Dr. A. ALISHER MD PhD AL SABAH & ZAIH HOSPITALS, MOH, KUWAIT

Ondansetron

Ondansetron

Chemical dataFormula C18H19N3O

Mol. mass

293.4 g/mol

Ondansetron

OndansetronPharmacokinetic dataBioavailability ~60%

Protein bindingMetabolism Half-life Excretion

70%-76%Hepatic (CYP3A4, CYP1A2,CYP2D6) 5.7 hours Renal

Ondansetron

OndansetronTo treat nausea and vomiting following

chemotherapy; PONV Its effects are thought to be on both peripheral and central nerves.

OndansetronReduce the activity of the Vagus

Nerve; Which is a nerve that activates the vomiting center in the medulla oblongata; A blockage of serotonin receptors in the chemoreceptor trigger zone.

Ondansetron

OndansetronIt does not have much effect on

vomiting due to motion sickness.

OndansetronOndansetron as developed in 1984 by scientists of the Glaxo's Laboratories

in London, UK. It is marketed by GlaxoSmithKline (GSK) under the trade name Zofran;

ONDANSETRON 9-methyl-3-((2-methyl-1H-imidazol-1-

yl)methyl)-2,3-dihydro-1H-carbazol-4(9H)one

Use in adult and pediatric

Zofran (Ondansetron Hydrochloride)

pts. Dose:0.1 mg/kg for children 2-12 yrs. If BW < 40 kg

NAUSEA / VOMITINGFor patients experiencing Nausea and/or Vomiting As a result of disease Medications or Acute Motion Sickness

NAUSEA / VOMITINGOndansetron: 4 mg IV/ IM

(Slow IV - 2-5 min.) (Repeat x 1 if no relief after 5 min.)

Post anesthetic ShiveringThe efficacy of Ondansetron for Postanesthetic Shivering, a common

occurrence after surgery.

Post anesthetic ShiveringOndansetron was found to be as effective as Pethidine

(Meperidine, Demerol) when given as a single IV dose before anesthesia.

Ondansetron blocks the 5HT3 receptor in the enteric

Irritable Bowel Syndrome

nervous system, and thereby reduces colonic contractions, sensory perception, and motility.

Irritable Bowel Syndrome5-HT3 antagonist, have

been shown to have this effect, which positively impacts IBS with diarrhea (IBS-D)

Irritable Bowel SyndromeOndansetron has been

effective in treating diarrhea-predominant IBS

Adult EmetogenicChemotherapy & Radiotherapy

8 mg PO, 1-2 hrs prior to

treatment Followed by 8 mg PO 12 hrs later.

Adult EmetogenicChemotherapy & Radiotherapy

8 mg IV before treatment

To protect against delayed or prolonged emesis after

the 1st 24 hr, continued PO PO: 8 mg BD for up to 5 days.

Highly Emetogenic Chemotherapy8-mg IV/IM before chemotherapy.Doses > 8 mg & up to 32 mg by IV

infusion. Alternatively, 8 mg by slow IV/IM before chemotherapy,

Highly Emetogenic ChemotherapyFollowed by 2 further IV/IM doses of 8 mg 2-4 hr apart or By infusion of 1 mg/hr for up to 24 hrs.8 mg BD PO for up to 5 days after

a course of treatment.

PONV Adult PatientsPrevention: 16 mg orally 1 hr.

prior to GA orSingle dose of 4 mg IM or slow IV

at induction of GA.

PONV Adult PatientsTreatment: Single dose of 4 mg IM

or slow IV.Patient with Hepatic Impairment Max: 8 mg daily.

Children:Prevention: 0.1 mg/kg4 mg IV before, at or after induction of

GA Treatment:0.1 mg/kg Up to a max: 4 mg IV

Observed During Clinical PracticeCardiovascular: Rarely and

predominantly with IV Ondansetron; Transient ECG changes including QT interval prolongation.

Observed During Clinical PracticeFlushing Rare cases of hypersensitivity

reactions

Observed During Clinical PracticeSevere Anaphylaxis Anaphylactoid reactions Angioedema

Observed During Clinical PracticeBronchospasm,

Shortness of breath,Hypotension,

Laryngeal edema,Stridor

Observed During Clinical PracticeLaryngospasm

ShockCardiopulmonary Arrest have

occurred during allergic reactions in pts receiving IV Ondansetron.

Observed During Clinical PracticeHepatobiliary: Liver enzyme

abnormalitiesLower Respiratory: Hiccups

Observed During Clinical PracticeNeurology: Oculogyric crisis, appearing alone, as well as with

other dystonic reactionsSkin: Urticaria

Special Senses: Eye Disorders:

Cases of transient blindness,

predominantly during IV administration; These cases of transient blindness were to resolve within a few minutes up to 48 hrs.

Mode of Action Serotonin (5-HT) receptor antagonist Blocking action take place in CNS at area

postema (chemoreceptor trigger zone) and

In peripheral nervous system on terminals of

Vagus Nerve

Indications Nausea and

Vomiting

Contraindications:

Hypersensitive to drug MH PE

ACS

Dosage 4 mg slow IV (over 2-5 min.) or 4 mg IM

Precautions In Pregnant Women

Breast-feeding Women Cross into breast milk Cause syncope if pushed IV to fast

PharmacokineticsAbsorption: Variable;

Bioavailability: 50- 60%;Distribution: 70 - 76% is

protein bound

PharmacokineticsMetabolism: Extensively metabolized.

Excretion:Primarily excreted in urineSome small amounts

excreted in feces Breast milk

PharmacokineticsHalf-life : 4 hrs.

On 27.07.2011: 120 Patients have Side Effects when taking Zofran

Top 10 overall Zofran side effects:

1

Nausea

15

2

Nausea and Vomiting

11

3

Pyrexia (Fever)

11

4

Hypotension

10

5

Confusion

9

6

Neutropenia (Agranulocytosis)

9

7

Dyspnoea (Breathing difficulty)

7

8

Dysphagia (Swallowing difficulty)

6

9

Cough

6

10

Dermatitis Nos

6

Top 10 long term Zofran Side Effects:

Name 1 2 Nausea Hypersomnia (Drowsiness) Anxiety Aggravated (Stress and anxiety) Headache Somnolence (Drowsiness) Acne Promethazine Hydrochloride Plain Confusion

Number of reports 3 2

34 5

22 2

67 8

11 1

910

Swelling Of Feet And LegsCancer Pain

11

Side Effects Drowsiness

Dizziness Fatigue

Side Effects Headache

Impaired Wound Healing Itch

Side Effects Bradicardia Fever Anxiety

Agitation