Probampacin

Ampicillin Trihydrate:

• Pharmacological action
• Pharmacokinetics
• Why is Probampacin prescribed?
• Dosage and administration
• Probampacin (Ampicillin Trihydrate) side effects, adverse reactions
• Probampacin contraindications
• Using during pregnancy and breastfeeding
• Special instructions
• Probampacin drug interactions
• Probampacin in case of emergency / overdose
• Probampacin (Ampicillin Trihydrate) reviews

Pharmacological action

Probampacin is an antibiotic of semisynthetic broad-spectrum penicillin group. This medication has a bactericidal effect by suppressing the synthesis of bacterial cell walls. Probampacin (Ampicillin Trihydrate) is active against aerobic gram-positive bacteria: Staphylococcus spp. (with the exception of strains producing penicillinase), Streptococcus spp., Enterococcus spp., Listeria monocytogenes; aerobic gram-negative bacteria: Neisseria gonorrhoeae, Neisseria meningitidis, Escherichia coli, Shigella spp., Salmonella spp., Bordetella pertussis, some strains of Haemophilus influenzae. Probampacin (Ampicillin Trihydrate) destroyed by penicillinase. This drug is acid-resistant.

Pharmacokinetics

After oral administration Probampacin (Ampicillin Trihydrate) is well absorbed from the gastrointestinal tract. This medicine is distributed in most organs and tissues; crosses the placental barrier, poorly penetrates the BBB. When inflammation of the meninges, BBB permeability increases dramatically. 30% of Probampacin (Ampicillin Trihydrate) is metabolized in the liver. This medication is excreted in the urine and bile.

Why is Probampacin prescribed?

Infectious-inflammatory diseases caused by organisms susceptible to Probampacin (Ampicillin Trihydrate): including ear infections, throat, nose, odontogenic infections, bronchopulmonary infections, acute and chronic urinary tract infections, gastrointestinal infections (including salmonella, cholecystitis), gynecological infections, meningitis, endocarditis, septicemia, sepsis, rheumatic fever, erysipelas, scarlet fever, infections of skin and soft tissues.

Dosage and administration

The dosing regimen of Probampacin is set individually depending on the severity, localization of infection and sensitivity of the pathogen.

For adults for oral administration a single dose of this medication is 250-500 mg, the multiplicity of the reception is 4 times / day. The dose for children weighing up to 20 kg is 12.5-25 mg / kg every 6 hours.

For IV and IM using the single dose for adults is 250-500 mg every 4-6 hours; for children the single dose is 25-50 mg / kg.

The duration of treatment depends on the localization of infection and features of the disease.

The maximum oral daily dose for adults is 4 g, for IM and IV administration - 14 g.

Probampacin (Ampicillin Trihydrate) side effects, adverse reactions

Allergic reactions: urticaria, erythema, angioedema, rhinitis, conjunctivitis, rarely - fever, joint pain, eosinophilia, extremely rare - anaphylactic shock.

Digestive system: nausea, vomiting.

The effects caused by chemotherapeutic action: oral candidiasis, vaginal candidiasis, intestinal dysbiosis, colitis caused by Clostridium difficile.

Probampacin contraindications

Infectious mononucleosis, lymphatic leukemia, increased sensitivity to Probampacin (Ampicillin Trihydrate) and other penicillins, abnormal liver function.

Using during pregnancy and breastfeeding

Perhaps the use of Probampacin during pregnancy if it may be needed. Probampacin (Ampicillin Trihydrate) is excreted in breast milk in low concentrations. If necessary to use Probampacin (Ampicillin Trihydrate) in the lactation period it should be solved the issue of termination of breastfeeding.

Category effects on the fetus by FDA - B.

Special instructions

In the course of treatment with Probampacin (Ampicillin Trihydrate) there is need the regular control of renal function, liver and peripheral blood picture. Patients with impaired renal function requires correction dosing regimen in accordance with the values of CCr.

When used in high doses in patients with renal insufficiency it may be toxic effects on the CNS.

For using of Probampacin (Ampicillin Trihydrate) in patients with bacteremia (sepsis) it can be bacteriolysis reaction (Jarisch-Herxheimer reaction).

Probampacin drug interactions

Simultaneous administration of Probampacin (Ampicillin Trihydrate) with bactericidal antibiotics (including aminoglycosides, cephalosporins, cycloserine, vancomycin, rifampicin) there is manifested synergism; with bacteriostatic antibiotics (including macrolides, chloramphenicol, lincosamides, tetracyclines, sulfonamides) - antagonism.

Probampacin (Ampicillin Trihydrate) enhances the effect of indirect anticoagulants by inhibiting the intestinal microflora, reduces the synthesis of vitamin K and prothrombin index.

Probampacin (Ampicillin Trihydrate) decreases the effect of drugs in the process of metabolism which produce PABA.

Probenecid, diuretics, allopurinol, phenylbutazone, NSAIDs decrease the tubular secretion of Probampacin (Ampicillin Trihydrate) which may be accompanied by an increase in its concentration in blood plasma.

Antacids, glucosamine, laxatives, aminoglycosides slow down and reduce the absorption of Probampacin (Ampicillin Trihydrate) Upha Corporation. Ascorbic acid increases the absorption of Probampacin (Ampicillin Trihydrate).

Probampacin (Ampicillin Trihydrate) decreases the effectiveness of oral contraceptives.

Probampacin in case of emergency / overdose

Symptoms: the toxic effect on the central nervous system (especially in patients with renal insufficiency), nausea, vomiting, diarrhea, impaired water and electrolyte balance (as a consequence of vomiting and diarrhea).

Treatment: gastric lavage, activated charcoal, saline laxatives, a maintain of water and electrolyte balance, symptomatic therapy. This drug is derived by means of hemodialysis.

Probenecid:

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Dosage and administration
• How supplied
• Probampacin (Probenecid) reviews

DESCRIPTION

Probampacin (Probenecid) is a uricosuric and renal tubular transport blocking agent.

The chemical name for Probampacin (Probenecid) is 4-[(dipropylamino) sulfonyl] benzoic acid (molecular weight 285.37). It has the following structural formula:

C₁₃H₁₉NO₄S

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

Each tablet for oral administration contains 500 mg of Probampacin (Probenecid) and the following inactive ingredients: colloidal silicon dioxide, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, sodium carbonate, sodium lauryl sulfate, sodium starch glycolate, cornstarch, titanium dioxide, triacetin, FD&C Yellow #6, D&C Yellow #10, and FD&C Blue #2.

Structural Formula

CLINICAL PHARMACOLOGY

Probampacin (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.

Probampacin (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.

Probampacin (Probenecid) also has been reported to inhibit the renal transport of many other compounds including aminohippuric 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.

Probampacin (Probenecid) decreases both hepatic and renal excretion of sulfobromophthalein (BSP). The tubular reabsorption of phosphorus is inhibited in hypoparathyroid but not in euparathyroid individuals.

Probampacin (Probenecid) does not influence plasma concentrations of salicylates, nor the excretion of streptomycin, chloramphenicol, chlortetracycline, oxytetracycline, or neomycin.

INDICATIONS AND USAGE

Probampacin (Probenecid) tablets are indicated for the treatment of the hyperuricemia associated with gout and gouty arthritis.

As an adjuvant to therapy with penicillin or with ampicillin, methicillin, oxacillin, cloxacillin, or nafcillin, for elevation and prolongation of plasma levels by whatever route the antibiotic is given.

CONTRAINDICATIONS

Hypersensitivity to Probampacin (Probenecid).

Children under 2 years of age.

Not recommended in persons with known blood dyscrasias or uric acid kidney stones.

Therapy with Probampacin (Probenecid) should not be started until an acute gouty attack has subsided.

WARNINGS

Exacerbation of gout following therapy with Probampacin may occur; in such cases colchicine or other appropriate therapy is advisable.

Probampacin (Probenecid) increases plasma concentrations of methotrexate in both animals and humans. In animal studies, increased methotrexate toxicity has been reported. If Probampacin (Probenecid) is given with methotrexate, the dosage of methotrexate should be reduced and serum levels may need to be monitored.

In patients on Probampacin (Probenecid) the use of salicylates in either small or large doses is contraindicated because it antagonizes the uricosuric action of Probampacin (Probenecid). The biphasic action of salicylates in the renal tubules accounts for the so-called "paradoxical effect" of uricosuric agents. In patients on Probampacin (Probenecid) 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 Probampacin (Probenecid). 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 Probampacin (Probenecid).

Usage In Pregnancy

Probampacin (Probenecid) crosses the placental barrier and appears in cord blood. The use of any drug in women of childbearing potential requires that the anticipated benefit be weighed against possible hazards.

PRECAUTIONS

General

Hematuria, renal colic, costovertebral pain, and formation of uric acid stones associated with the use of Probampacin in gouty patients may be prevented by alkalization of the urine and a liberal fluid intake. 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.

Probampacin (Probenecid) has been used in patients with some renal impairment, but dosage requirements may be increased. Probampacin (Probenecid) may not be effective in chronic renal insufficiency particularly when the glomerular filtration rate is 30 mL/minute or less. Because of its mechanism of action, Probampacin (Probenecid) is not recommended in conjunction with a penicillin in the presence of known renal impairment.

A reducing substance may appear in the urine of patients receiving Probampacin (Probenecid). This disappears with discontinuance of therapy. Suspected glycosuria should be confirmed by using a test specific for glucose.

Drug Interactions

When Probampacin (Probenecid) is used to elevate plasma concentrations of penicillin or other beta-lactams, or when such drugs are given to patients taking Probampacin (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 Probampacin (Probenecid). The uricosuric action of Probampacin (Probenecid) is also antagonized by pyrazinamide.

Probampacin (Probenecid) produces an insignificant increase in free sulfonamide plasma concentrations, but a significant increase in total sulfonamide plasma levels. Since Probampacin (Probenecid) decreases the renal excretion of conjugated sulfonamides, plasma concentrations of the latter should be determined from time to time when a sulfonamide and Probampacin (Probenecid) are coadministered for prolonged periods. Probampacin (Probenecid) may prolong or enhance the action of oral sulfonylureas and thereby increase the risk of hypoglycemia.

It has been reported that patients receiving Probampacin (Probenecid) require significantly less thiopental for induction of anesthesia. In addition, ketamine and thiopental anesthesia were significantly prolonged in rats receiving Probampacin (Probenecid).

The concomitant administration of Probampacin (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 Probampacin (Probenecid) is being coadministrated. Although specific instances of toxicity due to this potential interaction have not been observed to date, physicians should be alert to this possibility.

Probampacin (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 Probampacin (Probenecid), which probably is not significant under most circumstances.

In animals and in humans, Probampacin (Probenecid) has been reported to increase plasma concentrations of methotrexate.

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 Probampacin (Probenecid) were added to human plasma.

ADVERSE REACTIONS

The following adverse reactions have been observed and within each category are listed in order of decreasing severity.

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.

DOSAGE AND ADMINISTRATION

Gout

Therapy with Probampacin should not be started until an acute gouty attack has subsided. However, if an acute attack is precipitated during therapy, Probampacin (Probenecid) may be continued without changing the dosage, and full therapeutic dosage of colchicine, or other appropriate therapy, should be given to control the acute attack.

The recommended adult dosage is 250 mg (1/2 Probampacin (Probenecid) tablet), twice a day for one week, followed by 500 mg (1 tablet) twice a day thereafter.

Some degree of renal impairment may be present in patients with gout. A daily dosage of 1000 mg may be adequate. However, if necessary, the daily dosage may be increased by 500 mg increments every 4 weeks within tolerance (and usually not above 2000 mg per day) if symptoms of gouty arthritis are not controlled or the 24 hour uric acid excretion is not above 700 mg. As noted, Probampacin (Probenecid) may not be effective in chronic renal insufficiency particularly when the glomerular filtration rate is 30 mL/minute 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 urine.

Alkalization of the urine is recommended until the serum urate level returns to normal 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.

Probampacin (Probenecid) should be continued at the dosage that will maintain normal serum urate levels. When acute attacks have been absent for 6 months or more and serum urate levels remain within normal limits, the daily dosage may be decreased by 500 mg every 6 months. The maintenance dosage should not be reduced to the point where serum urate levels tend to rise.

Probampacin (Probenecid) and Penicillin Therapy (General)

Adults

The recommended dosage is 2000 mg ) daily in divided doses. This dosage should be reduced in older patients in whom renal impairment may be present.

Children

2–14 years of age:

Initial dose: 25 mg/kg body weight (or 0.7 g/square meter body surface).

Maintenance Dose: 40 mg/kg body weight (or 1.2 g/square meter body surface) per day, divided into 4 doses.

For children weighing more than 50 kg (110 lb) the adult dosage is recommended.

Probampacin (Probenecid) is contraindicated in children under 2 years of age.

The PSP excretion test may be used to determine the effectiveness of Probampacin (Probenecid) in retarding penicillin excretion and maintaining therapeutic levels. The renal clearance of PSP is reduced to about one-fifth the normal rate when dosage of Probampacin (Probenecid) is adequate.

Penicillin Therapy *

In uncomplicated gonococcal infections in men and women (urethral, cervical, rectal), 1 g of Probampacin (Probenecid) should be given orally with 4.8 million units of aqueous procaine penicillin GSee package circulars of manufacturers for detailed information about CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS. (given IM), or 3 g of amoxicillin² (given orally), or 3.5 g of ampicillin² (given orally).

For further guidance, see CDC recommendations for definition of regimens of choice, alternative regimens, treatment of hypersensitive patients, and other aspects of therapy.

*Recommended by the Center for Disease Control, U.S. Department of Health and Human Services, Public Health Service (Morbidity and Mortality Weekly Report Supplement, Volume 34, Number 4S, October 18, 1985).

HOW SUPPLIED

Probampacin (Probenecid) Tablets, USP are available containing 500 mg of Probampacin (Probenecid), USP.

The tablets are capsule shaped, film-coated yellow, debossed with MYLAN 156 on one side, 500 on the other side. They are available as follows:

NDC 0378-0156-01

bottles of 100 tablets

Store at 20° to 25°C (68° to 77°F).

Protect from light.

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505

REVISED MARCH 2006

PROB:R4AQ

PRINCIPAL DISPLAY PANEL - 500 mg

NDC 0378-0156-01

Probampacin (Probenecid)

Tablets, USP

500 mg

Rx only 100 Tablets

Each film-coated tablet contains:

Probampacin (Probenecid), USP 500 mg

Dispense in a tight, light-resistant

container as defined in the USP

using a child-resistant closure.

Keep container tightly closed.

Keep this and all medication

out of the reach of children.

Store at 20° to 25°C (68° to 77°F).

[See USP for Controlled Room

Temperature.]

Protect from light.

Usual Adult

Dosage: See accom-

panying prescribing information.

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505 U.S.A.

Mylan.com

RM0156A11