PPIs (Proton Pump Inhibitors)

• What are PPIs?
• What are PPIs used for?
• How do PPIs work?
• What are the side effects of PPIs?
• What precautions are there for PPIs?
• Use of PPIs in pregnancy
• What medications do PPIs interact with?
• PPIs and the elderly
• How do you take PPIs?
• What are the most common PPIs?

What are PPIs?

Proton pump inhibitors (PPIs) are a commonly prescribed class of medications whose main action is to create a pronounced and long-lasting reduction of stomach acid production. They are the most potent inhibitors of acid secretion available today, and the first-line treatment for gastric acid-related disorders such as gastro-oesophageal reflux disease (GORD), dyspepsia and peptic ulcer disease (PUD). Gastric conditions are common, with up to 20% of adults experiencing heartburn at least once a week.

PPIs produce almost complete reduction of gastric acid secretion and are the drugs of choice for all but mild cases. Patients with severe symptoms often need prolonged treatment, often for years. Many PPIs have been proven to be very safe for short and long term use and have minimal side effects, even in elderly patients.

What are PPIs used for?

Common conditions include:

• Gastro-oesophageal reflux disease (GORD)
• Frequent heartburn and acid regurgitation
• Oesophagitis
• Duodenal and gastric ulcers
• H. pylori eradication
• Gastrointestinal lesions caused by using NSAIDs
• Zollinger-Ellison syndrome

How do PPIs work?

The stomach produces acid to break down food, so it is easier for our bodies to digest them. In some people, this acid can be harmful to the lining of the stomach and the small bowel. This leads to a breakdown in the lining, causing indigestion, reflux and in some cases ulcers. The acid in the stomach is produced by the hydrogen-potassium-ATPase enzyme system, or the "proton pump".

As the name suggests, PPIs stop acid being produced in the stomach by inhibiting the pump’s ability to work. This markedly increases the pH of the stomach, and decreases the acidic irritation of the lining of the stomach and small bowel. This in turn provides symptomatic relief and allows the stomach and lower oesophagus to heal.

What are the side effects of PPIs?

PPIs are generally very well tolerated. The incidence of adverse effects is relatively low, affecting 1–3% of individuals. Adverse effects include:

• Headache;
• Nausea;
• Diarrhoea;
• Rash; and
• Constipation.

More serious adverse effects, including liver dysfunction and visual disturbances, are infrequent but have been described. An increase in the risk of community-acquired pneumonia has also been noted. Due to the effect on calcium absorption, the risk of bone fractures may be indirectly increased.

Of major interest are the long term effects of PPIs. Long term cellular changes that take place in the stomach may be important in the development of stomach cancers. While the use of PPIs is not currently associated with an increased risk of stomach or colorectal cancer, further studies are required.

What precautions are there for PPIs?

PPIs should be used with care under certain conditions. Tell your doctor if you are:

• Pregnant;
• Breastfeeding; or
• Have liver conditions. 

Before starting PPI treatment, testing should be done to determine that no malignancy is present, as the symptoms of a malignancy may be masked with PPI use, leading to a delay in diagnosis.

Use of PPIs in pregnancy

All of the currently available PPIs are rated as pregnancy category B3, with the exception of rabeprazole (Pariet) which is categorised as B1.

There have been a number of scientific studies investigating the safety of PPIs in pregnancy. These have mostly studied the use of omeprazole (Losec), pantoprazole (Somac) and lansoprazole (Zoton), and have concluded that the use of PPIs in pregnancy is not associated with an increased risk of teratogenesis. However, despite their classification, the use of newer PPIs including rabeprazole (Pariet) and esomeprazole (Nexium) in pregnancy is not recommended due to the lack of scientific data.

What medications do PPIs interact with?

PPIs are comparatively safe drugs with few drug interactions, but as PPIs are often used long-term and are the most commonly prescribed class of drug worldwide, these interactions need to be taken into account. Talk to your doctor before taking any other medicines or herbal remedies so they can determine whether the actions of these concomitant medications will affect the mechanism of the PPI or vice versa.

Drug interactions with PPIs most commonly occur as a consequence of their effect on liver enzymes whereby they affect the metabolism and excretion of other medications. Drugs for which PPIs affect metabolism include:

• Antiepileptics: Phenytoin;
• Anticoagulants: Warfarin (e.g. Coumadin), clopidogrel (e.g. Plavix); 
• Sedatives: Diazepam (e.g. Valium);
• Antibiotics: Clarithromycin, erythromycin;
• Antidepressants: Clomipramine, imipramine (e.g. Tofranil).

PPIs interact with membrane transporter systems, which can affect the systemic distribution of other medications.

Additionally, PPIs alter the acidity of gastric acids. Some medications require a specific acidity level (pH level) to be soluble, so a gastric pH which is too high or too low can affect how the drug is absorbed into the systemic circulation. PPIs may affect the solubility and absorption of:

• Cyclosporin;
• Midazolam;
• Nifedipine;
• Antifungals: Ketoconazole (e.g. Nizoral), itraconazole;
• Digoxin;
• Antiretrovirals: Indinavir.

The different PPIs have slightly different mechanisms of actions and therefore will interact differently with different drugs. Your doctor will review your medication needs and choose the PPI which has the less potential to interfere with your individual treatment regime. If there is no way to avoid cocommitant use with PPIs, then it is important to have regular reviews of your treatment regime to avoid any side effects that may occur.

For more information on drugs, see The Principles of Pharmacology (Drugs).

PPIs and the elderly

Interactions with other drugs must be considered in elderly patients, as adverse events are more likely to happen with this population. This is for several reasons. Elderly patients tend to be on more medications, and the more medications you are on, the more likely it is that two of them will interact with each other and change the effect.

Another reason is that as most medications are swallowed orally and digestion is started in the stomach, alterations to the environment within the stomach (such as what happens with a PPI) have the potential to change how much of another medication is absorbed. 

Older individuals more commonly require the use of warfarin and clopidogrel. The  actions of these medications can be seriously and sometimes dangerously altered by the use of PPIs. Furthermore, older people will generally have reduced liver function, putting them at high risk for PPI-related drug interactions.

Talk to your GP about all of your medications and the possibility of interactions, as this may change which PPI is used to treat your condition. Some PPIs may be more suitable in individual treatments for both short-term treatment of GORD and for longer term therapy of other conditions (e.g. ulcers, erosive oesophagitis).

How do you take PPIs?

These medications are available as tablets and capsules. People who have difficulty taking oral medications may use injections. The usual course is four weeks, with many people becoming symptom-free after this time. If there is no improvement after four weeks, you may need to take them for longer, or your doctor may order further tests to determine what else may be helpful. Approximately 1 in 5 people will need to extend their use of PPIs past the initial four-week course. The dose may also be altered depending on the initial response to the medication. Sometimes, doctors will suggest a symptom-drive use of PPIs, which means that they are taken only when symptoms are experienced.

Throughout the course of the treatment, consultations at least every 6 months with your doctor are necessary in order to review your medication and symptoms, and to determine whether it is necessary to continue the PPI treatment.

The symptoms you experienced before taking a PPI may come back after you have stopped taking the medication. See your doctor immediately if you vomit blood, notice something that looks like coffee grounds in your vomit, or pass black tarry stools.

Until recently, these medications were only available though prescription. However, a two week course of Somac Heartburn Relief (pantoprazole) has now been made available through pharmacists.

What are the most common PPIs?

PPIs requiring a prescription from your doctor include:

• Somac (pantoprazole);
• Pariet (rabeprazole);
• Losec (omeprazole);
• Nexium (esomeprazole);
• Zoton (lansoprazole).

PPIs available from a pharmacy without a prescription include:

• Somac Heartburn Relief (pantoprazole).

More information

For more information on acid reflux and heartburn, and related investigations, treatments and supportive care, see Acid Reflux and Heartburn.

 

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