PPI management

Treatment options

Mechanism of action

PPIs inhibit gastric acid secretion by irreversibly inhibiting the proton pump (H+/K+ -ATPase), thereby blocking gastric acid secretion (5).

Common Indications in Palliative Care

  • Dyspeptic symptoms unresolved by other medications/distressing to patient without
    treatment
  • Prevention and treatment of gastro-intestinal (GI) bleeding
  • Malignant Bowel Obstruction

Dosing

There is currently insufficient published evidence to recommend one PPI over another.
Accordingly, this guidance suggests that any of the following PPIs would be a reasonable option.
Reduce doses in severe hepatic impairment.

40mg diluted in 50mls 0.9% sodium chloride, administered by subcutaneous infusion
over 20 minutes – 1 hour as a single daily dose (1, 9)

20mg diluted to a total volume of 33mls (or 40mg to 66mls) using 0.9% sodium chloride
and administered by CSCI/24 hours (1, 7)

40mg, diluted in 10mls 0.9% sodium chloride, administered as a SC bolus over 2
minutes as a single daily dose (1, 10)

40mg diluted in 100mls 0.9% sodium chloride, administered by SC infusion over 3-4
hours as a single daily dose (1, 11)

Diluent

0.9% sodium chloride recommended

Compatibility

PPI injections/infusions are alkaline after reconstitution and should therefore not be
mixed with other medications(1).

Esomeprazole may appear yellow after mixing (1).

Side effects noted in the literature

Local site irritation (6, 7, 8).

(1, 5)

  • Maximum daily dose should be reduced in severe hepatic impairment
  • Rebound acid hypersecretion and dyspepsia can occur after stopping long term PPIs
  • May increase risk of gastro-intestinal infections e.g. clostridium difficile
  • May reduce absorption of vitamin B12
  • May increase risk fractures when used at high doses for >1 year (less likely in our cohort)
  • Severe hypomagnesaemia if used long term
  • Increased risk of pneumonia
  • Hyponatraemia (risk Syndrome Inappropriate ADH with PPI use)

Esomeprazole and omeprazole are weak-moderate inhibitors of CYP2C19. Important interactions include:

  • Inhibition of the metabolism of citalopram and escitalopram, increasing the risk of QT interval prolongation (see SSRIs and QT prolongation); the maximum daily dose should be reduced (see SPC) (10)
  • A reduction in the antithrombotic effect of clopidogrel (a pro-drug activated by CYP2C19); avoid concurrent use with any PPI, use an H2 antagonist instead (11)
  • Inhibition of the metabolism of diazepam
  • Inhibition of the metabolism of warfarin; isolated reports of raised INR with all PPIs. (9)

Role of other agents

H2 Receptor Antagonists

Although SC Ranitidine is no longer in production, famotidine is widely available and, although unlicensed for SC administration, there are reports of safe use via this route though evidence is lacking. Famotidine injection is not available in the UK but can be imported as a special product – liaise with your pharmacy teams for further advice and costings.

Suggested administration guidance as per PCF8:
Famotidine 20mg can be given IV b.d. diluted to 5mL with sodium chloride 0.9% and given over 2min

  • Famotidine 20mg SC b.d. as a SC infusion or neat bolus (case series poster, n=35) (11) or
  • Famotidine 40mg/24h CSCI, using WFI or sodium chloride 0.9% as diluent. (10)

Reduce doses in renal impairment

Prescribing information

Refer to local formulary/guidance – may be specialist use only. Some items are classed as hospital only and therefore will affect community availability.

  • Omeprazole 40mg powder for solution for infusion vials (pack of 5)
  • Esomeprazole 40mg powder for solution for injection vials (pack of 5)
  • Pantoprazole 40mg powder for solution for injection vial (pack of 1 or 5)
  • Famotidine 20mg/2ml injection vial – (requires fridge storage) – not available in UK unless special order/import

Disclaimer

These Guidelines are intended for use by healthcare professionals and the expectation is that they will use clinical judgement, medical, and nursing knowledge in applying the general principles and recommendations contained within. They are not meant to replace the many available texts on the subject of palliative care.

Some of the management strategies describe the use of drugs outside their licensed indications. They are, however, established and accepted good practice. Please refer to the current BNF for further guidance.

Whilst SPAGG takes every care to compile accurate information , we cannot guarantee its correctness and completeness, and it is subject to change. We do not accept responsibility for any loss, damage or expense resulting from the use of this information.