Rabifast-DSR Capsules

Rabeprazole Sodium and Domperidone capsule

Each hard gelatin capsule contains:

Rabeprazole Sodium IP …………………20 mg

(As gastro-resistant pellets)

Excipients ………………………………..q.s.

Colours: Red Oxide of Iron & Titanium Dioxide IP

Domperidone IP …………..……………30 mg

(As prolonged-release pellets)

Excipients …………………………..…..q.s.

Colour: Sunset Yellow

Capsule

Rabeprazole 20 mg and Domperidone 30 mg

4.1 Therapeutic Indication

Gastroesophageal reflux disease

4.2 Posology and method of administration

Adults

One capsule to be taken daily or as directed by the physician.

Special populations

Hepatic impairment

Contraindicated in moderate or severe hepatic impairment. Dose modification in mild hepatic impairment is however not needed.

Renal impairment

RABIFAST®-DSR capsule should not be used in patients with renal impairment.

Paediatric population

RABIFAST®-DSR capsule are not recommended for use in children

Method of administration

Capsule should be swallowed whole & not to be opened, chewed or crushed.

4.3 Contraindications

• Hypersensitivity to the active substances or to any of the excipients
• Pregnancy
• Breast feeding
• Prolactin-releasing pituitary tumour (prolactinoma)
• when stimulation of the gastric motility could be harmful e.g in patients with gastro-intestinal haemorrhage, mechanical obstruction or perforation
• in patients with moderate or severe hepatic impairment
• in patients who have known existing prolongation of cardiac conduction intervals, particularly QTc, patients with significant electrolyte disturbances or underlying cardiac diseases such as congestive heart failure
• co-administration with QT-prolonging drugs, at the exception of apomorphine
• co-administration with potent CYP3A4 inhibitors (regardless of their QT prolonging effects)

4.4 Special warnings and precautions for use

Rabeprazole

Symptomatic response to therapy with rabeprazole sodium does not preclude the presence of gastric or oesophageal malignancy, therefore the possibility of malignancy should be excluded. Patients on long-term treatment (particularly those treated for more than a year) should be kept under regular surveillance.

A risk of cross-hypersensitivity reactions with other proton pump inhibitor (PPI) or substituted benzimidazoles cannot be excluded.

Rabeprazole is not recommended for use in children due to a lack of data on safety and efficacy.

There have been post marketing reports of blood dyscrasias (thrombocytopenia and neutropenia). In the majority of cases where an alternative aetiology cannot be identified, the events were uncomplicated and resolved on discontinuation of rabeprazole.

Hepatic enzyme abnormalities have been seen in clinical trials and have also been reported since market authorisation. In the majority of cases where an alternative aetiology cannot be identified, the events were uncomplicated and resolved on discontinuation of rabeprazole.

No evidence of significant drug related safety problems was seen in a study of patients with mild to moderate hepatic impairment versus normal age and sex matched controls. However because there are no clinical data on the use of rabeprazole in the treatment of patients with severe hepatic dysfunction the prescriber is advised to exercise caution when treatment with Rabeprazole is first initiated in such patients.

Co-administration of Atazanavir with rabeprazole is not recommended

Treatment with PPIs, including rabeprazole, may possibly increase the risk of gastrointestinal infections such as Salmonella, Campylobacter and Clostridium difficile

Hypomagnesaemia

Severe hypomagnesaemia has been reported in patients treated with PPIs like rabeprazole for at least three months, and in most cases for a year. Serious manifestations of hypomagnesaemia such as fatigue, tetany, delirium, convulsions, dizziness and ventricular arrhythmia can occur but they may begin insidiously and be overlooked. In most affected patients, hypomagnesaemia improved after magnesium replacement and discontinuation of the PPI.

For patients expected to be on prolonged treatment or who take PPIs 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.

PPIs, especially if used in high doses and over long durations (>1 year), may modestly increase the risk of hip, wrist and spine fracture, predominantly in the elderly or in presence of other recognised risk factors. Observational studies suggest that PPIs may increase the overall risk of fracture by 10–40%. Some of this increase may be due to other risk factors. Patients at risk of osteoporosis should receive care according to current clinical guidelines and they should have an adequate intake of vitamin D and calcium.

Concomitant use of rabeprazole with methotrexate

Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients.

Influence on vitamin B12 absorption

Rabeprazole sodium, as all acid-blocking medicines, may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or a- chlorhydria. 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.

Subacute cutaneous lupus erythematosus (SCLE)

PPIs are associated with very infrequent cases of SCLE. If lesions occur, especially in sun-exposed areas of the skin, and if accompanied by arthralgia, the patient should seek medical help promptly and the health care professional should consider stopping Rabeprazole. SCLE after previous treatment with a PPI may increase the risk of SCLE with other PPIs.

Interference with laboratory tests

Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To avoid this interference, Rabeprazole treatment should be stopped for at least 5 days before CgA measurements. If CgA and gastrin levels have not returned to reference range after initial measurement, measurements should be repeated 14 days after cessation of PPI treatment.

Domperidone

Cardiovascular effects

Domperidone has been associated with prolongation of the QT interval on the electrocardiogram. During post-marketing surveillance, there have been very rare cases of QT prolongation and torsades de pointes in patients taking domperidone. These reports included patients with confounding risk factors, electrolyte abnormalities and concomitant treatment which may have been contributing factors.

Epidemiological studies showed that domperidone was associated with an increased risk of serious ventricular arrhythmias or sudden cardiac death. A higher risk was observed in patients older than 60 years, patients taking daily doses greater than 30 mg, and patients concurrently taking QT-prolonging drugs or CYP3A4 inhibitors.

Domperidone should be used at the lowest effective dose in adults and adolescents 12 years of age and older.

Domperidone is contraindicated in patients with known existing prolongation of cardiac conduction intervals, particularly QTc, in patients with significant electrolyte disturbances (hypokalaemia, hyperkalaemia, hypomagnesaemia), or bradycardia, or in patients with underlying cardiac diseases such as congestive heart failure due to increased risk of ventricular arrhythmia. Electrolyte disturbances (hypokalaemia, hyperkalaemia, hypomagnesaemia) or bradycardia are known to be conditions increasing the proarrythmic risk.

Treatment with domperidone should be stopped if signs or symptoms occur that may be associated with cardiac arrhythmia, and the patients should consult their physician. Patients should be advised to promptly report any cardiac symptoms.

Use with apomorphine

Domperidone is contra-indicated with QT prolonging drugs including apomorphine, unless the benefit of the co-administration with apomorphine outweighs the risks, and only if the recommended precautions for co-administration mentioned in the apomorphine PI are strictly fulfilled.

Renal impairment

The elimination half-life of domperidone is prolonged in severe renal impairment. For repeated administration, the dosing frequency of domperidone should be reduced depending on the severity of the impairment. The dose may also need to be reduced.

4.5 Drugs interactions

Rabeprazole

Rabeprazole sodium produces a profound and long lasting inhibition of gastric acid secretion. An interaction with compounds whose absorption is pH dependent may occur. Co-administration of rabeprazole sodium with ketoconazole or itraconazole may result in a significant decrease in antifungal plasma levels. Therefore, individual patients may need to be monitored to determine if a dosage adjustment is necessary when ketoconazole or itraconazole are taken concomitantly with rabeprazole.

In clinical trials, antacids were used concomitantly with the administration of rabeprazole and, in a specific drug-drug interaction study, no interaction with liquid antacids was observed.

Co-administration of atazanavir 300 mg/ritonavir 100 mg with omeprazole (40 mg once daily) or atazanavir 400 mg with lansoprazole (60 mg once daily) to healthy volunteers resulted in a substantial reduction in atazanavir exposure. The absorption of atazanavir is pH dependent.

Although not studied, similar results are expected with other proton pump inhibitors. Therefore PPIs, including rabeprazole, should not be co-administered with atazanavir

Methotrexate

Case reports, published population pharmacokinetic studies, and retrospective analyses suggest that concomitant administration of PPIs and methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate. However, no formal drug interaction studies of methotrexate with PPIs have been conducted.

Domperidone

The main metabolic pathway of domperidone is through CYP3A4. In vitro data suggest that the concomitant use of drugs that significantly inhibit this enzyme may result in increased plasma levels of domperidone.

Increased risk of occurrence of QT-interval prolongation, due to pharmacodynamic and/or pharmacokinetic interactions.

Concomitant use of the following substances is contraindicated

QTc prolonging medicinal products

• anti-arrhythmics class IA (e.g., Disopyramide, Hydroquinidine, Quinidine)
• anti-arrhythmics class III (e.g., Amiodarone, Dofetilide, Dronedarone, Ibutilide, Sotalol)
• certain anti-psychotics (e.g., Haloperidol, Pimozide, Sertindole)
• certain anti-depressants (e.g., Citalopram, Escitalopram)
• certain antibiotics (e.g., Erythromycin, Levofloxacin, Moxifloxacin, Spiramycin)
• certain antifungal agents (e.g., Pentamidine)
• certain antimalarial agents (in particular Halofantrine, Lumefantrine)
• certain gastro-intestinal medicines (e.g., Cisapride, Dolasetron, Prucalopride)
• certain antihistaminics (e.g., Mequitazine, Mizolastine)
• certain medicines used in cancer (e.g., Toremifene, Vandetanib, Vincamine)
• certain other medicines (e.g., Bepridil, Diphemanil, Methadone)
• Apomorphine, unless the benefit of the co-administration outweighs the risks, and only if the recommended precautions for co-administration are strictly fulfilled. Please refer to the Apomorphine PI.

Potent CYP3A4 inhibitors (regardless of their QT prolonging effects), i.e.:

• protease inhibitors
• systemic azole antifungals
• some macrolides (Erythromycin, Clarithromycin, Telithromycin)

Concomitant use of the following substances is not recommended

Moderate CYP3A4 inhibitors i.e. Diltiazem, Verapamil and some macrolides.

Concomitant use of the following substances requires caution in use

Caution with bradycardia and hypokalaemia-inducing drugs, as well as with the following macrolides involved in QT-interval prolongation: azithromycin and roxithromycin (clarithromycin is contra-indicated as it is a potent CYP3A4 inhibitor).

The above list of substances is representative and not exhaustive.

Separate in vivo pharmacokinetic/pharmacodynamic interaction studies with oral ketoconazole or oral erythromycin in healthy subjects confirmed a marked inhibition of domperidone's CYP3A4 mediated first pass metabolism by these drugs.

With the combination of oral domperidone 10mg four times daily and ketoconazole 200mg twice daily, a mean QTc prolongation of 9.8 msec was seen over the observation period, with changes at individual time points ranging from 1.2 to 17.5 msec. With the combination of domperidone 10mg four times daily and oral erythromycin 500mg three times daily, mean QTc over the observation period was prolonged by 9.9 msec, with changes at individual time points ranging from 1.6 to 14.3 msec. Both the Cmax and AUC of domperidone at steady state were increased approximately three-fold in each of these interaction studies. In these studies domperidone monotherapy at 10mg given orally four times daily resulted in increases in mean QTc of 1.6 msec (ketoconazole study) and 2.5 msec (erythromycin study), while ketoconazole monotherapy (200mg twice daily) led to increases in QTc of 3.8 and 4.9 msec, respectively, over the observation period.

4.6 Use in special populations

Pregnancy

Rabeprazole DSR capsule is contraindicated during pregnancy. Nursing Mothers Rabeprazole DSR must not be used during breast feeding.

4.7 Effects on ability to drive and use machines

Based on the pharmacodynamic properties and the adverse events profile, it is unlikely that Rabeprazole DSR would cause an impairment of driving performance or compromise the ability to use machinery. If, however, alertness is impaired due to somnolence, it is recommended that driving and operating complex machinery be avoided.

4.8 Undesirable effects

Rabeprazole

The most commonly reported adverse drug reactions, during controlled clinical trials with rabeprazole were headache, diarrhoea, abdominal pain, asthenia, flatulence, rash and dry mouth. The majority of adverse events experienced during clinical studies were mild or moderate in severity, and transient in nature.

The following adverse events have been reported from clinical trial and post-marketed experience.

Frequencies are defined as: common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data)

1. Includes facial swelling, hypotension and dyspnoea
2. Erythema, bullous reactions and hypersensitivity reactions have usually resolved after discontinuation of therapy.
3. Rare reports of hepatic encephalopathy have been received in patients with underlying cirrhosis. In treatment of patients with severe hepatic dysfunction the prescriber is advised to exercise caution when treatment with Rabeprazole is first initiated in such patients
4. See Special warnings and precautions for use

Domperidone

very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), Where frequency can not be estimated from clinical trials data, it is recorded as “Not known”.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to: medico@zuventus.com

Website: https://www.zuventus.com/drug-safety-reporting

4.9 Overdose

Symptoms: Symptoms of over dosage may include agitation, altered consciousness, convulsions, disorientation, somnolence and extrapyramidal reactions.

Treatment: There is no specific antidote, but in the event of overdose, standard symptomatic treatment should be given immediately. Gastric lavage as well as the administration of activated charcoal, may be useful. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation. Close medical supervision and supportive therapy is recommended.

Anticholinergic, anti-parkinson drugs may be helpful in controlling the extrapyramidal reactions.

5.1 Mechanism of Action

Rabeprazole

Rabeprazole sodium belongs to the class of anti-secretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or H2 histamine antagonist properties, but suppress gastric acid secretion by the specific inhibition of the H+/K+-ATPase enzyme (the acid or proton pump). The effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.

Domperidone

Domperidone is a dopamine antagonist with anti-emetic properties domperidone does not readily cross the blood-brain barrier. Its anti-emetic effect may be due to a combination of peripheral (gastrokinetic) effects and antagonism of dopamine receptors in the chemoreceptor trigger zone, which lies outside the blood-brain barrier in the area postrema. Studies in man have shown oral domperidone to increase lower esophaegeal pressure, improve antroduodenal motility and accelerate gastric emptying. There is no effect on gastric secretion.

5.2 Pharmacodynamic properties

Rabeprazole

As a weak base, rabeprazole is rapidly absorbed following all doses and is concentrated in the acid environment of the parietal cells. Rabeprazole is converted to the active sulphenamide form through protonation and it subsequently reacts with the available cysteines on the proton pump.

Systemic effects of rabeprazole sodium in the CNS, cardiovascular and respiratory systems have not been found to date. Rabeprazole sodium, given in oral doses of 20 mg for 2 weeks, had no effect on thyroid function, carbohydrate metabolism, or circulating levels of parathyroid hormone, cortisol, oestrogen, testosterone, prolactin, cholecystokinin, secretin, glucagon, follicle stimulating hormone (FSH), luteinising hormone (LH), renin, aldosterone or somatotrophic hormone.

Domperidone

Domperidone is a dopamine antagonist with anti-emetic properties domperidone does not readily cross the blood brain barrier. In domperidone users, especially in adults, extrapyramidal side effects are very rare, but domperidone promotes the release of prolactin from the pituitary. Its anti-emetic effect may be due to a combination of peripheral (gastrokinetic) effects and antagonism of dopamine receptors in the chemoreceptor trigger zone, which lies outside the blood-brain barrier in the area postrema. Animal studies, together with the low concentrations found in the brain, indicate a predominantly peripheral effect of domperidone on dopamine receptors. Studies in man have shown oral domperidone to increase lower oesophageal pressure, improve antroduodenal motility and accelerate gastric emptying. There is no effect on gastric secretion.

5.3 Pharmacokinetic properties

Rabeprazole

Absorption: Rabeprazole, an enteric-coated (gastro-resistant) formulation of rabeprazole sodium. This presentation is necessary because rabeprazole is acid-labile. Absorption of rabeprazole therefore begins only after the capsule leaves the stomach. Absorption is rapid, with peak plasma levels of rabeprazole occurring approximately 3.5 hours after a 20 mg dose. Peak plasma concentrations (Cmax) of rabeprazole and AUC are linear over the dose range of 10 mg to 40 mg. Absolute bioavailability of an oral 20 mg dose (compared to intravenous administration) is about 52 % due in large part to pre-systemic metabolism. Additionally, the bioavailability does not appear to increase with repeat administration. In healthy subjects the plasma half-life is approximately one hour (range 0.7 to 1.5 hours), and the total body clearance is estimated to be 283 ± 98 ml/min. There was no clinically relevant interaction with food. Neither food nor the time of day of administration of the treatment affect the absorption of rabeprazole sodium.

Distribution: Rabeprazole is approximately 97% bound to human plasma proteins.

Biotransformation and elimination: Rabeprazole sodium, as is the case with other members of the proton pump inhibitor (PPI) class of compounds, is metabolised through the cytochrome P450 (CYP450) hepatic drug metabolising system. In vitro studies with human liver microsomes indicated that rabeprazole sodium is metabolised by isoenzymes of CYP450 (CYP2C19 and CYP3A4). In these studies, at expected human plasma concentrations rabeprazole neither induces nor inhibits CYP3A4; and although in vitro studies may not always be predictive of in vivo status these findings indicate that no interaction is expected between rabeprazole and cyclosporin. In humans the thioether (M1) and carboxylic acid (M6) are the main plasma metabolites with the sulphone (M2), desmethyl-thioether (M4) and mercapturic acid conjugate (M5) minor metabolites observed at lower levels. Only the desmethyl metabolite (M3) has a small amount of anti-secretory activity, but it is not present in plasma.

Following a single 20 mg 14C labelled oral dose of rabeprazole sodium, no unchanged drug was excreted in the urine. Approximately 90 % of the dose was eliminated in urine mainly as the two metabolites: a mercapturic acid conjugate (M5) and a carboxylic acid (M6), plus two unknown metabolites. The remainder of the dose was recovered in faeces.

Domperidone

Absorption: Domperidone is rapidly absorbed after oral administration, with peak plasma concentrations occurring at approximately 1hr after dosing. The Cmax and AUC values of domperidone increased proportionally with dose in the 10 mg to 20 mg dose range. A 2- to 3-fold accumulation of domperidone AUC was observed with repeated four times daily (every 5 hr) dosing of domperidone for 4 days.

The low absolute bioavailability of oral domperidone (approximately 15%) is due to an extensive first-pass metabolism in the gut wall and liver. Although domperidone's bioavailability is enhanced in normal subjects when taken after a meal, patients with gastro-intestinal complaints should take domperidone 15-30 minutes before a meal. Reduced gastric acidity impairs the absorption of domperidone. Oral bioavailability is decreased by prior concomitant administration of cimetidine and sodium bicarbonate. The time of peak absorption is slightly delayed and the AUC somewhat increased when the oral drug is taken after a meal.

Distribution: Oral domperidone does not appear to accumulate or induce its own metabolism; a peak plasma level after 90 minutes of 21 ng/ml after two weeks oral administration of 30 mg per day was almost the same as that of 18 ng/ml after the first dose. Domperidone is 91-93% bound to plasma proteins. Distribution studies with radiolabelled drug in animals have shown wide tissue distribution, but low brain concentration. Small amounts of drug cross the placenta in rats.

Metabolism: Domperidone undergoes rapid and extensive hepatic metabolism by hydroxylation and N-dealkylation. In vitro metabolism experiments with diagnostic inhibitors revealed that CYP3A4 is a major form of cytochrome P-450 involved in the N-dealkylation of domperidone, whereas CYP3A4, CYP1A2 and CYP2E1 are involved in domperidone aromatic hydroxylation.

Excretion: Urinary and faecal excretions amount to 31 and 66% of the oral dose respectively. The proportion of the drug excreted unchanged is small (10% of faecal excretion and approximately 1% of urinary excretion). The plasma half-life after a single oral dose is 7-9 hours in healthy subjects but is prolonged in patients with severe renal insufficiency.

6.1 Animal Toxicology or Pharmacology

Rabeprazole

Non-clinical effects were observed only at exposures sufficiently in excess of the maximum human exposure that make concerns for human safety negligible in respect of animal data.

Studies on mutagenicity gave equivocal results. Tests in mouse lymphoma cell line were positive, but in vivo micronucleus and in vivo and in vitro DNA repair tests were negative. Carcinogenicity studies revealed no special hazard for humans.

Domperidone

Electrophysiological in vitro and in vivo studies indicate an overall moderate risk of domperidone to prolong the QT interval in humans. In in vitro experiments on isolated cells transfected with hERG and on isolated guinea pig myocytes, exposure ratios ranged between 26- 47-fold, based on IC50 values inhibiting currents through IKr ion channels in comparison to the free plasma concentrations in humans after administration of the maximum daily dose of 10 mg administered 3 times a day. Safety margins for prolongation of action potential duration in in vitro experiments on isolated cardiac tissues exceeded the free plasma concentrations in humans at maximum daily dose (10 mg administered 3 times a day) by 45-fold. Safety margins in in vitro pro-arrhythmic models (isolated Langendorff perfused heart) exceeded the free plasma concentrations in humans at maximum daily dose (10 mg administered 3 times a day) by 9- up to 45-fold. In in vivo models the no effect levels for QTc prolongation in dogs and induction of arrhythmias in a rabbit model sensitized for torsade de pointes exceeded the free plasma concentrations in humans at maximum daily dose (10 mg administered 3 times a day) by more than 22-fold and 435-fold, respectively. In the anesthetized guinea pig model following slow intravenous infusions, there were no effects on QTc at total plasma concentrations of 45.4 ng/mL, which are 3-fold higher than the total plasma levels in humans at maximum daily dose (10 mg administered 3 times a day). The relevance of the latter study for humans following exposure to orally administered domperidone is uncertain.

In the presence of inhibition of the metabolism via CYP3A4 free plasma concentrations of domperidone can rise up to 3-fold.

At a high, maternally toxic dose (more than 40 times the recommended human dose), teratogenic effects were seen in the rat. No teratogenicity was observed in mice and rabbits.

RABIFAST®-DSR is a combination of Rabeprazole sodium and Domperidone.

Rabeprazole sodium is a proton pump inhibitor. It is a substituted benzimidazole that inhibits gastric acid secretion.

Domperidone, a specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms

8.1 Incompatibilities

Not Applicable

8.2 Shelf-life

Refer to the pack

8.3 Packaging information

10 strips of 15 capsules each

8.4 Storage and handing instructions

• Store below 30°C. Protect from light and moisture.
• Keep out of reach of children.
• Capsule should be swallowed whole & not to be opened, chewed or crushed.

• Advice patient Not to take the medicine if the patient is

1. Are pregnant or think that you are pregnant.
2. Are breast-feeding.
3. Prolactin-releasing pituitary tumour (prolactinoma).
4. When stimulation of the gastric motility could be harmful e.g in patients with gastro-intestinal haemorrhage, mechanical obstruction or perforation.
5. In patients with moderate or severe hepatic impairment
6. In patients who have known existing prolongation of cardiac conduction intervals, particularly QTc, patients with significant electrolyte disturbances or underlying cardiac diseases such as congestive heart failure
7. Co-administration with QT-prolonging drugs, at the exception of apomorphine
8. Co-administration with potent CYP3A4 inhibitors (regardless of their QT prolonging effects)

• Acute Interstitial

Nephritis Advise the patient or caregiver to call the patient’s healthcare provider immediately if they experience signs and/or symptoms associated with acute interstitial nephritis

• Clostridium difficile-Associated Diarrhea

Advise the patient or caregiver to immediately call the patient’s healthcare provider if they experience diarrhea that does not improve

• Bone Fracture

Advise the patient or caregiver to report any fractures, especially of the hip, wrist or spine, to the patient’s healthcare provider

• Cutaneous and Systemic Lupus Erythematosus

Advise the patient or caregiver to immediately call the patient’s healthcare provider for any new or worsening of symptoms associated with cutaneous or systemic lupus erythematosus.

• Cyanocobalamin (Vitamin B-12) Deficiency

Advise the patient or caregiver to report any clinical symptoms that may be associated with cyanocobalamin deficiency to the patient’s healthcare provider if they have been receiving rabeprazole sodium delayed-release tablets for longer than 3 years

• Hypomagnesemia

Advise the patient or caregiver to report any clinical symptoms that may be associated with hypomagnesemia to the patient’s healthcare provider, if they have been receiving rabeprazole sodium delayed-release tablets for at least 3 months

• Drug Interactions

Advise patients to report to their healthcare provider if they are taking rilpivirine-containing products [see CONTRAINDICATIONS (4)], warfarin, digoxin or high-dose methotrexate

• Administration: Capsule should be swallowed whole & not to be opened, chewed or crushed. Do not take this medicine, if you are allergic to Rabeprazole
• Signs of an allergic reaction include a rash, itching or shortness of breath.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.
• If you have any further questions, ask your doctor or pharmacist.

July 2024