Prolex

Uses

Prolex is used where suppression of acid secretion is of therapeutic benefit. Prolex Is registered in the foltawing indications:

• Peptic ulcer diseases (PUD)
• Gastro-esophageal reflux diseases
• Treatment of ulcer resistant to M2 blocker
• Treatment of ulcer induced by NSAIDs
• Gl bleeding from stress or acid peptic diseases
• Eradication of Helicobacter pylori
• Zollinger-Ellison syndrome
• Prophylaxis for acid aspiration syndrome during induction of anesthesia

Prolex is also used to associated treatment for these conditions: Erosive Esophagitis, GERD With Erosive Esophagitis, Gastro-esophageal Reflux Disease (GERD), Healing, Heartburn, Helicobacter Pylori Infection, Stress Ulcers, Zollinger-Ellison Syndrome, Conditions where a reduction of gastric acid secretion is required, Pathological hypersecretory conditions

How Prolex works

Hydrochloric acid (HCl) secretion into the gastric lumen is a process regulated mainly by the H(+)/K(+)-ATPase of the proton pump, expressed in high quantities by the parietal cells of the stomach. ATPase is an enzyme on the parietal cell membrane that facilitates hydrogen and potassium exchange through the cell, which normally results in the extrusion of potassium and formation of HCl (gastric acid).

Proton pump inhibitors such as pantoprazole are substituted benzimidazole derivatives, weak bases, which accumulate in the acidic space of the parietal cell before being converted in the canaliculi (small canal) of the gastric parietal cell, an acidic environment, to active sulfenamide derivatives. This active form then makes disulfide bonds with important cysteines on the gastric acid pump, inhibiting its function. Specifically, pantoprazole binds to the sulfhydryl group of H+, K+-ATPase, which is an enzyme implicated in accelerating the final step in the acid secretion pathway. The enzyme is inactivated, inhibiting gastric acid secretion. The inhibition of gastric acid secretion is stronger with proton pump inhibitors such as pantoprazole and lasts longer than with the H(2) antagonists.

Dosage

Prolex dosage

Tablet:

The usual recommended adult oral dose is 40 mg given once daily, preferably in the morning with or without food. The duration of therapy is ranging from 2-8 weeks.

• Duodenal ulcers: Prolex 40 mg tablet once daily for 2-4 weeks.
• Gastric ulcer: Prolex 40 mg tablet once daily for 4-8 weeks.
• Reflux esophagitis: Prolex 40 mg tabletonce daily for 4-8 weeks.
• Ulcers induced by NSAIDs: Prolex 40 mg tablet once daily.
• Maintenance therapy: Maintenance therapy should involve the lowest effective dose of the drug. Prolex both 20 mg & 40 mg doses are safe and effective in maintaining patients with healed reflux esophagitis and PUD in remission.

IV Injection:

• Duodenal ulcer and gastric ulcer:40 mg once daily for 7-10 days
• Gastroesophageal reflux disease associatedwith a history of erosive esophagitis:40 mg once daily for 7-10 days
• Prevention of rebleeding in peptic ulcer:IV 80 mg, followed by 8 mg/hour infusion for 72 hours
• Prophylaxis of acid aspiration:80 mg IV every 12 h for 24 h, followed by 40mg every 12 h
• Long-term management of Zollinger-Ellison Syndrome and other pathological hypersecretory conditions: 80 mg IV every 12 hours, may increase to 80 mg every 8 hoursif needed, may titrate to higher doses depending on acid output.

DIRECTION FOR USE OF IV INJECTION: Prolex lyophilized powder and 0.9% Sodium Chloride Injection is for intravenous administration only and must not be given by any other route. Prolex IV injection should be given as a slow intravenous injection. The solution for IV injection is obtained by adding 10 ml 0.9% Sodium Chloride Injection to the vial containing powder. After reconstitution the injection should be given slowly over a period of at least 2 to 5 minutes. Use only freshly prepared solution. The reconstituted solution may be stored at room temperature (up to 30° C) for a maximum 4 hours.

DIRECTION FOR USE OF IV INFUSION: Prolex IV infusion should be given as an intravenous infusion over a period of approximately 15 minutes. Prolex IV infusion should be reconstituted with 10 ml of 0.9% Sodium Chloride Injection and further diluted (admixed) with 0.9% Sodium Chloride Injection or 5% Dextrose or Lactated Ringer's Injection to a final volume of 100 ml. The reconstituted solution may be stored at room temperature (up to 30° C) for a maximum 4 hours prior to further dilution. The admixed solution may be stored at room temperature (up to 30° C) and must be used within 24 hours from the time of initial reconstitution.

Side Effects

No potentially life-threatening effects have been reported with Prolex. Symptomatic adverse effects include headache and diarrhoea are two common reported adverse effects. Peripheral edema has been occasionally reported in female patients. Other side effects may include abdominal pain, dizziness, nausea, epigastric discomfort, flatulence, skin rash, pruritus etc.

Toxicity

Rat Oral LD 50 747 mg/kg

Tumorigenicity

Because of the chronic nature of GERD, there may be a potential for long-term administration of pantoprazole. In long-term rodent studies, pantoprazole was carcinogenic and its administration lead to rare types of gastrointestinal tumors. The relevance of these findings to tumor development in humans is unknown at this time.

Teratogenic Effects

This drug falls under pregnancy category B category. Reproduction studies have been performed in rats at oral doses up to 88 times the recommended human dose (RHD), as well as in rabbits at oral doses up to 16 times the RHD, and have shown no evidence of impaired fertility or harm to the fetus caused by pantoprazole. No adequate and well-controlled studies in pregnant women have been completed. Because animal reproduction studies are not always predictive of human response, this drug should only be used during pregnancy if clearly required.

Nursing Mothers

Prolex and its metabolites have been found to be excreted in the milk of rats. Prolex excretion in human milk has been found in a study performed with a single nursing mother after one 40 mg oral dose. The clinical relevance of this finding is not known, however, it is advisable to take note of this finding when considering pantoprazole use during nursing. Many drugs excreted in human breastmilk have a risk for serious adverse effects in nursing infants.

Precaution

Patients should be cautioned that Prolex tablet should not be split, crushed or chewed. The tablet should be swallowed whole, with or without food in the stomach. Concomitant administration of antacid does not affect the absorption of Prolex.

Interaction

There is no interaction with concomitantly administered antacids. No dosage adjustment is needed with combination use of the following drugs: Theophylline, Caffeine, Diazepam, Digoxin, Ethanol, Metoprolol, Nifedipine or Warfarin.

Food Interaction

• Take with or without food. The absorption is unaffected by food.

Prolex Drug Interaction

Moderate: atorvastatin, clopidogrel, levothyroxineMinor: aspirin, aspirin, duloxetine, cyanocobalaminUnknown: rosuvastatin, apixaban, omega-3 polyunsaturated fatty acids, pregabalin, metoprolol, metoprolol, albuterol, budesonide / formoterol, acetaminophen, ascorbic acid, cholecalciferol, alprazolam, cetirizine

Prolex Disease Interaction

Major: C. diffModerate: liver disease, bone fractures, hypomagnesemia

Volume of Distribution

The apparent volume of distribution of pantoprazole is approximately 11.0-23.6 L, distributing mainly in the extracellular fluid.

Elimination Route

Prolex is absorbed after oral administration as an enteric-coated tablet with maximum plasma concentrations attained within 2 – 3 hours and a bioavailability of 77% that does not change with multiple dosing . Following an oral dose of 40mg, the Cmax is approximately 2.5 μg/mL with a tmax of 2 to 3 hours. The AUC is approximately 5 μg.h/mL. There is no food effect on AUC (bioavailability) and Cmax.

Delayed-release tablets are prepared as enteric-coated tablets so that absorption of pantoprazole begins only after the tablet leaves the stomach.

Half Life

About 1 hour

Clearance

Adults: With intravenous administration of pantoprazole to extensive metabolizers, total clearance is 7.6-14.0 L/h. In a population pharmacokinetic analysis, the total clearance increased with increasing body weight in a non-linear fashion.

Children: clearance values in the children 1 to 5 years old with endoscopically proven GERD had a median value of 2.4 L/h.

Elimination Route

After a single oral or intravenous (IV) dose of 14C-labeled pantoprazole to healthy, normal metabolizing subjects, about 71% of the dose was excreted in the urine, with 18% excreted in the feces by biliary excretion. There was no kidney excretion of unchanged pantoprazole.

Pregnancy & Breastfeeding use

There are no adequate or well-controlled studies in pregnant women. Prolex should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether Prolex is excreted in human breast milk. Prolex should be used during lactation only if the potential benefit justifies the potential risk.

Contraindication

It is contraindicated in patients with known hypersensitivity to Prolex.

Acute Overdose

There are no known symptoms of overdosage in humans. Since Prolex is highly protein bound, it is not readily dialyzable. Apart from symptomatic and supportive management, no specific therapy is recommended.

Storage Condition

Store in a cool, dry place and away from light. Keep out of the reach of children.

Innovators Monograph

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