Drug interactions- summary

+ Aprepitant-

CYP3A4 inhibitors ( clarithromycin, diltiazem, itraconazole,ketoconazole, nefazodone,
nelfinavir, ritonavir, troleandomycin )-
concurrent use of CYP3A4 inhibitors increase plasma concentration. Use with caution

CYP3A4 inducers ( carbamazepine, phenytoin, rifampicin )-
coadmin may decrease aprepitant plasma concentration and reduce efficacy

Paroxetine + Aprepitant/ Aprepitant + Paroxetine-
concurrent use decreased AUC and Cmax conc of both aprepitant and paroxetine

Aprepitant + oral contraceptives  -
efficacy of oral contrceptives reducecd for 28 days after administration of last dose of
aprepitant . Alterenative or back up method of contraceptives are recommeneded

Aprepitant + CYP2C9 substrates ( tolubutamide, warfarin )-
Aprepitant is a CYp2C9 inducer and shown to induce metabolism of warfarin and tolbutamide
resulting in lower plasma levels in patients on warfarin. closely monitor international
normalized ratio in the 2 week period, particularly 7 to 10 days folowing initiation of
therapy

Aprepitant  + CYP3A4 substrates-  ( pimozide, cisapride, astemizole, terfenadizole,
dexamethasone, methyl predinsolone, midazolam, triazolam, docetaxel, pacitaxel,
etoposide, irinotecan, ifosofamide, imatinib, vinorelbine, vincristine)-
Aprepitant is a moderate inhibitor of CYP3AA4 and can increase plasma concentration
of coadministered  products that are metabolized through CYP3A4 .
Aprepitant is contraindicated  with astemizole, terfenadine, pimozide or cisapride.
Reduce  doses of dexamthasone and methylpredinsolone dose when given with
aprepitant

Adverse reactions-

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

GI -        abdominal pain   4%    anorexia   10%   constipation    10%    diarrhea   10%
             epigastric discomfort  3%     gastritis   4%         heartburn  4%   nausea  10%
             vomiting   6%

Haematologic/ lymphatic  -      neutropenia  3%

Respiratory -          hiccups    9%

Special senses -     tinnitus    3%

Miscellaneous -      dehydration   5%   fever    2%     mucous membrane disorder  2%

Hypersensitivity to the drug or components

Special precaution -
Chronic therapy - chronic continuous  use of aprepitant for preventioon of nausea and vomiting
is not recommened.

Hepatic function impairment- excecise caution when aprepitant is administered to patients
with severe hepatic function impairment

Pregnancy-
Use the drug during pregnancy only if clearly needed

Lactation- decide whether to discontinue breast feeding or the drug depending
upon the importance of the drug to the mother,

Children- safety and efficacy in children not established

Combination therapy for prevention of nausea and vomiting associated with chemotherapy

Dosage-
To be used in combination with a 5HT antagonst and corticosteroid.
!25mg 1 prior to chemoptherapy on Day 1 , then 80mg in the morining on Day 2 and Day3

Not recommeneded in patients below 18 years

1. Instruct patients to take aprepitant only as prescribed

2. Advice patients to their first dose  (125mg )  1 hour prior to chemioptherapy treatment
  for prevention of nauseand vomiting

3. Advice patients to take their medication 40mg capsule within 3 hours prior to
induction of anesthesia

4. Advice patients to report to their doctor about use of other non-prescription and
    prsecribtion drugs

5. Instruct patients on chronic warfarin therapy to heve their clotting status carefully monitored
   in the 2 week period particularly at 7 to 10 days following initiation of the 3 day regimen of
   of aprepitant with each chemotherapy cycle.

6. Advice patients aprepitant may reduce the efficacy of hormonal contrceptives.
    Advice patients to use alternative or back up methods of contraception.

Take with or without food

Pregnancy-
Use the drug during pregnancy only if clearly needed

Lactation-
Decide whether to discontinue breast feeding or the drug depending
upon the importance of the drug to the mother,

Children-
Safety and efficacy in children not established