5-HT3 Receptor Antagonists - Antiemetic/Antivertigo Agents
Drug Name:5-HT3 Receptor Antagonists - Antiemetic/Antivertigo Agents
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Patient Information
Pharmacology/ Pharmacokinetics
Interaction with Food
Pregnancy and lactation
Drug Interaction:
5-HT3 Receptor Antagonists include-
Alosetron, Dolasetron, Ondansetron, Palonosetron, Granisetron, Hydrolastron
Drug interactions -summary-
Atenolol + Dolasetron -
clerance of hydrodolasetron decreased when dolasetron was administered IV
concomittantly with atenolol
Carbamazepine + Ondensetron -
in patients treated with carbamazepine , clearance of ondensetron was increased and
ondensetron blood levels decreased
Cimetidine + Dolasteron -
blood levels of hydrodolalsetron increased when dolasetron was coadministred with
cimetidine
CYP1A2 inhibitors (eg cimetidine, fluvoxamine, quinolone antibiotics) + Alosetron-
fluvoxamine increased mean alosetron AUC and prolonged half life.
Coadministration is contraindicated
CYP3A4 inhibitors (eg clarithromycin, ketoconazole, protease inhibitors + Alosetron -
ketoconazole increased alosetron AUC. Use caution when adminstering together.
Use with caution when adminstering with CYP3A4 inhibitors
Phenobarbital + Granistetron-
hepatic enzyme iduction with phenobarbital resulted in an increase in total plasma
clearance of IV granisteron
Phenytoin + Ondensetron-
in patients treated with phenytoin, clearance of ondensetron was increased and
ondensetron blood levels decreased
Rifamycins + Dolasteron/ondensetron-
plasma concentration of dolasetron and dolasetron reduced
Ziprasidone + Dolasetron or - Dolasetron + Ziprsidone -
risk of life threatening arrhythmias including torsasedes de points increased.
Ziprasidone is contraindicated in patients taking dolasetron
Ondesetron + Cisplatin-
plasma cisplatin concentration may be decreased reducing therapeutic eftect.
May be necesary to increase cisplatin dose.
Ondansetron + Cyclophosphamide-
plasma cyclophosphamide decreased reducing therapeutic effect.
May be necessary to increase cycloposphamide dose.
Drug/food interactions-
Alosetron- alosetron absorption decreased by 25% when administred with food,
resulting in mean delay to peak concentration
Granisetron - when granisetron tablets were administrerd with AUC was decreased
and Cmax increased
Ondasetron - bioavailbility is enhanced by food
Indication:
5-HT3 Receptor Antagonists include-
Alosetron, Dolasetron, Ondansetron, Palonosetron, Granisetron, Hydrolastron
Adverse Reaction:
DOLASETRON- ( Oral and Injections)
Cardiovascular - Hypotension ( infrequent) atrial fibrillation/flutter,
bundle braepitaxich block ( left and right ) chest pain, edema,
extrasystole, nodal arrhythmias, orthostatic myocardial infarction,
palpitations, peripheral edema, peripheral ischemia,
Bradycardia, severe hypotension and syncope have been reported
immediately or closely following IV administration.
CNS- agitation, depersonalization, flushing, parathesia, sleep disorder,
tremor, vertigo ( infrequent ) abnormal dreaming, anxiety, ataxia,
confusion ,twitching ( rare )
Dermatologic - increase sweating, rash, ( infrequent )
GI- abnormal pain, anoexia, constipation, dyspepsia ( infrequent )
pancreatitis ( rare )
GU- acute renal failure, dysuria, ployuria ( rare )
Hematologic - anemia, epitaxis, hematuria, partial thromboplastin time prolonged,
purpra/hematoma, thrombocytopenia ( rare )
Hepatic - transcient increase in ALT and or AST values ( < 1% ),
hyperbilirubinemia, increased gamma-glutamyltransferace ( rare )
Metabolic - alkaline phosphatase inceased ( rare )
Musculoskeletal - arthalgia, myalgia ( rare )
Ophthalmic - abnormal vision ( infrequent ) photophobia ( rare )
Respiratory - bronchospasm, dyspnea ( rare )
Special senses - taste pervertion ( infrequent ) tinnitus ( rare )
Miscellaneous- anaphylactic reaction, facial edema, local pain or burning on
IV administration , urticaria ( rare )
Adverse reactions-
ALOSETRON-
GI - abdominal discomfort 6% constipation 27% GI discomfort 4%
nausea 5%
Cardiovasscular - tacarrhythmias ( 0.1 to 1% ) arrhythmias, extrasystoles , increased blood
pressure < 0.1%
CNS- anxiety (0.1 to 1%), confusion, depressive moods, dreams,
memory effects, tremors ( < 0.1% )
Dermatologic - sweating, urticaria ( 0.1 to 1% ) acne, allergic skin reactions,
alopecia, dermatitis, folliculitis hair loss, nail disorders,
skin infections < 0.1% )
GU - urinary frequency ( 0.1 to 1% ), bladder inflammation, diuresis,
female reproductive tract bleeding andhaemoerhage, fungal
reproductive infections, polyuria, sexual function disorders,
urinary tract haemorrhage ( < 0.1% )
Haemtologic/lymphatic - haemorrhage, lymphatic signs an symptoms ,
quantitative red cell haemoglobulin defects ( < 0.1% )
Lab test abnormalites- abnormal bilirubin levels , cholesystisis ( 0.1 to 1% )
Metabolic - disorders of calcium and phosphate metabolism fluid disturbances,
hyperglycemia, hypoglycemia, hypothalamus/ pitutiary hypofunction
( < 0.1% )
Musculokeletal - bone and skeltal pain, muscle pain, stiffness and rigidity ( < 0.1% )
Ophthalmic - light sensitivity < 0.1%
Respiratory - breathing disorders 0.1 to 1% ear , nose and throat infections ,
laryngitis, viral respiratory infections < 0.1%
Miscellaneous- cramps, fatigue, malaise, pain, temperature regulation
disturbances, 0.1 to 1% burning sensation, cold sensation,
fungal infection, hematoma, cold sensations, < 0.1%
Contra-Indications:
5-HT3 Receptor Antagonists include-
Alsetron, Dolasetron, Ondansetron, Palonosetron, Granisetron, Hydrolastron
Refer 5-HT3 Receptor Antagonists
Contraindication-
Aloserton - do not initiate in patients with constipation who are unable to understand or
unable to comply with physicians instructions
Coadministration with fluvoxamine
Dolasetron , granisetron , odansetron, polonosetron -
Hypersensitivity of the drug or its components
Special Precautions-
Constipation- serious complications , including obstruction, impaction, toxic mergacolon,
and secondary bowel ischemia have been reported with Alosetron.
Ischemic colitis- ischemic colitis has been reported in alosetron patients .
Discontinue immediately in patients with signs of ischemic colitis, such as rectal bleeding,
bloody diarrhea, or worsening of abdominal pain
Cardiac effects -Dolasetron can cause electrocardiogram ECG interval changes
Rarely and predominently with Ondensetron IV , transcient ECG changes including
QT interval prlongation have been reported
Administer Dolasetron and Polonsetron with caution in patients who develop cardiac interval
prolongation.
Peristalis- Ondansetron and Granisetron do not stimulate gastric or intestinal peristalsis.
They should not be used instead of nasogastric suction
Phenylketonuric patients - inform patients that Ondansetron orally disintegrating tablets
contain phenylamine ( a component of aspartame )
Benzyl alcohol - granisetron injection contains benzyl alcohol a preservative.
Benzyl alcohol has been associated with fatal gasping syndrome in premature infants.
Use Granisetron in pregnancy only if required
Hepatic function impairment- Do not use Alosetron in patients with severe heptic function
impairment. Use Alosetron with caution in patients with mild to moderate hepatic impairment
Pregnancy- use i5-HT 3 receptor antagonist in pregnancy only if the potential benefits
justifies the potential risk to the fetus.
Lactation- Alosetron and Ondensetron are excreted in breast milk. Excercise caution when
5-HT3 receptor antagonist is administered to a breast feeding woman.
Children- safety and efficacy of alosetron,palonosetron and oral Granisteron in children
have not been established
Elderly- Dose selection in elderly patients should be cautious starting with low end of
dosing range reflecting the greater freqency of decreased hepatic , renal, or cardiac function
and concomitant disease or other drug therapy
Patient Information:
Alosetron-
1. Counsel patients fully and on and ensure that understtand the risks and benefits of Alostetron
therapy. Patients should be fullyeducated ablout the use of the drug.
2. Patients should not start taking Alosetron it they are constipated
3. Patients should Immediately discontinue Alosetron and contact their doctor if they are constipated
or notice symptoms of ischemic colitis, such as worsening of abdominal pain, bloody diarrhea,
or blood in their stools.
4. Resume Alosetron only if their constipation has resolved and after consulting their doctor
3. Stop taking Alosteron and contact their doctor if Alosetron does not adequately control
IBS ( irritable bowel syndrome ) after 4 weeeks of taking 1mg twice a day
Ondansetron-
Phenylketonuric patients-
1. Inform patients not to remove Ondensetron orally disintegrating tablets from the blister until
prior to dosing and not to push the tablet through the foil.
2. Instruct patients to completely peel the off the blister with dry hands
3. Instruct patients to gently remove the tablet and immediately place it on the tongue to
dissolve and be swallowed with the saliva
Pharmacology/ Pharmacokinetics:
Pharmacology-
Selective 5-hydroxytryptamine3 ( 5-HT3) receptor antgonists are antinausent and aniti-emetic and
anti-IBS ( alsetron only ) agents with little or no affinity for other serotonin receptors , alpha or
beta adrenoreceptors or for dopamine D2 , histamine H1 , benzidiazepine, picrotoxin, or
opioid receptors.
Serotonin receptors of the 5-HT3 are located peripherally on vaginal nerve terminals ,enteric
neurons in GI tract and centrally in the chemoreceptor trigger zone.
During chemotherapy, mucosal enterochromaffin cells from the small intestine release serotonin
which stimulates the 5-HT3 receptors. This evokes vagal afferent discharge , inducing vomiting
Interaction with Food:
Alosetron- alosetron absorption decreased by 25% when administred with food,
resulting in mean delay to peak concentration
Granisetron - when granisetron tablets were administrered the AUC was decreased
and Cmax increased
Ondasetron - bioavailbility is enhanced by food
Pregnancy and lactation:
Pregnancy-
Use 5-HT 3 receptor antagonist in pregnancy only if the potential benefits
justifies the potential risk to the fetus.
Lactation-
Alosetron and Ondensetron are excreted in breast milk. Excercise caution when
5-HT3 receptor antagonist is administered to a breast feeding woman.
Children-
Safety and efficacy of alosetron, palonosetron and oral Granisteron in children
have not been established
Elderly-
Dose selection in elderly patients should be cautious starting with low end of
dosing range reflecting the greater freqency of decreased hepatic , renal, or cardiac function
and concomitant disease or other drug therapy