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
Colbenemid Side Effects, and Drug Interactions - Probenecid and Colchicine
Colbenemid Side Effects, and Drug Interactions - Probenecid and Colchicine
SIDE EFFECTS
The following adverse reactions have been observed and within each
category are listed in order
of decreasing severity.
Probenecid
Central Nervous System: headache,
dizziness.
Metabolic: precipitation
of acute gouty
arthritis.
Gastrointestinal: hepatic
necrosis, nausea,
anorexia, sore gums, vomiting
Genitourinary: nephrotic
syndrome, uric
acid stones with or without
hematuria, renal
colic, costovertebral
pain, urinary
frequency.
Hypersensitivity: anaphylaxis,
fever, urticaria,
pruritus.
Hematologic: aplastic anemia,
leukopenia, hemolytic
anemia which in some patients could be related to genetic
deficiency of glucose-6-phosphate
dehydrogenase in red blood
cells, anemia.
Integumentary: dermatitis,
alopecia, flushing.
Colchicine
Side effects due to colchicine
appear to be a function
of dosage. The possibility of increased colchicine
toxicity in the presence
of hepatic dysfunction should be considered. The appearance
of any of the following symptoms may require reduction
of dosage or discontinuance
of the drug.
Central Nervous System: peripheral
neuritis.
Musculoskeletal: muscular
weakness.
Gastrointestinal: nausea,
vomiting, abdominal
pain, or diarrhea may be
particularly troublesome in the presence of peptic
ulcer or spastic colon.
Hypersensitivity: urticaria.
Hematololgic: aplastic anemia,
agranulocytosis.
Integumentary: dermatitis,
purpura, alopecia.
At toxic doses, colchicine
may cause severe diarrhea,
generalized vascular damage, and renal
damage with hematuria
and oliguria.
DRUG INTERACTIONS
When probenecid
is used to elevate plasma
concentrations of penicillin, or other beta-lactams, or when such
drugs are given to patients taking probenecid therapeutically, high
plasma concentrations
of the other drug may increase the incidence
of adverse reactions associated with that drug. In the case
of penicillin, or other beta-lactams, psychic
disturbances have been reported.
The use of salicylates antagonizes the uricosuric
action of probenecid
(see WARNINGS). The uricosuric
action of probenecid
is also antagonized by pyrazinamide.
Probenecid produces an insignificant increase in free sulfonamide
plasma concentrations but a significant
increase in total sulfonamide
plasma levels. Since
probenecid decreases
the renal excretion
of conjugated sulfonamides, plasma concentrations of the latter
should be determined from time
to time when a sulfonamide
and probenecid and
colchicine are co-administered
for prolonged periods. Probenecid may prolong or enhance the action
of oral sulfonylureas and thereby increase the risk
of hypoglycemia.
It has been reported that patients receiving probenecid
require significantly less thiopental for induction
of anesthesia. In addition,
ketamine and thiopental anesthesia
were significantly prolonged in rats receiving probenecid.
The concomitant
administration
of probenecid increases
the mean plasma elimination
half-life of a number
of drugs which can lead
to increased plasma concentrations. These include agents such
as indomethacin, acetaminophen, naproxen, ketoprofen, meclofenamate,
lorazepam, and rifampin. Although the clinical
significance of this observation has not been established, a lower
dosage of the drug
may be required to produce a therapeutic
effect, and increases in dosage
of the drug in question
should be made cautiously and in small increments when probenecid
is being co-administrated. Although specific instances of toxicity
due to this potential
interaction have not been observed to date, physicians should be
alert to this possibility.
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.
In animals and in humans, probenecid
has been reported to increase plasma concentrations of methotrexate
(see WARNINGS).
Falsely high readings for theophylline
have been reported in an in vitro study, using the Schack
and Waxler technique, when therapeutic concentrations of theophylline
and probenecid were
added to human plasma.
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