What does NICE say about the use of PPIs for Dyspepsia?  In particular dose, side effects and risks?

All the information here is based on extracts from documents published by NICE and the most important points are in red type.

NICE recommends 3 different dose levels:

• Full or standard
• Low dose (on-demand dose)
• Double dose

NICE does not recommend any particular PPI drug over another

Doses should be taken 30 minutes before breakfast and (if needed) 30 minutes before the evening meal, to provide optimal control of gastric pH.

Contraindications and cautions

• Proton pump inhibitors (PPIs) should not be prescribed to people:
• With alarm symptoms before endoscopy. If the person is already taking a PPI and subsequently needs an endoscopy, the PPI should be stopped at least 2 weeks before the procedure.
• PPIs should be prescribed with caution to people:
• At risk of osteoporosis
• At risk of hypomagnesaemia — if possible, magnesium levels should be checked before starting PPI therapy and intermittently during long-term treatment, for example if the person is prescribed drugs that can cause hypomagnesaemia, such as digoxin and diuretics.

Adverse effects

Adverse effects of proton pump inhibitors (PPIs) are usually mild and reversible.

• Adverse effects include headache, diarrhoea, nausea, vomiting, abdominal pain, constipation, and dizziness.
• Less common adverse effects include dry mouth, peripheral oedema (swelling), sleep disturbance, fatigue, paraesthesia (numbness tingling), arthralgia (joint pain), myalgia (muscle pain), pruritus (itching), and rash.
• Rare or very rare adverse effects include:
• Subacute cutaneous lupus erythematosus (SCLE is a nasty skin condition), which can occur weeks, months, or years after exposure to a PPI. If suspected discontinue the PPI and seek specialist advice if needed [MHRA, 2015].
• Taste disturbance, hepatitis, jaundice, depression, confusion, hallucinations, hyponatraemia, blood cell problems (leucopenia, leucocytosis, pancytopenia, thrombocytopenia,) visual disturbances, sweating, photophobia, and hair loss (alopecia). 

• Long-term PPI treatment may be associated with uncommon, serious adverse effects such as:
• Hypomagnesaemia — symptoms include muscle twitching, tremors, vomiting, fatigue, and loss of appetite. Case reports after one year of PPI therapy but may occur after 3 months. This usually improves after magnesium replacement therapy and discontinuation of the PPI [MHRA, 2012].
• Increased risk of fractures — especially when used at high doses for over a year in the elderly [MHRA, 2012].
• Clostridium difficile infection — due to the effect of decreasing gastric acidity. Clostridium difficile also known as C. difficile or C. diff, is bacteria that can infect the bowel and cause diarrhoea. https://www.nhs.uk/conditions/c-difficile/
• Rebound acid hypersecretion syndrome — may occur after stopping long-term PPI therapy, although this may be more a theoretical risk than clinical phenomenon.

Drug interactions

Possible drug interactions with proton pump inhibitors (PPIs) include:

• Digoxin
• Warfarin
• Methotrexate
• Phenytoin
• Azole
• Clopidogrel
• Protease inhibitors (Atazanavir, Saquinavir, Tipranavir) 

All GP computer systems have built in software that identifies drug interactions when you add drugs. An issue can arise if some of the drugs are issued by the hospital without checking what you are on, and some of the drugs above may be started by the hospital.

NICE also conducted a Medicines Evidence Commentary in Sept 2019 looking at issues with long term use of PPIs

Having reviewed the evidence, it was concluded that the long-term use of PPIs did not increase the risk of death from any cause which had been a concern from one study.

They recommended an annual review including appropriate advice on stopping or stepping down treatment (may not be appropriate for treatment of Barrett’s and identified the major risks as 1. Fractures 2. Low Magnesium 3. Subacute cutaneous lupus erythematosus.

Don’t forget that PPIs are the main stay of treatment of Barrett’s, they are the best way to prevent progression, so most patients should be taking them long term.

The key message is to have an annual review to assess your risks of long-term side effects and in particular your bones and magnesium levels. In this way the benefits of PPIs far out way any risks and any risks will be detected early.