5-HT3 Receptor Antagonist

Aka: 5-HT3 Receptor Antagonist, 5-HT3 Antagonist, Serotonin 5-HT3 Receptor Antagonist, Ondansetron, Zofran, Granisetron, Kytril, Dolasetron, Anzemet, Palonosetron, Aloxi

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II. Indications

  1. Chemotherapy associated Nausea
  2. Radiation Therapy associated Nausea
  3. Vomiting refractory to first-line Antiemetics
  4. Theophylline Overdose
    1. Used instead of phenothiazines due to Seizure risk

III. Mechanism

  1. Blocks peripheral and central 5HT3 receptors
    1. Peripheral 5HT3 receptors at vagal nerve terminals
    2. Central 5HT3 receptors at chemoreceptor Trigger Zone in Medulla (area postrema controls Vomiting)

IV. Contraindications

  1. First trimester pregnancy (relative contraindication based on preliminary data)
    1. Previously thought to be safe in pregnancy
    2. FDA cautions use in Gestational age <10 weeks
    3. As of 2013, Ondansetron may be associated with 2 fold increased risk of congenital malformations
      1. Congenital Heart Defects
      2. Cleft Palate
    4. References
      1. (2014) Presc Lett 21(1): 5
      2. Anderka (2012) Birth Defects Res A Clin Mol Teratol 94(1):22-30 +PMID:22102545 [PubMed]
      3. Danielsson (2014) Reprod Toxicol 50:134-7 +PMID:25450422 [PubMed]

V. Adverse Effects

  1. Mild Headache
  2. Dizziness
  3. Malaise or Fatigue
  4. Constipation
  5. QT Prolongation
    1. More common with single doses >16 mg IV
    2. If QTc is already prolonged, Metoclopramide (Reglan) is a safe alternative without risk of QTc Prolongation
    3. Unlikely to cause harm (even at highest dose, Ondansetron prolongs QTc only 20 ms)
      1. Freedman (2014) Ann Emerg Med 64(1): 19-25 +PMID:24314899 [PubMed]
      2. Moffett (2016) Acad Emerg Med 23(1): 102-5 +PMID: 26720490 [PubMed]
  6. Serotonin Syndrome
    1. http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm351864.htm

VI. Dosing: Ondansetron (Zofran)

  1. Gastroenteritis using Ondansetron 4 mg ODT tabs
    1. Weight 8-15 kg: Ondansetron 2mg (half tab)
    2. Weight 15-30 kg: Ondansetron 4 mg (one tab)
    3. Weight >30 kg: Ondansetron 8 mg (two tabs)
    4. Freedman (2006) N Engl J Med 354:1698-705 [PubMed]
  2. Nausea with Chemotherapy
    1. Intravenous dosing
      1. Timing
        1. First dose: 30 minutes before Chemotherapy
        2. Subsequent dosing: 4 and 8 hours after first dose
      2. Adult: 32 mg IV over 15 min
      3. Child: 0.15 mg/kg IV over 15 min (maximum: 8 mg/dose)
    2. Oral dosing (ODT)
      1. Over age 12 years: 8 mg orally twice daily
      2. Age 4 to 11 years: 4 mg orally three times daily
      3. Age under 4 years: 0.15 mg/kg/dose (up to 4 mg)
  3. Nausea with Radiation Therapy (adult)
    1. Dose: 8 mg orally four times daily
  4. Surgery related Nausea (adult)
    1. Prevention: 8-16 mg orally 1 hour before surgery
    2. Treatment: 4 mg IV or IM over 2-5 minutes
    3. Efficacy
      1. Meta-analysis of 7 randomized trials, n=1043
      2. Works in only 25% of patients
      3. No more effective than less expensive drugs
      4. Tramer (1997) BMJ 314:1088-93 [PubMed]

VII. Dosing: Dolasetron (Anzemet)

  1. Nausea with Chemotherapy
    1. Dose: 1.8 mg/kg IV or PO for single dose to 100 mg
  2. Prevention of Surgery related Nausea
    1. Adult: 100 mg PO 2 hours before surgery
    2. Child: 1.2 mg/kg PO 2 hours before surgery
  3. Surgery related Nausea
    1. Adult: 12.5 mg IV for single dose
    2. Child: 0.35 mg/kg IV for single dose

VIII. Dosing: Granisetron (Kytril)

  1. Nausea with Chemotherapy (administer 30 minutes before)
    1. Intravenous: 10 ug/kg IV over 5 minutes
    2. Oral: 1 mg PO bid for 1 day
  2. Nausea with Radiation Therapy (adult)
    1. Dose: 2 mg PO 1 hour before each irradiation

IX. Preparations: Palonosetron (Aloxi)

  1. Indications: Preventing Chemotherapy indiuced Nausea
    1. Not effective in treating Nausea after it occurs
    2. Most effective in preventing delayed Emesis
      1. Longer half-life and higher 5-HT affinity
  2. Dosing: 25 mg IV 30 minutes before Chemotherapy
    1. Do not repeat dose more than once weekly

X. References

  1. Johnson (1993) Harriet Lane, Mosby, p. 521
  2. (2002) Tarascon Pocket Pharmacopoeia, p. 67
  3. (1998) Med Lett Drugs Ther 40(1026): 53-4 [PubMed]
  4. (1991) Med Lett Drugs Ther 33(847): 63-4 [PubMed]
  5. Bell and Lovecchio (2016) Crit Dec Emerg Med 30(8): 28

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Cost: Medications

ondansetron (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
ONDANSETRON 4 MG/5 ML SOLUTION Generic $0.45 per ml
ONDANSETRON 40 MG/20 ML VIAL Generic $0.12 per ml
ONDANSETRON HCL 4 MG TABLET Generic $0.13 each
ONDANSETRON HCL 4 MG/2 ML VIAL Generic $0.22 per ml
ONDANSETRON HCL 8 MG TABLET Generic $0.20 each
ONDANSETRON ODT 4 MG TABLET Generic $0.35 each
ONDANSETRON ODT 8 MG TABLET Generic $0.48 each
granisetron (on 10/19/2016 at Medicaid.Gov Survey of pharmacy drug pricing)
GRANISETRON HCL 1 MG TABLET Generic $1.56 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information.

Ontology: Ondansetron (C0061851)

Definition (NCI) A carbazole derivative with antiemetic activity. As a selective serotonin receptor antagonist, ondansetron competitively blocks the action of serotonin at 5HT3 receptors, resulting in suppression of chemotherapy- and radiotherapy-induced nausea and vomiting. (NCI04)
Definition (NCI_NCI-GLOSS) The active ingredient in a drug used to treat nausea and vomiting caused by cancer treatment. Ondansetron is a type of serotonin receptor antagonist and a type of antiemetic.
Definition (MSH) A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and has reported anxiolytic and neuroleptic properties.
Definition (CSP) competitive serotonin type 3 receptor antagonist used in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs; also has anxiolytic and neuroleptic properties.
Definition (PDQ) A carbazole derivative with antiemetic activity. As a selective serotonin receptor antagonist, ondansetron competitively blocks the action of serotonin at 5HT3 receptors, resulting in suppression of chemotherapy- and radiotherapy-induced nausea and vomiting. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=40693&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=40693&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1119" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D017294
SnomedCT 108418007, 372487007
LNC LP171625-9
English 4H-Carbazol-4-one, 1,2,3,9-tetrahydro-9-methyl-3-((2-methyl-1H-imidazol-1-yl)methyl)-, ondansetron, ondansetron (medication), ONDANSETRON, Ondansetron [Chemical/Ingredient], ONAD, Ondansetron, Ondansetron, (+,-)-Isomer, Ondansetron (product), Ondansetron (substance)
Swedish Ondansetron
Czech ondansetron
Finnish Ondansetroni
Russian ONDANSETRON, ОНДАНСЕТРОН
Japanese オンダンセトロン
Croatian ONDANSETRON
Spanish ondansetrona, ondansetrón (producto), ondansetrona (producto), ondansetrona (sustancia), ondansetrón (sustancia), ondansetrón, Ondansetrón
Polish Ondansetron
French Ondansétron
German Ondansetron
Italian Ondansetrone
Portuguese Ondansetron
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Granisetron (C0061863)

Definition (NCI_NCI-GLOSS) The active ingredient in a drug used to treat nausea and vomiting caused by cancer treatment. Granisetron is a type of serotonin receptor antagonist and a type of antiemetic.
Definition (NCI) An indazole derivative with antiemetic properties. As a selective serotonin receptor antagonist, granisetron competitively blocks the action of serotonin at 5-hydroxytryptamine3 (5-HT3) receptors, resulting in the suppression of chemotherapy- and radiotherapy-induced nausea and vomiting.
Definition (MSH) A serotonin receptor (5HT-3 selective) antagonist that has been used as an antiemetic for cancer chemotherapy patients.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D017829
SnomedCT 108424001, 372489005
English 1H-Indazole-3-carboxamide, 1-methyl-N-(9-methyl-9-azabicyclo(3.3.1)non-3-yl)-, endo-, granisetron, 1-Methyl-N-(9-methyl-endo-9-azabicyclo(3.3.1)non-3-yl)-1H-indazole-3-carboxamide, Granisetron [Chemical/Ingredient], Granisetron Transdermal System, 1-Methyl-N-(endo-9-Methyl-9-Azabicyclo(3.3.1)non-3-yl)-1H-Indazole-3-Carboxamide, GRANISETRON, Granisetron product, Granisetron (product), Granisetron (substance), GRAN, Granisetron
Swedish Granisetron
Czech granisetron
Finnish Granisetroni
Russian GRANISETRON, ГРАНИСЕТРОН
Japanese グラニセトロン
Spanish granisetrón (producto), granisetrona (producto), granisetrona, granisetrona (sustancia), granisetrón (sustancia), granisetrón, Granisetrón
Polish Granisetron
French Granisétron
German Granisetron
Italian Granisetrone
Portuguese Granisetron
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Kytril (C0107189)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D017829
English kytril, Kytril
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Zofran (C0206046)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D017294
English zofran, Zofran
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Dolasetron (C0209210)

Definition (NCI_NCI-GLOSS) The active ingredient in a drug used to treat nausea and vomiting caused by cancer treatment. Dolasetron is a type of serotonin receptor antagonist and a type of antiemetic.
Definition (NCI) An indole derivative and a potent serotonin 5-HT3 receptor antagonist with anti-emetic property. Dolasetron blocks the activity of serotonin released from the enterochromaffin cells of the small intestine by selectively inhibiting and inactivating 5-HT3 receptors located on the nerve terminals of the vagus nerve in the periphery and centrally in the chemoreceptor trigger zone of the area postrema. This results in suppression of signalling to trigger chemo- and radiotherapy induced nausea and vomiting.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C060344
SnomedCT 108421009, 372488002
English octahydro-3-oxo-2,6-methano-2H-quinolizin-8-yl 1H-indole-3-carboxylate, DOLASETRON, dolasetron, Dolasetron, Dolasetron (product), Dolasetron (substance)
Spanish dolasetrón (producto), dolasetrona, dolasetrona (producto), dolasetrona (sustancia), dolasetrón (sustancia), dolasetrón
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: palonosetron (C0220578)

Definition (NCI_NCI-GLOSS) The active ingredient in a drug used to treat nausea and vomiting caused by cancer treatment. Palonosetron is a type of serotonin receptor antagonist and a type of antiemetic.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C083418
SnomedCT 404851001, 404852008
English 2-QHBIQO, 2-(1-azabicyclo(2.2.2)oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz(de)isoquinolin-1-one, palonosetron [Chemical/Ingredient], palonosetron, PALONOSETRON, Palonosetron (product), Palonosetron (substance), Palonosetron
Spanish palonosetrón (sustancia), palonosetron (sustancia), palonosetron, palonosetrón (producto), palonosetrón
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Anzemet (C0718607)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C060344
English Anzemet, anzemet
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Aloxi (C1310735)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C083418
English Aloxi, aloxi
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Serotonin 5-HT3 Receptor Antagonists (C2936526)

Definition (MSH) Drugs that bind to but do not activate SEROTONIN 5-HT3 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT3 RECEPTOR AGONISTS.
Concepts Pharmacologic Substance (T121)
MSH D058831
English 5-HT3 Antagonist, Antagonist, 5-HT3, Antagonists, 5-HT3, Serotonin 5-HT3 Receptor Antagonists, Serotonin 5 HT3 Receptor Antagonists, 5-HT3 Antagonists, 5 HT3 Antagonists, 5 HT3 Antagonist
French Antagonistes des récepteurs 5-HT3 de la sérotonine, Antagonistes 5-HT3
German 5-HT3-Antagonisten, 5-HT3-Antagonist, Serotonin-5-HT3-Rezeptorantagonisten
Czech serotoninové 5-HT3 receptory - antagonisté, serotoninové receptory 5-HT3 - antagonisté, 5-HT3 antagonisté
Spanish Antagonistas del Receptor de Serotonina 5-HT3
Russian СЕРОТОНИНА 5-HT3 РЕЦЕПТОРОВ АНТАГОНИСТЫ, SEROTONINA 5-HT3 RETSEPTOROV ANTAGONISTY
Portuguese Antagonistas do Receptor 5-HT3 de Serotonina
Polish Antagoniści receptora serotoninowego 5-HT3
Italian Antagonisti dei recettori della serotonina 5-HT3
Derived from the NIH UMLS (Unified Medical Language System)

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