Active ingredients: Rabeprazole (Rabeprazole sodium)
Pariet 10 mg gastro-resistant tablets
Pariet 20 mg gastro-resistant tablets
Indications Why is Pariet used? What is it for?
Pariet tablets contain rabeprazole sodium as the active ingredient. This active substance belongs to a class of medicines called Proton Pump Inhibitors (PPIs). They work by decreasing the amount of acid your stomach produces.
Pariet tablets are used for the treatment of the following diseases:
- "Gastroesophageal reflux disease" (GERD), which can include heartburn. Gastroesophageal reflux disease occurs when acid and food passes from the stomach to the esophagus.
- Stomach ulcer or upper intestine ulcer. If these ulcers are infected with a bacterium called Helicobacter pylori (H. Pylori), you will also be prescribed antibiotics. Using Pariet tablets together with antibiotics allows the infection to be cleared. and healing of the ulcer. In addition, the therapy stops the infection and prevents the ulcer from returning.
- Zollinger-Ellison syndrome, when the stomach produces an extremely high amount of acid.
Contraindications When Pariet should not be used
Do not take Pariet
- If you are allergic (hypersensitive) to rabeprazole sodium or any of the other ingredients of Pariet.
- If you are or think you are pregnant.
- If you are breastfeeding.
Do not take Pariet if any of the above conditions apply to you. If you have any further questions, ask your doctor or pharmacist before taking Pariet tablets.
See also the section on Pregnancy and Lactation.
Precautions for use What you need to know before taking Pariet
Children
The use of Pariet is not recommended in children.
If you take a proton pump inhibitor such as PARIET, especially for longer than one year, you may have a slightly increased risk of fracture of the hip, wrist or spine. If you have osteoporosis or are taking corticosteroids (which may increase the risk of osteoporosis) consult your doctor.
Take special care with Pariet
Check with your doctor or pharmacist before taking Pariet:
- if you are allergic to other proton pump inhibitors or "imidazole substitutes"
- if you have liver or blood problems; these problems occurred in some patients and resolved upon discontinuation of Pariet treatment
- if you have been diagnosed with stomach cancer
- if you have ever had liver disease
- if you are taking atazanavir, for HIV infections
If you are unsure whether any of the above conditions may apply to you as well, talk to your doctor or pharmacist before taking Pariet tablets.
If you have severe diarrhea (watery or bloody) with symptoms such as fever, abdominal pain or tenderness, stop taking Pariet and contact your doctor.
Interactions Which drugs or foods can modify the effect of Pariet
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription or herbal products.
In particular, tell your doctor or pharmacist if you are taking any of the following medicines:
- Ketoconazole or itraconazole - used to treat fungal infections. Pariet may decrease the amount of these medicines in the blood. Your doctor may find it appropriate to change the dosage.
- Atazanavir - used to treat HIV infections. Pariet may decrease the amount of this medicine in the blood and should not be used together.
If you are unsure whether any of the above conditions may apply to you as well, talk to your doctor or pharmacist before taking Pariet tablets.
Warnings It is important to know that:
Pregnancy and breastfeeding
- Do not use Pariet if you are pregnant or think you are pregnant.
- Do not use Pariet if you are breastfeeding or planning to breastfeed.
Ask your doctor or pharmacist for advice before taking any medicine during pregnancy or breastfeeding.
Driving and using machines
You may feel sleepy while taking Pariet. If this happens, do not drive or use any tools or machines.
Dose, Method and Time of Administration How to use Pariet: Posology
Always take Pariet exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.
Assumption of Pariet
- Remove the tablet from the blister just before taking.
- Swallow the tablet whole with a glass of water. Do not chew or crush the tablets.
- Your doctor will give you information on how many tablets to take and for how long. This will depend on your condition.
- If you take this medicine for a long time, your doctor will need to monitor you.
Adults and Elderly
"Gastroesophageal reflux disease" (GERD)
Treatment of moderate to severe symptoms (symptomatic GERD)
- The recommended dose is 1 Pariet 10 mg tablet once a day for four weeks.
- Take the tablet in the morning before breakfast.
- If the symptoms recur after 4 weeks of treatment, your doctor may decide to continue treatment with 1 tablet of Pariet 10 mg for as long as he deems necessary.
Treatment of more severe symptoms (erosive or ulcerative GERD)
- The recommended dose is 1 Pariet 20 mg tablet once a day for 4-8 weeks.
- Take the tablet in the morning before breakfast.
Long-term symptom treatment (GERD maintenance therapy)
- The recommended dose is 1 tablet of Pariet 10 mg or 20 mg once a day for the time indicated by your doctor.
- Take the tablet in the morning before breakfast.
- Your doctor will want to review you at regular intervals to evaluate your symptoms and dosage.
Treatment of stomach ulcer (peptic ulcer)
- The recommended dose is 1 Pariet 20 mg tablet once a day for six weeks.
- Take the tablet in the morning before breakfast.
- Your doctor may instruct you to continue the treatment for another six weeks if your condition does not improve.
Treatment of bowel ulcer (duodenal ulcer)
- The recommended dose is 1 Pariet 20 mg tablet once a day for four weeks.
- Take the tablet in the morning before breakfast.
- Your doctor may instruct you to continue the treatment for another four weeks if your condition does not improve.
Treatment and prevention of ulcer caused by H. Pylori infections
- The recommended dose is 1 Pariet 20 mg tablet twice a day for seven days.
- Your doctor will also prescribe you to take antibiotics called amoxicillin and clarithromycin.
For more information on other medicines used in the treatment of Helicobacter pylori infection, please refer to their package leaflets.
Treatment of Zollinger-Ellison Syndrome, a condition in which the stomach produces a very high amount of acid.
- It is recommended to start treatment with 3 Pariet 20 mg tablets once a day.
- The dose can later be adjusted by your doctor based on your response to treatment.
If you are on long-term treatment, you will need to see your doctor at regular intervals to check your symptoms and review your dose.
Use in children
The medicine should not be used in children.
Patients with liver problems.
You will need to consult your doctor who will take special care at the start of your treatment with Pariet and throughout your therapy.
Overdose What to do if you have taken too much Pariet
If you take more Pariet than you should
If you take more tablets than prescribed, consult your doctor or the nearest hospital emergency department. Always take your tablets or the pack with you.
If you forget to take Pariet
- If you forget to take a dose, take it as soon as you remember. However, if it is already time for your next dose, skip the missed dose and continue as usual.
- If you forget to take your medicine for more than 5 days, call your doctor before taking the medicine again.
- Do not take a double dose (two doses at the same time) to make up for a forgotten tablet.
If you stop taking Pariet
Symptom relief usually comes on normally before the ulcer has completely healed. It is important not to stop taking the tablets until you tell your doctor.
If you have any further questions on the use of Pariet, ask your doctor or pharmacist.
Side Effects What are the side effects of Pariet
Like all medicines, Pariet can cause side effects, although not everybody gets them. The side effects are usually mild and resolve without stopping the medicine.
Stop taking Pariet and see your doctor immediately if you notice any of the side effects listed below - you may need urgent treatment:
- Allergic reactions - the signs could include: sudden swelling of the face, shortness of breath or low blood pressure, which could cause fainting or collapse.
- Frequent infections such as sore throat or fever or ulcers in the mouth or throat.
- Bruising or bleeding that occurs easily.
These side effects are rare (they occur in less than 1 in 1,000 people).
- Severe blistering of the skin or irritation or ulcers in the mouth and throat.
These side effects are very rare (they occur in less than 1 in 10,000 people).
Other possible side effects:
Common (occurring in less than 1 in 10 people)
- Infections
- Difficulty falling asleep
- Headache or dizziness
- Cough, cold, runny nose ("runny nose"), throat inflammation (pharyngitis)
- Effects on the stomach or intestines such as: abdominal pain, diarrhea, flatulence, nausea, vomiting or constipation
- Nonspecific pain, back pain
- Weakness, flu-like syndrome.
Uncommon (affects less than 1 in 100 people)
- Nervousness or sleepiness
- Lower respiratory tract infections (bronchitis)
- Stuffed and painful nose (sinusitis)
- Dry mouth
- Poor digestion or belching
- Rash or redness of the skin
- Pain in the muscles, legs or joints
- Bladder infections (urinary tract infections)
- Chest pain
- Chills or fever
- Liver problems (shown in blood tests).
Rare (occurs in less than 1 in 1,000 people)
- Loss of appetite (anorexia)
- Depression
- Hypersensitivity (including allergic reactions)
- Vision disturbances
- Inflammation of the mouth (stomatitis) or taste disturbances
- Upset stomach or stomach pain
- Liver problems including yellowing of the skin and whites of the eyes (jaundice)
- Skin rash with itching and blistering skin reactions
- Sweating
- Kidney problems
- Weight gain
- Changes in white blood cells (shown in blood tests) which can lead to frequent infections
- Reduction in blood platelets which can lead to bleeding or bruising more easily than normal.
Other possible side effects (frequency not known)
- Swelling of the chest in men
- Fluid retention
- Low levels of sodium in the blood which can lead to tiredness, confusion, muscle spasms, seizures and coma
- Patients who have had previous liver problems may very rarely experience encephalopathy (brain disease)
If you take PARIET for more than three months, your blood levels of magnesium may drop. Low magnesium levels can manifest themselves with fatigue, involuntary muscle contractions, disorientation, convulsions, dizziness, increased heart rate. If you have any of these symptoms, please consult your doctor immediately. Low levels of magnesium can also lead to a reduction in potassium or calcium levels in the blood. Your doctor should decide whether to check your blood magnesium levels periodically.
Don't be alarmed by this list of side effects. He may not manifest any. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Expiry and Retention
Keep Pariet out of the reach and sight of children.
Do not store above 25 ° C.
Do not refrigerate.
Do not use Pariet after the expiry date which is stated on the carton and blister. The expiry date refers to the last day of the month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What Pariet contains
Each Pariet 10 mg tablet contains 10 mg of rabeprazole sodium as the active ingredient.
The excipients are:
mannitol, magnesium oxide, low-substituted hyprolose, hyprolose, magnesium stearate, ethylcellulose, hypromellose phthalate, diacetylated monoglycerides, talc, titanium dioxide (E171), red iron oxide (E 172), carnauba wax and ink (white shellac, black iron oxide (E172), dehydrated ethyl alcohol, 1-butanol).
Each Pariet 20 mg tablet contains 20 mg of rabeprazole sodium as the active ingredient.
The excipients are:
mannitol, magnesium oxide, low-substituted hyprolose, hyprolose, magnesium stearate, ethylcellulose, hypromellose phthalate, diacetylated monoglycerides, talc, titanium dioxide (E171), yellow iron oxide (E 172), carnauba wax and ink (white shellac, iron red oxide (E 172), glycerin esterified with fatty acid, dehydrated ethyl alcohol, 1-butanol).
What Pariet looks like and contents of the pack
Pariet 10 mg gastro-resistant tablets are a pink, biconvex tablet with "E241" written on one side.
Pariet 20 mg gastro-resistant tablets are a yellow, biconvex tablet with "E243" on one side.
The tablets are packed in blisters of 1,7,14,15,25,28,30,50,56,75 or 120 tablets.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
PARIET FOOD-RESISTANT TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
PARIET 10 mg gastro-resistant tablets
10 mg of rabeprazole sodium, equivalent to 9.42 mg of rabeprazole
PARIET 20 mg gastro-resistant tablets
20 mg of rabeprazole sodium, equivalent to 18.85 mg of rabeprazole
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Gastro-resistant tablets.
PARIET 10 mg
Gastro-resistant, film-coated, biconvex, pink tablets with the imprint "E 241". shown on one side.
PARIET 20 mg
Gastro-resistant yellow, film-coated, biconvex tablets with the imprint "E 243". shown on one side.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
PARIET tablets are indicated for the treatment of:
• active duodenal ulcer
• active benign gastric ulcer
• symptomatic erosive or ulcerative gastroesophageal reflux disease (GERD)
• long-term therapy of gastroesophageal reflux disease (GERD maintenance therapy)
• symptomatic treatment of moderate to very severe gastroesophageal reflux disease (symptomatic GERD)
• Zollinger-Ellison syndrome
• eradication of Helicobacter pylori infection in combination with appropriate antibacterial regimens in patients with peptic ulcer (see section 4.2).
04.2 Posology and method of administration
Adults / seniors
Active duodenal ulcer and active benign gastric ulcer: The recommended oral dose in both active duodenal ulcer and active benign gastric ulcer is 20 mg once daily to be taken in the morning.
In most patients with active duodenal ulcer healing occurs within 4 weeks. However, some patients may require an additional 4 weeks of therapy to achieve healing.
Most patients with active benign gastric ulcer heal within 6 weeks. Again, however, an additional 6 weeks of therapy may be required for healing in some patients.
Erosive or ulcerative gastro-oesophageal reflux disease (GERD): The recommended oral dose in this condition is 20 mg once daily for 4 to 8 weeks.
Long-term treatment of gastroesophageal reflux disease (GERD maintenance therapy): For long-term therapy, one 10 mg or 20 mg tablet once daily is recommended, depending on the patient's response.
Treatment of symptoms of moderate to very severe gastroesophageal reflux disease (symptomatic GERD): 10 mg once daily in patients without esophagitis. If symptom control is not achieved within 4 weeks, the patient should be investigated further. Once symptoms have resolved, subsequent symptom control can be achieved by adopting a regimen of 10 mg once daily as needed, when needed.
Zollinger-Ellison syndrome
In adults, the recommended starting oral dose is 60 mg once daily. The posology can be increased up to the dose of 120 mg / day, according to the needs of the individual patient. Single daily doses up to 100mg / day can be administered. The 120 mg dose can be divided into 60 mg twice daily. Treatment should continue for as long as clinically indicated.
Eradication of H. pylori infection: Patients with H. pylori infection should be treated with eradication therapy. The following combination is recommended for a duration of 7 days:
Pariet 20 mg 2 times a day + clarithromycin 500 mg 2 times a day + amoxicillin 1 g 2 times a day.
For indications requiring once daily treatment, PARIET tablets should be swallowed in the morning, before eating; although in fact no interference has been shown on the activity of rabeprazole sodium by food or by the time of day in which the drug is taken, this treatment scheme facilitates patient compliance.
Patients should be advised not to chew or crush the tablets but to swallow them whole.
Patients with liver or kidney dysfunction
No dosage adjustments are required in patients with impaired hepatic or renal function.
For the use of PARIET in patients with severe hepatic dysfunction see section 4.4 Special warnings and precautions for use.
Children
The use of PARIET in children is not recommended as there is no experience with the use of the product in this patient group.
04.3 Contraindications
PARIET is contraindicated in patients with known hypersensitivity to rabeprazole sodium or to any of the excipients present in the tablets.
PARIET is contraindicated in pregnant or lactating women.
04.4 Special warnings and appropriate precautions for use
The symptomatic response to therapy with rabeprazole sodium does not exclude the presence of malignant gastric or esophageal pathologies; this possibility must therefore be excluded before starting treatment with PARIET.
Patients on long-term therapy (particularly those treated for more than one year) should be monitored regularly.
The risk of cross-hypersensitivity with other proton pump inhibitors cannot be excluded.
Patients should be advised not to chew or crumble the tablets, but to swallow them whole.
The use of PARIET in children is not recommended as there is no experience with the use of the product in this patient group.
There have been post-marketing reports of blood dyscrasia (thrombocytopenia and neutropenia). In most cases where an alternative etiology could not be identified, the severity of the events decreased or they resolved on discontinuation of rabeprazole.
Alterations in liver enzymes have been observed in clinical trials and have also been reported post-marketing. In most cases where an alternative etiology could not be identified, the events were uncomplicated and resolved with discontinuation of rabeprazole.
A study in patients with mild to moderate hepatic impairment did not reveal significant safety issues related to drug use other than those observed in the control group, similar in age and gender distribution. However, since there is no are clinical data on the use of PARIET in the treatment of patients with severe hepatic dysfunction, the physician is advised to take special care when administering PARIET for the first time to such patients.
Co-administration of atazanavir with PARIET is not recommended (see section 4.5).
Treatment with proton pump inhibitors, including PARIET, may increase the risk of gastrointestinal infections such as infections with Salmonella, Campylobacter And Clostridium difficile (see section 5.1).
Proton pump inhibitors, especially when used in high doses and for prolonged periods (> 1 year), may cause a slightly increased risk of hip, wrist and spine fractures, especially in elderly patients or in the presence of other known risk factors. Observational studies suggest that proton pump inhibitors may increase the overall risk of fracture by 10% to 40%. This increase may be partly due to other risk factors. Patients at risk of osteoporosis should receive treatment according to current clinical practice guidelines and must take an "adequate amount of vitamin D and calcium.
Proton pump inhibitors (PPIs) such as PARIET have been shown to cause severe hypomagnesaemia in patients treated for at least three months and in many cases for one year. Serious symptoms of hypomagnesaemia include fatigue, tetany, delirium, convulsions, dizziness, and ventricular arrhythmia. They can initially manifest insidiously and be neglected. Hypomagnesaemia in most patients improves after taking magnesium and discontinuing the proton pump inhibitor.
Healthcare professionals should consider measuring magnesium levels before initiating PPI treatment and periodically during treatment in patients on prolonged therapy and on therapy with digoxin or drugs that can cause hypomagnesaemia (eg diuretics).
Concomitant use of rabeprazole with methotrexate
The literature suggests that concomitant use of PPI with methotrexate (especially at high doses; see Summary of Product Characteristics of methotrexate) may increase and prolong serum levels of methotrexate and / or its metabolite, which can lead to toxicity. In case of administration of high doses of methotrexate, a temporary withdrawal of PPIs may be considered in some patients.
Influence on the absorption of vitamin B12
Rabeprazole sodium, like all acid-blocking drugs, can reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or a-hydrochloride. This should be taken into consideration in patients on long-term therapy with reduced body stores. or risk factors that reduce the absorption of vitamin B12 or if the respective clinical symptoms are observed.
04.5 Interactions with other medicinal products and other forms of interaction
Rabeprazole sodium produces an intense and lasting inhibition of stomach acid secretion. An interaction can occur with compounds whose absorption is pH dependent. Concomitant administration of rabeprazole sodium and ketoconazole or itraconazole may result in a significant reduction in the plasma levels of these antifungals. Therefore, the need for some patients to be monitored to determine if a dose adjustment is necessary when ketoconazole or itraconazole are taken concomitantly with PARIET should be considered.
In some clinical studies, antacid drugs were administered together with PARIET and, in a specific drug-drug interaction study, no interaction with liquid antacid drugs was observed.
Co-administration of atazanavir 300 mg / ritonavir 100 mg with omeprazole (40 mg single dose) or atazanavir 400 mg with lansoprazole (60 mg single dose) to healthy volunteers resulted in a substantial reduction in atazanavir exposure. The absorption of atazanavir was pH dependent. Although not studied, similar results are to be expected with other proton pump inhibitors as well.
Therefore proton pump inhibitors, including rabeprazole, should not be co-administered with atazanavir (see section 4.4).
Methotrexate
Clinical cases, published population pharmacokinetic studies and retrospective analyzes suggest that concomitant administration of PPI and methotrexate (especially at high doses; see the Summary of Product Characteristics of methotrexate) may increase and prolong serum levels of methotrexate and / or its hydroxymethotrexate metabolite. However, no formal drug interaction studies between methotrexate and PPI have been conducted.
04.6 Pregnancy and lactation
Pregnancy
There are no data on the safety of rabeprazole in pregnant women.
Reproduction studies in rats and rabbits did not reveal any negative effects on fertility or the fetus due to the administration of rabeprazole sodium, although a modest fetal-placental passage of the drug is found in the rat.
PARIET is contraindicated in pregnancy.
Feeding time
It is not known whether rabeprazole sodium is excreted in human breast milk. No studies have been conducted in lactating women.
However, rabeprazole sodium is excreted in rat mammary secretions.
PARIET should therefore not be used in breastfeeding women.
04.7 Effects on ability to drive and use machines
Based on the pharmacodynamic properties and the type of possible adverse events it is unlikely that PARIET will affect the ability to drive or use machines.
If, however, there is a reduction in alertness due to drowsiness, it is recommended not to drive and to avoid using complex machinery.
04.8 Undesirable effects
The most commonly reported adverse events with rabeprazole in controlled clinical trials were headache, diarrhea, abdominal pain, asthenia, flatulence, rash and dry mouth.
Most adverse events encountered during clinical trials were mild or moderate in intensity and transient.
The following adverse events have been reported from clinical trials or post-marketing experience. Frequency is defined as:
common (≥1 / 100;
1 Includes face edema, hypotension and dyspnoea.
2 Erythema, bullous reactions and allergic reactions generally resolved after discontinuation of treatment.
3 Rare cases of hepatic encephalopathy have been reported in patients with pre-existing cirrhosis. In the treatment of patients with severe hepatic dysfunction, the physician should exercise caution when treatment with PARIET is first administered in this type of patient (see section 4.4).
4 See section 4.4 Special warnings and precautions for use.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
04.9 Overdose
Experience to date with intentional or accidental overdose is limited. The established maximum exposure has not exceeded 60 mg / twice daily, or 160 mg / once daily. Effects are generally minimal, characteristic of the known adverse event profile, and reversible without further medical intervention. There is no known specific antidote. Rabeprazole sodium is highly protein bound and therefore cannot be eliminated by dialysis. As in any case of overdose, treatment is symptomatic and general supportive measures should be adopted.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Gastrointestinal system and metabolism. Drugs for the treatment of peptic ulcer and gastroesophageal reflux disease (GERD). Acid pump inhibitors.
ATC code: A02B C04.
Mechanism of action: Rabeprazole sodium belongs to the class of antisecretory compounds, benzimidazole derivatives, which do not possess anticholinergic activity or antagonistic properties on H2 receptors for histamine, but suppress stomach acid secretion by specific inhibition of the H + / K + -ATPase enzyme (the pump acid or protonic). The effect is dose-dependent and leads to the inhibition of acid secretion, either basal or stimulated, regardless of stimulation. Animal studies indicate that rabeprazole sodium rapidly disappears from both plasma and gastric mucosa after administration.
Being a weak base, rabeprazole is rapidly absorbed at all dose levels and is concentrated in the acidic environment of the parietal cells. Rabeprazole is converted to the active sulphenamide form by protonation and subsequently reacts with the cysteine molecules available on the proton pump.
Antisecretory activity: After oral administration of a 20 mg dose of rabeprazole sodium the onset of the antisecretory effect is observed within 1 hour, while the maximum effect is evident within 2-4 hours. The inhibition of both basal and food-stimulated acid secretion 23 hours after administration of the first dose of rabeprazole sodium is 69% and 82%, respectively, and the inhibition lasts for up to 48 hours. L Inhibitory effect of rabeprazole sodium on acid secretion increases slightly with repeated daily dosing, reaching steady-state inhibition after 3 days. When dosing is stopped, secretory activity normalizes within 2-3 days.
The reduction of gastric acidity due to various agents, including proton pump inhibitors such as rabeprazole, increases the amount of bacteria normally present in the gastrointestinal tract. Treatment with proton pump inhibitors could increase the risk of gastrointestinal infections such as infections from Salmonella, Campylobacter And Clostridium difficile.
Effects on serum gastrin: In clinical studies, patients were treated with 10 or 20 mg rabeprazole sodium once daily for up to 43 months. Serum gastrin levels increased during the first 2-8 weeks, reflecting inhibitory effects on acid secretion, and remained stable for the duration of therapy. Upon discontinuation of therapy, gastrin values then returned to pre-treatment levels, usually within 1-2 weeks.
The biopsy examination, conducted on samples taken from the antrum and fundus of the stomach of over 500 patients treated with rabeprazole sodium or comparator for up to 8 weeks, did not reveal any alterations in the histology of ECL cells, in the severity of the gastritis, in the incidence of atrophic gastritis and intestinal metaplasia or in the distribution of H. pylori infection.In over 250 patients monitored for 36 months of continuous therapy, no significant changes were observed in the controlled parameters before and after treatment.
Other effectsSystemic effects of rabeprazole sodium on the CNS, cardiovascular and respiratory systems have not been detected so far. Rabeprazole sodium, administered at an oral dose of 20 mg for 2 weeks, caused no effect on thyroid function, carbohydrate metabolism, circulating levels of parathyroid hormone, cortisol, estrogen, testosterone, prolactin, cholecystokinin, secretin, glucagon , follicle-stimulating hormone (FSH), luteinizing hormone (LH), renin, aldosterone or somatotropic hormone.
Studies in healthy subjects have shown that rabeprazole sodium has no clinically significant interactions with amoxicillin. Rabeprazole does not adversely affect the plasma concentrations of amoxicillin and clarithromycin during concomitant administration in the eradication of H. pylori infection of the upper gastrointestinal tract.
05.2 Pharmacokinetic properties
Absorption: PARIET represents a gastro-resistant tablet formulation containing rabeprazole sodium. This gastro-resistant coated formulation is required because rabeprazole sodium is acid labile. Absorption of rabeprazole therefore begins only after the tablet has passed the stomach. Absorption is rapid, with plasma concentrations of rabeprazole peaking approximately 3.5 hours after a 20 mg dose. Maximum plasma concentrations (Cmax) of rabeprazole and AUC values are linear over the dose range of 10 to 40 mg. The absolute bioavailability of an oral dose of 20 mg (compared with intravenous administration) is approximately 52% as pre-systemic metabolism is relevant. Furthermore, bioavailability does not appear to increase with repeated administration.
In healthy subjects, the plasma half-life is approximately 1 hour (range 0.7 to 1.5 hours) and the total body clearance value is estimated to be 283 ± 98 ml / min. There were no clinically relevant interactions with food. Neither food nor the timing of drug administration affect the absorption of rabeprazole sodium.
Distribution: in humans, about 97% of rabeprazole is bound to plasma proteins.
Metabolism and excretion: Rabeprazole sodium, like other drugs of the proton pump inhibitor class, is metabolised via the cytochrome P 450 (CYP450) system which metabolizes drugs in the liver. Education in vitro with human liver microsomes showed that rabeprazole sodium is metabolised by isoenzymes of the CYP450 system (CYP2C19 and CYP3A4). In these studies, rabeprazole had no inducing or inhibitory effects on CYP3A4 at human plasma concentrations; although studies in vitro may not always be predictive of the situation in vivo, these findings are indicative of an absence of interaction between rabeprazole and cyclosporine.
In humans, thioether (M1) and carboxylic acid (M6) are the major plasma metabolites. Sulphone (M & SUP2;), desmethylthioether (M4) and mercapturic acid conjugate (M5) are minor metabolites present at low levels.
Only the desmethyl metabolite (M & SUP3;) has a mild antisecretory activity, but is not present in plasma.
After a single 20 mg oral dose of 14C-labeled rabeprazole sodium there is no unchanged drug in the urine. Approximately 90% of the dose is excreted in the urine, mainly in the form of 2 metabolites, a conjugation product with mercapturic acid (M5) and a carboxylic acid (M6), plus two unidentified metabolites.
The remainder of the administered dose is recovered in the faeces.
Sex
There are no gender-related differences in pharmacokinetic parameters when related to body mass and height following administration of a single 20 mg dose of rabeprazole.
Renal dysfunction
It has been observed that in patients with severe chronic renal insufficiency and on maintenance dialysis (creatinine clearance ≤5 ml / min / 1.73 m2) the availability of rabeprazole is very similar to that found in healthy volunteers.
The AUC and Cmax values in these patients were approximately 35% lower than the corresponding values in healthy volunteers. The mean half-life of rabeprazole was 0.82 hours in healthy volunteers, 0.95 hours in patients during hemodialysis and 3.6 hours after dialysis.
Drug clearance in patients with renal dysfunction requiring maintenance hemodialysis was approximately 2 times that in healthy volunteers.
Hepatic dysfunction
After a single 20 mg dose of rabeprazole in patients with chronic, mild to moderate hepatic dysfunction, there was a doubling of AUC and a 2- or 3-fold increase compared to that observed in healthy volunteers. of the half-life of rabeprazole. However, after a repeated 20 mg daily dose for 7 days, the AUC value increased only 1.5-fold and the C value only 1.2-fold.
The half-life of rabeprazole in patients with impaired hepatic function was 12.3 hours while in healthy volunteers it was 2.1 hours.
The pharmacodynamic response (gastric pH control) in the two groups was clinically comparable.
Senior citizens
The elimination rate of rabeprazole is slightly reduced in the elderly. After 7 days of daily administration of 20 mg rabeprazole sodium the AUC values are nearly doubled, the C values are higher by approximately 60% and the t½ increased by approximately 30%. compared to what was found in young healthy volunteers.
However, there is no evidence of rabeprazole accumulation.
CYP2C19 polymorphism
After administration of a 20 mg daily dose of rabeprazole for 7 days, poor metabolisers of CYP2C19 had AUC and t½ values of approximately 1.9 and 1.6 times those seen for extensive metabolisers, while Cmax only increased. 40%.
05.3 Preclinical safety data
Non-clinical effects were observed only at dosages so high compared to the maximum expected human dose that the safety concerns of the product in humans were negligible compared to animal data. Mutagenicity studies yielded results. not unique. Tests on mouse lymphoma cell lines were positive but the micronucleus test in vivo and DNA repair tests in vivo and in vitro they were negative.
Carcinogenicity studies did not reveal any particular risks for humans.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
PARIET 10 mg
Core of the tablet: mannitol, magnesium oxide, low-substituted hyprolose, hyprolose, magnesium stearate;
Coating: ethylcellulose, magnesium oxide;
Gastrointestinal lining: hypromellose phthalate, diacetylated monoglycerides, talc, titanium dioxide (E171), red iron oxide (E172), carnauba wax;
Ink: white shellac, black iron oxide (E172), dehydrated ethyl alcohol, 1-butanol.
PARIET 20 mg
Core of the tablet: mannitol, magnesium oxide, low-substituted hyprolose, hyprolose, magnesium stearate;
Coating: ethylcellulose, magnesium oxide;
Gastrointestinal lining: hypromellose phthalate, diacetylated monoglycerides, talc, titanium dioxide (E171), yellow iron oxide (E 172), carnauba wax;
Ink: white shellac, red iron oxide (E 172), carnauba wax, glycerin esterified with fatty acids, dehydrated ethyl alcohol, 1-butanol.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
Do not store above 25 ° C. Do not refrigerate.
06.5 Nature of the immediate packaging and contents of the package
Aluminum / aluminum blister strip.
Pack sizes: blisters of 1, 7, 14, 15, 25, 28, 30, 50, 56, 75 or 120 tablets.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
JANSSEN-CILAG SpA
Via M. Buonarroti, 23
20093 COLOGNO MONZESE (Milan)
08.0 MARKETING AUTHORIZATION NUMBER
Pariet 10 mg gastro-resistant tablets, 14 tablets AIC n. 034216022
Pariet 10 mg gastro-resistant tablets, 7 tablets AIC n. 034216010
Pariet 10 mg gastro-resistant tablets, 28 tablets AIC n. 034216034
Pariet 10 mg gastro-resistant tablets, 56 tablets AIC n. 034216046
Pariet 10 mg gastro-resistant tablets, 15 tablets AIC n. 034216059
Pariet 10 mg gastro-resistant tablets, 30 tablets AIC n. 034216061
Pariet 10 mg gastro-resistant tablets, 75 tablets AIC n. 034216073
Pariet 10 mg gastro-resistant tablets, 120 tablets AIC n. 034216085
Pariet 20 mg gastro-resistant tablets, 14 tablets AIC n. 034216186
Pariet 20 mg gastro-resistant tablets, 7 tablets AIC n. 034216174
Pariet 20 mg gastro-resistant tablets, 28 tablets AIC n. 034216198
Pariet 20 mg gastro-resistant tablets, 56 tablets AIC n. 034216200
Pariet 20 mg gastro-resistant tablets, 15 tablets AIC n. 034216212
Pariet 20 mg gastro-resistant tablets, 30 tablets AIC n. 034216224
Pariet 20 mg gastro-resistant tablets, 75 tablets AIC n. 034216236
Pariet 20 mg gastro-resistant tablets, 120 tablets AIC n. 034216248
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
First Authorization: 3 March 1999
Renewal of the Authorization: 6 May 2008
10.0 DATE OF REVISION OF THE TEXT
07/2015
