Panvell Drug Interactions

Effect of Pantoprazole on the absorption of other medicinal products: Because of profound and long lasting inhibition of gastric acid secretion, Pantoprazole may reduce the absorption of drugs with a gastric pH dependent bioavailability, e.g. some azole antifungals such as Ketoconazole, Itraconazole, Posaconazole and other medicines such as Erlotinib.
Methotrexate: Concomitant use of high dose Methotrexate (e.g. 300 mg) and proton-pump inhibitors has been reported to increase Methotrexate levels in some 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 interaction 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 drugs also metabolized with these pathways, like Carbamazepine, Diazepam, Glibenclamide, Nifedipine, and an oral contraceptive containing Levonorgestrel and Ethinyl oestradiol, did not reveal clinically significant interactions.
Results from a range of interaction studies demonstrate that Pantoprazole does not affect the metabolism of active substances metabolized by CYP1A2 (such as Caffeine, Theophylline), CYP2C9 (such as Piroxicam, Diclofenac, Naproxen), CYP2D6 (such as Metoprolol), CYP2E1 (such as ethanol), or does not interfere with p-glycoprotein related absorption of digoxin.
There were no interactions with concomitantly administered antacids.
Interaction studies have also been performed by concomitantly administering pantoprazole with the respective antibiotics (Clarithromycin, Metronidazole, Amoxicillin). No clinically relevant interactions were found.
Tab: HIV protease inhibitors: Co-administration of pantoprazole is not recommended with HIV protease inhibitors for which absorption is dependent on acidic intragastric pH such as atazanavir due to significant reduction in their bioavailability (see Precautions).
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 the HIV protease inhibitors may need to be adjusted.
Coumarin anticoagulants (phenprocoumon or warfarin): Co-administration of pantoprazole with warfarin or phenprocoumon did not affect the pharmacokinetics of warfarin, phenprocoumon or INR. However, 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.
Medicinal products that inhibit or induce CYP2C19: Inhibitors of CYP2C19 such as fluvoxamine could increase the systemic exposure of pantoprazole. A dose reduction may be considered for patients treated long-term with high doses of pantoprazole, or those with hepatic impairment.
Enzyme inducers affecting CYP2C19 and CYP3A4 such as rifampicin and St John's wort (Hypericum perforatum) may reduce the plasma concentrations of PPIs that are metabolized through these enzyme systems.
IV: HIV medications (Atazanavir): Co-administration of Atazanavir and other HIV medications whose absorption is pH-dependent with PPI, might result in a substantial reduction in the bioavailability of these HIV medications and might impact the efficacy of these medicines. Therefore, the co-administration of proton pump inhibitors with Atazanavir is not recommended.
Coumarin anticoagulants (Phenprocoumon or Warfarin): Although no interaction during concomitant administration of Phenprocoumon or Warfarin has been observed in clinical pharmacokinetic studies, a few isolated cases of changes in International Normalised Ratio (INR) have been reported during concomitant treatment in the post-marketing period. Therefore, in patients treated with Coumarin anticoagulants (e.g. Phenprocoumon or Warfarin), monitoring of prothrombin time/INR is recommended after initiation, termination or during irregular use of Pantoprazole.