Controloc® 40: composition and dosage form
One gastro-resistant tablet contains 40 mg of pantoprazole in the form of pantoprazole sodium sesquihydrate. The medicine also comes in a second strength, 20 mg, and the difference between the two is not cosmetic: 20 mg and 40 mg have different lists of indications, so the figure on the box says nothing about "weaker or stronger" — it says what job the tablet was made for.
The rule for taking it is written on a line of its own and must not be broken: the tablet is neither chewed nor crushed but swallowed whole with water an hour before a meal. The coating is gastro-resistant precisely so that the substance passes through the stomach untouched.
How Controloc® 40 works
Pantoprazole is a substituted benzimidazole. In the acidic environment of the stomach's parietal cells it is converted into its active form and inhibits H+,K+-ATPase, that is, the last link in the production of hydrochloric acid. That is the whole point of it: the medicine switches off not the signal but the executor. Acetylcholine, histamine and gastrin go on giving orders, but there is no one left to carry them out, so pantoprazole works regardless of what has stimulated the secretion of acid.
The degree of inhibition depends on the dose and affects both basal and stimulated secretion, and the result is the same whether the medicine is taken by mouth or given intravenously. In most patients the symptoms are gone within two weeks. There is a reverse side too: the fall in acidity secondarily increases the secretion of gastrin, in proportion to how far the acidity has fallen. That increase is reversible and does not in itself interfere with treatment.
Indications
The 40 mg dose is used where the mucous membrane has to be healed or where too much acid is being produced. In adults and adolescents from 12 years of age — in reflux oesophagitis. In adults — in gastric and/or duodenal ulcer disease, in Zollinger-Ellison syndrome and other conditions associated with excessive secretion of hydrochloric acid, and also for the eradication of Helicobacter pylori in combination with suitable antibiotics, where the ulcer disease was caused by that bacterium.
Everything to do with prevention and with holding on to a result already achieved belongs, in pantoprazole's case, to the 20 mg dose: the symptomatic form of gastro-oesophageal reflux disease, long-term treatment and prevention of relapses of oesophagitis, and protection of the stomach and duodenum in at-risk patients who need to take non-selective anti-inflammatory drugs continuously. Hence the practical conclusion: 40 mg is a course dose, not a dose taken "just in case".
Method of administration and dosage
In reflux oesophagitis 40 mg a day is taken; in individual cases, particularly where there has been no response to other treatment, the dose is doubled to two tablets a day. In gastric and duodenal ulcer disease the dose is the same — one tablet a day, with the same possibility of doubling — and what differs is the length of treatment. Treatment of Zollinger-Ellison syndrome and other conditions with excessive acid secretion begins with 80 mg a day, that is, with two tablets, after which the dose is raised or lowered according to the results of gastric secretion testing; daily doses above 80 mg are divided into two administrations.
| What is being treated | Usual course | If that was not enough |
| Reflux oesophagitis | 40 mg a day, 4 weeks | extended by another 4 weeks; where there was no response to other treatment, the dose is doubled |
| Gastric ulcer | 40 mg a day, 4 weeks | in most cases the course is extended by another 4 weeks for complete healing |
| Duodenal ulcer | 40 mg a day, 2 weeks | it is usually enough to extend the treatment by another 2 weeks |
| H. pylori eradication | 40 mg twice a day with two antibiotics, 7 days | the course can be lengthened by another 7 days, up to two weeks in total |
| Zollinger-Ellison syndrome | 80 mg a day at the start | the dose is fitted to the gastric secretion readings; the duration of treatment is not limited |
There are three eradication regimens, and the choice between them follows the official local guidance on bacterial resistance. To the two tablets a day of the medicine one adds either amoxicillin 1000 mg and clarithromycin 500 mg twice a day, or metronidazole 400-500 mg (or tinidazole 500 mg) and clarithromycin 250-500 mg twice a day, or amoxicillin 1000 mg and metronidazole 400-500 mg (or tinidazole 500 mg) twice a day. The second tablet is taken an hour before the evening meal. The limits by patient group are short: children under 12 are not recommended the medicine because of a lack of data; in severe hepatic impairment the daily dose of pantoprazole must not exceed 20 mg, so the 40 mg tablet is unsuitable for such patients; in eradication regimens the medicine is not used in moderate and severe hepatic impairment or in impaired renal function. Outside eradication regimens neither age nor impaired renal function calls for a change of dose.
Contraindications
There is one formal prohibition: hypersensitivity to pantoprazole, to other substituted benzimidazoles, or to any of the excipients. When the medicine is used within a combination regimen, hypersensitivity to any of the drugs prescribed alongside it is added — that is, to the antibiotics of the eradication regimen.
The list is short, but it is misleading, because the real prohibitions for the 40 mg dose are scattered through other sections of the product information. Severe hepatic impairment limits the daily dose to twenty milligrams and thereby closes the door on this tablet.
Special warnings and precautions
With pantoprazole almost every warning is tied to duration: the longer it is taken, the longer the list of things worth checking becomes. That is exactly why treatment lasting more than a year is in itself grounds for regular medical supervision, even when the patient complains of nothing.
| What may happen | From what point | What is done |
| Severe hypomagnesaemia | in patients who have received proton pump inhibitors for at least 3 months and, in most of the described cases, for longer than a year | magnesium is measured before a long course begins and periodically thereafter, especially where digoxin or diuretics are taken at the same time; in the most severely affected patients, stopping the medicine and replacing magnesium helped |
| Fractures of the hip, wrist and spine | high doses and treatment lasting more than a year, above all in older people and where other risk factors are present | observational studies speak of a 10-40% rise in the overall risk of fracture; patients at risk of osteoporosis are given an adequate intake of vitamin D and calcium |
| Rise in liver enzyme activity | in severe hepatic impairment, particularly with prolonged use | enzyme activity is monitored regularly and, if it rises, treatment is stopped |
Two situations stand apart, unrelated to duration. The first is cancer alertness: marked unintentional weight loss, repeated vomiting, difficulty swallowing, vomiting of blood, anaemia and tarry stools, as well as a suspected gastric ulcer, require a tumour to be ruled out, because pantoprazole softens the symptoms and can delay the diagnosis; if the complaints persist despite treatment, the investigation is repeated. The second is atazanavir: the combination with proton pump inhibitors is not recommended and, if the doctor nonetheless considers it necessary, careful clinical monitoring extending to measurement of the viral load is needed, along with raising the atazanavir dose to 400 mg together with 100 mg of ritonavir and limiting pantoprazole to twenty milligrams a day.
Interaction with other medicines
Pantoprazole has a short list of real interactions and a long list of apparent ones. The real ones rest on a single property: by lowering acidity persistently, the medicine changes the absorption of those drugs whose bioavailability depends on the acidity of the stomach contents.
- the antifungal azoles — ketoconazole, itraconazole, posaconazole — and drugs such as erlotinib: their absorption may fall, and with it their effect;
- atazanavir and other HIV medicines whose absorption depends on acidity: their bioavailability may be reduced substantially, which is why the combination with proton pump inhibitors is not recommended;
- the coumarin anticoagulants, phenprocoumon and warfarin: no pharmacokinetic interaction was found in studies, but after the medicine reached the market the international normalised ratio changed in isolated cases;
- hence the rule for these patients: prothrombin time and INR are monitored after pantoprazole is started, after it is finished, and where its use is irregular.
The apparent interactions are noticeably more numerous, and it is useful to know them so as not to withdraw needed medicines for nothing. Pantoprazole is extensively metabolised by the liver through cytochrome P-450 — chiefly by demethylation via CYP2C19 and additionally by oxidation via CYP3A4 — but testing against drugs that travel the same routes found no clinically relevant interactions: not with carbamazepine and diazepam, not with glibenclamide and nifedipine, and not with oral contraceptives containing levonorgestrel and ethinylestradiol. The P-glycoprotein-dependent absorption of digoxin is not disturbed by pantoprazole, and no interactions have been found with antacids or with the antibiotics of the eradication regimens — clarithromycin, metronidazole and amoxicillin.
Pregnancy and breastfeeding
Everything here rests on three facts, and not one of them gives a clear answer. There is too little experience of use in pregnant women to draw conclusions. In animals pantoprazole had a harmful effect on reproduction. How far that result carries over to humans is unknown. Hence the cautious wording: pregnancy does not forbid the medicine, but it requires absolute necessity — a situation in which treatment cannot be done without.
With breastfeeding the position is different: the passage of pantoprazole into milk has been confirmed both in animals and in women, so the question is put as a choice between two things. The doctor and the patient decide what to stop — breastfeeding or the treatment — weighing the benefit of feeding for the child against the benefit of therapy for the mother.
Adverse effects
Adverse reactions occur in about 5% of patients. The commonest — in around 1% — are diarrhoea and headache. The uncommon ones include dizziness, sleep disturbance, nausea and vomiting, constipation, bloating and a feeling of abdominal fullness, dry mouth, pain and discomfort in the upper abdomen, skin rash, eczema and itching, weakness, tiredness and malaise, raised liver enzyme activity, and also fractures of the hip, wrist or spine.
Among the rare and very rare reactions, the ones that deserve attention are those that do not announce themselves through the usual complaints. From the blood these are agranulocytosis, classed as uncommon, and also thrombocytopenia, leucopenia and pancytopenia. From the liver — a rise in bilirubin and, with unknown frequency, damage to liver cells, jaundice and hepatic failure. From the skin — urticaria and angioedema, and also severe reactions of unknown frequency: Stevens-Johnson syndrome, Lyell's syndrome, erythema multiforme and photosensitivity.
Overdose
The overdose section is unusual for this medicine, because there is almost nothing to describe in it: no symptoms of overdose are known in humans. Even the intravenous administration of 240 mg over two minutes was well tolerated — an amount equal to six daily doses of the tablet.
There are two practical consequences. Pantoprazole binds to plasma proteins to a considerable degree, so it is poorly removed by dialysis. And there are simply no specific therapeutic recommendations for an overdose with clinical signs of poisoning: treatment remains symptomatic and supportive, and what is done is decided by the patient's condition.
How to get a prescription for Controloc® 40 online
The 40 mg dose is a course dose with a clear deadline: four weeks in oesophagitis and gastric ulcer, two in duodenal ulcer, seven days in eradication. That is why what matters to the doctor is not only what is troubling you but also what it has been confirmed by and how long you have already been taking a proton pump inhibitor. On e-zdrowie.com you fill in a medical questionnaire, the doctor reviews the answers and, if the medicine is suitable, issues an electronic prescription: the code arrives by message, and any Polish pharmacy will dispense the tablets against it.
Begin the questionnaire with the diagnosis and the tests: whether you have had a gastroscopy, whether Helicobacter pylori was confirmed and when, whether there is a report of an ulcer or of oesophagitis. Report liver and kidney disease: in severe hepatic impairment the daily dose is limited to 20 mg, and for eradication both moderate hepatic impairment and impaired renal function become obstacles. Name the medicines you take continuously: atazanavir and other HIV drugs, antifungal azoles, erlotinib, warfarin or phenprocoumon, digoxin and diuretics. And state how many months or years you have been taking proton pump inhibitors: after a year the doctor adds supervision, magnesium monitoring and attention to vitamin D and calcium intake to the prescription.
