FRONT 300mm

For the use of a Registered Medical Practitioner only Methotrexate

Concomitant use of high dose methotrexate (e.g. 300 mg) and proton-pump inhibitors has been reported to increase methotrexate levels in some

Pantoprazole Tablets IP 40 mg patients. Therefore, in settings where high-dose methotrexate is used, for example cancer and psoriasis, a temporary withdrawal of pantoprazole
may need to be considered.
Other interactions studies
Pantoprazole is extensively metabolized in the liver via the cytochrome P450 enzyme system. The main metabolic pathway is demethylation by
CYP2C19 and other metabolic pathways include oxidation by CYP3A4.
Interaction studies with medicinal products also metabolized with these pathways, like carbamazepine, diazepam, glibenclamide, nifedipine, and an
QUALITATIVE AND QUANTITATIVE COMPOSITION oral contraceptive containing levonorgestrel and ethinyl oestradiol did not reveal clinically significant interactions.
Each enteric coated tablet contains:
Pantoprazole Sodium IP An interaction of pantoprazole with other medicinal products or compounds, which are metabolized using the same enzyme system, cannot be
equivalent to Pantoprazole ...... 40 mg excluded.
Excipients ...................................... q.s. Results from a range of interaction studies demonstrate that pantoprazole does not affect the metabolism of active substances metabolised by CY-
Colours : Ferric Oxide USP-NF Yellow & Titanium Dioxide IP P1A2 (such as caffeine, theophylline), CYP2C9 (such as piroxicam, diclofenac, naproxen), CYP2D6 (such as metoprolol), CYP2E1 (such as ethanol)
Dosage Form and Strength or does not interfere with p-glycoprotein related absorption of digoxin.
pantoprazole 40 mg tablets There were no interactions with concomitantly administered antacids.
CLINICAL PARTICULARS Interaction studies have also been performed by concomitantly administering pantoprazole with the respective antibiotics (clarithromycin, metronida-
Therapeutic Indications zole, amoxicillin). No clinically relevant interactions were found.
For the treatment of gastric ulcer, duodenal ulcer, moderate and severe reflux oesophagitis.
Medicinal products that inhibit or induce CYP2C19
Posology and Method of Administration Inhibitors of CYP2C19 such as fluvoxamine could increase the systemic exposure of pantoprazole. A dose reduction may be considered for patients
Tablets should not be chewed or crushed and should be swallowed whole 1 hour before a meal with some water. treated long-term with high doses of pantoprazole, or those with hepatic impairment.
The recommended dosages of pantoprazole are outlined in Table 1. Enzyme inducers affecting CYP2C19 and CYP3A4 such as rifampicin and St John´s wort (Hypericum perforatum) may reduce the plasma concen-
Table 1: Recommended Dosing Schedule for Pantoprazole Tablets trations of PPIs that are metabolized through these enzyme systems.
Indication Dose Frequency Use in Special Populations
Pregnancy
Short-Term Treatment of EE Associated with GERD A moderate amount of data on pregnant women (between 300-1000 pregnancy outcomes) indicate no malformative or feto/ neonatal toxicity of
Adults 40 mg Once daily for up to 8 weeks* Pantoprazole.
Children (5 years and older) Animal studies have shown reproductive toxicity.
≥15 kg to <40 kg 20 mg Once daily for up to 8 weeks As a precautionary measure, it is preferable to avoid the use of Pantoprazole during pregnancy.
≥40 kg 40 mg
Maintenance of Healing of EE Breast-feeding
Animal studies have shown excretion of pantoprazole in breast milk. There is insufficient information on the excretion of pantoprazole in human milk
Adults 40 mg Once daily# but excretion into human milk has been reported. A risk to the newborns/infants cannot be excluded. Therefore, a decision on whether to discontinue
Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome breast-feeding or to discontinue/abstain from Pantoprazole therapy should take into account the benefit of breast-feeding for the child and the benefit
Adults 40 mg Twice daily** of Pantoprazole therapy for the woman.
For adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole may be considered. Fertility
#
Controlled studies did not extend beyond 12 months. There was no evidence of impaired fertility following the administration of pantoprazole in animal studies
Treatment of Gastric Ulcers Paediatric Patients (Below 12 Years of Age)
One tablet of pantoprazole per day. In individual cases, the dose may be doubled (increase to two tablets of pantoprazole daily), especially when 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.
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 Patients with Hepatic Impairment
will usually be achieved within a further 4 weeks. A daily dose of 20 mg pantoprazole (one tablet of 20 mg pantoprazole) should not be exceeded in patients with severe liver impairment. Pantoprazole
Treatment of Duodenal Ulcers must not be used in combination treatment for eradication of H. pylori in patients with moderate-to-severe hepatic dysfunction since currently no data
One tablet of pantoprazole per day. In individual cases, the dose may be doubled (increase to two tablets of pantoprazole daily), especially when there are available on the efficacy and safety of pantoprazole in combination treatment of these patients.
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 Patients with Renal Impairment
will be achieved in almost all cases within a further 2 weeks. No dose adjustment is necessary in patients with impaired renal function. Pantoprazole must not be used in combination treatment for eradication
Special Populations of H. pylori in patients with impaired renal function since currently no data are available on the efficacy and safety of pantoprazole in combination
Children below 12 years of age treatment for these patients.
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. Geriatric Use
Hepatic Impairment The incidence rates of adverse reactions and laboratory abnormalities in patients aged 65 years and older were similar to those associated with
A daily dose of 20 mg pantoprazole (1 tablet of 20 mg pantoprazole) should not be exceeded in patients with severe liver impairment. Pantoprazole patients younger than 65 years of age. No dose adjustment is necessary in elderly patients.
must not be used in combination treatment for eradication of H. pylori in patients with moderate to severe hepatic dysfunction since currently no data Effects on Ability to Drive and Use Machines
are available on the efficacy and safety of Pantoprazole in combination treatment of these patients. Pantoprazole has no or negligible influence on the ability to drive and use machines. Adverse drug reactions, such as dizziness and visual disturbanc-
Renal Impairment es, may occur. If affected, patients should not drive or operate machines
No dose adjustment is necessary in patients with impaired renal function. Pantoprazole must not be used in combination treatment for eradication Undesirable Effects
of H. pylori in patients with impaired renal function since currently no data are available on the efficacy and safety of pantoprazole in combination The following serious adverse reactions are described below and elsewhere in the labelling:
treatment for these patients. • Acute Interstitial Nephritis
Elderly • Clostridium difficile-associated Diarrhoea
No dose adjustment is necessary in elderly patients. • Bone Fracture
Contraindications • Cutaneous and Systemic Lupus Erythematosus
Pantoprazole tablets are contraindicated in case of hypersensitivity to the active substance, substituted benzimidazoles, or to any of the other excip- • Cyanocobalamin (Vitamin B12) Deficiency
ients of the tablet. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angio-oedema, bronchospasm, acute interstitial nephritis, • Hypomagnesaemia
and urticaria. Proton-pump inhibitors (PPIs), including pantoprazole tablets, are contraindicated with rilpivirine-containing products. • Fundic Gland Polyps
• Acute Kidney Injury
Special Warnings and Precautions for Use
Hepatic impairment Clinical Trials Experience
In patients with severe liver impairment, the liver enzymes should be monitored regularly during treatment with pantoprazole, particularly on long-term Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly
use. In the case of a rise of the liver enzymes, the treatment should be discontinued. compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Atrophic Gastritis Adults

Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated long-term with pantoprazole, particularly in patients 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
who were Helicobacter pylori positive 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.
Combination therapy
Table 2: Adverse Reactions Reported in Clinical Trials of Adult Patients with GERD at a Frequency of >2%
FRONT 400mm

In the case of combination therapy, the summaries of product characteristics of the respective medicinal products should be observed.
Pantoprazole (n=1,473) % Comparators (n=345) % Placebo (n=82) %
Gastric malignancy
Headache 12.2 12.8 8.5
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 Diarrhoea 8.8 9.6 4.9
suspected or present, malignancy should be excluded. Nausea 7.0 5.2 9.8
Abdominal pain 6.2 4.1 6.1
Further investigation is to be considered if symptoms persist despite adequate treatment. Vomiting 4.3 3.5 2.4
Co-administration with HIV protease inhibitors Flatulence 3.9 2.9 3.7
Co-administration of pantoprazole is not recommended with HIV protease inhibitors for which absorption is dependent on acidic intragastric pH such Dizziness 3.0 2.9 1.2
as atazanavir, due to significant reduction in their bioavailability. Arthralgia 2.8 1.4 1.2
Influence on vitamin B12 absorption
In patients with Zollinger-Ellison syndrome and other pathological hypersecretory conditions requiring long-term treatment, pantoprazole, as all Additional adverse reactions that were reported for pantoprazole in clinical trials with a frequency of ≤2% are listed below by body system:
acid-blocking medicines, may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be considered in BODY AS A WHOLE: allergic reaction, pyrexia, photosensitivity reaction, facial oedema
patients with reduced body stores or risk factors for reduced vitamin B12 absorption on long-term therapy or if respective clinical symptoms are GENERAL DISORDERS AT SITE OF ADMINISTRATION: asthenia, fatigue and malaise, body temperature increased; oedema peripheral
observed. GASTROINTESTINAL: diarrhoea; nausea/vomiting; abdominal distension and bloating; constipation; dry mouth; abdominal pain and discomfort,
hepatitis.
Clostridium difficile Associated Diarrhea HAEMATOLOGIC: leucopaenia, thrombocytopaenia, pancytopaenia
Published observational studies suggest that PPI therapy like pantoprazole may be associated with an increased risk of Clostridium difficile associ- IMMUNE SYSTEM DISORDERS: hypersensitivity (including anaphylactic reactions and anaphylactic shock)
ated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve. Patients should use the METABOLIC/NUTRITIONAL: elevated creatine kinase, generalised oedema, elevated triglycerides, liver enzymes (transaminases, gamma-GT) and
lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. bilirubin elevated, weight changes, hyperlipidaemias and lipid increase (triglycerides, cholesterol), hypocalcaemia and hypokalaemia.
Long term treatment MUSCULOSKELETAL: fracture of the hip, wrist or spine myalgia, arthralgia, muscle spasm.
In long-term treatment, especially when exceeding a treatment period of 1 year, patients should be kept under regular surveillance. PSYCHIATRIC AND NERVOUS SYSTEM DISORDERS: depression (and all aggravations), disorientation (and all aggravations), vertigo, taste dis-
orders, paraesthesia, sleep disorders
Gastrointestinal infections caused by bacteria SKIN AND APPENDAGES: rash/exanthema/eruption, urticaria, pruritus, angio-oedema
Treatment with Pantoprazole may lead to a slightly increased risk of gastrointestinal infections caused by bacteria such as Salmonella and Campy- SPECIAL SENSES: disturbances in vision/blurred vision
lobacter or C. difficile. REPRODUCTIVE SYSTEM AND BREAST DISORDERS: gynaecomastia
Pantoprazole, like all proton pump inhibitors (PPIs), might be expected to increase the counts of bacteria normally present in the upper gastrointes- Adverse reactions whose frequency of occurrence is not known but may occur include hyponatraemia, hypomagnesaemia, hallucination; confusion
tinal tract. (especially in pre-disposed patients, as well as the aggravation of these symptoms in case of pre-existence), hepatocellular injury; jaundice; hepato-
cellular failure, Stevens-Johnson syndrome; Lyell syndrome; erythema multiforme; photo-sensitivity; and interstitial nephritis.
Hypomagnesaemia
Severe hypomagnesaemia has been reported in patients treated with PPIs like pantoprazole for at least three months, and in most cases for a year. Paediatric Patients
Serious manifestations of hypomagnesaemia such as fatigue, tetany, delirium, convulsions, dizziness and ventricular arrhythmia can occur but they Safety of pantoprazole in the treatment of EE associated with GERD was evaluated in paediatric patients aged 1 year through 16 years in three
may begin insidiously and be overlooked. In most affected patients, hypomagnesaemia improved after magnesium replacement and discontinuation clinical trials. Safety trials involved paediatric patients with EE; however, as EE is uncommon in the paediatric population, 249 paediatric patients with
of the PPI. 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,
For patients expected to be on prolonged treatment or who take PPIs with digoxin or medicinal products that may cause hypomagnesaemia (e.g., vomiting, rash, and abdominal pain.
diuretics), health care professionals should consider measuring magnesium levels before starting PPI treatment and periodically during treatment.
Additional adverse reactions that were reported for pantoprazole in paediatric patients in clinical trials with a frequency of ≤4% are listed below by
Bone fractures body system:
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 BODY AS A WHOLE: allergic reaction, facial oedema
fracture, predominantly in the elderly or in presence of other recognised risk factors. Observational studies suggest that proton pump inhibitors may GASTROINTESTINAL: constipation, flatulence, nausea
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 METABOLIC/NUTRITIONAL: elevated triglycerides, elevated liver enzymes, elevated creatine kinase
care according to current clinical guidelines and they should have an adequate intake of vitamin D and calcium. MUSCULOSKELETAL: arthralgia, myalgia
Subacute cutaneous lupus erythematosus (SCLE) NERVOUS: dizziness, vertigo
Proton pump inhibitors are associated with very infrequent cases of SCLE. If lesions occur, especially in sun-exposed areas of the skin, and if accom- SKIN AND APPENDAGES: urticaria
panied by arthralgia, the patient should seek medical help promptly and the health care professional should consider stopping Pantoprazole. SCLE The following adverse reactions seen in adults in clinical trials were not reported in paediatric patients in clinical trials but are considered relevant to
after previous treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors. paediatric patients: photosensitivity reaction, dry mouth, hepatitis, thrombocytopaenia, generalised oedema, depression, pruritus, leucopaenia, and
blurred vision.
Tumourigenicity
Due to the chronic nature of GERD, there may be a potential for prolonged administration of pantoprazole. In long-term rodent studies, pantoprazole Postmarketing Experience
was carcinogenic and caused rare types of gastrointestinal tumours. The relevance of these findings to tumour development in humans is unknown. 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.
Concomitant Use of Pantoprazole with Methotrexate
These adverse reactions are listed below by body system:
Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate
GASTROINTESTINAL DISORDERS: fundic gland polyps
and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dosemethotrexate administration,
GENERAL DISORDERS AND ADMINISTRATION CONDITIONS: asthenia, fatigue, malaise
a temporary withdrawal of the PPI may be considered in some patients.
HAEMATOLOGIC: pancytopaenia, agranulocytosis
Interference with laboratory tests HEPATOBILIARY DISORDERS: hepatocellular damage, leading to jaundice and hepatic failure
Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To avoid this interference, Pantoprazole treat- IMMUNE SYSTEM DISORDERS: anaphylaxis (including anaphylactic shock), systemic lupus erythematosus
ment should be stopped for at least 5 days before CgA measurements. If CgA and gastrin levels have not returned to reference range after initial INFECTIONS AND INFESTATIONS: Clostridium difficile-associated diarrhoea
measurement, measurements should be repeated 14 days after cessation of proton pump inhibitor treatment. INVESTIGATIONS: weight changes
In Presence of Alarm Symptoms METABOLISM AND NUTRITIONAL DISORDERS: hyponatraemia, hypomagnesaemia, hypocalcemia, hypokalemia.
In the presence of any alarm symptom (e. g. significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis, anaemia or melaena) MUSCULOSKELETAL DISORDERS: Rhabdomyolysis, bone fracture
and when gastric ulcer is suspected or present, malignancy should be excluded, as treatment with pantoprazole may alleviate symptoms and delay NERVOUS: ageusia, dysgeusia
diagnosis. PSYCHIATRIC DISORDERS: hallucination, confusion, insomnia, somnolence
RENAL AND URINARY DISORDERS: acute tubulointerstitial nephritis
Co-administration with Atazanavir SKIN AND SUBCUTANEOUS TISSUE DISORDERS: severe dermatologic reactions (some fatal), including erythema multiforme, Stevens-Johnson
Co-administration of atazanavir with proton pump inhibitors is not recommended. If the combination of atazanavir with a proton pump inhibitor is syndrome, and toxic epidermal necrolysis (TEN, some fatal), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized
judged unavoidable, close clinical monitoring (e.g virus load) is recommended in combination with an increase in the dose of atazanavir to 400 mg exanthematous pustulosis (AGEP), angio-oedema (Quincke’s oedema) and cutaneous lupus erythematosus
with 100 mg of ritonavir. A pantoprazole dose of 20 mg per day should not be exceeded.
Reporting of Side Effects
Long-term Treatment 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
In long-term treatment, especially when exceeding a treatment period of 1 year, patients should be kept under regular surveillance. 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
Drug Interactions effects, you can help provide more information on the safety of this product.
Medicinal products with pH-dependent absorption pharmacokinetics Overdose
Because of profound and long lasting inhibition of gastric acid secretion, pantoprazole may interfere with the absorption of other medicinal products Experience in patients taking very high doses of pantoprazole (>240 mg) is limited. Spontaneous post marketing reports of overdose are generally
where gastric pH is an important determinant of oral availability, e.g. some azole antifungals such as ketoconazole, itraconazole, posaconazole and within the known safety profile of pantoprazole.
other medicine such as erlotinib.
Pantoprazole is not removed by haemodialysis. In case of overdosage, treatment should be symptomatic and supportive.
HIV protease inhibitors 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
Co-administration of pantoprazole is not recommended with HIV protease inhibitors for which absorption is dependent on acidic intragastric pH such toxicity were hypoactivity, ataxia, hunched sitting, limb-splay, lateral position, segregation, absence of ear reflex, and tremor.
as atazanavir due to significant reduction in their bioavailability. If the combination of HIV protease inhibitors with a proton pump inhibitor is judged
unavoidable, close clinical monitoring (e.g. virus load) is recommended. A pantoprazole dose of 20 mg per day should not be exceeded. Dosage of PHARMACOLOGICAL PROPERTIES
the HIV protease inhibitors may need to be adjusted. 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 se-
Coumarin anticoagulants (phenprocoumon or warfarin) cretory surface of the gastric parietal cell. This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus.
Co-administration of pantoprazole with warfarin or phenprocoumon did not affect the pharmacokinetics of warfarin, phenprocoumon or INR. However, 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).
there have been reports of increased INR and prothrombin time in patients receiving PPIs and warfarin or phenprocoumon concomitantly. Increases
in INR and prothrombin time may lead to abnormal bleeding, and even death. Patients treated with pantoprazole and warfarin or phenprocoumon may
need to be monitored for increase in INR and prothrombin time.
99338718

PACKAGING DEVELOPMENT
Product Name: Pantosec Tablets Material No. 99338718 Version: 01 Item : Leaflet Co-ordinator: Hemalata Artist: Manish Date: 05/09/2022
Ghadi

Colours : INK: Oil based Ink from DIC OR MICRO

BLUE WOOL TEST VALUE 5-8 Black
(LIGHT FASTENING DATA)

Design : Folded Reference: new word file Software : Indesign CC

Fonts : -------- Links: NA

Actual Size: 300 x 400 mm Size after Folding: 37.5 x 50 mm Pharmacode: -- Grain Direction : Parallel to length Screen : # __

Material: 54 GSM Maplitho Paper Varnish: NA Artwork Print Size:

actual scaled

Path: D:\Manish\April 2022 to March 2023\Hemalata Ghadi\Pantosec (Hetero)\99338718 Pantosec Tablets Leaflet India.indd

• Instructions / Remark : Checked by Artist Cordinator file loaded in Server Section Head
• Any deviation must be brought to the notice of packaging development
Pharma Code
co-ordinator immediately.
• For any clarification, please contact packaging development co-ordinator 2D Code
immediately. QR Code
NO CHANGES IN ARTWORK SHOULD BE DONE BY THE PRINTER
• The printer should verify the e-proof against the approved artwork before Bar Code
submitting for approval and the e-proof should have printer details . Artwork
Spell check
 BACK 300mm

Pharmacodynamic Properties 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,
Anti-secretory Activity more serious, disease:
Under maximal acid stimulatory conditions using pentagastrin, a dose-dependent decrease in gastric acid output occurs after a single dose of oral - An unintentional loss of weight
(20–80 mg) pantoprazole in healthy volunteers. Pantoprazole given once daily results in increasing inhibition of gastric acid secretion. Following the - Vomiting, particularly if repeated
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 - Vomiting blood; this may appear as dark coffee grounds in your vomit
increased to 85%. Pantoprazole suppressed acid secretion in excess of 95% in half of the subjects. Acid secretion returned to normal within a week - You notice blood in your stools, which may be black or tarry in appearance
after the last dose of pantoprazole; there was no evidence of rebound hypersecretion. - Difficulty in swallowing or pain when swallowing
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 - You look pale and feel weak (anaemia)
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 - Chest pain
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 - Stomach pain
pantoprazole on median pH from one double-blind crossover study are shown in Table 3. - 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
Table 3: Effect of Single Daily Doses of Oral Pantoprazole on Intra-Gastric pH could cause delay in diagnosing it. If your symptoms continue in spite of your treatment, further investigations will be considered.
Median pH on day 7 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
Time Placebo 20 mg 40 mg 80 mg any new and exceptional symptoms and circumstances whenever you see your doctor.
8 a.m. – 8 a.m. (24 hours)  1.3 2.9* 3.8*† 3.9*† Children and adolescents
8 a.m. – 10 p.m. (Daytime)  1.6 3.2* 4.4*† 4.8*† Pantoprazole is not recommended for use in children as it has not been proven to work in children below 12 years of age.
10 p.m. – 8 a.m. (Night-time) 1.2 2.1* 3.0* 2.6* Other medicines and pantoprazole
*Significantly different from placebo Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a
†Significantly different from 20 mg prescription. This is because Pantoprazole may influence the effectiveness of other medicines, so tell your doctor if you are taking the following:
Serum Gastrin Effects Medicines such as ketoconazole, itraconazole and posaconazole (used to treat fungal infections) or erlotinib (used for certain types of cancer) be-
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, cause Pantoprazole may stop these and other medicines from working properly.
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 - Warfarin and phenprocoumon, which affect the thickening, or thinning of the blood. You may need further checks.
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 - Medicines used to treat HIV-infection, such as atazanavir.
with mean increases of 3%, 26%, and 84% for the three pantoprazole dose groups. - 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.
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 - Fluvoxamine (used to treat depression and other psychiatric diseases) – if you are taking fluvoxamine your doctor may reduce the dose.
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 - Rifampicin (used to treat infections).
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 - St John’s wort (Hypericum perforatum) (used to treat mild depression).
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. Pregnancy and breastfeeding
There are no adequate data from the use of pantoprazole in pregnant women. Excretion into human milk has been reported.
Enterochromaffin-Like (ECL) Cell Effects 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
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- taking this medicine.
cell density, starting after the first year of use, which appeared to plateau after 4 years. 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.
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 Driving and using machines
increases in gastric ECL cell proliferation and gastric neuroendocrine (NE)-cell tumours. Gastric NE-cell tumours in rats may result from chronic eleva- Pantoprazole has no or negligible influence on the ability to drive and use machines. If you experience side effects like dizziness or disturbed vision,
tion of serum gastrin concentrations. The high density of ECL cells in the rat stomach makes this species highly susceptible to the proliferative effects you should not drive or operate machines.
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. ● How to take PANTOSEC 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.
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. Method of administration
Take the tablets 1 hour before a meal without chewing or breaking them and swallow them whole with some water.
Pharmacokinetic Properties The recommended dose is as follows:
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 dos- Adults and adolescents, 12 years of age and above
es from 10 mg to 80 mg. Pantoprazole does not accumulate, and its pharmacokinetics are unaltered with multiple daily dosing. Following oral or intra- - To treat reflux oesophagitis
venous administration, the serum concentration of pantoprazole declines biexponentially, with a terminal elimination half-life of approximately 1 hour. 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
In extensive metabolisers with normal liver function receiving an oral dose of the enteric-coated 40 mg pantoprazole tablet, the peak concentration between 4 and 8 weeks. Your doctor will tell you how long to take your medicine.
(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 Adults
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 - For the treatment of stomach and duodenal ulcers.
clearance is 7.6–14.0 L/hour, and its apparent volume of distribution is 11.0–23.6 L. 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
Absorption medicine. The treatment period for stomach ulcers is usually between 4 and 8 weeks. The treatment period for duodenal ulcers is usually between
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 2 and 4 weeks.
hours p.a., the maximum serum concentrations of about 2–3 mcg/ml are achieved and these values remain constant after multiple administration. Patients with kidney problems
Pharmacokinetics does not vary after single or repeated administration. In the dose range of 10–80 mg, the plasma kinetics of pantoprazole is linear If you have kidney problems, you should not take pantoprazole for the eradication of Helicobacter pylori.
after both oral and intravenous administration. Patients with liver problems
The absolute bioavailability from the tablet was found to be about 77%. Concomitant intake of food had no influence on the AUC, maximum serum 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
concentrations and, thus, bioavailability. Only the variability of the lag-time will be increased by concomitant food intake. 20 mg pantoprazole are available). If you suffer from moderate or severe liver problems, you should not take pantoprazole for eradication of
Distribution Helicobacter pylori.
Pantoprazole’s serum protein-binding is about 98%. Volume of distribution is about 0.15 l/kg. Use in children and adolescents
Elimination These tablets are not recommended for use in children below 12 years of age.
Pantoprazole is almost exclusively metabolised in the liver. The main metabolic pathway is demethylation by CYP2C19, with subsequent sulphate If you take more pantoprazole than you should
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 Consult your doctor or pharmacist. There are no known symptoms of overdose.
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 If you forget to take pantoprazole
elimination half-life does not correlate with the much longer duration of action (inhibition of acid secretion). Do not take a double dose to make up for a forgotten dose. Take your next, normal dose at the usual time.
Renal elimination represents the major route of excretion (about 80%) for the metabolites of pantoprazole; the rest is excreted with the faeces. The If you stop taking pantoprazole
main metabolite in both the serum and urine is desmethylpantoprazole, which is conjugated with sulphate. The half-life of the main metabolite (about Do not stop taking these tablets without first talking to your doctor or pharmacist.
1.5 hours) is not much longer than that of pantoprazole. If you have any further questions about the use of this medicine, ask your doctor, pharmacist or nurse.
Special Populations ● What are the possible side effects?
Poor Metabolisers Like all medicines, this medicine can cause side effects, although not everybody gets them.
Approximately 3% of the European population lack a functional CYP2C19 enzyme and are called poor metabolisers. In these individuals the me-
tabolism of pantoprazole is probably mainly catalysed by CYP3A4. After a single-dose administration of 40 mg pantoprazole, the mean area under If you get any of the following side effects, stop taking these tablets and tell your doctor immediately, or contact the casualty department
the plasma concentration-time curve was approximately 6 times higher in poor metabolisers than in subjects having a functional CYP2C19 enzyme at your nearest hospital:
(extensive metabolisers). Mean peak plasma concentrations were increased by about 60%. These findings have no implications for the posology of - 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
pantoprazole. (nettle rash), difficulties in breathing, allergic facial swelling (Quincke’s oedema/angio-oedema), severe dizziness with very fast heartbeat and
BACK 400mm

heavy sweating.
Renal Impairment - Serious skin conditions (frequency not known; frequency cannot be estimated from the available data): blistering of the skin and rapid
No dose reduction is recommended when pantoprazole is administered to patients with impaired renal function (including dialysis patients). As with deterioration of your general condition, erosion (including slight bleeding) of the eyes, nose, mouth/lips or genitals (Stevens-Johnson syndrome,
healthy subjects, pantoprazole’s half-life is short. Only very small amounts of pantoprazole are dialysed. Although the main metabolite has a moder- Lyell syndrome, erythema multiforme), and sensitivity to light.
ately delayed half-life (2–3 hours), excretion is still rapid and, thus, accumulation does not occur. - Other serious conditions (frequency not known: frequency cannot be estimated from the available data): acute kidney injury, yellowing of the
Hepatic Impairment skin or whites of the eyes (severe damage to liver cells, jaundice) or fever, rash, and enlarged kidneys sometimes with painful urination, and lower
Although for patients with liver cirrhosis (Child-Pugh classes A and B), the half-life values increased to between 7 and 9 hours and the AUC values back pain (serious inflammation of the kidneys), possibly leading to kidney failure.
increased by a factor of 5 to 7, the maximum serum concentration only increased slightly by a factor of 1.5, compared with healthy subjects. Other side effects
Geriatric Patients - Common (may affect up to 1 in 10 people)
A slight increase in the AUC and Cmax in elderly volunteers, compared with younger counterparts, is also not clinically relevant. Benign polyps in the stomach.
Paediatric Patients - Uncommon (may affect up to 1 in 100 people)
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 Headache; dizziness; diarrhoea; feeling sick, vomiting; bloating and flatulence (wind); constipation; dry mouth; abdominal pain and discomfort; skin
corresponding values in adults. 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)
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 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;
association between pantoprazole clearance and age or weight. The AUC and volume of distribution were in accordance with data from adults. raised body temperature; high fever; swelling of the extremities (peripheral oedema); allergic reactions; depression; breast enlargement in males.
NON-CLINICAL PROPERTIES - Very rare (may affect up to 1 in 10,000 people)
Animal Toxicology or Pharmacology Disorientation
Non-clinical data reveal no special hazard to humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity. - Not known (frequency cannot be estimated from the available data)
In the 2-year carcinogenicity studies in rats neuroendocrine neoplasms were found. In addition, squamous cell papillomas were found in the forestom- Hallucination, confusion (especially in patients with a history of these symptoms); decreased level in blood, decreased magnesium level in blood (see
ach of rats. The mechanism leading to the formation of gastric carcinoids by substituted benzimidazoles has been carefully investigated and allows section Before you take PANTOSEC Tablets), feeling of tingling, prickling, pins and needles, burning sensation or numbness, rash, possibly with
the conclusion that it is a secondary reaction to the massively elevated serum gastrin levels occurring in the rat during chronic high-dose treatment. pain in the joints; inflammation in the large bowel, that causes persistent watery diarrhoea.
In the 2-year rodent studies, an increased number of liver tumours was observed in rats and in female mice and was interpreted as being due to Side effects identified through blood tests
pantoprazole high metabolic rate in the liver. - Uncommon (may affect up to 1 in 100 people): an increase in liver enzymes.
A slight increase of neoplastic changes of the thyroid was observed in the group of rats receiving the highest dose (200 mg/kg). The occurrence of - 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,
these neoplasms is associated with the pantoprazole induced changes in the breakdown of thyroxine in the rat liver. As the therapeutic dose in man associated with high fever.
is low, no harmful effects on the thyroid glands are expected. - 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 number of white blood cells, which may lead to more frequent infections; coexisting abnormal reduction in the number of
In animal reproduction studies, signs of slight foetotoxicity were observed at doses above 5 mg/kg. Investigations revealed no evidence of impaired red and white blood cells, as well as platelets.
fertility or teratogenic effects. Penetration of the placenta was investigated in the rat and was found to increase with advanced gestation. As a result,
concentration of pantoprazole in the foetus is increased shortly before birth. 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
Description 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
The active ingredient in PANTOSEC Tablets (pantoprazole sodium) enteric-coated tablet, a PPI, is a substituted benzimidazole, sodium 5-(diflu- effects, you can help provide more information on the safety of this product.
oromethoxy)-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. ● How to store PANTOSEC Tablets
- Keep this medicine out of the sight and reach of children.
- Protect from moisture and keep at a temperature not exceeding 30⁰C.
- 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.
Pantoprazole sodium sesquihydrate is a white to off-white crystalline powder and is racemic. Pantoprazole has weakly basic and acidic properties. ● What are the ingredients?
Pantoprazole sodium sesquihydrate is freely soluble in water, very slightly soluble in phosphate buffer at pH 7.4, and practically insoluble in n-hexane. The active substance in PANTOSEC Tablets is pantoprazole. Each enteric-coated tablet contains pantoprazole sodium sesquihydrates equivalent
PHARMACEUTICAL PARTICULARS to Pantoprazole 40 mg.
Incompatibilities DETAILS OF THE MANUFACTURER
NA Manufactured by:
Shelf-Life Hetero Labs Limited (Unit-I)
See on the pack Village : Kalyanpur, Chakkan Road,
Tehsil : Baddi, Distt.: Solan,
Packaging information Himachal Pradesh - 173 205.
Alu-Alu Blister pack of 10 Tablets
Marketed by CIPLA LTD.
Storage and Handling Instructions Registered Office:
Store protected from moisture, at a temperature not exceeding 30°C. Cipla House, Peninsula Business Park, Ganpatrao Kadam Marg,
PATIENT COUNSELLING INFORMATION Lower Parel, Mumbai - 400 013, INDIA
● What is PANTOSEC Tablets? DETAILS OF PERMISSION OR LICENCE NUMBER WITH DATE
PANTOSEC Tablets contain the active substance pantoprazole. Pantoprazole is a selective ‘proton pump inhibitor’ (PPI), a medicine that reduces the MNB/06/328 date: 21.01.2021
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: DATE OF REVISION
- Reflux oesophagitis, which is an inflammation of your oesophagus (the tube that connects your throat to your stomach) accompanied by the 18.07.2022
regurgitation of stomach acid.
Pantoprazole is used to treat adults with stomach and duodenal ulcers.
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 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
99338718

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).