Aciphex

Name: Aciphex

What Is Aciphex (Rabeprazole)?

Aciphex is the brand name of the drug rabeprazole, which is used for the treatment of gastroesophageal reflux disease (GERD), a chronic digestive disorder.

In people with GERD, stomach acid and occasionally other stomach contents flow backward into the esophagus (the tube connecting the throat and stomach).

The condition causes heartburn and can damage the esophagus.

Aciphex belongs to a class of medications called proton pump inhibitors (PPIs), which inhibit an enzyme involved in producing acid in the stomach.

By reducing stomach acid, Aciphex relieves heartburn and other GERD symptoms of, such as belching and a bad taste in your throat. The drug also:

  • Helps heal a damaged esophagus
  • Prevents recurrence of heartburn symptoms
  • Treats ulcers (open sores) in the duodenum, the first part of the small intestine
  • Helps to eliminate the ulcer-causing bacterium Helicobacter pylori from the intestinal tract
  • Treats disorders that cause the stomach to produce excess acid, such as Zollinger-Ellison syndrome

Healthcare professionals sometimes prescribe Aciphex for off-label to treat functional dyspepsia, a condition that causes upset stomach and pain in the upper abdomen.

Aciphex may be used to treat GERD in children between 1 and 11 years old, as well as heartburn and other symptoms associated with GERD in adolescent children age 12 or older.

Aciphex was first was approved by the Food and Drug Administration (FDA) in 1999. Janssen Pharmaceuticals markets the drug.

In 2011, the consumer group Public Citizen petitioned the FDA to add black-box warnings to all PPIs, including Aciphex.

A black-box warning — the strongest warning possible on a drug label — would inform the user that there is an increase in risk of severe side effects, such as Clostridium difficile (C. diff) infection, irregular heartbeat, and hip fracture.

It would also state that rebound acid reflux, an increase in stomach acid, may also occur when you stop taking the drug after prolonged use.

In 2014, Public Citizen filed a lawsuit against the FDA for its failure to respond to the petition.

Aciphex Warnings

You shouldnt take Aciphex if youre hypersensitive to rabeprazole or other substituted benzimidazoles.

As with other PPIs, Aciphex may increase your risk of a C. difficile infection, which causes severe diarrhea.

Call your doctor immediately if you have watery stool, stomach pain, or persistent fever or all three infection symptoms.

Aciphex may increase your risk of hip, wrist, or spine fracture if youre taking multiple doses a day.

Additionally, prolonged use may cause a low magnesium level, which can lead to various symptoms. Inform your doctor if you experience:

  • Seizures
  • Dizziness
  • Abnormal heart rate
  • Jitteriness or tremors (uncontrollable shaking)
  • Muscle weakness
  • Spasms in the hands, feet, or voice box (larynx)
  • Cramps or muscle aches

Pregnancy and Aciphex

There's no evidence from animal studies that Aciphex harms developing fetuses, but research in pregnant women is inconclusive.

You should tell your doctor if you are pregnant or might become pregnant before taking this medicine.

Aciphex is excreted in rat milk, but it's not known if the same is true for human breast milk.

You shouldnt use this drug while breastfeeding a baby without first talking to your doctor.

Aciphex Side Effects

Common Side Effects of Aciphex

The most common side effects of Aciphex in adults are:

  • Pain
  • Sore throat
  • Gas
  • Constipation
  • Infection

In young children and adolescents, the most common side effects of Aciphex are:

  • Diarrhea
  • Pain
  • Headache

Less commonly, adolescents may experience nausea and vomiting.

Severe Side Effects of Aciphex

Allergic reactions to Aciphex may result in severe side effects, including:

  • Rash
  • Face swelling
  • Throat tightening
  • Difficulty breathing

Rare Side Effects of Aciphex

Rare side effects in adults include:

  • Headache
  • Abdominal pain
  • Diarrhea
  • Dry mouth
  • Dizziness
  • Swollen arms and legs
  • Decreased liver function, resulting in worsening brain function
  • Hepatitis (liver inflammation)
  • Muscle or joint pain

What special precautions should I follow?

Before taking rabeprazole,

  • tell your doctor and pharmacist if you are allergic to rabeprazole, dexlansoprazole (Dexilant), esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), any other medications, or any of the ingredients in rabeprazole tablets. Ask your pharmacist for a list of the ingredients.
  • tell your doctor if you are taking rilpivirine (Edurant, in Complera, Odefsey). Your doctor will probably tell you not to take rabeprazole if you are taking this medication.
  • tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: certain antibiotics, anticoagulants ('blood thinners') such as warfarin (Coumadin), atazanavir (Reyataz), cyclosporine (Neoral, Sandimmune), digoxin (Lanoxin), diuretics ('water pills'), ketoconazole (Nizoral), iron supplements, and methotrexate (Rheumatrex, Trexall). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor if you have or have ever had a low level of magnesium in your blood or liver disease.
  • tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking rabeprazole, call your doctor.
  • if you are 50 years of age or older, ask your doctor if it is safe for you to take rabeprazole. The risk that you may develop a severe form of diarrhea caused by bacteria or that you may fracture your wrist, hip, or spine may be higher if you are an older adult.

What brand names are available for rabeprazole?

Aciphex

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Rabeprazole side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • severe stomach pain, diarrhea that is watery or bloody;

  • seizure (convulsions);

  • kidney problems--urinating more or less than usual, blood in your urine, swelling, rapid weight gain;

  • symptoms of low magnesium--dizziness, confusion; fast or uneven heart rate; tremors (shaking) or jerking muscle movements; feeling jittery; muscle pain or weakness, muscle spasms in your hands and feet; cough or choking feeling; or

  • signs of bleeding (if you also take warfarin)--headaches, unusual weakness, dizziness; unusual bleeding (nosebleeds, bleeding gums); red or pink urine; abnormal vaginal bleeding or heavy menstrual flow; bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds; or any bleeding that will not stop.

Common side effects may include:

  • headache;

  • sore throat;

  • diarrhea, constipation; or

  • stomach pain, gas, nausea, vomiting.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

AcipHex Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability with 20 mg dose is about 52%.1 Repeated dosing does not affect pharmacokinetics.1

Onset

Within 1 hour.1 23 Median inhibition of 24-hour gastric acidity is 88% of maximum after first dose.1

Food

High-fat meal may delay absorption but does not affect extent.1 20 23

Special Populations

AUC increased 50–60% in Japanese males receiving a different rabeprazole formulation.1

AUC doubled in patients with mild to moderate compensated cirrhosis.1 Peak plasma concentrations and AUCs increased 20% in patients with mild to moderate hepatic impairment.1

In geriatric patients, peak plasma concentration increased by 60% and AUCs doubled.1

Distribution

Extent

Not known whether rabeprazole crosses the placenta or is distributed into milk.1

Prolonged binding to gastric parietal proton pump enzyme.1 3

Plasma Protein Binding

Approximately 96%.1

Elimination

Metabolism

Metabolized in the liver, principally by CYP3A and CYP2C19.1 7 8 9 Principal thioether and sulphone metabolites found in plasma are inactive.1

Elimination Route

Excreted as metabolites in urine (90%); remainder in feces.1

Half-life

1–2 hours.1

Special Populations

In patients with mild to moderate compensated cirrhosis, elimination half-life was 2–3 times greater, and clearance decreased to less than one-half.1

In patients with poor CYP2C19 metabolizer phenotype, metabolism is slower than in those with extensive (or rapid) metabolizer phenotype.1

Advice to Patients

  • Importance of swallowing tablets whole, without crushing or chewing.1

  • Importance of advising patients that use of multiple daily doses of the drug for an extended period of time may increase the risk of fractures of the hip, wrist, or spine.305 1

  • Risk of hypomagnesemia; importance of immediately reporting and seeking care for any cardiovascular or neurologic manifestations (e.g., palpitations, dizziness, seizures, tetany).1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1 23 Antacids may be used concomitantly as needed for pain relief.1 19

  • Possible increased risk of Clostridium difficile infection; importance of contacting clinician if persistent watery stools, abdominal pain, and fever occur.335

  • Importance of women informing their clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Uses For Aciphex

Rabeprazole is used to treat duodenal ulcers, gastroesophageal reflux disease (GERD), and Zollinger-Ellison syndrome. It may also be used together with antibiotics to treat ulcers associated with infections caused by the H. pylori bacteria. Rabeprazole is a proton pump inhibitor (PPI) that decreases the amount of acid produced by the stomach.

This medicine is available only with your doctor's prescription.

Use in specific populations

8.1 Pregnancy 

Risk Summary

There are no available human data on Aciphex use in pregnant women to inform the drug associated risk. The background risk of major birth defects and miscarriage for the indicated populations are unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies.  No evidence of adverse developmental effects were seen in animal reproduction studies with rabeprazole administered during organogenesis at 13 and 8 times the human area under the plasma concentration-time curve (AUC) at the recommended dose for GERD, in rats and rabbits, respectively [see Data].

Changes in bone morphology were observed in offspring of rats treated with oral doses of a different PPI through most of pregnancy and lactation [see Data].  Advise pregnant women of the potential risk to a fetus.

Data

Animal Data

Embryo-fetal developmental studies have been performed in rats during organogenesis at intravenous doses of rabeprazole up to 50 mg/kg/day (plasma AUC of 11.8 µg•hr/mL, about 13 times the human exposure at the recommended oral dose for GERD) and rabbits at intravenous doses up to 30 mg/kg/day (plasma AUC of 7.3 µg•hr/mL, about 8 times the human exposure at the recommended oral dose for GERD) and have revealed no evidence of harm to the fetus due to rabeprazole.

Administration of rabeprazole to rats in late gestation and during lactation at an oral dose of 400 mg/kg/day (about 195-times the human oral dose based on mg/m2) resulted in decreases in body weight gain of the pups.

A pre- and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone development was performed with a different PPI at about 3.4 to 57 times an oral human dose on a body surface area basis. Decreased femur length, width and thickness of cortical bone, decreased thickness of the tibial growth plate, and minimal to mild bone marrow hypocellularity were noted at doses of this PPI equal to or greater than 3.4 times an oral human dose on a body surface area basis.  Physeal dysplasia in the femur was also observed in offspring after in utero and lactational exposure to the PPI at doses equal to or greater than 33.6 times an oral human dose on a body surface area basis.  Effects on maternal bone were observed in pregnant and lactating rats in a pre- and postnatal toxicity study when the PPI was administered at oral doses of 3.4 to 57 times an oral human dose on a body surface area basis.  When rats were dosed from gestational day 7 through weaning on postnatal day 21, a statistically significant decrease in maternal femur weight of up to 14% (as compared to placebo treatment) was observed at doses equal to or greater than 33.6 times an oral human dose on a body surface area basis.

8.2 Lactation

Risk Summary

Lactation studies have not been conducted to assess the presence of rabeprazole in human milk, the effects of rabeprazole on the breastfed infant, or the effects of rabeprazole on milk production.  Rabeprazole is present in rat milk. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for Aciphex and any potential adverse effects on the breastfed infant from Aciphex or from the underlying maternal condition.

8.4 Pediatric Use

The safety and effectiveness of Aciphex delayed-release tablets have been established in pediatric patients for adolescent patients 12 years of age and older for the treatment of symptomatic GERD. Use of Aciphex delayed-release tablets in this age group is supported by  adequate and well controlled studies in adults and a multicenter, randomized, open-label, parallel-group study in 111 adolescent patients 12 to 16 years of age. Patients had a clinical diagnosis of symptomatic GERD, or suspected or endoscopically proven GERD and were randomized to either 10 mg or 20 mg once daily for up to 8 weeks for the evaluation of safety and efficacy.  The adverse reaction profile in adolescent patients was similar to that of adults.  The related reported adverse reactions that occurred in ≥2% of patients were headache (5%) and nausea (2%).  There were no adverse reactions reported in these studies that were not previously observed in adults. 

The safety and effectiveness of Aciphex delayed-release tablets have not been established in pediatric patients for:

  • Healing of Erosive or Ulcerative GERD
  • Maintenance of Healing of Erosive or Ulcerative GERD
  • Treatment of Symptomatic GERD
  • Healing of Duodenal Ulcers
  • Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence
  • Treatment of Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome

Aciphex delayed-release 20 mg tablets are not recommended for use in pediatric patients less than 12 years of age because the tablet strength exceeds the recommended dose for these patients [see Dosage and Administration (2)].  For pediatric patients 1 year to less than 12 years of age consider another rabeprazole formulation.  The safety and effectiveness of a different dosage form and dosage strength of rabeprazole has been established in pediatric patients 1 to 11 years for the treatment of GERD.

Juvenile Animal Data

Studies in juvenile and young adult rats and dogs were performed.  In juvenile animal studies rabeprazole sodium was administered orally to rats for up to 5 weeks and to dogs for up to 13 weeks, each commencing on Day 7 post-partum and followed by a 13-week recovery period.  Rats were dosed at 5, 25, or 150 mg/kg/day and dogs were dosed at 3, 10, or 30 mg/kg/day.  The data from these studies were comparable to those reported for young adult animals.  Pharmacologically mediated changes, including increased serum gastrin levels and stomach changes, were observed at all dose levels in both rats and dogs.  These observations were reversible over the 13-week recovery periods.  Although body weights and/or crown-rump lengths were minimally decreased during dosing, no effects on the development parameters were noted in either juvenile rats or dogs.

When juvenile animals were treated for 28 days with a different PPI at doses equal to or greater than 34 times the daily oral human dose on a body surface area basis, overall growth was affected and treatment-related decreases in body weight (approximately 14%) and body weight gain, and decreases in femur weight and femur length were observed.  

8.5 Geriatric Use

Of the total number of subjects (n=2009) in clinical studies of Aciphex delayed-release tablets, 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.

8.6 Hepatic Impairment

Administration of Aciphex delayed-release tablets to patients with mild to moderate hepatic impairment (Child-Pugh Class A and B, respectively) resulted in increased exposure and decreased elimination [see Clinical Pharmacology (12.3)].  No dosage adjustment is necessary in patients with mild to moderate hepatic impairment. There is no information in patients with severe hepatic impairment (Child-Pugh Class C).  Avoid use of Aciphex delayed-release tablets in patients with severe hepatic impairment; however, if treatment is necessary, monitor patients for adverse reactions [see Warnings and Precautions (5), Adverse Reactions (6)].

Aciphex Overview

Aciphex is a prescription medication used to treat digestive problems such as heartburn and acid reflux.  Aciphex belongs to a group of drugs called proton-pump inhibitors (PPIs). It works by reducing the amount of acid produced in the stomach.

Aciphex comes in a delayed release tablet and is usually taken once a day.

Swallow Aciphex tablets whole. Do not chew, crush or split Aciphex tablets.

Common side effects of Aciphex include headache, sore throat, and constipation.

Side Effects of Aciphex

Serious side effects have been reported with Aciphex. See the “Drug Precautions” section.

Common side effects with Aciphex include the following

  • headache
  • pain
  • sore throat
  • gas
  • infection
  • constipation

People who are taking multiple daily doses of proton pump inhibitor medicines for a long period of time may have an increased risk of fractures of the hip, wrist, or spine.

This is not a comple list of Aciphex side effects. Ask your doctor or pharmacist for more information.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Aciphex Interactions

Tell your doctor about all of the medicines you are taking or are planning to take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

  • atazanavir (Reyataz)
  • cyclosporine (Sandimmune, Neoral)
  • digoxin (Lanoxin)
  • ketoconazole (Nizoral)
  • warfarin (Coumadin)
  • theophylline (THEO-24 Thelair)
  • diazepam (Valium)
  • phenytoin (Dilantin)
  • antibiotics

Aciphex Precautions

Serious side effects have been reported with Aciphex including the following:

  • serious allergic reactions. Tell your doctor if you have any of the following symptoms:
  • rash
  • face swelling
  • throat tightness
  • difficulty breathing
  • low blood magnesium. Tell your doctor right away if you have any of these symptoms:
    • seizures
    • dizziness
    • abnormal or fast heart beat
    • jitteriness
    • jerking movements or shaking (tremors)
    • muscle weakness
    • spasms of the hands and feet
    • cramps or muscle aches
    • spasm of the voice box

Your doctor may check the level of magnesium in your body before you start taking Aciphex, during treatment, or if you will be taking Aciphex for a long period of time.

  • Clostridium difficile (C. difficile) associated diarrhea. Tell your healthcare provider if you experience any or all of the following symptoms:
  • watery diarrhea (at least three bowel movements per day for two or more days)
  • loss of appetite
  • abdominal pain or tenderness
  • nausea
  • fever

Do not take Aciphex if you are:

  • allergic to any of the ingredients in Aciphex
  • allergic to other proton pump inhibitors
  • less than 12 years of age

Other Requirements

Store Aciphex in a dry place at room temperature, 59°F to 86°F (15°C to 30°C).

Keep Aciphex and all medicines out of the reach of children.

Adverse Effects

1-10%

Headache (2-10%)

Constipation (2%)

Diarrhea (2-5%)

Flatulence (3%)

Pain (3%)

Pharyngitis (3%)

Abdominal pain (4%)

<1%

Agitation

Agranulocytosis

Alopecia

Anemia

Angioedema

Chest pain

Delirium

Erythema multiforme

Hypokalemia

Hypomagnesemia

Hyponatremia

Jaundice

Leukocytosis

Leukopenia

Migraine

Osteoporosis related fracture

Rhabdomyolysis

Stevens-Johnson syndrome

Sudden death

Toxic epidermal necrolysis

Abnormal taste

Postmarketing Reports

Cutaneous and systemic lupus erythematosus

Cyanocobalamin (vitamin B-12) deficiency

What should I avoid while taking AcipHex?

This medicine can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or bloody, call your doctor. Do not use anti-diarrhea medicine unless your doctor tells you to.

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