1.PROTONIX HISTORY
How was Protonix discovered?

Protonix is a product of Wyeth Pharmaceuticals. 

Wyeth Pharmaceuticals received the US FDA approval to manufacture Protonix in March 2001. 

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

2.PROTONIX FACTS

Wyeth, formerly known as American Home Products, is one of the largest pharmaceutical companies in the world. They are headquartered in New Jersey. They are known for manufacturing the over-the-counter drugs as well as the prescription drugs. 

Wyeth Consumer Healthcare
Wyeth Consumer Healthcare operates in over 65 countries. The division had sales of $2.5 million in 2004 and is the fifth largest over-the-counter health products company in the world.

Wyeth Pharmaceuticals
Wyeth Pharmaceuticals, formerly Wyeth-Ayerst Laboratories, is the original company founded by the Wyeth brothers, originally known as John Wyeth and Brother. They focus on the research, develop, and marketing of prescription drugs. The pharmaceuticals division is further subdivided into five subdivisions: Wyeth Research, Prescription Products, Biopharmaceuticals, Vaccines, and Nutritionals.

Fort Dodge Animal Health
Fort Dodge was founded in 1912 and became a division of Wyeth in 1945. They are a leading manufacturer of prescription and over-the-counter drugs for veterinary medicine as well as livestock. 

3.ABOUT PROTONIX MEDICATION

What Is GERD?

GERD stands for Gastro Esophageal Reflux Disease. "Gastro" refers to the stomach. Esophageal refers to the esophagus, the tube that carries food from the mouth to the stomach. Reflux means to back-up or flow backwards. GERD is a condition in which acid; bile and partially digested food in the stomach back up into the esophagus.

 

• Partially digested food contains a strong acid. It also contains powerful enzymes that break down food. When acid and enzymes come into contact with the esophagus, they cause irritation, inflammation, pain, and other symptoms.
• The stomach lining has a special protective layer that protects the stomach from acid attack. However, this protective layer does not exist in the esophagus, making it vulnerable to damage from Stomach acid and digestive enzymes

• Many people think that heartburn (or acid indigestion) is a separate disease. It actually is one symptom of GERD. Heartburn is an unpleasant burning sensation behind the breastbone that usually occurs after a meal.
• Most individuals with GERD also have hiatal hernias, which make it easier for stomach contents to reflux into the esophagus. A hiatal hernia occurs when part of the stomach bulges into the chest cavity through an opening in the diaphragm (hiatus). The diaphragm is a sheet of muscle that separates the stomach cavity from the chest cavity.

What are the symptoms of GERD?

Heartburn is the most common symptom of GERD. It feels like a burning chest pain right behind the breastbone. Pain may move upward toward the throat. It often is worse after meals. Bending over or lying down also may make heartburn worse. Standing up may bring relief. Heartburn often occurs after going to bed at night.

Other GERD symptoms include:

• Burping-up, or regurgitation, of sour-tasting, acidy material into the mouth.
• Difficult or painful swallowing.
• Sore throat, hoarseness, and/or cough.
• Wheezing in people with asthma.

GERD also occurs in young children who may have the same symptoms as adults but cannot describe them. The only noticeable symptoms in infants and children may be vomiting, coughing, wheezing or other respiratory problems, and failure to gain weight normally.

What Causes GERD?

GERD occurs when a muscle at the lower end of the esophagus does not work properly. The muscle is called the lower esophageal sphincter (LES). Sphincters are ring-like bands of muscle that contract, or squeeze together, to close off body passageways. The body has many sphincters. Perhaps the most familiar is the anal sphincter, which seals off the rectum between bowel movements. 

• The LES acts like a one-way valve that closes off the esophagus. It allows food to travel freely downward into the stomach. But it also seals off the stomach, preventing partially digested food from refluxing, or passing back up, through the esophagus.
• Normally, the LES closes immediately after a person swallows food, keeping irritating Stomach acid and digestive enzymes out of the esophagus.
• In individuals with GERD, the LES may not close in a normal way or relaxes inappropriately between swallows. Stomach juices and partially digested food may flow back up and burn the lower esophagus. The result is heartburn and other symptoms of GERD.  

Treating Acid Reflux Disease

There is a range of treatment options for acid reflux disease and associated symptoms. It's best to talk to your doctor about which treatment might work best for you.

Antacids are available without a prescription (over-the-counter, or "OTC") and are used primarily for heartburn. Typically, they can provide limited, short-term relief. If you are experiencing heartburn two or more days a week, even though you've tried some over-the-counter treatments and changed your diet, it may be a sign of something more serious, and you should talk to your doctor.

H2 blockers are available over-the-counter and by prescription. They get their name from the way they block one particular stimulus of acid production. H2 blockers reduce the amount of acid that is produced in the stomach, but not as much as Proton pump inhibitors. If you continue to suffer from heartburn while you are taking an H2 blocker, you should see your doctor. Your doctor may develop a different treatment plan.

Proton pump inhibitors (PPIs) are available by prescription. PPIs block the final stage of acid production. They are very effective and can relieve symptoms in most people who have acid reflux disease.

Protonix contains the active ingredient pantoprazole, which is a type of medicine called a Proton pump inhibitor. Protonix works by reducing the production of Stomach acid.

Stomach acid is produced as a normal part of the digestive process. When we digest food, the cells lining the inside of the stomach use a mechanism called a proton pump to produce Stomach acid. Protonix works by stopping the proton pumps from working. This reduces the production of Stomach acid.

Protonix reduces the amount of acid in the stomach and duodenum. This helps to heal peptic ulcers and helps to prevent them from recurring. Protonix also helps to relieve the symptoms of reflux oesophagitis.

Protonix may also be given together with antibiotics to destroy bacteria (Helicobacter pylori) that, if present in the stomach, can contribute to the formation of ulcers. 

4.PROTONIX EFFECTIVENESS
When is Protonix best taken?

Protonix is prepared as an enteric-coated tablet so that absorption of pantoprazole begins only after the tablet leaves the stomach. Peak serum concentration (Cmax) and area under the serum concentration time curve (AUC) increase in a manner proportional to oral and intravenous doses from 10 mg to 80 mg. Protonix does not accumulate and its pharmacokinetics are unaltered with multiple daily dosing.

Absorption
The absorption of Protonix dose is rapid, with a Cmax of 2.5 µg/ mL that occurs approximately 2.5 hours after single or multiple oral 40- mg Protonix doses. Protonix dose is well absorbed; it undergoes little first- pass metabolism resulting in an absolute bioavailability of approximately 77%. Protonix absorption is not affected by concomitant administration of antacids. Administration of Protonix with food may delay its absorption up to 2 hours or longer; however, the Cmax and the extent of Protonix absorption (AUC) are not altered. Thus, Protonix dose may be taken without regard to timing of meals. 

Distribution
The apparent volume of distribution of Protonix is approximately 11.0- 23.6L, distributing mainly in extracellular fluid. The serum protein binding of Protonix is about 98%, primarily to albumin.

Metabolism
Protonix is extensively metabolized in the liver through the cytochrome P450 (CYP) system. Protonix metabolism is independent of the route of administration (intravenous or oral). The main metabolic pathway is demethylation, by CYP2C19, with subsequent sulfation; other metabolic pathways include oxidation by CYP3A4. There is no evidence that any of the Protonix metabolites have significant pharmacologic activity. CYP2C19 displays a known genetic polymorphism due to its deficiency in some sub- populations (e. g. 3% of Caucasians and African- Americans and 17- 23% of Asians). Although these sub- populations of slow pantoprazole metabolizers have elimination half- life values of 3.5 to 10.0 hours, they still have minimal accumulation (=< 23%) with once daily dosing.

Elimination
After a single oral dose of 14 C- labeled Protonix to healthy, normal metabolizer volunteers, approximately 71% of the Protonix dose was excreted in the urine with 18% excreted in the feces through biliary excretion. There was no renal excretion of unchanged Protonix. 

5.PROTONIX EFFECTS ON SPECIAL POPULATION
(How do different people react to Protonix?

Geriatric
Only slight to moderate increases in Protonix AUC (43%) and Cmax (26%) were found in elderly volunteers (64 to 76 years of age) after repeated oral administration, compared with younger subjects. No dosage adjustment is recommended based on age.

Pediatric
The pharmacokinetics of Protonix have not been investigated in patients <18 years of age.

Gender
There is a modest increase in Protonix AUC and Cmax in women compared to men. However, weight- normalized clearance values are similar in women and men. No dosage adjustment is needed based on gender.

6.PROTONIX EFFECTS ON MEDICAL CONDITIONS
(How does Protonix affect your existing condition/ailment?

Renal Impairment

In patients with severe renal impairment, pharmacokinetic parameters for Protonix were similar to those of healthy subjects. No dosage adjustment is necessary in patients with renal impairment or in patients undergoing hemodialysis.

Hepatic Impairment

In patients with mild to severe hepatic impairment, maximum Protonix concentrations increased only slightly (1.5- fold) relative to healthy subjects. Although serum half- life values increased to 7- 9 hours and AUC values increased by 5- to 7- fold in hepatic- impaired patients, these increases were no greater than those observed in slow CYP2C19 metabolizers, where no dosage frequency adjustment is warranted. These pharmacokinetic changes in hepatic- impaired patients result in minimal drug accumulation following once daily multiple- dose administration. No dosage adjustment is needed in patients with mild to severe hepatic impairment. 

7.OTHER/ALTERNATE USES OF PROTONIX
(What else does Protonix treat?)

Protonix is also used effectively in the treatment of nighttime GERD.

Nighttime GERD is gastroesophageal reflux occurring at night.

Nighttime GERD may worsen the damage to the esophagus, since acid reflux may be prolonged when lying down. Frequent and persistent nighttime heartburn can be a symptom of erosive Gastroesophageal reflux disease, or erosive GERD in which sores develop in the lining of the esophagus.

 

8.ADVERSE/SIDE EFFECTS of PROTONIX
(What are the side effects of Protonix?)

Worldwide, more than 11,100 patients have been treated with Protonix in clinical trials involving various dosages and duration of treatment. In general, Protonix has been well tolerated in both short-term and long-term trials.

In two U. S. controlled clinical trials involving Protonix 10, 20, or 40 mg doses for up to 8 weeks, there were no dose related effects on the incidence of adverse events. The following adverse events considered by investigators to be possibly, probably or definitely related to drug occurred in 1% or more in the individual studies of GERD patients on therapy with Protonix.

Most Frequent Adverse Events Reported as Drug Related in Short-term Domestic Trials
	% Incidence
	Study 300-US		Study 301-US
Study Event	PROTONIX (n = 521)	Placebo (n = 82)	PROTONIX (n = 161)	Nizatidine (n = 82)
Headache	6	6	9	13
Diarrhea	4	1	6	6
Flatulence	2	2	4	0
Abdominal pain	1	2	4	4
Rash	<1	0	2	0
Eructation	1	1	0	0
Insomnia	<1	2	1	1
Hyperglycemia	1	0	<1	0
Note: Only adverse events with an incidence greater than or equal to the comparators are shown.

In international short-term double-blind or open-label, clinical trials involving 20 to 80 mg per day, the following adverse events were reported to occur in 1% or more of 2805 GERD patients receiving Protonix for up to 8 weeks.

Adverse Events in GERD Patients in Short-term International Trials
	% Incidence
Study Event	Pantoprazole Total (N=2805)	Ranitidine 300 mg (N=594)	Omeprazole 20 mg (N=474)	Famotidine 40 mg (N=239)
Headache	2	3	2	1
Diarrhea	2	2	2	<1
Abdominal pain	1	1	<1	<1

In two U. S. controlled clinical trials involving Protonix 10, 20, or 40 mg doses for up to 12 months, the following adverse events considered by investigators to be possibly, probably or definitely related to drug occurred in 1% or more of GERD patients on long-term therapy.

Most Frequent Adverse Events Reported as Drug Related in Long- term Domestic Trials
	% Incidence
Study Event	PROTONIX (n = 536)	Ranitidine (n = 185)
Headache	5	2
Abdominal pain	3	1
Liver function tests abnormal	2	<1
Nausea	2	2
Vomiting	2	2

In addition, in these short and long- term domestic and international trials, the following treatment- emergent events, regardless of causality, occurred at a rate of = 1% in pantoprazole- treated patients: anxiety, arthralgia, asthenia, back pain, bronchitis, chest pain, constipation, cough increased, dizziness, dyspepsia, dyspnea, flu syndrome, gastroenteritis, gastrointestinal disorder, hyperlipemia, hypertonia, infection, liver function tests abnormal, migraine, nausea, neck pain, pain, pharyngitis, rectal disorder, rhinitis, SGPT increased, sinusitis, upper respiratory tract infection, urinary frequency, urinary tract infection, and vomiting.

Additional treatment- emergent adverse experiences occurring in <1% of pantoprazole- treated patients from these trials are listed below by body system. In most instances the relationship to pantoprazole was unclear.

BODY AS A WHOLE : abscess, allergic reaction, chills, cyst, face edema, fever, generalized edema, heat stroke, hernia, laboratory test abnormal, malaise, moniliasis, neoplasm, non-specified drug reaction, photosensitivity reaction.

CARDIOVASCULAR SYSTEM : abnormal electrocardiogram, angina pectoris, arrhythmia, atrial fibrillation/ flutter, cardiovascular disorder, chest pain substernal, congestive heart failure, hemorrhage, hypertension, hypotension, myocardial infarction, myocardial ischemia, palpitation, retinal vascular disorder, syncope, tachycardia, thrombophlebitis, thrombosis, vasodilatation.

DIGESTIVE SYSTEM : anorexia, aphthous stomatitis, cardiospasm, colitis, dry mouth, duodenitis, dysphagia, enteritis, esophageal hemorrhage, esophagitis, gastrointestinal carcinoma, gastrointestinal hemorrhage, gastrointestinal moniliasis, gingivitis, glossitis, halitosis, hematemesis, increased appetite, melena, mouth ulceration, oral moniliasis, periodontal abscess, periodontitis, rectal hemorrhage, stomach ulcer, stomatitis, stools abnormal, tongue discoloration, ulcerative colitis.

ENDOCRINE SYSTEM : diabetes mellitus, glycosuria, goiter.

HEPATO- BILIARY SYSTEM : biliary pain, hyperbilirubinemia, cholecystitis, cholelithiasis, cholestatic jaundice, hepatitis, alkaline phosphatase increased, gamma glutamyl transpeptidase increased, SGOT increased.

HEMIC AND LYMPHATIC SYSTEM : anemia, ecchymosis, eosinophilia, hypochromic anemia, iron deficiency anemia, leukocytosis, leukopenia, thrombocytopenia.

METABOLIC AND NUTRITIONAL : dehydration, edema, gout, peripheral edema, thirst, weight gain, weight loss.

MUSCULOSKELETAL SYSTEM : arthritis, arthrosis, bone disorder, bone pain, bursitis, joint disorder, leg cramps, neck rigidity, myalgia, tenosynovitis.

NERVOUS SYSTEM : abnormal dreams, confusion, convulsion, depression, dry mouth, dysarthria, emotional lability, hallucinations, hyperkinesia, hypesthesia, libido decreased, nervousness, neuralgia, neuritis, neuropathy, paresthesia, reflexes decreased, sleep disorder, somnolence, thinking abnormal, tremor, vertigo.

RESPIRATORY SYSTEM: asthma, epistaxis, hiccup, laryngitis, lung disorder, pneumonia, voice alteration.

SKIN AND APPENDAGES : acne, alopecia, contact dermatitis, dry skin, eczema, fungal dermatitis, hemorrhage, herpes simplex, herpes zoster, lichenoid dermatitis, maculopapular rash, pruritus, skin disorder, skin ulcer, sweating, urticaria. 

SPECIAL SENSES : abnormal vision, amblyopia, cataract specified, deafness, diplopia, ear pain, extraocular palsy, glaucoma, otitis externa, taste perversion, tinnitus.

UROGENITAL SYSTEM : albuminuria, balanitis, breast pain, cystitis, dysmenorrhea, dysuria, epididymitis, hematuria, impotence, kidney calculus, kidney pain, nocturia, prostatic disorder, pyelonephritis, scrotal edema, urethral pain, urethritis, urinary tract disorder, urination impaired, vaginitis.

Postmarketing Reports

There have been spontaneous reports of adverse events with the postmarketing use of Protonix. These reports include the following:

BODY AS A WHOLE : anaphylaxis (including anaphylactic shock), angioedema (Quincke's edema).

DIGESTIVE SYSTEM : increased salivation, nausea, pancreatitis.

HEMIC AND LYMPHATIC SYSTEM : pancytopenia. 

HEPATO-BILIARY SYSTEM : hepatocellular damage leading to jaundice and hepatic failure.

MUSCULOSKELETAL SYSTEM : elevated CPK (creatine phosphokinase), rhabdomyolysis.

NERVOUS SYSTEM : confusion, hypokinesia, speech disorder, vertigo.

SKIN AND APPENDAGES : severe dermatologic reactions, including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis (TEN, some fatal).

SPECIAL SENSES : anterior ischemic optic neuropathy, blurred vision, tinnitus.

UROGENITAL SYSTEM : interstitial nephritis