2018)

Low/minimal emetogenic risk oral agent: Oral: 8 to 16 mg/day on an as-needed basis (Hesketh 2018)

Gastroparesis, symptomatic treatment of nausea and vomiting (alternative agent) (off-label use): Note: For patients with persistent symptoms refractory to prokinetic therapy. No data available; recommendations for use and dose are based on expert opinion: Oral: 4 to 8 mg 3 times daily (ACG [Camilleri 2013]; Camilleri 2018)

Nausea and/or vomiting, acute, severe (off-label use): Note: Use has primarily been evaluated in patients with undifferentiated nausea/vomiting presenting to the emergency department; however, clinical experience also suggests utility in nausea/vomiting due to viral gastroenteritis, acute mountain sickness, and a variety of other medical conditions associated with severe, self-limiting acute nausea/vomiting (Alexandraki 2018; Gallagher 2018).

Oral, IV, IM: 4 mg as a single dose (Barrett 2011; Braude 2008; Egerton-Warburton 2014; Patanwala 2010; Patka 2011; Salvucci 2011). Note: For parenteral therapy, IV administration is preferred over IM when possible (Salvucci 2011).

Postoperative nausea and vomiting (PONV), prevention:

Moderate- to high-risk patients: Note: In patients at moderate risk, may combine ondansetron with other prophylactic interventions (eg, another antiemetic agent from a different pharmacologic class, modification of anesthetic technique, acupuncture); in patients at high risk, combine 3 or more interventions (Apfel 2004; Feinleib 2018; Gan 2014)

Usual dose: IV: 4 mg as a single dose at the end of surgery (Gan 2014)

Alternative strategy: Oral (oral disintegrating tablet or oral soluble film): 8 mg as a single dose given 30 to 60 minutes prior to surgery (Gan 2014; Grover 2009; Kenny 1992)

Low-risk patients:Although prophylaxis is not always indicated in low-risk patients, consensus guidelines acknowledge that some experts may administer an antiemetic in these patients; however, clinicians are also advised that this strategy comes with the potentially unnecessary risk of rare adverse effects (Gan 2014). If ondansetron is given, the dosing is the same as for moderate- to high-risk patients.

Post-discharge management in high-risk patients: Limited data available; dosage regimen studied in a single clinical trial: Oral (oral disintegrating tablet or oral soluble film): 8 mg to be taken on discharge and in the morning of postoperative days 1 and 2 (Pan 2008)

Postoperative nausea and vomiting (PONV), treatment or rescue therapy (off-label use): IV: 4 mg as a single dose when a prophylactic agent was not utilized (treatment) or following failure of an agent utilized as prophylaxis (rescue therapy) (Gan 2014). Note: Rescue therapy should always include an antiemetic from a different class than the one used for prophylaxis, unless a potentially inadequate dose was initially administered or the effect of the first drug has worn off (>6 hours since initial dose for most 5-HT3 receptor antagonists) (Feinleib 2018; Gan 2014). However, some experts do not recommend repeat administration of a 5-HT3 antagonist unless triple therapy has been used for prophylaxis and no alternatives are available for rescue that were not used for prophylaxis (Gan 2014).

Pregnancy-associated nausea and vomiting, severe or refractory (off-label use): Note: May be considered for adjunctive treatment of nausea and vomiting when symptoms persist following initial pharmacologic therapy (ACOG 2018).

Patients without hypovolemia: Oral, IV (bolus): 4 mg every 8 hours, as needed, added to current treatment regimen (Abas 2014; ACOG 2018; Oliveira 2014). If necessary, some experts increase to a maximum of 8 mg/dose (Niebyl 2010; Smith 2018)

Patients with hypovolemia: Note: For patients with persistent symptoms despite intravenous fluid replacement: IV: 8 mg administered over 15 minutes every 12 hours, added to current treatment regimen (ACOG 2018). Some experts use 4 to 8 mg administered as an IV bolus every 8 hours until stabilization (Smith 2018).

Radiation therapy-associated nausea and vomiting, prevention:

High-emetogenic risk radiation therapy (total body irradiation):

Radiation day(s):

IV (off-label): 8 mg or 0.15 mg/kg (maximum: 16 mg/dose) once daily or twice daily prior to each fraction of radiation; give in combination with dexamethasone (ASCO [Hesketh 2017]; MASCC/ESMO [Roila 2016])

Oral: 8 mg once daily or twice daily administered 1 to 2 hours prior to each fraction of radiation; give in combination with dexamethasone (ASCO [Hesketh 2017]) or, in one clinical trial of 4 days of hyperfractionated total body irradiation, 8 mg (without dexamethasone) was administered 1.5 hours prior to every fraction of radiation (3 times daily for the first 3 days and twice daily on day 4) (Spitzer 2000)

Post-radiation days:

IV (off-label), Oral: The appropriate duration of therapy following radiotherapy days is not well defined; ASCO guidelines recommend continuing ondansetron once daily or twice daily on the day after each day of radiation (ASCO [Hesketh 2017])

Moderate-emetogenic risk radiation therapy (upper abdomen, craniospinal irradiation [off-label use]):

Radiation day(s):

IV (off-label): 8 mg or 0.15 mg/kg (maximum: 16 mg/dose) once daily or twice daily prior to each fraction of radiation; may give with or without dexamethasone before the first 5 fractions (ASCO [Hesketh 2017]; MASCC/ESMO [Roila 2016])

Oral: 8 mg once daily or twice daily administered 1 to 2 hours prior to each fraction of radiation; may give with or without dexamethasone before the first 5 fractions (ASCO [Hesketh 2017]) or, in clinical trials involving upper abdomen radiation (high-dose single exposure or multiple-day fractionated course), 8 mg 3 times daily (without dexamethasone) has been given; doses were administered 1 to 2 hours prior to radiation therapy (Priestman 1990; Priestman 1993).

Vertigo-associated nausea and vomiting (alternative agent) (off-label use): Limited data available:

IV (preferred), IM: 4 to 8 mg once for acute symptoms (Furman 2018)

Oral: 4 mg every 8 to 12 hours (Furman 2018; Rice 1995)

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric
Oral: No dosing adjustment required; refer to adult dosing.

IV: Single IV doses >16 mg are no longer recommended due to the potential for QT prolongation (FDA 2012). In patients ≥75 years, Canadian recommendations place additional restrictions to limit initial IV doses to ≤8 mg due to this risk (Health Canada 2014).

Dosing: Renal Impairment: Adult
IV: No dosage adjustment is necessary.

Oral: No dosage adjustment is necessary; however, according to the manufacturer, there is no experience for oral ondansetron in renal impairment beyond first-day administration (has not been studied beyond day 1).

Dosing: Hepatic Impairment: Adult
Mild to moderate impairment: No dosage adjustment necessary.

Severe impairment (Child-Pugh class C):

IV: Day 1: Maximum daily dose: 8 mg; however, according to the manufacturer, there is no experience beyond first-day administration (has not been studied beyond day 1)

Oral: Maximum daily dose: 8 mg

Dosing: Pediatric
Chemotherapy-induced nausea and vomiting, prevention:

Prevention of nausea and vomiting associated with emetogenic chemotherapy: Infants ≥6 months, Children, and Adolescents: IV: 0.15 mg/kg/dose (maximum: 16 mg/dose) over 15 minutes for 3 doses, with the first dose administered 30 minutes prior to chemotherapy, followed by subsequent doses administered 4 and 8 hours after the first dose

Prevention of nausea and vomiting associated with moderately emetogenic chemotherapy: Oral:

Children 4 to 11 years: 4 mg 30 minutes before chemotherapy; repeat 4 and 8 hours after initial dose, then 4 mg 3 times a day for 1 to 2 days after completion of chemotherapy.

Children ≥12 years:

Tablet: 8 mg 30 minutes before chemotherapy; repeat 8 hours after initial dose, then 8 mg twice daily (every 12 hours) for 1 to 2 days after completion of chemotherapy.

Soluble film: 8 mg orally twice a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose, then 8 mg twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy.

Guideline recommendations: Prevention of chemotherapy-induced nausea and vomiting:

Pediatric Oncology Group of Ontario (POGO)(off-label dosing; Dupuis 2013; Patel 2017):

Highly emetogenic chemotherapy: Infants ≥1 month and Children <12 years: IV, Oral: 0.15 mg/kg/dose (5 mg/m2/dose) prior to chemotherapy and then every 8 hours; maximum recommended IV dose: 16 mg. Antiemetic regimen also includes dexamethasone

Highly emetogenic chemotherapy: Children ≥12 years and Adolescents: IV, Oral: 0.15 mg/kg/dose (5 mg/m2/dose) prior to chemotherapy and then every 8 hours; maximum recommended IV dose: 16 mg. Antiemetic regimen includes dexamethasone and if no known or suspected drug interactions, aprepitant.

Moderately emetogenic chemotherapy: Infants ≥1 month, Children, and Adolescents: IV, Oral: 0.15 mg/kg/dose (5 mg/m2/dose; maximum: 8 mg dose); prior to chemotherapy and then every 12 hours. Antiemetic regimen also includes dexamethasone.

Low emetogenicity chemotherapy: Infants ≥1 month, Children, and Adolescents: IV, Oral: 0.3 mg/kg/dose (10 mg/m2/dose; maximum IV dose: 16 mg) prior to chemotherapy

Postoperative nausea and vomiting (PONV), prevention:

Infants ≥1 month and Children ≤12 years: IV:

≤40 kg: 0.1 mg/kg as a single dose over 2 to 5 minutes

>40 kg: 4 mg as a single dose over 2 to 5 minutes

Adolescents >12 years: IV, IM: Refer to adult dosing.

Dosing: Renal Impairment: Pediatric
IV: No dosage adjustment is necessary.

Oral: No dosage adjustment is necessary; however, there is no experience for oral ondansetron in renal impairment beyond first-day administration (has not been studied beyond day 1)

Dosing: Hepatic Impairment: Pediatric
There are no pediatric-specific recommendations; based on experience in adult patients, no adjustment may be necessary for mild to moderate hepatic impairment; for severe impairment, dosing adjustment suggested.

Use: Labeled Indications
Cancer chemotherapy-induced nausea and vomiting:

IV: Prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy (including high-dose cisplatin).

Oral:

Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy (including cisplatin ≥50 mg/m2).

Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.

Postoperative nausea and/or vomiting: IV, IM, Oral: Prevention of postoperative nausea and/or vomiting (PONV). If nausea/vomiting occur in a patient who had not received prophylactic ondansetron, IV ondansetron may be administered to prevent further episodes.

Limitations of use: Routine prophylaxis for PONV in patients with minimal expectation of nausea and/or vomiting is not recommended, although use is recommended in patients when nausea and vomiting must be avoided in the postoperative period, even if the incidence of PONV is low.

Radiotherapy-associated nausea and vomiting: Oral: Prevention of nausea and vomiting associated with radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen.

* See Uses in AHFS Essentials for additional information.

Use: Off-Label
Carcinoid syndrome-associated diarrhea, severe, refractoryLevel of Evidence [C]
Data from a limited number of patients (case reports) suggest that ondansetron may be of benefit in the management of severe carcinoid syndrome associated-diarrhea that is refractory to preferred agents (eg, somatostatin analogues) Ref.

Gastroparesis, symptomatic treatment of nausea and vomiting (alternative agent in patients with persistent symptoms refractory to prokinetic therapy)Level of Evidence [C]
Expert opinion suggests the utility of ondansetron as an alternative agent in patients with persistent nausea and vomiting refractory to prokinetic therapy Ref. There are no published data evaluating the role of antiemetics, including ondansetron, in the treatment of this condition.

Nausea and/or vomiting, acute, severeLevel of Evidence [C]
Limited data from a small number of randomized and nonrandomized trials, primarily in the emergency department setting, suggest benefit with ondansetron in the treatment of severe, acute undifferentiated nausea and/or vomiting Ref; however, definitive, high-quality trials supporting efficacy are lacking Ref.

Clinical experience also suggests the utility of ondansetron in the treatment of severe, acute nausea and vomiting due to a variety of self-limiting etiologies such as viral gastroenteritis Ref, acute mountain sickness Ref, or a variety of other medical conditions associated with severe nausea/vomiting.

Postoperative nausea and vomiting, treatment or rescue therapyLevel of Evidence [G]
Based on the Society for Ambulatory Anesthesia guidelines for the management of postoperative nausea, it is reasonable to administer a 5-HT3 receptor antagonist for the treatment of postoperative nausea and vomiting when a prophylactic agent was not utilized or as rescue therapy when an agent from a different class was utilized as prophylaxis and failed.

Pregnancy-associated nausea and vomiting, severe or refractoryLevel of Evidence [B, G]
Based on the Society of Obstetricians and Gynaecologists of Canada guideline on nausea and vomiting of pregnancy and the American College of Obstetricians and Gynecologists practice bulletin, the use of ondansetron may be considered in the treatment of severe or refractory nausea and vomiting when preferred agents have failed Ref.

Vertigo-associated nausea and vomitingLevel of Evidence [C]
Data from a small, open-label, pilot study and clinical experience suggests the utility of ondansetron in the acute treatment of nausea and vomiting associated with vertigo Ref.

Level of Evidence Definitions
Level of Evidence Scale
Clinical Practice Guidelines
Antiemetics in oncology setting:

American Society of Clinical Oncology, Antiemetics: Clinical Practice Guideline Updates, July 2017

Multinational Association of Supportive Care in Cancer (MASCC)/European Society for Medical Oncology (ESMO), “Antiemetic Guidelines,” Updated 2016

National Comprehensive Cancer Network® (NCCN), Clinical Practice Guidelines in Oncology™, Antiemesis

Pediatric Oncology Group of Ontario, Guideline for the Prevention of Acute Nausea and Vomiting Due to Antineoplastic Medication in Pediatric Cancer Patients, 2013

Pediatric Oncology Group of Ontario, Guideline for the Prevention of Acute Chemotherapy-Induced Nausea and Vomiting in Pediatric Cancer Patients: A Focused Update, 2017

Antiemetics in postoperative setting:

Society for Ambulatory Anesthesiology, Consensus Guidelines for the Management of Postoperative Nausea and Vomiting, 2014

Administration: IM
Should be given undiluted.

Administration: IV
IVPB: Infuse diluted solution over 15 minutes

Chemotherapy-induced nausea and vomiting: Give first dose 30 minutes prior to beginning chemotherapy.

IV push: Prevention of postoperative nausea and vomiting: Single doses may be administered IV injection as undiluted solution over at least 30 seconds but preferably over 2 to 5 minutes

Administration: Injectable Detail
pH: 3 to 4

Administration: Oral
Oral dosage forms should be given 30 minutes prior to chemotherapy; 1 to 2 hours before radiation; 30 to 60 minutes prior to surgery or induction of anesthesia

Orally disintegrating tablets: Do not remove from blister until needed. Peel backing off the blister, do not attempt to push tablet through the foil. Using dry hands, place tablet on tongue and allow to dissolve. Swallow with saliva (no need to administer with liquids).

Oral soluble film: Do not remove from pouch until immediately before use. Using dry hands, place film on top of tongue and allow to dissolve (4 to 20 seconds). Swallow with or without liquid. If using more than one film, each film should be allowed to dissolve completely before administering the next film.

Dietary Considerations
Some products may contain phenylalanine.

Storage/Stability
Oral soluble film: Store between 20°C and 25°C (68°F and 77°F). Store pouches in cartons; keep film in individual pouch until ready to use.

Oral solution: Store between 15°C and 30°C (59°F and 86°F). Protect from light.

Tablet: Store between 2°C and 30°C (36°F and 86°F).

Vial: Store between 2°C and 30°C (36°F and 86°F). Protect from light. Chemically and physically stable when mixed in D5W or NS for 48 hours at room temperature; however, diluents generally do not contain a preservative and sterile precautions should be observed. After dilution, do not use beyond 24 hours.

Premixed bag in D5W: Store at 20°C to 25°C (68°F to 77°F), excursions permitted from 15°C to 30°C (59°F to 86°F); may refrigerate; avoid freezing and excessive heat; protect from light.

Preparation for Administration
Vial:

Prevention of chemotherapy-induced nausea and vomiting: Dilution is required prior to IV infusion. Dilute in 50 mL D5W or NS. In pediatric patients between 6 months and 1 year of age and/or ≤10 kg, may dilute in 10 to 50 mL D5W or NS, depending on fluid needs of the patient. Use diluted solutions within 24 hours of preparation.

Prevention of postoperative nausea and vomiting: No dilution is required.

Compatibility
See Trissel’s IV Compatibility Database

Extemporaneously Prepared
Note: Commercial oral solution is available (0.8 mg/mL)

If commercial oral solution is unavailable, a 0.8 mg/mL syrup may be made with ondansetron tablets, Ora-Plus® (Paddock), and any of the the following syrups: Cherry syrup USP, Syrpalta® (HUMCO), Ora-Sweet® (Paddock), or Ora-Sweet® Sugar-Free (Paddock). Crush ten 8 mg tablets in a mortar and reduce to a fine powder (flaking of the tablet coating occurs). Add 50 mL Ora-Plus® in 5 mL increments, mixing thoroughly; mix while adding the chosen syrup in incremental proportions to almost 100 mL; transfer to a calibrated bottle, rinse mortar with syrup, and add sufficient quantity of syrup to make 100 mL. Label "shake well" and "refrigerate". Stable for 42 days refrigerated (Trissel 1996).

Rectal suppositories: Calibrate a suppository mold for the base being used. Determine the displacement factor (DF) for ondansetron for the base being used (Fattibase® = 1.1; Polybase® = 0.6). Weigh the ondansetron tablet(s). Divide the tablet weight by the DF; this result is the weight of base displaced by the drug. Subtract the weight of base displaced from the calculated weight of base required for each suppository. Grind the ondansetron tablets in a mortar and reduce to a fine powder. Weigh out the appropriate weight of suppository base. Melt the base over a water bath (<55°C). Add the ondansetron powder to the suppository base and mix well. Pour the mixture into the suppository mold and cool. Stable for at least 30 days refrigerated (Tenjarla 1998).

Tenjarla SN, Ward ES, and Fox JL, "Ondansetron Suppositories: Extemporaneous Preparation, Drug Release, Stability and Flux Through Rabbit Rectal Membrane," Int J Pharm Compound, 1998, 2(1):83-8.

Trissel LA, Trissel's Stability of Compounded Formulations, Washington, DC: American Pharmaceutical Association, 1996.

Medication Patient Education with HCAHPS Considerations
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, loss of strength and energy, constipation, diarrhea, anxiety, or injection site irritation. Have patient report immediately to prescriber angina, passing out, bradycardia, tachycardia, abnormal heartbeat, numbness or tingling, severe fatigue, abdominal pain, difficult urination, abnormal movements, vision changes, seizures, dizziness, chills, or signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Medication Safety Issues
Sound-alike/look-alike issues:
Contraindications
Hypersensitivity to ondansetron or any component of the formulation; concomitant use with apomorphine

Warnings/Precautions
Concerns related to adverse effects:

• Hypersensitivity: Hypersensitivity reactions (including anaphylaxis and bronchospasm) have been reported; discontinue if hypersensitivity occurs. Use with caution in patients allergic to other 5-HT3 receptor antagonists; cross-reactivity has been reported.

• QT prolongation: ECG changes, including dose-dependent QT interval prolongation, have been observed with ondansetron use. Cases of torsades de pointes have also been reported. Selective 5-HT3 antagonists, including ondansetron, have been associated with a number of dose-dependent increases in ECG intervals (eg, PR, QRS duration, QT/QTc, JT), usually occurring 1 to 2 hours after IV administration. Single doses >16 mg ondansetron IV are no longer recommended due to the potential for an increased risk of QT prolongation. In most patients, these changes are not clinically relevant; however, when used in conjunction with other agents that prolong these intervals or in those at risk for QT prolongation, arrhythmia may occur. When used with agents that prolong the QT interval (eg, Class I and III antiarrhythmics) or in patients with cardiovascular disease, clinically relevant QT interval prolongation may occur resulting in torsades de pointes. A number of trials have shown that 5-HT3 antagonists produce QT interval prolongation to variable degrees. Avoid ondansetron use in patients with congenital long QT syndrome. Use caution and monitor ECG in patients with other risk factors for QT prolongation (eg, medications known to prolong QT interval, electrolyte abnormalities [hypokalemia or hypomagnesemia], heart failure, bradyarrhythmias, and cumulative high-dose anthracycline therapy). Reduction in heart rate may also occur with the 5-HT3 antagonists. IV formulations of 5-HT3 antagonists have more association with ECG interval changes, compared to oral formulations.

• Serotonin syndrome: Serotonin syndrome has been reported with 5-HT3 receptor antagonists, predominantly when used in combination with other serotonergic agents (eg, SSRIs, SNRIs, MAOIs, mirtazapine, fentanyl, lithium, tramadol, and/or methylene blue). Some of the cases have been fatal. The majority of serotonin syndrome reports due to 5-HT3 receptor antagonist have occurred in a postanesthesia setting or in an infusion center. Serotonin syndrome has also been reported following overdose of ondansetron. Monitor patients for signs of serotonin syndrome, including mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis, dizziness, flushing, hyperthermia); neuromuscular changes (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination); gastrointestinal symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. If serotonin syndrome occurs, discontinue 5-HT3 receptor antagonist treatment and begin supportive management.

Disease-related concerns:

• Hepatic impairment: Dose limitations are recommended for patients with severe hepatic impairment (Child-Pugh class C); use with caution in mild-moderate hepatic impairment; clearance is decreased and half-life increased in hepatic impairment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.

• Phenylalanine: Orally-disintegrating tablets contain phenylalanine.

Other warnings/precautions:

• Chemotherapy-associated emesis: Antiemetics are most effective when used prophylactically (Roila 2016). If emesis occurs despite optimal antiemetic prophylaxis, re-evaluate emetic risk, disease, concurrent morbidities and medications to assure antiemetic regimen is optimized (ASCO [Hesketh 2017]).

• Ileus or gastric distention: Ondansetron does not stimulate gastric or intestinal peristalsis (do not use in place of nasogastric suction). Ondansetron may mask progressive ileus and/or gastric distension; monitor for decreased bowel activity.

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations
Elderly have a slightly decreased hepatic clearance rate. This does not, however, require a dose adjustment.

Pregnancy Risk Factor
B

Pregnancy Considerations
Adverse events were not observed in animal reproduction studies. Ondansetron readily crosses the human placenta in the first trimester of pregnancy and can be detected in fetal tissue (Siu 2006). Due to pregnancy-induced physiologic changes, clearance of ondansetron may increase as pregnancy progresses (Lemon 2016).

Although ondansetron has been evaluated for the treatment of nausea and vomiting of pregnancy, current guidelines note data related to fetal safety are conflicting (ACOG 2018); ondansetron is generally reserved for use when other agents have failed (Arsenault 2002). Because a dose-dependent QT-interval prolongation occurs with use, the manufacturer recommends ECG monitoring in patients with electrolyte abnormalities (which can be associated with some cases of NVP; Koren 2012). An international consensus panel recommends that 5-HT3 antagonists (including ondansetron) should not be withheld in pregnant patients receiving chemotherapy for the treatment of gynecologic cancers, when chemotherapy is given according to general recommendations for chemotherapy use during pregnancy (Amant 2009).

Breast-Feeding Considerations
It is not known if ondansetron is present in breast milk. According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Briggs' Drugs in Pregnancy & Lactation

• Ondansetron

Adverse Reactions
Note: Percentages reported in adult patients unless otherwise specified.

>10%:

Central nervous system: Headache (oral: 9% to 27%; IV: 17%), fatigue (oral: ≤9% to 13%), malaise (oral: ≤9% to 13%)

Gastrointestinal: Constipation (6% to 11%)

1% to 10%:

Central nervous system: Drowsiness (IV: ≤8%), sedation (IV: ≤8%), (dizziness (7%), agitation (oral: ≤6%), anxiety (oral: ≤6%), paresthesia (IV: 2%), sensation of cold (IV: 2%)

Dermatologic: Pruritus (2% to 5%), skin rash (1%)

Gastrointestinal: Diarrhea (oral: 6% to 7%; IV: Children 1 to 24 months of age: 2%)

Genitourinary: Gynecologic disease (oral: 7%), urinary retention (oral: 5%)

Hepatic: Increased serum ALT (>2 times ULN: 1% to 5%; transient), increased serum AST (>2 times ULN: 1% to 5%; transient)

Local: Injection site reaction (IV: 4%; includes burning sensation at injection site, erythema at injection site, injection site pain)

Respiratory: Hypoxia (oral: 9%)

Miscellaneous: Fever (2% to 8%)

<1%, postmarketing, and/or case reports: Abdominal pain, accommodation disturbance, anaphylactoid reaction, anaphylaxis, angina pectoris, angioedema, atrial fibrillation, bradycardia, bronchospasm, bullous skin disease, cardiac arrhythmia, cardiorespiratory arrest (IV), chest pain, chills, depression of ST segment on ECG, dyspnea, dystonic reaction, ECG changes, extrapyramidal reaction (IV), flushing, hepatic failure (when used with other hepatotoxic medications), hiccups, hypersensitivity reaction, hypokalemia, hypotension, ischemic heart disease, laryngeal edema, laryngospasm (IV), liver enzyme disorder, mucosal tissue reaction, myocardial infarction, neuroleptic malignant syndrome, oculogyric crisis, palpitations, positive lymphocyte transformation test, prolonged Q-T interval on ECG (dose dependent), second-degree atrioventricular block, serotonin syndrome, shock (IV), Stevens-Johnson syndrome, stridor, supraventricular tachycardia, syncope, tachycardia, tonic-clonic seizures, torsades de pointes, toxic epidermal necrolysis, transient blindness (lasted ≤48 hours), transient blurred vision (following infusion), urticaria, vascular occlusive events, ventricular premature contractions, ventricular tachycardia, weakness, xerostomia

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Serotonin 5-HT3 Antagonist Allergy

Metabolism/Transport Effects
Substrate of CYP1A2 (minor), CYP2C9 (minor), CYP2D6 (minor), CYP2E1 (minor), CYP3A4 (major), P-glycoprotein/ABCB1; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions
Apomorphine: Antiemetics (5HT3 Antagonists) may enhance the hypotensive effect of Apomorphine. Risk X: Avoid combination

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Domperidone: May enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Risk D: Consider therapy modification

FLUoxetine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Risk C: Monitor therapy

Haloperidol: Ondansetron may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

MetFORMIN: Ondansetron may increase the serum concentration of MetFORMIN. Risk C: Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Risk D: Consider therapy modification

Panobinostat: Ondansetron may enhance the arrhythmogenic effect of Panobinostat. Risk C: Monitor therapy

Pentamidine (Systemic): May enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy

Pimozide: May enhance the QTc-prolonging effect of Ondansetron. Risk X: Avoid combination

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Risk D: Consider therapy modification

QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Antidepressants (Moderate Risk): Ondansetron may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Antipsychotics (Moderate Risk): Ondansetron may enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Pimozide. Risk C: Monitor therapy

QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Kinase Inhibitors (Moderate Risk): Ondansetron may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Miscellaneous Agents (Moderate Risk): May enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Domperidone. Risk C: Monitor therapy

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): Ondansetron may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Quinolone Antibiotics (Moderate Risk): Ondansetron may enhance the QTc-prolonging effect of QT-prolonging Quinolone Antibiotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Risk C: Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Serotonin Modulators: Antiemetics (5HT3 Antagonists) may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline. Risk C: Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

Tapentadol: Antiemetics (5HT3 Antagonists) may diminish the analgesic effect of Tapentadol. Risk C: Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

TraMADol: Antiemetics (5HT3 Antagonists) may diminish the analgesic effect of TraMADol. Risk C: Monitor therapy

Food Interactions
Tablet: Food slightly increases the extent of absorption. Management: Administer without regard to meals.

Gene Testing May Be Considered

• CYP2D6 - Ondansetron

Genes of Interest

• Cytochrome P450, Family 3, Subfamily A, Polypeptide 4

Monitoring Parameters
ECG (if applicable in high-risk or elderly patients); potassium, magnesium. Monitor for signs of serotonin syndrome; monitor for decreased bowel activity.

Advanced Practitioners Physical Assessment/Monitoring
Assess allergy history (selective 5-HT3 receptor antagonists) prior to administering. Avoid use in presence of, or potential for, cardiac conduction abnormalities (eg, QT prolongation, medication known to prolong QT interval, electrolyte abnormalities). Oral and IV doses have different schedules and should not be administered on "PRN" basis.

Nursing Physical Assessment/Monitoring
Allergy history to selective 5-HT3 receptor antagonists should be assessed prior to administering. Assess other drugs patient may be taking that may prolong QT interval. IV: Follow infusion specifics. Oral and IV doses have different schedules and should not be administered on "PRN" basis.

Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Film, Oral:

Zuplenz: 4 mg (1 ea [DSC], 10 ea [DSC], 30 ea); 8 mg (1 ea [DSC], 10 ea [DSC], 30 ea)

Solution, Injection, as hydrochloride [strength expressed as base]:

Zofran: 40 mg/20 mL (20 mL [DSC]) [contains methylparaben, propylparaben]

Generic: 4 mg/2 mL (2 mL); 40 mg/20 mL (20 mL)

Solution, Injection, as hydrochloride [strength expressed as base, preservative free]:

Generic: 4 mg/2 mL (2 mL)

Solution, Oral, as hydrochloride [strength expressed as base]:

Zofran: 4 mg/5 mL (50 mL) [strawberry flavor]

Generic: 4 mg/5 mL (50 mL)

Tablet, Oral:

Generic: 24 mg

Tablet, Oral, as hydrochloride [strength expressed as base]:

Zofran: 4 mg, 8 mg

Generic: 4 mg, 8 mg, 24 mg

Tablet Disintegrating, Oral:

Zofran ODT: 4 mg [DSC], 8 mg [DSC] [contains aspartame, methylparaben sodium, propylparaben sodium; strawberry flavor]

Generic: 4 mg, 8 mg

Dosage Forms: Canada
Information with regard to form, strength, and availability of products uniquely available in Canada but currently not available in the US. Refer also to Dosage forms.

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Anatomic Therapeutic Chemical (ATC) Classification

• A04AA01

Generic Available (US)
May be product dependent

Pricing: US
Film (Zuplenz Oral)

4 mg (per each): $38.61

8 mg (per each): $38.61

Solution (Ondansetron HCl Injection)

4 mg/2 mL (per mL): $0.28 - $1.35

40 mg/20 mL (per mL): $0.16 - $1.25

Solution (Ondansetron HCl Oral)

4 mg/5 mL (per mL): $4.78 - $4.80

Solution (Zofran Oral)

4 mg/5 mL (per mL): $5.66

Tablet, orally-disintegrating (Ondansetron Oral)

4 mg (per each): $22.25 - $23.11

8 mg (per each): $36.66 - $38.50

Tablets (Ondansetron HCl Oral)

4 mg (per each): $0.54 - $24.89

8 mg (per each): $0.64 - $41.53

24 mg (per each): $105.50 - $106.51

Tablets (Zofran Oral)

4 mg (per each): $27.91

8 mg (per each): $46.48

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action
Ondansetron is a selective 5-HT3-receptor antagonist which blocks serotonin, both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone

Pharmacodynamics/Kinetics
Onset of action: ~30 minutes

Absorption: Oral: 100%; nonlinear absorption occurs with increasing oral doses; Zofran ODT tablets are bioequivalent to Zofran tablets; absorption does not occur via oral mucosa

Distribution: Vd:

Infants and Children: Surgical patients:

1 to 4 months: 3.5 L/kg

5 to 24 months: 2.3 L/kg

3 to 12 years: 1.65 L/kg

Children and Adolescents: Cancer patients: 4 to 18 years: 1.9 L/kg

Adults: 1.9 L/kg

Protein binding, plasma: 70% to 76%

Metabolism: Extensively hepatic via hydroxylation, followed by glucuronide or sulfate conjugation; CYP1A2, CYP2D6, and CYP3A4 substrate; some demethylation occurs

Bioavailability: Oral: 50% to 70% due to some first-pass metabolism; in cancer patients (adults), 85% to 87% bioavailability possibly related to changes in metabolism

Half-life elimination:

Children: Cancer patients: Children and Adolescents: 4 to 18 years: 2.8 hours; Surgical patients: Infants 1 to 4 months: 6.7 hours; Infants and Children 5 months to 12 years: 2.9 hours

Adults: 3 to 6 hours; Mild-to-moderate hepatic impairment (Child-Pugh classes A and B): 12 hours; Severe hepatic impairment (Child-Pugh class C): 20 hours

Time to peak: Oral: ~2 hours; Oral soluble film: ~1 hour

Excretion: Urine (44% to 60% as metabolites, ~5% as unchanged drug); feces (~25%)

Clearance:

Cancer patients: Children and Adolescents 4 to 18 years: 0.599 L/kg/hour

Surgical patients: Infants and Children: 1 to 4 months: 0.401 L/kg/hour; 5 to 24 months: 0.581 L/kg/hour; 3 to 12 years: 0.439 L/kg/hour

Adult (normal): 19 to 40 years: 0.381 L/kg/hour; 61 to 74 years: 0.319 L/kg/hour; >75 years: 0.262 L/kg/hour

Pharmacodynamics/Kinetics: Additional Considerations
Renal function impairment: Mean plasma clearance is reduced by 41% (IV) and 50% (oral) in patients with severe renal impairment (CrCl <30 mL/minute).

Hepatic function impairment: Clearance is reduced 2- to 3-fold and the volume of distribution is increased. The half-life is increased to 20 hours in patients with severe hepatic impairment.

Geriatric: In elderly patients >75 years of age, there is a reduction in clearance and an increase in elimination half-life.

Gender: The extent and rate of absorption is greater in women than in men. There is slower clearance, a smaller volume of distribution, and higher bioavailability in women.

Local Anesthetic/Vasoconstrictor Precautions
Ondansetron is one of the drugs confirmed to prolong the QT interval and is accepted as having a risk of causing torsade de pointes. The risk of drug-induced torsade de pointes is extremely low when a single QT interval prolonging drug is prescribed. In terms of epinephrine, it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, mepivacaine and levonordefrin [Carbocaine® 2% with Neo-Cobefrin®]) be used with caution.

Dental Health Professional Considerations
Ondansetron is a safer alternative than phenothiazines (ie, promethazine) for the treatment of moderate-to-severe postoperative nausea and vomiting. The cost can be a limitation.

Also see Local Anesthetic/Vasoconstrictor Precautions

Effects on Dental Treatment
Ondansetron is an alternative to phenothiazines (ie, promethazine) for the treatment of moderate-to-severe postoperative nausea and vomiting. Ondansetron prolongs the QT interval in a dose-dependent manner. Avoid ondansetron in patients with congenital long QT syndrome.

Effects on Bleeding
No information available to require special precautions

Related Information

• Drug-Induced Prolongation of the QT Interval and Torsades de Pointes
• Management of Chemotherapy-Induced Nausea and Vomiting in Adults
• Prevention of Chemotherapy-Induced Nausea and Vomiting in Children

Index Terms
GR38032R; Ondansetron HCl; Ondansetron Hydrochloride

FDA Approval Date
January 04, 1991
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Brand Names: International
Apulset (BD); Avessa (LU); Avessaron (BE); Cedantron (ID); Cetron (AR); Danac (MX); Dantron (TH, ZA); Emeset (IN, LK); Emetron (HU); Emiset (BD); Emistop (ZW); Emizof (IE); Emodan (PH); Enset (PH); Finaber (PY); Frazon (ID); Glotron (ID); Invomit (ID); Izofran (CL, UY); Lartron (MX); Mefoz (ID); Modifical (CO, EC); Narfoz (ID); Nausedron (BR); Ofran (LK); Ondak (CO); Ondant (KR); Ondavell (ID, PH, SG, TH); Ondawi (LK); Ondem (UA); Ondran (IE); Onetic (ID); Onsat (BD); Onset-8 (PH); Onsetron (KR); Onsett (TZ, ZW); Onsia (TH); Onzet (PH); Onzod (TW); Osetron (AU, BD); Periset (BD); Setofilm (ES, GB); Setronax (HK, MY, SG, VN); Trondamet (HK); Vomceran (ID); Vometron (ID); Vomiof (IN); Vomiz (TW); Yatrox (ES); Yunorm (UA); Zemitron (QA); Zetron (TH); Zilfujim (AU); Zofetron (UA); Zofran (AE, AR, AT, AU, BB, BE, BF, BG, BH, BJ, BM, BR, BS, BZ, CH, CI, CN, CY, CZ, DE, DK, EC, EE, EG, ES, ET, FI, GB, GH, GM, GN, GY, HK, HN, HR, HU, ID, IE, IL, IQ, IR, IS, IT, JM, JO, JP, KE, KR, KW, LB, LR, LT, LU, LV, LY, MA, ML, MR, MT, MU, MW, MX, MY, NE, NG, NL, NO, NZ, OM, PE, PH, PK, PL, PT, PY, QA, RU, SA, SC, SD, SE, SI, SK, SL, SN, SR, SY, TN, TR, TT, TW, TZ, UA, UG, VE, VN, YE, ZM, ZW); Zofran Melt (AE, BH, KW, QA, SA); Zofran ODT (BB); Zofran Zydis (CR, DO, GT, KR, NI, NZ, PA, SV); Zofron (GR); Zofsetron (BE); Zophren (FR)

Also, links won't work for you guys unless you for some reason are logged into lexicomp.

The US is fantastic, all you need is a doctor to write for it. It's not a huge deal though since you can't really abuse it in anyway.

 

@Evan

I know that in the US you can get this without any special permissions, etc. Speaking of that, have you heard of Dipyrone? If you live in the US, I'd appreciate if you check if you can find that in a local pharmacy. I heard that its completely banned in the US, yet, Dipyrone here can be purchased without a prescription in my country.
https://en.wikipedia.org/wiki/Metamizole#/media/File:Metamizole_legal_status_by_country2.png
https://en.wikipedia.org/wiki/Metamizole#/media/File:Metamizole_legal_status_by_country2.png

 

Lol @ such strict regulations on a drug that has no potential for recreational abuse. "Yeah bro, took these anti-nausea pills, wasn't gonna throw up to begin with but now I'm for sure not...gotta hit up my dealer for more"

 

I know, it's very frustrating. It has no serious side effects, and is relatively safe. I think it might have something to do with a limited quantity in pharmacies - they want to have enough for cancer people, so non-cancer people don't take everything, or something. It should have been over the counter.

 

Not available, I've never even heard of it, but we have really good OTC options so no real need for it.

Issue is less abuse, and more side effects/interactions.

Drugs are classed based on abuse level, yes, but also therapeutic uses. Because it has little abuse potential (none really), it's only really gated by a doctor deciding whether or not you need it. Most people don't, and it's a bit more hardcore than a person who has N/V needs when there's adequate OTC options.

Generally im all for free use, but I'm also believe the control doctors and pharmacists have is good because most people don't even know much about the drugs they're taking, let alone being responsible to follow pros/cons with legend drugs. The average person can't read above a 4th grade level, and doesn't understand that when a doctor asks what sort of medication and supplements they take, that it means stuff you buy off the shelf at a pharmacy and all the crap they get in health food stores like vitamins. Reality is, most people aren't really qualified to have that sort of say and be very sure about their decision.

Supply isn't an issue in the US as far as I know, it's just a matter of making sure only people who need it get it, so less people are taking drugs when they don't need to.

That said, OTC are dangerous enough... looking at you Tylenol. People don't need access to all the shit behind the counter.

 

Well, to me it sounds like your country has a much better prescription system than here. Not all doctors agree to prescribe a certain medicine, and in regards to Zofran, I had to go to a hospital and receive a special permission from a manager. I waited a number of days and received it. Only after showing this permission to pharmacies, they can sell me a Zofran. I bought a large amount and put it in my home, so in case I need it, I wont have to go through the procedure again. I dont think I'll ever need it again, and glad I don't. Also, a good warning to others - never take Metoclopramide. It has very bad side effects, including a type of depression which makes you suicidal. I almost jumped off a bridge when I took it. It seems like the doctor didn't tell me about it before I took it, he was kinda stupid.

 

I wasn't at all implying that it should be made OTC. As you mentioned, we have effective antiemetic options already available (such as Gravol) which cover the bases for most. I just meant that his country and their requirements seem unnecessarily strict--needing some form of special prescription/approval from a hospital rather than a normal script from a traditional gp or gastroenterologist.

I don't disagree with your last statement at all. Granted, there are plenty of less than ideal (to put it nicely) pharmacists and physicians out there as well.

When it comes to side effects such as that of which you listed it's highly individual and not set in stone by any means. While your pharmacist/prescribing doctor both should have spoken with you regarding the risks and potential side effects of the medication, what you experienced is likely an uncommon side effect rather than a common one. There are undoubtedly plenty of people who use(d) it without experiencing depression and/or suicidal thoughts. It's great that you recognized it was the medication prior to doing anything irrational though!

 

His example is dumb, I don't know why they would do that (it sounds like its a matter of protocal though), but in general, that sort of thing catches a lot. Dentist cant prescribe more than (I think) 7 days of narcotics, Vets theoretically get flagged for things that don't make much sense (things that are toxic for cats, doses of narcotics for dogs that would kill a person --> seen both personally)

The more doctors stick to their specialty and drugs, the less likely you are to get stupid doctors, and stupid pharmacists, giving drugs to unknowing people.

On a completely different note, I'm sure there's thing that happen in the US that most other countries do that is on par in "head scratching". First thing that comes to mind is the crap that happens with insurance but that's a different issue entirely.