Timentin Injection

Dosage Form: injection, solution
TIMENTIN®

(sterile ticarcillin disodium and clavulanate potassium)

FOR INTRAVENOUS ADMINISTRATION

PHARMACY BULK PACKAGE

NOT FOR DIRECT INFUSION

RECONSTITUTED STOCK SOLUTION MUST BE TRANSFERRED AND FURTHER DILUTED FOR IV INFUSION.

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

PACKAGE DESCRIPTION

TIMENTIN is available in a 31-gram Pharmacy Bulk Package. This sterile dosage form contains multiple-single doses for use in a pharmacy admixture program for the preparation of parenteral fluids.

PRODUCT DESCRIPTION

TIMENTIN is a sterile injectable antibacterial combination consisting of the semisynthetic antibiotic ticarcillin disodium and the β-lactamase inhibitor clavulanate potassium (the potassium salt of clavulanic acid) for intravenous administration. Ticarcillin is derived from the basic penicillin nucleus, 6-amino-penicillanic acid.

Chemically, ticarcillin disodium is N-(2-Carboxy-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-6-yl)-3-thiophenemalonamic acid disodium salt and may be represented as:

Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus. It is a β-lactam structurally related to the penicillins and possesses the ability to inactivate a wide variety of β-lactamases by blocking the active sites of these enzymes. Clavulanic acid is particularly active against the clinically important plasmid-mediated β-lactamases frequently responsible for transferred drug resistance to penicillins and cephalosporins.

Chemically, clavulanate potassium is potassium (Z)-(2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate and may be represented structurally as:

TIMENTIN is supplied as a white to pale yellow powder for reconstitution. TIMENTIN is very soluble in water, its solubility being greater than 600 mg/mL. The reconstituted solution is clear, colorless or pale yellow, having a pH of 5.5 to 7.5.

For the 3.1-gram dosage of TIMENTIN, the theoretical sodium content is 4.51 mEq (103.6 mg) per gram of TIMENTIN. The theoretical potassium content is 0.15 mEq (6 mg) per gram of TIMENTIN.

Timentin Injection - Clinical Pharmacology

After an intravenous infusion (30 min.) of 3.1 grams of TIMENTIN, peak serum concentrations of both ticarcillin and clavulanic acid are attained immediately after completion of infusion. Ticarcillin serum levels are similar to those produced by the administration of equivalent amounts of ticarcillin alone with a mean peak serum level of 330 mcg/mL. The corresponding mean peak serum level for clavulanic acid was 8 mcg/mL. (See following table.)

SERUM LEVELS IN ADULTS

AFTER A 30-MINUTE IV INFUSION OF TIMENTIN®

TICARCILLIN SERUM LEVELS (mcg/mL)

Dose	0	15 min.	30 min.	1 hr.	1.5 hr.	3.5 hr.	5.5 hr.
3.1 gram	324	223	176	131	90	27	6
	(293 to 388)	(184 to 293)	(135 to 235)	(102 to 195)	(65 to 119)	(19 to 37)	(5 to 7)

CLAVULANIC ACID SERUM LEVELS (mcg/mL)

Dose	0	15 min.	30 min.	1 hr.	1.5 hr.	3.5 hr.	5.5 hr.
3.1 gram	8.0	4.6	2.6	1.8	1.2	0.3	0
	(5.3 to 10.3)	(3.0 to 7.6)	(1.8 to 3.4)	(1.6 to 2.2)	(0.8 to 1.6)	(0.2 to 0.3)

The mean area under the serum concentration curve was 485 mcg•hr/mL for ticarcillin and 8.2 mcg•hr/mL for clavulanic acid.

The mean serum half-lives of ticarcillin and clavulanic acid in healthy volunteers are 1.1 hours and 1.1 hours, respectively.

In pediatric patients receiving approximately 50 mg/kg of TIMENTIN (30:1 ratio ticarcillin to clavulanate), mean ticarcillin serum half-lives were 4.4 hours in neonates (n = 18) and 1.0 hour in infants and children (n = 41). The corresponding clavulanate serum half-lives averaged 1.9 hours in neonates (n = 14) and 0.9 hour in infants and children (n = 40). Area under the serum concentration time curves averaged 339 mcg•hr/mL in infants and children (n = 41), whereas the corresponding mean clavulanate area under the serum concentration time curves was approximately 7 mcg•hr/mL in the same population (n = 40).

Approximately 60% to 70% of ticarcillin and approximately 35% to 45% of clavulanic acid are excreted unchanged in urine during the first 6 hours after administration of a single dose of TIMENTIN to normal volunteers with normal renal function. Two hours after an intravenous injection of 3.1 grams of TIMENTIN, concentrations of ticarcillin in urine generally exceed 1,500 mcg/mL. The corresponding concentrations of clavulanic acid in urine generally exceed 40 mcg/mL. By 4 to 6 hours after injection, the urine concentrations of ticarcillin and clavulanic acid usually decline to approximately 190 mcg/mL and 2 mcg/mL, respectively. Neither component of TIMENTIN is highly protein bound; ticarcillin has been found to be approximately 45% bound to human serum protein and clavulanic acid approximately 25% bound.

Somewhat higher and more prolonged serum levels of ticarcillin can be achieved with the concurrent administration of probenecid; however, probenecid does not enhance the serum levels of clavulanic acid.

Ticarcillin can be detected in tissues and interstitial fluid following parenteral administration.

Penetration of ticarcillin into bile and pleural fluid has been demonstrated. The results of experiments involving the administration of clavulanic acid to animals suggest that this compound, like ticarcillin, is well distributed in body tissues.

An inverse relationship exists between the serum half-life of ticarcillin and creatinine clearance. The dosage of TIMENTIN need only be adjusted in cases of severe renal impairment. (See DOSAGE AND ADMINISTRATION.)

Ticarcillin may be removed from patients undergoing dialysis; the actual amount removed depends on the duration and type of dialysis.

Microbiology

Ticarcillin is a semisynthetic antibiotic with a broad spectrum of bactericidal activity against many gram-positive and gram-negative aerobic and anaerobic bacteria.

Ticarcillin is, however, susceptible to degradation by β-lactamases, and therefore, the spectrum of activity does not normally include organisms which produce these enzymes.

Clavulanic acid is a β-lactam, structurally related to the penicillins, which possesses the ability to inactivate a wide range of β-lactamase enzymes commonly found in microorganisms resistant to penicillins and cephalosporins. In particular, it has good activity against the clinically important plasmid-mediated β-lactamases frequently responsible for transferred drug resistance.

The formulation of ticarcillin with clavulanic acid in TIMENTIN protects ticarcillin from degradation by β-lactamase enzymes and effectively extends the antibiotic spectrum of ticarcillin to include many bacteria normally resistant to ticarcillin and other β-lactam antibiotics. Thus, TIMENTIN possesses the distinctive properties of a broad-spectrum antibiotic and a β-lactamase inhibitor. Ticarcillin/clavulanic acid has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

Gram-Positive Aerobes

Staphylococcus aureus (β-lactamase and non–β-lactamase–producing)∗

Staphylococcus epidermidis (β-lactamase and non–β-lactamase–producing)∗

∗Staphylococci that are resistant to methicillin/oxacillin must be considered resistant to ticarcillin/clavulanic acid.

Gram-Negative Aerobes

Citrobacter species (β-lactamase and non–β-lactamase–producing)

Enterobacter species including E. cloacae (β-lactamase and non–β-lactamase–producing)

(Although most strains of Enterobacter species are resistant in vitro, clinical efficacy has been demonstrated with TIMENTIN in urinary tract infections and gynecologic infections caused by these organisms.)

Escherichia coli (β-lactamase and non–β-lactamase–producing)

Haemophilus influenzae (β-lactamase and non–β-lactamase–producing)†

Klebsiella species including K. pneumoniae (β-lactamase and non–β-lactamase–producing)

Pseudomonas species including P. aeruginosa (β-lactamase and non–β-lactamase–producing)

Serratia marcescens (β-lactamase and non–β-lactamase–producing)

†β-lactamase–negative, ampicillin-resistant (BLNAR) strains of H. influenzae must be considered resistant to ticarcillin/clavulanic acid.

Anaerobic Bacteria

Bacteroides fragilis group (β-lactamase and non–β-lactamase–producing)

Prevotella (formerly Bacteroides) melaninogenicus (β-lactamase and non–β-lactamase–producing)

The following in vitro data are available, but their clinical significance is unknown.

The following strains exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for ticarcillin/clavulanic acid. However, with the exception of organisms shown to respond to ticarcillin alone, the safety and effectiveness of ticarcillin/clavulanic acid in treating infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.

Gram-Positive Aerobes

Staphylococcus saprophyticus (β-lactamase and non–β-lactamase–producing)

Streptococcus agalactiae‡ (Group B)

Streptococcus bovis‡

Streptococcus pneumoniae‡ (penicillin-susceptible strains only)

Streptococcus pyogenes‡

Viridans group streptococci‡

Gram-Negative Aerobes

Acinetobacter baumannii (β-lactamase and non–β-lactamase–producing)

Acinetobacter calcoaceticus (β-lactamase and non–β-lactamase–producing)

Acinetobacter haemolyticus (β-lactamase and non–β-lactamase–producing)

Acinetobacter lwoffi (β-lactamase and non–β-lactamase–producing)

Moraxella catarrhalis (β-lactamase and non–β-lactamase–producing)

Morganella morganii (β-lactamase and non–β-lactamase–producing)

Neisseria gonorrhoeae (β-lactamase and non–β-lactamase–producing)

Pasteurella multocida (β-lactamase and non–β-lactamase–producing)

Proteus mirabilis (β-lactamase and non–β-lactamase–producing)

Proteus penneri (β-lactamase and non–β-lactamase–producing)

Proteus vulgaris (β-lactamase and non–β-lactamase–producing)

Providencia rettgeri (β-lactamase and non–β-lactamase–producing)

Providencia stuartii (β-lactamase and non–β-lactamase–producing)

Stenotrophomonas maltophilia (β-lactamase and non–β-lactamase–producing)

Anaerobic Bacteria

Clostridium species including C. perfringens, C. difficile, C. sporogenes, C. ramosum, and C. bifermentans (β-lactamase and non–β-lactamase–producing)

Eubacterium species

Fusobacterium species including F. nucleatum and F. necrophorum (β-lactamase and non–β-lactamase–producing)

Peptostreptococcus species‡

Veillonella species‡

‡These are non–β-lactamase–producing strains, and therefore, are susceptible to ticarcillin.

In vitro synergism between TIMENTIN and gentamicin, tobramycin, or amikacin against multiresistant strains of Pseudomonas aeruginosa has been demonstrated.

Susceptibility Testing

Dilution Techniques

Quantitative methods are used to determine antimicrobial MICs. These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on a dilution method1,3 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of ticarcillin/clavulanate potassium powder.

The recommended dilution pattern utilizes a constant level of 2 mcg/mL clavulanic acid in all tubes with varying amounts of ticarcillin. MICs are expressed in terms of the ticarcillin concentration in the presence of clavulanic acid at a constant 2 mcg/mL. The MIC values should be interpreted according to the following criteria:

RECOMMENDED RANGES FOR TICARCILLIN/CLAVULANIC ACID SUSCEPTIBILITY TESTING*

For Pseudomonas aeruginosa:

MIC (mcg/mL)		Interpretation
≤64		Susceptible (S)
≥128		Resistant (R)

For Enterobacteriaceae:

MIC (mcg/mL)		Interpretation
≤16		Susceptible (S)
32-64		Intermediate (I)
≥128		Resistant (R)

For Staphylococci†:

MIC (mcg/mL)		Interpretation
≤8		Susceptible (S)
≥16		Resistant (R)

* Expressed as concentration of ticarcillin in the presence of clavulanic acid at a constant 2 mcg/mL.

† Staphylococci that are susceptible to ticarcillin/clavulanic acid but resistant to methicillin/oxacillin must be considered as resistant.

A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard ticarcillin/clavulanate potassium powder should provide the following MIC values3:

Microorganism		MIC (mcg/mL)‡
Escherichia coli	ATCC 25922	4-16
Escherichia coli	ATCC 35218	8-32
Pseudomonas aeruginosa	ATCC 27853	8-32
Staphylococcus aureus	ATCC 29213	0.5-2

‡ Expressed as concentration of ticarcillin in the presence of clavulanic acid at a constant 2 mcg/mL.

Diffusion Techniques

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2,3 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 85 mcg of ticarcillin/clavulanate potassium (75 mcg ticarcillin plus 10 mcg clavulanate potassium) to test the susceptibility of microorganisms to ticarcillin/clavulanic acid.

Reports from the laboratory providing results of the standard single-disk susceptibility test with an 85 mcg of ticarcillin/clavulanate potassium (75 mcg ticarcillin plus 10 mcg clavulanate potassium) disk should be interpreted according to the following criteria:

RECOMMENDED RANGES FOR TICARCILLIN/CLAVULANIC ACID SUSCEPTIBILITY TESTING

For Pseudomonas aeruginosa:

Zone Diameter (mm)		Interpretation
≥15		Susceptible (S)
≤14		Resistant (R)

For Enterobacteriaceae:

Zone Diameter (mm)		Interpretation
≥20		Susceptible (S)
15-19		Intermediate (I)
≤14		Resistant (R)

For Staphylococci §

Zone Diameter (mm)		Interpretation
≥23		Susceptible (S)
≤22		Resistant (R)

§ Staphylococci that are resistant to methicillin/oxacillin must be considered as resistant to ticarcillin/clavulanic acid.

Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for ticarcillin/clavulanic acid.

As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 85 mcg of ticarcillin/clavulanate potassium (75 mcg ticarcillin plus 10 mcg clavulanate potassium) disk should provide the following zone diameters in these laboratory test quality control strains:

Microorganism		Zone Diameter (mm)
Escherichia coli	ATCC 25922	24-30
Escherichia coli	ATCC 35218	21-25
Pseudomonas aeruginosa	ATCC 27853	20-28
Staphylococcus aureus	ATCC 25923	29-37

Anaerobic Techniques

For anaerobic bacteria, the susceptibility to ticarcillin/clavulanic acid can be determined by standardized test methods3,4. The MIC values obtained should be interpreted according to the following criteria:

RECOMMENDED RANGES FOR TICARCILLIN/CLAVULANIC ACID SUSCEPTIBILITY TESTING║

MIC (mcg/mL)		Interpretation
≤32		Susceptible (S)
64		Intermediate (I)
≥128		Resistant (R)

║ Expressed as concentration of ticarcillin in the presence of clavulanic acid at a constant 2 mcg/mL.

Interpretation is identical to that stated above for results using dilution techniques.

As with other susceptibility techniques, the use of laboratory control microorganisms is required to control the technical aspects of the laboratory standardized procedures. Standardized ticarcillin/clavulanate potassium powder should provide the following MIC values:

		Agar dilution	Broth microdilution
		MIC Range	MIC Range
Microorganism		(mcg/mL)║	(mcg/mL)║
Bacteroides thetaiotaomicron	ATCC 29741	0.5-2	0.5-2
Eubacterium lentum	ATCC 43055	16-64	8-32

║ Expressed as concentration of ticarcillin in the presence of clavulanic acid at a constant 2 mcg/mL.

Indications and Usage for Timentin Injection

TIMENTIN is indicated in the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions listed below:

Septicemia (including bacteremia) caused by β-lactamase–producing strains of Klebsiella spp.*, E. coli*, S. aureus*, or P. aeruginosa* (or other Pseudomonas species*)

Lower Respiratory Infections caused by β-lactamase–producing strains of S. aureus, H. influenzae*, or Klebsiella spp.*

Bone and Joint Infections caused by β-lactamase–producing strains of S. aureus

Skin and Skin Structure Infections caused by β-lactamase–producing strains of S. aureus, Klebsiella spp.*, or E. coli*

Urinary Tract Infections (complicated and uncomplicated) caused by β-lactamase–producing strains of E. coli, Klebsiella spp., P. aeruginosa* (or other Pseudomonas spp.*), Citrobacter spp.*, Enterobacter cloacae*, S. marcescens*, or S. aureus*

Gynecologic Infections endometritis caused by β-lactamase–producing strains of P. melaninogenicus*, Enterobacter spp. (including E. cloacae*), E. coli, K. pneumoniae*, S. aureus, or S. epidermidis

Intra-abdominal Infections peritonitis caused by β-lactamase–producing strains of E. coli, K. pneumoniae, or B. fragilis* group

*Efficacy for this organism in this organ system was studied in fewer than 10 infections.

NOTE: For information on use in pediatric patients (≥3 months of age) see PRECAUTIONS—Pediatric Use and CLINICAL STUDIES sections. There are insufficient data to support the use of TIMENTIN in pediatric patients under 3 months of age or for the treatment of septicemia and/or infections in the pediatric population where the suspected or proven pathogen is H. influenzae type b.

While TIMENTIN is indicated only for the conditions listed above, infections caused by ticarcillin-susceptible organisms are also amenable to treatment with TIMENTIN due to its ticarcillin content. Therefore, mixed infections caused by ticarcillin-susceptible organisms and β-lactamase–producing organisms susceptible to ticarcillin/clavulanic acid should not require the addition of another antibiotic.

Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing infection and to determine their susceptibility to ticarcillin/clavulanic acid. Because of its broad spectrum of bactericidal activity against gram-positive and gram-negative bacteria, TIMENTIN is particularly useful for the treatment of mixed infections and for presumptive therapy prior to the identification of the causative organisms. TIMENTIN has been shown to be effective as single drug therapy in the treatment of some serious infections where normally combination antibiotic therapy might be employed. Therapy with TIMENTIN may be initiated before results of such tests are known when there is reason to believe the infection may involve any of the β-lactamase–producing organisms listed above.

Based on the in vitro synergism between ticarcillin/clavulanic acid and aminoglycosides against certain strains of P. aeruginosa, combined therapy has been successful, especially in patients with impaired host defenses. Both drugs should be used in full therapeutic doses.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of TIMENTIN and other antibacterial drugs, TIMENTIN 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

TIMENTIN is contraindicated in patients with a history of hypersensitivity reactions to any of the penicillins.

Warnings

SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC) REACTIONS HAVE BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY. THESE REACTIONS ARE MORE LIKELY TO OCCUR IN INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY AND/OR A HISTORY OF SENSITIVITY TO MULTIPLE ALLERGENS. THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE REACTIONS WHEN TREATED WITH CEPHALOSPORINS. BEFORE INITIATING THERAPY WITH TIMENTIN, CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS, OR OTHER ALLERGENS. IF AN ALLERGIC REACTION OCCURS, TIMENTIN SHOULD BE DISCONTINUED AND THE APPROPRIATE THERAPY INSTITUTED. SERIOUS ANAPHYLACTIC REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE PROVIDED AS INDICATED.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including TIMENTIN, 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.

When very high doses of TIMENTIN are administered, especially in the presence of impaired renal function, patients may experience convulsions. (See ADVERSE REACTIONS and OVERDOSAGE.)

Precautions

General

While TIMENTIN possesses the characteristic low toxicity of the penicillin group of antibiotics, periodic assessment of organ system functions, including renal, hepatic, and hematopoietic function, is advisable during prolonged therapy.

Bleeding manifestations have occurred in some patients receiving β-lactam antibiotics. These reactions have been associated with abnormalities of coagulation tests such as clotting time, platelet aggregation, and prothrombin time and are more likely to occur in patients with renal impairment. If bleeding manifestations appear, treatment with TIMENTIN should be discontinued and appropriate therapy instituted.

TIMENTIN has only rarely been reported to cause hypokalemia; however, the possibility of this occurring should be kept in mind particularly when treating patients with fluid and electrolyte imbalance. Periodic monitoring of serum potassium may be advisable in patients receiving prolonged therapy.

The theoretical sodium content is 4.51 mEq (103.6 mg) per gram of TIMENTIN. This should be considered when treating patients requiring restricted salt intake.

As with any penicillin, an allergic reaction, including anaphylaxis, may occur during administration of TIMENTIN, particularly in a hypersensitive individual.

The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind, particularly during prolonged treatment. If superinfections occur, appropriate measures should be taken.

Prescribing TIMENTIN 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.

Information for Patients

Patients should be counseled that antibacterial drugs, including TIMENTIN, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When TIMENTIN 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 TIMENTIN 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 2 or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Drug/Laboratory Test Interactions

As with other penicillins, the mixing of TIMENTIN with an aminoglycoside in solutions for parenteral administration can result in substantial inactivation of the aminoglycoside.

Probenecid interferes with the renal tubular secretion of ticarcillin, thereby increasing serum concentrations and prolonging serum half-life of the antibiotic.

In common with other antibiotics, ticarcillin disodium/clavulanate potassium may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.

High urine concentrations of ticarcillin may produce false-positive protein reactions (pseudoproteinuria) with the following methods: Sulfosalicylic acid and boiling test, acetic acid test, biuret reaction, and nitric acid test. The bromphenol blue (MULTI-STIX®) reagent strip test has been reported to be reliable.

The presence of clavulanic acid in TIMENTIN may cause a nonspecific binding of IgG and albumin by red cell membranes leading to a false-positive Coombs test.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate carcinogenic potential. However, results from assays for gene mutation in vitro using bacteria (Ames tests) and yeast, and for chromosomal effects in vitro in human lymphocytes, and in vivo in mouse bone marrow (micronucleus test) indicate that TIMENTIN is without any mutagenic potential.

Pregnancy (Category B)

Reproduction studies have been performed in rats given doses up to 1,050 mg/kg/day and have revealed no evidence of impaired fertility or harm to the fetus due to TIMENTIN. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when TIMENTIN is administered to a nursing woman.

Pediatric Use

The safety and effectiveness of TIMENTIN have been established in the age group of 3 months to 16 years. Use of TIMENTIN in these age groups is supported by evidence from adequate and well-controlled studies of TIMENTIN in adults with additional efficacy, safety, and pharmacokinetic data from both comparative and non-comparative studies in pediatric patients. There are insufficient data to support the use of TIMENTIN in pediatric patients under 3 months of age or for the treatment of septicemia and/or infections in the pediatric population where the suspected or proven pathogen is H. influenzae type b.

In those patients in whom meningeal seeding from a distant infection site or in whom meningitis is suspected or documented, or in patients who require prophylaxis against central nervous system infection, an alternate agent with demonstrated clinical efficacy in this setting should be used.

Geriatric Use

 An analysis of clinical studies of TIMENTIN was conducted to determine whether subjects aged 65 and over respond differently from younger subjects. Of the 1,078 subjects treated with at least one dose of TIMENTIN, 67.5% were <65 years old, and 32.5% were ≥65 years old.  No overall differences in safety or efficacy were observed between these subjects and younger subjects, and other reported clinical experience have not identified differences in responses between the elderly and younger patients, but a greater sensitivity of some older individuals cannot be ruled out.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see DOSAGE and ADMINISTRATION). 

TIMENTIN contains 103.6 mg (4.51 mEq) of sodium per gram of TIMENTIN. At the usual recommended doses, patients would receive between 1,285 and 1,927 mg/day (56 and 84 mEq) of sodium. The geriatric population may respond with a blunted natriuresis to salt loading. This may be clinically important with regard to such diseases as congestive heart failure.

Adverse Reactions

As with other penicillins, the following adverse reactions may occur:

Hypersensitivity Reactions

Skin rash, pruritus, urticaria, arthralgia, myalgia, drug fever, chills, chest discomfort, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, and anaphylactic reactions.

Central Nervous System

Headache, giddiness, neuromuscular hyperirritability, or convulsive seizures.

Gastrointestinal D

Trihist-D

Generic Name: pheniramine/ pyrilamine/ phenyltoloxamine/ phenylpropanolamine (fen IR a meen/pie RILL a meen/fen ill toe LOX a meen/fen ill proe pa NOLE a meen)

Brand Names: Delhist D, Delhistine D, Histine-D, Iohist D, KG-Hist D, Liqui-Histine-D, Metahistine D, Multihist D, Multihistamine-D, Poly-D, Poly-Histine-D, Prohistine-D, Trihist-D

What is Trihist-D (pheniramine/ pyrilamine/ phenyltoloxamine/ phenylpropanolamine)?

Pheniramine, pyrilamine, and phenyltoloxamine are antihistamines. They block the effects of the naturally occurring chemical histamine in the body. Pheniramine, pyrilamine, and phenyltoloxamine prevent sneezing; itchy, watery eyes and nose; and other symptoms of allergies and hay fever.

Phenylpropanolamine is a decongestant. It constricts (shrinks) blood vessels (veins and arteries). This reduces the blood flow to certain areas and allows nasal and respiratory (breathing) passages to open up.

Pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine is used to treat nasal congestion and sinusitis (inflammation of the sinuses) associated with allergies, hay fever, and the common cold.

Phenylpropanolamine, an ingredient in this product, has been associated with an increased risk of hemorrhagic stroke (bleeding into the brain or into tissue surrounding the brain) in women. Men may also be at risk. Although the risk of hemorrhagic stroke is low, the U.S. Food and Drug Administration (FDA) recommends that consumers not use any products that contain phenylpropanolamine.

Pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about Trihist-D (pheniramine/ pyrilamine/ phenyltoloxamine/ phenylpropanolamine)?

Phenylpropanolamine, an ingredient in this product, has been associated with an increased risk of hemorrhagic stroke (bleeding into the brain or into tissue surrounding the brain) in women. Men may also be at risk. Although the risk of hemorrhagic stroke is low, the U.S. Food and Drug Administration (FDA) recommends that consumers not use any products that contain phenylpropanolamine.

Use caution when driving, operating machinery, or performing other hazardous activities. Pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine may cause dizziness or drowsiness. If you experience dizziness or drowsiness, avoid these activities. Use alcohol cautiously. Alcohol may increase drowsiness and dizziness while taking this medication.

Do not take more of this medication than is recommended. If your symptoms do not improve, or if they worsen, talk to your doctor.

Who should not take Trihist-D (pheniramine/ pyrilamine/ phenyltoloxamine/ phenylpropanolamine)?

Do not take pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine if you have taken a monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), phenelzine (Nardil), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects.

Before taking this medication, tell your doctor if you have

• kidney disease,


• liver disease,


• 
  

  diabetes,

  
  


• 
  

  glaucoma,

  
  


• 
  

  any type of heart disease or high blood pressure,

  
  


• 
  

  thyroid disease,

  
  


• 
  

  emphysema or chronic bronchitis, or

  
  


• 
  

  difficulty urinating or an enlarged prostate.

  
  

You may not be able to take pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine, or you may require a dosage adjustment or special monitoring during treatment if you have any of the conditions listed above.

Pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine is in the FDA pregnancy category B. This means that it is unlikely to harm an unborn baby. Do not take this medication without first talking to your doctor if you are pregnant. Pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine passes into breast milk and may harm a nursing infant. Do not take this medication without first talking to your doctor if you are breast-feeding a baby. If you are over 65 years of age, you may be more likely to experience side effects from pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine. You may require a lower dose of this medication. Read the package label for directions or consult your doctor or pharmacist before treating a child with this medication. Children are more susceptible than adults to the effects of medicines and may have unusual reactions.

How should I take Trihist-D (pheniramine/ pyrilamine/ phenyltoloxamine/ phenylpropanolamine)?

Take pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine exactly as directed. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.

Take each dose with a full glass of water. Do not crush, chew, or break the long-acting or sustained-release forms of this medication. Swallow them whole. If you are unsure about the formulation of the medicine, ask your pharmacist for help.

If you cannot swallow the tablets or capsules, look for a liquid form of this medication.

To ensure that you get a correct dose, measure the liquid form of pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine with a special dose-measuring spoon or cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist where you can get one.

Do not take more of this medication than is recommended. An overdose can cause serious harm.

Do not take pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine for longer than 7 days in a row. If your symptoms do not improve, if they get worse, or if you have a fever, talk to your doctor.

Store pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the missed dose as soon as you remember. However, if it is almost time for the next dose, skip the missed dose and take only the next regularly scheduled dose. Do not take a double dose of this medication.

What happens if I overdose?

Seek emergency medical attention.

Symptoms of a pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine overdose include a dry mouth, large pupils, flushing, nausea, and vomiting.

What should I avoid while taking Trihist-D (pheniramine/ pyrilamine/ phenyltoloxamine/ phenylpropanolamine)?

Use caution when driving, operating machinery, or performing other hazardous activities. Pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine may cause dizziness or drowsiness. If you experience dizziness or drowsiness, avoid these activities. Use alcohol cautiously. Alcohol may increase drowsiness and dizziness while taking pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine.

Trihist-D (pheniramine/ pyrilamine/ phenyltoloxamine/ phenylpropanolamine) side effects

Serious side effects are unlikely to occur. Stop taking pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine and seek emergency medical attention if you experience an allergic reaction (difficulty breathing; closing of your throat; swelling of your lips, tongue, or face; or hives).

Other, less serious side effects may be more likely to occur. Continue to take pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine and talk to your doctor or try another similar medication if you experience

• 
  

  dryness of the eyes, nose, and mouth;

  
  


• 
  

  drowsiness or dizziness;

  
  


• 
  

  blurred vision;

  
  


• 
  

  difficulty urinating; or

  
  


• 
  

  excitation in children.

  
  

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.

What other drugs will affect Trihist-D (pheniramine/ pyrilamine/ phenyltoloxamine/ phenylpropanolamine)?

Do not take pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine if you have taken a monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), phenelzine (Nardil), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects.

Do not take other over-the-counter cough, cold, allergy, diet, or sleep aids while taking pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine without first talking to your doctor or pharmacist. Other medications may also contain pheniramine, pyrilamine, phenyltoloxamine, phenylpropanolamine, or other similar drugs. You may accidentally take too much of these medicines.

Pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine may increase the effects of other drugs that cause drowsiness, including antidepressants, alcohol, other antihistamines, pain relievers, anxiety medicines, seizure medicines, and muscle relaxants. Dangerous sedation, dizziness, or drowsiness may occur if pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine is taken with any of these medications.

Drugs other than those listed here may also interact with pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including herbal products.

More Trihist-D resources

• Trihist-D Drug Interactions
• Trihist-D Support Group
• 0 Reviews for Trihist-D - Add your own review/rating

Compare Trihist-D with other medications

• Allergies
• Eye Dryness/Redness
• Eye Redness/Itching
• Hay Fever
• Nasal Congestion
• Rhinorrhea
• Sinusitis
• Upper Respiratory Tract Infection

Where can I get more information?

• Your pharmacist has additional information about pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine written for health professionals that you may read.

What does my medication look like?

Pheniramine/pyrilamine/phenyltoloxamine/phenylpropanolamine is available with a prescription under the brand names Poly-Histine-D (capsules and elixir) and Liqui-Histine Elixir. Other brand or generic formulations may also be available. Ask your pharmacist any questions you have about this medication, especially if it is new to you.

Kaopectate

Generic Name: bismuth subsalicylate (BIZ muth sub sa LISS i late)

Brand Names: Bismarex, Bismatrol, Bismatrol Maximum Strength, Kao-Tin Bismuth Subsalicylate Formula, Kaopectate, Maalox Total Stomach Relief, Peptic Relief, Pepto-Bismol, Pepto-Bismol Maximum Strength, Pink Bismuth

What is Kaopectate (bismuth subsalicylate)?

Bismuth subsalicylate is an antacid and anti-diarrhea medication.

Bismuth subsalicylate is used to treat diarrhea, nausea, heartburn, indigestion, and upset stomach.

Bismuth subsalicylate may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Kaopectate (bismuth subsalicylate)?

This medication should not be given to a child or teenager who has a fever, especially if the child also has flu symptoms or chicken pox. Salicylates can cause a serious and sometimes fatal condition called Reye's syndrome in children. You should not use bismuth subsalicylate if you have a stomach ulcer, a recent history of stomach or intestinal bleeding, or if you are allergic to salicylates such as aspirin, Doan's Extra Strength, Salflex, Tricosal, and others.

Do not take more than 8 doses in one day (24 hours).

Bismuth subsalicylate can cause you to have a black or darkened tongue. This is a harmless side effect.

This medication can also cause unusual results with certain medical tests, thyroid scans, or stomach x-rays. Tell any doctor who treats you that you have recently taken bismuth subsalicylate.

What should I discuss with my health care provider before taking Kaopectate (bismuth subsalicylate)?

This medication should not be given to a child or teenager who has a fever, especially if the child also has flu symptoms or chicken pox. Subsalicylate can cause a serious and sometimes fatal condition called Reye's syndrome in children. You should not use bismuth subsalicylate if you are allergic to it, or if you have:

• 
  

  a stomach ulcer;

  
  


• 
  

  a recent history of stomach or intestinal bleeding; or

  
  


• 
  

  if you are allergic to salicylates such as aspirin, Doan's Extra Strength, Salflex, Tricosal, and others.

  
  

Ask a doctor or pharmacist if it is safe for you to take this medicine if you have:

• 
  

  fever;

  
  


• 
  

  mucus in your stools;

  
  


• 
  

  diabetes;

  
  


• 
  

  arthritis; or

  
  


• 
  

  gout.

  
  

Do not take bismuth subsalicylate without medical advice if you are pregnant. Bismuth subsalicylate can pass into breast milk and may harm a nursing baby. Do not use this medication without medical advice if you are breast-feeding a baby.

How should I take Kaopectate (bismuth subsalicylate)?

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended.

Do not take more than 8 doses in one day (24 hours). Shake the liquid medicine well just before you measure a dose. Measure the liquid with a special dose-measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

The chewable tablet must be chewed before you swallow it.

Bismuth subsalicylate can cause you to have a black or darkened tongue. This is a harmless side effect.

This medication can also cause unusual results with certain medical tests, thyroid scans, or stomach x-rays. Tell any doctor who treats you that you have recently taken bismuth subsalicylate.

Store at room temperature away from moisture and heat. Do not freeze.

What happens if I miss a dose?

Since bismuth subsalicylate is taken as needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose. Do not take more than 8 doses in one day (24 hours).

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include increased thirst, anxiety, muscle spasm, ringing in your ears, dizziness, confusion, severe headache, problems with speech or vision, severe stomach pain, or worsening diarrhea or vomiting.

What should I avoid while taking Kaopectate (bismuth subsalicylate)?

Ask your doctor or pharmacist before taking other antacids or diarrhea medications together with bismuth subsalicylate.

Kaopectate (bismuth subsalicylate) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop taking this medicine and call your doctor at once if you have a serious side effect such as:

• 
  

  hearing loss or ringing in your ears;

  
  


• 
  

  diarrhea lasting longer than 2 days; or

  
  


• 
  

  worsened stomach symptoms.

  
  

Less serious side effects include:

• 
  

  constipation;

  
  


• 
  

  dark colored stools; or

  
  


• 
  

  black or darkened tongue.

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Kaopectate (bismuth subsalicylate)?

Ask a doctor or pharmacist if it is safe for you to use bismuth subsalicylate if you are also using any of the following drugs:

• 
  

  a blood thinner such as warfarin (Coumadin, Jantoven);

  
  


• 
  

  insulin or oral diabetes medications;

  
  


• 
  

  probenecid (Benemid);

  
  


• 
  

  an antibiotic such as doxycycline (Doryx, Oracea, Periostat, Vibramycin), minocycline (Dynacin, Minocin, Solodyn), or tetracycline (Ala-Tet, Brodspec, Panmycin, Sumycin, Tetracap);

  
  


• 
  

  medication used to prevent blood clots, such as alteplase (Activase), tenecteplase (TNKase), urokinase (Abbokinase); or

  
  


• 
  

  other salicylates such as aspirin, Nuprin Backache Caplet, Kaopectate, KneeRelief, Pamprin Cramp Formula, Pepto-Bismol, Tricosal, Trilisate, and others.

  
  

This list is not complete and other drugs may interact with bismuth subsalicylate. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Kaopectate resources

• Kaopectate Side Effects (in more detail)
• Kaopectate Use in Pregnancy & Breastfeeding
• Kaopectate Drug Interactions
• Kaopectate Support Group
• 0 Reviews for Kaopectate - Add your own review/rating

• Kaopectate Advanced Consumer (Micromedex) - Includes Dosage Information


• Kaopectate MedFacts Consumer Leaflet (Wolters Kluwer)


• Bismuth Subsalicylate Professional Patient Advice (Wolters Kluwer)


• Bismatrol Chewable Tablets MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Kaopectate with other medications

• Diarrhea
• Diarrhea, Chronic
• Helicobacter Pylori Infection
• Indigestion
• Lymphocytic Colitis

Where can I get more information?

• Your pharmacist can provide more information about bismuth subsalicylate.

See also: Kaopectate side effects (in more detail)

Sodium Sulfacetamide and Sulfur Aqueous Gel

Dosage Form: gel
10% Sodium Sulfacetamide and Sulfur 5% Aqueous Gel (in a Urea vehicle)

Rx only

DESCRIPTION:  Sodium sulfacetamide is a sulfonamide with antibacterial activity.  Sulfur acts as a keratolytic agent.  Chemically, sodium sulfacetamide is N-[(4-aminophenyl)sulfonyl]-acetamide, monosodium salt, monohydrate. The structural formula is:

Each mL of 10% Sodium Sulfacetamide 5% Sulfur Aqueous Gel (in a Urea vehicle) contains 100 mg of sodium sulfacetamide and 50 mg of sulfur in an emulsion base containing 10% Urea, propylene glycol, isopropyl myristate, mineral oil, polysorbate 60, sorbitan monostearate, cetyl alcohol, cocoglycerides, stearyl alcohol, benzyl alcohol, glyceryl stearate and PEG 100 stearate, dimethicone, fragrance, disodium EDTA, xanthan gum, zinc pyrithione, sodium thiosulfate, purified water, magnesium aluminum silicate, and methyl paraben.

CLINICAL PHARMACOLOGY:  The most widely accepted mechanism of action of sulfonamides is the Woods-Fildes theory, which is based on the fact that sulfonamides act as competitive antagonists to para-aminobenzoic acid (PABA), an essential component for bacterial growth.  While absorption through intact skin has not been determined, sodium sulfacetamide is readily absorbed from the gastrointestinal tract when taken orally and excreted in the urine, largely unchanged.  The biological half-life has variously been reported as 7 to 12.8 hours.  The exact mode of action of sulfur in the treatment of acne is unknown, but it has been reported that it inhibits the growth of Propionibacterium acnes and the formation of free fatty acids.

INDICATIONS: 10% Sodium Sulfacetamide 5% Sulfur Aqueous Gel (in a Urea vehicle) is indicated in the topical control of acne vulgaris, acne rosacea and seborrheic dermatitis.

CONTRAINDICATIONS: 10% Sodium Sulfacetamide 5% Sulfur Aqueous Gel (in a Urea vehicle) is contraindicated for patients having known hypersensitivity to sulfonamides, sulfur or any other component of this preparation.  10% Sodium Sulfacetamide 5% Sulfur Aqueous Gel (in a Urea vehicle) is not to be used in patients with kidney disease.

WARNINGS: Rarely, sensitivity to sodium sulfacetamide may occur. Therefore, caution and careful supervision should be observed when prescribing this drug tor patients who may be prone to hypersensitivity to topical sulfonamides. Systemic toxic reactions such as agranulocytosis, acute hemolytic anemia, purpura hemorrhagica, drug fever, jaundice, and contact dermatitis indicate hypersensitivity to sulfonamides. Use particular caution on areas of denuded or abraded skin.

FOR EXTERNAL USE ONLY. Keep away from eyes.

Keep out of reach of children. Keep tube tightly closed.

PRECAUTIONS: General - If irritation develops, use of the product should be discontinued and appropriate therapy instituted.  Patients should be carefully observed for possible local irritation or sensitization during long-term therapy.  The object of this therapy is to achieve desquamation without irritation, but sodium sulfacetamide and sulfur can cause reddening  and scaling of the epidermis.  These side effects are not unusual in the treatment of acne vulgaris, but patients should be cautioned about the possibility.

Information for Patients - Avoid contact with eyes, eyelids, lips and mucous membranes. If accidental contact occurs, rinse with water. If excessive irritation develops, discontinue use and consult your physician.

Carcinogenesis, Mutagenesis and Impairment of Fertility - Long-term studies in animals have not been performed to evaluate carcinogenic potential.

Pregnancy - Category C. Animal reproduction studies have not been conducted with 10% Sodium Sulfacetamide 5% Sulfur Aqueous Gel (in a Urea vehicle). It is also not known whether 10% Sodium Sulfacetamide 5% Sulfur Aqueous Gel (in a Urea vehicle) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. 10% Sodium Sulfacetamide 5% Sulfur Aqueous Gel (in a Urea vehicle) should be given to a pregnant woman only if clearly needed.

Nursing Mothers - It is not known whether sodium sulfacetamide is excreted in human milk following topical use of 10% Sodium Sulfacetamide 5% Sulfur Aqueous Gel (in a Urea vehicle). However, small amounts of orally administered sulfonamides have been reported to be excreted in human milk. For this reason, and because many drugs are excreted in human milk, caution should be exercised when 10% Sodium Sulfacetamide 5% Sulfur Aqueous Gel (in a Urea vehicle) is administered to a nursing woman.

Pediatric Use: Safety and effectiveness in children under the age of 12 years have not been established.

ADVERSE REACTIONS: Rarely, sodium sulfacetamide may cause local irritation.

Call your physician for medical advice about side effects.

DOSAGE AND ADMINISTRATION:

10% Sodium Sulfacetamide 5% Sulfur Aqueous Gel (in a Urea vehicle): Cleanse affected areas. Apply a thin film into affected areas 1 to 3 times daily, or as directed by a physician.

HOW SUPPLIED:

10% Sodium Sulfacetamide 5% Sulfur Aqueous Gel (in a Urea vehicle): is available in a 1.5 fl. oz (45 g) tube, NDC 42808-0111-45

Store 10% Sodium Sulfacetamide 5% Sulfur Aqueous Gel (in a Urea vehicle): at 15 to 30°C (59 to 86°F).

Protect from freezing.

Manufactured in the U.S.A. for Exact-Rx, Inc., Melville, NY 11747

00-0111-45-205-00

Iss:6/11

PACKAGE LABEL - 1.5 oz (45 g)

For External Use Only

NDC 42808-0111-45        Rx Only

Sodium

Sulfacetamide

& Sulfur

(Sodium Sulfacetamide 10%

& Sulfur 5% in a Urea Vehicle)

10%/5%

AQUEOUS GEL

Exact-Rx.

INCORPORATED

Net Wt. 1.5 oz (45 g)

SODIUM SULFACETAMIDE, SULFUR   sodium sulfacetamide, sulfur  gel

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 42808-111 Route of Administration TOPICAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength SULFACETAMIDE SODIUM (SULFACETAMIDE) SULFACETAMIDE SODIUM 100 mg  in 1 g SULFUR (SULFUR) SULFUR 50 mg  in 1 g

Inactive Ingredients Ingredient Name Strength UREA   PROPYLENE GLYCOL   ISOPROPYL MYRISTATE   MINERAL OIL   POLYSORBATE 60   SORBITAN MONOSTEARATE   CETYL ALCOHOL   COCO-GLYCERIDES   STEARYL ALCOHOL   BENZYL ALCOHOL   GLYCERYL MONOSTEARATE   POLYOXYL 100 STEARATE   DIMETHICONE   EDETATE DISODIUM   XANTHAN GUM   PYRITHIONE ZINC   SODIUM THIOSULFATE   WATER   MAGNESIUM ALUMINUM SILICATE   METHYLPARABEN

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 42808-111-45 1 TUBE In 1 CARTON contains a TUBE 1 45 g In 1 TUBE This package is contained within the CARTON (42808-111-45)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
unapproved drug other		08/01/2011

Labeler - Exact-Rx, Inc. (137953498)

Revised: 08/2011Exact-Rx, Inc.

More Sodium Sulfacetamide and Sulfur Aqueous Gel resources

• Sodium Sulfacetamide and Sulfur Aqueous Gel Side Effects (in more detail)
• Sodium Sulfacetamide and Sulfur Aqueous Gel Use in Pregnancy & Breastfeeding
• Sodium Sulfacetamide and Sulfur Aqueous Gel Drug Interactions
• Sodium Sulfacetamide and Sulfur Aqueous Gel Support Group
• 18 Reviews for Sodium Sulfacetamide and Sulfur Aqueous - Add your own review/rating

Compare Sodium Sulfacetamide and Sulfur Aqueous Gel with other medications

• Acne
• Rosacea
• Seborrheic Dermatitis

Tri-Vi-Flor with Iron

Generic Name: multivitamin with iron and fluoride (MUL tee VYE ta min with EYE urn and FLOOR ide)

Brand Names: MyKidz Iron FL, PhluoriVit with Iron, Poly Vitamin with Fluoride with Iron, Poly-Vi-Flor with Iron, Tri Vites with Fluoride and Iron, Tri-Vi-Flor with Iron

What is Tri-Vi-Flor with Iron (multivitamin with iron and fluoride)?

Multivitamins provide essential vitamins and minerals that are not taken in to the body through diet.

Iron is a mineral that helps maintain your body's red blood cells.

Fluoride strengthens tooth enamel, which helps prevent dental cavities. In most major U.S. communities, fluoride is put into the water supply.

Multivitamin with iron and fluoride is used as a supplement to the diet of infants and children who do not receive adequate fluoride through drinking water. Multivitamin with iron and fluoride is also used to prevent tooth decay in people treated with radiation, which may cause dryness of the mouth and increased risk of tooth decay.

Multivitamin with iron and fluoride may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Tri-Vi-Flor with Iron (multivitamin with iron and fluoride)?

Taking in too much fluoride can cause an irreversible condition called fluorosis. This condition can permanently damage teeth and possibly other cells in the body.

Do not use this medicine without the advice of a doctor. Multivitamin with iron and fluoride should not be used if the level of fluoride in the drinking water is adequate (0.6 parts per million or higher).Check with your local water department if you are unsure about the level of fluoride in the drinking water.

Be sure that a child using this medicine is not taking in extra amounts of fluoride by swallowing toothpaste, or drinking water from sources that contain adequate levels of fluoride.

Do not take this medication with milk, other dairy products, calcium supplements, or antacids that contain calcium. Calcium may cause your body to absorb less of the multivitamin with iron and fluoride. Avoid taking any other multivitamin product within 2 hours before or after you take multivitamin with iron and fluoride. Taking similar vitamin products together at the same time can result in a vitamin overdose or serious side effects.

What should I discuss with my healthcare provider before taking Tri-Vi-Flor with Iron (multivitamin with iron and fluoride)?

Taking in too much fluoride can cause an irreversible condition called fluorosis. This condition can permanently damage teeth and possibly other cells in the body.

Do not use this medicine without the advice of a doctor. Multivitamin with iron and fluoride should not be used if the level of fluoride in the drinking water is adequate (0.6 parts per million or higher). Check with your local water department if you are unsure about the level of fluoride in the drinking water. FDA pregnancy category C. It is not known whether this medication is harmful to an unborn baby. Before using multivitamin with iron and fluoride, tell your doctor if you are pregnant or plan to become pregnant during treatment. Multivitamin with iron and fluoride can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take Tri-Vi-Flor with Iron (multivitamin with iron and fluoride)?

Use this medication exactly as it was prescribed for you. Do not use the medication in larger amounts, or use it for longer than recommended by your doctor.

Take each dose of this medicine with a full glass of water.

The chewable tablet must be chewed or allowed to dissolve in the mouth before swallowing it. You may also allow the tablet to dissolve in drinking water, fruit juice, or infant formula (but not milk or other dairy products).

Do not give a chewable tablet to a child younger than 4 years old. The child may choke on the tablet. Use only liquid forms of this medicine in young children.

Measure the liquid form of multivitamin with iron and fluoride using a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist where you can get one.

The liquid may also be mixed with water, fruit juice, or infant formula.

It is important to take multivitamin with iron and fluoride regularly to get the most benefit.

Brush teeth regularly, at least two times each day, or after meals. This will help prevent tooth discoloration.

Store this medication at room temperature away from moisture and heat. Do not allow the liquid to freeze.

Keep multivitamin with iron and fluoride in the original contain it came in. Storing multivitamin with iron and fluoride in a glass container can ruin the medication.

What happens if I miss a dose?

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine. An overdose of this medicine can be fatal.

Overdose symptoms may include nausea, vomiting, stomach pain, diarrhea, drowsiness, fast heart rate, fainting, and seizure (convulsions).

What should I avoid while taking Tri-Vi-Flor with Iron (multivitamin with iron and fluoride)?

Avoid using other multivitamins or mineral supplements that also contain iron. Getting too much iron can cause serious medical problems or death.

Avoid taking any other multivitamin product within 2 hours before or after you take multivitamin with iron and fluoride. Taking similar vitamin products together at the same time can result in a vitamin overdose or serious side effects.

Be sure that a child using this medicine is not taking in extra amounts of fluoride by swallowing toothpaste, or drinking water from sources that contain adequate levels of fluoride.

Do not take this medication with milk, other dairy products, calcium supplements, or antacids that contain calcium. Calcium may cause your body to absorb less of the multivitamin with iron and fluoride.

Tri-Vi-Flor with Iron (multivitamin with iron and fluoride) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

This medication may cause the tooth enamel to become discolored. This is a rare side effect that has occurred mainly with large doses or long-term use of multivitamin with iron and fluoride. Stop using this medication and call your dentist or doctor at once if you notice any change in the appearance of your teeth.

Less serious side effects may include:

• 
  

  stomach upset;

  
  


• 
  

  headache; or

  
  


• 
  

  weakness.

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Tri-Vi-Flor with Iron (multivitamin with iron and fluoride)?

There may be other drugs that can interact with multivitamin with iron and fluoride. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More Tri-Vi-Flor with Iron resources

• Tri-Vi-Flor with Iron Use in Pregnancy & Breastfeeding
• Tri-Vi-Flor with Iron Drug Interactions
• Tri-Vi-Flor with Iron Support Group
• 0 Reviews for Tri-Vi-Flor with Iron - Add your own review/rating

• Multivitamin with Iron and Fluoride Drops MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Tri-Vi-Flor with Iron with other medications

• Dietary Supplementation

Where can I get more information?

• Your pharmacist can provide more information about multivitamin with iron and fluoride.

Trobicin

spectinomycin

Dosage Form: injectable suspension

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

For intramuscular Injection

Trobicin Description

Trobicin Sterile Powder contains spectinomycin hydrochloride which is an aminocyclitol antibiotic produced by a species of soil microorganism designated as Streptomyces spectabilis. Sterile spectinomycin hydrochloride is the pentahydrated dihydrochloride salt of spectinomycin. The structural formula is represented below:

Spectinomycin hydrochloride is isolated as a white to pale buff crystalline dihydrochloride pentahydrate powder, molecular weight 495, and is stable in the dry state for 36 months.

Trobicin - Clinical Pharmacology

Trobicin Sterile Powder is rapidly absorbed after intramuscular injection. A single, two-gram injection produces peak serum concentrations averaging about 100 mcg/mL at one hour; a single, four-gram injection produces peak serum concentrations averaging 160 mcg/mL at two hours. Average serum concentrations of 15 mcg/mL for the two-gram dose and 31 mcg/mL for the four-gram dose were present eight hours after dosing.

Microbiology

Spectinomycin hydrochloride is an inhibitor of protein synthesis in the bacterial cell; the site of action is the 30S ribosomal subunit.

In vitro studies have shown spectinomycin hydrochloride to be active against most strains of Neisseria gonorrhoeae (minimum inhibitory concentration <7.5 to 20 mcg/mL).

Definitive in vitro studies have shown no cross-resistance of N. gonorrhoeae between spectinomycin hydrochloride and penicillin. The antibiotic is not significantly bound to plasma protein.

Indications and Usage for Trobicin

Trobicin Sterile Powder is indicated in the treatment of acute gonorrheal urethritis and proctitis in the male and acute gonorrheal cervicitis and proctitis in the female when due to susceptible strains of Neisseria gonorrhoeae. Men and women with known recent exposure to gonorrhea should be treated as those known to have gonorrhea.

The in vitro susceptibility of Neisseria gonorrhoeae to spectinomycin hydrochloride can be tested by agar diluted methods. Trobicin Susceptibility Powder is available for this purpose and its package insert should be consulted for details.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Trobicin Sterile Powder and other antibacterial drugs, Trobicin Sterile Powder 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

The use of Trobicin Sterile Powder is contraindicated in patients previously found hypersensitive to it.

Warnings

Spectinomycin hydrochloride is not effective in the treatment of syphilis. Antibiotics used in high doses for short periods of time to treat gonorrhea may mask or delay the symptoms of incubating syphilis. Since the treatment of syphilis demands prolonged therapy with any effective antibiotic, patients being treated for gonorrhea should be closely observed clinically. All patients with gonorrhea should have a serologic test for syphilis at the time of diagnosis. Patients treated with spectinomycin hydrochloride should have a follow-up serologic test for syphilis after three months.

Contains benzyl alcohol. Benzyl alcohol has been reported to be associated with a fatal "Gasping Syndrome" in premature infants and an increased incidence of neurologic and other complications.

Precautions

The usual precautions should be observed with atopic individuals.

The clinical effectiveness of Trobicin Sterile Powder should be monitored to detect evidence of development of resistance by Neisseria gonorrhoeae.

Prescribing Trobicin Sterile Powder 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.

Information for Patients

Patients should be counseled that antibacterial drugs including Trobicin Sterile Powder should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Trobicin Sterile Powder 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 Trobicin Sterile Powder or other antibacterial drugs in the future.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Genotoxicity of spectinomycin hydrochloride was evaluated in six assay test systems including two Ames tests, two micronucleus tests in mice, unscheduled DNA synthesis in rat primary hepatocytes, and a chromosomal aberration test in Chinese hamster ovary cells. Spectinomycin was not shown to be mutagenic or genotoxic in these tests.

No adverse effects on fertility or general reproductive performance were observed when spectinomycin was administered subcutaneously to rats at dose levels up to 300 mg/kg (equivalent to the recommended maximum human dose based on mg/m2). A three-generation reproduction study in rats administered spectinomycin hydrochloride orally at dose levels up to 400 mg/kg (equivalent to the recommended maximum human dose based on mg/m2) produced no evidence of drug-induced toxicity during growth, gestation, or lactation periods of any parental generation. Pregnancy rates of the 400 mg/kg/day groups were consistently lower than those of the control groups. A histopathological examination of the testes and ovaries of the third generation animals was normal.

Pregnancy

Teratogenic Effects

Pregnancy Category B

Spectinomycin was not teratogenic or embryocidal when orally or subcutaneously administered to rats at doses of 300 mg/kg/day (equivalent to the recommended maximum human dose based on mg/m2). No teratogenic effects were observed when spectinomycin was administered intraperitoneally to mice or rats at dose levels of 400 or 1600 mg/kg/day, respectively. Spectinomycin was administered intramuscularly or subcutaneously to pregnant rabbits at dose levels up to 300 mg/kg/day (equivalent to the recommended maximum human dose based on mg/m2). Embryonic and fetal development were unaffected by treatment. Since there are no controlled studies of spectinomycin in pregnant women, and because animal reproduction studies are not always predictive of human responses, spectinomycin should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when spectinomycin is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in the pediatric population have not been established. (See WARNINGS.)

Adverse Reactions

The following reactions were observed during the single dose clinical trials: soreness at the injection site, urticaria, dizziness, nausea, chills, fever and insomnia.

During multiple dose subchronic tolerance studies in normal human volunteers, the following were noted: a decrease in hemoglobin, hematocrit and creatinine clearance; elevation of alkaline phosphatase, BUN and SGPT. In single and multiple dose studies in normal volunteers, a reduction in urine output was noted. Extensive renal function studies demonstrated no consistent changes indicative of renal toxicity.

A few cases of anaphylaxis or anaphylactoid reactions have been reported. If serious allergic reactions occur, the usual agents (epinephrine, corticosteroids, and/or antihistamines) should be available for emergency use. In cases of severe anaphylaxis, airway support and oxygen may also be required.

Overdosage

Information on overdosage in humans is not available. Hemodialysis has been reported to aid in the removal of intravenously administered spectinomycin from the body.

Kusumi R, Metzler C, Fass R; Pharmacokinetics of Spectinomycin in Volunteers with Renal Insufficiency, Chemotherapy, 27:95–98 (1981).

Trobicin Dosage and Administration

Preparation of Drug for Intramuscular Injection

Trobicin Sterile Powder, 2 grams: reconstitute with 3.2 mL of the accompanying diluent.1

Shake vials vigorously immediately after adding diluent and before withdrawing dose. It is recommended that disposable syringes and needles be used to avoid contamination with penicillin residue, especially when treating patients known to be highly sensitive to penicillin. Use of a 20-gauge needle is recommended.

1

Bacteriostatic Water for Injection with Benzyl Alcohol 0.945% w/v added as preservative.

Dosage

Intramuscular injections should be made deep into the upper outer quadrant of the gluteal muscle.

Adults (Men and Women)—Inject 5 mL intramuscularly for a 2-gram dose. This is also the recommended dose for patients being treated after failure of previous antibiotic therapy.

In geographic areas where antibiotic resistance is known to be prevalent, initial treatment with 4 grams (10 mL) intramuscularly is preferred. The 10-mL injection may be divided between two gluteal injection sites.

STORAGE CONDITIONS

Store unreconstituted product at controlled room temperature 20° to 25°C (68° to 77°F) [see USP]. Store prepared suspension at controlled room temperature 20° to 25°C (68° to 77°F) and use within 24 hours.

How is Trobicin Supplied

Contains benzyl alcohol. (See WARNINGS.)

Trobicin Sterile Powder is available as:

Trobicin Sterile Powder, 2-gram vial NDC 0009-0566-01—with one ampoule of Bacteriostatic Water for Injection with Benzyl Alcohol 0.945% w/v added as preservative. When reconstituted with 3.2 mL of the accompanying diluent, each vial yields a sufficient quantity for withdrawal of 5 mL of a suspension containing 400 mg spectinomycin per mL (as the hydrochloride). Five mL provides 2 grams spectinomycin. For intramuscular use only.

Trobicin Susceptibility Powder—100 mg. See package insert for in vitro testing procedure.

Rx only

LAB-0230-3.0

Revised August 2006

Trobicin  spectinomycin  kit

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0009-0566

Packaging # NDC Package Description Multilevel Packaging 1 0009-0566-01 1 KIT In 1 PACKAGE, COMBINATION None

QUANTITY OF PARTS Part # Package Quantity Total Product Quantity Part 1 1 VIAL   5 MILLILITER  in 1  Part 2 1 AMPULE   3.2 MILLILITER  in 1

Part 1 of 2 Trobicin  spectinomycin hydrochloride  injection, powder, for suspension

Product Information       Route of Administration INTRAMUSCULAR DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength spectinomycin hydrochloride (spectinomycin) Active 400 MILLIGRAM  In 1 MILLILITER

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 5 mL (MILLILITER) In 1 VIAL None

Part 2 of 2 BACTERIOSTATIC WATER  water  injection, solution

Product Information       Route of Administration INTRAMUSCULAR DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength Water Inactive   Benzyl Alcohol Inactive

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 3.2 mL (MILLILITER) In 1 AMPULE None

Revised: 03/2007Pharmacia and Upjohn, Co.

More Trobicin resources

• Trobicin Side Effects (in more detail)
• Trobicin Drug Interactions
• Trobicin Support Group
• 0 Reviews for Trobicin - Add your own review/rating

• Trobicin Concise Consumer Information (Cerner Multum)


• Trobicin Monograph (AHFS DI)


• Trobicin Advanced Consumer (Micromedex) - Includes Dosage Information


• Spectinomycin Professional Patient Advice (Wolters Kluwer)

Compare Trobicin with other medications

• Gonococcal Infection
• Gonococcal Infection, Disseminated
• Gonococcal Infection, Uncomplicated

Stalevo 150

Generic Name: carbidopa, entacapone, and levodopa (KAR bi DOE pa, en TAK a pone, LEE voe DOE pa)

Brand Names: Stalevo 100, Stalevo 125, Stalevo 150, Stalevo 200, Stalevo 50, Stalevo 75

What is Stalevo 150 (carbidopa, entacapone, and levodopa)?

Levodopa is converted to a chemical called dopamine (DOE pa meen) in the brain. Symptoms of Parkinson's disease may be caused by low levels of dopamine in the brain. Carbidopa helps prevent the breakdown of levodopa before it can reach the brain and take effect. Entacapone increases levels of levodopa in the body.

The combination of carbidopa, entacapone, and levodopa is used to treat Parkinson symptoms such as muscle stiffness, tremors, spasms, and poor muscle control.

Carbidopa, entacapone, and levodopa may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Stalevo 150 (carbidopa, entacapone, and levodopa)?

You should not use this medication if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), or tranylcypromine (Parnate) in the last 14 days.

You should not take this medication if you are allergic to carbidopa (Lodosyn), entacapone (Comtan), or levodopa (Larodopa), or if you have narrow-angle glaucoma, unusual skin lesions, or a history of skin cancer.

Tell your doctor about all of your medical conditions, especially heart disease, high blood pressure, asthma or other breathing problems, liver or kidney disease, a hormonal disease, an ulcer, glaucoma, or mental illness. Also tell your doctor about all the medications you use.

It may take up to several weeks of using carbidopa, entacapone, and levodopa before your symptoms improve. Talk with your doctor if your symptoms do not improve or if the effects of this medication seem to wear off quickly in between doses. Do not stop using carbidopa, entacapone, and levodopa without first talking to your doctor.

What should I discuss with my healthcare provider before taking Stalevo 150 (carbidopa, entacapone, and levodopa)?

Do not take this medication if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), or tranylcypromine (Parnate) in the last 14 days.

You should not take this medication if you are allergic to carbidopa (Lodosyn), entacapone (Comtan), or levodopa (Larodopa), or if you have:

• 
  

  narrow-angle glaucoma;

  
  


• 
  

  unusual skin lesions that have not been checked by a doctor; or

  
  


• 
  

  a history of malignant melanoma (skin cancer).

  
  

To make sure you can safely take this medication, tell your doctor if you have any of these other conditions:

• 
  

  heart disease, high blood pressure, coronary artery disease, a heart rhythm disorder, or a prior heart attack;

  
  


• 
  

  asthma, chronic obstructive pulmonary disease (COPD), or other breathing disorder;

  
  


• 
  

  kidney disease, liver disease, or bile duct obstruction;

  
  


• 
  

  an endocrine (hormonal) disease;

  
  


• 
  

  a stomach or intestinal ulcer;

  
  


• 
  

  glaucoma; or

  
  


• 
  

  depression or other mental illness.

  
  

You may have increased sexual urges, unusual urges to gamble, or other intense urges while taking this medication. Talk with your doctor if you believe you have any intense or unusual urges while taking this medicine.

Carbidopa, entacapone, and levodopa may cause hallucinations (the sensation of hearing or seeing something that is not there). Call your doctor if you experience hallucinations.

Some people taking Parkinson's disease medications have developed skin cancer (melanoma). However, people with Parkinson's disease may have a higher risk of melanoma. Talk to your doctor about this risk and what skin symptoms to watch for. You may need to have regular skin exams.

FDA pregnancy category C. It is not known whether carbidopa, entacapone, and levodopa will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. Carbidopa, entacapone, and levodopa may pass into breast milk and could harm a nursing baby. You should not breast-feed while you are taking carbidopa, entacapone, and levodopa.

How should I take Stalevo 150 (carbidopa, entacapone, and levodopa)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. Take your medicine at regular intervals to keep a steady amount of the drug in your body at all times.

Drink plenty of liquids while you are taking this medication. It may take up to several weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve after a few weeks of treatment. Also tell your doctor if the effects of this medication seem to wear off quickly in between doses. Call your doctor if you have ongoing vomiting or diarrhea, or if you are sweating more than usual. You can easily become dehydrated while taking this medication, which can lead to severely low blood pressure or a serious electrolyte imbalance. Do not stop using carbidopa, entacapone, and levodopa without first talking to your doctor. You may need to use less and less before you stop the medication completely.

This medication can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using carbidopa, entacapone, and levodopa.

Store at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Overdose symptoms may include weakness, loss of coordination, trouble breathing, fainting, or seizure (convulsions).

What should I avoid while taking Stalevo 150 (carbidopa, entacapone, and levodopa)?

Carbidopa, entacapone, and levodopa may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Avoid taking iron supplements or eating a diet that is high in protein (protein sources include meat, eggs, and cheese). These things can make it harder for your body to digest and absorb carbidopa, entacapone, and levodopa.

Stalevo 150 (carbidopa, entacapone, and levodopa) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have a serious side effect such as:

• 
  

  nausea, sweating, feeling like you might pass out (especially when you first start taking this medication);

  
  


• 
  

  depression, confusion, hallucinations, unusual thoughts or behavior, thoughts about hurting yourself;

  
  


• 
  

  worsening symptoms such as tremors, twitching or uncontrollable movements of your eyes, lips, tongue, face, arms, or legs;

  
  


• 
  

  severe or ongoing diarrhea, extreme thirst, increased urination, weight loss, leg discomfort, muscle weakness or limp feeling, uneven heart rate;

  
  


• 
  

  feeling very thirsty or hot, being unable to urinate, heavy sweating, or hot and dry skin;

  
  


• 
  

  fast, pounding, or uneven heartbeats;

  
  


• 
  

  chest pain or heavy feeling, pain spreading to the arm or shoulder, general ill feeling;

  
  


• 
  

  tight feeling in your chest, new or worsening cough, fever, trouble breathing;

  
  


• 
  

  easy bruising or bleeding, bloody or tarry stools, coughing up blood;

  
  


• 
  

  pain or burning when you urinate; or

  
  


• 
  

  unexplained muscle pain, tenderness, or weakness.

  
  

Less serious side effects may include:

• 
  

  stomach pain or upset, loss of appetite, constipation;

  
  


• 
  

  dry mouth, changes in your sense of taste;

  
  


• 
  

  unusual skin changes. mild rash or itching;

  
  


• 
  

  dizziness or drowsiness, headache, blurred vision;

  
  


• 
  

  muscle cramps, back pain; or

  
  


• 
  

  agitation or anxiety, sleep problems (insomnia), strange dreams.

  
  

You may notice that your sweat, urine, or saliva appears dark in color, such as red, brown, or black. This is not a harmful side effect, but it may cause staining of your clothes or bed sheets.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Stalevo 150 (carbidopa, entacapone, and levodopa)?

Cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety can add to sleepiness caused by carbidopa, entacapone, and levodopa. Tell your doctor if you regularly use any of these other medicines, or any other Parkinson's medications.

Tell your doctor about all other medicines you use, especially:

• 
  

  apomorphine (Apokyn);

  
  


• 
  

  cholestyramine (Prevalite, Questran);

  
  


• 
  

  dobutamine (Dobutrex);

  
  


• 
  

  epinephrine (Epi-Pen, and others);

  
  


• 
  

  isoniazid (for treating tuberculosis);

  
  


• 
  

  isoproterenol (Isuprel, Medihaler-Iso);

  
  


• 
  

  methyldopa (Aldomet);

  
  


• 
  

  metoclopramide (Reglan);

  
  


• 
  

  papaverine (Pavabid, Papacon, Pavagen, Pavacot);

  
  


• 
  

  phenytoin (Dilantin);

  
  


• 
  

  probenecid (Benemid);

  
  


• 
  

  blood pressure medication;

  
  


• 
  

  an antibiotic such as ampicillin, chloramphenicol, erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin, Pediazole, and others), or rifampin (Rifadin, Rifater, Rifamate);

  
  


• 
  

  an antidepressant such as amitriptyline (Elavil, Vanatrip, Limbitrol), doxepin (Sinequan), imipramine (Janimine, Tofranil), nortriptyline (Pamelor), and others; or

  
  


• 
  

  medicines to treat psychiatric disorders, such as chlorpromazine (Thorazine), haloperidol (Haldol), prochlorperazine (Compazine), risperidone (Risperdal), and others.

  
  

This list is not complete and other drugs may interact with carbidopa, entacapone, and levodopa. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Stalevo 150 resources

• Stalevo 150 Side Effects (in more detail)
• Stalevo 150 Use in Pregnancy & Breastfeeding
• Drug Images
• Stalevo 150 Drug Interactions
• Stalevo 150 Support Group
• 0 Reviews for Stalevo50 - Add your own review/rating

• Stalevo 150 Advanced Consumer (Micromedex) - Includes Dosage Information


• Carbidopa/Entacapone/Levodopa MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Stalevo 150 with other medications

• Parkinson's Disease

Where can I get more information?

• Your pharmacist can provide more information about carbidopa, entacapone, and levodopa.

See also: Stalevo50 side effects (in more detail)