Proton pump inhibitors include-

Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole, Pramiprazole

Refer - Omeprazole

Proton pump inhibitors causes a profound and long lasting inhibition of gastric acid secretion. Therefore esomeprazole, lanzoprazole , omeprazole ,pantoprazole and rabeprazole, may interfere with the absoption of drugs where gastric pH is an important detreminant of bioavailability ( eg.ketoconazole, ampicillin, iron salts, digoxin, cyanocobalamin )

CYP450 system - There have been reports of interaction between omeprazole and certain drugs metabolized via the CYP450 system ( eg. cyclosporine, disulfram, benzodiazepines ).

Esmoprazole , lansoprazole, pantoprazole, and rabeprazole are extensively metabolised by CYP2C19 and CYP34A . in clinical studies antacids were used conomittantly with these agents Esomeprazole is extensively metabolised in the liver by CYP2C19 and CYP3A4 Esomeprazole inhibits gastric acid secretion.

Therefore esomeprazole may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability eg. ketoconazole, iron salts, and digoxin.

Co-administration of oral contraceptives, diazepam,phenytoin, or quinidine did not seem to change the pharmacokinetic profile of esomeprazole.

Co-administration of esomeprazole, clarithromycin and amoxycillin has resulted in increase in the plasma levels of esomeprazole and 14-hydoxyclarithromycin.

Headache, diarrhea, abdominal pain, nausea, flatulance, drymouth, constipation, increased creatinine, uric acid, increased or decreased hemoglobin, white blood cell count, platelets, increased bilirubin,alkaline phosphatase, ALT AST, hypokalemia, hyponutremia, hyperkalemia, hypernatremia, altered thyroid function tests.

Hypersensivity

Special precautions:

Symptomatic response to therapy with esomeprazole does not preclude the presence of gastric malignancy Atropic gastritis has been noted occassionally in gastric corpus biopsies from patients treated long-term omeprazolem, of which esomeprazole is an enantiomer

Caution to be taken while giving to nursing mothers.

Safety and efficacy in pediatric patients have not been established. For patients with severe liver impairment, a dose of 20mg of esomeprazole should not be exceeded.

No adequate and well-controlled studies on pregnant women. There are reports of congential abnormallities occuring in infants born to women who have received omeprazole during pregnancy.

Approved - December 2001

Indication-

Gastroesophageal disease-

Dosage-

20mg or 40mg once daily for 4 weeks Maintenace dose - 20mg once daily.

Missed dose- -

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

GASTRO OSEPHAGEAL REFLUX DISEASE (GORD)

Evidence Based Medicine (MIMS- March 2003)

Beneficial

1. Proton Pump Inhibitors such as omeprazole, Lansoprazole, pantoprazole

2. H-2 Antagonists such as cimetidine, ranitidine, famotidine, (less than proton pump inhibitors)

3. Fundoplication

Likely to be beneficial

1. Medical and surgical tretment of GORD in selected patients with extraoesophageal manifestations.

Unknown effectiveness

1. Medical and surgical treatment of GORD in patients with Barrets oesophagus

2. Surgical treatment for non erosive oesophagitis

Key Points

1. One systemic review of randomised clinical trials has found proton inhibitors to be more effective than H-2 antagonists in both erosive and non-erosive oesophagitis. One trial has found no significant differences in the effectiveness of different proton pump inhibitors

2. Surgical treatment has not been adequately evaluated in controlled clinical trials. Medical and surgical treatments have not been adequately compared

3. It is not clear whether patients with Barretts oesophagitis benefit from medical or surgical treatment of their gastro oesophageal reflux

4. There is limited, conflicting evidence on the basis on the benefits of treating gastro oesophageal reflux in patients with extra oesophageal manifestations (such as asthma)

Refer - Omeprazole

Patient Information

Elderly-                                                                                                                            No dosage adjustments required

Renal function impairment-                                                                                               For patients with severe hepatic impairment (Child- Pugh class C) , do not exceed a dose of esomeprazole 20mg.

No dosage adjustment is necessary in patients with mild to moderate liver impairment (Child- Pugh calsses A and B)

Administration-                                                                                                           Take espomeprazole at least 1 before eating

Delayed Release Capsules-                                                                                        Capsules can be swaollowed whole or can be opened and mixed with applesauce     

Difficulty in swallowing -                                                                                                Add  1 tablte spoon of applesauce to an empty bowl and open  the delayed release capsule . Carefully empty the granules inside the capsule onto to the applesauce. Granules should be mixed with the applesauce and swallowed immediately. The applesauce must not be hot and should be soft enough to be swallowed immediately without chewing. Do not store the granules/applesauce for future use

Administration of capsule for nasogastric tube-                                                           The delayed release capsule can be opened and the intact mixture can be emptied into a 60ml Cathether tipped syringe and mixed with 50 L of water. It is important to only use a catherter tipped syringe when administering esmoprezole through a naso-gastric (NG)  tube. 

Replace the plunger and shake the syringe vigourously for 15 seconds. Hold the syringe up and check for granules remaining in the tip. Attach the syringe to an NG tube and deliver the contents of the syringe through the NG tube into the stomach.

After administering the granules , flesh the NG tube with additional water. Do not administer the granules if they have dissolved or disintrgrated. The suspension must be usedimmediately after preparation. 

Pharmacology:

Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+ - AATPase in the gastric parietal cell. By acting specifically on the proton pump, esomeprazole blocks the final step of acid production, thus reducing gastric acidity

Pharmacokinetics:

After oral administration peak plasma levels occur at approximately 1.5 hours. At repeated once daily dosing with 40mg, the systemic bioavailability is approximately 90% compared to 64% after a single dose of 40mg. Esomeprazole should be taken atleast one hour before meals Esomeprazole is 97% bound to pasma proteins.

The plasma elimination half-life of esomeprazole is approximately 1- 1.5 hours. Less than 1% of parent drug is excreted in the urine.

Approximately 80% of an oral dose of esomeprazole is excreted as inactive metabolites in the urine, and the the reminder is found as inactive metabolites in the feces..

Esomeprazole should be taken atleast one hour before meals.

Pregnancy-

No adequate and well-controlled studies on pregnant women.

There are reports of congential abnormallities occuring in infants born to women who have received omeprazole during pregnancy.