Prevacid Naprapac (Lansoprazole / Naproxen) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

NAPROSYN

The use of NSAIDs in patients who are receiving ACE inhibitors may potentiate renal disease states (see PRECAUTIONS, NAPROSYN Renal Effects).

In vitro studies have shown that naproxen anion, because of its affinity for protein, may displace from their binding sites other drugs that are also albumin-bound (see CLINICAL PHARMACOLOGY, NAPROSYN Pharmacokinetics).

Theoretically, the naproxen anion itself could likewise be displaced. Short-term controlled studies failed to show that taking the drug significantly affects prothrombin times when administered to individuals on coumarin-type anticoagulants. Caution is advised nonetheless, since interactions have been seen with other nonsteroidal agents of this class. Similarly, patients receiving the drug and a hydantoin, sulfonamide or sulfonylurea should be observed for signs of toxicity to these drugs (see CLINICAL STUDIES, NAPROSYN General Information).

Concomitant administration of naproxen and aspirin is not recommended because naproxen is displaced from its binding sites during the concomitant administration of aspirin, resulting in lower plasma concentrations and peak plasma levels.

The natriuretic effect of furosemide has been reported to be inhibited by some drugs of this class. Inhibition of renal lithium clearance leading to increases in plasma lithium concentrations has also been reported. Naproxen and other nonsteroidal anti-inflammatory drugs can reduce the antihypertensive effect of propranolol and other beta-blockers.

Probenecid given concurrently increases naproxen anion plasma levels and extends its plasma half-life significantly.

Caution should be used if naproxen is administered concomitantly with methotrexate. Naproxen, and other nonsteroidal anti-inflammatory drugs have been reported to reduce the tubular secretion of methotrexate in an animal model, possibly increasing the toxicity of methotrexate.

PREVACID

Lansoprazole is metabolized through the cytochrome P₄₅₀ system, specifically through the CYP3A and CYP2C19 isozymes. Studies have shown that lansoprazole does not have clinically significant interactions with other drugs metabolized by the cytochrome P₄₅₀ system, such as warfarin, antipyrine, indomethacin, ibuprofen, phenytoin, propranolol, prednisone, diazepam, or clarithromycin in healthy subjects. These compounds are metabolized through various cytochrome P₄₅₀ isozymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A. When lansoprazole was administered concomitantly with theophylline (CYP1A2, CYP3A), a minor increase (10%) in the clearance of theophylline was seen. Because of the small magnitude and the direction of the effect on theophylline clearance, this interaction is unlikely to be of clinical concern. Nonetheless, individual patients may require additional titration of their theophylline dosage when lansoprazole is started or stopped to ensure clinically effective blood levels.

In a study of healthy subjects neither the pharmacokinetics of warfarin enantiomers nor prothrombin time were affected following single or multiple 60 mg doses of lansoprazole. However, there have been reports of increased International Normalized Ratio (INR) and prothrombin time in patients receiving proton pump inhibitors, including lansoprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time.

Lansoprazole has also been shown to have no clinically significant interaction with amoxicillin.

In a single-dose crossover study examining lansoprazole 30 mg and omeprazole 20 mg each administered alone and concomitantly with sucralfate 1 gram, absorption of the proton pump inhibitors was delayed and their bioavailability was reduced by 17% and 16%, respectively, when administered concomitantly with sucralfate. Therefore, proton pump inhibitors should be taken at least 30 minutes prior to sucralfate. In clinical trials, antacids were administered concomitantly with PREVACID Delayed-Release Capsules; this did not interfere with its effect.

Lansoprazole causes a profound and long-lasting inhibition of gastric acid secretion; therefore, it is theoretically possible that lansoprazole may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (e.g., ketoconazole, ampicillin esters, iron salts, digoxin).

OVERDOSAGE

PREVACID^® NapraPAC™ (375 or 500)

In case of an overdose, patients should contact a physician, poison control center, or emergency room. There are no data suggesting increased toxicity of the combination of naproxen and lansoprazole compared with individual components.

NAPROSYN

Significant naproxen overdosage may be characterized by drowsiness, heartburn, indigestion, nausea or vomiting. In the event that ANAPROX/ANAPROX-DS, ALEVE, or naproxen sodium is taken with PREVACID^® NapraPAC™ (375 or 500), earlier and higher blood levels may be anticipated due to the rapid absorption of naproxen sodium. A few patients have experienced seizures, but it is not clear whether or not these were drug-related. It is not known what dose of the drug would be life-threatening. The oral LD₅₀ of the drug is 543 mg/kg in rats, 1234 mg/kg in mice, 4110 mg/kg in hamsters, and greater than 1000 mg/kg in dogs.

Should a patient ingest a large number of tablets, accidentally or purposefully, the stomach may be emptied and usual supportive measures employed. In animals 0.5 g/kg of activated charcoal was effective in reducing plasma levels of naproxen. Hemodialysis does not decrease the plasma concentration of naproxen because of the high degree of its protein binding.

PREVACID

Oral doses up to 5000 mg/kg in rats (approximately 1300 times the 30 mg human dose based on body surface area) and mice (about 675.7 times the 30 mg human dose based on body surface area) did not produce deaths or any clinical signs.

Lansoprazole is not removed from the circulation by hemodialysis. In one reported case of overdose, the patient consumed 600 mg of lansoprazole with no adverse reaction.

CONTRAINDICATIONS

PREVACID^® NapraPAC™ (375 or 500) is contraindicated in patients with known hypersensitivity or allergic reactions to any component of the formulations of PREVACID, NAPROSYN, or over-the-counter products containing naproxen.

Naproxen is also contraindicated in patients in whom aspirin or other nonsteroidal anti-inflammatory/analgesic drugs induce the syndrome of asthma, rhinitis, and nasal polyps. Both types of reactions have the potential of being fatal. Anaphylactoid reactions to naproxen, whether of the true allergic type or the pharmacologic idiosyncratic (eg, aspirin hypersensitivity syndrome) type, usually but not always occur in patients with a known history of such reactions. Therefore, careful questioning of patients for such things as asthma, nasal polyps, urticaria, and hypotension associated with nonsteroidal anti-inflammatory drugs before starting therapy is important. In addition, if such symptoms occur during therapy, treatment should be discontinued.