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It is not known whether rabeprazole sodium is excreted in human breast Inilk and there are no
studies in lactating women.、Since many drugs are excreted in milk and because of the potential
for adverse reactions to nursing infants from rabeprazole sodium, a decision should be made to
discontinue nursing or discontinue the drug, taking into account the importance of the drudg to
the mother.

INTERACTIONS WITH OTHER MEDICINES

Effect of rabeprazole sodium on other drugs - demonstrated interactions

盛 Vo studies with human jliver microsomes indicated tnat rabeprazole sodium is metabolised
by isoenzymes 0f CYP450 (CYP2C19 and CYP3A4).

C/opdogre/: Clopidogrel is metabolised to 失 active metabolite by CYP2C19. InhibiHon of
CYP2C19 by rabeprazole would be expected to result in reduced drug levels of fhe active
metabolite of clopidogrel and a reduction in its antipiatelet activity and thnerefore itS clinical
efficacy. Concomitant use of rabeprazole with clopidogrel shouid be discouraged.

Cyejospo77: 7 Vo incubations employing human liver microsomes indicated that rabeprazole
inhibited cyclosporin metabolism with an ICs。 of 62 micromolar, a concentration that IS over 50
times higher than the Ca。 in healthy volunteers following 14 days dosing with 20 mg
・rabeprazole. Although の Myo studies may not always be predictive of an 訪 vo status these
findings indicate that no interaction iS expected between rabeprazole and Cyclosporim.

eo7exafe: case reports,、pubiished population pharmacokinetic studies, and retrospective
analyses suggest tnat concomitant administration of PPls and methotrexate (primarily at high
dose: see methotrexate prescribing Information) may elevate and prolong serum levels of
methotrexate and/or its metabojite hydroxymethotrexate. However, no formai drug interaction
studies of methotrexate witnh PPIS have been conducted.

りjgoxp: A 2296 jncrease in trough digoxin evels was observed in normal subjects given both
drugs concomitantly.

Ke7ocongzo/e: A 33% decrease in ketoconazole levejls was observed In normal subjects given
both drugs concomiitantly.

Aaza7avが Co-administration of atazanavir with other proton pumD hipitors resulted in 8
substantial reduction in atazanavir exposure. The absorption of atazanavir is pH dependert.
Therefore, PARIET 10 should not be co-adrministered with atazanavir.

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Patients may need to De monitored when these drugs are taken together with PARIET 10.
Effect of rabeprazole sodium oni other drugs - theoretical interactions

Rabeprazole sodium produces sustained inhibition of gastric acid secretion. An interaction with
compounds whose absorption depends on gastrc pH may occur due to the magnitude of acid
suppression see with rabeprazole sodium.

Effect of rabeprazole sodium on other drugS ・ poiential interactions that have peen
eXCluded

Studies in healtny subjects have shown that rabeprazole sodium does not have ciinicaly
significant interactions with other drugs metabolised by the CYP450 system. 「hese studies
included the drugs warfarin and theophylline (as single oral doses), phenytoin (as a single
ntravenous dose with supplemental oral dosing), diazepam (as a single intravenous dOse) and
amoxycillin (as single and mujHple oral doses).

Taking PARIET 10 with antacids produces no ciinicaliy relevant changes in plasma rabeprazole
sodium concentrations.

6 PARIET10(150409)PPI

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