For the use of a Registered Medical Practitioner or a Hospital or a Laboratory only

Generic Name

Pantoprazole Tablets IP 40 mg

BRAND NAME

PANTOSEC 40 Tablets

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each enteric coated tablet contains:

Pantoprazole Sodium IP

equivalent to Pantoprazole 40 mg

Colours: Titanium Dioxide IP & Yellow Oxide of Iron

DOSAGE FORM AND STRENGTH

Pantoprazole Gastro-resistant tablets 40 mg

CLINICAL PARTICULARS
Therapeutic Indications
For the treatment of gastric ulcer, duodenal ulcer, Zollinger Ellison Syndrome and
Gastro-Esophageal reflux disease.
Posology and Method of Administration

Tablets should not be chewed or crushed and should be swallowed whole 1 hour before
a meal with some water.

The recommended dosages of pantoprazole are outlined in Table 1.

Table 1: Recommended Dosing Schedule for Pantoprazole Tablets

Indication Dose Frequency

Short-Term Treatment of EE Associated with GERD

1
 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 EE

Adults 40 mg Once daily#

Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome

Adults 40 mg Twice daily**

For adult patients who have not healed after 8 weeks of treatment, an additional 8-week
course of pantoprazole may be considered.
#
Controlled studies did not extend beyond 12 months.

Treatment of Gastric Ulcers

One tablet of pantoprazole per day. In individual cases, the dose may be doubled
(increase to two tablets of pantoprazole daily), especially when there has been no
response to other treatment. A 4-week period is usually required for the treatment of
gastric ulcers. If this is not sufficient, healing will usually be achieved within a further 4
weeks.

Treatment of Duodenal Ulcers

One tablet of pantoprazole per day. In individual cases, the dose may be doubled
(increase to two tablets of pantoprazole daily), especially when there has been no
response to other treatment. A duodenal ulcer generally heals within 2 weeks. If a 2-week
period of treatment is not sufficient, healing will be achieved in almost all cases within a
further 2 weeks.

Special Populations

2
Children below 12 years of age

Pantoprazole is not recommended for use in children below 12 years of age due to limited
data on safety and efficacy in this age group.

Hepatic Impairment

A daily dose of 20 mg pantoprazole (1 tablet of 20 mg pantoprazole) should not be

exceeded in patients with severe liver impairment. Pantoprazole must not be used in
combination treatment for eradication of H. pylori in patients with moderate to severe
hepatic dysfunction since currently no data are available on the efficacy and safety of
Pantoprazole in combination treatment of these patients.

Renal Impairment

No dose adjustment is necessary in patients with impaired renal function. Pantoprazole

must not be used in combination treatment for eradication of H. pylori in patients with
impaired renal function since currently no data are available on the efficacy and safety of
pantoprazole in combination treatment for these patients.

Elderly

No dose adjustment is necessary in elderly patients.

Contraindications

Pantoprazole tablets are contraindicated in case of hypersensitivity to the active

substance, substituted benzimidazoles, or to any of the other excipients of the tablet.
Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angio-oedema,
bronchospasm, acute interstitial nephritis, and urticaria. Proton-pump inhibitors (PPIs),
including pantoprazole tablets, are contraindicated with rilpivirine-containing products.

Special Warnings and Precautions for Use

Presence of Gastric malignancy

Symptomatic response to pantoprazole may mask the symptoms of gastric malignancy

and may delay diagnosis. In the presence of any alarm symptom (e. g. significant
unintentional weight loss, recurrent vomiting, dysphagia, haematemesis, anaemia or
melaena) and when gastric ulcer is suspected or present, malignancy should be
excluded. 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.

Acute Tubointerstitial Nephritis

3
Acute tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and may
occur at any point during PPI therapy. Patients may present with varying signs and
symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of
decreased renal function (e.g., malaise, nausea, anorexia). In reported case series, some
patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g.,
fever, rash or arthralgia). Discontinue pantoprazole sodium delayed-release tablets if
acute interstitial nephritis develops.

Clostridium difficile Associated Diarrhea

Published observational studies suggest that PPI therapy like pantoprazole 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. Patients should use the lowest dose and shortest duration of PPI therapy
appropriate to the condition being treated.

Bone fractures

Proton pump inhibitors, especially if used in high doses and over long durations (>1 year),
may modestly increase the risk of hip, wrist and spine fracture, predominantly in the
elderly or in presence of other recognised risk factors. Observational studies suggest that
proton pump inhibitors may increase the overall risk of fracture by 10-40%. Some of this
increase may be due to other risk factors. Patients at risk of osteoporosis should receive
care according to current clinical guidelines and they should have an adequate intake of
vitamin D and calcium.

Severe Cutaneous Adverse Reactions

Severe cutaneous adverse reactions, including erythema multiforme, Stevens-Johnson

syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and
systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP)
have been reported in association with the use of PPIs. Discontinue PANTOSEC 40 at
the first signs or symptoms of severe cutaneous adverse reactions or other signs of
hypersensitivity and consider further evaluation.

Cutaneous and Systemic Lupus Erythematosus

4
Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have
been reported in patients taking PPIs, including pantoprazole sodium. 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 sub-acute 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. 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 cytopaenia
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 pantoprazole sodium delayed-
release tablets, discontinue the drug and refer the patient to the appropriate specialist for
evaluation. Most patients improve with discontinuation of the PPI alone in 4–12 weeks.
Serological testing (e.g. ANA) may be positive and elevated serological test results may
take longer to resolve than clinical manifestations.

Co-administration with HIV protease inhibitors

Co-administration of pantoprazole is not recommended with HIV protease inhibitors for

which absorption is dependent on acidic intragastric pH such as atazanavir, due to
significant reduction in their bioavailability. If the combination of HIV protease inhibitors
with a PPI is judged unavoidable, close clinical monitoring (e.g. virus load) is
recommended. A pantoprazole sodium dose of 20 mg per day should not be exceeded.
Dosage of the HIV protease inhibitors may need to be adjusted.

Cyanocobalamin (Vitamin B12) Deficiency

Generally, 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
B12) 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.

Hypomagnesaemia and Mineral Metabolism

5
Severe hypomagnesaemia has been reported in patients treated with PPIs like
pantoprazole for at least three months, and in most cases for a year. Serious
manifestations of hypomagnesaemia such as fatigue, tetany, delirium, convulsions,
dizziness and ventricular arrhythmia can occur but they may begin insidiously and be
overlooked. In most affected patients, hypomagnesaemia improved after magnesium
replacement and discontinuation of the PPI.
For patients expected to be on prolonged treatment or who take PPIs with digoxin or
medicinal products that may cause hypomagnesaemia (e.g., diuretics), health care
professionals should consider measuring magnesium levels before starting PPI treatment
and periodically during treatment.
Consider monitoring magnesium and calcium levels prior to initiation of pantoprazole and
periodically while on treatment in patients with a preexisting risk of hypocalcemia (e.g.,
hypoparathyroidism). Supplement with magnesium and/or calcium as necessary. If
hypocalcemia is refractory to treatment, consider discontinuing the PPI.

Tumourigenicity
Due to the chronic nature of GERD, there may be a potential for prolonged administration
of pantoprazole. In long-term rodent studies, pantoprazole was carcinogenic and caused
rare types of gastrointestinal tumours. The relevance of these findings to tumour
development in humans is unknown.

Fundic Gland Polyps

PPI use is associated with an increased risk of fundic gland polyps that increases with
long-term use, especially beyond 1 year. Most PPI users who developed fundic gland
polyps were asymptomatic and fundic gland polyps were identified incidentally on
endoscopy. Use the shortest duration of PPI therapy appropriate to the condition being
treated.

Interference with Investigations for Neuroendocrine Tumours

Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in

gastric acidity. The increased CgA level may cause false-positive results in diagnostic
investigations for neuroendocrine tumours. Healthcare providers should temporarily stop
pantoprazole sodium delayed-release tablet treatment at least 14 days before assessing
CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are
performed (e.g. for monitoring), the same commercial laboratory should be used for
testing, as reference ranges between tests may vary.

Interference with Urine Screen for THC

6
There have been reports of false-positive urine screening tests for tetrahydrocannabinol
(THC) in patients receiving PPIs, including pantoprazole sodium delayed-release tablets.

Concomitant Use of Pantoprazole 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-
dosemethotrexate administration, a temporary withdrawal of the PPI may be considered
in some patients.
Drug Interactions

Antiretrovirals
Clinical The effect of PPIs on antiretroviral drugs is variable. The clinical
Impact: importance and the mechanisms behind these interactions are not
always known.
• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine,
atazanavir, and nelfinavir) when used concomitantly with
pantoprazole
may reduce antiviral effect and promote the development of drug
resistance.
• Increased exposure of other antiretroviral drugs (e.g., saquinavir)
when used concomitantly with pantoprazole may increase toxicity of
the antiretroviral drugs.
• There are other antiretroviral drugs which do not result in clinically
relevant interactions with pantoprazole.
Intervention: Rilpivirine-containing products: Concomitant use with pantoprazole is
contraindicated. See prescribing information.
Atazanavir: See prescribing information for atazanavir for dosing
information.
Nelfinavir: Avoid concomitant use with pantoprazole. See prescribing
information for nelfinavir.
Saquinavir: See the prescribing information for saquinavir and
monitor for potential saquinavir toxicities.
Other antiretrovirals: See prescribing information.
Warfarin
Clinical Increased INR and prothrombin time in patients receiving PPIs,
Impact: including
pantoprazole, and warfarin concomitantly. Increases in INR and
prothrombin
time may lead to abnormal bleeding and even death.
Intervention: Monitor INR and prothrombin time. Dose adjustment of warfarin may
be needed to maintain target INR range. See prescribing information
for warfarin.
Clopidogrel

7
Clinical Concomitant administration of pantoprazole and clopidogrel in
Impact: healthy subjects had no clinically important effect on exposure to the
active metabolite of clopidogrel or clopidogrel-induced platelet
inhibition.
Intervention: No dose adjustment of clopidogrel is necessary when administered
with an approved dose of pantoprazole.
Methotrexate
Clinical Concomitant use of PPIs with methotrexate (primarily at high dose)
Impact: may elevate and prolong serum concentrations of methotrexate
and/or its metabolite hydroxymethotrexate, possibly leading to
methotrexate toxicities. No formal
drug interaction studies of high-dose methotrexate with PPIs have
been conducted [see Warnings and Precautions].
Intervention: A temporary withdrawal of pantoprazole may be considered in some
patients receiving high-dose methotrexate.
Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib,
dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole)
Clinical Pantoprazole can reduce the absorption of other drugs due to its
Impact: effect on reducing intragastric acidity.
Intervention: Mycophenolate mofetil (MMF): Co-administration of pantoprazole
sodium 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 PANTOPRAZOLE and MMF. Use
PANTOPRAZOLE with caution in transplant patients receiving MMF.
Interactions with Investigations of Neuroendocrine Tumors
Clinical CgA levels increase secondary to PPI-induced decreases in gastric
Impact: acidity. The
increased CgA level may cause false positive results in diagnostic
investigations for neuroendocrine tumors.
Intervention: Temporarily stop PANTOPRAZOLE treatment at least 14 days
before assessing CgA levels and consider repeating the test if initial
CgA levels are high. If serial tests are performed (e.g., for
monitoring), the same commercial laboratory should be used for
testing, as reference ranges between tests may vary.
False Positive Urine Tests for THC
Clinical There have been reports of false positive urine screening tests for
Impact: tetrahydrocannabinol (THC) in patients receiving PPIs [see Warnings
and Precautions ].
Intervention: An alternative confirmatory method should be considered to verify
positive results.

8
Use in Special Populations

Pregnant women

Risk Summary

Available data from published observational studies did not demonstrate an association
of major malformations or other adverse pregnancy outcomes with pantoprazole.

In animal reproduction studies, no evidence of adverse development outcomes was

observed with pantoprazole. Reproduction studies have been performed in rats at oral
doses up to 450 mg/kg/day (about 88 times the recommended human dose) and rabbits
at oral doses up to 40 mg/kg/day (about 16 times the recommended human dose) with
administration of pantoprazole during organogenesis in pregnant animals and have
revealed no evidence of harm to the fetus due to pantoprazole in this study (see Data).

A pre-and postnatal development toxicity study in rats with additional endpoints to

evaluate the effect on bone development was performed with pantoprazole sodium. Oral
pantoprazole doses of 5, 15, and 30 mg/kg/day (approximately 1, 3, and 6 times the
human dose of 40 mg/day) were administered to pregnant females from gestation day
(GD) 6 through lactation day (LD) 21. Changes in bone morphology were observed in
pups exposed to pantoprazole in utero and through milk during the period of lactation as
well as by oral dosing from postnatal day (PND) 4 through PND 21 [see Use in Specific
Populations (8.4)]. There were no drug-related findings in maternal animals. Advise
pregnant women of the potential risk of fetal harm.

The estimated background risk of major birth defects and miscarriage for the indicated
population is unknown. All pregnancies have a background risk of birth defect, loss or
other adverse outcomes. In the U.S. general population, the estimated background risk
of major birth defects and miscarriage in the clinically recognized pregnancies is 2 to 4%
and 15 to 20%, respectively.

Data

Human Data

Available data from published observational studies failed to demonstrate an association

of adverse pregnancy-related outcomes and pantoprazole use. Methodological limitations
of these observational studies cannot definitely establish or exclude any drug-associated
risk during pregnancy. In a prospective study by the European Network of Teratology
Information Services, outcomes from a group of 53 pregnant women administered median
daily doses of 40 mg pantoprazole were compared to a control group of 868 pregnant
women who did not take any proton pump inhibitors (PPIs). There was no difference in
the rate of major malformations between women exposed to PPIs and the control group,
corresponding to a Relative Risk (RR)=0.55, [95% Confidence Interval (CI) 0.08-3.95]. In
a population-based retrospective cohort study covering all live births in Denmark from
1996 to 2008, there was no significant increase in major birth defects during analysis of
9
first trimester exposure to pantoprazole in 549 live births. A meta-analysis that compared
1,530 pregnant women exposed to PPIs in at least the first trimester with 133,410
unexposed pregnant women showed no significant increases in risk for congenital
malformations or spontaneous abortion with exposure to PPIs (for major malformations
OR=1.12 ([95% CI 0.86-1.45] and for spontaneous abortions OR=1.29 [95% CI 0.84-
1.97]).

Animal Data

Reproduction studies have been performed in rats at oral pantoprazole doses up to 450
mg/kg/day (about 88 times the recommended human dose based on body surface area)
and in rabbits at oral doses up to 40 mg/kg/day (about 16 times the recommended
human dose based on body surface area) with administration of pantoprazole sodium
during organogenesis in pregnant animals. The studies have revealed no evidence of
impaired fertility or harm to the fetus due to pantoprazole.

A pre-and postnatal development toxicity study in rats with additional endpoints to

evaluate the effect on bone development was performed with pantoprazole sodium. Oral
pantoprazole doses of 5, 15, and 30 mg/kg/day (approximately 1, 3, and 6 times the
human dose of 40 mg/day on a body surface area basis) were administered to pregnant
females from gestation day (GD) 6 through lactation day (LD) 21. On postnatal day (PND
4) through PND 21, the pups were administered oral doses at 5, 15, and 30 mg/kg/day
(approximately 1, 2.3, and 3.2 times the exposure (AUC) in humans at a dose of 40 mg).
There were no drug-related findings in maternal animals. During the preweaning dosing
phase (PND 4 to 21) of the pups, there were increased mortality and/or moribundity and
decreased body weight and body weight gain at 5 mg/kg/day (approximately equal
exposures (AUC) in humans receiving the 40 mg dose) and higher doses. On PND 21,
decreased mean femur length and weight and changes in femur bone mass and geometry
were observed in the offspring at 5 mg/kg/day (approximately equal exposures (AUC) in
humans at the 40 mg dose) and higher doses. The femur findings included lower total
area, bone mineral content and density, periosteal and endosteal circumference, and
cross-sectional moment of inertia. There were no microscopic changes in the distal femur,
proximal tibia, or stifle joints. Changes in bone parameters were partially reversible
following a recovery period, with findings on PND 70 limited to lower femur metaphysis
cortical/subcortical bone mineral density in female pups at 5 mg/kg/day (approximately
equal exposures (AUC) in humans at the 40 mg dose) and higher doses.

Lactating women

Risk Summary

Pantoprazole has been detected in breast milk of a nursing mother after a single 40
mg oral dose of pantoprazole. There were no effects on the breastfed infant (see
Data). There are no data on pantoprazole effects on milk production.

10
The developmental and health benefits of breastfeeding should be considered along
with the mother’s clinical need for PANTOPRAZOLE and any potential adverse effects
on the breastfed child from pantoprazole or from the underlying maternal condition.

Data

The breast milk of a 42-year-old woman receiving 40 mg of oral pantoprazole, at 10

months postpartum, was studied for 24 hours, to demonstrate low levels of pantoprazole
present in the breast milk. Pantoprazole was detectable in milk only 2 and 4 hours after
the dose with milk levels of approximately 36 mcg/L and 24 mcg/L, respectively. A milk-
to-plasma ratio of 0.022 was observed at 2 hours after drug administration. Pantoprazole
was not detectable (<10 mcg/L) in milk at 6, 8 and 24 hours after the dose. The relative
dose to the infant was estimated to be 7.3 mcg of pantoprazole, which is equivalent to
0.14% of the weight-adjusted maternal dose. No adverse events in the infant were
reported by the mother.

Paediatric Patients

The safety and effectiveness of pantoprazole for short-term treatment (up to eight
weeks) of EE associated with GERD have been established in pediatric patients 1 year
through 16 years of age. Effectiveness for EE has not been demonstrated in patients
less than 1 year of age. In addition, for patients less than 5 years of age, there is no
appropriate dosage strength in an age-appropriate formulation available. Therefore,
pantoprazole is indicated for the short-term treatment of EE associated with GERD for
patients 5 years and older. The safety and effectiveness of pantoprazole for pediatric
uses other than EE have not been established.

1 year through 16 years of age

Use of pantoprazole in pediatric patients 1 year through 16 years of age for short-term
treatment (up to eight weeks) of EE associated with GERD is supported by: a)
extrapolation of results from adequate and well-controlled studies that supported the
approval of pantoprazole for treatment of EE associated with GERD in adults, and b)
safety, effectiveness, and pharmacokinetic studies performed in pediatric patients [see
Clinical Studies (14.1), Clinical Pharmacology (12.3)].

Safety of pantoprazole in the treatment of EE associated with GERD in pediatric patients

1 through 16 years of age was evaluated in three multicenter, randomized, double-blind,
parallel-treatment studies, involving 249 pediatric patients, including 8 with EE (4 patients
ages 1 year to 5 years and 4 patients 5 years to 11 years). The children ages 1 year to 5
years with endoscopically diagnosed EE (defined as an endoscopic Hetzel-Dent score
≥2) were treated once daily for 8 weeks with one of two dose levels of pantoprazole
(approximating 0.6 mg/kg or 1.2 mg/kg). All 4 of these patients with EE were healed
(Hetzel-Dent score of 0 or 1) at 8 weeks. Because EE is uncommon in the pediatric
population, predominantly pediatric patients with endoscopically-proven or symptomatic
GERD were also included in these studies. Patients were treated with a range of doses
of pantoprazole once daily for 8 weeks. For safety findings see Adverse Reactions (6.1).

11
Because these pediatric trials had no placebo, active comparator, or evidence of a
dose response, the trials were inconclusive regarding the clinical benefit of
pantoprazole for symptomatic GERD in the pediatric population. The effectiveness of
pantoprazole for treating symptomatic GERD in pediatric patients has not been
established.

Although the data from the clinical trials support use of pantoprazole for the short-term
treatment of EE associated with GERD in pediatric patients 1 year through 5 years, there
is no commercially available dosage formulation appropriate for patients less than 5
years of age [see Dosage and Administration (2)].

In a population pharmacokinetic analysis, clearance values in the children 1 to 5 years

old with endoscopically proven GERD had a median value of 2.4 L/h. Following a 1.2
mg/kg equivalent dose (15 mg for ≤12.5 kg and 20 mg for >12.5 to <25 kg), the plasma
concentrations of pantoprazole were highly variable and the median time to peak plasma
concentration was 3 to 6 hours. The estimated AUC for patients 1 to 5 years old was 37%
higher than for adults receiving a single 40 mg tablet, with a geometric mean AUC value
of 6.8 μg•hr/mL.

Neonates to less than one year of age

Pantoprazole was not found to be effective in a multicenter, randomized, double-blind,

placebo-controlled, treatment-withdrawal study of 129 pediatric patients 1 through 11
months of age. Patients were enrolled if they had symptomatic GERD based on medical
history and had not responded to non-pharmacologic interventions for GERD for two
weeks. Patients received pantoprazole daily for four weeks in an open-label phase, then
patients were randomized in equal proportion to receive pantoprazole treatment or
placebo for the subsequent four weeks in a double-blind manner. Efficacy was assessed
by observing the time from randomization to study discontinuation due to symptom
worsening during the four-week treatment-withdrawal phase. There was no statistically
significant difference between pantoprazole and placebo in the rate of discontinuation.

In this trial, the adverse reactions that were reported more commonly (difference
of ≥4%) in the treated population compared to the placebo population were
elevated CK, otitis media, rhinitis, and laryngitis.

In a population pharmacokinetic analysis, the systemic exposure was higher in patients

less than 1 year of age with GERD compared to adults who received a single 40 mg
dose (geometric mean AUC was 103% higher in preterm infants and neonates receiving
single dose of 2.5 mg of PANTOPRAZOLE, and 23% higher in infants 1 through 11
months of age receiving a single dose of approximately 1.2 mg/kg). In these patients,
the apparent clearance (CL/F) increased with age (median clearance: 0.6 L/hr, range:
0.03 to 3.2 L/hr).

These doses resulted in pharmacodynamic effects on gastric but not esophageal pH.
Following once daily dosing of 2.5 mg of pantoprazole in preterm infants and neonates,
there was an increase in the mean gastric pH (from 4.3 at baseline to 5.2 at steady-state)

12
and in the mean % time that gastric pH was > 4 (from 60% at baseline to 80% at steady-
state). Following once daily dosing of approximately 1.2 mg/kg of pantoprazole in infants
1 through 11 months of age, there was an increase in the mean gastric pH (from 3.1 at
baseline to 4.2 at steady-state) and in the mean % time that gastric pH was > 4 (from
32% at baseline to 60% at steady-state). However, no significant changes were observed
in mean intraesophageal pH or % time that esophageal pH was <4 in either age group.

Because pantoprazole was not shown to be effective in the randomized, placebo-

controlled study in this age group, the use of pantoprazole for treatment of symptomatic
GERD in infants less than 1 year of age is not indicated.

Animal Toxicity Data

In a pre-and post-natal development study in rats, the pups were administered oral doses
of pantoprazole at 5, 15, and 30 mg/kg/day (approximately 1, 2.3, and 3.2 times the
exposure (AUC) in children aged 6 to 11 years at a dose of 40 mg) on postnatal day
(PND 4) through PND 21, in addition to lactational exposure through milk. On PND 21,
decreased mean femur length and weight and changes in femur bone mass and
geometry were observed in the offspring at 5 mg/kg/day (approximately equal exposures
(AUC) in children aged 6 to 11 years at the 40 mg dose) and higher doses. Changes in
bone parameters were partially reversible following a recovery period.

In neonatal/juvenile animals (rats and dogs) toxicities were similar to those observed in
adult animals, including gastric alterations, decreases in red cell mass, increases in lipids,
enzyme induction and hepatocellular hypertrophy. An increased incidence of eosinophilic
chief cells in adult and neonatal/juvenile rats, and atrophy of chief cells in adult rats and
in neonatal/juvenile dogs, was observed in the fundic mucosa of stomachs in repeated-
dose studies. Full to partial recovery of these effects were noted in animals of both age
groups following a recovery period.

Patients with Hepatic Impairment

In patients with mild to severe hepatic impairment (Child-Pugh A to C cirrhosis), maximum

pantoprazole concentrations increased only slightly (1.5-fold) relative to healthy subjects.
Although serum half-life values increased to 7-9 hours and AUC values increased by 5-
to 7-fold in hepatic-impaired patients, these increases were no greater than those
observed in CYP2C19 poor metabolizers, where no dosage adjustment is warranted.
These pharmacokinetic changes in hepatic-impaired patients result in minimal drug
accumulation following once-daily, multiple-dose administration. Doses higher than 40
mg/day have not been studied in hepatically impaired patients.

Patients with Renal Impairment

In patients with severe renal impairment, pharmacokinetic parameters for pantoprazole

were similar to those of healthy subjects.

13
Geriatric Use

The incidence rates of adverse reactions and laboratory abnormalities in patients aged
65 years and older were similar to those associated with patients younger than 65 years
of age. No dose adjustment is necessary in elderly patients.

Effects on Ability to Drive and Use Machines

Pantoprazole has no or negligible influence on the ability to drive and use machines.
Adverse drug reactions, such as dizziness and visual disturbances, may occur. If affected,
patients should not drive or operate machines

Undesirable Effects

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

 Acute Tubulointerstitial Nephritis

 Clostridium difficile-associated Diarrhoea
 Bone Fracture
 Severe Cutaneous Adverse Reactions
 Cutaneous and Systemic Lupus Erythematosus
 Cyanocobalamin (Vitamin B12) Deficiency
 Hypomagnesaemia and Mineral Metabolism
 Fundic Gland Polyps
 Acute Kidney Injury

Clinical Trials Experience

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

Adults

Safety in nine randomised comparative US clinical trials in patients with GERD included
1,473 patients on oral pantoprazole (20 mg or 40 mg), 299 patients on an H2-receptor
antagonist, 46 patients on another PPI, and 82 patients on placebo. The most frequently
occurring adverse reactions are listed in Table 2.

Table 2: Adverse Reactions Reported in Clinical Trials of Adult Patients with

GERD at a Frequency of >2%

14
 Pantoprazole Comparators Placebo
(n=1,473) (n=345) (n=82)
% % %

Headache 12.2 12.8 8.5

Diarrhoea 8.8 9.6 4.9

Nausea 7.0 5.2 9.8

Abdominal pain 6.2 4.1 6.1

Vomiting 4.3 3.5 2.4

Flatulence 3.9 2.9 3.7

Dizziness 3.0 2.9 1.2

Arthralgia 2.8 1.4 1.2

Additional adverse reactions that were reported for pantoprazole in clinical trials with a
frequency of ≤2% are listed below by body system:

Body as a whole: allergic reaction, pyrexia, photosensitivity reaction, facial oedema

General disorders at site of administration: asthenia, fatigue and malaise, body

temperature increased; oedema peripheral

Gastrointestinal: constipation; dry mouth; hepatitis.

Haematologic: leucopaenia, thrombocytopaenia,

Metabolic/nutritional: elevated creatine kinase, generalised oedema, elevated

triglycerides, liver enzymes (transaminases, gamma-GT) and bilirubin elevated.

Musculoskeletal: myalgia.

Psychiatric and nervous system disorders: depression, vertigo.

Skin and appendages: rash, urticaria, pruritus

15
Special senses: blurred vision

Paediatric Patients

Safety of pantoprazole in the treatment of EE associated with GERD was evaluated in

paediatric patients aged 1 year through 16 years in three clinical trials. Safety trials
involved paediatric patients with EE; however, as EE is uncommon in the paediatric
population, 249 paediatric patients with endoscopically-proven or symptomatic GERD
were also evaluated. All adult adverse reactions to pantoprazole are considered relevant
to paediatric patients. In patients aged 1 year through 16 years, the most commonly
reported (>4%) adverse reactions include URI, headache, fever, diarrhoea, vomiting,
rash, and abdominal pain.

Additional adverse reactions that were reported for pantoprazole in paediatric patients in
clinical trials with a frequency of ≤4% are listed below by body system:

Body as a whole: allergic reaction, facial oedema

Gastrointestinal: constipation, flatulence, nausea

Metabolic/nutritional: elevated triglycerides, elevated liver enzymes, elevated creatine

kinase

Musculoskeletal: arthralgia, myalgia

Nervous: dizziness, vertigo

Skin and appendages: urticaria

The following adverse reactions seen in adults in clinical trials were not reported in
paediatric patients in clinical trials but are considered relevant to paediatric patients:
photosensitivity reaction, dry mouth, hepatitis, thrombocytopaenia, generalised oedema,
depression, pruritus, leucopaenia, and blurred vision.

Zollinger-Ellison (ZE) Syndrome

In clinical studies of ZE Syndrome, adverse reactions reported in 35 patients taking

pantoprazole 80 mg/day to 240 mg/day for up to 2 years were similar to those reported in
adult patients with GERD.

Post marketing Experience

The following adverse reactions have been identified during post-approval use of
pantoprazole. 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.

These adverse reactions are listed below by body system:

16
Gastrointestinal disorders: fundic gland polyps

General disorders and administration conditions: asthenia, fatigue, malaise

Haematologic: pancytopaenia, agranulocytosis

Hepatobiliary disorders: hepatocellular damage, leading to jaundice and hepatic failure

Immune system disorders: anaphylaxis (including anaphylactic shock), systemic lupus

erythematosus

Infections and infestations: Clostridium difficile-associated diarrhoea

Investigations: weight changes

Metabolism and nutritional disorders: hyponatraemia, hypomagnesaemia, hypocalcemia,

hypokalemia.

Musculoskeletal disorders: Rhabdomyolysis, bone fracture

Nervous: ageusia, dysgeusia

Psychiatric disorders: hallucination, confusion, insomnia, somnolence

Renal and urinary disorders: acute tubulointerstitial nephritis

Skin and subcutaneous tissue disorders: severe dermatologic reactions (some fatal),
including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal
necrolysis (TEN, some fatal), drug reaction with eosinophilia and systemic symptoms
(DRESS), acute generalized exanthematous pustulosis (AGEP), angio-oedema
(Quincke's oedema) and cutaneous lupus erythematosus

Reporting of Side Effects

If you experience any side effects, talk to your doctor or pharmacist or write to
[email protected]. You can also report side effects directly via the National
Pharmacovigilance Programme of India by calling on 1800 180 3024 or you can report to
Cipla Ltd. on 1800 267 7779. By reporting side effects, you can help provide more
information on the safety of this product.

Overdose

Experience in patients taking very high doses of pantoprazole (>240 mg) is limited.
Spontaneous post marketing reports of overdose are generally within the known safety
profile of pantoprazole.

Pantoprazole is not removed by haemodialysis. In case of overdosage, treatment should

be symptomatic and supportive.

17
Single oral doses of pantoprazole at 709 mg/kg, 798 mg/kg and 887 mg/kg were lethal to
mice, rats and dogs, respectively. The symptoms of acute toxicity were hypoactivity,
ataxia, hunched sitting, limb-splay, lateral position, segregation, absence of ear reflex,
and tremor.

PHARMACOLOGICAL PROPERTIES
Mechanism of Action

Pantoprazole is a 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 to the (H+, K+)-ATPase results in a
duration of anti-secretory effect that persists longer than 24 hours for all doses tested
(20–120 mg).

Pharmacodynamic Properties

Anti-secretory Activity

Under maximal acid stimulatory conditions using pentagastrin, a dose-dependent

decrease in gastric acid output occurs after a single dose of oral (20–80 mg) pantoprazole
in healthy volunteers. Pantoprazole given once daily results in increasing inhibition of
gastric acid secretion. Following the initial oral dose of 40 mg pantoprazole, a 51% mean
inhibition was achieved by 2.5 hours. With once-a-day dosing for 7 days, the mean
inhibition was increased to 85%. Pantoprazole suppressed acid secretion in excess of
95% in half of the subjects. Acid secretion returned to normal within a week after the last
dose of pantoprazole; there was no evidence of rebound hypersecretion.

In a series of dose-response studies, pantoprazole, at oral doses ranging from 20 to 120

mg, caused dose-related increases in median basal gastric pH and in the percent of time
gastric pH was >3 and >4. Treatment with 40 mg of pantoprazole produced significantly
greater increases in gastric pH than the 20 mg dose. Doses higher than 40 mg (60, 80,
120 mg) did not result in further significant increases in median gastric pH. The effects of
pantoprazole on median pH from one double-blind crossover study are shown in Table 3.

Table 3: Effect of Single Daily Doses of Oral Pantoprazole on Intra-Gastric pH

Median pH on day 7

Time Placebo 20 mg 40 mg 80 mg

8 a.m. – 8 a.m. 1.3 2.9* 3.8*† 3.9*†

(24 hours)

18
 8 a.m. – 10 p.m. 1.6 3.2* 4.4*† 4.8*†
(Daytime)

10 p.m. – 8 a.m. 1.2 2.1* 3.0* 2.6*

(Night-time)

*Significantly different from placebo

†Significantly different from 20 mg

Serum Gastrin Effects

Fasting serum gastrin levels were assessed in two double-blind studies of the acute
healing of EE in which 682 patients with GERD received 10, 20, or 40 mg of pantoprazole
for up to 8 weeks. At 4 weeks of treatment, there was an increase in mean gastrin levels
of 7%, 35%, and 72% over pre-treatment values in the 10, 20, and 40 mg treatment
groups, respectively. A similar increase in serum gastrin levels was noted at the 8-week
visit with mean increases of 3%, 26%, and 84% for the three pantoprazole dose groups.

In long-term international studies involving over 800 patients, a 2- to 3-fold mean increase
from the pre-treatment fasting serum gastrin level was observed in the initial months of
treatment with pantoprazole at doses of 40 mg per day during GERD maintenance studies
and at 40 mg or higher per day in patients with refractory GERD. Fasting serum gastrin
levels generally remained at approximately 2 to 3 times baseline for up to 4 years of
periodic follow-up in clinical trials. Following short-term treatment with pantoprazole
delayed-release tablets, elevated gastrin levels return to normal by at least 3 months.

Enterochromaffin-Like (ECL) Cell Effects

In 39 patients treated with oral pantoprazole 40–240 mg daily (majority receiving 40–80
mg) for up to 5 years, there was a moderate increase in ECL-cell density, starting after
the first year of use, which appeared to plateau after 4 years.

In a nonclinical study in Sprague-Dawley rats, lifetime exposure (24 months) to

pantoprazole at doses of 0.5–200 mg/kg/day resulted in dose-related increases in gastric
ECL cell proliferation and gastric neuroendocrine (NE)-cell tumours. Gastric NE-cell
tumours in rats may result from chronic elevation of serum gastrin concentrations. The
high density of ECL cells in the rat stomach makes this species highly susceptible to the
proliferative effects of elevated gastrin concentrations produced by PPIs. However, there
were no observed elevations in serum gastrin following the administration of pantoprazole
at a dose of 0.5 mg/kg/day.

19
In a separate study, a gastric NE-cell tumour without concomitant ECL-cell proliferative
changes was observed in 1 female rat following 12 months of dosing with pantoprazole
at 5 mg/kg/day and a 9 month off-dose recovery.

Endocrine Effects

In a clinical pharmacology study, PANTOPRAZOLE 40 mg given once daily for 2 weeks

had no effect on the levels of the following hormones: cortisol, testosterone,
triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), thyronine-
binding protein, parathyroid hormone, insulin, glucagon, renin, aldosterone, follicle-
stimulating hormone, luteinizing hormone, prolactin, and growth hormone.

In a 1-year study of GERD patients treated with PANTOPRAZOLE 40 mg or 20 mg, there

were no changes from baseline in overall levels of T3, T4, and TSH.

Pharmacokinetic Properties

Pantoprazole tablets are prepared as enteric-coated tablets so that absorption of

pantoprazole begins only after the tablet leaves the stomach. Peak serum concentration
(Cmax) and area under the serum concentration time curve (AUC) increase in a manner
proportional to oral and intravenous doses from 10 mg to 80 mg. Pantoprazole does not
accumulate, and its pharmacokinetics are unaltered with multiple daily dosing. Following
oral or intravenous administration, the serum concentration of pantoprazole declines
biexponentially, with a terminal elimination half-life of approximately 1 hour.

In extensive metabolisers with normal liver function receiving an oral dose of the enteric-
coated 40 mg pantoprazole tablet, the peak concentration (Cmax) is 2.5 mcg/mL; the time
to reach the peak concentration (tmax) is 2.5 hours, and the mean total area under the
plasma concentration versus time curve (AUC) is 4.8 mcg•h/mL (range: 1.4–13.3
mcg•h/mL). Following intravenous administration of pantoprazole to extensive
metabolisers, its total clearance is 7.6–14.0 L/hour, and its apparent volume of distribution
is 11.0–23.6 L.

Absorption

Pantoprazole is rapidly absorbed and the maximal plasma concentration is achieved even
after one single 40 mg oral dose. On average at about 2.5 hours p.a., the maximum serum
concentrations of about 2–3 mcg/ml are achieved and these values remain constant after
multiple administration.

Pharmacokinetics does not vary after single or repeated administration. In the dose range
of 10–80 mg, the plasma kinetics of pantoprazole is linear after both oral and intravenous
administration.

The absolute bioavailability from the tablet was found to be about 77%. Concomitant
intake of food had no influence on the AUC, maximum serum concentrations and, thus,
bioavailability. Only the variability of the lag-time will be increased by concomitant food
intake.

20
Distribution

The apparent volume of distribution of pantoprazole is approximately 11 to 23.6 L,

distributing mainly in extracellular fluid. The serum protein binding of pantoprazole is
about 98%, primarily to albumin.

Elimination

Metabolism

Pantoprazole is almost exclusively metabolised in the liver. The main metabolic pathway
is demethylation by CYP2C19, with subsequent sulphate conjugation; other metabolic
pathways include oxidation by CYP3A4. Terminal half-life is about 1 hour and clearance
is about 0.1 l/hour/kg. There were a few cases of subjects with delayed elimination.
Because of the specific binding of pantoprazole to the proton pumps of the parietal cell,
the elimination half-life does not correlate with the much longer duration of action
(inhibition of acid secretion).

Excretion

Renal elimination represents the major route of excretion (about 80%) for the metabolites
of pantoprazole; the rest is excreted with the faeces. The main metabolite in both the
serum and urine is desmethylpantoprazole, which is conjugated with sulphate. The half-
life of the main metabolite (about 1.5 hours) is not much longer than that of pantoprazole.

Special Populations

Poor Metabolisers

Approximately 3% of the European population lack a functional CYP2C19 enzyme and

are called poor metabolisers. In these individuals the metabolism of pantoprazole is
probably mainly catalysed by CYP3A4. After a single-dose administration of 40 mg
pantoprazole, the mean area under the plasma concentration-time curve was
approximately 6 times higher in poor metabolisers than in subjects having a functional
CYP2C19 enzyme (extensive metabolisers). Mean peak plasma concentrations were
increased by about 60%. These findings have no implications for the posology of
pantoprazole.

Renal Impairment

In patients with severe renal impairment, pharmacokinetic parameters for pantoprazole

were similar to those of healthy subjects.

Hepatic Impairment

In patients with mild to severe hepatic impairment (Child-Pugh A to C cirrhosis), maximum

pantoprazole concentrations increased only slightly (1.5-fold) relative to healthy subjects.
Although serum half-life values increased to 7-9 hours and AUC values increased by 5-

21
to 7-fold in hepatic-impaired patients, these increases were no greater than those
observed in CYP2C19 poor metabolizers, where no dosage adjustment is warranted.
These pharmacokinetic changes in hepatic-impaired patients result in minimal drug
accumulation following once-daily, multiple-dose administration. Doses higher than 40
mg/day have not been studied in hepatically impaired patients.

Male and Female Patients

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.

In pediatric patients ages 1 through 16 years there were no clinically relevant effects of
gender on clearance of pantoprazole, as shown by population pharmacokinetic analysis.

Geriatric Patients

A slight increase in the AUC and Cmax in elderly volunteers, compared with younger
counterparts, is also not clinically relevant.

Paediatric Patients

Following administration of single oral doses of 20 mg or 40 mg pantoprazole to children

aged 5 to 16 years, the AUC and Cmax were in the range of corresponding values in adults.

Following administration of single intravenous doses of 0.8 mg or 1.6 mg/kg pantoprazole

to children aged 2 to 16 years, there was no significant association between pantoprazole
clearance and age or weight. The AUC and volume of distribution were in accordance
with data from adults.

NON-CLINICAL PROPERTIES
Animal Toxicology or Pharmacology
Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 24-month carcinogenicity study, Sprague-Dawley rats were treated orally with

pantoprazole doses of 0.5 to 200 mg/kg/day, about 0.1 to 40 times the exposure on a
body surface area basis of a 50 kg person dosed with 40 mg/day. In the gastric fundus,
treatment with 0.5 to 200 mg/kg/day produced enterochromaffin-like (ECL) cell
hyperplasia and benign and malignant neuroendocrine cell tumors in a dose-related
manner. In the forestomach, treatment with 50 and 200 mg/kg/day (about 10 and 40 times
the recommended human dose on a body surface area basis) produced benign
squamous cell papillomas and malignant squamous cell carcinomas. Rare
gastrointestinal tumors associated with pantoprazole treatment included an
adenocarcinoma of the duodenum with 50 mg/kg/day and benign polyps and
adenocarcinomas of the gastric fundus with 200 mg/kg/day. In the liver, treatment with
0.5 to 200 mg/kg/day produced dose-related increases in the incidences of hepatocellular
adenomas and carcinomas. In the thyroid gland, treatment with 200 mg/kg/day produced

22
increased incidences of follicular cell adenomas and carcinomas for both male and female
rats.

In a 24-month carcinogenicity study, Fischer 344 rats were treated orally with doses of 5
to 50 mg/kg/day of pantoprazole, approximately 1 to 10 times the recommended human
dose based on body surface area. In the gastric fundus, treatment with 5 to 50 mg/kg/day
produced enterochromaffin-like (ECL) cell hyperplasia and benign and malignant
neuroendocrine cell tumors. Dose selection for this study may not have been adequate
to comprehensively evaluate the carcinogenic potential of pantoprazole.

In a 24-month carcinogenicity study, B6C3F1 mice were treated orally with doses of 5 to
150 mg/kg/day of pantoprazole, 0.5 to 15 times the recommended human dose based on
body surface area. In the liver, treatment with 150 mg/kg/day produced increased
incidences of hepatocellular adenomas and carcinomas in female mice. Treatment with
5 to 150 mg/kg/day also produced gastric-fundic ECL cell hyperplasia.

A 26-week p53 +/-transgenic mouse carcinogenicity study was not positive.

Pantoprazole was positive in the in vitro human lymphocyte chromosomal aberration

assays, in one of two mouse micronucleus tests for clastogenic effects, and in the in vitro
Chinese hamster ovarian cell/HGPRT forward mutation assay for mutagenic effects.
Equivocal results were observed in the in vivo rat liver DNA covalent binding assay.
Pantoprazole was negative in the in vitro Ames mutation assay, the in vitro unscheduled
DNA synthesis (UDS) assay with rat hepatocytes, the in vitro AS52/GPT mammalian cell-
forward gene mutation assay, the in vitro thymidine kinase mutation test with mouse
lymphoma L5178Y cells, and the in vivo rat bone marrow cell chromosomal aberration
assay.

There were no effects on fertility or reproductive performance when pantoprazole was

given at oral doses up to 500 mg/kg/day in male rats (98 times the recommended human
dose based on body surface area) and 450 mg/kg/day in female rats (88 times the
recommended human dose based on body surface area).

Description

The active ingredient in PANTOSEC 40 Tablets (pantoprazole sodium) enteric-coated

tablet, a PPI, is a substituted benzimidazole, sodium 5-(difluoromethoxy)-2-[[(3,4-
dimethoxy-2- pyridinyl)methyl] sulfinyl]-1H-benzimidazole sesquihydrate, a compound
that inhibits gastric acid secretion. Its empirical formula is C16H14F2N3NaO4S x 1.5 H2O,
with a molecular weight of 432.4.

23
Pantoprazole sodium sesquihydrate is a white to off-white crystalline powder and is
racemic. Pantoprazole has weakly basic and acidic properties. Pantoprazole sodium
sesquihydrate is freely soluble in water, very slightly soluble in phosphate buffer at pH
7.4, and practically insoluble in n-hexane.

PHARMACEUTICAL PARTICULARS
Incompatibilities

NA

Shelf-Life

Please see on the strip

Packaging information

PANTOSEC 40 tablet …… 20×10 Alu- Alu Blister

Storage and Handling Instructions

Store protected from moisture, at a temperature not exceeding 30°C.

PATIENT COUNSELLING INFORMATION

● What is PANTOSEC 40 Tablets?

PANTOSEC 40 Tablets contain the active substance pantoprazole. Pantoprazole is a

selective ‘proton pump inhibitor’ (PPI), a medicine that reduces the amount of acid
produced in your stomach. It is used for treating acid-related diseases of the stomach and
intestine.

Pantoprazole is used to treat adults and adolescents, 12 years of age and above, for the
following:

- Reflux oesophagitis, which is an inflammation of your oesophagus (the tube that

connects your throat to your stomach) accompanied by the regurgitation of
stomach acid.

Pantoprazole is used to treat adults with stomach and duodenal ulcers.

24
Do not take if you have an allergy to this drug

This product should not be used by patients who are hypersensitive to any of the
ingredients.

● Before you take PANTOSEC 40 Tablets, tell your HCP about other conditions you
have and medications you may be taking

- If you have severe liver problems. Please tell your doctor if you ever had
problems with your liver in the past because your liver enzymes need to be
checked more frequently, especially when you are taking pantoprazole as a long-
term treatment. In the case of an increase in liver enzymes, the treatment should
be stopped.
- If you have reduced body stores or risk factors for reduced vitamin B12 and
receive long-term treatment with pantoprazole. As with all acid-reducing
agents, pantoprazole may lead to a reduced absorption of vitamin B12.
- If you are taking HIV protease inhibitors such as atazanavir (for the treatment
of HIV-infection) at the same time as pantoprazole, ask your doctor for specific
advice.
- Taking a PPI such as pantoprazole, especially over a period of more than 1
year, may slightly increase your risk of fracture in the hip, wrist or spine. Tell
your doctor if you have osteoporosis or if you are taking corticosteroids (which can
increase the risk of osteoporosis).
- If you are on pantoprazole for more than 3 months it is possible that the
levels of magnesium in your blood may fall. Low levels of magnesium can be
seen as fatigue, involuntary muscle contractions, disorientation, convulsions,
dizziness, and increased heart rate. If you get any of these symptoms, please tell
your doctor promptly. Low levels of magnesium can also lead to a reduction in
potassium or calcium levels in the blood. Your doctor may decide to perform
regular blood tests to monitor your levels of magnesium.
- If you have ever had a skin reaction after treatment with a medicine similar to
pantoprazole that reduces stomach acid.
- If you get a rash on your skin, especially in areas exposed to the sun, tell your
doctor as soon as you can, as you may need to stop your treatment with
pantoprazole. Remember to also mention any other ill-effects such as pain in your
joints.
- If you are due to have a specific blood test (chromogranin A).

Tell your doctor immediately, before or after taking this medicine, if you notice any of
the following symptoms, which could be a sign of another, more serious, disease:

- An unintentional loss of weight

- Vomiting, particularly if repeated

- Vomiting blood; this may appear as dark coffee grounds in your vomit

- You notice blood in your stools, which may be black or tarry in appearance
25
- Difficulty in swallowing or pain when swallowing

- You look pale and feel weak (anaemia)

- Chest pain

- Stomach pain

- Severe and/or persistent diarrhoea, because this medicine has been associated with a
small increase in infectious diarrhoea

Your doctor may decide that you need some tests to rule out malignant disease because
pantoprazole also alleviates the symptoms of cancer and could cause delay in diagnosing
it. If your symptoms continue in spite of your treatment, further investigations will be
considered.

If you take pantoprazole on a long-term basis (longer than 1 year), your doctor will
probably keep you under regular surveillance. You should report any new and exceptional
symptoms and circumstances whenever you see your doctor.

Children and adolescents

Pantoprazole is not recommended for use in children as it has not been proven to work
in children below 12 years of age.

Other medicines and pantoprazole

Tell your doctor or pharmacist if you are taking, have recently taken or might take any
other medicines, including medicines obtained without a prescription. This is because
Pantoprazole may influence the effectiveness of other medicines, so tell your doctor if
you are taking the following:

Medicines such as ketoconazole, itraconazole and posaconazole (used to treat fungal

infections) or erlotinib (used for certain types of cancer) because Pantoprazole may stop
these and other medicines from working properly.

- Warfarin and phenprocoumon, which affect the thickening, or thinning of the blood. You
may need further checks.

- Medicines used to treat HIV-infection, such as atazanavir.

- Methotrexate (used to treat rheumatoid arthritis, psoriasis, and cancer) – if you are taking
methotrexate your doctor may temporarily stop your Pantoprazole treatment because
pantoprazole can increase levels of methotrexate in the blood.

- Fluvoxamine (used to treat depression and other psychiatric diseases) – if you are taking
fluvoxamine your doctor may reduce the dose.

- Rifampicin (used to treat infections).

26
- St John’s wort (Hypericum perforatum) (used to treat mild depression).

Pregnancy and breastfeeding

There are no adequate data from the use of pantoprazole in pregnant women. Excretion
into human milk has been reported.

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have
a baby, ask your doctor or pharmacist for advice before taking this medicine.

You should use this medicine only if your doctor considers the benefit for you greater than
the potential risk for your unborn child or baby.

Driving and using machines

Pantoprazole has no or negligible influence on the ability to drive and use machines. If
you experience side effects like dizziness or disturbed vision, you should not drive or
operate machines.

● How to take PANTOSEC 40 Tablets

Always take this medicine exactly as your doctor or pharmacist has told you. Check with
your doctor or pharmacist if you are not sure.

Method of administration

Take the tablets 1 hour before a meal without chewing or breaking them and swallow
them whole with some water.

The recommended dose is as follows:

Adults and adolescents, 12 years of age and above

- To treat reflux oesophagitis

The usual dose is one tablet a day. Your doctor may tell you to increase to two tablets
daily. The treatment period for reflux oesophagitis is usually between 4 and 8 weeks. Your
doctor will tell you how long to take your medicine.

Adults

- For the treatment of stomach and duodenal ulcers.

The usual dose is one tablet a day. After consultation with your doctor, the dose may be
doubled. Your doctor will tell you how long to take your medicine. The treatment period
for stomach ulcers is usually between 4 and 8 weeks. The treatment period for duodenal
ulcers is usually between 2 and 4 weeks.

Patients with kidney problems

27
If you have kidney problems, you should not take pantoprazole for the eradication of
Helicobacter pylori.

Patients with liver problems

If you suffer from severe liver problems, you should not take more than one tablet 20 mg
pantoprazole a day (for this purpose, tablets containing 20 mg pantoprazole are
available). If you suffer from moderate or severe liver problems, you should not take
pantoprazole for eradication of Helicobacter pylori.

Use in children and adolescents

These tablets are not recommended for use in children below 12 years of age.

If you take more pantoprazole than you should

Consult your doctor or pharmacist. There are no known symptoms of overdose.

If you forget to take pantoprazole

Do not take a double dose to make up for a forgotten dose. Take your next, normal dose
at the usual time.

If you stop taking pantoprazole

Do not stop taking these tablets without first talking to your doctor or pharmacist.

If you have any further questions about the use of this medicine, ask your doctor,
pharmacist or nurse.

● What are the possible side effects?

Like all medicines, this medicine can cause side effects, although not everybody gets
them.

If you get any of the following side effects, stop taking these tablets and tell your
doctor immediately, or contact the casualty department at your nearest hospital:

- Serious allergic reactions (frequency rare; may affect up to 1 in 1,000 people):

swelling of the tongue and/or throat, difficulty in swallowing, hives (nettle rash), difficulties
in breathing, allergic facial swelling (Quincke’s oedema/angio-oedema), severe dizziness
with very fast heartbeat and heavy sweating.

- Serious skin conditions (frequency not known; frequency cannot be estimated from
the available data): blistering of the skin and rapid deterioration of your general condition,
erosion (including slight bleeding) of the eyes, nose, mouth/lips or genitals (Stevens-
Johnson syndrome, Lyell syndrome, erythema multiforme), and sensitivity to light.

28
- Other serious conditions (frequency not known: frequency cannot be estimated from
the available data): acute kidney injury, yellowing of the skin or whites of the eyes (severe
damage to liver cells, jaundice) or fever, rash, and enlarged kidneys sometimes with
painful urination, and lower back pain (serious inflammation of the kidneys), possibly
leading to kidney failure.

Other side effects

- Common (may affect up to 1 in 10 people)

Benign polyps in the stomach.

- Uncommon (may affect up to 1 in 100 people)

Headache; dizziness; diarrhoea; feeling sick, vomiting; bloating and flatulence (wind);
constipation; dry mouth; abdominal pain and discomfort; skin rash, exanthema, eruption;
itching; feeling weak, exhausted or generally unwell; sleep disorders; fracture of the hip,
wrist or spine.

- Rare (may affect up to 1 in 1,000 people)

Distortion or complete lack of the sense of taste; disturbances in vision such as blurred
vision; hives; pain in the joints; muscle pains; weight changes; raised body temperature;
high fever; swelling of the extremities (peripheral oedema); allergic reactions; depression;
breast enlargement in males.

- Very rare (may affect up to 1 in 10,000 people)

Disorientation

- Not known (frequency cannot be estimated from the available data)

Hallucination, confusion (especially in patients with a history of these symptoms);

decreased level in blood, decreased magnesium level in blood (see section Before you
take PANTOSEC 40 Tablets), feeling of tingling, prickling, pins and needles, burning
sensation or numbness, rash, possibly with pain in the joints; inflammation in the large
bowel, that causes persistent watery diarrhoea.

Side effects identified through blood tests

- Uncommon (may affect up to 1 in 100 people): an increase in liver enzymes.

- Rare (may affect up to 1 in 1,000 people): an increase in bilirubin; increased fat levels
in blood; sharp drop in circulating granular white blood cells, associated with high fever.

- Very rare (may affect up to 1 in 10,000 people): a reduction in the number of blood
platelets, which may cause you to bleed or bruise more than normal; a reduction in the

29
number of white blood cells, which may lead to more frequent infections; coexisting
abnormal reduction in the number of red and white blood cells, as well as platelets.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist or write to
[email protected]. You can also report side effects directly via the National
Pharmacovigilance Programme of India by calling on 1800 180 3024 or you can report to
Cipla Ltd. on 1800 267 7779. By reporting side effects, you can help provide more
information on the safety of this product.

● How to store PANTOSEC 40 Tablets

- Keep this medicine out of the sight and reach of children.

- Store protected from moisture, at a temperature not exceeding 30°C .

- Do not use this medicine after the expiry date, which is stated on the carton and the
container after EXP. The expiry date refers to the last day of that month.
- This medicine does not require any special storage conditions.
- Do not throw away any medicines via wastewater or household waste. Ask your
pharmacist how to throw away medicines you no longer use. These measures will help
to protect the environment.

● What are the ingredients?

The active substance in PANTOSEC 40 Tablets is pantoprazole. Each enteric-coated

tablet contains Pantoprazole Sodium IP Equivalent to Pantoprazole 40 mg

DETAILS OF THE MANUFACTURERS

Mfd. By: Innova Captab Ltd.
1281/1, Hilltop Indl. Estate, Near EPIP Phase – I,
Jharmajri, Baddi – 173 205 (H.P.)

Marketed by Cipla Ltd.

Registered Office:
Cipla House, Peninsula Business Park,
Ganpatrao Kadam Marg
Lower Parel
Mumbai – 400 013, India

DETAILS OF PERMISSION OR LICENCE NUMBER WITH DATE

M.L. MNB/16/970 dated 22/03/2023

DATE OF REVISION

23/03/2023

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