Rabeprazole Sodium Delayed-release

RABEPRAZOLE SODIUM DELAYED-RELEASE- rabeprazole sodium capsule, delayed release
Sarras Health, LLC

1 INDICATIONS AND USAGE

Rabeprazole sodium delayed-release capsules are indicated for treatment of Gastroesophageal Reflux Disease (GERD) in pediatric patients 1 to 11 years of age for up to 12 weeks.

2 DOSAGE AND ADMINISTRATION

2.1 Dosage Regimen

Rabeprazole sodium delayed-release capsules are recommended for up to 12 weeks in pediatric patients 1 to 11 years of age and is dosed by body weight:

• Less than 15 kg: 5 mg once daily with the option to increase to 10 mg once daily, if inadequate response.
• 15 kg or more: 10 mg once daily.

2.2 Administration Recommendations

• Take the dose 30 minutes before a meal.
• Do not swallow the capsule whole.
• Open a capsule and sprinkle entire contents on a small amount of soft food (e.g., applesauce, fruit or vegetable based baby food, or yogurt) or empty contents into a small amount of liquid (e.g., infant formula, apple juice, or pediatric electrolyte solution). Food or liquid should be at or below room temperature.
• Do not chew or crush the granules.
• Take the entire dose within 15 minutes of preparation.
• Do not store mixture for future use.
• Take a missed dose as soon as possible. If it is almost time for the next dose, skip the missed dose and go back to the normal schedule. Do not take 2 doses at the same time.

3 DOSAGE FORMS AND STRENGTHS

Rabeprazole sodium delayed-release capsules (sprinkle) are provided as:

• 10 mg: transparent yellow and opaque white No. 2 capsule imprinted with “↑” on the capsule cap and “ACX 10mg” on the capsule body.

4 CONTRAINDICATIONS

• Rabeprazole sodium delayed-release capsules are contraindicated in patients with known hypersensitivity to rabeprazole, substituted benzimidazoles, or to any component of the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, and urticaria [see Adverse Reactions (6)].
• PPIs, including rabeprazole sodium delayed-release capsules, are contraindicated with rilpivirine-containing products [see Drug Interactions (7)].

5 WARNINGS AND PRECAUTIONS

5.1 Presence of Gastric Malignancy

In adults, symptomatic response to therapy with rabeprazole sodium delayed-release capsules 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. In older patients, also consider an endoscopy.

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 rabeprazole sodium delayed-release capsules 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 rabeprazole sodium. Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction. Discontinue rabeprazole sodium delayed-release capsules if acute interstitial nephritis develops [see Contraindications (4)].

5.4 Clostridium difficile -Associated Diarrhea

Published observational studies suggest that PPI therapy like rabeprazole sodium delayed-release capsules 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.

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)].

Rabeprazole sodium delayed-release capsules are indicated for short-term treatment up to 12 weeks. Treatment for longer than 12 weeks is not recommended.

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 rabeprazole sodium delayed-release capsules, 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 rabeprazole sodium delayed-release capsules.

5.8 Hypomagnesemia

Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in adult 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)].

Rabeprazole sodium delayed-release capsules are indicated for short-term treatment of up to 12 weeks. Treatment for longer than 12 weeks is not recommended.

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 levels 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)].