Drug Facts
Composition & Profile
Identifiers & Packaging
16 HOW SUPPLIED/STORAGE AND HANDLING Pantoprazole Sodium Delayed-Release Tablets USP, 40 mg are yellow colored, oval shaped, biconvex, enteric-coated tablets imprinted with ‘I’ and ‘52’ with brown ink on one side and plain on other side. NDC: 70518-0860-00 NDC: 70518-0860-01 PACKAGING: 90 in 1 BOTTLE PLASTIC PACKAGING: 28 in 1 BLISTER PACK Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Repackaged and Distributed By: Remedy Repack, Inc. 625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762; PRINCIPAL DISPLAY PANEL DRUG: Pantoprazole Sodium GENERIC: Pantoprazole Sodium DOSAGE: TABLET, DELAYED RELEASE ADMINSTRATION: ORAL NDC: 70518-0860-0 NDC: 70518-0860-1 COLOR: yellow SHAPE: OVAL SCORE: No score SIZE: 12 mm IMPRINT: I;52 PACKAGING: 90 in 1 BOTTLE, PLASTIC PACKAGING: 28 in 1 BLISTER PACK ACTIVE INGREDIENT(S): PANTOPRAZOLE SODIUM 40mg in 1 INACTIVE INGREDIENT(S): CALCIUM STEARATE CROSPOVIDONE (15 MPA.S AT 5%) FERRIC OXIDE YELLOW HYDROXYPROPYL CELLULOSE (90000 WAMW) HYPROMELLOSE 2910 (3 MPA.S) MANNITOL METHACRYLIC ACID - ETHYL ACRYLATE COPOLYMER (1:1) TYPE A SODIUM CARBONATE TRIETHYL CITRATE AMMONIA FERROSOFERRIC OXIDE FERRIC OXIDE RED ISOPROPYL ALCOHOL BUTYL ALCOHOL PROPYLENE GLYCOL SHELLAC Remedy_Label
- 16 HOW SUPPLIED/STORAGE AND HANDLING Pantoprazole Sodium Delayed-Release Tablets USP, 40 mg are yellow colored, oval shaped, biconvex, enteric-coated tablets imprinted with ‘I’ and ‘52’ with brown ink on one side and plain on other side. NDC: 70518-0860-00 NDC: 70518-0860-01 PACKAGING: 90 in 1 BOTTLE PLASTIC PACKAGING: 28 in 1 BLISTER PACK Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Repackaged and Distributed By: Remedy Repack, Inc. 625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762
- PRINCIPAL DISPLAY PANEL DRUG: Pantoprazole Sodium GENERIC: Pantoprazole Sodium DOSAGE: TABLET, DELAYED RELEASE ADMINSTRATION: ORAL NDC: 70518-0860-0 NDC: 70518-0860-1 COLOR: yellow SHAPE: OVAL SCORE: No score SIZE: 12 mm IMPRINT: I;52 PACKAGING: 90 in 1 BOTTLE, PLASTIC PACKAGING: 28 in 1 BLISTER PACK ACTIVE INGREDIENT(S): PANTOPRAZOLE SODIUM 40mg in 1 INACTIVE INGREDIENT(S): CALCIUM STEARATE CROSPOVIDONE (15 MPA.S AT 5%) FERRIC OXIDE YELLOW HYDROXYPROPYL CELLULOSE (90000 WAMW) HYPROMELLOSE 2910 (3 MPA.S) MANNITOL METHACRYLIC ACID - ETHYL ACRYLATE COPOLYMER (1:1) TYPE A SODIUM CARBONATE TRIETHYL CITRATE AMMONIA FERROSOFERRIC OXIDE FERRIC OXIDE RED ISOPROPYL ALCOHOL BUTYL ALCOHOL PROPYLENE GLYCOL SHELLAC Remedy_Label
Overview
The active ingredient in pantoprazole sodium delayed-release tablets, USP a PPI, is a substituted benzimidazole, sodium 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]sulfinyl]-1 H -benzimidazole sesquihydrate, a compound that inhibits gastric acid secretion. Its molecular formula is C 16 H 14 F 2 N 3 NaO 4 S x 1.5 H 2 O, with a molecular weight of 432.4. The structural formula is: Pantoprazole sodium USP is a white to off-white powder and is racemic. Pantoprazole has weakly basic and acidic properties. Pantoprazole sodium USP is freely soluble in water, very slightly soluble in phosphate buffer at pH 7.4, and practically insoluble in n-hexane. The stability of the compound in aqueous solution is pH-dependent. The rate of degradation increases with decreasing pH. At ambient temperature, the degradation half-life is approximately 2.8 hours at pH 5 and approximately 220 hours at pH 7.8. Pantoprazole sodium USP is supplied as a delayed-release tablet, available in two strengths 20 mg pantoprazole (equivalent to 22.56 mg of pantoprazole sodium USP) and 40 mg pantoprazole (equivalent to 45.1 mg of pantoprazole sodium USP). Pantoprazole sodium delayed-release tablets, USP contains the following inactive ingredients: calcium stearate, crospovidone, ferric oxide, hydroxypropyl cellulose, hypromellose, mannitol, methacrylic acid and ethyl acrylate copolymer dispersion, sodium carbonate, and triethyl citrate. The tablets are imprinted with brown ink containing ammonium hydroxide, iron oxide black, iron oxide red, iron oxide yellow, isopropyl alcohol, N-butyl alcohol, propylene glycol, and shellac glaze in ethanol. Pantoprazole sodium delayed-release tablets (40 mg and 20 mg) complies USP dissolution test 3. chemical structure
Indications & Usage
Pantoprazole sodium delayed-release tablets are indicated for: Pantoprazole sodium is a proton pump inhibitor (PPI) indicated for the following: Short-Term Treatment of Erosive Esophagitis Associated with Gastroesophageal Reflux Disease (GERD) (1.1) Maintenance of Healing of Erosive Esophagitis (1.2) Pathological Hypersecretory Conditions Including Zollinger-Ellison (ZE) Syndrome (1.3) 1.1 Short-Term Treatment of Erosive Esophagitis Associated With Gastroesophageal Reflux Disease (GERD) Pantoprazole sodium is indicated in adults and pediatric patients five years of age and older for the short-term treatment (up to 8 weeks) in the healing and symptomatic relief of erosive esophagitis (EE). For those adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole sodium may be considered. Safety of treatment beyond 8 weeks in pediatric patients has not been established. 1.2 Maintenance of Healing of Erosive Esophagitis Pantoprazole sodium is indicated for maintenance of healing of EE and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with GERD. Controlled studies did not extend beyond 12 months. 1.3 Pathological Hypersecretory Conditions Including Zollinger-Ellison (ZE) Syndrome Pantoprazole sodium is indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison (ZE) Syndrome.
Dosage & Administration
* Controlled studies did not extend beyond 12 months See full prescribing information for administration instructions Indication Dose Frequency Short-Term Treatment of Erosive Esophagitis Associated With GERD ( 2.1 ) Adults 40 mg Once Daily for up to 8 wks Children (5 years and older) ≥ 15 kg to < 40 kg 20 mg Once Daily for up to 8 wks ≥ 40 kg 40 mg Maintenance of Healing of Erosive Esophagitis ( 2.1 ) Adults 40 mg Once Daily* Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome ( 2.1 ) Adults 40 mg Twice Daily 2.1 Recommended Dosing Schedule Pantoprazole sodium is supplied as delayed-release tablets. The recommended dosages are outlined in Table 1. Table 1: Recommended Dosing Schedule for Pantoprazole Sodium * For adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole sodium may be considered. ** Dosage regimens should be adjusted to individual patient needs and should continue for as long as clinically indicated. Doses up to 240 mg daily have been administered. *** Controlled studies did not extend beyond 12 months Indication Dose Frequency Short-Term Treatment of Erosive Esophagitis Associated With GERD Adults 40 mg Once daily for up to 8 weeks* Children (5 years and older) ≥ 15 kg to < 40 kg 20 mg Once daily for up to 8 weeks ≥ 40 kg 40 mg Maintenance of Healing of Erosive Esophagitis Adults 40 mg Once daily*** Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome Adults 40 mg Twice daily** 2.2 Administration Instructions Directions for method of administration of pantoprazole sodium is presented in Table 2. Table 2: Administration Instructions * Do not split, chew, or crush pantoprazole sodium delayed-release tablets. Formulation Route Instructions* Delayed-Release Tablets Oral Swallowed whole, with or without food Take a missed dose as soon as possible. If it is almost time for the next dose, skip the missed dose and take the next dose at the regular scheduled time. Do not take 2 doses at the same time. Swallow pantoprazole sodium delayed-release tablets whole, with or without food in the stomach. For patients unable to swallow a 40 mg tablet, two 20 mg tablets may be taken. Concomitant administration of antacids does not affect the absorption of pantoprazole sodium delayed-release tablets.
Warnings & Precautions
Gastric Malignancy: In adults, symptomatic response does not preclude presence of gastric malignancy. Consider additional follow-up and diagnostic testing. ( 5.1 ) Acute Tubulointerstitial Nephritis : Discontinue treatment and evaluate patients. ( 5.2 ) Clostridium difficile- Associated Diarrhea : PPI therapy may be associated with increased risk of Clostridium difficile- associated diarrhea. ( 5.3 ) Bone Fracture: Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. ( 5.4 ) Severe Cutaneous Adverse Reactions : Discontinue at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. ( 5.5 ) Cutaneous and Systemic Lupus Erythematosus : Mostly cutaneous; new onset or exacerbation of existing disease; discontinue pantoprazole sodium and refer to specialist for evaluation. ( 5.6 ) Cyanocobalamin (Vitamin B-12) Deficiency : Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin. ( 5.7 ) Hypomagnesemia and Mineral Metabolism : Reported rarely with prolonged treatment with PPIs. ( 5.8 ) Fundic Gland Polyps: Risk increases with long-term use, especially beyond one year. Use the shortest duration of therapy. ( 5.10 ) 5.1 Presence of Gastric Malignancy In adults, symptomatic response to therapy with pantoprazole sodium does not preclude the presence of gastric malignancy. 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. 5.2 Acute Tubulointerstitial Nephritis 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 and evaluate patients with suspected acute TIN [see Contraindications (4) ]. 5.3 Clostridium difficile -Associated Diarrhea Published observational studies suggest that PPI therapy like pantoprazole sodium 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 [see Adverse Reactions (6.2) ] . Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. 5.4 Bone Fracture Several published observational studies suggest that 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 osteoporosis-related fractures should be managed according to established treatment guidelines [see Dosage and Administration (2) , Adverse Reactions (6.2) ] . 5.5 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 [see Adverse Reactions (6.2) ] . Discontinue pantoprazole sodium at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. 5.6 Cutaneous and Systemic Lupus Erythematosus 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 erythematous cases were CLE. The most common form of CLE reported in patients treated with PPIs was subacute 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. Systemic lupus erythematosus (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 cytopenia 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, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks. Serological testing (e.g., ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations. 5.7 Cyanocobalamin (Vitamin B-12) 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 B-12) 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. 5.8 Hypomagnesemia and Mineral Metabolism Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, and in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients. 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 [see Adverse Reactions (6.2) ] . Consider monitoring magnesium and calcium levels prior to initiation of pantoprazole sodium 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. 5.9 Tumorigenicity Due to the chronic nature of GERD, there may be a potential for prolonged administration of pantoprazole sodium. In long-term rodent studies, pantoprazole was carcinogenic and caused rare types of gastrointestinal tumors. The relevance of these findings to tumor development in humans is unknown [see Nonclinical Toxicology (13.1) ] . 5.10 Fundic Gland Polyps PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use, especially beyond one 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. 5.11 Interference with Investigations for Neuroendocrine Tumors 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 tumors. Healthcare providers should temporarily stop pantoprazole sodium 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 [see Clinical Pharmacology (12.2) ] . 5.12 Interference with Urine Screen for THC There have been reports of false-positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs, including pantoprazole sodium [see Drug Interactions (7) ]. 5.13 Concomitant Use of Pantoprazole Sodium 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-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients [see Drug Interactions (7) ].
Contraindications
Pantoprazole sodium is contraindicated in patients with known hypersensitivity to any component of the formulation or any substituted benzimidazole. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see Warnings and Precautions (5.2) , Adverse Reactions (6) ]. Proton pump inhibitors (PPIs), including pantoprazole sodium, are contraindicated in patients receiving rilpivirine-containing products [see Drug Interactions (7) ] . Patients with known hypersensitivity to any component of the formulation or to substituted benzimidazoles ( 4 ) Patients receiving rilpivirine-containing products ( 4 , 7 )
Adverse Reactions
The following serious adverse reactions are described below and elsewhere in labeling: Acute Tubulointerstitial Nephritis [see Warnings and Precautions (5.2) ] Clostridium difficile- Associated Diarrhea [see Warnings and Precautions (5.3) ] Bone Fracture [see Warnings and Precautions (5.4) ] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.5) ] Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.6) ] Cyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions (5.7) ] Hypomagnesemia and Mineral Metabolism [see Warnings and Precautions (5.8) ] Fundic Gland Polyps [see Warnings and Precautions (5.10) ] Most common adverse reactions are: For adult use (>2%): headache, diarrhea, nausea, abdominal pain, vomiting, flatulence, dizziness, and arthralgia. ( 6.1 ) For pediatric use (>4%): URI, headache, fever, diarrhea, vomiting, rash, and abdominal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience The adverse reaction profiles for Protonix for delayed-release oral suspension and pantoprazole sodium delayed-release tablets are similar. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Adults Safety in nine randomized comparative U.S. clinical trials in patients with GERD included 1,473 patients on oral pantoprazole sodium (20 mg or 40 mg), 299 patients on an H 2 -receptor antagonist, 46 patients on another PPI, and 82 patients on placebo. The most frequently occurring adverse reactions are listed in Table 3. Table 3: Adverse Reactions Reported in Clinical Trials of Adult Patients with GERD at a Frequency of >2% Pantoprazole Sodium (n=1473) % Comparators (n=345) % Placebo (n=82) % Headache 12.2 12.8 8.5 Diarrhea 8.8 9.6 4.9 Nausea 7 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 2.9 1.2 Arthralgia 2.8 1.4 1.2 Additional adverse reactions that were reported for pantoprazole sodium in clinical trials with a frequency of ≤2% are listed below by body system: Body as a Whole : allergic reaction, pyrexia, photosensitivity reaction, facial edema Gastrointestinal: constipation, dry mouth, hepatitis Hematologic: leukopenia, thrombocytopenia Metabolic/Nutritional: elevated CK (creatine kinase), generalized edema, elevated triglycerides, liver enzymes elevated Musculoskeletal: myalgia Nervous: depression, vertigo Skin and Appendages : urticaria, rash, pruritus Special Senses: blurred vision Pediatric Patients Safety of pantoprazole sodium in the treatment of EE associated with GERD was evaluated in pediatric patients ages 1 year through 16 years in three clinical trials. Safety trials involved pediatric patients with EE; however, as EE is uncommon in the pediatric population, 249 pediatric patients with endoscopically-proven or symptomatic GERD were also evaluated. All adult adverse reactions to pantoprazole sodium are considered relevant to pediatric patients. In patients ages 1 year through 16 years, the most commonly reported (>4%) adverse reactions include: URI, headache, fever, diarrhea, vomiting, rash, and abdominal pain. For safety information in patients less than 1 year of age see Use in Specific Populations (8.4) . Additional adverse reactions that were reported for pantoprazole sodium in pediatric patients in clinical trials with a frequency of ≤4% are listed below by body system: Body as a Whole: allergic reaction, facial edema Gastrointestinal: constipation, flatulence, nausea Metabolic/Nutritional: elevated triglycerides, elevated liver enzymes, elevated CK (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 pediatric patients in clinical trials, but are considered relevant to pediatric patients: photosensitivity reaction, dry mouth, hepatitis, thrombocytopenia, generalized edema, depression, pruritus, leukopenia, and blurred vision. Zollinger-Ellison (ZE) Syndrome In clinical studies of ZE Syndrome, adverse reactions reported in 35 patients taking pantoprazole sodium 80 mg/day to 240 mg/day for up to 2 years were similar to those reported in adult patients with GERD. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of pantoprazole sodium. 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: Gastrointestinal Disorders: fundic gland polyps General Disorders and Administration Conditions: asthenia, fatigue, malaise Hematologic: pancytopenia, agranulocytosis Hepatobiliary Disorders: hepatocellular damage leading to jaundice and hepatic failure Immune System Disorders: anaphylaxis (including anaphylactic shock), systemic lupus erythematosus Infections and Infestations: C lostridium difficile associated diarrhea Investigations: weight changes Metabolism and Nutritional Disorders: hypomagnesemia, hypocalcemia, hypokalemia, hyponatremia Musculoskeletal Disorders: rhabdomyolysis, bone fracture Nervous: ageusia, dysgeusia Psychiatric Disorders: hallucination, confusion, insomnia, somnolence Renal and Genitourinary Disorders: acute tubulointerstitial nephritis, erectile dysfunction Skin and Subcutaneous Tissue Disorders: severe dermatologic reactions (some fatal), including erythema multiforme, SJS/TEN, DRESS, AGEP, angioedema (Quincke’s edema) and cutaneous lupus erythematosus
Drug Interactions
Table 4 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with pantoprazole sodium and instructions for preventing or managing them. Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs. Table 4: Clinically Relevant Interactions Affecting Drugs Co-Administered with Pantoprazole Sodium and Interactions with Diagnostics Antiretrovirals Clinical Impact: The effect of PPIs on antiretroviral drugs is variable. The clinical 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 sodium are contraindicated [see Contraindications (4) ] . See prescribing information. Atazanavir: See prescribing information for atazanavir for dosing information. Nelfinavir: Avoid concomitant use with pantoprazole sodium. 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 Impact: Increased INR and prothrombin time in patients receiving PPIs, 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 Clinical Impact: Concomitant administration of pantoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition [see Clinical Pharmacology (12.3) ]. Intervention: No dose adjustment of clopidogrel is necessary when administered with an approved dose of pantoprazole sodium. Methotrexate Clinical Impact: Concomitant use of PPIs with methotrexate (primarily at high dose) 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 (5.13) ] . Intervention: A temporary withdrawal of pantoprazole sodium 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 Impact: Pantoprazole can reduce the absorption of other drugs due to its 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 [see Clinical Pharmacology (12.3) ] . The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving pantoprazole sodium and MMF. Use pantoprazole sodium with caution in transplant patients receiving MMF. See the prescribing information for other drugs dependent on gastric pH for absorption. Interactions with Investigations of Neuroendocrine Tumors Clinical Impact: CgA levels increase secondary to PPI-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors [see Warnings and Precautions (5.11) , Clinical Pharmacology (12.2) ] . Intervention: Temporarily stop pantoprazole sodium 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 Impact: There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs [see Warnings and Precautions (5.12) ] . Intervention: An alternative confirmatory method should be considered to verify positive results. See full prescribing information for a list of clinically important drug interactions ( 7 )
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