Aciphex

Name: Aciphex

Which drugs or supplements interact with rabeprazole?

There have been reports of an increase in the effect of the blood thinner, warfarin (Coumadin), by rabeprazole which theoretically could lead to increased bleeding. Patients taking warfarin should be monitored more frequently if they begin taking rabeprazole. Rabeprazole may reduce the elimination of cyclosporin in the liver, thereby increasing cyclosporin levels in the blood and potentially leading to cyclosporin toxicity. The absorption of certain drugs may be affected by changes in stomach acidity. Rabeprazole and other PPIs that reduce stomach acid reduce the absorption and concentration in blood of ketoconazole (Nizoral) and increase the absorption and concentration in blood of digoxin (Lanoxin). This may lead to reduced effectiveness of ketoconazole or increased digoxin toxicity, respectively. PPIs may decrease blood levels of atazanavir (Reyataz).

What else should I know about rabeprazole?

What preparations of rabeprazole are available?

Tablets (Delayed release): 20 mg

How should I keep rabeprazole stored?

Rabeprazole should be stored at room temperature, 15 C - 30 C (59 F - 86 F) and should be kept away from moisture.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Precautions While Using Aciphex

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if this medicine is working properly and to decide if you should continue to take it. Blood and other laboratory tests may be needed to check for unwanted effects.

Do not use rabeprazole together with medicines containing rilpivirine (eg, Complera®, Edurant®, Odefsey®).

Check with your doctor right away if you have a decrease in how much or how often you urinate, bloody or cloudy urine, swelling of the feet or lower legs, rash, or a fever. These may be symptoms of a serious kidney problem.

This medicine may cause diarrhea, and in some cases it can be severe. Do not take any medicine to treat diarrhea without first checking with your doctor. If you have any questions or if mild diarrhea continues or gets worse, check with your doctor.

This medicine may increase your risk of having fractures of the hip, wrist, and spine. This is more likely if you take several doses per day or use it for 1 year or more. Call your doctor right away if you have severe bone pain or are unable to walk or sit normally.

Cutaneous or systemic lupus erythematosus may occur or gets worse in lupus patients and are taking PPI. Call your doctor right away if you have a joint pain or skin rash on your cheeks or arms that gets worse when exposed in the sun.

This medicine may cause hypomagnesemia (low magnesium in the blood). Your doctor may check your blood levels if you are taking this medicine for more than 1 year or if you are taking certain medicines together with rabeprazole. Check with your doctor right away if you have drowsiness, a loss of appetite, mood or mental changes, muscle spasms or twitching, seizures, nausea or vomiting, trembling, or unusual tiredness or weakness.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Warnings and precautions

5.1 Presence of Gastric Malignancy

In adults, symptomatic response to therapy with Aciphex does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a PPI.

5.2 Interaction with Warfarin

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 Aciphex delayed-release tablets and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time [see Drug Interactions (7)].

5.3 Acute Interstitial Nephritis

Acute interstitial nephritis has been observed in patients taking PPIs including Aciphex.  Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction.  Discontinue Aciphex if acute interstitial nephritis develops [see Contraindications (4)].

5.4 Clostridium difficile-Associated Diarrhea

Published observational studies suggest that PPI therapy like Aciphex may be associated with an increased risk of Clostridium difficile-associated diarrhea, especially in hospitalized patients.  This diagnosis should be considered for diarrhea that does not improve [see Adverse Reactions (6.2)].

Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.

Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents.  For more information specific to antibacterial agents (clarithromycin and amoxicillin) indicated for use in combination with Aciphex, refer to Warnings and Precautions sections of the corresponding prescribing information.

5.5 Bone Fracture

Several published observational studies in adults suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine.  The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer).  Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.  Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines [see Dosage and Administration (2), Adverse Reactions (6.2)].

5.6 Cutaneous and Systemic Lupus Erythematosus

Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including rabeprazole. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematosus cases were CLE.

The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Generally, histological findings were observed without organ involvement.

Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. PPI associated SLE is usually milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The majority of patients presented with rash; however, arthralgia and cytopenia were also reported.

Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients receiving Aciphex, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks.  Serological testing (e.g. ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations.

5.7 Cyanocobalamin (Vitamin B-12) Deficiency

Daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B-12) caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed in patients treated with Aciphex.

5.8 Hypomagnesemia

Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI.

For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), healthcare professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions (6.2)].

5.9 Interaction with Methotrexate

Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum concentrations 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 [see Drug Interactions (7)].

Overdosage

Seven reports of accidental overdosage with rabeprazole have been received.  The maximum reported overdose was 80 mg.  There were no clinical signs or symptoms associated with any reported overdose.  Patients with Zollinger-Ellison syndrome have been treated with up to 120  mg rabeprazole once daily.  No specific antidote for rabeprazole is known.  Rabeprazole is extensively protein bound and is not readily dialyzable.

In the event of overdosage, treatment should be symptomatic and supportive.  

If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.

Description

The active ingredient in Aciphex delayed-release tablets is rabeprazole sodium, which is a proton pump inhibitor.  It is a substituted benzimidazole known chemically as 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl]-methyl]sulfinyl]-1H–benzimidazole sodium salt.  It has an empirical formula of C18H20N3NaO3S and a molecular weight of 381.42.  Rabeprazole sodium is a white to slightly yellowish-white solid.  It is very soluble in water and methanol, freely soluble in ethanol, chloroform, and ethyl acetate and insoluble in ether and n-hexane.  The stability of rabeprazole sodium is a function of pH; it is rapidly degraded in acid media, and is more stable under alkaline conditions.  The structural figure is:

Figure 1

Aciphex is available for oral administration as delayed-release, enteric-coated tablets containing 20 mg of rabeprazole sodium.

Inactive ingredients of the 20 mg tablet are carnauba wax, crospovidone, diacetylated monoglycerides, ethylcellulose, hydroxypropyl cellulose, hypromellose phthalate, magnesium stearate, mannitol, propylene glycol, sodium hydroxide, sodium stearyl fumarate, talc, and titanium dioxide.  Iron oxide yellow is the coloring agent for the tablet coating.  Iron oxide red is the ink pigment.

Inform MD

Before you taking Aciphex, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

  • have any liver problems
  • have any allergies
  • are pregnant or planning to become pregnant
  • are breastfeeding

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. 

Aciphex Usage

  • Take Aciphex exactly as prescribed.
  • Do not change your dose or stop taking Aciphex unless you talk to your doctor. Take Aciphex for as long as it is prescribed even if you feel better.
  • Continue to take this medication for as long as it is prescribed, even if you feel better.
  • Aciphex is usually taken once a day.
  • Your doctor will tell you the time of day to take Aciphex.
  • Aciphex can be taken with or without food. 
  • Swallow each Aciphex tablet whole with water.
  • Do not chew, crush, or split Aciphex tablets because this will damage the tablet and the medicine will not work. Tell your doctor if you cannot swallow tablets whole. You may need a different medicine.
  • If you miss a dose of Aciphex, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your normal schedule. Do not take 2 doses at the same time.

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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 to AcipHex: 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 lupus - new or worsening joint pain, skin rash on your cheeks and arms (worsens in sunlight);

  • 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 AcipHex 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.

What other drugs will affect AcipHex?

Tell your doctor about all your current medicines and any you start or stop using, especially:

  • methotrexate (Otrexup, Rasuvo,Trexall); or

  • warfarin (Coumadin, Jantoven).

This list is not complete. Other drugs may interact with rabeprazole, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

For Healthcare Professionals

Applies to rabeprazole: oral delayed release capsule, oral delayed release tablet, oral tablet extended release

General

The most commonly reported side effects are headache, diarrhea, and abdominal pain.[Ref]

Gastrointestinal

Very common (10% or more): Diarrhea (up to 21%), abdominal pain (up to 16%), vomiting (up to 14%)
Common (1% to 10%): Nausea, constipation, flatulence, benign fundic gland polyps
Uncommon (0.1% to 1%): Dyspepsia, dry mouth, eructation
Rare (0.01% to 0.1%): Gastritis, stomatitis
Postmarketing reports: Clostridium difficile-associated diarrhea[Ref]

Other

Common (1% to 10%): Infection, non-specific pain, influenza-like illness, asthenia
Uncommon (0.1% to 1%): Chills, pyrexia/fever
Postmarketing reports: Sudden death, facial swelling[Ref]

Respiratory

Common (1% to 10%): Cough, pharyngitis, rhinitis
Uncommon (0.1% to 1%): Bronchitis, sinusitis
Postmarketing reports: Dyspnea, interstitial pneumonia[Ref]

Nervous system

Common (1% to 10%): Headache, dizziness, taste disturbance/perversion
Uncommon (0.1% to 1%): Somnolence, hepatic encephalopathy
Postmarketing reports: Coma, vertigo[Ref]

Hepatic encephalopathy occurred in patients with underlying cirrhosis.[Ref]

Musculoskeletal

Common (1% to 10%): Back pain, myalgia
Uncommon (0.1% to 1%): Leg cramps, arthralgia, fracture of hip/wrist/spine
Postmarketing reports: Rhabdomyolysis, bone fractures[Ref]

Dermatologic

Common (1% to 10%): Rash
Uncommon (0.1% to 1%): Erythema
Rare (0.01% to 0.1%): Pruritus, sweating, bullous reactions
Very rare (less than 0.01%): Erythema multiforme, toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome
Frequency not reported: Subacute cutaneous lupus erythematosus
Postmarketing reports: Urticarial skin eruptions, other drug eruptions, severe dermatological reactions, systemic lupus erythematosus, fatal TEN[Ref]

Erythema and bullous reactions usually resolved after discontinuation.[Ref]

Psychiatric

Common (1% to 10%): Insomnia
Uncommon (0.1% to 1%): Nervousness
Rare (0.01% to 0.1%): Depression
Frequency not reported: Confusion
Postmarketing reports: Disorientation, delirium[Ref]

Cardiovascular

Common (1% to 10%): Chest pain
Frequency not reported: Peripheral edema
Postmarketing reports: Hypotension[Ref]

Hepatic

Uncommon (0.1% to 1%): Increased hepatic enzymes
Rare (0.01% to 0.1%): Hepatitis, jaundice[Ref]

Increased hepatic enzymes occurred in patients with underlying cirrhosis.[Ref]

Genitourinary

Uncommon (0.1% to 1%): Urinary tract infection[Ref]

Hematologic

Rare (0.01% to 0.1%): Neutropenia, leukopenia, thrombocytopenia, leukocytosis
Postmarketing reports: Pancytopenia, agranulocytosis, bicytopenia, hemolytic anemia, increase in prothrombin time/INR[Ref]

Increased prothrombin time/INR occurred in patients taking warfarin concomitantly.[Ref]

Metabolic

Rare (0.01% to 0.1%): Anorexia, weight gain
Frequency not reported: Hypomagnesemia, hyponatremia
Postmarketing reports: Hyperammonemia[Ref]

Renal

Rare (0.01% to 0.1%): Interstitial nephritis[Ref]

Ocular

Rare (0.01% to 0.1%): Visual disturbance
Postmarketing reports: Blurred vision[Ref]

Endocrine

Frequency not reported: Gynecomastia
Postmarketing reports: TSH elevations[Ref]

Hypersensitivity

Hypersensitivity reactions included facial swelling, hypotension, dyspnea, erythema, and bullous reactions; these reactions typically resolved after discontinuation.[Ref]

Rare (0.01% to 0.1%): Hypersensitivity
Postmarketing reports: Acute systemic allergic reactions, anaphylaxis/anaphylactic reactions, angioedema[Ref]

Some side effects of Aciphex may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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