A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Prevacid NapraPAC Side Effects, and Drug Interactions - Naproxen and Lansoprazole
Prevacid NapraPAC Side Effects, and Drug Interactions - Naproxen and Lansoprazole
SIDE EFFECTS
NAPROSYN
The following adverse reactions are divided into three parts
based on frequency and whether or not the possibility exists of a causal relationship
between naproxen and these adverse events. In those reactions listed as "Probable
Causal Relationship" there is at least 1 case for each adverse reaction
where there is evidence to suggest that there is a causal relationship between
drug usage and the reported event.
Adverse reactions reported in controlled clinical trials in
960 patients treated for rheumatoid arthritis or osteoarthritis are listed below.
In general, reactions in patients treated chronically were reported 2 to 10
times more frequently than they were in short-term studies in the 962 patients
treated for mild to moderate pain or for dysmenorrhea. The most frequent complaints
reported related to the gastrointestinal tract.
A clinical study found gastrointestinal reactions to be more
frequent and more severe in rheumatoid arthritis patients taking daily doses
of 1500 mg naproxen compared to those taking 750 mg naproxen.
The following adverse reactions are divided into three parts
based on frequency and causal relationship.
Incidence greater than 1% (Probable Causal Relationship): Gastrointestinal
- constipation*, heartburn*, abdominal pain*, nausea*, dyspepsia, diarrhea,
stomatitis; Central Nervous System - headache*, dizziness*, drowsiness*,
lightheadedness, vertigo; Dermatologic - itching (pruritus)*, skin eruptions*,
ecchymoses*, sweating, purpura; Special Senses - tinnitus*, hearing disturbances,
visual disturbances; Cardiovascular - edema*, dyspnea*, palpitations;
General - thirst
*Incidence of reported reaction between 3% and 9%. Those reactions
occurring in less than 3% of the patients are unmarked.
Incidence less than 1% (Probable Causal Relationship): The
following adverse reactions were reported less frequently than 1% during controlled
clinical trials and through voluntary reports since marketing. Those reactions
observed through voluntary reporting since marketing of NAPROSYN are underlined.
Gastrointestinal - abnormal liver function tests, colitis, gastrointestinal bleeding
and/or perforation, hematemesis, jaundice,
pancreatitis, melena, vomiting; Renal - glomerular nephritis, hematuria,
hyperkalemia, interstitial nephritis, nephrotic syndrome, renal disease,
renal failure, renal papillary necrosis; Hematologic - agranulocytosis, eosinophilia,
granulocytopenia, leukopenia, thrombocytopenia; Central Nervous System -depression, dream
abnormalities, inability to concentrate, insomnia, malaise, myalgia,
muscle weakness; Dermatologic - alopecia, photosensitive dermatitis, urticaria,
skin rashes, photosensitivity reactions resembling porphyria cutanea
tarda, epidermolysis bullosa; Special Senses -
hearing impairment;
Cardiovascular - congestive
heart failure; Respiratory - eosinophilic
pneumonitis; General - anaphylactoid reactions,
angioneurotic edema, menstrual disorders, pyrexia (chills and fever)
Incidence less than 1% (Causal Relationship Unknown): These
observations are being listed to serve as alerting information to the physician.
Hematologic - aplastic anemia, hemolytic anemia; Central Nervous System
- aseptic meningitis, cognitive dysfunction; Dermatologic - epidermal necrolysis, erythema
multiforme, Stevens-Johnson syndrome;Gastrointestinal
- nonpeptic gastrointestinal
ulceration, ulcerative stomatitis; Cardiovascular
- vasculitis; General - hyperglycemia,
hypoglycemia
PREVACID
Clinical
Worldwide, over 10,000 patients have been treated with lansoprazole
in Phase 2-3 clinical trials involving various dosages and durations of treatment.
The adverse reaction profiles for PREVACID Delayed-Release Capsules and PREVACID
for Delayed-Release Oral Suspension are similar. In general, lansoprazole treatment
has been well-tolerated in both short-term and long-term trials.
The following adverse events were reported by the treating
physician to have a possible or probable relationship to drug in 1% or more
of PREVACID-treated patients and occurred at a greater rate in PREVACID-treated
patients than placebo-treated patients in Table 4.
|
Table 4 Incidence of Possibly or Probably Treatment-Related
Adverse Events in Short-Term, Placebo-Controlled Studies
|
| |
PREVACID
|
Placebo
|
| |
(N= 2768)
|
(N= 1023)
|
|
Body System/Adverse Event
|
%
|
%
|
|
Body as a Whole
|
|
|
|
Abdominal Pain
|
2.1
|
1.2
|
|
Digestive System
|
|
|
|
Constipation
|
1.0
|
0.4
|
|
Diarrhea
|
3.8
|
2.3
|
|
Nausea
|
1.3
|
1.2
|
Headache was also seen at greater than 1% incidence but was
more common on placebo. The incidence of diarrhea was similar between patients
who received placebo and patients who received lansoprazole 15 mg and 30 mg,
but higher in the patients who received lansoprazole 60 mg (2.9%, 1.4%, 4.2%,
and 7.4%, respectively).
The most commonly reported possibly or probably treatment-related
adverse event during maintenance therapy was diarrhea.
In the risk reduction study of PREVACID for NSAID-associated
gastric ulcers, the incidence of diarrhea for patients treated with PREVACID
was 5%, misoprostol 22%, and placebo 3%.
Additional adverse experiences occurring in <1% of patients
or subjects in domestic trials are shown below. Refer to Postmarketing for adverse
reactions occurring since the drug was marketed.
Body as a Whole – abdomen enlarged, allergic reaction,
asthenia, back pain, candidiasis, carcinoma, chest pain (not otherwise specified),
chills, edema, fever, flu syndrome, halitosis, infection (not otherwise specified),
malaise, neck pain, neck rigidity, pain, pelvic pain; Cardiovascular System
- angina, arrhythmia, bradycardia, cerebrovascular accident/cerebral
infarction, hypertension/hypotension, migraine, myocardial infarction, palpitations,
shock (circulatory failure), syncope, tachycardia, vasodilation; Digestive
System – abnormal stools, anorexia, bezoar, cardiospasm, cholelithiasis,
colitis, dry mouth, dyspepsia, dysphagia, enteritis, eructation, esophageal
stenosis, esophageal ulcer, esophagitis, fecal discoloration, flatulence, gastric
nodules/fundic gland polyps, gastritis, gastroenteritis, gastrointestinal anomaly,
gastrointestinal disorder, gastrointestinal hemorrhage, glossitis, gum hemorrhage,
hematemesis, increased appetite, increased salivation, melena, mouth ulceration,
nausea and vomiting, nausea and vomiting and diarrhea, oral moniliasis, rectal
disorder, rectal hemorrhage, stomatitis, tenesmus, thirst, tongue disorder,
ulcerative colitis, ulcerative stomatitis; Endocrine System - diabetes
mellitus, goiter, hypothyroidism; Hemic and Lymphatic System -
anemia, hemolysis, lymphadenopathy; Metabolic and Nutritional Disorders -
gout, dehydration, hyperglycemia/hypoglycemia, peripheral edema, weight gain/loss;
Musculoskeletal System - arthralgia, arthritis, bone disorder, joint
disorder, leg cramps, musculoskeletal pain, myalgia, myasthenia, synovitis;
Nervous System - abnormal dreams, agitation, amnesia, anxiety, apathy,
confusion, convulsion, depersonalization, depression, diplopia, dizziness, emotional
lability, hallucinations, hemiplegia, hostility aggravated, hyperkinesia, hypertonia,
hypesthesia, insomnia, libido decreased/increased, nervousness, neurosis, paresthesia,
sleep disorder, somnolence, thinking abnormality, tremor, vertigo; Respiratory
System - asthma, bronchitis, cough increased, dyspnea, epistaxis, hemoptysis,
hiccup, laryngeal neoplasia, pharyngitis, pleural disorder, pneumonia, respiratory
disorder, upper respiratory inflammation/infection, rhinitis, sinusitis, stridor;
Skin and Appendages - acne, alopecia, contact dermatitis, dry skin, fixed
eruption, hair disorder, maculopapular rash, nail disorder, pruritus, rash,
skin carcinoma, skin disorder, sweating, urticaria; Special Senses -
abnormal vision, blurred vision, conjunctivitis, deafness, dry eyes, ear disorder,
eye pain, otitis media, parosmia, photophobia, retinal degeneration, taste loss,
taste perversion, tinnitus, visual field defect; Urogenital System -
abnormal menses, breast enlargement, breast pain, breast tenderness, dysmenorrhea,
dysuria, gynecomastia, impotence, kidney calculus, kidney pain, leukorrhea,
menorrhagia, menstrual disorder, penis disorder, polyuria, testis disorder,
urethral pain, urinary frequency, urinary tract infection, urinary urgency,
urination impaired, vaginitis.
Postmarketing
On-going Safety Surveillance:
Additional adverse experiences have been reported since lansoprazole has
been marketed. The majority of these cases are foreign-sourced and a
relationship to lansoprazole has not been established. Because these
events were reported voluntarily from a population of unknown size,
estimates of frequency cannot be made. These events are listed below by
COSTART body system.
Body as a Whole - anaphylactoid-like reaction; Digestive
System - hepatotoxicity, pancreatitis, vomiting; Hemic and Lymphatic
System - agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia,
neutropenia, pancytopenia, thrombocytopenia, and thrombotic thrombocytopenic
purpura; Skin and Appendages – severe dermatologic reactions including
erythema multifome, Stevens-Johnson syndrome, toxic epidermal necrolysis (some
fatal); Special Senses - speech disorder; Urogenital System - urinary
retention.
Laboratory Values
The following changes in laboratory parameters for lansoprazole
were reported as adverse events:
Abnormal liver function tests, increased SGOT (AST), increased
SGPT (ALT), increased creatinine, increased alkaline phosphatase, increased
globulins, increased GGTP, increased/decreased/abnormal WBC, abnormal AG ratio,
abnormal RBC, bilirubinemia, eosinophilia, hyperlipemia, increased/decreased
electrolytes, increased/decreased cholesterol, increased glucocorticoids, increased
LDH, increased/decreased/abnormal platelets, and increased gastrin levels. Urine
abnormalities such as albuminuria, glycosuria, and hematuria were also reported.
Additional isolated laboratory abnormalities were reported.
In the placebo controlled studies, when SGOT (AST) and SGPT
(ALT) were evaluated, 0.4% (4/978) placebo patients and 0.4% (11/2677) lansoprazole
patients had enzyme elevations greater than three times the upper limit of normal
range at the final treatment visit. None of these lansoprazole patients reported
jaundice at any time during the study.
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 antiinflammatory 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 P 450 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).
Drug/Laboratory Test Interactions
NAPROSYN
Naproxen may decrease platelet aggregation and prolong bleeding
time. This effect should be kept in mind when bleeding times are determined.
The administration of naproxen may result in increased urinary
values for 17-ketogenic steroids because of an interaction between the drug
and/or its metabolites with m-dinitrobenzene used in this assay. Although 17-hydroxy-corticosteroid
measurements (Porter-Silber test) do not appear to be artifactually altered,
it is suggested that therapy with naproxen be temporarily discontinued 72 hours
before adrenal function tests are performed if the Porter-Silber test is to
be used.
Naproxen may interfere with some urinary assays of 5-hydroxy
indoleacetic acid (5HIAA).
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