Proton pump inhibitors - subcutaneous administration

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Note: Administration via the subcutaneous route is off-label use.

• For use only when the oral or intravenous routes are not available or appropriate.
• May be recommended by a palliative care specialist for treatment of:
  • symptoms from cancer-related bowel obstruction
  • severe reflux symptoms, oesophagitis or gastritis
  • treatment of a gastrointestinal bleed, or
  • gastroprotection in high-risk patients.

Contraindicated in patients with known allergy to PPIs, substituted benzimidazoles or any excipient.

Refer to the British National Formulary (BNF) or Summary of Product Characteristics (SPC) for a full list of contraindications.

Liver impairment 

In severe liver impairment, dose reduction may be required. Refer to the specific medicine SPC.

Renal impairment 

Dose adjustment is not required in patients with impaired renal function.

Monitoring

Ongoing monitoring is required to determine if:

• a clinical benefit has been achieved
• signs of site reactions are present, and
• the subcutaneous route is still the most appropriate, and consider switching to the oral route, if possible.

Drug interactions 

PPIs increase gastric pH.

• Absorption will be reduced for the following medications:
  • some antiretroviral medications
  • tyrosine kinase inhibitors
  • some antifungals (including itraconazole capsules, posaconazole suspension and ketoconazole).

Absorption of digoxin can be increased with concomitant use.

Esomeprazole and omeprazole are inhibitors of the liver enzyme CYP2C19 and interactions with substrates can be clinically relevant:

• inhibition of citalopram and escitalopram metabolism increases the risk of QT prolongation, a reduced maximum daily dose may be required
• inhibition of the metabolism of diazepam, and
• inhibition of the metabolism of warfarin metabolism.

Tacrolimus and methotrexate levels can be affected when administered with a PPI.

Side effects

• Commonly caused side effects include headache, abdominal pain, constipation, diarrhoea, flatulence, nausea or vomiting and site reactions.
• Gastrointestinal infections, such as clostridium difficile, are more prevalent in patients treated with PPIs as a result of the increased gastric pH.
• Hypomagnesaemia, vitamin B12 deficiency and hyponatraemia (risk of syndrome of inappropriate antidiuretic hormone secretion with PPI use).

Esomeprazole

Short subcutaneous infusion (SSCI)

• Reconstitute and dilute the 20 mg or 40 mg dose in 50 mL of sodium chloride 0.9% and infuse subcutaneously over about 30 minutes.

Continuous subcutaneous infusion (CSCI)

• Reconstitute and dilute the 20 mg or 40 mg dose to a minimum of 17 mL with sodium chloride 0.9% and infuse over 24 hours via a syringe pump.

Omeprazole

Short subcutaneous infusion (SSCI)

• Reconstitute a 40 mg vial and dilute to 100 mL with sodium chloride 0.9%. Infuse subcutaneously over 3 to 4 hours as a single daily dose.

Pantoprazole

Continuous subcutaneous infusion (CSCI)

• There is one published case report of pantoprazole administered as a CSCI. In some centres in Scotland, pantoprazole is used when neither omeprazole nor esomeprazole are available.
• Reconstitute and dilute the 40 mg dose to a minimum of 17 mL with sodium chloride 0.9% and infuse over 24 hours via a syringe pump.

Discontinuing subcutaneous PPIs: 

Discontinue subcutaneous PPIs if:

• the treatment is ineffective
• the patient is experiencing side effects, or
• the oral or IV route for administration is recovered.

Rebound acid hypersecretion and dyspepsia can occur after stopping long-term PPIs. 

• Important: PPI injectable solutions are alkaline and are given alone via a separate syringe pump.
• The diluted solution of esomeprazole may have a yellow colour.
• All PPI infusions should be protected from light exposure.

Agar, M et al. The use of subcutaneous omeprazole in the treatment of dyspepsia in palliative care patients. Journal of Pain and Symptom Management. 2004; 28 (6); 529-530.

Desmidt,T and Constans,T. Subcutaneous infusion of esomeprazole in elderly patients in palliative care: A report of two cases. Journal of the American Geriatrics Society. 2009; Vol 57 (9): 1724-1725

Hindmarsh, J et al. Administering esomeprazole subcutaneously via a syringe driver in the palliative demographic: A case series. Journal of clinical pharmacy and therapeutics. 2022; Vol 47 (5): 694-698

Michelon H et al. Subcutaneous pantoprazole in an elderly palliative care patient. BMJ Supportive and Palliative Care. 2022; 12 (e2): e187-e188. 

Woodman, M et al. Esomeprazole for subcutaneous infusion: compatibility with other alkaline medications. BMJ Supportive and Palliative Care. 2023; 13 (e3): e751-e753