Side Effects of Aciphex (rabeprazole)

Aciphex (rabeprazole) is a proton pump inhibitor (PPI) used to treat acid-caused conditions such as

• stomach and duodenal ulcers,
• gastroesophageal reflux disease (GERD), and
• Zollinger-Ellison Syndrome.

It also is used with antibiotics for eradicating Helicobacter pylori infections of the stomach that, along with acid, are responsible for many ulcers.

Aciphex, like other PPIs, blocks the pump in the wall of the stomach that secretes acid into the stomach. By blocking the pump, the secretion of acid into the stomach is decreased, and this allows ulcers in the stomach and esophagus to heal. 

Common side effects of Aciphex include

• diarrhea,
• nausea,
• vomiting,
• constipation,
• rash,
• headaches,
• dizziness,
• nervousness,
• abnormal heartbeat,
• muscle pain,
• weakness,
• leg cramps, and
• water retention.

Serious side effects of Aciphex include

• severe stomach pain,
• watery or bloody diarrhea,
• seizure,
• kidney problems,
• low magnesium, and
• signs of bleeding (in patients who also take warfarin).

Drug interactions of Aciphex include warfarin, which can lead to increased bleeding when taken with Aciphex.

Aciphex may reduce the elimination of cyclosporine in the liver, thereby increasing cyclosporine levels in the blood and potentially leading to cyclosporine toxicity.

The absorption of certain drugs may be affected by changes in stomach acidity. Aciphex and other PPIs that reduce stomach acid reduce the absorption and concentration in blood of ketoconazole and increase the absorption and concentration in blood of digoxin, which may lead to reduced effectiveness of ketoconazole or increased digoxin toxicity, respectively.

PPIs may decrease blood levels of atazanavir.

Use of Aciphex in pregnant women has not been adequately evaluated. Aciphex has not been studied in nursing women. Consult your doctor before breastfeeding.

Rabeprazole like other PPIs has few side effects. The most common side effects are:

• diarrhea,
• nausea,
• vomiting,
• constipation,
• rash, and
• headaches.

Other side effects include:

• dizziness,
• nervousness,
• abnormal heartbeat,
• muscle pain,
• weakness,
• leg cramps, and
• water retention.

The following serious adverse reactions are described below and elsewhere in labeling:

• Acute Interstitial Nephritis
• Clostridium difficile-Associated Diarrhea
• Bone Fracture
• Cutaneous and Systemic Lupus Erythematosus
• Cyanocobalamin (Vitamin B-12) Deficiency
• Hypomagnesemia

Clinical Studies Experience

Because clinical trials are conducted under varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adults

The data described below reflect exposure to Aciphex delayed-release tablets in 1064 adult patients exposed for up to 8 weeks. The studies were primarily placebo- and active-controlled trials in adult patients with Erosive or Ulcerative Gastroesophageal Reflux Disease (GERD), Duodenal Ulcers and Gastric Ulcers.

The population had a mean age of 53 years (range 18-89 years) and had a ratio of approximately 60% male: 40% female. The racial distribution was

• 86% Caucasian,
• 8% African American,
• 2% Asian, and
• 5% other.

Most patients received either 10 mg, 20 mg or 40 mg per day of Aciphex delayed-release tablets.

An analysis of adverse reactions appearing in ≥2% of patients treated with Aciphex delayed-release tablets (n=1064) and with a greater frequency than placebo (n=89) in controlled North American and European acute treatment trials, revealed the following adverse reactions:

• pain (3% vs. 1%),
• pharyngitis (3% vs. 2%),
• flatulence (3% vs. 1%),
• infection (2% vs. 1%), and
• constipation (2% vs. 1%).

Three long-term maintenance studies consisted of a total of 740 adult patients; at least 54% of adult patients were exposed to Aciphex delayed-release tablets for 6 months and at least 33% were exposed for 12 months.

Of the 740 adult patients, 247 (33%) and 241 (33%) patients received 10 mg and 20 mg of Aciphex delayed-release tablets, respectively, while 169 (23%) patients received placebo and 83 (11%) received omeprazole.

The safety profile of rabeprazole in the maintenance studies in adults was consistent with what was observed in the acute studies.

Less common adverse reactions seen in controlled clinical trials (<2% of patients treated with Aciphex delayed-release tablets and greater than placebo) and for which there is a possibility of a causal relationship to rabeprazole, include the following:

• headache,
• abdominal pain,
• diarrhea,
• dry mouth,
• dizziness,
• peripheral edema,
• hepatic enzyme increase,
• hepatitis,
• hepatic encephalopathy,
• myalgia, and
• arthralgia.

Combination Treatment With Amoxicillin And Clarithromycin

In clinical trials using combination therapy with rabeprazole plus amoxicillin and clarithromycin (RAC), no adverse reactions unique to this drug combination were observed.

In the U.S. multicenter study, the most frequently reported drug related adverse reactions 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 reactions or laboratory changes with amoxicillin or clarithromycin, refer to their respective prescribing information, Adverse Reactions section.

Pediatrics

In a multicenter, open-label study of adolescent patients 12 to 16 years of age with a clinical diagnosis of symptomatic GERD or endoscopically proven GERD, the adverse event profile was similar to that of adults. The adverse reactions reported without regard to relationship to Aciphex delayed-release tablets that occurred in ≥2% of 111 patients were

• headache (9.9%),
• diarrhea (4.5%),
• nausea (4.5%),
• vomiting (3.6%), and
• abdominal pain (3.6%).

The related reported adverse reactions that occurred in ≥2% of patients were

• headache (5.4%) and
• nausea (1.8%).

There were no adverse reactions reported in this study that were not previously observed in adults.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of rabeprazole. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

Blood and Lymphatic System Disorders: agranulocytosis, hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia

Ear and Labyrinth Disorders: vertigo

Eye Disorders: blurred vision

General Disorders and Administration Site Conditions: sudden death

Hepatobiliary Disorders: jaundice

Immune System Disorders: anaphylaxis, angioedema, systemic lupus erythematosus, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal)

Infections and Infestations: Clostridium difficile-associated diarrhea

Investigations: Increases in prothrombin time/INR (in patients treated with concomitant warfarin), TSH elevations

Metabolism and Nutrition Disorders: hyperammonemia, hypomagnesemia

Musculoskeletal System Disorders: bone fracture, rhabdomyolysis

Nervous System Disorders: coma

Psychiatric Disorders: delirium, disorientation

Renal and Urinary Disorders: interstitial nephritis

Respiratory, Thoracic and Mediastinal Disorders: interstitial pneumonia

Skin and Subcutaneous Tissue Disorders: severe dermatologic reactions including bullous and other drug eruptions of the skin, cutaneous lupus erythematosus, erythema multiforme

Table 2 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with Aciphex delayed-release tablets and instructions for preventing or managing them.

Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs.

Table 2: Clinically Relevant Interactions Affecting Drugs Co-Administered with Aciphex Delayed-Release Tablets and Interactions with Diagnostics