Esomeprazole

Esomeprazole belongs to the proton pump inhibitor family, the PPIs. It is a prodrug: the molecule swallowed is inactive and only takes on its active form after being cleaved by acid, within the secretory canaliculi of the parietal cells of the stomach. There, it specifically blocks the H+/K+ ATPase proton pump, the enzyme that controls the final step of acid secretion at the surface of these cells. By neutralising this pump, esomeprazole shuts down the production of gastric acid at its source.

Once absorbed, the molecule is mostly metabolised by the CYP2C19 isoenzyme of the liver, which forms the hydroxy and desmethyl metabolites; the remainder passes through CYP3A4, which forms the sulfone metabolite. Its half-life in plasma is short, on the order of 1 to 1.5 hours. This brevity in the blood contrasts with the duration of the effect: by binding to the pump, esomeprazole blocks secretion well beyond its circulating presence. CYP2C19 is also the gateway for several interactions, which we return to below.

Esomeprazole reduces the acidity of the stomach. It is prescribed for so-called acid-related conditions, foremost among them gastro-oesophageal reflux, when the acidic contents of the stomach rise back up towards the oesophagus. This reflux causes burning, discomfort behind the breastbone and, over time, irritation of the lining. By lowering the amount of acid produced, the medicine cuts the aggression at its root rather than simply neutralising the acid already present.

It is also indicated in erosive oesophagitis, the form in which the lining of the oesophagus is already damaged by acid. Here, the objective goes beyond relieving symptoms: the aim is to let the wall heal, which requires acidity to stay durably low. It is this dual purpose, easing the discomfort and allowing repair, that explains why the treatment often extends over time and follows a precise protocol.

The timing of the dose matters as much as the dose itself. Esomeprazole is swallowed at least one hour before a meal, because proton pumps become active at the moment of eating: the medicine is then present when the pumps are running, which strengthens its effectiveness. For a single dose per day, it is taken in the morning, before breakfast. Taken after a meal or at random times, it works less well.

Regularity is the key with this class of medicines. Because the effect builds up over several days and the molecule blocks the pumps durably, a missed or delayed dose loses ground. The dose is not changed and the treatment is not stopped on one’s own initiative, even once the discomfort has gone: stopping is decided with the doctor, because interrupting too early can let the symptoms return or halt the healing that is under way.

The most common adverse effects are digestive and neurological, and they remain moderate. In trials on the healing of erosive oesophagitis, headache was the most frequent effect: 5.5% of people on 20 mg and 5% on 40 mg, with diarrhoea occurring with no difference from the control groups. In symptomatic reflux in adults, diarrhoea, headache and abdominal pain were each reported in about 4% of patients. Nausea, flatulence, constipation and dry mouth appeared at comparable rates across the treatment groups.

Other effects emerge only when the treatment is prolonged and at high doses. A drop in blood magnesium, or hypomagnesaemia, can occur; correcting it most often requires a magnesium supply and stopping the PPI. Daily use over a long period, for example beyond three years, can lead to malabsorption of vitamin B12, because gastric acid takes part in its release from food. Finally, an increased risk of fracture of the hip, wrist or spine has been observed in people receiving high doses over a prolonged period.

By lowering the acidity of the stomach, esomeprazole also affects the way certain nutrients are released and then absorbed. Vitamin B12 is the clearest example: acid helps detach it from food, and a long treatment can hinder its absorption. It is found in products of animal origin, fish, meat, poultry, eggs, milk and dairy products. Magnesium, which prolonged treatment can lower, is found in spinach, nuts and wholemeal bread.

Other intakes deserve to stay well looked after because they depend in part on the pH of the stomach. Iron is better supplied by red meat, beans, chickpeas, nuts and dried apricots; calcium by cheese, kale and sardines whose bones are eaten. A varied plate, rich in green vegetables, fish and nuts, already covers a large share of these needs. When a treatment durably alters the ground, a targeted supply makes sense, in addition to the treatment and never in its place.

Two mechanisms account for most of the interactions. Through CYP2C19, esomeprazole reduces the formation of the active metabolite of clopidogrel, the antiplatelet agent, so much so that the two should not be combined. Through the reduction in acidity, it lowers the absorption of medicines whose bioavailability depends on pH: atazanavir, nelfinavir, rilpivirine, ketoconazole, iron salts, erlotinib and mycophenolate mofetil. Conversely, it can raise and prolong the concentrations of methotrexate, especially at high dose, with a risk of toxicity, and interact with warfarin, with a possible rise in the INR, as with digoxin, tacrolimus, cilostazol and diazepam.

Monitoring follows directly from these effects. It is advised to measure blood magnesium before starting a prolonged treatment, then to check it periodically. Any combination with an anticoagulant, methotrexate or one of the medicines mentioned calls for close surveillance, decided by the doctor or the pharmacist. Reporting all of one’s treatments, including those taken without a prescription, makes it possible to anticipate these interactions rather than discover them on a test result.