Toprazole tablets- for H.pylori& hyperacidity

Toprazole is a drug that contains pantoprazole (this substance belongs to a class of drugs called proton pump inhibitors.), Which are used to treat reflux, heartburn and stomach ulcers, and it is superior to ranitidine (150 mg twice a day), and it is important to take each dose of Toprazole with at least one full glass of water (200 milliliters of water), you should also continue to use it for the entire period prescribed by your doctor, even if your condition improves and you no longer feel any symptoms.

Toprazole

What is Toprazole?

  • Toprazole is a drug that is produced as Enteric Coated Tablet. Each tablet contains pantoprazole as an active ingredient, and its concentration is 40 mg per tablet.
  • Toprazole, produced by Tabuk Pharma-KSA.
  • this drug is a prescription drug.

Why is Toprazole prescribed?

Toprazole  is a drug that works to reduce stomach acidity, and doctors usually prescribe this medicine in patients with any of the following conditions:

  • Treatment or prevention of stomach ulcers caused by infection with H.pylori , in combination with appropriate antibiotic therapy.
  • Treatment or prevention of stomach ulcers caused by the use of analgesics, in patients at risk, with the need for continuous treatment of NSAIDs.
  • Esophageal muscle reflux disease (GERD disease: a disease characterized by heartburn and burning that causes erosion in the esophageal muscle wall if not treated).
  • In diseases where gastric acid secretions increase, such as some digestive system tumors such as Zollinger-Ellison’s disease.

PREGNANCY AND LACTATION

Pregnancy

There are no adequate data from the use of pantoprazole in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown. Pantoprazole should not be used during pregnancy unless clearly necessary.

Lactation

Excretion into human milk has been reported. Therefore a decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with Pantoprazole should be made taking into account the benefit of breast-feeding to the child and the benefit of Pantoprazole therapy to women.

What is the dose of Toprazole ?

Your dose, form (concentration) of your medication, and how often you take the medicine, depend on:

  • Your age.
  • The condition being treated.
  • How severe your condition is.
  • Your other medical conditions.
  • How do you react to the first dose.

The following is the recommended dosage for adults and adolescents aged 12 years and over (Toprazole less than 12 years old is not recommended):

  • Dosage for reflux esophagitis: once daily per day before eating, for 4 weeks.
  • Eradication of H.pylori: twice daily before eating for two weeks.
  • For stomach ulcers: once daily  before eating, for 4-8 weeks.
  • For the treatment of duodenal ulcer: once daily, before eating, for 2-4 weeks.
  • Zollinger-Ellison disease treatment: twice daily  before eating and for an indefinite period.

For-Arabic-Information

Toprazole -Arabic-Information

Special populations

Children below 12 years of age

Toprazole is not recommended for use in children below 12 years of age due to limited data in this age group.

Hepatic Impairment

A daily dose of 20 mg pantoprazole should not be exceeded in patients with severe liver impairment. Pantoprazole must not be used in combination treatment for eradication of H.pylori in patients with moderate to severe hepatic dysfunction since currently no data are available on the efficacy and safety of Pantoprazole in combination treatment of these patients.

Renal impairment

No dose adjustment is necessary in patients with impaired renal function.

Dosage in impaired renal patients and elderly

Toprazole must not be used in combination treatment for eradication of H.pylori in patients with impaired renal dysfunction since currently no data are available on the efficacy and safety of Pantoprazole in combination treatment of these patients.

Elderly

No dose adjustment is necessary in elderly patients.

CONTRAINDICATIONS

Hypersensitivity to the active substance, substituted benzimidazoles, or to any of the excipients

SPECIAL WARNINGS AND PRECAUTIONS FOR USE

Hepatic Impairment

In patients with severe liver impairment, the liver enzymes should be monitored regularly during therapy, particularly on long-term use. In the case of a rise of the liver enzymes, the treatment should be discontinued.

Co-administration with NSAlDs

The use of Toprazole 40 mg as a preventive of gastro-duodenal ulcers induced by non-selective non-steroidal anti-inflammatory drugs (NSAIDs) should be restricted to patients who require continued NSAID treatment and have an increased risk to develop gastrointestinal complications .The increased risk should be assessed according to individual risk factors, e.g. high age(  ≥ 65 years ) , history of gastric or duodenal ulcer or upper gastrointestinal bleeding.

In presence of alarm symptoms

  • In the presence of any alarm symptom e.g. significant unintentional weight loss, recurrent vomiting, dysphagia, hematemesis, anemia or melena) and when gastric ulcer is suspected or present, malignancy should be excluded, as treatment with pantoprazole may alleviate symptoms and delay diagnosis.
  • Further investigation is to be considered if symptoms persist despite adequate treatment.

Co-administration with atazanavir

Co-administration of atazanavir with proton pump inhibitors is not recommended. If the combination of atazanavir with a proton pump inhibitor is judged unavoidable , close clinical monitoring (e.g. virus load) is recommended in combination with an increase in the dose of atazanavir to 400 mg with 100 mg of ritonavir . A pantoprazole dose of 20 mg per day should not be exceeded.

Influence on vitamin B12 absorption

Pantoprazole, as all acid-blocking medicines, may reduce the absorption of vitamin B12 (cyanocobalamin ) due to  hypo- or achlorhydria. This should be considered in patients with reduced body stores or risk factors for reduced vitamin B12 absorption on long-term therapy or if respective clinical symptoms are observed.

Long term treatment

In long-term treatment, especially when exceeding a treatment period of 1 year , patient should be kept under regular surveillance .

Gastrointestinal infections caused by bacteria

Pantoprazole, like all proton pump inhibitors ( PPIs ), might  be expected to increase the counts of bacteria normally present in the upper gastrointestinal tract. Treatment with the  Pantoprazole may lead to a slightly increased risk of gastrointestinal infections caused by bacteria such as Salmonella and Campylobacter.

Bone Fracture

“Several published observational studies suggest that proton pump inhibitor (PPI) therapy may be associated with an’ increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to the established treatment guidelines:’

Hypomagnesaemia

  • Prescription proton pump inhibitor (PP I) drugs may cause low’ serum magnesium levels (hypomagnesaemia) if taken for’ prolonged periods of time (in most cases, longer than one year), magnesium supplementation alone did not improve’ low serum magnesium levels and the PPI had to be’ discontinued,
  • Low serum magnesium levels can result in serious adverse events including muscle spasm (tetany), irregular heartbeat, (arrhythmias), and convulsions (seizures); however, patients do not always have these symptoms. Treatment of Hypomagnesaemia generally requires magnesium supplements.
  • Treatment in patients taking a PPI and who have hypomagnesaemia may also require stopping the PPI.
  • For patients expected to be on prolonged treatment or who take PPls with digoxin or drugs that may cause hypomagnesaemia (e.g. diuretics), health care professionals should consider measuring magnesium levels before starting PPI treatment and periodically during treatment.

INTERACTION WITH OTHER MEDICINAL PRODUCTS 

Effect of pantoprazole(Toprazole) on the absorption of other medicinal product because of profound and long lasting inhibition of gastric acid secretion, pantoprazole . may reduce the absorption of drugs with a’ gastric pH dependent bioavailability  e.g. some azole antifungals as ketoconazole, itraconazole, posaconazole and other medicine as erlotinib.

HIV medications (atazanavir)

Co-administration of atazanavir and other HIV medications whose absorption is PH-dependent with proton-pump inhibitors might result in a substantial reduction in the bioavailability  of these HIV medications and might impact the efficacy of these medicines. Therefore, the co-administration of proton pump inhibitors with atazanavir is not recommended.

Coumarin anticoagulants (phenprocoumon or warfarin)

Although no interaction during concomitant administration of phenprocoumon or warfarin has been observed in clinical pharmacokinetic studies, a few isolated cases of changes in International Normalised Ratio (INR) have been reported during concomitant treatment in the post-marketing period. Therefore, in patients treated with coumarin anticoagulants (e.g. phenprocoumon or warfarin), monitoring of  prothrombin time / INR is recommended after initiation, termination or during irregular use of pantoprazole.

Methotrexate

  • Use caution when administering high-dose methotrexate to patients receiving proton pump inhibitor (PPI) therapy.
  • Case reports and published population pharmacokinetic studies suggest  that concomitant use of some PPls, such omeprazole , esomeprazole and pantoprazole with  methotrexate (primarily at high dose), may elevate an prolong serum levels of methotrexate and/or its metabolite hydroxy methotrexate , possibly leading to methotrexate toxicities .
  • In two of these cases, delayed methotrexate elimination was observed when high-dose methotrexate was co-administered with PPls, but was not observed when methotrexate was co-administered with ranitidine. However, no formal drug interaction studies of methotrexate with ranitidine have been conducted.

Other interactions studies

  • Pantoprazole is extensively metabolized in the liver via the cytochrome P450 enzyme system. The main metabolic pathway is demethylation by CYP2C19 and other metabolic pathways include oxidation by CYP3A4.
  • Interaction studies with drugs also metabolized with these pathways, like carbamazepine, diazepam, glibenclamide, nifedipine, and an oral contraceptive containing levonorgestrel and ethinyl oestradiol did not reveal clinically significant interactions.
  • Results from a range of interaction studies demonstrate that pantoprazole does not effect the metabolism of active substances metabolised by CYP1 A2 (such as caffeine, theophylline), CYP2C9 (such as piroxicam, diclofenac, naproxen), CYP206 (such as metoprolol), CYP2E1 (such as ethanol) or does not interfere with p-glycoprotein related absorption of digoxin.
  • There were no interactions with concomitantly administered antacids.
  • Interaction studies have also been performed administering pantoprazole concomitantly with the respective antibiotics (clarithromycin, metronidazole, amoxicillin). No clinically relevant interactions were found.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES

Adverse drug reactions such as dizziness and visual disturbances may occur. If affected, patients should not drive or operate machines.

UNDESIRABLE EFFECTS

Approximately 5% of patients can be expected to experience adverse drug reactions (ADRs). The most commonly reported ADRs are diarrhea and headache, both occurring in approximately 1%  of patients.

 lists adverse reactions reported with pantoprazole, ranked under the following frequency classification: Very common (“1/10); common (1/100 to <1/10); uncommon (“1/1,000 to <1/100); rare (“1/10,000 to≤111,000) ; very rare (≤1/10,000), not known (cannot be estimated from the available data).

For all adverse reactions reported from post-marketing experience, it is not possible to apply any Adverse Reaction frequency and therefore they are mentioned with a “not known” frequency.

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Blood and lymphatic system ADRs

  • Agranulocytosis  ( rare ).
  • Thrombocytopenia ; leucopenia ; pancytopenia ( very rare ) .

Immune system ADRs

Hypersensitivity ( including anaphylactic reactions and anaphylactic shock ) – rare .

Metabolism and nutrition disorders

Hyperlipidaemia and lipid increases ( triglycerides, cholesterol ) ; weight changes – rare .

Psychiatric disorder

  • Sleep disorder ( uncommon ) .
  • Depression ( and all aggravations ) – rare .
  • Disorientation ( and all aggravations ) – very rare .
  • Hallucination ; confusion ( especially in pre- disposed patients , as well as the aggravation of these symptoms in case of pre-existence ) .

Nervous system disorder

  • Headache ; dizziness ( uncommon ) .
  • Taste disorder ( rare ).

Eye disorders

  • Disturbance in vision / blurred vision ( rare ) .

Gastrointestinal disorders

  • Diarrahea ; nausea / vomiting , abdominal distension and bloating ; constipation ; dry mouth ; abdominal pain and discomfort ( uncommon ) .

Hepatopbiliar disorders

  • Liver enzymes increased ( transaminases , gama – GT ) – UNCOMMON .
  • Bilirubin increased ( rare ) .

Skin and subcutaneous tissue disorders

  • Rash / exanthema / eruption ; pruritus ( uncommon ) .
  • Urticaria ; angioedema ( rare ) .
  • Stevens Johnson syndrome ; lyell syndrome ; Erythema multiforme ; photosensitivity ( not known ) .

Musculoskeletal and connective tissue disorders

  • Fracture of the hip , wrist or spine ( uncommon ) .
  • Arthralgia ; myalgia ( rare ) .

Renal and urinary disorders

  • Interstitial nephritis (  not known ) .

Reproductive system and breast disorders

  • Gynaecomastia ( rare ) .

General disorders and administration site conditions

  • Asthenia , fatigue and malasia  ( uncommon ) .

POST MARKETING REPORTS

  • Musculoskeletal : bone fracture .

OVERDOSE

There are no known symptoms of over-dosage in man. Doses up to 240 mg administered intravenously over two minutes were well tolerated. As pantoprazole is extensively protein bound, it is not readily dialyzable.

In the case of overdose with clinical signs of intoxication, apart from symptomatic and supportive treatment, no specific therapeutic recommendations can be made.