Drug interactions- summary-

+ Fosaprepitant-

CYP3A4 inducers eg, carbamazepine, phenytoin, rifampin-
coadministration may decrease aprepitant plasma concentration and rduce efficacy

CYP3A4 inhibtors eg, clarithromycin, itraconazole, ketoconazole, nefazodone, nelifinavir,
ritonavir, trolendomycin-
concurrent use of CYP3A4 inhibitors may increase aprepitant oncentration,
Use with caution

Diltiazem + fosaprepitant /Fosaprepitant + Diltiazem-
coadmin resulted in increase concentraions of diltiazem and aprepitant

Paroxetine + Fosaprepitant / Fosaprepitant + Paroxetine-
concurent use decreased  AUC  and cmax of aprepitant and paroxetine

Fosaprepitant+

Astemazole, cisapride, pimozide, terfenadine -
risk of threatening arrhthmias may be increased . Fosaprepitant is  contraindicated
with astemizole, cisapride, pimozide or terfenadine

Benzidiozepine eg alprazolam, midazolam, triazolam-
plasma conc. of these drugs may be elevated increasing pharmacologic effects
and adverse reactions.

Chemotherapy agents eg  docetaxel, etoposide, ifosamide, imatinib, irinotecan,
pacitaxel, vinblastine, vincristine, vinorelbine-
aprepitant is a moderate inhibitor of CYP3A4 and can increase chemotherapy drugs
that are metabolized yhtough  CYP3A4 . Use with caution.

Contraceptives-
efficacy of hormonal contraceptives during and 28 days follwing the last dose may be
reduced. Use aletrenative methodsof contraception during treatment and for 1 month
following last dose of aprepitant

Corticosteroids eg dexamthasone, methylprednisolone -
reduce oral dexamethasone dose by about 50% when coadministered with fosaprepitant followed
by aprepitant ( 125mg and 80mg regimen)
reduce dose of methylprednisolone IV by about 25% and oral dose by about 50% when
coadministered with fosaprepitant/ aprepitant

CYP2C9  substrates eg tolubutamide, warfarin-
aprepitant CYP2C9  inducer induces metabolism of tolubutamide resulting in
lower plasma conc. In patients on warfarin therapy monitor the international
normalized closely ratio closely in the 2 week period.
 

Prevention of nausea and vomiting associated with chemotherapy

Adverse reactions-

CNS -   Asthenia/fatigue  16%,    dizziness 6%   headache  7%   insomnia 2%

GI -      Abdominal pain  4%   anorexia 9%   constipation 9%   diarrhea  9%
            epigastric discomfort   4%     gastitis  4%    heartburn 5%    vomiting 7% 

Miscellaneous -  Dehydration  5%   fever 2%   hiccups  9%    
                            mucous membrane disorder  2%  neutropenia  3% tinnitus 3%

Lab test abnormalites-  ALT increased  5%    AST increased 3%  BUN increased 4%
                                serum creatinase increased  3%    proteinuria  6%      

Hypersensitivitiy  to the drug or other components

Special precations-
Chronic use-  chronic continuous use of fosaprepitant for prevention of nausea or
vomiting is not recommended

Hepatic function impairment -  excercise caution when fosaprepitant or aprepitant is
administerd to these patients 

Pregnancy - use the drug during pregnancy only if needed

Lactation- decide whether to discontinue breast feeding or the drug  taking into consideration
the importance of the drug to the mother.

Children- safety and efficacy in children have not been established

Elderly- dosage adjustments is not necessary. Observe caution.

i. Prevention of acute and delayed nausea and vomiting associated 

Indication

Prevention of nausea and vomiting associated with chemotherapy

Dosage-
3-day chemotheapy induced nause and vomiting-

Day 1 - aprepitant 80mg orally 
on day 2 and 3  in addition to a corticosteroid  and 5-hydroxytriptamine  type 3 ( 5-HT3 )
antagonist as per table -

Fosaprepitant 115mg may be substituted for aprepitant 125mg prior to chemotherapy on day 1
only of  the chemotherapy induced nausea and vomiting regimen as a regimen as an infusion
administered over 15 minutes

                               Day 1                  Day   2           Day  3
Aprepitant          125mg orally     80mg orally    80mg orally      

Dxamethasone  12mg orally        none                 none

Ondensetron        2* 8mg orally   none                 none                                     

1. Advice patients to report the use of other prescrition or non prescription medication
   or herbal products

2. Instruct patients on warfarin therapy to have their clotting status closely monitored  in
    the 2 week period period  paticularly at 7 to 10 days following initiation of 3 day regimen
    of foasprepitant followed by aprepitant with each chemotherapy cycle.

3. Administration of fosaprepitant  may result efficacy of hormonal contraceptives.
   Advice patients to use alternative methods of contraception during treatment with
   fosaprepitant and for 1 month following the last dose of 3 day aprepitant regimen

Pregnancy -
Use the drug during pregnancy only if needed

Lactation-
Decide whether to discontinue breast feeding or the drug  taking into consideration
the importance of the drug to the mother.

Children-
Safety and efficacy in children have not been established

Elderly-
Dosage adjustments is not necessary. Observe caution.