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
Voltaren Side Effects, and Drug Interactions - Diclofenac
Voltaren Side Effects, and Drug Interactions - Diclofenac
SIDE EFFECTS
Adverse reaction information
is derived from blinded, controlled, and open-label clinical
trials, as well as worldwide marketing experience. In the description
below, rates of more common events represent clinical study results;
rarer events are derived principally from marketing experience and
publications, and accurate rate
estimates are generally not possible.
In 718 patients treated for shorter periods, i.e., 2 weeks or less,
with Cataflam Immediate-Release Tablets, adverse reactions were
reported one-half to one-tenth as frequently as by patients treated
for longer periods. In a 6-month, double-blind trial comparing Cataflam
Immediate-Release Tablets (N=196) versus Voltaren Delayed-Release
Tablets (N=197) versus ibuprofen (N=197), adverse reactions were
similar in nature and frequency. In
controlled clinical trials, the incidence
of adverse reactions for Voltaren Delayed-Release Tablets and Voltaren-XR
Extended-Release Tablets at comparable doses were similar.
The incidence of
common adverse reactions (greater than 1%) is based upon controlled
clinical trials in
1,543 patients treated up to 13 weeks with Voltaren Delayed-Release
Tablets. By far the most common adverse effects were gastrointestinal
symptoms, most of them minor, occurring in about 20%, and leading
to discontinuation in about 3%, of patients. Peptic ulcer or G.I.
bleeding occurred in
clinical trials in
0.6% (95% confidence interval: 0.2% to 1%) of approximately 1,800
patients during their first 3 months of diclofenac treatment
and in 1.6% (95% confidence interval: 0.8% to 2.4%) of approximately
800 patients followed for 1 year.
Gastrointestinal symptoms were followed in frequency
by central nervous system
side effects such
as headache (7%) and
dizziness (3%).
Meaningful (exceeding 3 times the Upper Limit of Normal) elevations
of ALT (SGPT) or AST
(SGOT) occurred at an overall rate
of approximately 2% during the first 2 months of Voltaren treatment.
Unlike aspirin-related elevations, which occur more frequently in
patients with rheumatoid
arthritis, these elevations were more frequently observed in patients
with osteoarthritis (2.6%) than in patients with rheumatoid
arthritis (0.7%).
Marked elevations (exceeding 8 times the ULN) were seen in 1% of
patients treated for 2-6 months (see WARNINGS,
Hepatic Effects).
The following adverse reactions were reported in patients treated
with diclofenac:
Incidence Greater Than 1% Causal Relationship Probable
(All derived from clinical
trials.) *Incidence, 3% to 9% (incidence of unmarked reactions is
l%-3%).
Body as a Whole: Abdominal pain
or cramps,* headache,* fluid retention,
abdominal distention.
Digestive: Diarrhea,* indigestion,* nausea,* constipation,*
flatulence, liver test
abnormalities,* P.B. i.e.,
peptic ulcer,
with or without bleeding
and/or perforation,
or bleeding without
ulcer (see above and also
WARNINGS).
Nervous System: Dizziness.
Skin and Appendages: Rash, pruritus.
Special Senses: Tinnitus.
Incidence Less Than 1% - Causal Relationship Probable
(Adverse reactions reported only in worldwide marketing experience
or in the literature, not seen in clinical
trials, are considered rare and are italicized.)
Body as a Whole: Malaise, swelling
of lips and tongue, photosensitivity, anaphylaxis, anaphylactoid
reactions.
Cardiovascular: Hypertension, congestive heart
failure.
Digestive: Vomiting, jaundice,
melena, esophageal
lesions, aphthous
stomatitis, dry mouth
and mucous membranes,
bloody diarrhea, hepatitis,
hepatic necrosis,
cirrhosis, hepatorenal
syndrome, appetite change, pancreatitis
with or without concomitant
hepatitis, colitis.
Hemic and Lymphatic: Hemoglobin decrease, leukopenia,
thrombocytopenia, eosinophilia, hemolytic
anemia, aplastic anemia,
agranulocytosis, purpura, allergic purpura.
Metabolic and Nutritional Disorders: Azotemia.
Nervous System: Insomnia, drowsiness,
depression, diplopia,
anxiety, irritability, aseptic meningitis,
convulsions.
Respiratory: Epistaxis, asthma,
laryngeal edema.
Skin and Appendages: Alopecia, urticaria,
eczema, dermatitis, bullous eruption,
erythema multiforme
major, angioedema,
Stevens-Johnson syndrome.
Special Senses: Blurred vision, taste
disorder, reversible and irreversible
hearing loss, scotoma.
Urogenital: Nephrotic syndrome,
proteinuria, oliguria,
interstitial nephritis,
papillary necrosis,
acute renal
failure.
Incidence Less Than 1% - Causal Relationship Unknown
(The following reactions have been reported in patients taking
diclofenac under circumstances that do not permit a clear attribution
of the reaction to diclofenac. These reactions are being included
as alerting information to physicians. Adverse reactions reported
only in worldwide marketing experience or in the literature, not
seen in clinical trials,
are considered rare and are italicized.)
Body as a Whole: Chest pain.
Cadiovascular: Palpitations, flushing, tachycardia,
premature ventricular
contractions, myocardial
infarction, hypotension.
Digestive: Intestinal perforation.
Hemic and Lymphatic: Bruising.
Metabolic and Nutritional Disorders: Hypoglycemia,
weight loss.
Nervous System: Paresthesia, memory
disturbance, nightmares, tremor, tic, abnormal coordination,
disorientation, psychotic
reaction.
Respiratory: Dyspnea, hyperventilation,
edema of pharynx.
Skin and Appendages: Excess perspiration,
exfoliative dermatitis.
Special Senses: Vitreous floaters, night blindness,
amblyopia.
Urogenital: Urinary frequency, nocturia,
hematuria, impotence,
vaginal bleeding.
DRUG INTERACTIONS
Aspirin: Concomitant administration
of diclofenac and aspirin is not recommended because diclofenac
is displaced from its binding sites during the concomitant
administration
of aspirin, resulting in lower plasma concentrations, peak plasma
levels, and AUC values.
Anticoagulants: While studies have not shown diclofenac
to interact with anticoagulants of the warfarin type, caution should
be exercised, nonetheless, since interactions have been seen with
other NSAIDs. Because prostaglandins play
an important role in hemostasis,
and NSAIDs affect platelet
function as well, concurrent
therapy with all NSAIDs,
including diclofenac, and warfarin requires close monitoring of
patients to be certain that no
change in their anticoagulant
dosage is required.
Digoxin, Methotrexate, Cyclosporine: Diclofenac,
like other NSAIDs, may affect
renal prostaglandins and
increase the toxicity of certain drugs. Ingestion of diclofenac
may increase serum concentrations
of digoxin and methotrexate
and increase cyclosporine’s nephrotoxicity. Patients who begin taking
diclofenac or who increase their diclofenac dose or any other NSAID
while taking digoxin, methotrexate, or cyclosporine may develop
toxicity characteristics
for these drugs. They should be observed closely, particularly if
renal function
is impaired. In the case
of digoxin, serum levels should be monitored.
Lithium: Diclofenac decreases lithium
renal clearance and increases
lithium plasma
levels. In patients taking
diclofenac and lithium concomitantly, lithium
toxicity may develop.
Oral Hypoglycemics: Diclofenac does not alter glucose
metabolism in normal
subjects nor does it alter the effects of oral
hypoglycemic agents. There are rare reports, however, from marketing
experiences, of changes in effects of insulin
or oral hypoglycemic agents
in the presence of diclofenac that necessitated changes in the doses
of such agents. Both hypo-
and hyperglycemic effects have been reported. A direct causal relationship
has not been established, but physicians should consider the possibility
that diclofenac may alter a diabetic
patient’s response
to insulin or oral hypoglycemic
agents.
Diuretics: Diclofenac and other NSAIDs
can inhibit the activity of diuretics. Concomitant treatment
with potassium-sparing diuretics may be associated with increased
serum potassium
levels.
Other Drugs: In small groups of patients (7-10/interaction
study), the concomitant
administration
of azathioprine, gold, chloroquine, D-penicillamine, prednisolone,
doxycycline, or digitoxin
did not significantly affect the peak levels and AUC
values of diclofenac. Phenobarbital toxicity has been reported to
have occurred in a patient
on chronic phenobarbital
treatment following the initiation of diclofenac therapy.
Protein Binding
In vitro, diclofenac interferes minimally or not at all with the
protein binding of salicylic acid
(20% decrease in binding), tolbutamide, prednisolone (10% decrease
in binding), or warfarin. Benzylpenicillin, ampicillin, oxacillin,
chlortetracycline, doxycycline, cephalothin, erythromycin, and sulfamethoxazole
have no influence in vitro
on the protein binding
of diclofenac in human serum.
Drug/Laboratory Test Interactions
Effect on Blood Coagulation: Diclofenac increases
platelet aggregation time
but does not affect bleeding
time, plasma thrombin
clotting time, plasma
fibrinogen, or factors
V and VII to XII. Statistically significant changes in prothrombin
and partial thromboplastin
times have been reported in normal
volunteers. The mean changes
were observed to be less than 1 second in both instances, however,
and are unlikely to be clinically important. Diclofenac is a prostaglandin
synthetase inhibitor,
however, and all drugs that inhibit prostaglandin
synthesis interfere
with platelet function
to some degree; therefore, patients who may be adversely affected
by such an action should
be carefully observed.
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