Probenecid and colchicine

Probenecid and colchicine contains probenecid, which is a uricosuric agent, and colchicine, which has antigout activity, the mechanism of which is unknown.

Probenecid is the generic name for 4-[(dipropylamino) sulfonyl] benzoic acid. The structural formula is represented below:

C13H19NO4S....................M.W. 285.36

Probenecid is a white or nearly white, fine, crystalline powder. It is soluble in dilute alkali, in alcohol, in chloroform, and in acetone; it is practically insoluble in water and in dilute acids.

Colchicine is an alkaloid obtained from various species of Colchicum. The chemical name for colchicine is (S)-N-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[α]heptalen-7-yl) acetamide. The structural formula is represented below:

C22H25NO6.................................M.W. 399.44

Colchicine consists of pale yellow scales or powder; it darkens on exposure to light. Colchicine is soluble in water, freely soluble in alcohol and in chloroform, and slightly soluble in ether. Each tablet for oral administration contains 500 mg of probenecid and 0.5 mg of colchicine.

Each tablet also contains the following inactive ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate and sodium starch glycolate.

Probenecid is a uricosuric and renal tubular blocking agent. It inhibits the tubular reabsorption of urate, thus increasing the urinary excretion of uric acid 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 reported to inhibit the renal transport of many other compounds including amino hippuric acid (PAH), aminosalicylic acid (PAS), indomethacin, sodium iodomethamate and related iodinated organic acids, 17-ketosteroids, pantothenic acid, phenolsulfonphthalein (PSP), sulfonamides, and sulfonylureas. 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 in euparathyroid individuals.

Probenecid does not influence 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 to 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 leucopenia that is followed by leukocytosis.

Colchicine has other pharmacologic actions in animals: It alters neuromuscular function, intensifies gastrointestinal activity by neurogenic stimulation, increases sensitivity to central depressants, heightens response to sympathomimetic compounds, depresses the respiratory center, constricts blood vessels, causes hypertension by central vasomotor stimulation, and lowers body temperature.

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

This medication will not stop a gout attack that has already started. Your doctor may prescribe other medications to treat your gout. Keep taking colchicine and probenecid on a regular schedule, even if you take other gout medications.

Before using colchicine and probenecid, tell your doctor if you have:

• heart disease;
• kidney disease or a history of kidney stones;
• liver disease;
• a blood disease;
• stomach problems such as an ulcer or severe intestinal disorder;
• if you drink large amounts of alcohol; or
• if you are receiving a cancer treatment, including chemotherapy or radiation.

If you have any of these conditions, you may not be able to use colchicine and probenecid, or you may need a dosage adjustment or special tests during treatment.

Colchicine and probenecid may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether this medication passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

This medication can cause you to have unusual results with certain medical tests. Tell any doctor who treats you that you are using colchicine and probenecid.

Older adults may be more sensitive to the side effects of this medication.

Avoid drinking alcohol, which can raise uric acid levels in your blood and may also increase your risk of stomach problems caused by colchicine and probenecid.

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, vomiting, nausea, anorexia, sore gums.

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 colchicines 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.

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.

Read the entire FDA prescribing information for Probenecid and Colchicine (Probenecid and Colchicine)

Probenecid and colchicine combination is used to treat gout or gouty arthritis.

The probenecid in probenecid and colchicine helps to prevent gout attacks by removing extra uric acid from the body. The colchicine in probenecid and colchicine also helps to prevent gout attacks. Although colchicine may also be used to relieve an attack of gout, this requires more colchicine than this combination medicine contains. Probenecid and colchicine combination does not cure gout. probenecid and colchicine will help prevent gout attacks only as long as you continue to take it.

Probenecid and colchicine combination is available only with your doctor's prescription.

Your doctor should check your progress at regular visits while you are taking probenecid and colchicine.

Before you have any medical tests, tell the person in charge that you are taking probenecid and colchicine. The results of some tests may be affected by probenecid or by colchicine.

For diabetic patients:

• The probenecid in this combination medicine may cause false test results with copper sulfate urine sugar tests (e.g., Clinitest®), but not with glucose enzymatic urine sugar tests (e.g., Clinistix®). If you have any questions about this, check with your health care professional.

Taking aspirin or other salicylates may lessen the effects of the probenecid in this combination medicine. This will depend on the dose of aspirin or other salicylate that you take, and on how often you take it. Also, drinking large amounts of alcoholic beverages may increase the chance of stomach problems and may increase the amount of uric acid in your blood. Therefore, do not take aspirin or other salicylates or drink alcoholic beverages while you are taking probenecid and colchicine, unless you have first checked with your doctor.

For patients taking 4 tablets or more of probenecid and colchicine a day:

• Stop taking probenecid and colchicine immediately and check with your doctor as soon as possible if severe diarrhea, nausea or vomiting, or stomach pain occurs while you are taking probenecid and colchicine.