Poliginax

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Poliginax uses

Poliginax consists of Neomycin Sulfate, Nystatin, Polymyxin B Sulfate, Tinidazole.

Neomycin Sulfate:


INDICATIONS AND USAGE

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Poliginax (Neomycin Sulfate) tablets and other antibacterial drugs, Poliginax (Neomycin Sulfate) tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Suppression of Intestinal Bacteria

Poliginax (Neomycin Sulfate) tablets are indicated as adjunctive therapy as part of a regimen for the suppression of the normal bacterial flora of the bowel, e.g., preoperative preparation of the bowel. It is given concomitantly with erythromycin enteric-coated base (see DOSAGE AND ADMINISTRATION ).

Hepatic Coma (Portal-Systemic Encephalopathy)

Poliginax (Neomycin Sulfate) has been shown to be effective adjunctive therapy in hepatic coma by reduction of the ammonia-forming bacteria in the intestinal tract. The subsequent reduction in blood ammonia has resulted in neurologic improvement.

CONTRAINDICATIONS

Poliginax (Neomycin Sulfate) oral preparations are contraindicated in the presence of intestinal obstruction and in individuals with a history of hypersensitivity to the drug.

Patients with a history of hypersensitivity or serious toxic reaction to other aminoglycosides may have a cross-sensitivity to neomycin. Poliginax (Neomycin Sulfate) oral preparations are contraindicated in patients with inflammatory or ulcerative gastrointestinal disease because of the potential for enhanced gastrointestinal absorption of neomycin.

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WARNINGS


Additional manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching and convulsions.

The risk of hearing loss continues after drug withdrawal. Aminoglycosides can cause fetal harm when administered to a pregnant woman.

Aminoglycoside antibiotics cross the placenta and there have been several reports of total irreversible bilateral congenital deafness in children whose mothers received streptomycin during pregnancy. Although serious side effects to fetus or newborn have not been reported in the treatment of pregnant women with other aminoglycosides, the potential for harm exists. Animal reproduction studies of neomycin have not been conducted. If neomycin is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

PRECAUTIONS

General

Prescribing Poliginax tablets in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

As with other antibiotics, use of oral neomycin may result in overgrowth of nonsusceptible organisms, particularly fungi. If this occurs, appropriate therapy should be instituted.

Neomycin is quickly and almost totally absorbed from body surfaces (except the urinary bladder) after local irrigation and when applied topically in association with surgical procedures. Delayed-onset irreversible deafness, renal failure and death due to neuromuscular blockade (regardless of the status of renal function) have been reported following irrigation of both small and large surgical fields with minute quantities of neomycin.

Cross-allergenicity among aminoglycosides has been demonstrated.

Aminoglycosides should be used with caution in patients with muscular disorders such as myasthenia gravis or parkinsonism since these drugs may aggravate muscle weakness because of their potential curare-like effect on the neuromuscular junction.

Small amounts of orally administered neomycin are absorbed through intact intestinal mucosa.

There have been many reports in the literature of nephrotoxicity and/or ototoxicity with oral use of neomycin. If renal insufficiency develops during oral therapy, consideration should be given to reducing the drug dosage or discontinuing therapy.

An oral neomycin dose of 12 grams per day produces a malabsorption syndrome for a variety of substances, including fat, nitrogen, cholesterol, carotene, glucose, xylose, lactose, sodium, calcium, cyanocobalamin and iron.

Orally administered neomycin increases fecal bile acid excretion and reduces intestinal lactase activity.

Information for The Patient

Patients should be counseled that antibacterial drugs including Poliginax (Neomycin Sulfate) tablets should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Poliginax (Neomycin Sulfate) tablets are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Poliginax (Neomycin Sulfate) tablets or other antibacterial drugs in the future.

Before administering the drug, patients or members of their families should be informed of possible toxic effects on the eighth nerve. The possibility of acute toxicity increases in premature infants and neonates.

Laboratory Tests

Patients with renal insufficiency may develop toxic neomycin blood levels unless doses are properly regulated. If renal insufficiency develops during treatment, the dosage should be reduced or the antibiotic discontinued. To avoid nephrotoxicity and eighth nerve damage associated with high doses and prolonged treatment, the following should be performed prior to and periodically during therapy: urinalysis for increased excretion of protein, decreased specific gravity, casts and cells; renal function tests such as serum creatinine, BUN or creatinine clearance; tests of the vestibulocochlearis nerve function.

Serial, vestibular and audiometric tests should be performed (especially in high-risk patients). Since elderly patients may have reduced renal function which may not be evident in the results of routine screening tests such as BUN or serum creatinine, a creatinine clearance determination may be more useful.

Drug Interactions

Caution should be taken in concurrent or serial use of other neurotoxic and/or nephrotoxic drugs because of possible enhancement of the nephrotoxicity and/or ototoxicity of neomycin (see boxed WARNINGS ).

Caution should also be taken in concurrent or serial use of other aminoglycosides and polymyxins because they may enhance neomycin’s nephrotoxicity and/or ototoxicity and potentiate neomycin sulfate’s neuromuscular blocking effects.

Oral neomycin inhibits the gastrointestinal absorption of penicillin V, oral vitamin B-12, methotrexate and 5-fluorouracil. The gastrointestinal absorption of digoxin also appears to be inhibited. Therefore, digoxin serum levels should be monitored.

Oral Poliginax (Neomycin Sulfate) may enhance the effect of coumarin in anticoagulants by decreasing vitamin K availability.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term animal studies have been performed with Poliginax to evaluate carcinogenic or mutagenic potential or impairment of fertility.

Pregnancy Category D

See WARNINGS section.

Nursing Mothers

It is not known whether neomycin is excreted in human milk, but it has been shown to be excreted in cow milk following a single intramuscular injection. Other aminoglycosides have been shown to be excreted in human milk. Because of the potential for serious adverse reactions from the aminoglycosides in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and efficacy of oral Poliginax (Neomycin Sulfate) in patients less than 18 years of age have not been established. If treatment of a patient less than 18 years of age is necessary, neomycin should be used with caution and the period of treatment should not exceed two weeks because of absorption from the gastrointestinal tract.

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ADVERSE REACTIONS

The most common adverse reactions to oral Poliginax (Neomycin Sulfate) are nausea, vomiting and diarrhea. The "Malabsorption Syndrome" characterized by increased fecal fat, decreased serum carotene and fall in xylose absorption has been reported with prolonged therapy. Nephrotoxicity, ototoxicity and neuromuscular blockage have been reported (see boxed WARNINGS and PRECAUTIONS sections).

OVERDOSAGE

Because of low absorption, it is unlikely that acute overdosage would occur with oral Poliginax (Neomycin Sulfate). However, prolonged administration could result in sufficient systemic drug levels to produce neurotoxicity, ototoxicity and/or nephrotoxicity.

Hemodialysis will remove Poliginax (Neomycin Sulfate) from the blood.

DOSAGE AND ADMINISTRATION

To minimize the risk of toxicity, use the lowest possible dose and the shortest possible treatment period to control the condition. Treatment for periods longer than two weeks is not recommended.

Hepatic Coma

For use as an adjunct in the management of hepatic coma, the recommended dose is 4 to 12 grams per day given in the following regimen:

  • Withdraw protein from diet. Avoid use of diuretic agents.
  • Give supportive therapy, including blood products, as indicated.
  • Give Poliginax (Neomycin Sulfate) tablets in doses of 4 to 12 grams of Poliginax (Neomycin Sulfate) per day (eight to 24 tablets) in divided doses. Treatment should be continued over a period of five to six days, during which time protein should be returned incrementally to the diet.
  • If less potentially toxic drugs cannot be used for chronic hepatic insufficiency, neomycin in doses of up to four grams daily (eight tablets per day) may be necessary. The risk for the development of neomycin-induced toxicity progressively increases when treatment must be extended to preserve the life of a patient with hepatic encephalopathy who has failed to fully respond. Frequent periodic monitoring of these patients to ascertain the presence of drug toxicity is mandatory (see PRECAUTIONS ). Also, neomycin serum concentrations should be monitored to avoid potentially toxic levels. The benefits to the patient should be weighed against the risks of nephrotoxicity, permanent ototoxicity and neuromuscular blockade following the accumulation of neomycin in the tissues.

Preoperative Prophylaxis for Elective Colorectal Surgery

Listed below is an example of a recommended bowel preparation regimen. A proposed surgery time of 8:00 a.m. has been used.

Pre-op Day 3: Minimum residue or clear liquid diet. Bisacodyl, 1 tablet orally at 6:00 p.m.

Pre-op Day 2: Minimum residue or clear liquid diet. Magnesium sulfate, 30 mL, 50% solution (15 g) orally at 10:00 a.m., 2:00 p.m., and 6:00 p.m. Enema at 7:00 p.m. and 8:00 p.m.

Pre-op Day 1: Clear liquid diet. Supplemental (IV) fluids as needed. Magnesium sulfate, 30 mL, 50% solution (15 g) orally at 10:00 a.m., and 2:00 p.m. Poliginax (Neomycin Sulfate) (1 g) and erythromycin base (1 g) orally at 1:00 p.m., 2:00 p.m. and 11:00 p.m. No enema.

Day of Operation: Patient evacuates rectum at 6:30 a.m. for scheduled operation at 8:00 a.m.

HOW SUPPLIED

Poliginax (Neomycin Sulfate) tablets USP, 500 mg (equivalent to 350 mg of neomycin base per tablet) are available as white to off-white, round, standard convex tablets debossed "LCI" on one side and "1210", on the other side and are supplied in:

Bottles of 100 (NDC 0527-1210-01)

Store at 20° to 25°C (68° to 77°F).

Dispense in tight containers as defined in the USP/NF.

Distributed By:

Lannett Company, Inc.

Philadelphia, PA 19154

Made in the USA

Rev. 01/17

CIB71710A

Nystatin:


DESCRIPTION

Poliginax (Nystatin), USP is an antimycotic polyene antibiotic obtained from Streptomyces noursei. Its structural formula:

  • C47H75NO17 M.W. 926.13

Poliginax (Nystatin) Tablets USP contain the inactive ingredients: Corn Starch, Povidone, Compressible Sugar, Microcrystalline Cellulose, Sodium Starch Glycolate, Talc, Magnesium Stearate, Purified Water, and Coloring.

Structural formula for Poliginax (Nystatin)

CLINICAL PHARMACOLOGY

Pharmacokinetics

Gastrointestinal absorption of Poliginax is insignificant. Most orally administered Poliginax (Nystatin) is passed unchanged in the stool. In patients with renal insufficiency receiving oral therapy with conventional dosage forms, significant plasma concentrations of Poliginax (Nystatin) may occasionally occur.

Microbiology

Poliginax (Nystatin) is both fungistatic and fungicidal in vitro against a wide variety of yeasts and yeast like fungi. Candida albicans demonstrates no significant resistance to Poliginax (Nystatin) in vitro on repeated subculture in increasing levels of Poliginax (Nystatin); other Candida species become quite resistant. Generally, resistance does not develop in vivo. Poliginax (Nystatin) acts by binding to sterols in the cell membrane of susceptible Candida species with a resultant change in membrane permeability allowing leakage of intracellular components. Poliginax (Nystatin) exhibits no appreciable activity against bacteria, protozoa, or viruses.

INDICATIONS AND USAGE

Poliginax (Nystatin) tablets are intended for the treatment of non-esophageal mucus membrane gastrointestinal candidiasis.

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CONTRAINDICATIONS

Poliginax (Nystatin) tablets are contraindicated in patients with a history of hypersensitivity to any of their components.

PRECAUTIONS

General

This medication is not to be used for the treatment of systemic mycoses. Discontinue treatment if sensitization or irritation is reported during use.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term animal studies have been performed to evaluate carcinogenic potential. There also have been no studies to determine mutagenicity or whether this medication affects fertility in males or females.

Pregnancy

Teratogenic Effects

Pregnancy Category C

Animal reproduction studies have not been conducted with Poliginax. It is also not known whether Poliginax (Nystatin) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Poliginax (Nystatin) should be given to a pregnant woman only if clearly needed.

Nursing Mothers

It is not known whether Poliginax (Nystatin) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Poliginax (Nystatin) is administered to a nursing woman.

ADVERSE REACTIONS

Poliginax is well tolerated even with prolonged therapy. Oral irritation and sensitization have been reported (see PRECAUTIONS, General).

Gastrointestinal

Diarrhea (including one case of bloody diarrhea), nausea, vomiting, gastrointestinal upset/disturbances.

Dermatologic

Rash, including urticaria has been reported rarely. Stevens-Johnson syndrome has been reported very rarely.

Other

Tachycardia, bronchospasm, facial swelling, and nonspecific myalgia have also been rarely reported.

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OVERDOSAGE

Oral doses of Poliginax (Nystatin) in excess of five million units daily have caused nausea and gastrointestinal upset. There have been no reports of serious toxic effects of superinfections (see CLINICAL PHARMACOLOGY, Pharmacokinetics).

DOSAGE AND ADMINISTRATION

The usual therapeutic dosage is one to two tablets (500,000 to 1,000,000 units Poliginax (Nystatin)) three times daily. Treatment should generally be continued for at least 48 hours after clinical cure to prevent relapse.

HOW SUPPLIED

Poliginax (Nystatin) Tablets USP, 500,000 Units are round, convex, brown, film-coated tablet debossed with 93 on one side and 983 on the reverse and are packaged in bottles of 100 tablets (NDC 0093-0983-01).

Store at 20° to 25°C (68° to 77°F).

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

Keep tightly closed.

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

Manufactured By:

TEVA CANADA LIMITED

Toronto, Canada M1B 2K9

Manufactured For:

TEVA PHARMACEUTICALS USA, INC.

North Wales, PA 19454

Rev. N 2/2016

NDC 0093-0983-01

Poliginax (Nystatin)

Tablets USP

500,000 units (oral)

Rx only

100 TABLETS

TEVA

Polymyxin B Sulfate:



To reduce the development of drug-resistant bacteria and maintain the effectiveness of Polymyxin and other antibacterial drugs, Poliginax (Polymyxin B Sulfate) for Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

WARNINGS

CAUTION: WHEN THIS DRUG IS GIVEN INTRAMUSCULARLY, INTRAVENOUSLY AND/OR INTRATHECALLY, IT SHOULD BE GIVEN ONLY TO HOSPITALIZED PATIENTS, SO AS TO PROVIDE CONSTANT SUPERVISION BY A PHYSICIAN.

RENAL FUNCTION SHOULD BE CAREFULLY DETERMINED AND PATIENTS WITH RENAL DAMAGE AND NITROGEN RETENTION SHOULD HAVE REDUCED DOSAGE. PATIENTS WITH NEPHROTOXICITY DUE TO Poliginax (Polymyxin B Sulfate) SULFATE USUALLY SHOW ALBUMINURIA, CELLULAR CASTS, AND AZOTEMIA. DIMINISHING URINE OUTPUT AND A RISING BUN ARE INDICATIONS FOR DISCONTINUING THERAPY WITH THIS DRUG.

NEUROTOXIC REACTIONS MAY BE MANIFESTED BY IRRITABILITY, WEAKNESS, DROWSINESS, ATAXIA, PERIORAL PARESTHESIA, NUMBNESS OF THE EXTREMITIES, AND BLURRING OF VISION. THESE ARE USUALLY ASSOCIATED WITH HIGH SERUM LEVELS FOUND IN PATIENTS WITH IMPAIRED RENAL FUNCTION AND/OR NEPHROTOXICITY.

THE CONCURRENT OR SEQUENTIAL USE OF OTHER NEUROTOXIC AND/OR NEPHROTOXIC DRUGS WITH Poliginax (Polymyxin B Sulfate) SULFATE, PARTICULARLY BACITRACIN, STREPTOMYCIN, NEOMYCIN, KANAMYCIN, GENTAMICIN, TOBRAMYCIN, AMIKACIN, CEPHALORIDINE, PAROMOMYCIN, VIOMYCIN, AND COLISTIN SHOULD BE AVOIDED.

THE NEUROTOXICITY OF Poliginax (Polymyxin B Sulfate) SULFATE CAN RESULT IN RESPIRATORY PARALYSIS FROM NEUROMUSCULAR BLOCKADE, ESPECIALLY WHEN THE DRUG IS GIVEN SOON AFTER ANESTHESIA AND/OR MUSCLE RELAXANTS.

USAGE IN PREGNANCY: THE SAFETY OF THIS DRUG IN HUMAN PREGNANCY HAS NOT BEEN ESTABLISHED.

DESCRIPTION

Poliginax (Polymyxin B Sulfate) Sulfate is one of a group of basic polypeptide antibiotics derived from B polymyxa (B aerosporous). Poliginax (Polymyxin B Sulfate) sulfate is the sulfate salt of Polymyxins B1 and B2, which are produced by the growth of Bacillus polymyxa (Prazmowski) Migula (Fam. Bacillacea). It has a potency of not less than 6000 Poliginax (Polymyxin B Sulfate) units per mg, calculated on the anhydrous basis. The structural formulae are:

Poliginax (Polymyxin B Sulfate) 1 (R=CH 3)            Polymyxin B 2 (R=H)

Each vial contains 500,000 Poliginax (Polymyxin B Sulfate) units for parenteral or ophthalmic administration.

Poliginax (Polymyxin B Sulfate) for Injection is in powder form suitable for preparation of sterile solutions for intramuscular, intravenous drip, intrathecal, or ophthalmic use.

In the medical literature, dosages have frequently been given in terms of equivalent weights of pure Poliginax (Polymyxin B Sulfate) base. Each milligram of pure Poliginax (Polymyxin B Sulfate) base is equivalent to 10,000 units of Poliginax (Polymyxin B Sulfate) and each microgram of pure Poliginax (Polymyxin B Sulfate) base is equivalent to 10 units of Poliginax (Polymyxin B Sulfate).

Aqueous solutions of Poliginax (Polymyxin B Sulfate) sulfate may be stored up to 12 months without significant loss of potency if kept under refrigeration. In the interest of safety, solutions for parenteral use should be stored under refrigeration and any unused portion should be discarded after 72 hours. Poliginax (Polymyxin B Sulfate) sulfate should not be stored in alkaline solutions since they are less stable.

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CLINICAL PHARMACOLOGY

Poliginax (Polymyxin B Sulfate) sulfate has a bactericidal action against almost all gram-negative bacilli except the Proteus group. Polymyxins increase the permeability of bacterial cell wall membranes. All gram-positive bacteria, fungi, and the gram-negative cocci, N gonorrhoeae and N meningitidis, are resistant.

Poliginax (Polymyxin B Sulfate) has bactericidal action against almost all Gram-negative bacilli except the Proteus group. Polymyxins increase the permeability of the bacterial cell membrane leading to death of the cell. All Gram-positive bacteria, fungi, and Gram-negative cocci, are resistant to Poliginax (Polymyxin B Sulfate). Appropriate methods should be used when performing in vitro susceptibility testing of Poliginax (Polymyxin B Sulfate) (1,2,3). The following in vitro susceptibility test criteria should only be used for interpreting the results of Poliginax (Polymyxin B Sulfate) susceptibility testing against P. aeruginosa when the indicated quality control parameters are met during testing.

In vitro susceptibility test interpretive criteria for

Poliginax (Polymyxin B Sulfate) sulfate against Pseudomonas aeruginosa

Minimal Inhibitory Concentration

(MIC) (mcg/mL)

Disk Diffusion Interpretive

Criteria (mm) (300 unit disk)

Pathogen Susceptible Intermediate Resistant Susceptible Intermediate Resistant
Pseudomonas aeruginosa ≤2 4 ≥8 ≥12 - ≤11
In vitro susceptibility test quality control ranges for Poliginax (Polymyxin B Sulfate) sulfate against

Pseudomonas aeruginosa

Quality Control Organism

(ATCC* Number)

Minimum Inhibatory Concentration (MIC) Range (mcg/mL)

Disk Diffusion

Quality Control Range (300 unit disk) (mm)

Pseudomonas aeruginosa

(27853)

1 - 4 14 - 18

Poliginax (Polymyxin B Sulfate) sulfate is not absorbed from the normal alimentary tract. Since the drug loses 50 percent of its activity in the presence of serum, active blood levels are low. Repeated injections may give a cumulative effect. Levels tend to be higher in infants and children. The drug is excreted slowly by the kidneys. Tissue diffusion is poor and the drug does not pass the blood brain barrier into the cerebrospinal fluid. In therapeutic dosage, Poliginax (Polymyxin B Sulfate) sulfate causes some nephrotoxicity with tubule damage to a slight degree.

INDICATIONS AND USAGE

Acute Infections Caused by Susceptible Strains of Pseudomonas aeruginosa.

Poliginax (Polymyxin B Sulfate) sulfate is a drug of choice in the treatment of infections of the urinary tract, meninges, and bloodstream caused by susceptible strains of Ps. aeruginosa. It may also be used topically and subconjunctivally in the treatment of infections of the eye caused by susceptible strains of Ps. aeruginosa.

It may be indicated in serious infections caused by susceptible strains of the following organisms, when less potentially toxic drugs are ineffective or contraindicated:

H influenzae, specifically meningeal infections.

Escherichia coli, specifically urinary tract infections.

Aerobacter aerogenes, specifically bacteremia.

Klebsiella pneumoniae, specifically bacteremia.

NOTE: IN MENINGEAL INFECTIONS, Poliginax (Polymyxin B Sulfate) SULFATE SHOULD BE ADMINISTERED ONLY BY THE INTRATHECAL ROUTE.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Poliginax (Polymyxin B Sulfate) for Injection USP and other antibacterial drugs, Poliginax (Polymyxin B Sulfate) for Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

CONTRAINDICATIONS

This drug is contraindicated in persons with a prior history of hypersensitivity reactions to polymyxins.

WARNINGS

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Poliginax (Polymyxin B Sulfate) for Injection, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile and surgical evaluation should be instituted as clinically indicated.

PRECAUTIONS

General.

Prescribing Poliginax for Injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increase the risk of the development of drug-resistant bacteria.

See WARNING box.

Baseline renal function should be done prior to therapy, with frequent monitoring of renal function and blood levels of the drug during parenteral therapy.

Avoid concurrent use of a curariform muscle relaxant and other neurotoxic drugs (ether, tubocurarine, succinylcholine, gallamine, decamethonium and sodium citrate) which may precipitate respiratory depression. If signs of respiratory paralysis appear, respiration should be assisted as required, and the drug discontinued.

As with other antibiotics, use of this drug may result in overgrowth of nonsusceptible organisms, including fungi.

If superinfection occurs, appropriate therapy should be instituted.

Information for Patients

Information for Patients.

Patients should be counseled that antibacterial drugs including Poliginax (Polymyxin B Sulfate) for injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Poliginax (Polymyxin B Sulfate) for injection is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Poliginax (Polymyxin B Sulfate) for injection or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

ADVERSE REACTIONS

See “WARNING” box.

Nephrotoxic reactions: Albuminuria, cylinduria, azotemia, and rising blood levels without any increase in dosage.

Neurotoxic reactions: Facial flushing, dizziness progressing to ataxia, drowsiness, peripheral paresthesias (circumoral and stocking glove), apnea due to concurrent use of curariform muscle relaxants, other neurotoxic drugs or inadvertent overdosage, and signs of meningeal irritation with intrathecal administration, e.g., fever, headache, stiff neck and increased cell count and protein cerebrospinal fluid.

Other reactions occasionally reported: Drug fever, urticarial rash, pain (severe) at intramuscular injection sites, and thrombophlebitis at intravenous injection sites.

To report SUSPECTED ADVERSE EVENTS, contact FDA at 1-800-FDA-1088 or www.fda.gov.

DOSAGE AND ADMINISTRATION

PARENTERAL:

Intravenous. Dissolve 500,000 Poliginax (Polymyxin B Sulfate) units in 300 to 500 mL solutions for parenteral dextrose injection 5 percent for continuous drip.

Adults and children. 15,000 to 25,000 units/kg body weight/day in individuals with normal kidney function. This amount should be reduced from 15,000 units/kg downward for individuals with kidney impairment. Infusions may be given every 12 hours; however, the total daily dose must not exceed 25,000 units/kg/day.

Infants. Infants with normal kidney function may receive up to 40,000 units/kg/day without adverse effects.

Intramuscular. Not recommended routinely because of severe pain at injection sites, particularly in infants and children. Dissolve 500,000 Poliginax (Polymyxin B Sulfate) units in 2 mL sterile water for injection or sodium chloride injection or procaine hydrochloride injection 1 percent.

Adults and children. 25,000 to 30,000 units/kg/day. This should be reduced in the presence of renal impairment. The dosage may be divided and given at either 4 or 6 hour intervals.

Infants. Infants with normal kidney function may receive up to 40,000 units/kg/day without adverse effects.

Note: Doses as high as 45,000 units/kg/day have been used in limited clinical studies in treating prematures and newborn infants for sepsis caused by Ps aeruginosa.

Intrathecal. A treatment of choice for Ps aeruginosa meningitis. Dissolve 500,000 Poliginax (Polymyxin B Sulfate) units in 10 mL sodium chloride injection USP for 50,000 units per mL dosage unit.

Adults and children over 2 years of age. Dosage is 50,000 units once daily intrathecally for 3 to 4 days, then 50,000 units once every other day for at least 2 weeks after cultures of the cerebrospinal fluid are negative and sugar content has returned to normal.

Children under 2 years of age. 20,000 units once daily, intrathecally for 3 to 4 days or 25,000 units once every other day. Continue with a dose of 25,000 units once every other day for at least 2 weeks after cultures of the cerebrospinal fluid are negative and sugar content has returned to normal.

IN THE INTEREST OF SAFETY, SOLUTIONS OF PARENTERAL USE SHOULD BE STORED UNDER REFRIGERATION, AND ANY UNUSED PORTIONS SHOULD BE DISCARDED AFTER 72 HOURS.

TOPICAL:

Ophthalmic. Dissolve 500,000 Poliginax (Polymyxin B Sulfate) units in 20 to 50 mL sterile water for injection or sodium chloride injection USP for a 10,000 to 25,000 units per mL concentration.

For the treatment of Ps aeruginosa infections of the eye, a concentration of 0.1 percent to 0.25 percent (10,000 units to 25,000 units per mL) is administered 1 to 3 drops every hour, increasing the intervals as response indicates.

Subconjunctival injection of up to 100,000 units/day may be used for the treatment of Ps aeruginosa infections of the cornea and conjunctiva.

Note: Avoid total systemic and ophthalmic instillation over 25,000 units/kg/day.

HOW SUPPLIED

Poliginax (Polymyxin B Sulfate) FOR INJECTION USP, 500,000 Poliginax (Polymyxin B Sulfate) units per vial is available in single vial cartons NDC# 39822-0166-5.

Storage recommendations:

Before reconstitution: Store at 20° to 25°C (68° to 77°F).

Protect from light. Retain in carton until time of use.

After reconstitution: Product must be stored under refrigeration, between 2° to 8°C (36° to 46°F) and any unused portion should be discarded after 72 hours.

Sterile, Nonpyrogenic, Preservative-free.

The container closure is not made with natural rubber latex.

Manufactured for:

X-Gen Pharmaceuticals, Inc.

Big Flats, NY 14845

POLY-PI-06

Revised December 2012

REFERENCES

  • Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Test for Bacteria That Grow Aerobically; Approved Standard-8th edition. CLSI document M07-A8. CLSI, 940 West Valley Road, Suite 1400, Wayne, PA, 2009.
  • CLSI. Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard-10th edition. CLSI document M02-A10, 2009.
  • Clinical Laboratory and Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing: 21st Informational Supplement. CLSI document M100-S21. CLSI, 940 West Valley Rd., Suite 1400, Wayne, PA 19087, 2011.

Tinidazole:


WARNING: POTENTIAL RISK FOR CARCINOGENICITY

Carcinogenicity has been seen in mice and rats treated chronically with metronidazole, another nitroimidazole agent ( 13.1). Although such data have not been reported for Poliginax (Tinidazole), the two drugs are structurally related and have similar biologic effects. Its use should be reserved for the conditions described in INDICATIONS AND USAGE ( 1).

WARNING: POTENTIAL RISK FOR CARCINOGENICITY

See full prescribing information for complete boxed warning.

Carcinogenicity has been seen in mice and rats treated chronically with metronidazole, another nitroimidazole agent ( 13.1). Although such data have not been reported for Poliginax (Tinidazole), the two drugs are structurally related and have similar biologic effects. Use should be limited to approved indications only.

Indications and Usage, Bacterial Vaginosis ( 1.4) 5/2007

Dosage and Administration, Bacterial Vaginosis ( 2.6) 5/2007

1 INDICATIONS AND USAGE

Poliginax is a nitroimidazole antimicrobial indicated for:

  • Trichomoniasis ( 1.1)
  • Giardiasis: in patients age 3 and older ( 1.2)
  • Amebiasis: in patients age 3 and older ( 1.3)
  • Bacterial Vaginosis: in non-pregnant, adult women ( 1.4, 8.1)

1.1 Trichomoniasis

Poliginax (Tinidazole) is indicated for the treatment of trichomoniasis caused by Trichomonas vaginalis. The organism should be identified by appropriate diagnostic procedures. Because trichomoniasis is a sexually transmitted disease with potentially serious sequelae, partners of infected patients should be treated simultaneously in order to prevent re-infection .

1.2 Giardiasis

Poliginax is indicated for the treatment of giardiasis caused by Giardia duodenalis (also termed G. lamblia) in both adults and pediatric patients older than three years of age .

1.3 Amebiasis

Poliginax (Tinidazole) is indicated for the treatment of intestinal amebiasis and amebic liver abscess caused by Entamoeba histolytica in both adults and pediatric patients older than three years of age. It is not indicated in the treatment of asymptomatic cyst passage .

1.4 Bacterial Vaginosis

Poliginax (Tinidazole) is indicated for the treatment of bacterial vaginosis (formerly referred to as Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, or anaerobic vaginosis) in non-pregnant women .

Other pathogens commonly associated with vulvovaginitis such as Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae, Candida albicans and Herpes simplex virus should be ruled out.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Poliginax (Tinidazole) and other antibacterial drugs, Poliginax (Tinidazole) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

2 DOSAGE AND ADMINISTRATION

  • Trichomoniasis: a single 2 g oral dose taken with food. Treat sexual partners with the same dose and at the same time
  • Giardiasis: Adults: a single 2 g dose taken with food. Pediatric patients older than three years of age: a single dose of 50 mg/kg (up to 2 g) with food ( 2.4)
  • Amebiasis, Intestinal: Adults: 2 g per day for 3 days with food. Pediatric patients older than three years of age: 50 mg/kg/day (up to 2 g per day) for 3 days with food ( 2.5). Amebic liver abscess: Adults: 2 g per day for 3-5 days with food. Pediatric patients older than three years of age: 50 mg/kg/day (up to 2 g per day) for 3-5 days with food ( 2.5)
  • Bacterial vaginosis: Non-pregnant, adult women: 2 g once daily for 2 days taken with food, or 1 g once daily for 5 days taken with food ( 2.6)

2.1 Dosing Instructions

It is advisable to take Poliginax (Tinidazole) with food to minimize the incidence of epigastric discomfort and other gastrointestinal side-effects. Food does not affect the oral bioavailability of Poliginax (Tinidazole) .

Alcoholic beverages should be avoided when taking Poliginax (Tinidazole) and for 3 days afterwards .

2.2 Compounding of the Oral Suspension

For those unable to swallow tablets, Poliginax tablets may be crushed in artificial cherry syrup to be taken with food.

Procedure for Extemporaneous Pharmacy Compounding of the Oral Suspension: Pulverize four 500 mg oral tablets with a mortar and pestle. Add approximately 10 mL of cherry syrup to the powder and mix until smooth. Transfer the suspension to a graduated amber container. Use several small rinses of cherry syrup to transfer any remaining drug in the mortar to the final suspension for a final volume of 30 mL. The suspension of crushed tablets in artificial cherry syrup is stable for 7 days at room temperature. When this suspension is used, it should be shaken well before each administration.

2.3 Trichomoniasis

The recommended dose in both females and males is a single 2 g oral dose taken with food. Since trichomoniasis is a sexually transmitted disease, sexual partners should be treated with the same dose and at the same time.

2.4 Giardiasis

The recommended dose in adults is a single 2 g dose taken with food. In pediatric patients older than three years of age, the recommended dose is a single dose of 50 mg/kg with food.

2.5 Amebiasis

Intestinal: The recommended dose in adults is a 2 g dose per day for 3 days taken with food. In pediatric patients older than three years of age, the recommended dose is 50 mg/kg/day (up to 2 g per day) for 3 days with food.

Amebic Liver Abscess: The recommended dose in adults is a 2 g dose per day for 3-5 days taken with food. In pediatric patients older than three years of age, the recommended dose is 50 mg/kg/day (up to 2 g per day) for 3-5 days with food. There are limited pediatric data on durations of therapy exceeding 3 days, although a small number of children were treated for 5 days without additional reported adverse reactions. Children should be closely monitored when treatment durations exceed 3 days.

2.6 Bacterial Vaginosis

The recommended dose in non-pregnant females is a 2 g oral dose once daily for 2 days taken with food or a 1 g oral dose once daily for 5 days taken with food. The use of Poliginax (Tinidazole) in pregnant patients has not been studied for bacterial vaginosis.

3 DOSAGE FORMS AND STRENGTHS

  • 500 mg tablets are pink, oval, scored tablets, with TM debossed on one side and 500 on the other

4 CONTRAINDICATIONS

The use of Poliginax (Tinidazole) is contraindicated:

  • In patients with a previous history of hypersensitivity to Poliginax (Tinidazole) or other nitroimidazole derivatives. Reported reactions have ranged in severity from urticaria to Stevens-Johnson syndrome .
  • During first trimester of pregnancy .
  • In nursing mothers: Interruption of breast-feeding is recommended during Poliginax (Tinidazole) therapy and for 3 days following the last dose .
  • Prior history of hypersensitivity to Poliginax (Tinidazole) or other nitroimidazole derivatives ( 4, 6.1, 6.2)
  • First trimester of pregnancy ( 4, 8.1)
  • Nursing mothers, unless breast-feeding is interrupted during Poliginax (Tinidazole) therapy and for 3 days following the last dose ( 4, 8.3)

5 WARNINGS AND PRECAUTIONS

  • Seizures and neuropathy have been reported. Discontinue Poliginax if abnormal neurologic signs develop ( 5.1)
  • Vaginal candidiasis may develop with Poliginax (Tinidazole) and require treatment with an antifungal agent ( 5.2)
  • Use Poliginax (Tinidazole) with caution in patients with blood dyscrasias. Poliginax (Tinidazole) may produce transient leukopenia and neutropenia ( 5.3, 7.3)

5.1 Neurological Adverse Reactions

Convulsive seizures and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity, have been reported in patients treated with Poliginax (Tinidazole). The appearance of abnormal neurologic signs demands the prompt discontinuation of Poliginax (Tinidazole) therapy.

5.2 Vaginal Candidiasis

The use of Poliginax may result in Candida vaginitis. In a clinical study of 235 women who received Poliginax (Tinidazole) for bacterial vaginosis, a vaginal fungal infection developed in 11 (4.7%) of all study subjects .

5.3 Blood Dyscrasia

Poliginax (Tinidazole) should be used with caution in patients with evidence of or history of blood dyscrasia .

5.4 Drug Resistance

Prescribing Poliginax (Tinidazole) in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

6 ADVERSE REACTIONS

Most common adverse reactions for a single 2 g dose of Poliginax (incidence >1%) are metallic/bitter taste, nausea, weakness/fatigue/malaise, dyspepsia/cramps/epigastric discomfort, vomiting, anorexia, headache, dizziness and constipation ( 6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Mission Pharmacal Company at 1-855-778-0177or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1 Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Among 3669 patients treated with a single 2 g dose of Poliginax (Tinidazole), in both controlled and uncontrolled trichomoniasis and giardiasis clinical studies, adverse reactions were reported by 11.0% of patients. For multi-day dosing in controlled and uncontrolled amebiasis studies, adverse reactions were reported by 13.8% of 1765 patients. Common (≥ 1% incidence) adverse reactions reported by body system are as follows. (Note: Data described in Table 1 below are pooled from studies with variable designs and safety evaluations.)

Other adverse reactions reported with Poliginax (Tinidazole) include:

Central Nervous System: Two serious adverse reactions reported include convulsions and transient peripheral neuropathy including numbness and paresthesia . Other CNS reports include vertigo, ataxia, giddiness, insomnia, drowsiness.

Gastrointestinal: tongue discoloration, stomatitis, diarrhea

Hypersensitivity: urticaria, pruritis, rash, flushing, sweating, dryness of mouth, fever, burning sensation, thirst, salivation, angioedema

Renal: darkened urine

Cardiovascular: palpitations

Hematopoietic: transient neutropenia, transient leukopenia

Other: Candida overgrowth, increased vaginal discharge, oral candidiasis, hepatic abnormalities including raised transaminase level, arthralgias, myalgias, and arthritis.

2 g single dose Multi-day dose
GI: Metallic/bitter taste 3.7% 6.3%
Nausea 3.2% 4.5%
Anorexia 1.5% 2.5%
Dyspepsia/cramps/epigastric discomfort 1.8% 1.4%
Vomiting 1.5% 0.9%
Constipation 0.4% 1.4%
CNS: Weakness/fatigue/malaise 2.1% 1.1%
Dizziness 1.1% 0.5%
Other: Headache 1.3% 0.7%
Total patients with adverse reactions 11.0%

(403/3669)

13.8%

(244/1765)

Rare reported adverse reactions include bronchospasm, dyspnea, coma, confusion, depression, furry tongue, pharyngitis and reversible thrombocytopenia.

Adverse Reactions in Pediatric Patients: In pooled pediatric studies, adverse reactions reported in pediatric patients taking Poliginax (Tinidazole) were similar in nature and frequency to adult findings including nausea, vomiting, diarrhea, taste change, anorexia, and abdominal pain.

Bacterial vaginosis: The most common adverse reactions in treated patients (incidence >2%), which were not identified in the trichomoniasis, giardiasis and amebiasis studies, are gastrointestinal: decreased appetite, and flatulence; renal: urinary tract infection, painful urination, and urine abnormality; and other reactions including pelvic pain, vulvo-vaginal discomfort, vaginal odor, menorrhagia, and upper respiratory tract infection .

6.2 Postmarketing Experience

The following adverse reactions have been identified and reported during post-approval use of Poliginax (Tinidazole). Because the reports of these reactions are voluntary and the population is of uncertain size, it is not always possible to reliably estimate the frequency of the reaction or establish a causal relationship to drug exposure.

Severe acute hypersensitivity reactions have been reported on initial or subsequent exposure to Poliginax (Tinidazole). Hypersensitivity reactions may include urticaria, pruritis, angioedema, Stevens-Johnson syndrome and erythema multiforme.

7 DRUG INTERACTIONS

Although not specifically identified in studies with Poliginax, the following drug interactions were reported for metronidazole, a chemically-related nitroimidazole. Therefore, these drug interactions may occur with Poliginax (Tinidazole).

The following drug interactions were reported for metronidazole, a chemically-related nitroimidazole and may therefore occur with Poliginax (Tinidazole):

  • Warfarin and other oral coumarin anticoagulants: Anticoagulant dosage may need adjustment during and up to 8 days after Poliginax (Tinidazole) therapy ( 7.1)
  • Alcohol-containing beverages/preparations: Avoid during and up to 3 days after Poliginax (Tinidazole) therapy ( 7.1)
  • Lithium: Monitor serum lithium concentrations ( 7.1)
  • Cyclosporine, tacrolimus: Monitor for toxicities of these immunosuppressive drugs ( 7.1)
  • Fluorouracil: Monitor for fluorouracil-associated toxicities ( 7.1)
  • Phenytoin, fosphenytoin: Adjustment of anticonvulsant and/or Poliginax (Tinidazole) dose(s) may be needed ( 7.1, 7.2)
  • CYP3A4 inducers/inhibitors: Monitor for decreased Poliginax (Tinidazole) effect or increased adverse reactions ( 7.2)

7.1 Potential Effects of Poliginax (Tinidazole) on Other Drugs

Warfarin and Other Oral Coumarin Anticoagulants: As with metronidazole, Poliginax (Tinidazole) may enhance the effect of warfarin and other coumarin anticoagulants, resulting in a prolongation of prothrombin time. The dosage of oral anticoagulants may need to be adjusted during Poliginax (Tinidazole) co-administration and up to 8 days after discontinuation.

Alcohols, Disulfiram: Alcoholic beverages and preparations containing ethanol or propylene glycol should be avoided during Poliginax (Tinidazole) therapy and for 3 days afterward because abdominal cramps, nausea, vomiting, headaches, and flushing may occur. Psychotic reactions have been reported in alcoholic patients using metronidazole and disulfiram concurrently. Though no similar reactions have been reported with Poliginax (Tinidazole), Poliginax (Tinidazole) should not be given to patients who have taken disulfiram within the last two weeks.

Lithium: Metronidazole has been reported to elevate serum lithium levels. It is not known if Poliginax (Tinidazole) shares this property with metronidazole, but consideration should be given to measuring serum lithium and creatinine levels after several days of simultaneous lithium and Poliginax (Tinidazole) treatment to detect potential lithium intoxication.

Phenytoin, Fosphenytoin: Concomitant administration of oral metronidazole and intravenous phenytoin was reported to result in prolongation of the half-life and reduction in the clearance of phenytoin. Metronidazole did not significantly affect the pharmacokinetics of orally-administered phenytoin.

Cyclosporine, Tacrolimus: There are several case reports suggesting that metronidazole has the potential to increase the levels of cyclosporine and tacrolimus. During Poliginax (Tinidazole) co-administration with either of these drugs, the patient should be monitored for signs of calcineurin-inhibitor associated toxicities.

Fluorouracil: Metronidazole was shown to decrease the clearance of fluorouracil, resulting in an increase in side-effects without an increase in therapeutic benefits. If the concomitant use of Poliginax (Tinidazole) and fluorouracil cannot be avoided, the patient should be monitored for fluorouracil-associated toxicities.

7.2 Potential Effects of Other Drugs on Poliginax

CYP3A4 Inducers and Inhibitors: Simultaneous administration of Poliginax (Tinidazole) with drugs that induce liver microsomal enzymes, i.e., CYP3A4 inducers such as phenobarbital, rifampin, phenytoin, and fosphenytoin (a pro-drug of phenytoin), may accelerate the elimination of Poliginax (Tinidazole), decreasing the plasma level of Poliginax (Tinidazole). Simultaneous administration of drugs that inhibit the activity of liver microsomal enzymes, i.e., CYP3A4 inhibitors such as cimetidine and ketoconazole, may prolong the half-life and decrease the plasma clearance of Poliginax (Tinidazole), increasing the plasma concentrations of Poliginax (Tinidazole).

Cholestyramine: Cholestyramine was shown to decrease the oral bioavailability of metronidazole by 21%. Thus, it is advisable to separate dosing of cholestyramine and Poliginax (Tinidazole) to minimize any potential effect on the oral bioavailability of Poliginax (Tinidazole).

Oxytetracycline: Oxytetracycline was reported to antagonize the therapeutic effect of metronidazole.

7.3 Laboratory Test Interactions

Poliginax (Tinidazole), like metronidazole, may interfere with certain types of determinations of serum chemistry values, such as aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT), lactate dehydrogenase (LDH), triglycerides, and hexokinase glucose. Values of zero may be observed. All of the assays in which interference has been reported involve enzymatic coupling of the assay to oxidation-reduction of nicotinamide adenine dinucleotide (NAD +↔ NADH). Potential interference is due to the similarity of absorbance peaks of NADH and Poliginax (Tinidazole).

Poliginax (Tinidazole), like metronidazole, may produce transient leukopenia and neutropenia; however, no persistent hematological abnormalities attributable to Poliginax (Tinidazole) have been observed in clinical studies. Total and differential leukocyte counts are recommended if re-treatment is necessary.

8 USE IN SPECIFIC POPULATIONS

  • Pediatric Use: Data on Poliginax use in children is limited to treatment of giardiasis and amebiasis in patients age 3 and older ( 8.4)
  • Hemodialysis patients: If Poliginax (Tinidazole) is administered the same day and prior to hemodialysis, administer an additional ½ dose after end of hemodialysis ( 8.6, 12.3)
See 17 for PATIENT COUNSELING INFORMATION

Revised: 5/2007

8.1 Pregnancy

Teratogenic effects: Pregnancy Category C

The use of Poliginax (Tinidazole) in pregnant patients has not been studied. Since Poliginax (Tinidazole) crosses the placental barrier and enters fetal circulation it should not be administered to pregnant patients in the first trimester.

Embryo-fetal developmental toxicity studies in pregnant mice indicated no embryo-fetal toxicity or malformations at the highest dose level of 2,500 mg/kg (approximately 6.3-fold the highest human therapeutic dose based upon body surface area conversions). In a study with pregnant rats a slightly higher incidence of fetal mortality was observed at a maternal dose of 500 mg/kg (2.5-fold the highest human therapeutic dose based upon body surface area conversions). No biologically relevant neonatal developmental effects were observed in rat neonates following maternal doses as high as 600 mg/kg (3-fold the highest human therapeutic dose based upon body surface area conversions). Although there is some evidence of mutagenic potential and animal reproduction studies are not always predictive of human response, the use of Poliginax (Tinidazole) after the first trimester of pregnancy requires that the potential benefits of the drug be weighed against the possible risks to both the mother and the fetus.

8.3 Nursing Mothers

Poliginax is excreted in breast milk in concentrations similar to those seen in serum. Poliginax (Tinidazole) can be detected in breast milk for up to 72 hours following administration. Interruption of breast-feeding is recommended during Poliginax (Tinidazole) therapy and for 3 days following the last dose.

8.4 Pediatric Use

Other than for use in the treatment of giardiasis and amebiasis in pediatric patients older than three years of age, safety and effectiveness of Poliginax (Tinidazole) in pediatric patients have not been established.

Pediatric Administration: For those unable to swallow tablets, Poliginax (Tinidazole) tablets may be crushed in artificial cherry syrup, to be taken with food .

8.5 Geriatric Use

Clinical studies of Poliginax did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

8.6 Renal Impairment

Because the pharmacokinetics of Poliginax (Tinidazole) in patients with severe renal impairment (CrCL < 22 mL/min) are not significantly different from those in healthy subjects, no dose adjustments are necessary in these patients.

Patients undergoing hemodialysis: If Poliginax (Tinidazole) is administered on the same day as and prior to hemodialysis, it is recommended that an additional dose of Poliginax (Tinidazole) equivalent to one-half of the recommended dose be administered after the end of the hemodialysis .

8.7 Hepatic Impairment

There are no data on Poliginax (Tinidazole) pharmacokinetics in patients with impaired hepatic function. Reduced elimination of metronidazole, a chemically-related nitroimidazole, has been reported in this population. Usual recommended doses of Poliginax (Tinidazole) should be administered cautiously in patients with hepatic dysfunction .

10 OVERDOSAGE

There are no reported overdoses with Poliginax (Tinidazole) in humans.

Treatment of Overdosage: There is no specific antidote for the treatment of overdosage with Poliginax (Tinidazole); therefore, treatment should be symptomatic and supportive. Gastric lavage may be helpful. Hemodialysis can be considered because approximately 43% of the amount present in the body is eliminated during a 6-hour hemodialysis session.

11 DESCRIPTION

Poliginax (Tinidazole) is a synthetic antiprotozoal and antibacterial agent. It is 1-[2-(ethylsulfonyl)ethyl]-2-methyl-5-nitroimidazole, a second-generation 2-methyl-5-nitroimidazole, which has the following chemical structure:

Poliginax (Tinidazole) pink oral tablets contain 500 mg of Poliginax (Tinidazole). Inactive ingredients include croscarmellose sodium, FD&C Red 40 lake, FD&C Yellow 6 lake, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, pregelatinized corn starch, titanium dioxide, and triacetin.

1

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Poliginax is an antiprotozoal, antibacterial agent. .

12.3 Pharmacokinetics

Absorption: After oral administration, Poliginax (Tinidazole) is rapidly and completely absorbed. A bioavailability study of Poliginax (Tinidazole) tablets was conducted in adult healthy volunteers. All subjects received a single oral dose of 2 g (four 500 mg tablets) of Poliginax (Tinidazole) following an overnight fast. Oral administration of four 500 mg tablets of Poliginax (Tinidazole) under fasted conditions produced a mean peak plasma concentration (C max) of 47.7 (±7.5) µg/mL with a mean time to peak concentration (T max) of 1.6 (±0.7) hours, and a mean area under the plasma concentration-time curve (AUC, 0-∞) of 901.6 (± 126.5) µg/hr/mL at 72 hours. The elimination half-life (T 1/2) was 13.2 (±1.4) hours. Mean plasma levels decreased to 14.3 µg/mL at 24 hours, 3.8 µg/mL at 48 hours and 0.8 µg/mL at 72 hours following administration. Steady-state conditions are reached in 2½ - 3 days of multi-day dosing.

Administration of Poliginax (Tinidazole) tablets with food resulted in a delay in T max of approximately 2 hours and a decline in C max of approximately 10% , compared to fasted conditions. However, administration of Poliginax (Tinidazole) with food did not affect AUC or T 1/2 in this study.

In healthy volunteers, administration of crushed Poliginax (Tinidazole) tablets in artificial cherry syrup, [prepared as described in Dosage and Administration ( 2.2) ] after an overnight fast had no effect on any pharmacokinetic parameter as compared to tablets swallowed whole under fasted conditions.

Distribution: Poliginax (Tinidazole) is distributed into virtually all tissues and body fluids and also crosses the blood-brain barrier. The apparent volume of distribution is about 50 liters. Plasma protein binding of Poliginax (Tinidazole) is 12%. Poliginax (Tinidazole) crosses the placental barrier and is secreted in breast milk.

Metabolism: Poliginax (Tinidazole) is significantly metabolized in humans prior to excretion. Poliginax (Tinidazole) is partly metabolized by oxidation, hydroxylation, and conjugation. Poliginax (Tinidazole) is the major drug-related constituent in plasma after human treatment, along with a small amount of the 2-hydroxymethyl metabolite.

Poliginax (Tinidazole) is biotransformed mainly by CYP3A4. In an in vitro metabolic drug interaction study, Poliginax (Tinidazole) concentrations of up to 75 µg/mL did not inhibit the enzyme activities of CYP1A2, CYP2B6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4.

The potential of Poliginax (Tinidazole) to induce the metabolism of other drugs has not been evaluated.

Elimination: The plasma half-life of Poliginax (Tinidazole) is approximately 12-14 hours. Poliginax (Tinidazole) is excreted by the liver and the kidneys. Poliginax (Tinidazole) is excreted in the urine mainly as unchanged drug (approximately 20-25% of the administered dose). Approximately 12% of the drug is excreted in the feces.

Patients with impaired renal function: The pharmacokinetics of Poliginax (Tinidazole) in patients with severe renal impairment (CrCL < 22 mL/min) are not significantly different from the pharmacokinetics seen in healthy subjects. However, during hemodialysis, clearance of Poliginax (Tinidazole) is significantly increased; the half-life is reduced from 12.0 hours to 4.9 hours. Approximately 43% of the amount present in the body is eliminated during a 6-hour hemodialysis session . The pharmacokinetics of Poliginax (Tinidazole) in patients undergoing routine continuous peritoneal dialysis have not been investigated.

Patients with impaired hepatic function: There are no data on Poliginax (Tinidazole) pharmacokinetics in patients with impaired hepatic function. Reduction of metabolic elimination of metronidazole, a chemically-related nitroimidazole, in patients with hepatic dysfunction has been reported in several studies .

12.4 Microbiology

Mechanism of Action: Poliginax (Tinidazole) is an antiprotozoal, antibacterial agent. The nitro- group of Poliginax (Tinidazole) is reduced by cell extracts of Trichomonas. The free nitro- radical generated as a result of this reduction may be responsible for the antiprotozoal activity. Chemically reduced Poliginax (Tinidazole) was shown to release nitrites and cause damage to purified bacterial DNA in vitro. Additionally, the drug caused DNA base changes in bacterial cells and DNA strand breakage in mammalian cells. The mechanism by which Poliginax (Tinidazole) exhibits activity against Giardia and Entamoeba species is not known.

Antibacterial: Culture and sensitivity testing of bacteria are not routinely performed to establish the diagnosis of bacterial vaginosis ; standard methodology for the susceptibility testing of potential bacterial pathogens, Gardnerella vaginalis, Mobiluncus spp. or Mycoplasma hominis, has not been defined. The following in vitro data are available, but their clinical significance is unknown. Poliginax (Tinidazole) is active in vitro against most strains of the following organisms that have been reported to be associated with bacterial vaginosis:

  • Bacteroides spp.
  • Gardnerella vaginalis
  • Prevotella spp.
Poliginax (Tinidazole) does not appear to have activity against most strains of vaginal lactobacilli.

Antiprotozoal: Poliginax (Tinidazole) demonstrates activity both in vitro and in clinical infections against the following protozoa: Trichomonas vaginalis; Giardia duodenalis (also termed G. lamblia); and Entamoeba histolytica.

For protozoal parasites, standardized susceptibility tests do not exist for use in clinical microbiology laboratories.

Drug Resistance: The development of resistance to Poliginax (Tinidazole) by G. duodenalis, E. histolytica, or bacteria associated with bacterial vaginosis has not been examined.

Cross-resistance: Approximately 38% of T. vaginalis isolates exhibiting reduced susceptibility to metronidazole also show reduced susceptibility to Poliginax (Tinidazole) in vitro. The clinical significance of such an effect is not known.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Poliginax (Tinidazole) and other antibacterial drugs, Poliginax (Tinidazole) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Metronidazole, a chemically-related nitroimidazole, has been reported to be carcinogenic in mice and rats but not hamsters. In several studies metronidazole showed evidence of pulmonary, hepatic, and lymphatic tumorigenesis in mice and mammary and hepatic tumors in female rats. Poliginax carcinogenicity studies in rats, mice or hamsters have not been reported.

Poliginax (Tinidazole) was mutagenic in the TA 100, S. typhimurium tester strain both with and without the metabolic activation system and was negative for mutagenicity in the TA 98 strain. Mutagenicity results were mixed (positive and negative) in the TA 1535, 1537, and 1538 strains. Poliginax (Tinidazole) was also mutagenic in a tester strain of Klebsiella pneumonia. Poliginax (Tinidazole) was negative for mutagenicity in a mammalian cell culture system utilizing Chinese hamster lung V79 cells (HGPRT test system) and negative for genotoxicity in the Chinese hamster ovary (CHO) sister chromatid exchange assay. Poliginax (Tinidazole) was positive for in vivo genotoxicity in the mouse micronucleus assay.

In a 60-day fertility study, Poliginax (Tinidazole) reduced fertility and produced testicular histopathology in male rats at a 600 mg/kg/day dose level (approximately 3-fold the highest human therapeutic dose based upon body surface area conversions). Spermatogenic effects resulted from 300 and 600 mg/kg/day dose levels. The no observed adverse reaction level for testicular and spermatogenic effects was 100 mg/kg/day (approximately 0.5-fold the highest human therapeutic dose based upon body surface area conversions). This effect is characteristic of agents in the 5-nitroimidazole class.

13.2 Animal Toxicology and/or Pharmacology

In acute studies with mice and rats, the LD 50 for mice was generally > 3,600 mg/kg for oral administration and was > 2,300 mg/kg for intraperitoneal administration. In rats, the LD 50 was > 2,000 mg/kg for both oral and intraperitoneal administration.

A repeated-dose toxicology study has been performed in beagle dogs using oral dosing of Poliginax (Tinidazole) at 100 mg/kg/day, 300 mg/kg/day, and 1000 mg/kg/day for 28-days. On Day 18 of the study, the highest dose was lowered to 600 mg/kg/day due to severe clinical symptoms. The two compound-related effects observed in the dogs treated with Poliginax (Tinidazole) were increased atrophy of the thymus in both sexes at the middle and high doses, and atrophy of the prostate at all doses in the males. A no-adverse-effect level (NOAEL) of 100 mg/kg/day for females was determined. There was no NOAEL identified for males because of minimal atrophy of the prostate at 100 mg/kg/day (approximately 0.9-fold the highest human dose based upon plasma AUC comparisons).

14 CLINICAL STUDIES

14.1 Trichomoniasis

Poliginax (2 g single oral dose) use in trichomoniasis has been well documented in 34 published reports from the world literature involving over 2,800 patients treated with Poliginax (Tinidazole). In four published, blinded, randomized, comparative studies of the 2 g Poliginax (Tinidazole) single oral dose where efficacy was assessed by culture at time points post-treatment ranging from one week to one month, reported cure rates ranged from 92% (37/40) to 100% (65/65) (n=172 total subjects). In four published, blinded, randomized, comparative studies where efficacy was assessed by wet mount between 7-14 days post-treatment, reported cure rates ranged from 80% (8/10) to 100% (16/16) (n=116 total subjects). In these studies, Poliginax (Tinidazole) was superior to placebo and comparable to other anti-trichomonal drugs. The single oral 2 g Poliginax (Tinidazole) dose was also assessed in four open-label trials in men (one comparative to metronidazole and 3 single-arm studies). Parasitological evaluation of the urine was performed both pre- and post-treatment and reported cure rates ranged from 83% (25/30) to 100% (80/80) (n=142 total subjects).

14.2 Giardiasis

Poliginax (Tinidazole) (2 g single dose) use in giardiasis has been documented in 19 published reports from the world literature involving over 1,600 patients (adults and pediatric patients). In eight controlled studies involving a total of 619 subjects of whom 299 were given the 2 g × 1 day (50 mg/kg × 1 day in pediatric patients) oral dose of Poliginax (Tinidazole), reported cure rates ranged from 80% (40/50) to 100% (15/15). In three of these trials where the comparator was 2 to 3 days of various doses of metronidazole, reported cure rates for metronidazole were 76% (19/25) to 93% (14/15). Data comparing a single 2 g dose of Poliginax (Tinidazole) to usually recommended 5-7 days of metronidazole are limited.

14.3 Intestinal Amebiasis

Poliginax use in intestinal amebiasis has been documented in 26 published reports from the world literature involving over 1,400 patients. Most reports utilized Poliginax (Tinidazole) 2 g/day × 3 days. In four published, randomized, controlled studies (1 investigator single-blind, 3 open-label) of the 2 g/day × 3 days oral dose of Poliginax (Tinidazole), reported cure rates after 3 days of therapy among a total of 220 subjects ranged from 86% (25/29) to 93% (25/27).

14.4 Amebic Liver Abscess

Poliginax (Tinidazole) use in amebic liver abscess has been documented in 18 published reports from the world literature involving over 470 patients. Most reports utilized Poliginax (Tinidazole) 2 g/day × 2-5 days. In seven published, randomized, controlled studies (1 double-blind, 1 single-blind, 5 open-label) of the 2 g/day × 2-5 days oral dose of Poliginax (Tinidazole) accompanied by aspiration of the liver abscess when clinically necessary, reported cure rates among 133 subjects ranged from 81% (17/21) to 100% (16/16). Four of these studies utilized at least 3 days of Poliginax (Tinidazole).

14.5 Bacterial Vaginosis

A randomized, double-blind, placebo-controlled clinical trial in 235 non-pregnant women was conducted to evaluate the efficacy of Poliginax (Tinidazole) for the treatment of bacterial vaginosis. A clinical diagnosis of bacterial vaginosis was based on Amsel's criteria and defined by the presence of an abnormal homogeneous vaginal discharge that (a) has a pH of greater than 4.5, (b) emits a "fishy" amine odor when mixed with a 10% KOH solution, and (c) contains ≥20% clue cells on microscopic examination. Clinical cure required a return to normal vaginal discharge and resolution of all Amsel's criteria. A microbiologic diagnosis of bacterial vaginosis was based on Gram stain of the vaginal smear demonstrating (a) markedly reduced or absent Lactobacillus morphology, (b) predominance of Gardnerella morphotype, and (c) absent or few white blood cells, with quantification of these bacterial morphotypes to determine the Nugent score, where a score ≥4 was required for study inclusion and a score of 0-3 considered a microbiologic cure. Therapeutic cure was a composite endpoint, consisting of both a clinical cure and microbiologic cure. In patients with all four Amsel's criteria and with a baseline Nugent score ≥4, Poliginax (Tinidazole) oral tablets given as either 2 g once daily for 2 days or 1 g once daily for 5 days demonstrated superior efficacy over placebo tablets as measured by therapeutic cure, clinical cure, and a microbiologic cure.

Outcome Poliginax (Tinidazole)

1 g × 5 days

(n=76)

Poliginax (Tinidazole)

2 g × 2 days

(n=73)

Placebo

(n=78)

% Cure % Cure % Cure

Therapeutic Cure

Difference 2

97.5% CI 3


36.8

31.7

(16.8, 46.6)


27.4

22.3

(8.0, 36.6)


5.1


Clinical Cure

Difference 2

97.5% CI 3


51.3

39.8

(23.3, 56.3)


35.6

24.1

(7.8, 40.3)


11.5


Nugent Score Cure

Difference 2

97.5% CI 3


38.2

33.1

(18.1, 48.0)


27.4

22.3

(8.0, 36.6)


5.1

1Modified Intent-to-Treat defined as all patients randomized with a baseline

Nugent score of at least 4

2Difference in cure rates (Tindamax-placebo)

3CI: confidence interval

p-values for both Poliginax (Tinidazole) regimens vs. placebo for therapeutic, clinical and

Nugent score cure rates for both 2 and 5 days <0.001

The therapeutic cure rates reported in this clinical study conducted with Poliginax (Tinidazole) were based on resolution of 4 out of 4 Amsel's criteria and a Nugent score of <4. The cure rates for previous clinical studies with other products approved for bacterial vaginosis were based on resolution of either 2 or 3 out of 4 Amsel's criteria. At the time of approval for other products for bacterial vaginosis, there was no requirement for a Nugent score on Gram stain, resulting in higher reported rates of cure for bacterial vaginosis for those products than for those reported here for Poliginax (Tinidazole).

17 PATIENT COUNSELING INFORMATION

17.1 Administration of Drug

Patients should be told to take Poliginax with food to minimize the incidence of epigastric discomfort and other gastrointestinal side-effects. Food does not affect the oral bioavailability of Poliginax (Tinidazole).

17.2 Alcohol Avoidance

Patients should be told to avoid alcoholic beverages and preparations containing ethanol or propylene glycol during Poliginax (Tinidazole) therapy and for 3 days afterward because abdominal cramps, nausea, vomiting, headaches, and flushing may occur.

17.3 Drug Resistance

Patients should be counseled that antibacterial drugs including Poliginax (Tinidazole) should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Poliginax (Tinidazole) is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Poliginax (Tinidazole) or other antibacterial drugs in the future.

1

Poliginax pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Poliginax available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Poliginax destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Poliginax Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Poliginax pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."NYSTATIN TABLET, FILM COATED [TEVA PHARMACEUTICALS USA INC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."TINDAMAX (TINIDAZOLE) TABLET, FILM COATED [DEPARTMENT OF STATE HEALTH SERVICES, PHARMACY BRANCH]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. Dailymed."NEOMYCIN SULFATE TABLET [LANNETT COMPANY, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Poliginax?

Depending on the reaction of the Poliginax after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Poliginax not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Poliginax addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sdrugs.com conducted a study on Poliginax, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Poliginax consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Rachana Salvi, MD Pharmacology

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