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
Naprosyn Side Effects, and Drug Interactions - Naproxen
Naprosyn Side Effects, and Drug Interactions - Naproxen
SIDE EFFECTS
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 ( see CLINICAL
PHARMACOLOGY).
In controlled clinical trials with about 80 pediatric patients and in well-
monitored, open- label studies with about 400 pediatric patients with juvenile
arthritis treated with naproxen, the incidence of rash and prolonged bleeding
times were increased, the incidence of gastrointestinal and central nervous
system reactions were about the same, and the incidence of other reactions were
lower in pediatric patients than in adults.
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 are italicized.
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
Drug/ Laboratory Test Interactions:
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- di- nitrobenzene used in this assay. Although 17- hydroxycorticosteroid
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).
Carcinogenesis: A 2- year study was performed in rats to evaluate
the carcinogenic potential of naproxen at rat doses of 8, 16, and 24 mg/ kg/
day ( 50, 100, and 150 mg/ m 2 ). The maximum dose used was 0.28 times the systemic
exposure to humans at the recommended dose. No evidence of tumorigenicity was
found.
Pregnancy: Teratogenic Effects: Pregnancy Category B
. Reproduction studies have been performed in rats at 20 mg/ kg/ day ( 125
mg/ m 2 / day, 0.23 times the human systemic exposure), rabbits at 20 mg/ kg/
day ( 220 mg/ m 2 / day, 0.27 times the human systemic exposure), and mice at
170 mg/ kg/ day ( 510 mg/ m 2 / day, 0.28 times the human systemic exposure)
with no evidence of impaired fertility or harm to the fetus due to the drug.
There are no adequate and well- controlled studies in pregnant women. Because
animal reproduction studies are not always predictive of human response, naproxen
should not be used during pregnancy unless clearly needed.
Nonteratogenic Effects: There is some evidence to suggest that when
inhibitors of prostaglandin synthesis are used to delay preterm labor there
is an increased risk of neonatal complications such as necrotizing enterocolitis,
patent ductus arteriosus and intracranial hemorrhage. Naproxen treatment given
in late pregnancy to delay parturition has been associated with persistent pulmonary
hypertension, renal dysfunction and abnormal prostaglandin E levels in preterm
infants. Because of the known effect of drugs of this class on the human fetal
cardiovascular system ( closure of ductus arteriosus), use during third trimester
should be avoided.
Nursing Mothers: The naproxen anion has been found in the milk
of lactating women at a concentration of approximately 1% of that found in plasma.
Because of the possible adverse effects of prostaglandin- inhibiting drugs on
neonates, use in nursing mothers should be avoided.
Pediatric Use: Safety and effectiveness in pediatric patients
below the age of 2 years have not been established. Pediatric dosing recommendations
for juvenile arthritis are based on well- controlled studies ( see DOSAGE
AND ADMINISTRATION). There are no adequate effectiveness or dose- response
data for other pediatric conditions, but the experience in juvenile arthritis
and other use experience have established that single doses of 2.5 to 5 mg/
kg ( as naproxen suspension, see DOSAGE AND
ADMINISTRATION), with total daily dose not exceeding 15 mg/ kg/ day,
are well tolerated in pediatric patients over 2 years of age.
DRUG INTERACTIONS
The use of NSAIDs in patients who are receiving ACE inhibitors may potentiate
renal disease states ( see PRECAUTIONS:
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:
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:
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 betablockers.
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, naproxen sodium 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.
Due to the gastric pH elevating effects of H 2 - blockers, sucralfate and intensive
antacid therapy, concomitant administration of EC- NAPROSYN is not recommended.
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