Note: This document contains side effect information about lansoprazole / naproxen. Some dosage forms listed on this page may not apply to the brand name Prevacid NapraPAC.

Applies to lansoprazole/naproxen: oral kit.

Cardiovascular

Cardiovascular side effects have been reported rarely. These have included angina, myocardial infarction, hypertension, and hypotension in patients taking lansoprazole, but the etiology of these cardiovascular problems was not specifically attributed to lansoprazole. Necrotizing arteritis has been reported in dogs. However, the clinical implications for human use have not been determined. (In humans, one case of ischemic optic neuropathy has been tentatively associated with the use of the related drug omeprazole).

Cardiovascular side effects associated with naproxen have included peripheral edema (3% to 9%) and palpitations (3%). Blood pressure may be elevated by naproxen, which may have clinical relevance in patients with comorbid illnesses. Cardiovascular side effects reported in less than 1% of patients have included hypertension, tachycardia, syncope, arrhythmia, hypotension, myocardial infarction, congestive heart failure, and vasculitis.^[Ref]

Nonsteroidal anti-inflammatory drugs (NSAIDs) may elevate blood pressure and increase the risk of the initiation of antihypertensive therapy. NSAIDs may antagonize the blood-pressure lowering effect of antihypertensive medications in patients already being treated with antihypertensive drugs.

The cumulative rate of serious cardiovascular thromboembolic adverse events (heart attacks, angina pectoris, and peripheral vascular events) observed in the Vioxx Gastrointestinal Outcomes research (Vigor) study has been reported to occur in a smaller percentage of patients taking naproxen compared to rofecoxib (0.6% vs. 1.8% respectively).^[Ref]

Dermatologic

Excessive sun exposure may play a role in cases of skin eruptions resembling porphyria cutanea tarda. Biochemical evidence of porphyria, such as elevated serum porphyrins, is lacking in these cases. Photosensitivity reactions have also been associated with lesions resembling those of epidermolysis bullosa.

Although rarely reported with the use of naproxen, a 14-year-old girl is diagnosed with periareolar fixed drug eruption after taking naproxen during menses for dysmenorrhea.^[Ref]

Dermatologic side effects associated with lansoprazole have included skin rash in 4.3% of treated patients. Rarely, toxic epidermal necrolysis and erythema multiforme have been reported.

Dermatologic side effects reported in 3% to 9% of patients have included pruritus, skin eruptions, and ecchymoses. Dermatologic side effects associated with naproxen have also included sweating (less than 3%), purpura (less than 3%), exfoliative dermatitis (less than 1%), and rash (1% to 10% or less). Skin eruptions have been reported in patients receiving the controlled release formulation of naproxen. Dermatologic side effects reported in postmarketing experience in less than 1% of patients have included alopecia, erythema multiforme, photosensitive dermatitis, photosensitivity reactions, including rare cases resembling porphyria cutanea tarda (pseudoporphyria) or epidermolysis bullosa.^[Ref]

Gastrointestinal

Gastrointestinal side effects associated with lansoprazole have included diarrhea (in 3.2% to 11.6% of treated patients), abdominal pain (1.8% to 4.3%), and nausea (1.4%). Vomiting and constipation have been reported less often.

Gastrointestinal side effects associated with naproxen have commonly included constipation (3% to 9%), general abdominal discomfort (3% to 9%), nausea (3% to 9%), dyspepsia (less than 3%), diarrhea (less than 3%), stomatitis (less than 3%), flatulence (1% to 10%), bleeding/perforation (1% to 10% or less), vomiting (1% to 10% or less), and GI ulcers (gastric/duodenal) (1% to 10% or less). Gastrointestinal side effects reported in less than 1% of patients have included rectal bleeding, dry mouth, esophagitis, gastritis, glossitis, pancreatitis, and eructation. Serious gastrointestinal side effects have included peptic ulcerations, and, in rare cases, gastrointestinal hemorrhage or perforation. Ulcerative esophagitis, eosinophilic colitis, allergic sialadenitis, and pancreatitis have been reported. Heartburn and stomatitis have been reported in patients receiving the controlled release formulation of naproxen. Gastrointestinal side effects reported in postmarketing experience in less than 1% of patients have included perforation, hematemesis, colitis, nonpeptic GI ulceration, and ulcerative stomatitis.^[Ref]

Case series report of lansoprazole-associated microscopic colitis was confirmed by pathology studies of random biopsies of colon in six patients who developed chronic watery diarrhea. Patients completely recovered within 4 to 10 days after discontinuation of therapy.

Because peptic irritation may be asymptomatic, occasional monitoring of the hematocrit and of the stool for occult blood loss is recommended.

Patients with a history of serious gastrointestinal events or alcohol abuse are at increased risk for severe gastrointestinal side effects. Naproxen should be used with caution in these patients.

The combination of naproxen and alendronate has been reported to have a synergistic effect in the development of gastric ulcers.^[Ref]

Genitourinary

Genitourinary side effects associated with lansoprazole have been reported rarely. Impotence has been reported in some patients and a poorly described "testes disorder" has been reported in one patient.

Genitourinary side effects associated with naproxen reported in less than 1% of patients have included dysuria, oliguria, polyuria, and proteinuria. Genitourinary side effects reported in postmarketing experience in less than 1% of patients have included menstrual disorders.^[Ref]

Hematologic

Thrombocytopenia has been reported in an 85-year-old man after the second dose of lansoprazole 60 mg while in the hospital. Platelet count returned to normal values few days after drug was stopped.^[Ref]

Hematologic side effects reported during the postmarketing phase of lansoprazole have included agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, and thrombocytopenic purpura.

Hematologic side effects associated with naproxen have included platelet dysfunction resulting in increased bleeding times (1% to 10%), anemia (1% to 10%), and decreased hematocrit (1% to 2%). Hematologic side effects reported in less than 1% of patients have included neutropenia, thrombocytopenia, agranulocytosis, lymphadenopathy, pancytopenia, and melena. Hematologic side effects reported in postmarketing experience in less than 1% of patients have included eosinophilia, leucopenia, granulocytopenia, hemolytic anemia, and aplastic anemia.^[Ref]

Hepatic

Elevations in liver function tests three times normal values, for SGOT (AST) and SGPT (ALT), are reported in 0.4% of patients that participated in the placebo controlled studies for lansoprazole.

Naproxen-induced hepatitis has been associated with a fatal outcome in some cases.^[Ref]

Hepatic side effects associated with lansoprazole have included elevations of GGT and other liver function tests in a small number of patients.

Hepatic side effects associated with naproxen have included elevations in liver function tests (1% to 15%), jaundice (less than 1%), and hepatitis (less than 1%).^[Ref]

Hypersensitivity

Hypersensitivity side effects associated with lansoprazole have been rarely reported. A few cases of eosinophilia have been reported and a single case of glottis edema.

Hypersensitivity to naproxen is rare, but may result in an erythematous or urticarial rash (less than 1%), Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, and bronchospasm, especially in patients with aspirin-sensitive asthma. Anaphylactoid reactions (less than 1%) have been reported as well. Hypersensitivity side effects reported in postmarketing experience reported in less than 1% of patients have included anaphylactoid reactions, angioneurotic edema. Hypersensitivity has been implicated in cases of renal failure, pneumonitis, and colitis.^[Ref]

Musculoskeletal

Musculoskeletal side effects have included muscle spasm (tetany), arthralgia, aggravation of arthritis, arthropathy, cramps, fibromyalgia syndrome, hernia, hypertonia, polymyalgia rheumatica, and back pain. Myalgia and bone fracture have also been reported.

There have been postmarketing reports of increased risk of bone fracture associated with lansoprazole.

Musculoskeletal side effects associated with naproxen reported in postmarketing experience in less than 1% of patients have included malaise, myalgia, asthenia, and muscle weakness.^[Ref]

A 50-year-old white woman developed severe myalgia one week after starting lansoprazole. The patient also was found to have eosinophilia. The severity of pain worsened to the point where she had to quit her job and could not sleep at night. The patient eventually recovered after stopping lansoprazole and being treated with prednisone.

Two weeks after treatment with lansoprazole 30 mg daily, a 46-year-old woman, fully compliant with her thyroid medication, was diagnosed with tetany. Her signs and symptoms responded immediately to intravenous administration of 10% calcium gluconate (20 mL) over 20 minutes; oral calcium carbonate, 2 g; and 0.25 mg calcitriol, and she fully recovered. Hypocalcemia is known to occur in subtotal thyroidectomy and in achlorhydria.^[Ref]

Nervous system

Nervous system side effects associated with lansoprazole have included headache in as many as 23% of treated patients (although most investigators have reported a much lower incidence), dizziness, pain, and convulsions.

Nervous system side effects associated with naproxen have included dizziness (3% to 9%), headache (3% to 9%), drowsiness (3% to 9%), lightheadedness (less than 3%), and vertigo (less than 3%). Nervous system side effects reported in 1% of patients have included somnolence, tremors, convulsions, coma, and paresthesia.^[Ref]

The manufacturer reports that headache occurs more often in placebo treated patients than in lansoprazole treated patients.^[Ref]

Oncologic

Oncologic side effects have not been reported in humans. Drugs which increase gastric pH would be anticipated to stimulate release of gastrin. Animal studies have demonstrated an increase in plasma gastrin concentrations following the administration of lansoprazole. In addition, lifelong high-dose animal studies have revealed a dose-related increase in the incidence of gastric enterochromaffin-like (ECL) cell carcinoids (especially in female rats). However, to date, human studies of up to 1 year have not found any suggestion of gastric carcinoid formation due to lansoprazole use.^[Ref]

Immunologic

Immunologic side effects associated with naproxen reported in less than 1% of patients have included infection and sepsis. Immunologic side effects reported in postmarketing experience in less than 1% of patients have included aseptic meningitis and cystitis.^[Ref]

Psychiatric

Psychiatric side effects associated with lansoprazole have been extremely uncommon but may include depression and anxiety.

Psychiatric side effects associated with naproxen reported in less than 1% of patients have included hallucinations, confusion, inability to concentrate, anxiety, and nervousness. Psychiatric side effects associated with naproxen reported in postmarketing experience in less than 1% of patients have included depression, dream abnormalities, insomnia, and cognitive dysfunction.^[Ref]

Respiratory

Several cases of pulmonary infiltration accompanied by eosinophilia have been reported in the literature. Fever, malaise, and respiratory symptoms are typically present. Discontinuation of naproxen results in resolution of symptoms.^[Ref]

Respiratory side effects associated with lansoprazole have included rhinitis and pharyngitis in 1% to 2% of treated patients. Cough and influenza-like symptoms have been reported less frequently. Dyspnea has been reported in patients receiving controlled release naproxen.

Respiratory side effects associated with naproxen patients have included dyspnea (3% to 9%), asthma (less than 1%), respiratory depression (less than 1%), and pneumonia (less than 1%). Respiratory side effects reported in postmarketing experience in less than 1% of patients have included eosinophilic pneumonitis. Several cases of pulmonary infiltration accompanied by eosinophilia have been reported with naproxen. Fever, malaise, and respiratory symptoms are typically present. Discontinuation of naproxen results in resolution of symptoms.^[Ref]

Other

Other side effects associated with naproxen have included tinnitus (3% to 9%), hearing disturbances (less than 3%), thirst (less than 3%), weight changes (less than 1%), appetite changes (less than 1%), fever (less than 1%), and death (less than 1%). Other side effects reported in postmarketing experience in less than 1% of patients have included hearing impairment, and pyrexia (chills and fever).^[Ref]

Renal

Renal side effects associated with lansoprazole have included the development of mild renal insufficiency, nephrotic syndrome (with or without renal failure), acute renal failure due to tubulointerstitial nephritis, papillary necrosis, and acute tubular necrosis. Hypersensitivity may play a role in some cases of renal failure.

Renal side effects associated with naproxen reported in 1% to 10% of patients have included abnormal renal function. Renal side effects reported in postmarketing experience in less than 1% of patients have included glomerular nephritis, hematuria, hyperkalemia, interstitial nephritis, nephritic syndrome, renal disease, renal failure, and renal papillary necrosis. A case-control study suggested that patients who consumed 5000 or more pills containing NSAIDs during their lifetime may be at increased risk of end-stage renal disease.^[Ref]

Metabolic

Metabolic side associated with naproxen reported in postmarketing in less than 1% of patients have included hyperglycemia and hypoglycemia.^[Ref]

Ocular

Ocular side effects associated with naproxen have included visual disturbances (less than 3%), blurred vision (less than 1%), and conjunctivitis (less than 1%), and keratopathy.^[Ref]