CONTROLOC ® 20 (Enteric-coated tablets)
® 40 (Enteric-coated tablets)

® 20
Each tablet contains 22,6 mg pantoprazole sodium sesquihydrate equivalent to 20 mg
® 40
Each tablet contains 45,1 mg pantoprazole sodium sesquihydrate equivalent to 40 mg pantoprazole.

A.11.4.3 Medicines acting on the gastro-intestinal tract.

Site and mechanism of action
Pantoprazole is a proton pump inhibitor, i.e., it inhibits specifically and dose proportionally H+,K+ -ATPase, the enzyme which is responsible for gastric acid secretion in the parietal cells of the stomach.
Pantoprazole is a substituted benzimidazole which accumulates in the acidic compartment of the parietal cells after absorption. In the parietal cell it is protonated and chemically re-arranged to the active inhibitor, a cyclic sulphenamide, which binds to the H+,K+-ATPase, thus inhibiting the proton pump and causing suppression of stimulated and basal gastric acid secretion after single and multiple intravenous and oral pantoprazole dosing. Because pantoprazole acts distal to the receptor level, it can influence gastric acid secretion irrespective of the nature of the stimulus.
Pantoprazole exerts its full effect in a strongly acidic environment (pH<3) and remains mostly inactive at higher pH values, which explains its selectivity for the acid secreting parietal cells of the stomach. Therefore, the complete pharmacological and therapeutic effect for pantoprazole can only be achieved in the acid-secreting parietal cells. By means of a feedback mechanism this effect is diminished at the same rate as acid secretion is inhibited.
Effect on gastric acid secretion
The mean inhibition of pentagastrin stimulated acid output after 40 mg/day is 85% after seven days, 2½ to 3½ hours after dosing. After stopping the intake of pantoprazole, there is no evidence of rebound hypersecretion and 7 days after taking the last dose, the acid output is normal.
Pantoprazole maintains the physiological pH-rhythm. The values, however, are shifted to higher levels. During the night, periods with pH values approximating placebo have been found. Although pantoprazole has a half-life of approximately 1 hour, the antisecretory effect increases during repeated once daily administration, demonstrating that the duration of action markedly exceeds the serum elimination half-life.
Absorption and distribution
Pantoprazole is unstable in acid and is administered orally in the form of an enteric-coated tablet. Absorption takes place in the small intestine. On average, the maximum serum/plasma concentrations are approximately 2 to 3 micrograms/mL about 2½ hours after administration of 40 mg pantoprazole daily, as a single or multiple dose in healthy volunteers. The absolute systemic bioavailability of pantoprazole from single and multiple oral doses of pantoprazole is approximately 77%.
Following intravenous administration pantoprazole serum/plasma concentrations decline biexponentially. The terminal half-life (t½) is about 1 hour. The total serum clearance is approximately 0,1 L/h/kg and the volume of distribution is about 0,15 L/kg respectively.
The plasma kinetics for pantoprazole after both oral and intravenous administration are linear over the dose range 10-80 mg.
Pantoprazole is almost exclusively metabolised in the liver. The main metabolite is desmethylpantoprazole which is conjugated with sulphate.
Renal elimination represents the most important route of excretion (approximately 80%) for the metabolites of pantoprazole. The balance is excreted with the faeces. The half-life of the main metabolite is approximately 1½ hours which is slightly longer than that of pantoprazole.
Pharmacokinetic profile in patients
In subpopulations of subjects suffering from mild to moderately severe liver cirrhosis, the half-life increases from 1 hour to between 7 to 9 hours. The AUC values are increased by a factor of 6 to 8, while the maximum serum concentration increases by a factor of only 1½ in comparison with healthy subjects.
In patients with renal impairment the half-life of the main metabolite is moderately increased but there is no accumulation at therapeutic doses. The half-life of pantoprazole in patients with renal impairment is comparable to the half-life of pantoprazole in healthy subjects. Pantoprazole is poorly dialysable. A slight increase in AUC and C
max occurs in elderly volunteers compared with younger people.
Concomitant intake of food has no influence on the bioavailability.
Pantoprazole may reduce or increase the absorption of drugs whose bioavailibility is pH-dependant e.g. ketokonazole.
Studies in humans reveal no interaction with the cytochrome P450-system of the liver. There was no induction of the cytochrome P450-system after chronic administration as shown with marker antipyrine and no interactions were observed after concomitant administration of pantoprazole with either antipyrine, diazepam, theophylline, digoxin, oral contraceptives, phenytoin, nifedipine, carbamazepine, diclofenac, metoprolol, glibenclamide, ethanol, and caffeine. Concomitant administration of warfarin or phenprocoumon has no influence on its effect on coagulation factors.
Antacids do not interact with pantoprazole.

®40 is indicated for the short-term treatment of duodenal ulcer, gastric ulcer and reflux esophagitis. If the duodenal ulcer has been demonstrated to be associated with Helicobacter pylori infection, CONTROLOC®40 used in combination with appropriate antibiotics may be useful.
®20 is indicated for the symptomatic improvement (e.g. heartburn, acid regurgitation, pain on swallowing) and healing of mild gastro-esophageal reflux disease (GERD).
®20 is indicated for long-term management and prevention of relapse in gastro-esophageal reflux disease (GERD).

Hypersensitivity to pantoprazole.
Safety in pregnancy and during lactation has not been established.
Safety and efficacy in children have not been established.
Severely impaired liver function.