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
  

5-HT3 Receptor Antagonists include-
Alosetron, Dolasetron, Ondansetron, Palonosetron, Granisetron, Hydrolastron

Irritable bowel syndrome

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% )

Hematologic/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%

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 -
Hypeesensitivity 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 imediately 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

Special risk patients - debilated patients or patients taking additional medications that
decrease GI motility may be at greater risk for serious complications from constipation.
Therefore, excercise appropriate caution and follow-up if Alosetron is prescribed to
these patients

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 exreted 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

the fetus 

Indication-
Irritable bowel syndrome

Dosage-
Maximum dose 1mg twice daily

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

Special risk patients - debilated patients or patients taking additional medications that
decrease GI motility may be at greater risk for serious complications from constipation.
Therefore, excercise appropriate caution and follow-up if Alosetron is prescribed to
these patients

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. Immediately discontinue Alosetron and contact their doctor if they are constipated
   or 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 disintrgrating 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

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
  

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 exreted 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