Rabeprazole + Amoxicillin + Clarithromycin

Uses

Amoxicillin, Clarithromycin & Rabeprazol combination is used for the eradication of H. pylori in active chronic gastric, duodenal and gastric ulcers.
Use in Geriatrics: Elderly patients may suffer from asymptomatic renal and hepatic dysfunction. Care should be taken when administering to this patient population.

Renal Dose Adjustments: No adjustment recommended.

Mild to moderate hepatic impairment: No adjustment recommended.

Severe hepatic impairment: Use with caution.

Rabeprazole + Amoxicillin + Clarithromycin is also used to associated treatment for these conditions: Acute Bacterial Sinusitis (ABS), Acute Otitis Media, Acute Otitis Media (AOM), Bacterial Infections, Community Acquired Pneumonia (CAP), Duodenal ulcer caused by helicobacter pylori, Genitourinary infections, Helicobacter Pylori Infection, Lower Respiratory Tract Infection (LRTI), Peptic Ulcer With H. Pylori Infection, Sinusitis, Skin and Subcutaneous Tissue Bacterial Infections, Urinary Tract Infection, Acute, uncomplicated Gonorrhea, Ear, nose, and throat infectionsAcute Bacterial Exacerbation of Chronic Bronchitis (ABECB), Acute maxillary sinusitis, Bacterial Infections, Bartonellosis, Community Acquired Pneumonia (CAP), Duodenal ulcer caused by helicobacter pylori, Infective Endocarditis, Lyme Disease, Mycobacterial Infections, Otitis Media (OM), Pertussis, Streptococcal Pharyngitis, Streptococcal tonsillitis, Uncomplicated skin and subcutaneous tissue bacterial infectionsDuodenal Ulcer, Gastric Ulcer, Gastro-esophageal Reflux Disease (GERD), Heartburn, Helicobacter Pylori Infection, NSAID Associated Gastric Ulcers, Non-erosive Reflux Esophagitis Disease (NERD), Vomiting, Zollinger-Ellison Syndrome, Erosive reflux esophagitis

How Rabeprazole + Amoxicillin + Clarithromycin works

Amoxicillin competitively inhibits penicillin-binding protein 1 and other high molecular weight penicillin binding proteins. Penicillin bind proteins are responsible for glycosyltransferase and transpeptidase reactions that lead to cross-linking of D-alanine and D-aspartic acid in bacterial cell walls. Without the action of penicillin binding proteins, bacteria upregulate autolytic enzymes and are unable to build and repair the cell wall, leading to bacteriocidal action.

Clarithromycin is first metabolized to 14-OH clarithromycin, which is active and works synergistically with its parent compound. Like other macrolides, it then penetrates bacteria cell wall and reversibly binds to domain V of the 23S ribosomal RNA of the 50S subunit of the bacterial ribosome, blocking translocation of aminoacyl transfer-RNA and polypeptide synthesis. Clarithromycin also inhibits the hepatic microsomal CYP3A4 isoenzyme and P-glycoprotein, an energy-dependent drug efflux pump.

Rabeprazole belongs to a class of antisecretory compounds (substituted benzimidazole proton-pump inhibitors) that do not exhibit anticholinergic or histamine H2-receptor antagonist properties, but suppress gastric acid secretion by inhibiting the gastric H⁺/K⁺ATPase (hydrogen-potassium adenosine triphosphatase) at the secretory surface of the gastric parietal cell. Because this enzyme is regarded as the acid (proton) pump within the parietal cell, rabeprazole has been characterized as a gastric proton-pump inhibitor. Rabeprazole blocks the final step of gastric acid secretion. In gastric parietal cells, rabeprazole is protonated, accumulates, and is transformed to an active sulfenamide. When studied in vitro, rabeprazole is chemically activated at pH 1.2 with a half-life of 78 seconds.

Dosage

Rabeprazole + Amoxicillin + Clarithromycin dosage

Each tablet twice daily for 7-14 days or as per the physician's advice.

Suspension: Shake the bottle well before adding water. Then add 12 tea spoonful (60 ml) of boiled and cooled water to the bottle and shake well to make 100 ml suspension.

Amoxycillin 500 mg Injection:

• Intramuscular : Add 2.5 ml water for injection to Amoxycillin 500 mg injection vial.
• Intravenous : Dissolve Amoxycillin 500 mg injection in 10 ml water for injection.

This may be given with or without meals.

The usual duration of treatment is 6 to 14 days.

Children older than 12 years: As for adults.

Eradication of H. pylori in patients with duodenal ulcers: Adults: The usual duration of treatment is 6 to 14 days.

45 ml of water is to be added to the granules in the bottle and shaken to yield 70 ml of reconstituted suspension. The concentration of clarithromycin in the reconstituted suspension is 125 mg per 5 ml.

Side Effects

Adverse reactions which were reported as possibly or probably related to treatment (<3%) in clinical trials when all three components of this therapy were given concomitantly are listed below and divided by body systems.

Digestive system: Nausea, vomiting, diarrhoea, dark stools, dry mouth, glossitis, oral moniliasis, stomatitis, tongue discoloration; Musculoskeletal system: Myalgia;

Nervous System: Confusion, headache, dizziness; Skin: Skin reactions; Urogenital System: Vaginitis, vaginal moniliasis.

Toxicity

Patients experiencing an overdose may present with hematuria, oliguria, abdominal pain, acute renal failure, vomiting, diarrhea, rash, hyperactivity, and drowsiness. Treat overdose with symptomatic and supportive treatment, which may include emesis or hemodialysis.

Symptoms of toxicity include diarrhea, nausea, abnormal taste, dyspepsia, and abdominal discomfort. Transient hearing loss with high doses has been observed. Pseudomembraneous colitis has been reported with clarithromycin use. Allergic reactions ranging from urticaria and mild skin eruptions to rare cases of anaphylaxis and Stevens-Johnson syndrome have also occurred. Rare cases of severe hepatic dysfunctions also have been reported. Hepatic failure is usually reversible, but fatalities have been reported. Clarithromycin may also cause tooth decolouration which may be removed by dental cleaning. Fetal abnormalities, such as cardiovascular defects, cleft palate and fetal growth retardation, have been observed in animals. Clarithromycin may cause QT prolongation.

Precaution

Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on Amoxicillin therapy.

Interaction

Rabeprazole is metabolized through the cytochrome P450 system, specially through the CYP3A and CYP2C19 isozymes. Studies have shown that Rabeprazole does not have clinically significant interactions with other drugs metabolized by the cytochrome P450 system, such as warfarin, antipyrine, indomethacin, ibuprofen, phenytoin, propranolol, prednisolone, diazepam, clarithromycin or terfenadine in healthy subjects. Use of Clarithromycin in patients who are receiving theophylline may be associated with an increase of serum theophylline concentrations. There have been reports of interactions of erythromycin and/or clarithromycin with carbamazepine, cyclosporine, tacrolimus, hexobarbital, phenytoin, alfetanil, disopyramide, lovastatin, bromocriptine, valproate, terfenadine, cisapride, pimozide & astemizole.

Volume of Distribution

The central volume of distribution of amoxicillin is 27.7L.

Elimination Route

Amoxicillin is approximately 60% bioavailable. A 250mg dose of oral amoxicillin reaches a C_max 3.93±1.13mg/L with a T_max 1.31±0.33h and an AUC of 27.29±4.72mg*h/L. A 875mg dose of oral amoxicillin reaches a C_max 11.21±3.42mg/L with a T_max 1.52±0.40h and an AUC of 55.04±12.68mg*h/L.

Clarithromycin is well-absorbed, acid stable and may be taken with food.

Absolute bioavailability is approximately 52%.

Half Life

The half life of amoxicillin is 61.3 minutes.

3-4 hours

1-2 hours (in plasma)

Clearance

The mean clearance of amoxicillin is 21.3L/h.

Elimination Route

125mg to 1g doses of amoxicillin are 70-78% eliminated in the urine after 6 hours.

After a 250 mg tablet every 12 hours, approximately 20% of the dose is excreted in the urine as clarithromycin, while after a 500 mg tablet every 12 hours, the urinary excretion of clarithromycin is somewhat greater, approximately 30%.

Following a single 20 mg oral dose of 14C-labeled rabeprazole, approximately 90% of the drug was eliminated in the urine, primarily as thioether carboxylic acid; its glucuronide, and mercapturic acid metabolites.

Pregnancy & Breastfeeding use

There were no adequate and well-controlled studies of in pregnant women. Should be used during pregnancy only if the potential benefit justifies the potential risk of the mother.

Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug therapy, taking into account the importance of the therapy to the mother.

Clarithromycin should not be used in pregnant women except in clinical circumstances where no alternative therapy is appropriate. Amoxicillin is excreted in human milk in very small amounts. There are no available human data on Rabeprazol use in pregnant women to inform the drug associated risk.

Contraindication

This drug is contraindicated in patients with known hypersensitivity to any of its component.

Special Warning

Clarithromycin may be used in neonates and children in appropriate doses.

Use in pediatric patients: The safety and effectiveness of Rabeprazole in pediatric patients have not been established.

Acute Overdose

There has been no experience of overdoses with Rabeprazole. In case of overdosage of Amoxicillin, medication is discontinued, treatment should be symptomatic and supportive measures are institued as required. Overdosage of Clarithromycin can cause gastrointestinal symptoms such as abdominal pain, vomiting, nausea and diarrhea.

Storage Condition

Store in a cool and dry place, protected from light.

Innovators Monograph

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