Description and composition of Epirazole
Epirazole is a substituted benzimidazole and a member of the Proton Pump Inhibitors.
It contains Omeprazole as its active ingredient. It also contains inert ingredients called excipients in sufficient quantities.
Proton pump inhibitors are a group of molecules which inhibit the final phase of gastric acid secretion.
Omeprazole is a white to off-white crystalline powder that melts with decomposition at about 155 degrees Celsius.
It is freely soluble in ethanol and methanol, slightly soluble in acetone and isopropanol and very Slightly soluble in water.
It comes in different dosage forms and strength. These include capsules, injections, suspension and tablets.
Commonly available strength include:
- Packets: 2.5 mg , 10 mg
- Suspension 2 mg/ml
- Tablets: 20 mg
- Capsules: 10 mg, 20 mg, and 40 mg
- Injections: 40 mg
Mechanism of Action of Epirazole
How Epirazole works: it suppress gastric acid secretion by specific inhibition of H+/K+ATPase enzyme system at the secretory surface of the gastric parietal cell.
Because this enzyme is regarded as the acid (proton) pump within the gastric mucosa, omeprazole has been characterized as a gastric acid pump inhibitor in that it blocks the final step of acid production.
This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.
Animal studies indicate that after rapid disappearance from plasma, omeprazole can be found within the gastric mucosa for a day or more.
Pharmacodynamics of Epirazole
After oral administration, the onset of antisecretory effect of omeprazole occurs within one hour, with the maximum effect occurring within two hours.
Inhibition of secretion is about 50% of maximum at 24 hours and the duration of inhibition lasts up to 72 hours.
The antisecretory effect lasts far longer than would be expected from the very short (<Hr) half life, apparently due to the prolonged binding to the parietal H/KATPase enzyme.
When the drug is discontinued, secretory activity returns gradually, over 3 to 5 days.
The inhibitory effect of omeprazole on acid secretion increases with repeated once-daily dosing, reaching a plateau after four days.
Single daly doses of omeprazole ranging from 10mg to 40mg have produced 100% inhibition of 24-hour acidity in some patients
Omeprazole, given in oral doses of 30mg or 40mg for 2 to 4 weeks, had no effect on thyroid function, carbohydrate metabolism or circulating levels of parathyroid hormone, cortisol, estradiol, testosterone, prolactin, cholecystokininor secretin.
No effect on gastric emptying of the solid and liquid components of a test meal was demonstrated after a single dose of omeprazole 90 mg.
As do other agents that elevate intragastric pH, omeprazole administered for 14 days in healthy subjects produced a significant increase in the intragastric concentration of viable bacteria.
The patter of the bactera species was unchanged from that commonly found in saliva.
All changes resolved within three days of stopping treatment
Pharmacokinetics of Epirazole
Epirazole capsules contain an enteric-coated granule formulation of omeprazole so that absorption of omeprazole begins only after the granules leave the stomach.
Absorption is rapid, with peak plasma levels of omeprazole occurring within 0.5 to 3.5hours.
Peak plasma concentrations of omeprazole and AUC are approximately proportional to doses up to 40mg, but because of a saturated first-pass effect, a greater than Iinear response in peak plasma concentration and AUC occur with doses greater than 40mg.
Absolute bioavailability (compared with intravenous administration) is about 40% at doses of 20-40mg, due in large part to presystemic metabolism.
In healthy subjects, the plasma half life is 0.5-1 hour, and the total body 500 600mL/min.
Protein binding is approximately 95%
Omeprazole is extensively metabolized by the cytochrome P450 (CYP) enzyme system.
Following single dose oral administration of a buffered solution of omeprazole, little amount unchanged drug was excreted in urine.
The remainder of the dose was recoverable in faeces. This implies a significant biliary excretion of the metabolites of omeprazole.
Three metabolites have been identified in plasma -the sulfide and sulfone derivatives of omeprazole, and hydroxyomeprazole.
These metabolites have very little or no antisecretory activity
The elimination rate of omeprazole was somewhat decreased in the elderly, and bioavailability was increased.
Omeprazole was 76% bioavailable when a single 40mg oral dose (buffered solution) was administered to healthy elderly volunteers, versus 58% in young volunteers given the same dose.
Nearly 70% of the dose was recovered in urine as metabolites of omeprazole and no unchanged drug was detected.
The plasma clearance of omeprazole was 250mL/min (about half that of young volunteers).
In patients with chronic hepatic disease the bioavailability increased to approximately 100% compared with an IV dose, reflecting decreased first-pass effect, and the plasma half-life of the drug increased to nearly 3hours compared with the Half-Life in normal subjects of 0.5-1 hour.
Plasma clearance averaged 70mL/min, compared with 500-600ml/min, in normal subjects.
Dose reduction particularly when maintenance of healing of erosive esophagitis is indicated in patients with hepatic impairment.
In patients with chronic renal impairment, whose creatinine clearance ranged between 10 and 62mL/min, the disposition of omeprazole was very similar to that in healthy volunteers, although there was a slight increase in bioavailability.
Because urinary excretion is a primary route of excretion of omeprazole metabolites, their elimination slowed in proportion to the decreased creatinine clearance.
No dose reduction is necessary in patients with renal impairment
Uses of Epirazole
Epirazole is indicated in the following conditions:
- Heartburns (pyrosis).
- Gastroesophageal reflux disease (GERD)
- Stress ulceration.
- Gastric and duodenal ulcers
- Zollinger-Ellison syndrome
- Acid related disorders
- Prophylaxis in long-term NSAID therapy and acid aspiration
1. Duodenal Ulcers
Omeprazole is indicated for short-term treatment of active duodenal ulcer in adults.
Most patients heal within four weeks.
Some patients may require additional four week of therapy.
In combination with appropriate antibacterial agents, Omeprazole is indicated for treatment of patients with H. pylori infection and duodenal ulcer (active or upto 1 year history) to eradicate H.pylori in adults.
2. Gastric ulcers
Omeprazole is indicated for short-term treatment (48 weeks) of active benign gastric ulcer in adults.
3. Gastroesophageal reflux disease (GERD) – symptomatic GERD
Omeprazole is indicated for the treatment of heartburn and other symptoms associated with GERD-Erosive Esophagitis.
The efficacy of omeprazole use for longer than 8 weeks in these patients has not been established.
If a patient does not respond to 8 weeks of treatment, a additional 4 weeks of treatment may be given.
If there is recurrence of erosive esophagitis or GERD symptoms (eg. Heartburn), an additional 4-8 weeks course of omeprazole may be considered.
4. Maintenance of healing of erosive esophagitis
Omeprazole is indicated for the maintenance of healing of erosive esophagitis.
5. Pathologic Hypersecretory Condition
Omeprazole is indicated for the long-term treatment of pathologic Hypersecretory conditions (e.g, zollinger-ellison syndrome, multiple endocrine adenomas and systemic mastocytosis) in adults.
Dosage and Administration of Epirazole
This section discusses how the dosage and how to take Omeprazole
1. Active Duodenal Ulcer
For short treatment of active duodenal ulcer, the recommended adult oral dose of Omeprazole is 20mg once daily.
Most patients heal within four weeks. Some patients may require additional four weeks of therapy.
2. Gastric Ulcer
The recommended adult dose is 40 mg of Omeprazole daily for 4-8 weeks.
The recommended oral dose for the treatment of patients with symptomatic GERD and esophageal lesions is 20mg daily for 4 weeks.
The recommended adult oral dose for the treatment of patients with esophagitis and accompanying symptoms due to GERD is 20mg daily for 4 weeks.
4. Maintenance of healing of erosive esophagitis:
The recommended adult dose is 20mg daily.
5. Helicobacter pylori eradication for the reduction of the risk of duodenal ilcer recurrence
1. Triple therapy:
In patients with an ulcer present at the time of initiation of therapy, an additional 18 days of Omeprazole 20mg once daily is recommended for ulcer healing and symptomatic relief
2. Dual Therapy:
The recommended adult oral regimen is Omeprazole 20mg plus clarithromycin 500mg three times day for 14 days.
In patients with an ulcer at the time of initiation of therapy, an additional 14 days of omeprazole 20mg once daily is recommended for ulcer healing and symptom relief.
6. Pathological hypersecretory conditions
The dosage of omeprazole in patients with pathological hypersecretory conditions varies with the individual patient.
The recommended adult oral dose is 60mg once daily. Doses should be adjusted to individual patient needs and should continue for as long as clinically indicated.
Doses up to 120mg three times daily have been administered.
Epirazole Dosage in Pediatric Patients
For the treatment of GERD and maintenance of healing of erosive esophagus, the recommended daily dose for pediatric patients 1 to 16 years of age is as follows:
- 5 <10kg :5mg
- 10 < 20kg: 10mg
- More than/ equal to 20kg : 20mg
On a per kg basis, the doses of omeprazole required to heal erosive esophagitis in pediatric patients are greater than those for adults
Drugs Interactions with Epirazole
Some products that may interact with this drug include: cilostazol, clopidogrel, methotrexate (especially high-dose treatment), rifampin, St John’s wort.
Some products need stomach acid so that the body can absorb them properly.
Omeprazole decreases stomach acid, so it may change how well these products work.
Some affected products include atazanavir, erlotinib, nelfinavir, pazopanib, rilpivirine, certain azole antifungals (itraconazole, ketoconazole, posaconazole), among others.
Omeprazole is very similar to esomeprazole.
Do not use any medications containing esomeprazole while using omeprazole.
This medication may interfere with certain laboratory tests, possibly causing false test results.
Make sure laboratory personnel and all your doctors know you use this drug.
Contraindications of Epirazole
This section discusses when not to use this drug.
Epirazole is contraindicated in patients with known hypersensitivity to substituted benzimidazoles or any component of the formulation.
Hypersensitivity reactions may include anaphylactic shock, anaphylaxis, angioedema, bronchospasm, interstitial nephritis, and urticaria.
Side Effects of Epirazole
The side effects of Epirazole include the following:
- abdominal pain
- gas (flatulence)
- upper respiratory infection
- acid reflux
Less common side effects:
- bone fracture (osteoporosis related)
- deficiency of granulocytes in the blood
- loss of appetite
- gastric polyps
- hip fracture
- hair loss
- chronic inflammation of the stomach
- destruction of skeletal muscle
- taste changes
- abnormal dreams
Rare side effects
- liver damage
- inflammation within the kidney
- dermatologic disorder, potentially life threatening (toxic epidermal necrolysis)
This document does not contain all possible side effects and other side effects may occur.
Check with your medical professional for additional information about side effects.