Basics for everyone

1. PANTOPRAZOLE
Lakshmi Narayana M

2. Topics to follow….
Introduction
Mechanism of action
Pharmacokinetics
Indications
Recommended dosing schedule
Dose adjustments
Not to prescribe or take care
Possible side effects of pantoprazole

3. Proton pump inhibitors (PPIs) are a group of drugs whose main
action is a pronounced and long-lasting reduction of gastric acid
production
• Omeprazole
• Lansoprazole
• Dexlansoprazole
• Esomeprazole
• Pantoprazole
• Rabeprazole
• Ilaprazole
INTRODUCTION

4. INTRODUCTION
Pantoprazole is a substituted benzimidazole and proton pump inhibitor drug
that inhibits gastric acid secretion. It is used to treat gastroesophageal reflux
disease (GERD), a condition that causes gastric juices to flow upward from
your stomach and into the oesophagus. It also treats conditions in which the
stomach makes excess acid, such as Zollinger-Ellison syndrome. it works to
shut off the acid-pumping cells in your stomach. It reduces the amount of
stomach acid and helps to reduce painful symptoms related to
gastroesophageal reflux disease (GERD).

5. MECHANISM OF ACTION
Pantoprazole is a proton pump inhibitor (PPI) that suppresses the
final step in gastric acid production by covalently binding to the
(H+, K+)-ATPase enzyme system at the secretory surface of the
gastric parietal cell. This effect leads to inhibition of both basal and
stimulated gastric acid secretion, irrespective of the stimulus. The
binding of pantoprazole to H+/K+-ATPase is irreversible in nature,
and effectively inhibits acid secretion until new enzyme is
synthesized.
MOA

6. PHARMACOKINETICS
Rapidly absorbed after oral administration. On set of action is within
2¬4 hours, duration of action is about 24 hours. Peak concentration
(Cmax) is 2.5 μg/mL; the time to reach the peak concentration
(tmax) is 2.5 h. The drug is subject to low first pass¬ hepatic
excretion, the oral bioavailability is 77%. approximately 71% of the
dose was excreted in the urine, with 18% excreted in the feces
through biliary excretion. There was no renal excretion of
unchanged pantoprazole.

7. Contd….
Geriatric
Only slight to moderate increases in pantoprazole AUC (43%) and
Cmax (26%) were found in elderly volunteers (64 to 76 years of
age) after repeated oral administration, compared with younger
subjects. No dosage adjustment is recommended based on age

8. Children and Adolescents 6 through 16 Years of Age
Contd….
6-11 YEARS
(N=12)
12-16 YEARS
(N=11)
Cmax (Pg/mL)a 1.8 1.8
tmax (h)b 2.0 2.0
AUC (μg•h/mL)a 6.9 5.5
CL/F (L/h)b 6.6 6.8

9. DOSE ADJUSTMENTS
Gender
There is a modest increase in pantoprazole AUC and Cmax in women
compared to men. However, weight-normalized clearance values are
similar in women and men. No dosage adjustment is recommended
based on gender.
Renal Impairment
In patients with severe renal impairment, pharmacokinetic parameters
for pantoprazole were similar to those of healthy subjects. No dosage
adjustment is necessary in patients with renal impairment or in
patients undergoing hemodialysis.

10. Contd….
Hepatic Impairment
No dosage adjustment is needed in patients with mild to severe
hepatic impairment.

11. INDICATIONS
• To treat ulcers in the stomach and the part of the gut called the
duodenum.
• To reduce acid reflux which may cause heartburn or inflammation of
the gullet (oesophagitis). These conditions are sometimes called gastro-
oesophageal reflux disease (GORD).
• As one part of treatment to get rid of Helicobacter pylori - a germ
(bacterium) found in the stomach, which can cause ulcers.
• To help prevent and treat ulcers associated with anti-inflammatory
medicines called non-steroidal anti-inflammatory drugs (NSAIDs).
• In a rare condition called Zollinger-Ellison syndrome.
• In other conditions where it is helpful to reduce acid in the stomach.

12. RECOMMENDED DOSING
SCHEDULE
INDICATION DOSE FREQUENCY
Short-Term Treatment of Erosive Esophagitis Associated with GERD
Adults 40 mg Once daily for up to 8 weeks
Children (5 years and older)
≥ 15 kg to < 40 kg 20 mg Once daily for up to 8 weeks
≥ 40 kg 40 mg
Maintenance of Healing of Erosive Esophagitis
Adults 40 mg Once daily
Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome
Adults 40 mg Twice daily

13. NOT TO PRESCRIBE OR TAKE
CARE
Pregnancy:
Pregnancy Category B, this drug should be used during pregnancy
only if clearly needed
Nursing Mothers
Pantoprazole excretion in human milk has been detected in a study
of a single nursing mother after a single 40 mg oral dose. The
clinical relevance of this finding is not known. Many drugs which
are excreted in human milk have a potential for serious adverse
reactions in nursing infants.

14. Contd….
Tumorigenicity
In long-term rodent studies, pantoprazole was carcinogenic and
caused rare types of gastrointestinal tumors. The relevance of these
findings to tumor development in humans is unknown
Bone Fracture
Several published observational studies suggest that proton pump
inhibitor (PPI) therapy may be associated with an increased risk
for osteoporosis-related fractures of the hip, wrist, or spine

15. POSSIBLE SIDE EFFECTS
Common
• Gastrointestinal: abdominal pain (6%), diarrhea (9%), nausea
(7%), vomiting (4%)
• Neurologic: headache (12%), dizziness (3%)

16. Contd….
Rare
• Gastrointestinal: constipation, dry mouth, hepatitis
• Blood problems: low white blood cell count, thrombocytopenia
• Immunologic: Stevens-Johnson syndrome, toxic epidermal
necrolysis
• Metabolic: elevated creatine kinase, elevated cholesterol levels,
elevated liver enzymes (AST/ALT), swelling
• Musculoskeletal: Muscle disorders, bone fracture and infection,
Clostridium difficile infection, osteoporosis-related hip fracture,
rhabdomyolysis

17. Contd….
Long-term
• Osteoporosis and bone fracture have been observed in patients on
high-dose and/or long term (over 1 year) prescription proton pump
inhibitors
• Hypomagnesia has been observed in patients on medications like
pantoprazole when taken for longer periods of time (generally 1
year or more, although cases have been reported with regimens as
short as 3 months)