Proton Pump Inhibitors

Introduction

Proton pump inhibitors (PPI) is commonly prescribed in government hospital setting to treat GERD and peptic ulcers, especially after ranitidine product recall.

In an overview, all PPIs are similar in terms of efficacy and adverse effects but might be different in terms of potential to cause drug interactions (e.g. PPIs with clopidogrel).

NOTE: There has been concern on the concomitant administration of a histamine receptor antagonist and proton pump inhibitor.

  • First, this management could be deemed as a polypharmacy and second, it has been hypothesized that histamine 2 receptor antagonists might interfere with the action of proton pump inhibitors when the drugs are given concomitantly.
  • However, a 2015 study found that when a proton pump inhibitor and histamine 2 receptor antagonist were administered concomitantly 30 minutes before breakfast, the histamine 2 receptor antagonist did not decrease the acid suppressive ability of the PPI, rather it improved gastric acid control. However, this area of interest still needs more prospective study to testify.



Method of Administration

Since meal is the main stimulus of proton pump activity, oral PPI should be taken about 30 minutes before a meal.

NOTE: Dexilant (dexlansoprazole) delayed release capsule can be taken without regards to meals due to its dual delayed-release formulation.



Precautions

If a patient develops symptoms such as black stools or vomit that looks like coffee ground, they should seek immediate medical attention. What we worried is if there is any internal bleeding in gastric despite the use of PPI.



Stepping-Down Approach

The ongoing use of PPI should be assessed regularly. Some epidemiological studies suggest possible associations between PPI use and increased risk of Clostridium difficile infection, pneumonia, fracture, iron deficiency and chronic kidney disease.

The 3 key considerations in stepping-down approach of PPIs are:

  • Stopping treatment (unless patient has severe esophagitis or complicated disease)
  • Intermittent use when symptoms develop
  • Step down to low-dose therapy



Esomeprazole Controversy

Though many practitioners think that giving esomeprazole (S-enantiomer) is more effective than omeprazole (its racemate), however, in terms of evidence base, the therapeutic benefit of chiral switch of omeprazole is questionable considering the substantially greater economic burden involved.

Just two years before the omeprazole expired, AstraZenca patented S-omeprazole in pure form, pointing out that since some people metabolize R-omeprazole slowly, pure S-omeprazole treatment would give higher dose efficiency and less variation between individuals.

However, in studies, AstraZeneca scientists compared 20 and 40 mg Nexium with 20 mg Omeprazole.

When you searched across the internet, there is even a 2002 GERD study which concludes as such: esomeprazole 40 mg provides more effective acid control than twice the standard dose of omeprazole.

  • However, when you read the abstract, they are effectively comparing esomeprazole 40 mg with omeprazole 40 mg.

Are all these valid comparisons? Should not they feel the need to prove that esomeprazole 10 mg is at least as effective as omeprazole 20 mg?

A systematic review published in 2015 comparing equivalent doses of omeprazole and esomeprazole concluded that:

  • Overall, S-omeprazole appeared to be as effective as omeprazole when used at equivalent doses in treating ulcers as part of triple therapy, and in controlling 24 h intragastric pH. For both omeprazole and S-omeprazole, the differences between 20 and 40 mg doses, if any, are marginal.



PPI Extemporaneous Formulation

Last month, an ex-colleague whatsapped me, does your facility prepare pantoprazole 2 mg/ml suspension?

Technically, you may find the formulation in Extemporaneous Formulation, 2015 and some hospital do prepare it. However, at the hospital that I am practicing now, we only prepare omeprazole 2 mg/ml suspension (although pantoprazole is the cheapest proton pump inhibitor).

Here are our reasonings:

  • Normally, we prepare proton pump inhibitor in liquid form mainly for neonate or paediatric population. You may find recommended dosing of omeprazole for infants and children in British National Formulary for Children, but not the same goes to pantoprazole. Hence, we still have to keep omeprazole suspension in hospital formulary, even if facility decided to start preparing pantoprazole suspension.
  • Moreover, a 2003 study shows that the peak plasma concentration of pantoprazole suspended in sodium bicarbonate solution is the same as the tablet administered orally, but bioavailability is reduced to 75% of oral bioequivalent.

Although Nexium MUPS (esomeprazole) tablet is readily dispersible in non-carbonated water, but it is not necessarily for the generic brands available on the market (please refer to product leaflets).



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