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
Clinoril Side Effects, and Drug Interactions - Sulindac
Clinoril Side Effects, and Drug Interactions - Sulindac
SIDE EFFECTS
The following adverse reactions were reported in clinical trials or have been reported since the drug was marketed. The probability exists of a causal relationship between CLINORIL and these adverse reactions. The adverse reactions which have been observed in clinical trials encompass observations in 1,865 patients, including 232 observed for at least 48 weeks.
Incidence Greater Than 1%
Gastrointestinal
The most frequent types of adverse reactions occurring with CLINORIL are
gastrointestinal; these include gastrointestinal pain (10%), dyspepsia***,
nausea*** with or without vomiting, diarrhea***, constipation***,
flatulence, anorexia and gastrointestinal cramps.
Dermatologic
Rash***, pruritus.
Central Nervous System
Dizziness***, headache***, nervousness.
Special Senses
Tinnitus.
Miscellaneous
Edema (see PRECAUTIONS).
Incidence Less Than 1 in 100
Gastrointestinal
Gastritis, gastroenteritis or colitis. Peptic ulcer and gastrointestinal
bleeding have been reported. GI perforation and intestinal strictures (diaphragms)
have been reported rarely.
Liver function abnormalities; jaundice, sometimes with fever; cholestasis;
hepatitis; hepatic failure.
There have been rare reports of sulindac metabolites in common bile duct
"sludge" and in biliary calculi in patients with symptoms of cholecystitis
who underwent a cholecystectomy.
Pancreatitis (see PRECAUTIONS).
Ageusia; glossitis.
Dermatologic
Stomatitis, sore or dry mucous membranes, alopecia, photosensitivity.
Erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome,
and exfoliative dermatitis have been reported.
Cardiovascular
Congestive heart failure, especially in patients with marginal cardiac function;
palpitation; hypertension.
Hematologic
Thrombocytopenia; ecchymosis; purpura; leukopenia; agranulocytosis; neutropenia;
bone marrow depression, including aplastic anemia; hemolytic anemia; increased
prothrombin time in patients on oral anticoagulants (see PRECAUTIONS).
Genitourinary
Urine discoloration; dysuria; vaginal bleeding; hematuria; proteinuria; crystalluria;
renal impairment, including renal failure; interstitial nephritis; nephrotic
syndrome.
Renal calculi containing sulindac metabolites have been observed rarely.
Metabolic
Hyperkalemia.
Musculoskeletal
Muscle weakness.
Psychiatric
Depression; psychic disturbances including acute psychosis.
Nervous System
Vertigo; insomnia; somnolence; paresthesia; convulsions; syncope; aseptic
meningitis.
Special Senses
Blurred vision; visual disturbances; decreased hearing; metallic or bitter
taste.
Respiratory
Epistaxis.
Hypersensitivity Reactions
Anaphylaxis; angioneurotic edema; bronchial spasm; dyspnea.
Hypersensitivity vasculitis.
A potentially fatal apparent hypersensitivity syndrome has been reported.
This syndrome may include constitutional symptoms (fever, chills, diaphoresis,
flushing), cutaneous findings (rash or other dermatologic reactions ¾
see above), conjunctivitis, involvement of major organs (changes in liver
function including hepatic failure, jaundice, pancreatitis, pneumonitis with
or without pleural effusion, leukopenia, leukocytosis, eosinophilia, disseminated
intravascular coagulation, anemia, renal impairment, including renal failure),
and other less specific findings (adenitis, arthralgia, arthritis, myalgia,
fatigue, malaise, hypotension, chest pain, tachycardia).
Causal Relationship Unknown
A rare occurrence of fulminant necrotizing fasciitis, particularly in association
with Group A b-hemolytic streptococcus, has been
described in persons treated with non-steroidal anti-inflammatory agents,
sometimes with fatal outcome (see also PRECAUTIONS, General).
Other reactions have been reported in clinical trials or since the drug was
marketed, but occurred under circumstances where a causal relationship could
not be established. However, in these rarely reported events, that possibility
cannot be excluded. Therefore, these observations are listed to serve as alerting
information to physicians.
Cardiovascular
Arrhythmia.
Metabolic
Hyperglycemia.
Nervous System
Neuritis.
Special Senses
Disturbances of the retina and its vasculature.
Miscellaneous
Gynecomastia.
*** Incidence between 3% and 9%. Those reactions occurring in 1% to 3% of patients are not marked with an asterisk.
DRUG INTERACTIONS
DMSO should not be used with sulindac. Concomitant administration has been reported to reduce the plasma levels of the active sulfide metabolite and potentially reduce efficacy. In addition, this combination has been reported to cause peripheral neuropathy.
Although sulindac and its sulfide metabolite are highly bound to protein, studies in which CLINORIL was given at a dose of 400 mg daily, have shown no clinically significant interaction with oral anticoagulants or oral hypoglycemic agents. However, patients should be monitored carefully until it is certain that no change in their anticoagulant or hypoglycemic dosage is required. Special attention should be paid to patients taking higher doses than those recommended and to patients with renal impairment or other metabolic defects that might increase sulindac blood levels.
The concomitant administration of aspirin with sulindac significantly depressed the plasma levels of the active sulfide metabolite. A double-blind study compared the safety and efficacy of CLINORIL 300 or 400 mg daily given alone or with aspirin 2.4 g/day for the treatment of osteoarthritis. The addition of aspirin did not alter the types of clinical or laboratory adverse experiences for CLINORIL; however, the combination showed an increase in the incidence of gastrointestinal adverse experiences. Since the addition of aspirin did not have a favorable effect on the therapeutic response to CLINORIL, the combination is not recommended.
The concomitant use of CLINORIL with other NSAIDs is not recommended due to the increased possibility of gastrointestinal toxicity, with little or no increase in efficacy.
Caution should be used if CLINORIL is administered concomitantly with methotrexate. Non-steroidal anti-inflammatory drugs have been reported to decrease the tubular secretion of methotrexate and to potentiate its toxicity.
Administration of non-steroidal anti-inflammatory drugs concomitantly with cyclosporine has been associated with an increase in cyclosporine-induced toxicity, possibly due to decreased synthesis of renal prostacyclin. NSAIDs should be used with caution in patients taking cyclosporine, and renal function should be carefully monitored.
The concomitant administration of CLINORIL and diflunisal in normal volunteers resulted in lowering of the plasma levels of the active sulindac sulfide metabolite by approximately one-third.
Probenecid given concomitantly with sulindac had only a slight effect on plasma sulfide levels, while plasma levels of sulindac and sulfone were increased. Sulindac was shown to produce a modest reduction in the uricosuric action of probenecid, which probably is not significant under most circumstances.
Neither propoxyphene hydrochloride nor acetaminophen had any effect on the plasma levels of sulindac or its sulfide metabolite.
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