preloder

Rabeprazole Sodium


Rabeprazole Sodium

is a

proton pump inhibitor

(PPI) to reduce stomach acid and is

used for

the
treatment
of

gastroesophageal reflux disease

(GERD),

duodenal

ulcers

, and

used in

combination with

antibiotics

to treat

Helicobacter pylori

(H. pylori) bacterial infections in the

stomach

.
Dosing
Adult

dosing

:

Important Note:
Beers Criteria:

Use

caution or avoid

use as

potentially inappropriate in older adults

Duodenal ulcer disease:
20 mg

ORALLY

once daily after the morning meal for up to 4 weeks

Duodenal ulcer disease; Triple therapy – Helicobacter pylori

gastrointestinal tract

infection:

20 mg

ORALLY

twice daily in combination with

amoxicillin

1000 mg twice daily and

clarithromycin 500 mg

twice daily for 7 days (FDA

dosage

)

Clarithromycin triple regimen:
20 to 40 mg

ORALLY

twice daily in combination with

clarithromycin 500 mg

ORALLY

twice daily and either

amoxicillin

1g

ORALLY

twice daily or metronidazole 500 mg

ORALLY

3 times per day; continue regimen for 14 days (guideline

dosage

)

Sequential regimen:
20 mg

ORALLY

twice daily plus

amoxicillin

1g

ORALLY

twice daily for 5 to 7 days; then follow with

clarithromycin 500 mg

twice daily; metronidazole or

tinidazole 500mg

twice daily; and

rabeprazole 20 mg

twice daily for 5 to 7 days (guideline

dosage

)

Levofloxacin

triple regimen:
20 mg

ORALLY

twice daily in combination with

amoxicillin

1g

ORALLY

twice daily and

Levofloxacin

500 mg

ORALLY

once daily; continue regimen for 10 to 14 days (guideline

dosage

).

Gastric hypersecretion:
Initial; 60 mg

ORALLY

once daily; individualize

dose to

patient needs;

doses

up to 100 mg/day or 60 mg twice daily have been

used

.

Gastroesophageal reflux disease:
20 mg

ORALLY

once daily up to 4 weeks

Gastroesophageal reflux disease; Erosive or ulcerative:
20 mg

ORALLY

once daily for 4 to 8 weeks

Helicobacter pylori

gastrointestinal tract

infection – Peptic ulcer disease; Quadruple therapy:

Bismuth quadruple regimen:
20 mg

ORALLY

twice daily in combination with tetracycline 500 mg

ORALLY

4 times per day; metronidazole 250 mg

ORALLY

4 times per day or 500 mg

ORALLY

3 or 4 times per day; and either bismuth subcitrate 120 to 300 mg

ORALLY

4 times per day or bismuth subsalicylate 300 mg

ORALLY

4 times per day; continue regimen for 10 to 14 days (guideline

dosage

)

Concomitant regimen:
20 mg

ORALLY

twice daily in combination with

amoxicillin

1 g

ORALLY

twice daily;

clarithromycin 500 mg

ORALLY

twice daily; and metronidazole or

tinidazole 500mg

ORALLY

twice daily; continue regimen for 10 to 14 days (guideline

dosage

)

Hybrid regimen:
20 mg

ORALLY

twice daily plus

amoxicillin

1g

ORALLY

twice daily for 7 days; then follow with

amoxicillin

1 g twice daily;

clarithromycin 500 mg

twice daily; metronidazole or

tinidazole 500mg

twice daily; and

rabeprazole 20 mg

twice daily for 7 days (guideline

dosage

)

Levofloxacin

sequential regimen:
20 to 40 mg

ORALLY

twice daily plus

amoxicillin

1g

ORALLY

twice daily for 5 to 7 days; then follow with

amoxicillin

1g

ORALLY

twice daily; metronidazole or

tinidazole 500mg

ORALLY

twice daily;

rabeprazole 20 mg

ORALLY

twice daily; and

Levofloxacin

500 mg

ORALLY

once daily for 5 to 7 days (guideline

dosage

)

LOAD regimen:
40 mg

ORALLY

once daily in combination with

Levofloxacin

250 mg

ORALLY

once daily; doxycycline 100 mg

ORALLY

once daily; and nitazoxanide 500 mg twice daily; continue regimen for 7 to 10 days (guideline

dosage

).

Pediatric

dosing

:

Important Note:
Beers Criteria:

Use

caution or avoid

use

as potentially inappropriate in older adults.

General

Dosage

Information:

Safety and efficacy for
treatment
of GERD not established in pediatric patients younger than 1 year

Gastroesophageal reflux disease:
12 years or older:
20 mg

ORALLY

once daily up to 8 weeks

1 to 11 years:
15 kg or greater; 10mg (manufacturer

dose

) to 20mg (study

dose

)

ORALLY

once daily for up to

12 weeks



1 to 11 years:
less than 15kg; 5 mg

ORALLY

once daily for up to

12 weeks

; may increase to 10 mg

ORALLY

once daily if inadequate response.

Indications
FDA-Labeled Indications:

Allergic

conjunctivitis


Allergic

rhinitis

;

Perennial

and

seasonal


Anaphylaxis; Adjunct

Dermatographic

urticaria


Hypersensitivity reaction

; to blood or

plasma

; or mild

allergic

skin manifestations


Urticaria

due to

cold


Vasomotor

rhinitis



Non-FDA Labeled Indications:

Loss of appetite


Pruritus


Schizophrenia


Spasticity

Spinal cord

injury



Mechanism of Action

Rabeprazole Sodium

is a gastric

proton pump inhibitor

that does not possess anticholinergic or

histamine H(2)-receptor antagonist

properties. It suppresses

gastric acid secretion

by inhibiting the gastric H+; K+-ATPase at the secretory surface of parietal

cells

Adverse Effect
Common:
Gastrointestinal:

Abdominal pain

(3.6% to 5%)

Diarrhea

(up to 5%)

Nausea

(4.5%)

Vomiting

(3.6%)

Neurologic:

Headache

(up to 9.9%)

Serious:
Dermatologic:

Cutaneous lupus erythematosus


Erythema multiforme


Stevens-Johnson syndrome


Toxic

epidermal

necrolysis



Gastrointestinal:

Clostridium difficile

diarrhea



Immunologic:

Anaphylaxis


Systemic

lupus

erythematosus



Musculoskeletal:

Fracture of bone


Rhabdomyolysis



Renal:

Interstitial

nephritis

, Acute

Contraindication
Concomitant

use of

rilpivirine-containing products

Hypersensitivity reactions, including anaphylaxis, anaphylactic shock, angioedema, bronchospasm,

acute interstitial nephritis

, and urticaria, to
rabeprazole
; substituted

benzimidazoles

; or any component of the product

Interaction
Drugs Metabolized by CYP450:
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

Warfarin:
There have been reports of increased INR and prothrombin time in patients receiving

proton pump inhibitor

, including
rabeprazole
and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death

Cyclosporine:
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 20mg of
rabeprazole
. This degree of inhibition is similar to that by omeprazole at equivalent concentrations

Compounds Dependent on Gastric pH for Absorption:
Due to its effects on

gastric acid secretion

;
rabeprazole
can reduce the absorption of

drugs

where gastric pH is an important determinant of their bioavailability. Like with other

drugs

that decrease the intragastric acidity; the absorption of

drugs

such as ketoconazole;

atazanavir

; iron salts; erlotinib; and

mycophenolate mofetil

(MMF) can decrease, while the absorption of

drugs

such as digoxin can increase during
treatment
with
rabeprazole

Concomitant
treatment
with
rabeprazole
(20mg daily) and ketoconazole in healthy subjects decreased the bioavailability of ketoconazole by 30% and increased the AUC and Cmax for digoxin by 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.
Concomitant

use of

atazanavir

and

PPIs

is not recommended. Co- administration of

atazanavir

with

PPIs

is expected to substantially decrease

atazanavir

plasma

concentrations and thereby reduce its therapeutic effect.
Co-administration of

PPIs

in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite; mycophenolic acid (MPA); possibly due to a decrease in MMF solubility at an increased gastric pH. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving

PPIs

and MMF.

use

rabeprazole
with caution in transplant patients receiving MMF

Drugs Metabolized by CYP2C19:
In a clinical study in Japan evaluating
rabeprazole
in adult 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-hydroxy

clarithromycin

Concomitant administration of

clarithromycin

with other

drugs

can lead to serious adverse reactions due to drug interactions Because of these drug interactions;

clarithromycin

is contraindicated for co-administration with certain

drugs



Methotrexate:
Case reports; published population pharmacokinetic studies; and retrospective analyses suggest that concomitant administration of

PPIs

and methotrexate (primarily at high

dose

; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxy methotrexate. However, no formal drug interaction studies of methotrexate with

PPIs

have been conducted

Clopidogrel:
Concomitant administration of
rabeprazole
and clopidogrel in healthy subjects had no clinically meaningful effect on exposure to the active metabolite of clopidogrel. No

dose

adjustment of clopidogrel is necessary when administered with an approved

dose of

rabeprazole


Major:
Acalabrutinib (probable)

atazanavir

(theoretical)
Bosutinib (theoretical)
Capecitabine (probable)
Cilostazol (theoretical)
Clopidogrel (established)
Dasatinib (theoretical)
Digoxin (probable)
Erlotinib (probable)
Eslicarbazepine Acetate (theoretical)
Gefitinib (theoretical)
Ketoconazole (theoretical)
Ledipasvir (theoretical)
Methotrexate (theoretical)

Mycophenolate mofetil

(theoretical)
Nelfinavir (probable)
Neratinib (probable)
Nilotinib (theoretical)
Pazopanib (established)
Saquinavir (theoretical)
Secretin Human (theoretical)
Sunitinib (probable)
Velpatasvir (theoretical)
Vismodegib (theoretical)

Moderate:
Levothyroxine (Probable)

Phamacokinetics
Absorption:
Time for Maximum

plasma

Concentration (Tmax):
Oral; delayed-release
tablet
: 2 to

5 hours


10 mg granules empty

stomach

:

2.5 hours



Bioavailability:
Oral; delayed-release
tablet
: approximately 52%

Effect of

food
(delayed-release
tablet
):
Maximum

plasma

concentration (Cmax) and AUC not significantly altered; Tmax may be delayed up to

4 hours

with high-fat meal; may be taken with or without meals

Effect of

food
(delayed-release granules):
Decreased Maximum

plasma

concentration (Cmax) and AUC; Tmax delayed; should be taken

30 minutes

before a meal

Distribution:

plasma

Protein Binding: 96.3%

Metabolism:
Hepatic: extensive via CYP3A, CYP2C19, and systemic non-enzymatic reduction
Metabolites: desmethyl
rabeprazole
, thioether, and sulphone
Substrate of CYP2C19

Excretion:
Fecal: approximately 10% primarily as metabolites
Renal: approximately 90% primarily as metabolites

Dialyzable: No

Total body clearance:
Adult: 4 to 8 mL/min/kg
1 to 11 years: 8 to 13.5L/

hours



Elimination:
1 to

2 hours


Cirrhosis (mild to moderate): 2- to 3-fold longer

Precaution
Beers Criteria:
Avoid scheduled

use in

older adults for longer than 8 weeks due to risk of Clostridium difficile infection and

bone

loss and fractures; unless needed for high-risk patients (e.g.; oral corticosteroids, chronic NSAID

use

) erosive esophagitis; pathological hypersecretory condition; or need for maintenance
treatment
(e.g.; due to failure of drug discontinuation or histamine-2 blockers).

Concomitant

use

:

Use

with nelfinavir should be avoided.

Dermatologic:
New or worsening cutaneous lupus erythematosus has been reported within weeks to years after continuous drug therapy; avoid using for longer than medically indicated and discontinue

use

if suspected.

Endocrine and metabolic:
Vitamin B12 deficiency may occur with prolonged

use

(e.g. greater than 1 to

2 years

); monitoring recommended.

Hypomagnesemia has been reported in patients treated with

proton pump inhibitor

for at least 3 months; tetany; arrhythmias; and seizures may occur; monitoring recommended with prolonged

use

or concomitant

drugs

that may cause hypomagnesemia; discontinuation may be required.

Gastrointestinal:
Symptomatic response does not preclude the presence of gastric malignancy in adults Clostridium difficile-associated diarrhea may occur; especially in hospitalized patients;

use

lowest

dose

and shortest duration.

Immunologic:
New or worsening

systemic lupus erythematosus

has been reported within days to years of
treatment
initiation; avoid using for longer than medically indicated and discontinue

use

if suspected.

Musculoskeletal:
Osteoporosis-related

bone

fracture of hip; wrist; or spine may occur; especially with higher (multiple daily)

doses

or longer duration of therapy (1 year or longer);

use

lowest

dose

and shortest
treatment
duration

Renal:

Acute interstitial nephritis

; generally considered an idiopathic hypersensitivity reaction; has been reported; discontinuation required.

Pregnancy Category
Fetal Risk cannot be ruled out
Breast Feeding
Infant Risk cannot be ruled out
Monitoring
GERD:
Decreased abdominal and gastroesophageal discomfort may indicate efficacy.

Peptic ulcer:
Endoscopic improvement may indicate efficacy.

Serum magnesium:
Routine screening is not necessary; consider screening prior to initiation and periodically during prolonged therapy.

Serum vitamin B12:
Although no routine screening is needed; may consider screening every 1 to

2 years

for deficiency in patients receiving prolonged therapy.

How to Take or Administration
Oral:
Delayed-release
tablet
:
May be taken with or without
food
; swallow whole; do not chew, crush, or split For

duodenal

ulcers

,
tablet
should be taken after the morning meal; for

Helicobacter pylori

eradication, the 3-drug combination should be taken together with the morning and evening meals

Delayed-release capsule:
In children 1 to 11 years of age, administer

30 minutes

prior to meal
Open capsule and sprinkle entire contents on small amount of soft
food
or liquid that is at or below room temperature; take within

15 minutes


Do not chew or crush granules
Do not store prepared mixture for future

use



Dosage Form
Oral Tablet (Enteric Coated):
20 mg


Oral Capsule, Delayed Release:
5 mg
10 mg

Treatment
Management of Mild to Moderate Toxicity:
treatment
is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with severe diarrhea and/or vomiting.

Management of Severe Toxicity:
treatment
is symptomatic and supportive. Significant toxicity is not expected after an

overdose

.

Toxicology

Doses

up to 2400 mg (120 times the usual recommended clinical

dose

) resulted in transient effects (e.g.; drowsiness, confusion and tachycardia), with no serious events reported when taken alone.
Patient Counselling or Clinical Teaching
Warn patient to report diarrhea that does not improve and consult healthcare professional prior to taking

antidiarrheal

medicine

Counsel patient to report symptoms of cutaneous or

systemic lupus erythematosus



Advise patient using multiple daily

doses

for longer than a year to report symptoms of osteoporosis-related fractures (e.g., hip, wrist, and spine)

Side effects

may include

abdominal

pain

,

diarrhea

,

nausea

,

vomiting

,

flatulence

,

constipation

,

Pharyngitis

, and

headaches



Counsel patient to report symptoms of hypomagnesemia

Delayed-release capsules: Advise patient not to swallow capsule whole. Contents of capsule must be sprinkled on small amount of soft
food
or in liquid and consumed within

15 minutes

after mixing and

30 minutes

before a meal

Delayed-release tablets: Instruct patient with a

duodenal

ulcer to take drug after a meal. A patient with

Helicobacter pylori

infection should take drug with
food


Category of Rabeprazole Sodium :
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