Pharmacy Drug Information

H o s p i t a l Ke n i n g a u M AY- J U N E 2 0 1 6
Chief Editor: Vivila Bubuyan Editor: Sivaraj Raman

PROTON PUMP INHIBITORS

¨ PPIs are prodrugs that are generally administered as enteric-coated tablets/capsules

¨ PPIs are converted to their active form by gastric acid and, once active, inhibit both basal and
stimulated gastric acid production

+
¨ PPI binds irreversibly to hydrogen/K ATPase
enzyme (proton pump) on gastric parietal
cells and blocks the secretion of hydrogen
ions, which combine with chloride ions in the
stomach lumen to form gastric acid

¨ Suppressing gastric acid secretion enables healing of oesophagitis associated with gastro-oesophageal
reflux disease (GERD) and peptic ulcers, as well as providing relief from symptoms associated with
these acid–peptic disorders

Duration of Acid Suppression Time to Steady State

¨ The duration of acid inhibition by a PPI is around
48 hours
¨ Acid secretion is restored by the synthesis of new
proton pumps and activation of resting proton
pumps
¨ PPIs only bind to active proton pumps and have
a short half–life (1–2 hours), so only around 70%
of pumps are inhibited with a single oral dose
¨ It takes 2 to 3 days to reach steady-state
inhibition of gastric acid
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INDICATIONS
¨ All PPIs at equivalent doses have similar efficacy and adverse effects for most patients but may differ in
their potential to cause medicine interactions

SIDE EFFECTS
¨ Although all PPIs have similar adverse effects, frequency of a given adverse effect and medicine
interactions may differ between PPIs

COMMON ADVERSE EVENTS (>1%) UNCOMMON ADVERSE EVENTS (0.1-1%)

The frequency of the most common adverse effects Uncommon or infrequent adverse effects that
with omeprazole and lansoprazole are comparable may be experienced by PPI users include:
to that of placebo and histamine receptor · rash/itch
antagonists · insomnia
· headache · fatigue
· abdominal pain · dizziness
· nausea
· vomiting UNCOMMON ADVERSE EVENTS (<0.1%)
· diarrhea · gynaecomastia · raised liver
· constipation · myalgia enzymes
· myopathy · hepatitis
· arthralgia · jaundice
· blurred vision · thrombocytopaenia
· taste disturbance · leucopenia
· interstitial nephritis · hypersensitivity
· peripheral oedema reactions

References:
http://www.nps.org.au/medicines/
https://www.uspharmacist.com/article/overuse-of-proton-pump-inhibitors-in-the-hospitalized-patient
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COMPARISON : EFFECTIVENESS
· Generally all PPIs have equal potency and effectiveness but some PPIs have advantages over one
another in certain diseases
· Esomeprazole is more superior than omeprazole in healing erosive oesophagitis
· If in short term effect, esomperazole is more effective in healing oesophagitis compared to
pantoprazole
· Generally for the long term effect, esomeprazole, pantoprazole, lansoprazole are equally effective in
treating mild to moderate esophagitis

COMPARISON with PANTOPRAZOLE

· Pantoprazole and omeprazole are safe and effective but pantoprazole is more effective than
omeprazole in healing acute and benign gastric ulcer
· Pantoprazole has less interaction with clopidogrel compared to omeprazole
· Pantoprazole also is more safe in pregnancy since it is in category B while omeprazole is in category C.

DOSE EQUIVALENCE

1
Change from the 2004 dose, specifically for severe oesophagitis, agreed by the GDG during the
update of CG17
2
Off-label dose for GERD

References:
https://www.nice.org.uk/guidance/cg184/chapter/appendix-a-dosage-information-on-proton-pump-inhibitors
Proton Pump Inhibitors: U.S. Food and Drug Administration-Approved Indications and Dosages for Use in Adults
http://consumerhealthchoices.org/wp-content/uploads/2012/01/BBD-PPIs-Full
 COMMON CLINICAL QUESTIONS

Do PPIs cause rebound hypersecretion?

· Rebound hypersecretion can occur in a number of patients taking PPIs for at least two months.
· Degree of rebound hypersecretion is directly related to gastrin levels and duration of PPI use.
· Symptoms of rebound hypersecretion may last three months or more, and can lead to inappropriate
continued use of PPIs.
· Consider tapering PPIs to successfully discontinue and limit hypersecretion.
· Recommend reducing the dose, if not at the minimum dose per day.
· Extend dosing interval to every other day and possibly every third day for a week or longer.
· Recommend antacids/ H2-blockers as needed for breakthrough symptoms after PPI discontinuation.

Is there an association between PPI use and cardiovascular events?

· In 2007, the FDA concluded that there was no relationship between PPIs and adverse cardiac events.
· In 2015, a data mining study found there MAY be an association of PPI exposure with risk for MI in the
general population.
· A proposed mechanism is that PPIs might lead to increased plasma levels of ADMA and
decreased levels of nitrous oxide.
· Elevated ADMA is associated with an increased risk of CV disease.
· Randomized clinical trials do NOT show an increased risk for MI with PPI use.
· A causal relationship between PPIs and cardiovascular events has not been firmly established.
· Recommend ensuring PPIs have a clear indication and using the lowest effective dose.

Is there evidence to support on-demand dosing with PPIs?

· On-demand dosing involves starting therapy when symptoms begin and stopping therapy when
symptoms resolve.
· PPIs are not approved for on-demand dosing, but patients still use them this way with good results.
· Patient satisfaction is sometimes improved with on-demand dosing compared to daily regimens.
· Consider on-demand dosing for non-erosive GERD and mild erosive oesophagitis.

How should self-medication with OTC PPIs be addressed?

· PPIs are heavily advertised and readily available OTC.
· Encourage the following non-pharmacologic/lifestyle management first-line for GERD symptoms:
· Elevating head of the bed six inches
· Avoiding meals two to three hours before bedtime
· Weight loss, if appropriate
· Smoking cessation
· Psychological stress reduction, if necessary
· Ensure adequate sleep (limited data exists)
· Recommend limiting duration of self-medication to 14 days per treatment, and no more than three
treatments per year.

Adapted from:
PL Detail-Document, Proton Pump Inhibitors: Appropriate Use and Safety Concerns. Pharmacist’s Letter/Prescriber’s Letter.
April 2016

For any comments or question, kindly contact Drug Information Service, Pharmacy Department (EXT:4214)