1. PRILOSEC HISTORY

How was Prilosec discovered?
Prilosec was introduced by Procter and Gamble (P&G) in 1988 and was approved by the FDA in 1989.

The P&G has its presence in almost 80 countries worldwide. What began as a small, family-operated soap and candle company now provides products and services of superior quality and value to consumers in 140 countries

Note: World-drugs.net sells generic version of Prilosec

2. PRILOSEC FACTS

Prilosec (omeprazole) is a proton-pump inhibitor for acid-related diseases, which is the world's largest-selling gastrointestinal product market.

Prilosec is effectively used for

• acute use in peptic ulcer disease and/or reflux esophagitis
• maintenance use in reflux esophagitis and/or duodenal ulcer
• the management of Helicobacter pylori-positive duodenal ulcer disease and H.pylori-positive gastric ulcer disease in 46 countries (in combination with appropriate antibiotics)
• gastroduodenal ulceration associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs)
• acid-related dyspepsia
• severe reflux esophagitis in children
• aspiration pneumonitis/prophylaxis

3. ABOUT PRILOSEC MEDICATION

Prilosec contains the active ingredient omeprazole, which is a type of medicine called a proton pump inhibitor. Prilosec acts in the stomach to decrease the production of stomach acid.

Proton pumps are found on cells that line the stomach and are used by these cells to produce stomach acid. Prilosec works by inhibiting the action of the Proton pumps, and this reduces the production of stomach acid.

Stomach acid is produced in the stomach as a normal part of the digestive process. Normally the linings of the stomach and duodenum (an area of the intestine directly after the stomach) are protected by a layer that resists acid attack. However, if this layer is damaged, or large amounts of stomach acid are formed, an ulcer can develop on the lining of the stomach or duodenum. This is called a peptic ulcer.

Acid produced in the stomach can also sometimes flow back into the food pipe (oesophagus). This is called gastro-oesophageal reflux disease (GERD), and can cause pain and a burning sensation known as heartburn. It can also irritate and damage the lining of the oesophagus, causing a condition called reflux oesophagitis.

By reducing the production of stomach acid Prilosec can be used to treat all these and other conditions.

Prilosec stops excess acid flowing back into the food pipe and can be used to relieve heartburn symptoms associated with acid reflux. Prilosec also allows the oesophagus to heal in reflux oesophagitis.

Diagrammatic representation for the mechanism of action of Prilosec.

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By reducing the amount of acid in the stomach and duodenum omeprazole also allows peptic ulcers to heal, and prevents them from recurring. Prilosec also relieves the symptoms of indigestion caused by excess stomach acid.

Prilosec can be used to prevent and treat peptic ulcers that can occur as a side effect of non-steroidal anti-inflammatory drugs (NSAIDs), such as diclofenac. In addition it can relieve side effects such as indigestion that can be associated with these medicines.

Prilosec is also given together with antibiotics to help eradicate bacteria called Helicobacter pylori from the stomach. These bacteria can contribute to the formation of peptic ulcers. Prilosec helps create an environment in the gut in which the antibiotics can be more effective at killing the bacteria.

Prilosec is used in varying doses and for varying lengths of time depending on the condition being treated.

4. PRILOSEC EFFECTIVENESS

When is Prilosec best taken?
Prilosec Delayed-Release Capsules contain an enteric-coated granule formulation of omeprazole (because omeprazole is acid-labile), 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 3.5 hours. Peak plasma concentrations of omeprazole and AUC are approximately proportional to doses up to 40 mg, but because of a saturable first-pass effect, a greater than linear response in peak plasma concentration and AUC occurs with doses greater than 40 mg. Absolute bio-availability is about 30-40% at doses of 20-40 mg, due in large part to presystemic metabolism. In healthy subjects the plasma half-life is 0.5 to 1 hour, and the total body clearance is 500-600 ml/min. Protein binding is approximately 95%.

The bioavailability of omeprazole increases slightly upon repeated administration of Prilosec Delayed-Release Capsules.

Following single dose oral administration of a buffered solution of omeprazole, little if any unchanged drug was excreted in urine. The majority of the dose (about 77%) was eliminated in urine as at least six metabolites. Two were identified as hydroxyomeprazole and the corresponding carboxylic acid. The remainder of the dose was recoverable in feces. 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.

In patients with chronic hepatic disease, the bioavailability increased to approximately 100% compared to an I.V. dose, reflecting decreased first-pass effect, and the plasma half-life of the drug increased to nearly 3 hours compared to the half-life in normals of 0.5-1 hour. Plasma clearance averaged 70 ml/min, compared to a value of 500-600 ml/min in normal subjects.

In patients with chronic renal impairment, whose creatinine clearance ranged between 10 and 62 mL/min/1.73 m, 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 Prilosec metabolites, their elimination slowed in proportion to the decreased creatinine clearance.

The elimination rate of omeprazole was somewhat decreased in the elderly, and bioavailability was increased. Prilosec was 76% bioavailable when a single 40 mg oral dose of Omeprazole (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 250 ml/min (about half that of young volunteers) and its plasma half-life averaged one hour, about twice that of young healthy volunteers.

In pharmacokinetic studies of single 20 mg Prilosec doses, an increase in AUC of approximately four-fold was noted in Asian subjects compared to Caucasians.

Dose adjustment, particularly where maintenance of healing of erosive esophagitis is indicated, for the hepatically impaired and Asian subjects should be considered.

Prilosec Delayed-Release Capsule 40 mg was bioequivalent when administered with and without applesauce. However, Prilosec Delayed-Release Capsule 20 mg was not bioequivalent when administered with and without applesauce. When administered with applesauce, a mean 25% reduction in C max was observed without a significant change in AUC for Prilosec Delayed-Release Capsule 20 mg. The clinical relevance of this finding is unknown.

The pharmacokinetics of Prilosec has been investigated in pediatric patients of different ages.

5. PRILOSEC EFFECTS ON SPECIAL POPULATION

How do different people react to Prilosec?
Nursing Mothers
It is not known whether Prilosec is excreted in human milk. In rats, Prilosec administration during late gestation and lactation at doses of 13.8 to 138 mg/kg/day (35 to 345 times the human dose) resulted in decreased weight gain in pups. Because many drugs are excreted in human milk, because of the potential for serious adverse reactions in nursing infants from omeprazole, and because of the potential for tumorigenicity shown for Prilosec in rat carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue Prilosec , taking into account the importance of the drug to the mother.

Pediatric Use
The safety and effectiveness of Prilosec has been established in the age group 2 years to 16 years for the treatment of acid-related gastrointestinal diseases, including the treatment of symptomatic GERD, treatment of erosive esophagitis, and the maintenance of healing of erosive esophagitis. The safety and effectiveness of Prilosec have not been established for pediatric patients less than 2 years of age. Use of Prilosec in the age group 2 years to 16 years is supported by evidence from adequate and well-controlled studies of Prilosec in adults with additional clinical, pharmacokinetic, and safety studies performed in pediatric patients.

Geriatric Use
Prilosec was administered to over 2000 elderly individuals (>/= 65 years of age) in clinical trials in the US and Europe. There were no differences in safety and effectiveness between the elderly and younger subjects. Other reported clinical experience has not identified differences in response between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.

Pharmacokinetic studies have shown the elimination rate was somewhat decreased in the elderly and bioavailability was increased. The plasma clearance of Prilosec was 250 ml/min (about half that of young volunteers) and its plasma half-life averaged one hour, about twice that of young healthy volunteers. However, no dosage adjustment is necessary in the elderly.

6. PRILOSEC EFFECTS ON MEDICAL CONDITIONS

How does Prilosec affect your existing condition/ailment?
It is safe to take antacids as needed while you are taking Prilosec but do not take antacids at the same time as your dose of Prilosec. If you need antacids, take them at least 2 hours before or after your Prilosec. Cigarette smoking will block the beneficial effects of Prilosec. You should not smoke or chew tobacco when taking this drug.

While Prilosec is quite effective in healing peptic ulcers and treating severe reflux Esophagitis, it does not exert any long-term protective action once the medication has been discontinued. In most patients, Prilosec, or a less medication, must be taken on a long-term basis to keep the problem under control. This is especially true for patients with chronic heartburn due to acid reflux. Patients with gastric or duodenal ulcers due to Helicobacter pylori may often stop all ulcer medications once the infection is cured. You should be alert to the possibility of recurrence of symptoms anytime after stopping the drug. If you suspect that your problem has returned, contact your doctor.

7. OTHER/ALTERNATE USES OF PRILOSEC

What else does Prilosec treat?
Prilosec is used in combination with antibiotics for eradicating H.Pylori infection of the stomach.

8.ADVERSE/SIDE EFFECTS of PRILOSEC

What are the side effects of Prilosec?
Prilosec Delayed-Release Capsules were generally well tolerated during domestic and international clinical trials in 3096 patients.

In the U.S. clinical trial population of 465 patients (including duodenal ulcer, Zollinger-Ellison syndrome and resistant ulcer patients), the following adverse experiences were reported to occur in 1% or more of patients on therapy with Prilosec . Numbers in parentheses indicate percentages of the adverse experiences considered by investigators as possibly, probably or definitely related to Prilosec :

	Omeprazole (n = 465)	Placebo (n = 64)
Headache	6.9 (2.4)	6.3
Diarrhea	3.0 (1.9)	3.1 (1.6)
Abdominal   Pain	2.4 (0.4)	3.1
Nausea	2.2 (0.9)	3.1
URI	1.9	1.6
Dizziness	1.5 (0.6)	0.0
Vomiting	1.5 (0.4)	4.7
Rash	1.5 (1.1)	0.0
Constipation	1.1 (0.9)	0.0
Cough	1.1	0.0
Asthenia	1.1 (0.2)	1.6 (1.6)
Back Pain	1.1	0.0

The following adverse reactions, which occurred in 1% or more of Prilosec -treated patients, have been reported in international double-blind, and open-label, clinical trials in which 2,631 patients and subjects received Prilosec .

Incidence of Adverse Experiences >/= 1% Causal Relationship not Assessed
	Omeprazole (n = 2631)	Placebo (n = 120)
Body as a Whole, site unspecified
Abdominal pain	5.2	3.3
Asthenia	1.3	0.8
Digestive System
Constipation	1.5	0.8
Diarrhea	3.7	2.5
Flatulence	2.7	5.8
Nausea	4.0	6.7
Vomiting	3.2	10.0
Acid regurgitation	1.9	3.3
Nervous System/Psychiatric
Headache	2.9	2.5

Additional adverse experiences occurring in < 1% of patients or subjects in domestic and/or international trials, or occurring since the drug was marketed, are shown below within each body system. In many instances, the relationship to Prilosec was unclear.

Body as a Whole : Allergic reactions, including, rarely, anaphylaxis, fever, pain, fatigue, malaise, abdominal swelling

Cardiovascular : Chest pain or angina, tachycardia, bradycardia, palpitation, elevated blood pressure, peripheral edema

Gastrointestinal : Pancreatitis (some fatal), anorexia, irritable colon, flatulence, fecal discoloration, esophageal candidiasis, mucosal atrophy of the tongue, dry mouth. During treatment with omeprazole, gastric fundic gland polyps have been noted rarely. These polyps are benign and appear to be reversible when treatment is discontinued.

Gastro-duodenal carcinoids have been reported in patients with ZE syndrome on long-term treatment with Prilosec. This finding is believed to be a manifestation of the underlying condition, which is known to be associated with such tumors.

Hepatic : Mild and, rarely, marked elevations of liver function tests [ALT (SGPT), AST (SGOT), (gamma)-glutamyl transpeptidase, alkaline phosphatase, and bilirubin (jaundice)]. In rare instances, overt liver disease has occurred, including hepatocellular, cholestatic, or mixed hepatitis, liver necrosis (some fatal), hepatic failure (some fatal), and hepatic encephalopathy.

Metabolic/Nutritional : Hyponatremia, hypoglycemia, weight gain

Musculoskeletal : Muscle cramps, myalgia, muscle weakness, joint pain, leg pain

Nervous System/Psychiatric : Psychic disturbances including depression, aggression, hallucinations, confusion, insomnia, nervousness, tremors, apathy, somnolence, anxiety, dream abnormalities; vertigo; paresthesia; hemifacial dysesthesia

Respiratory : Epistaxis, pharyngeal pain

Skin : Rash and, rarely, cases of severe generalized skin reactions including toxic epidermal necrolysis (TEN; some fatal), Stevens-Johnson syndrome, and erythema multiforme (some severe); purpura and/or petechiae (some with rechallenge); skin inflammation, urticaria, angioedema, pruritus, alopecia, dry skin, hyperhidrosis

Special Senses : Tinnitus, taste perversion

Urogenital : Interstitial nephritis (some with positive rechallenge), urinary tract infection, microscopic pyuria, urinary frequency, elevated serum creatinine, proteinuria, hematuria, glycosuria, testicular pain, gynecomastia

Hematologic : Rare instances of pancytopenia, agranulocytosis (some fatal), thrombocytopenia, neutropenia, anemia, leucocytosis, and hemolytic anemia have been reported.

The incidence of clinical adverse experiences in patients greater than 65 years of age was similar to that in patients 65 years of age or less.