Each tablet for oral administration contains: Active ingredients: 500 mg of Probenecid and 0.5 mg of Colchicine.
Inactive ingredients: Maize Starch, Prosolv SMCC 90* (Silicificd Microcrystalline Cellulose), Plasidone 5630, Sodium Starch Glycolate, Sodium lauryl Sulphate, Aerosil-200, Magnesium Stearate, Pruv (Sodium stceryt fumarate).
* Prosolv SMCC 9Oconlains: – Microcrystalline Cellulose (Avicel) – Colloidal Silicon Dioxide. (Aerosil)
CLINICAL PHARMACOLOGY :
Probenecid is a uricosuric and renal tubular blocking agent. I! inhibits the tubular reabsorption of urate, thus increasing the urinary excretion of uric add and decreasing serum urate levels. Effective uricosuria reduces the miscible urate pool, retards urate deposition, and promotes resorption of urate deposits. Probenecid inhibits the tubular secretion of penicillin and usually increases penicillin plasma levels by any route the antibiotic is given. A 2-fold to 4-fold elevation has been demonstrated for various penicillins.
Probenecid also has been reponed to inhibit the renal transport of many other compounds including amino hippunc aCid (PAJij, aminosalicylic acid (PAS), Indomethacin, sodium iodomethamateanrl related- iodinated organic acids, 17-ketosteroids, pantothenic acid, phenolsulfonphtha1ein (PSP), sulfonamides, and sulfonyl ureas. See also Drug Interactions.
Probenecid decreases both hepatic and renal excretion of sulfobromophthalein (BSP). The tubular reabsorption of phosphorus is inhibited in hypoparathyroid but not ineuparathyroid individuals.
Probenecid does not innuence plasma concentrations of salicylates, nor the excretion of streptomycin, chloramphenicol, chlortetracycline. oxytetracycline, or neomycin. The mode of action of colchicine in gout is unknown. It is not an analgesic, though it relieves pain in acute attacks of gout. It is not a uricosuric agent and will not prevent progression of gout 10 chronic gouty arthritis. It does have a prophylactic. suppressive effect that helps to reduce the incidence of acute attacks and to relieve the residual pain and mild discomfort that patients with gout occasionally feel. In man and certain other animals. colchicine can produce a temporary leukopenia that is followed by leukocytosis.
INDICATIONS AND USAGE :
For the treatment of chronic gouty arthritis when complicated by frequent, recurrent acute attacks of gout.
Hypersensitivity to this product or to probenecid or colchicine.
Goutyless tablets are contraindicated in children under 2 years of age.
Not recommended in persons with known blood dyscrasias or uric acid kidney stones Therapy with Goutyless should not be started until an acute gouty attack has subsided.
Probenecid crosses the placental barrier and appears in cord blood. Colchicine can arrest cell division in animals and plants. In certain species of animals under certain conditions, colchicine has produced teratogenic effects. The possibility of such effects in humans also has been reponed. Because of the colchicine component, Goutyless is contraindicated in pregnant patients.
Exacerbation of gout following therapy with Probenecid and Colchicine may occur; in such cases additional colchicine or other appropriate therapy is advisable probenecid increases plasma
concentrations of methotrexate in both animals and humans. In animal studies, increased methotrexate toxicity has been reported. If Probenecid and Colchicine is given with methotrexate, the dosage of methotrexate should be reduced and serum levels may need to be monitored. In patients on Probenecid and Colchicine the use of salicyletes in either small or large doses is contraindicated because it antagonizes the uricosuric action of probenecid. The biphasic action of salicylates in the renal tubules accounts for the so-called “paradoxical effect” of uricosuric agents. In patients on Gouryless who require a mild analgesic agent the use of acetaminophen rather than small doses of salicylates would be preferred.
Rarely, severe allergic reactions and anaphylaxis have been reported with the use of Probenecid and Colchicine. Most of these have been reported to occur within several hours after readministration
following prior usage of the drug. The appearance of hypersensitivity reactions requires cessation of therapy with Probenecid and Colchicine.
Colchicine has been reported to adversely affect spermatogenesis in animals. Reversible azoospermia has been reported in onc patient.
Not used in cases of prostatic hyperplasia and patients with increased intraocular pressure and glaucoma.
Hematuria, renal colic, costovertebral pain, and formation of uric acid stones associated with the use of Goutyless in gouty patients may be prevented by alkalization of the urine and a liberal fluid intake (see
DOSAGE AND ADMINISTRATION). In these cases when alkali is administered, the acid-base balance of the patient should be watched. Use with caution in patients with a history of peptic ulcer.
Probenecid and Colchicine has been used in patients with some renal impairment but dosage requirements may be increased. Probenecid and Colchicine may not be effective in chronic renal insufficiency particularly when the glomerular filtration rate is 30 mUminute or less. A reducing substance may appear in thc urine of peuents recetvmg probenecid. This disappears with discontinuance of therapy. Suspected glycosuria should be confirmed by using a test specific for glucose. Adequate animal studies have not been conducted to determine tbe carcinogenicity potentia! of probenecid
or this drug combination. Since colchicine is an established mutagen, its ability to act as a carcinogen must be suspected and administration of Probenecid and Colchicine should involve a weighing of the benefit-vs-risk when long-term administration is contemplated.
DRUG INTERACTIONS :
When probenecid is used to elevate plasma concentrations of penicillin, or other beta-lactams, or when such drugs arc 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 asrgnificunr increase in total sulfonamide plasma levels. Since probenecid decreases the excretion of conjugated sulfonamidcs, plasma concentrations of the latter should be determined fro time to time when a sulfonemidc and Probenecid and Colchicine arc coadministered for prolonged periods. Probenecid may prolong or enhance the action of oral sulfonylurcas and thereby increase the
risk of hypogJyccmia. It has been reported that patients receiving probenecid require significantly less thiopental for induction
of anesthcsia. In addition, keraminc and thiopental enesthesia 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 agcnts such as indomethacin.
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 reponed to increase plasma concentrations of methotrexate
Falsely high readings forthcopbylline have been reported in an In vitro study, using the Schack and Waxier technique, wben therapeutie ccnceceaucns ofthcophylhne and probenecid were added to human plasma
ADVERSE REACTIONS :
The following adverse reactions have been observed and wnhm each category are listed in order of decreasing seventy Probenecid
Central Nervous System: headache, dizziness. Metabolie: precipitation of acute gouty arthntis. Gastrointestinal: hepatic necrosis. vomiting, nausea, anorexia, sore gwns.
Genitourinary: nephrotic syndrome, uric acid stones with or without hematwia, renal colic, costovertebral pain, urinary frequency.
Hypersensitivity: anaphylaxis, fever, urticaria, pruritus.
Hematologic: aplastic anemia, leukopenia, hemolync anemra which in some patients could be related to genetic deficiency of glucose-6-phosphate debydrogenase in red blood cells, anemia.
Integumentary: dermatitis, alopecia, flushing.
Side effects due to colchicine appear to be a function of dosage. The possibility of increased colchicinefollowing 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.
Hematologic: 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.
DOSACE AND ADMINISTRATION :
Therapy with Probenecid and Colchicine should not be started until an acute gouty attack has subsided. However, ifan acute attack is precipitated during therapy, Goutyless may be continued without changing the dosage, and additional colchicine or other appropriate therapy should be given to control the acute attack.
The recommended adult dosage is I tablet of Probenecid and Colchicine daily for one week, followed by 1 tablet twice a day thereafter.
Some degree of renal impairment may be present in patients with gout. A daily dosage of 2 tablets may be adequate. However, if necessary, the daily dosage may be increased by I tablet every four weeks within tolerance (and usually not above 4 tablets per day) if symptoms of gouty arthritis are not controlled or the 24 hour unc aeid excretion is not above 700 mg.As noted, Probenecid may not be effective in chronic renal insufficiency particularly when the glomerular filtration rate is 30 mbmiaute or less. Gastric intolerance may be indicative of overdosage, and may be corrected by decreasing the dosage. As uric acid tends to crystallize out of an acid urine, a liberal fluid intake is recommended, as well as sufficient sodium bicarbonate (3 to 7.5 g daily) or potassium citrate (7.5 g daily) to maintain an alkaline unne (see PRECAUTIONS).
Alkalization oftbc urine is recommended until the serum urate level returns to nomud limits and tophaceous deposits disappear. i.e., during the period when urinary excretion of uric acid is at a high level. Thereafter, alkalization of the urine and the usual restriction of purine-prodUCing foods may be somewhat relaxed.
Probenecid and Colchicine(or probenecid) should be conunued at the dosage that will maintain normal serum urate levels. When acute attacks have been absent for six months or more and serum urate levels remain within normal limits. the daily dosage of Gouty less may be decreased by I tablet every six months. The maintenance dosage should not be reduced to the point where serum urate levels lend to rise.
HOW SUPPLIED :
Carton box contams I or 2 Of 3 (Opaque P.V.C Alwn.) stnps each of 10 tablets + Leaflet.
Store at temperature not exceed 30″C , in dry place.
Keep Oul of reach of children
MANUFACTURED BY :
october pharma s.a.e – egypt