PANTOCID 40 enteric-coated tablets.
(and dosage form):
PANTOCID 40 enteric-coated tablets.
PANTOCID 40: Each tablet contains 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 tot the active inhibitor, a cyclic sulphonamide, 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
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 of 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 to 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 with impaired liver or renal function
For patients with mild to moderately severe hepatic cirrhosis the elimination half-life values increase from 1 hour to between 7 to 9 hours. The AUC values increase by a factor of 6 to 8, while the maximum serum concentration only increases by a factor of 1,5 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 dialysed.
A slight increase in AUC and Cmax occurs in elderly volunteers compared with younger people.
PANTOCID 40 is indicated for the short-term treatment of duodenal ulcer, gastric ulcer and reflux oesophagitis. If the duodenal ulcer has been demonstrated to be associated with Helicobacter pylori infection, PANTOCID 40 used in combination with appropriate antibiotics may be useful.
PANTOCID 40 is indicated for the treatment of Zollinger-Ellison Syndrome.
Hypersensitivity to pantoprazole.
Safety and efficacy in children has not been established.
Severely impaired liver function. (See Special precautions).
Concomitant intake of food has no influence on the bioavailability.
PANTOCID 40 may reduce or increase the absorption of medicines whose bioavailability is pH-dependent, e.g. ketoconazole.
The active ingredient of PANTOCID 40 is metabolised in the liver via the cytochrome P450 enzyme system. An interaction of PANTOCID 40 with other drugs or compounds which are metabolised using the same enzyme system cannot be excluded.
No clinically significant interactions were, however, observed in specific tests with a number of such drugs or compounds, namely antipyrine, caffeine, carbamazepine, diazepam, diclofenac, digoxin, ethanol, glibenclamide, metoprolol, naproxen, nifedipine, phenytoin, piroxicam, theophylline, warfarin and oral contraceptives.
PREGNANCY AND LACTATION
Safety in pregnancy and during lactation has not been established.
DOSAGE AND DIRECTIONS FOR USE
The recommended once daily dose of PANTOCID 40 should be taken in the morning. PANTOCID 40 should be swallowed whole with a little water either before or during breakfast.
The recommended oral dose is 40 mg of PANTOCID 40 once daily. The total treatment with intravenous and oral pantoprazole should be 2 to 4 weeks. If the duodenal ulcer has been demonstrated to be associated with Helicobacter pylori infection, 40 mg of PANTOCID 40 used in combination with appropriate antibiotics may be useful.
The recommended oral dose is 40 mg of PANTOCID 40 once daily for 4 to 8 weeks.
In the case of a suspected gastric ulcer, malignancy of the gastric ulcer should be excluded, as treatment could conceal the symptoms and may delay diagnosis.
The recommended oral dose is 40 mg of PANTOCID 40 once daily in the morning for 4 to 8 weeks.
For the management of Zollinger-Ellison Syndrome patients should start their treatment with a daily dose of 80 mg of PANTOCID 40. Thereafter, the dose can be titrated up or down, as needed using measurements of gastric acid secretion as a guide. With doses above 80 mg daily, the dose should be divided and given twice daily.
Long-term management and prevention of relapse in Gastro Esophageal Reflux Disease (GERD)
For long-term management a maintenance dose of one 20 mg pantoprazole tablet per day is recommended, increasing to 40 mg PANTOCID 40 per day if a relapse occurs. After healing of the relapse, the dose can be reduced to 20 mg of pantoprazole. Experience with long-term administration is limited.
No dosage adjustment is necessary in the elderly.
Impaired renal and liver function
No dosage adjustment is required in the presence of impaired renal function. A daily dose of 20 mg of pantoprazole should not be exceeded in patients with mild to moderately severe liver impairment (see Pharmacokineticsand Special precautions).
SIDE EFFECTS AND SPECIAL PRECAUTIONS
Very common (10%); common (1% - <10%); uncommon (0,1% - <1%); rare (0,01% - <0,1%) very rare (<0,01%) including isolated cases.
Blood and lymphatic system
Very rare: Leukopenia, thrombocytopenia.
Common: Gastro-intestinal complaints such as upper abdominal pain, diarrhoea, constipation or flatulence.
Uncommon: Nausea, vomiting.
Rare: Dry mouth.
General disorders and administration site conditions
Very rare: Injection site thrombophlebitis and peripheral oedema.
Very rare: Severe hepatocellular damage leading to jaundice with or without hepatic failure.
Immune system disorders
Very rare: Anaphylactic reactions including anaphylactic shock.
Very rare: Increased liver enzymes (transaminases, gamma-GT), elevated triglycerides and increased body temperature.
Musculoskeletal, connective tissue and bone disorders
Very rare: Myalgia.
Nervous system disorders
Uncommon: Dizziness or disturbances in vision (blurred vision).
Very rare: Mental depression.
Renal and urinary system disorders
Very rare: Interstitial nephritis.
Skin and subcutaneous tissue disorders
Uncommon: Allergic reactions such as pruritus, and skin rash.
Very rare: Urticaria, angioedema and severe skin reactions such as Stevens-Johnson Syndrome, erythema multiforme, Lyell Syndrome and photosensitivity.
In patients with severe liver impairment the liver enzymes should be monitored regularly during treatment with PANTOCID 40, particularly on long-term use. In the case of a rise of the liver enzymes PANTOCID 40 should be discontinued. PANTOCID 40 is not indicated for mild gastro-intestinal complaints such as nervous dyspepsia.
Prior to treatment the possibility of malignancy of gastric ulcer or a malignant disease of the oesophagus should be excluded, as the treatment with PANTOCID 40 may alleviate the symptoms of malignant ulcers and can thus delay diagnosis.
Diagnosis of reflux oesophagitis should be confirmed by endoscopy.
Daily treatment with any acid-blocking medicines over a long period of time (e.g. longer than 3 years) may lead to malabsorption of cyanocobalamin caused by hypo- or achlorhydria. Rare cases of cyanocobalamin deficiency under acid-blocking therapy have been reported in the literature. This should be considered when respective clinical symptoms are observed.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
There are no known symptoms of overdosage in man. No specific therapeutic recommendation can be made in cases of overdosage.
PANTOCID 40: Yellow, circular, biconvex, coated tablet imprinted 124on one side and plain on other side.
PANTOCID 40 is available in pack sizes of 30s, 90s and 1000s packed in white smooth round HDPE containers.
Store below 25ºC. Protect form light and moisture.
KEEP OUT OF REACH OF CHILDREN.
NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION
Pharmaplan (Pty) Ltd.
106 16th Road
DATE OF PUBLICATION OF THIS INSERT
1 December 2006
Version: 15 March 2006, submitted May 2006
Source: Pharmaceutical Industry - 2/5/2007
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