Heart & Hypertension :: Buy ACIPHEX (RABEPRAZOLE) Online, Gastrointestinal prescription drugs and medications, prescription free

Active Ingredients:
Rabeprazole Therapeutic actions: ACIPHEX® delayed-release tablets are enteric-coated to allow rabeprazole sodium, which is acid labile, to pass through the stomach relatively intact. After oral administration of 20 mg ACIPHEX®, peak plasma concentrations (Cmax) of rabeprazole occur over a range of 2.0 to 5.0 hours (Tmax). The rabeprazole Cmax and AUC are linear over an oral dose range of 10 mg to 40 mg. There is no appreciable accumulation when doses of 10 mg to 40 mg are administered every 24 hours; the pharmacokinetics of rabeprazole are not altered by multiple dosing. The plasma half-life ranges from 1 to 2 hours.
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What is it used for?:
(Indications:) Healing of Erosive or Ulcerative Gastroesophageal Reflux Disease GERD)

ACIPHEX® is indicated for short-term (4 to 8 weeks) treatment in the healing and symptomatic relief of erosive or ulcerative gastroesophageal reflux disease (GERD). For those patients who have not healed after 8 weeks of treatment, an additional 8-week course of ACIPHEX® may be considered.
Maintenance of Healing of Erosive or Ulcerative Gastroesophageal Reflux Disease (GERD)

ACIPHEX® is indicated for maintaining healing and reduction in relapse rates of heartburn symptoms in patients with erosive or ulcerative gastroesophageal reflux disease (GERD Maintenance). Controlled studies do not extend beyond 12 months.
Treatment of Symptomatic Gastroesophageal Reflux Disease (GERD)

ACIPHEX® is indicated for the treatment of daytime and nighttime heartburn and other symptoms associated with GERD.
Healing of Duodenal Ulcers

ACIPHEX® is indicated for short-term (up to four weeks) treatment in the healing and symptomatic relief of duodenal ulcers. Most patients heal within four weeks.
Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence

ACIPHEX® in combination with amoxicillin and clarithromycin as a three drug regimen, is indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or history within the past 5 years) to eradicate H. pylori. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence.

In patients who fail therapy, susceptibility testing should be done. If resistance to clarithromycin is demonstrated or susceptibility testing is not possible, alternative antimicrobial therapy should be instituted.
Treatment of Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome

ACIPHEX® is indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome.

Contraindications and cautions:
Rabeprazole is contraindicated in patients with known hypersensitivity to rabeprazole, substituted benzimidazoles or to any component of the formulation. Clarithromycin is contraindicated in patients with known hypersensitivity to any macrolide antibiotic.

Concomitant administration of clarithromycin with pimozide and cisapride is contraindicated. There have been post-marketing reports of drug interactions when clarithromycin and/or erythromycin are co-administered with pimozide resulting in cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsade de pointes) most likely due to inhibition of hepatic metabolism of pimozide by erythromycin and clarithromycin. Fatalities have been reported. (Please refer to full prescribing information for clarithromycin.)

Amoxicillin is contraindicated in patients with a known hypersensitivity to any penicillin. (Please refer to full prescribing information for amoxicillin.)

WARNINGS

CLARITHROMYCIN SHOULD NOT BE USED IN PREGNANT WOMEN EXCEPT IN CLINICAL CIRCUMSTANCES WHERE NO ALTERNATIVE THERAPY IS APPROPRIATE. If pregnancy occurs while taking clarithromycin, the patient should be apprised of the potential hazard to the fetus. (See WARNINGS in prescribing information for clarithromycin.)

Amoxicillin: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens.

There have been well-documented reports of individuals with a history of penicillin hypersensitivity reactions who have experienced severe hypersensitivity reactions when treated with a cephalosporin. Before initiating therapy with any penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillin, cephalosporin, and other allergens. If an allergic reaction occurs, amoxicillin should be discontinued and the appropriate therapy instituted. (See WARNINGS in prescribing information for amoxicillin.)

SERIOUS ANAPHYLACTIC REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED.

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including clarithromycin and amoxicillin, and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of “antibiotic-associated colitis”.

After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to discontinuation of the drug alone. In moderate to severe cases, consideration should be given to management with fluid and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against
Clostridium difficile colitis.

PRECAUTIONS
General

Symptomatic response to therapy with rabeprazole does not preclude the presence of gastric malignancy. Patients with healed GERD were treated for up to 40 months with rabeprazole and monitored with serial gastric biopsies. Patients without H. pylori infection (221 of 326 patients) had no clinically important pathologic changes in the gastric mucosa.

Patients with H. pylori infection at baseline (105 of 326 patients) had mild or moderate inflammation in the gastric body or mild inflammation in the gastric antrum. Patients with mild grades of infection or inflammation in the gastric body tended to change to moderate, whereas those graded moderate at baseline tended to remain stable. Patients with mild grades of infection or inflammation in the gastric antrum tended to remain stable. At baseline 8% of patients had atrophy of glands in the gastric body and 15% had atrophy in the gastric antrum. At endpoint, 15% of patients had atrophy of glands in the gastric body and 11% had atrophy in the gastric antrum. Approximately 4% of patients had intestinal metaplasia at some point during follow-up, but no consistent changes were seen. Steady state interactions of rabeprazole and warfarin have not been adequately evaluated in patients. There have been reports of increased INR and prothrombin time in patients receiving a proton pump inhibitor and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with a proton pump inhibitor and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time. Information for Patients Patients should be cautioned that ACIPHEX® delayed-release tablets should be swallowed whole. The tablets should not be chewed, crushed, or split. ACIPHEX® can be taken with or without food. Please see accompanying FDA-approved patient labeling Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 88/104-week carcinogenicity study in CD-1 mice, rabeprazole at oral doses up to 100 mg/kg/day did not produce any increased tumor occurrence. The highest tested dose produced a systemic exposure to rabeprazole (AUC) of 1.40µg
•hr/mL which is 1.6 times the human exposure (plasma AUC0-∞ = 0.88µg
•hr/mL) at the recommended dose for GERD (20 mg/day). In a 104-week carcinogenicity study in Sprague-Dawley rats, males were treated with oral doses of 5, 15, 30 and 60 mg/kg/day and females with 5, 15, 30, 60 and 120 mg/kg/day. Rabeprazole produced gastric enterochromaffin-like (ECL) cell hyperplasia in male and female rats and ECL cell carcinoid tumors in female rats at all doses including the lowest tested dose. The lowest dose (5 mg/kg/day) produced a systemic exposure to rabeprazole (AUC) of about 0.1µg
•hr/mL which is about 0.1 times the human exposure at the recommended dose for GERD. In male rats, no treatment related tumors were observed at doses up to 60 mg/kg/day producing a rabeprazole plasma exposure (AUC) of about 0.2µg
•hr/mL (0.2 times the human exposure at the recommended dose for GERD). Rabeprazole was positive in the Ames test, the Chinese hamster ovary cell (CHO/HGPRT) forward gene mutation test and the mouse lymphoma cell (L5178Y/TK+/–) forward gene mutation test. Its demethylated-metabolite was also positive in the Ames test.
Rabeprazole was negative in the in vitro Chinese hamster lung cell chromosome aberration test, the in vivo mouse micronucleus test, and the in vivo and ex vivo rat hepatocyte unscheduled DNA synthesis (UDS) tests. Rabeprazole at intravenous doses up to 30 mg/kg/day (plasma AUC of 8.8µg
•hr/mL, about 10 times the human exposure at the recommended dose for GERD) was found to have no effect on fertility and reproductive performance of male and female rats. Pregnancy Teratogenic Effects.
Pregnancy Category B: Teratology studies have been performed in rats at intravenous doses up to 50 mg/kg/day (plasma AUC of 11.8µg
•hr/mL, about 13 times the human exposure at the recommended dose for GERD) and rabbits at intravenous doses up to 30 mg/kg/day (plasma AUC of 7.3µg
•hr/mL, about 8 times the human exposure at the recommended dose for GERD) and have revealed no evidence of impaired fertility or harm to the fetus due to rabeprazole. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Nursing Mothers

Following intravenous administration of 14C-labeled rabeprazole to lactating rats, radioactivity in milk reached levels that were 2- to 7-fold higher than levels in the blood. It is not known if unmetabolized rabeprazole is excreted in human breast milk. Administration of rabeprazole to rats in late gestation and during lactation at doses of 400 mg/kg/day (about 195-times the human dose based on mg/m2) resulted in decreases in body weight gain of the pups. Since many drugs are excreted in milk, and because of the potential for adverse reactions to nursing infants from rabeprazole, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and effectiveness of rabeprazole in pediatric patients have not been established.

Use in Women

Duodenal ulcer and erosive esophagitis healing rates in women are similar to those in men.
Adverse events and laboratory test abnormalities in women occurred at rates similar to those in men.

Geriatric Use

Of the total number of subjects in clinical studies of ACIPHEX®, 19% were 65 years and over, while 4% were 75 years and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Side effects:
Worldwide, over 2900 patients have been treated with rabeprazole in Phase II-III clinical trials involving various dosages and durations of treatment. In general, rabeprazole treatment has been well-tolerated in both short-term and long-term trials. The adverse events rates were generally similar between the 10 and 20 mg doses.
Incidence in Controlled North American and European Clinical Trials

In an analysis of adverse events assessed as possibly or probably related to treatment appearing in greater than 1% of ACIPHEX® patients and appearing with greater frequency than placebo in controlled North American and European trials, the incidence of headache was 2.4% (n=1552) for ACIPHEX® versus 1.6% (n=258) for placebo. In short and long-term studies, the following adverse events, regardless of causality, were reported in ACIPHEX®-treated patients. Rare events are those reported in ≤ 1/1000 patients.

Body as a Whole: asthenia, fever, allergic reaction, chills, malaise, chest pain substernal, neck rigidity, photosensitivity reaction.
Rare: abdomen enlarged, face edema, hangover effect.
Cardiovascular System: hypertension, myocardial infarct, electrocardiogram abnormal, migraine, syncope, angina pectoris, bundle branch block, palpitation, sinus bradycardia, tachycardia.
Rare: bradycardia, pulmonary embolus, supraventricular tachycardia, thrombophlebitis, vasodilation, QTC prolongation and ventricular tachycardia.
Digestive System: diarrhea, nausea, abdominal pain, vomiting, dyspepsia, flatulence, constipation, dry mouth, eructation, gastroenteritis, rectal hemorrhage, melena, ano-rexia, cholelithiasis, mouth ulceration, stomatitis, dysphagia, gingivitis, cholecystitis, increased appetite, abnormal stools, colitis, esophagitis, glossitis, pancreatitis, proctitis.
Rare: bloody diarrhea, cholangitis, duodenitis, gastrointestinal hemorrhage, hepatic encephalopathy, hepatitis, hepatoma, liver fatty deposit, salivary gland enlargement, thirst.
Endocrine System: hyperthyroidism, hypothyroidism.
Hemic & Lymphatic System: anemia, ecchymosis, lymphadenopathy, hypochromic anemia.
Metabolic & Nutritional Disorders: peripheral edema, edema, weight gain, gout, dehydration, weight loss.
Musculo-Skeletal System: myalgia, arthritis, leg cramps, bone pain, arthrosis, bursitis.
Rare: twitching.
Nervous System: insomnia, anxiety, dizziness, depression, nervousness, somnolence, hypertonia, neuralgia, vertigo, convulsion, abnormal dreams, libido decreased, neuropathy, paresthesia, tremor.
Rare: agitation, amnesia, confusion, extrapyramidal syndrome, hyperkinesia.
Respiratory System: dyspnea, asthma, epistaxis, laryngitis, hiccup, hyperventilation.
Rare: apnea, hypoventilation.
Skin and Appendages: rash, pruritus, sweating, urticaria, alopecia.
Rare: dry skin, herpes zoster, psoriasis, skin discoloration.
Special Senses: cataract, amblyopia, glaucoma, dry eyes, abnormal vision, tinnitus, otitis media.
Rare: corneal opacity, blurry vision, diplopia, deafness, eye pain, retinal degeneration, strabismus.
Urogenital System: cystitis, urinary frequency, dysmenorrhea, dysuria, kidney calculus, metrorrhagia, polyuria.
Rare: breast enlargement, hematuria, impotence, leukorrhea, menorrhagia, orchitis, urinary incontinence.
Laboratory Values: The following changes in laboratory parameters were reported as adverse events: abnormal platelets, albuminuria, creatine phosphokinase increased, erythrocytes abnormal, hypercholesteremia, hyperglycemia, hyperlipemia, hypokalemia, hyponatremia, leukocytosis, leukorrhea, liver function tests abnormal, prostatic specific antigen increase, SGPT increased, urine abnormality, WBC abnormal.

In controlled clinical studies, 3/1456 (0.2%) patients treated with rabeprazole and 2/237 (0.8%) patients treated with placebo developed treatment-emergent abnormalities (which were either new on study or present at study entry with an increase of 1.25 x baseline value) in SGOT (AST), SGPT (ALT), or both. None of the three rabeprazole patients experienced chills, fever, right upper quadrant pain, nausea or jaundice.

Combination Treatment with Amoxicillin and Clarithromycin:
In clinical trials using combination therapy with rabeprazole plus amoxicillin and clarithromycin (RAC), no adverse events unique to this drug combination were observed. In the U.S. multicenter study, the most frequently reported drug related adverse events for patients who received RAC therapy for 7 or 10 days were diarrhea (8% and 7%) and taste perversion (6% and 10%), respectively. No clinically significant laboratory abnormalities particular to the drug combinations were observed. For more information on adverse events or laboratory changes with amoxicillin or clarithromycin, refer to their respective package prescribing information, ADVERSE REACTIONS section.

Post-Marketing Adverse Events: Additional adverse events reported from worldwide marketing experience with rabeprazole sodium are: sudden death; coma and hyperammonemia; jaundice; rhabdomyolysis; disorientation and delirium; anaphylaxis; angioedema; bullous and other drug eruptions of the skin; severe dermatologic reactions, including toxic epidermal necrolysis (some fatal), Stevens-Johnson syndrome, and erythema multiforme; interstitial pneumonia; interstitial nephritis; and TSH elevations. In most instances, the relationship to rabeprazole sodium was unclear. In addition, agranulocytosis, hemolytic anemia, leukopenia, pancytopenia, and thrombocytopenia have been reported. Increases in prothrombin time/INR in patients treated with concomitant warfarin have been reported.

Interactions:
Rabeprazole is metabolized by the cytochrome P450 (CYP450) drug metabolizing enzyme system. Studies in healthy subjects have shown that rabeprazole does not have clinically significant interactions with other drugs metabolized by the CYP450 system, such as warfarin and theophylline given as single oral doses, diazepam as a single intravenous dose, and phenytoin given as a single intravenous dose (with supplemental oral dosing). Steady state interactions of rabeprazole and other drugs metabolized by this enzyme system have not been studied in patients. There have been reports of increased INR and prothrombin time in patients receiving proton pump inhibitors, including rabeprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. In vitro incubations employing human liver microsomes indicated that rabeprazole inhibited cyclosporine metabolism with an IC50 of 62 micromolar, a concentration that is over 50 times higher than the Cmax in healthy volunteers following 14 days of dosing with 20 mg of rabeprazole. This degree of inhibition is similar to that by omeprazole at equivalent concentrations.

Rabeprazole produces sustained inhibition of gastric acid secretion. An interaction with compounds which are dependent on gastric pH for absorption may occur due to the magnitude of acid suppression observed with rabeprazole. For example, in normal subjects, co-administration of rabeprazole 20 mg QD resulted in an approximately 30% decrease in the bioavailability of ketoconazole and increases in the AUC and Cmax for digoxin of 19% and 29%, respectively. Therefore, patients may need to be monitored when such drugs are taken concomitantly with rabeprazole. Co-administration of rabeprazole and antacids produced no clinically relevant changes in plasma rabeprazole concentrations.

In a clinical study in Japan evaluating rabeprazole in patients categorized by CYP2C19 genotype (n=6 per genotype category), gastric acid suppression was higher in poor metabolizers as compared to extensive metabolizers. This could be due to higher rabeprazole plasma levels in poor metabolizers. Whether or not interactions of rabeprazole sodium with other drugs metabolized by CYP2C19 would be different between extensive metabolizers and poor metabolizers has not been studied. Combined Administration with Clarithromycin

Combined administration consisting of rabeprazole, amoxicillin, and clarithromycin resulted in increases in plasma concentrations of rabeprazole and 14-hydroxyclarithromycin.

Concomitant administration of clarithromycin with pimozide and cisapride is contraindicated

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