Symptomatic response to therapy with pantoprazole does not preclude the presence of gastric malignancy.
Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated longterm
with pantoprazole, particularly in patients who were H. pylori positive.
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 B-12) caused by hypoor
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.
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.
Several published observational studies suggest that proton pump inhibitor (PPI) therapy may be
associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The
risk of fracture was increased in patients who received high-dose, defined as multiple daily doses,
and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest
duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosisrelated
fractures should be managed according to established treatment guidelines.
Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with
PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include
tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required
magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged
treatment or who take PPIs with medications such as digoxin or drugs that may cause
hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium
levels prior to initiation of PPI treatment and periodically.
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 tumors. The relevance of these findings to tumor development in humans is
Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose) may
elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to
methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of the PPI
may be considered in some patients.
In a clinical pharmacology study, pantoprazole delayed release 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
In a 1-year study of GERD patients treated with pantoprazole delayed release 40 mg or 20 mg, there
were no changes from baseline in overall levels of T3, T4, and TSH.
Caution is advised when the drug is administered to patients with cerebrovascular events including
risk factors for stroke.
Caution is also advised when levosulpiride is given to patients with cardiac insufficiency.
Levosulpiride should not be used when gastrointestinal stimulation of motility can be harmful, e.g., in
presence of gastrointestinal hemorrhage, mechanical obstructions or perforations.
Levosulpiride may cause drowsiness in some patients, especially at higher doses, thus patients
should be advised to exercise caution when driving or operating machinery.
Pregnancy & Lactation
Enteric coated pantoprazole sodium and sustained release levosulpiride capsule is contraindicated
during pregnancy and lactation.