Pantoprazole

Pharmacogenomics:

Pantoprazole is extensively metabolised in the liver, mainly by CYP2C19 into desmethlypantoprazole.

CYP2C19 genotypes have been linked to PPI exposure, in which lower exposure is associated with treatment failure while higher exposure is associated with improved efficacy. Higher exposure and long-term use of PPIs have also been associated with adverse effects.

The allele frequency of CYP2C19*2 (c.681G > A; rs4244285), the most common CYP2C19 non-functional allele, is approx 60% in Oceanians, approx 25-30% in Asians, and approx 15% in Europeans and Africans. The increased functional allele CYP2C19*17 (c.-806C > T; rs12248560) is most common in African, European, and Near Eastern populations, with approx 20% allele frequency.

Royal Dutch Pharmacists Association - Pharmacogenetics Working Group (DPWG) Guideline as of November 2018:

Phenotype	Description	Recommendations
CYP2C19 ultrarapid metaboliser	Patients may have reduced pantoprazole concentrations resulting in lower effectiveness of pantoprazole.	For Helicobacter pylori (H. pylori) eradication therapy: Use 5-fold higher dose and advise patients to inform the doctor if dyspepsia symptoms persist. For other indications: Be alert for reduced effectiveness and use a 5-fold higher dose if necessary. Advise patients to report persisting symptoms of dyspepsia.

The DPWG guideline recommends to consider CYP2C19 genotyping on an individual basis before initiating pantoprazole.

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline as of August 2020:

Phenotype and Genotype	Implications	Recommendations
CYP2C19 ultrarapid metaboliser Individuals carrying 2 increased functional alleles e.g. *17/*17	Decreased pantoprazole plasma concentrations as compared with CYP2C19 normal metabolisers and are at increased risk of therapeutic failure.	Increase starting daily dose by 100%. Daily dose may be given in divided doses. Monitor for efficacy.
CYP2C19 rapid metaboliser Individuals carrying 1 normal functional allele and 1 increased functional allele e.g. *1/*17	Decreased pantoprazole plasma concentrations as compared with CYP2C19 normal metabolisers and are at increased risk of therapeutic failure.	Initiate standard starting daily dose. Consider increasing the dose by 50-100% for the treatment of Helicobacter pylori (H. pylori) infection and erosive oesophagitis. Daily dose may be given in divided doses. Monitor for efficacy.
CYP2C19 normal metaboliser Individuals carrying 2 normal functional alleles e.g. *1/*1	Normal pantoprazole metabolism but may be at increased risk of therapeutic failure as compared with CYP2C19 intermediate and poor metabolisers.	Initiate standard starting daily dose. Consider increasing the dose by 50-100% for the treatment of H. pylori infection and erosive oesophagitis. Daily dose may be given in divided doses. Monitor for efficacy.
CYP2C19 intermediate metaboliser Individuals carrying 1 normal functional allele and 1 non-functional allele or 1 increased functional allele and 1 non-functional allele e.g. *1/*2, *1/*3, *2/*17, *3/*17	Increased pantoprazole plasma concentration as compared with CYP2C19 normal metabolisers and are at increased chance of efficacy and potential toxicity.	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and once efficacy is achieved, consider a 50% reduction in daily dose. Monitor for continued efficacy.
CYP2C19 poor metaboliser Individuals carrying 2 non-functional alleles e.g. *2/*2, *3/*3, *2/*3	Increased pantoprazole plasma concentrations as compared with CYP2C19 normal metabolisers and are at increased chance of efficacy and potential toxicity.	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and once efficacy is achieved, consider a 50% reduction in daily dose. Monitor for continued efficacy.

Treatment recommendations may vary among countries. Refer to local guidelines for the latest recommendations.

Eradication of Helicobacter pylori associated with peptic ulcer disease:
Moderate to severe: Contraindicated.

Gastro-oesophageal reflux disease; Reflux oesophagitis; Zollinger-Ellison syndrome; Prophylaxis of NSAID-induced ulcers; Duodenal ulcer; Gastric ulcer:
Severe: Max: 20 mg daily.

Eradication of Helicobacter pylori associated with peptic ulcer disease:
Moderate to severe: Contraindicated.

Pantoprazole DR oral susp: Should be taken on an empty stomach. Administer granules only in apple juice or applesauce (for stability in proper pH). Do not chew/crush. May administer via feeding tubes. Consult product literature for specific instructions.
Pantoprazole DR tab: May be taken with or without food. Swallow whole & do not break/crush.

Granules for oral susp: Empty the contents of the packet into 5 mL of apple juice. Stir for 5 seconds, then swallow immediately. Alternatively, sprinkle granules on 1 teaspoon of applesauce, then swallow immediately. Powder for solution for IV inj: Reconstitute vial with 10 mL of NaCl 0.9% solution. IV infusion: Further dilute with 100 mL of dextrose 5% in water or NaCl 0.9% solution.

Concomitant use with rilpivirine-containing products. When used for eradication of Helicobacter pylori: Moderate to severe renal and hepatic impairment.

Patient with personal history, family history or risk factors for SCLE; risk factors for fractures; familial adenomatous polyposis. May mask symptoms of gastric malignancy. CYP2C19 ultrarapid, rapid, normal, intermediate or poor metabolisers. Severe hepatic impairment. Children. Pregnancy and lactation.

Significant: Subacute cutaneous lupus erythematosus (SCLE), SLE; Clostridiodes difficile-associated diarrhoea (CDAD); gastrointestinal infections (Salmonella, Campylobacter); hip, wrist and spine fractures (long-term use or high doses); fundic gland polyps; hypomagnesaemia, vitamin B₁₂ deficiency, acute tubulointerstitial nephritis.
Gastrointestinal disorders: Diarrhoea, nausea, vomiting, abdominal distention and bloating, constipation, abdominal pain and discomfort, dry mouth.
General disorders and administration site conditions: Asthenia, malaise, fatigue, inj site thrombophlebitis.
Investigations: Increased liver enzymes.
Nervous system disorders: Headache, dizziness.
Psychiatric disorders: Sleep disorders.
Skin and subcutaneous tissue disorders: Rash, pruritus, exanthema, eruption.
Potentially Fatal: Severe cutaneous adverse reactions (e.g. erythema multiforme, Stevens-Johnson syndrome [SJS], toxic epidermal necrolysis, acute generalised exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms [DRESS]).

This drug may cause dizziness and visual disturbances, if affected, do not drive or operate machinery.

Monitor Mg, Ca and serum gastrin levels. Assess for signs of bone loss and fractures, CDAD, SCLE or SLE.

May decrease the plasma concentration of rilpivirine, atazanavir and and nelfinavir. May diminish the therapeutic effect of clopidogrel. May interfere with the absorption of medicines where gastric acid is a significant determinant of bioavailability (e.g. ketoconazole, itraconazole, erlotinib). May increase INR and prothrombin time with warfarin or phenprocoumon. May increase the serum concentration of methotrexate and saquinavir. Increased systemic exposure with CYP2C19 inhibitors (e.g. fluvoxamine). Reduced plasma concentration with CYP2C19 and CYP3A4 inducers (e.g. rifampicin).

Reduced plasma concentration with St. John's wort.

May increase the serum chromogranin A (CgA) levels which may cause false-positive result in the diagnostic test for neuroendocrine tumours. May result in false-positive urine screen for tetrahydrocannabinol (THC).

Description:
Mechanism of Action: Pantoprazole is a substituted benzimidazole gastric antisecretory agent and is also known as a proton pump inhibitor (PPI). It blocks the final step in gastric acid production by specific inhibition of H⁺/K⁺ adenosine triphosphatase (ATPase) enzyme system present on the secretory surface of the gastric parietal cell, thereby suppressing gastric acid secretion.
Onset: Acid secretion: 2.5 hours (oral); 15-30 minutes (IV).
Duration: 24 hours.
Pharmacokinetics:
Absorption: Rapidly absorbed. Bioavailability: Approx 77%. Time to peak plasma concentration: Approx 2-2.5 hours.
Distribution: Enters breast milk. Volume of distribution: 11-23.6 L. Plasma protein binding: Approx 98%, mainly to albumin.
Metabolism: Extensively metabolised in the liver via demethylation by CYP2C19 into desmethylpantoprazole; small amounts by CYP3A4, CYP2D6 and CYP2C9.
Excretion: Mainly via urine (71% as metabolites); faeces (18%). Elimination half-life: 1 hour.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4679, Pantoprazole. https://pubchem.ncbi.nlm.nih.gov/compound/Pantoprazole. Accessed Mar. 27, 2025.

Store between 20-25°C. Protect from light.

Antacids, Antireflux Agents & Antiulcerants

A02BC02 - pantoprazole ; Belongs to the class of proton pump inhibitors. Used in the treatment of peptic ulcer and gastro-oesophageal reflux disease (GERD).

Lima JJ, Thomas CD, Barbino J et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing. Clinical Pharmacology & Therapeutics. 2020;0(0):1-7. doi:10.1002/cpt.2015. Accessed 08/03/2024

AFT Pharmaceuticals Ltd. Pantoprazole-AFT 40 mg Powder for Injection data sheet 28 August 2024. Medsafe. http://www.medsafe.govt.nz. Accessed 17/01/2025.

Annotation of DPWG Guideline for Pantoprazole and CYP2C19. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org. Accessed 31/03/2025.

Annotation of FDA Label for Pantoprazole and CYP2C19. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org. Accessed 08/03/2024.

Anon. CYP2C19 - Pantoprazole (Pharmacogenomics). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/03/2024.

Anon. Pantoprazole Sodium. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 08/03/2024.

Anon. Pantoprazole. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/03/2024.

Buckingham R (ed). Pantoprazole. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/03/2024.

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing. Clinical Pharmacogenetics Implementation Consortium (CPIC). https://cpicpgx.org. Accessed 08/03/2024.

Conpanzole Enteric Coated Tablet 20 mg and 40 mg (Y.S.P. Industries [M] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 17/01/2025.

Joint Formulary Committee. Pantoprazole. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/03/2024.

Pantoprazole 20 mg Gastro-resistant Tablets (Milpharm Limited). MHRA. https://products.mhra.gov.uk. Accessed 08/03/2024.

Pantoprazole 20 mg Gastro-resistant Tablets (Sandoz Hong Kong Limited). MIMS Hong Kong. http://www.mims.com/hongkong. Accessed 17/01/2025.

Pantoprazole Sandoz 40 mg Powder for Solution for Injection (Sandoz Products Malaysia Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 17/01/2025.

Pantoprazole Sandoz Gastro-resistant Tablet 40 mg (Sandoz Products Malaysia Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 08/03/2024.

Pantoprazole Sodium for Suspension (Ajanta Pharma USA Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 12/03/2024.

Protium I.V. 40 mg Powder for Solution for Injection (Takeda UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 08/03/2024.

Protonix Delayed-Release Tablet and Granule (Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 08/03/2024.

Protonix IV Injection, Powder for Solution (Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 08/03/2024.

Viatris Ltd. Panzop Relief, 20 mg and 40 mg, Gastro-resistant Tablet data sheet 9 February 2024. Medsafe. http://www.medsafe.govt.nz. Accessed 08/03/2024.