AddressAmylin Pharmaceuticals, Inc. , 9360 Towne Centre Drive San Diego , California 92121 Contact DetailsPhone: (858) 552-2200Website: http://www.amylin.com Careers: http://careers.amylin.com/ |
Wednesday, 18 July 2012
Amylin Pharmaceuticals, Inc.
Saturday, 14 July 2012
Erythromycin and Benzoyl Peroxide
Erythromycin-Benzoyl Peroxide Topical Gel
Topical Gel: erythromycin (3%), benzoyl peroxide (5%)
For Dermatological Use Only – Not for Ophthalmic Use
Reconstitute Before Dispensing
Erythromycin and Benzoyl Peroxide Description
Erythromycin-Benzoyl Peroxide Topical Gel contains erythromycin [(3R*, 4S*, 5S*, 6R*, 7R*, 9R*, 11R*, 12R*, 13S*, 14R*) - 4 - [(2,6 - Dideoxy - 3 - C - methyl - 3 - O - methyl - α - L - ribo - hexopyranosyl) - oxy] - 14 - ethyl - 7,12,13 - trihydroxy - 3,5,7,9,11,13 - hexa - methyl - 6 - [[3,4,6 - trideoxy - 3 - (dimethylamino) - β - D - xylo - hexopyranosyl]oxy]oxacyclotetradecane - 2,10 - dione]. Erythromycin is a macrolide antibiotic produced from a strain of Saccharopolyspora erythraea (formerly Streptomyces erythreus). It is a base and readily forms salts with acids.
Chemically, erythromycin is (C37H67NO13). It has the following structural formula:
Erythromycin has the molecular weight of 733.94. It is a white crystalline powder and has a solubility of approximately 1 mg/mL in water and is soluble in alcohol at 25°C.
Erythromycin-Benzoyl Peroxide Topical Gel also contains benzoyl peroxide for topical use. Benzoyl peroxide is an antibacterial and keratolytic agent.
Chemically, benzoyl peroxide is (C14H10O4). It has the following structural formula:
Benzoyl peroxide has the molecular weight of 242.23. It is a white granular powder and is sparingly soluble in water and alcohol and soluble in acetone, chloroform and ether.
Each gram of Erythromycin-Benzoyl Peroxide Topical Gel contains, as dispensed, 30 mg (3%) of erythromycin and 50 mg (5%) of benzoyl peroxide in a base of purified water USP, Carbomer Homopolymer Type C, alcohol 20%, sodium hydroxide NF, docusate sodium and fragrance.
Erythromycin and Benzoyl Peroxide - Clinical Pharmacology
The exact mechanism by which erythromycin reduces lesions of acne vulgaris is not fully known; however, the effect appears to be due in part to the antibacterial activity of the drug.
Benzoyl peroxide has a keratolytic and desquamative effect which may also contribute to its efficacy. Benzoyl peroxide has been shown to be absorbed by the skin where it is converted to benzoic acid.
MICROBIOLOGY
Erythromycin acts by inhibition of protein synthesis in susceptible organisms by reversibly binding to 50 S ribosomal subunits, thereby inhibiting translocation of aminoacyl transfer-RNA and inhibiting polypeptide synthesis. Antagonism has been demonstrated in vitro between erythromycin, lincomycin, chloramphenicol and clindamycin.
Benzoyl peroxide is an antibacterial agent which has been shown to be effective against Propionibacterium acnes, an anaerobe found in sebaceous follicles and comedones. The antibacterial action of benzoyl peroxide is believed to be due to the release of active oxygen.
Indications and Usage for Erythromycin and Benzoyl Peroxide
Erythromycin-Benzoyl Peroxide Topical Gel is indicated for the topical treatment of acne vulgaris.
Contraindications
Erythromycin-Benzoyl Peroxide Topical Gel is contraindicated in those individuals who have shown hypersensitivity to any of its components.
Warnings
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including erythromycin, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.
Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of "antibiotic-associated colitis."
After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation and treatment with an antibacterial drug clinically effective against C. difficile colitis.
Precautions
General
For topical use only; not for ophthalmic use. Concomitant topical acne therapy should be used with caution because a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating or abrasive agents. If severe irritation develops, discontinue use and institute appropriate therapy.
The use of antibiotic agents may be associated with the overgrowth of nonsusceptible organisms including fungi. If this occurs, discontinue use and take appropriate measures.
Avoid contact with eyes and all mucous membranes.
Information for Patients
Patients using Erythromycin-Benzoyl Peroxide Topical Gel should receive the following information and instructions:
- This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes, nose, mouth, and all mucous membranes.
- This medication should not be used for any disorder other than that for which it was prescribed.
- Patients should not use any other topical acne preparation unless otherwise directed by physician.
- Patients should report to their physician any signs of local adverse reactions.
- Erythromycin-Benzoyl Peroxide Topical Gel may bleach hair or colored fabric.
- Keep product refrigerated and discard after 3 months.
CARCINOGENESIS, MUTAGENESIS AND IMPAIRMENT OF FERTILITY
Data from a study using mice known to be highly susceptible to cancer suggests that benzoyl peroxide acts as a tumor promoter. The clinical significance of this is unknown.
No animal studies have been performed to evaluate the carcinogenic and mutagenic potential or effects on fertility of topical erythromycin. However, long-term (2-year) oral studies in rats with erythromycin ethylsuccinate and erythromycin base did not provide evidence of tumorigenicity. There was no apparent effect on male or female fertility in rats fed erythromycin (base) at levels up to 0.25% of diet.
Pregnancy
Teratogenic Effects
Pregnancy CATEGORY C
Animal reproduction studies have not been conducted with Erythromycin-Benzoyl Peroxide Topical Gel or benzoyl peroxide.
There was no evidence of teratogenicity or any other adverse effect on reproduction in female rats fed erythromycin base (up to 0.25% diet) prior to and during mating, during gestation and through weaning of two successive litters.
There are no well-controlled trials in pregnant women with Erythromycin-Benzoyl Peroxide Topical Gel. It also is not known whether Erythromycin-Benzoyl Peroxide Topical Gel can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Erythromycin-Benzoyl Peroxide Topical Gel should be given to a pregnant woman only if clearly needed.
Nursing Women
It is not known whether Erythromycin-Benzoyl Peroxide Topical Gel is excreted in human milk after topical application. However, erythromycin is excreted in human milk following oral and parenteral erythromycin administration. Therefore, caution should be exercised when erythromycin is administered to a nursing woman.
Pediatric Use
Safety and effectiveness of this product in pediatric patients below the age of 12 have not been established.
Adverse Reactions
In controlled clinical trials, the incidence of adverse reactions associated with the use of Erythromycin-Benzoyl Peroxide Topical Gel was approximately 3%. These were dryness and urticarial reaction.
The following additional local adverse reactions have been reported occasionally: irritation of the skin including peeling, itching, burning sensation, erythema, inflammation of the face, eyes and nose, and irritation of the eyes. Skin discoloration, oiliness and tenderness of the skin have also been reported.
Erythromycin and Benzoyl Peroxide Dosage and Administration
Erythromycin-Benzoyl Peroxide Topical Gel should be applied twice daily, morning and evening, or as directed by a physician, to affected areas after the skin is thoroughly washed, rinsed with warm water and gently patted dry.
How Supplied and Compounding Directions:
| Size (Net Weight) | NDC 45802-083- | Benzoyl Peroxide Gel | Active Erythromycin Powder (In Plastic Vial) | 70% Ethyl Alcohol To Be Added |
|---|---|---|---|---|
| 23.3 grams (as dispensed) | 02 | 20 grams | 0.8 grams | 3 mL |
| 46.6 grams (as dispensed) | 86 | 40 grams | 1.6 grams | 6 mL |
Prior to dispensing, tap vial until all powder flows freely. Add indicated amount of room temperature 70% ethyl alcohol to vial (to the mark) and immediately shake to completely dissolve erythromycin. Add this solution to gel and stir until homogeneous in appearance (1 to 1½ minutes). Erythromycin-Benzoyl Peroxide Topical Gel should then be stored under refrigeration. Do not freeze. Place a 3-month expiration date on the label.
NOTE: Prior to reconstitution, store at room temperature between 15° and 30°C (59° – 86°F).
After reconstitution, store under refrigeration between 2° and 8°C (36° – 46°F).
Do not freeze. Keep tightly closed. Keep out of the reach of children.
Manufactured by:
sanofi-aventis Canada Inc.,
Laval, Quebec, Canada H7L 4A8
Distributed by:
Perrigo®
Allegan, MI 49010
Revised May 2010
©2010 sanofi-aventis U.S. LLC
Erythromycin-Benzoyl Peroxide Topical Gel
| PLEASE READ COMPLETE COMPOUNDING DIRECTIONS |
| NOTE: TAP VIAL UNTIL ALL POWDER FLOWS FREELY. ADD ROOM TEMPERATURE 70% ETHYL ALCOHOL TO VIAL (TO THE MARK) AND IMMEDIATELY SHAKE/DISSOLVE COMPLETELY. |
PRINCIPAL DISPLAY PANEL - 46.6g Jar Carton
PERRIGO®
NDC 45802-083-86
Erythromycin-
Benzoyl Peroxide
Topical Gel
For Topical Use Only
One 46.6g Jar
(as dispensed)
Rx Only
| ERYTHROMYCIN-BENZOYL PEROXIDE Erythromycin and Benzoyl Peroxide gel | ||||||||||||||||||||
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| NDA | NDA050557 | 03/29/2004 | |
| Labeler - Perrigo New York Inc (078846912) |
| Registrant - sanofi-aventis Canada, Inc. (251046934) |
| Establishment | |||
| Name | Address | ID/FEI | Operations |
| sanofi-aventis Canada, Inc. | 251046934 | MANUFACTURE, ANALYSIS, LABEL, PACK | |
Wednesday, 11 July 2012
Medebar Suspension
Dosage Form: suspension
LAFAYETTE
MEDEBAR™ PLUS
BARIUM SULFATE SUSPENSION
Rx only
Medebar Suspension Description
Medebar Plus is a fruity-cola flavored, low viscosity (rapid flow), ready-to-use suspension, for x-ray examinations of the gastrointestinal tract.
It contains 100% w/v (55% w/w) barium sulfate USP, dispersing agent, vegetable gums, simethicone, preservatives, flavoring, saccharin sodium and water. Barium sulfate has the empirical formula of BaSO4.
Medebar Suspension - Clinical Pharmacology
Barium sulfate is an insoluble material which, because of its density, provides a positive contrast during x-ray examination. Barium sulfate is an inert radiopaque material which is not absorbed or metabolized and is eliminated intact from the body in a manner similar to other non-absorbed inorganic materials. Excretion rate is a function of gastrointestinal transit time.
Indications and Usage for Medebar Suspension
Medebar Plus is indicated for use as a contrast medium in x-ray diagnosis of the gastrointestinal tract. The suspension may be administered without dilution for double contrast colon, single contrast esophagus, small bowel and enteroclysis examinations. Aqueous dilutions of Medebar Plus may be used for single contrast stomach and single contrast colon examinations.
Contraindications
Barium sulfate products are contraindicated in patients with known or suspected obstruction of the colon, known or suspected gastrointestinal tract perforation, suspected tracheoesophageal fistula, obstructing lesions of the small intestine, pyloric stenosis, inflammation or neoplastic lesions of the rectum, recent rectal biopsy, or known hypersensitivity to barium sulfate formulations.
Known hypersensitivity or allergy to latex is a contraindication for the use of balloon retention enema tips containing latex. The use of a retention cuff enema tip is not necessary or desirable in patients with normal sphincter tone. The presence of adequate sphincter tone can be judged by preliminary rectal digital examination.
The use of rectal balloon is contraindicated in patients having a history of pencil stools, recent rectal surgery or low rectal anastomosis, perianal inflammation, colitis, rectal stricture or other suspected lesions that could lead to further injury through distention by a rectal balloon or when proctitis or other rectal conditions such as inflammatory or neoplastic diseases are suspected.
Warnings
Serious adverse reactions, including death, have been reported with the administration of barium sulfate formulations and are usually associated with the technique of administration, the underlying pathological condition and/or patient hypersensitivities.
Oral administration of barium sulfate suspension by an infant sucking a bottle and administration of large quantities by catheter are reported to be likely to result in aspiration into the tracheobronchial tree.
Vomiting following oral administration of barium sulfate may lead to aspiration pneumonitis. Cardiopulmonary arrest leading to fatality has been reported in infants following aspiration. Aspiration of smaller amounts may cause inflammation.
Barium sulfate preparations used as radiopaque media contain a number of additives to provide diagnostic properties and patient palatability. Allergic responses following the use of barium sulfate suspensions have been reported. In patients with increased cranial pressure, barium sulfate suspension enemas present an additional risk of further increasing intracranial pressure.
Barium sulfate suspension intravasation can be a serious complication. Mortality has been reported as a result of vaginal or rectal intravasation and is believed to be due to massive pulmonary embolism occurring within minutes of the inciting event.
Skin irritation, redness, inflammation and hives have been reported in infants and small children following spillage of barium sulfate suspension on their skin. These responses are thought to be caused by the flavors and/or preservatives used in the product.
Barium sulfate suspension has been reported to cause obstruction of the small bowel (impaction) in pediatric patients with cystic fibrosis. It has also been reported to cause fluid overload from the absorption of water during studies in infants when Hirschsprung’s Disease is suspected.
Care must be taken during the insertion of an enema tip into the patient to prevent application of pressure to the vagus nerve which can lead to vasovagal reactions and syncopal episodes. Cardiac arrhythmia or other cardiovascular side effects can occur as a result of colon distension.
Precautions
General
Diagnostic procedures which involve the use of radiopaque contrast agents should be carried out under the direction of personnel with the requisite training and with a thorough knowledge of the particular procedure to be performed. A history of bronchial asthma, atopy, as evidenced by hay fever and eczema, a family history of allergy, or a previous reaction to a contrast agent warrant special attention. Caution should be exercised with the use of radiopaque media in severely debilitated patients and in those with marked hypertension or advanced cardiac disease.
Anaphylactic and allergic reactions have been reported during double contrast examinations in which glucagon has been used.
Ingestion of barium sulfate suspension is not recommended in patients with a history of food aspiration. If barium sulfate suspension is aspirated into the larynx, further administration of the suspension should be immediately discontinued.
Patient preparation for diagnostic gastrointestinal examinations frequently requires cathartics and a liquid diet. The various preparations can result in water loss for the patient. Patients should be rehydrated quickly following a barium sulfate suspension examination of the gastrointestinal tract. In patients with reduced colon motility, saline cathartics may be required after the barium sulfate suspension enema. Saline cathartics are recommended on a routine basis in patients with a history of constipation unless clinically contraindicated.
Where enema tips are used, care must be taken during insertion into the patient, since forceful or too deep insertion may cause tearing or perforation of the rectum. Insertion of an enema tip should be done only after digital examination by qualified medical personnel. When balloon retention tips are used, care should be taken to avoid over-inflation of the balloon, since overfilling or asymmetrical filling may cause displacement of the tip. Such a displacement can lead to rectal perforation or barium sulfate granulomas. Inflation of the balloon should be done under fluoroscopic control by qualified medical personnel. Do not unnecessarily move the enema tip once inserted.
A specially designed enema tip is required for a barium sulfate suspension examination of a colostomy patient.
Intubation of an enteroclysis catheter should be done by qualified medical personnel. Perforation of the duodenum has been reported.
Because of reported anaphylactoid reactions to latex, the use of non-latex gloves during the procedure should be considered.
Pregnancy
Safe use of barium sulfate during pregnancy has not been established. Barium sulfate should be used in pregnant women only if the possible benefits outweigh the potential risks. Elective radiography of the abdomen is considered to be contraindicated during pregnancy due to the risk to the fetus from radiation exposure. Radiation is known to cause harm to the unborn fetus exposed in utero.
Adverse Reactions
Adverse reactions accompanying the use of barium sulfate formulations are infrequent and usually mild, though severe reactions (approximately 1 in 500,000) and fatalities (approximately 1 in 2,000,000) have occurred. Procedural complications are rare, but may include aspiration pneumonitis, barium sulfate impaction, granuloma formation, intravasation, embolization and peritonitis following intestinal perforation, vasovagal and syncopal episodes, and fatalities. EKG changes have been shown to occur following or during barium sulfate suspension enemas. It is of the utmost importance to be completely prepared to treat any such occurrence.
Due to the increased likelihood of allergic reactions in atopic patients, a complete history of known and suspected allergies as well as allergic-like symptoms, such as rhinitis, bronchial asthma, eczema and urticaria, must be obtained prior to any medical procedure.
Aspiration of large amounts of barium sulfate suspension may cause pneumonitis or nodular granulomas of interstitial lung tissues and lymph nodes; asphyxiation and death have been reported.
Transient bacteremia, beginning almost immediately and lasting up to 15 minutes, may occur during rectal administration of barium sulfate suspension, and rarely septicemia has been reported.
A rare mild allergic reaction would most likely be generalized pruritis, erythema or urticaria (approximately 1 in 100,000 reactions). Such reactions will often respond to an antihistamine. More serious reactions (approximately 1 in 500,000) may result in laryngeal edema, bronchospasm or hypotension.
Severe reactions which may require emergency measures are often characterized by peripheral vasodilation, hypotension, reflex tachycardia, dyspnea, bronchospasm, agitation, confusion and cyanosis, progressing to unconsciousness. Treatment should be initiated immediately according to established standard of care.
Apprehensive patients may develop weakness, pallor, tinnitus, diaphoresis and bradycardia following the administration of any diagnostic agent. Such reactions are usually non-allergic in nature.
Allergic reactions to the enema examination accessories, in particular to retention catheters (tips) with latex cuffs, can occur. Such reactions could occur immediately and result in the previously mentioned acute allergic-like responses or might be delayed in appearance and result in a contact dermatitis. Known atopic patients, particularly those with a history of asthma or eczema, should be evaluated for alternative methods of administration in order to avoid these adverse reactions. These plastic / rubber accessories are disposable, single-use devices that must not be reused or left in the body cavity for an extended period of time.
Postmarketing Experiences
The following adverse experiences have been reported in patients receiving products containing barium sulfate. These adverse experiences are listed alphabetically: abdominal cramping, abdominal pain, diarrhea, fever, foreign body trauma relating to procedural complications, headache, laryngeal burning and irritation, leukocytosis, nausea, procedural site reactions, rash and vomiting.
Overdosage
In rare instances, immediate repeat oral examinations utilizing standard dosages may lead to severe stomach cramps and diarrhea. Cases reported implicate total dose in the range of 30 ounces (900 mL) of suspension. Instances of this type have resolved spontaneously and they are not considered to be life-threatening.
Medebar Suspension Dosage and Administration
Patient Preparation
Successful examination of the upper gastrointestinal tract requires that the stomach be empty and essentially free of fluid. This can usually be accomplished by instructing the patient to abstain from eating or drinking anything after the evening meal before the examination. The preparation for small bowel examinations, done separately or combined with an upper gastrointestinal series, is the same.
For examinations of the colon, the patient should be given a low solid diet for a minimum of 24 hours before the examination. Laxatives should also be used to clean the colon. In order to obtain thorough cleansing of the colon, a 2 liter water enema one hour before the examination may be necessary.
Suspension Preparation
The volume and concentration used will vary depending upon the method of patient preparation, the desired level of contrast density, individual variation in patient anatomy and radiographic equipment. The following dilutions are suggested for Medebar Plus:
| TEST | DILUTION FORMULA | % BARIUM SULFATE (w/v) |
| Double Contrast Colon | Medebar Plus undiluted | 100 |
| Single Contrast Esophagus | Medebar Plus undiluted | 100 |
| Small Bowel, Enteroclysis | Medebar Plus undiluted | 100 |
| Single Contrast Stomach | Medebar Plus undiluted or diluted 1:1 with water | 100 50 |
| Single Contrast Colon | From 7 to 3 parts water to 1 part Medebar Plus | 14-33 |
| Shake VIGOROUSLY prior to use. | ||
Double Contrast Colon Examination:
The examination should be performed by properly trained medical personnel only. Approximately 500 mL Medebar Plus is required to reach the splenic flexure, and it should be introduced by an enema administration system.
An enema administration system with 1/2” ID tubing, such as Medebar Plus Kit or Aircon is used for ease of administration. The usual method uses introduced air to move the column of barium sulfate suspension around the hepatic flexure and into the cecum. Patient positioning is critical during this process to ensure that air does not get ahead of the barium column. Such an eventuality may reduce the volume of suspension that reaches the cecum, and will adversely affect the quality of its coating. Conversely, should excessive quantities of suspension flood the cecum, double contrast views may be obscured by the barium pool.
Double Contrast Colon Examination with Medebar Plus Kit
The following procedure is suggested for double contrast examination of a well prepared, adult colon using Medebar Plus Kit (650 mL Medebar Plus). The actual procedure used will depend upon patient symptoms and conditions as well as physician preference and judgement.
Shake the Medebar Plus bottle well and attach the tubing unit.
With the patient in the left lateral position and the right knee flexed, insert the enema tip and inflate the retention cuff. Introduce a small amount of Medebar Plus into the rectal area. Check the rectal area by fluoroscopy for contraindications.
Place the table slightly Trendelenburg. With the fluoroscopy unit off, introduce the remainder of the Medebar Plus. Close the clamp on the large bore tubing. Introduce approximately five pumps of air into the patient using the blue multi-puff insufflator provided with each case.
Turn the patient LAO and introduce five pumps of air. Turn the patient prone, bring the table horizontal and introduce five pumps of air. Turn the patient RAO and introduce five pumps of air. Position the patient right lateral and introduce five pumps of air. If, at this point, the barium sulfate suspension has not coated the cecum, tilt the patient slightly head up. This should bring the barium sulfate suspension pool to the cecum.
Next turn the patient supine and tilt the table slightly Trendelenburg. Turn the patient LPO and bring the table to horizontal. Turn the patient left lateral and position the table with the patient slightly head up. This should cause the barium sulfate suspension pool to collect in the rectal area.
Place the Medebar Plus bottle on the floor and open the 1/2” tubing clamp to drain excess barium sulfate suspension from the rectum. The physician may prefer to have the patient either left lateral or prone for rectal drainage. When drainage is complete, close the tubing clamp. Spot films of the rectosigmoid may now be obtained.
Fluoroscopy is then used to evaluate colon distension. Introduce additional air to provide optimum distension as determined by the physician. Removal of the enema tip at this time is optional, according to the preference of the examiner. Rotate the patient slowly 360° taking spot films and overhead radiographs.
For single patient use only. Properly discard unused portion.
How is Medebar Suspension Supplied
Catalog No. 129794. NDC 68240-737-90. 900 mL bottle; twelve (12) bottles per case.
Medebar Plus Kit. Catalog No. 129722. NDC 68240-737-65. 650 mL bottles. Six (6) bottles with six (6) enema tip-tubing assemblies per case.
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). Protect from freezing.
Shake VIGOROUSLY prior to use.
Medebar™ All trademark rights reserved.
DIN: 02216388
Distributed in Canada by:
tyco Healthcare
Pointe-Claire, QC, Canada H9R 5H8
Establishment License # 100689-A
Made in Mexico
Manufactured by:
Mallinckrodt Inc.
St. Louis, MO 63042 USA
www.Mallinckrodt.com
MID 1295215
Rev 03/2009
DOUBLE CONTRAST
LOWER G.I.
- Fast-flowing
- 100% w/v
- Dilute for single contrast
tyco
Healthcare
Mallinckrodt
Package Label - Principal Display Panel - 900 mL Bottle
L A F A Y E T T E
MEDEBAR™ PLUS
BARIUM SULFATE SUSPENSION
DOUBLE CONTRAST / LOWER G.I. EXAMS
Rx only
NDC 68240-737-90
Catalog No. 129794
A fruity-cola flavored, low viscosity, ready-to-use 100% w/v (55% w/w) barium sulfate USP suspension for x-ray examinations of the gastrointestinal tract.
Contents: Barium sulfate USP, dispersing agent, vegetable gums, simethicone, preservatives, flavoring, saccharin sodium and water.
Contraindications: Do not use in patients with suspected gastrointestinal tract perforation or known hypersensitivity to barium sulfate formulations.
Dosage and Administration: See package insert for complete instructions.
Shake VIGOROUSLY prior to use.
For single patient use only. Properly discard unused portion.
Storage: Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). Protect from freezing.
Net Contents: 900 mL
DIN: 02216388
Distributed in Canada by:
tyco Healthcare
Pointe-Claire, QC, Canada H9R 5H8
Establishment License # 100689-A
Made in Mexico
Manufactured by Mallinckrodt Inc.
St. Louis, MO 63042 USA
www.Mallinckrodt.com
MID 1600170
Rev 03/2009
O3™ ANTIMICROBIAL TECHNOLOGY
tyco/Healthcare
MALLINCKRODT
| MEDEBAR PLUS barium sulfate suspension | ||||||||||||||||||||||||||||||
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| unapproved other | 12/01/2009 | ||
| Labeler - Mallinckrodt, Inc. (810407189) |
| Establishment | |||
| Name | Address | ID/FEI | Operations |
| Mallinckrodt Medical, S.A. de C.V. | 810407189 | analysis, manufacture | |
More Medebar Suspension resources
- Medebar Suspension Side Effects (in more detail)
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- 1 Review for Medebar - Add your own review/rating
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- Computed Tomography
Tuesday, 10 July 2012
Leventa Solution
Dosage Form: FOR ANIMAL USE ONLY
leventa® 30mL
Each mL of LEVENTA® (levothyroxine sodium, U.S.P.) oral solution provides 1 mg synthetic crystalline levothyroxine sodium (L-thyroxine).
CAUTION
Federal law restricts this drug to use by or on the order of a licensed veterinarian.
INDICATION
Thyroid replacement therapy in dogs with hypothyroidism. Hypothyroidism is the generalized metabolic disease resulting from deficiency of the thyroid hormones, L-thyroxine (T4) and triiodothyronine (T3). LEVENTA® oral solution will provide L-thyroxine (T4) as a substrate for the physiologic deiodination to triiodothyronine (T3). Administration of L-thyroxine (T4), identical to the L-thyroxine (T4) secreted endogenously by the normal thyroid gland, will result in complete physiologic thyroid replacement. L-thyroxine (T4) acts to stimulate metabolism, growth, development and differentiation of tissues. It increases the rate of energy exchange and the maturation rate of the epiphyses.
The clinical diagnosis of hypothyroidism should be completed by evaluation of the thyroid hormone of the dog, i.e. measurement of serum levels of total (or preferably free) thyroxine (T4) and thyroid stimulating hormone (TSH). A low total (or free) T4 concentration combined with high TSH concentration is strongly suggestive for primary hypothyroidism.
PHARMACOLOGY
Levothyroxine sodium acts, as does endogenous L-thyroxine (T4), to stimulate metabolism, growth, development and differentiation of tissues. It increases the rate of energy exchange and the maturation rate of the epiphyses. Levothyroxine sodium is absorbed rapidly from the gastrointestinal tract after oral administration. Following absorption, the compound becomes bound to the serum alpha globulin fraction.
DOSAGE
The adequate dose rate has to be defined individually for each dog. Treatment should be initiated at a recommended dose rate of 20 µg L-thyroxine/kg once daily and re-evaluated every 4 weeks by monitoring T4 serum levels 4 to 6 hours post-treatment. According to the T4 levels, the veterinarian will decide to adjust the dose rate if needed. Once the dosage suitable to solve the hypothyroidism clinical and hormonal condition of the dog is determined (maintenance dosage), serum T4 levels 4 to 6 hours post-treatment should be checked every 6 months. The usual maintenance dosage 20 µg L-thyroxine/kg once daily.
ADMINISTRATION
Remove child resistant cap and insert oral dosing syringe into the plastic push-in adapter. Invert bottle and gently draw back syringe plunger to the desired dose. Return the bottle to the upright position and remove syringe.
LEVENTA® oral solution may be given orally to dogs directly into the mouth or may be mixed with their food. If mixed with their food, consumption should be monitored. The conditions at treatment administration (time, relation to feeding, diet) should be standardized.
Contraindications
L-thyroxine therapy is contraindicated in thyrotoxicosis, acute myocardial infarction and uncorrected adrenal insufficiency. Use in pregnant bitches has not been evaluated.
Adverse Reactions
There are no particular adverse reactions associated with L-thyroxine therapy at the recommended dosage levels. Overdosage will result in the signs of thyrotoxicosis listed under Precautions.
Precautions
The effects of L-thyroxine therapy are slow to manifest. Overdosage of any thyroid drug may produce the signs and symptoms of thyrotoxicosis including, but not limited to: polydipsia, polyuria, polyphagia, reduced heat tolerance and hyperactivity or personality change. Administer with caution to animals with clinically significant heart disease, hypertension or other complications for which a sharply increased metabolic rate might prove hazardous.
INFORMATION FOR DOG OWNERS
Hypothyroidism in Dogs
Canine hypothyroidism is usually due to destruction of the thyroid gland. In most cases the cause is immune disease called lymphocytic thyroiditis; however, in some cases the cause of this destruction is unknown. In less than 10 percent of cases, hypothyroidism is secondary, due to a lack of thyroid stimulating hormone (TSH). TSH is produced by the pituitary gland in the brain. Lack of TSH can occur as a congenital disorder (birth defect) where there is a malformation of the pituitary gland, or as an acquired disorder in adult dogs due to the growth of a pituitary brain tumor.
Hypothyroidism usually occurs in middle-aged and older dogs although the condition will sometimes be seen in younger dogs of the larger breeds. Neutered animals of either sex are also frequently affected, regardless of age. The following clinical signs of hypothyroidism can be observed in dogs:
- Metabolic signs:
lethargy; lack of endurance; increased sleeping; reduced interest, alertness and excitability; slow heart rate; weak heart beat and pulse; preference for warmth; low body temperature; cool skin; increased body weight.
- Dermatologic (skin) signs:
flaking of skin (dandruff); thickening of skin; increased pigmentation of skin; puffy face; drooping of the upper eyelids; tragic facial expression; dry, coarse, thin or sparse coat; slow regrowth of hair after clipping; retarded turnover of hair.
- Musculoskeletal signs:
stiff and slow movements, dragging of front feet, head tilt, disturbed balance, paralysis of one side of the face.
- Reproductive signs:
shortening or absence of estrus (heat), lack of libido
- Gastrointestinal signs:
dry feces, occasional diarrhea
- Hematology and biochemistry signs:
high blood cholesterol (hypercholesterolemia), anemia.
How is Leventa Solution Supplied
LEVENTA® oral solution (L-thyroxine 1 mg/mL) is available in 30 mL bottles closed with childproof caps. Each bottle is provided with a 1 mL dosing syringe to be used for administration.
STORAGE INFORMATION
Store refrigerated at 2- 8°C (37- 46° F), protect from light. After first opening, store in refrigerator (2-8 ° C) and use the product within six months.
KEEP OUT OF THE REACH OF CHILDREN.
FOR ANIMAL USE ONLY
Distributed by:
Intervet Inc.
Summit, NJ 07901
www.leventa.com
1-800-521-5767
Made in France
Intervet
Schering-Plough Animal Health
PRINCIPAL DISPLAY PANEL - 30mL Carton
leventa®
(levothyroxine
sodium)
Oral
Solution
for
Dogs
1.0 mg/mL
30mL
Intervet
Schering-Plough Animal Health
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| Unapproved drug other | 08/05/2010 | ||
| Labeler - Schering Corporation (001317601) |
| Establishment | |||
| Name | Address | ID/FEI | Operations |
| Intervet Production S.A. | 771867553 | MANUFACTURE | |
Monday, 9 July 2012
Nitroglycerin
Pronunciation: NYE-troe-GLIS-er-in
Generic Name: Nitroglycerin
Brand Name: Generic only. No brands available.
Nitroglycerin is used for:
Treating high blood pressure during surgery, controlling congestive heart failure associated with heart attack, treating chest pain in certain patients, and lowering blood pressure during surgery.
Nitroglycerin is a nitrate. It works by relaxing (widening) blood vessels. Chest pain occurs when the heart needs more oxygen than it can get. Relaxing blood vessels allows blood to flow more easily. This reduces the heart's workload and the amount of oxygen needed by the heart.
Do NOT use Nitroglycerin if:
- you are allergic to any ingredient in Nitroglycerin
- you have had a stroke or other bleeding in the brain, swelling of the sac surrounding the heart, or interference of blood returning to the heart
- you are taking a phosphodiesterase type 5 inhibitor (eg, sildenafil, tadalafil, vardenafil)
Contact your doctor or health care provider right away if any of these apply to you.
Before using Nitroglycerin:
Some medical conditions may interact with Nitroglycerin. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
- if you are pregnant, planning to become pregnant, or are breast-feeding
- if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
- if you have allergies to medicines, foods, or other substances
- if you drink alcoholic beverages
- if you have a history of other heart problems (eg, heart failure, enlarged heart, heart attack), overactive thyroid, stroke or other bleeding in the brain, or recent head injury
- if you have anemia, low blood pressure, dehydration, or low blood volume
Some MEDICINES MAY INTERACT with Nitroglycerin. Tell your health care provider if you are taking any other medicines, especially any of the following:
- Beta-blockers (eg, propranolol), calcium channel blockers (eg, diltiazem), diuretics (eg, furosemide, hydrochlorothiazide), medicines for high blood pressure, phenothiazines (eg, thioridazine), or phosphodiesterase type 5 inhibitors (eg, sildenafil) because the risk of low blood pressure and dizziness on standing may be increased
- Salicylates (eg, aspirin) because they may increase the risk of Nitroglycerin's side effects
- Long-acting nitrates (eg, nitroglycerin patch) because they may decrease Nitroglycerin's effectiveness
- Alteplase because it may decrease Nitroglycerin's effectiveness
- Heparin because its effectiveness may be decreased by Nitroglycerin
This may not be a complete list of all interactions that may occur. Ask your health care provider if Nitroglycerin may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
How to use Nitroglycerin:
Use Nitroglycerin as directed by your doctor. Check the label on the medicine for exact dosing instructions.
- Nitroglycerin is usually given as an injection at your doctor's office, hospital, or clinic. If you will be using Nitroglycerin at home, a health care provider will teach you how to use it. Be sure you understand how to use Nitroglycerin. Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.
- Nitroglycerin must be mixed only in glass containers and administered with the set provided. Do not mix with other medicines.
- Nitroglycerin is not for direct injection but must be diluted before use in either dextrose 5% or sodium chloride 0.9% for injection.
- If you miss a dose of Nitroglycerin, contact your doctor right away.
Ask your health care provider any questions you may have about how to use Nitroglycerin.
Important safety information:
- Nitroglycerin may cause dizziness, lightheadedness, or blurred vision. These effects may be worse if you take it with alcohol or certain medicines. Use Nitroglycerin with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.
- Do not drink alcohol while you are using Nitroglycerin. Alcohol toxicity has occurred in patients on high-dose intravenous injection. Certain medicines (eg, disulfiram, cephalosporins, furazolidone, metronidazole, monoamine oxidase inhibitors [MAOIs]) may increase the risk of alcohol toxicity if you drink alcohol while using Nitroglycerin.
- Check with your doctor before you drink alcohol while you are using Nitroglycerin. Drinking alcohol may increase the risk of low blood pressure with Nitroglycerin.
- Nitroglycerin may cause dizziness, lightheadedness, or fainting. Sit down while taking Nitroglycerin to avoid falling caused by lightheadedness or dizziness.
- Contact your doctor right away if you develop slow heartbeat or new or worsening chest pain after you take Nitroglycerin.
- Tell your doctor or dentist that you take Nitroglycerin before you receive any medical or dental care, emergency care, or surgery.
- Nitroglycerin contains propylene glycol, which may interfere with some triglyceride tests.
- Lab tests, including heart function, blood pressure, and blood electrolyte levels, may be performed while you use Nitroglycerin. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.
- Use Nitroglycerin with caution in the ELDERLY; they may be more sensitive to its effects.
- Nitroglycerin is not recommended for use in CHILDREN; safety and effectiveness in children have not been confirmed.
- PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Nitroglycerin while you are pregnant. It is not known if Nitroglycerin is found in breast milk. If you are or will be breast-feeding while you are using Nitroglycerin, check with your doctor. Discuss any possible risks to your baby.
When used for long periods of time without a break, Nitroglycerin may not work as well. This is known as TOLERANCE. Increasing the dose is not effective in managing tolerance to Nitroglycerin. Tolerance to other nitrates or nitrites may also occur. Be sure to have a "nitrate-free" period of time each day to help prevent this tolerance. Talk with your doctor if Nitroglycerin stops working well. Do not take more than prescribed.
Some people who use Nitroglycerin for a long time without a break may develop a physical need to continue taking it. This is known as physical DEPENDENCE. If you use Nitroglycerin without a break and then suddenly stop using it, you may get WITHDRAWAL symptoms. These may include chest pain, heart attack, or possibly sudden death. Be sure to have a "nitrate-free" period of time each day; this may help prevent dependence and withdrawal problems.
Possible side effects of Nitroglycerin:
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Dizziness, lightheadedness, or fainting when sitting up or standing; flushing of face and neck; headache; irritation at the injection site; nausea; vomiting.
Seek medical attention right away if any of these SEVERE side effects occur:
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blurred vision; dry mouth; fainting; flushing; heavy sweating; irregular heartbeat; new or worsening chest pain; pale skin; pounding in the chest; rapid heartbeat; severe dizziness or headache; severe or persistent nausea or vomiting; shortness of breath; slow heartbeat; swelling of the hands, ankles, or feet; unusual weakness.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
See also: Nitroglycerin side effects (in more detail)
If OVERDOSE is suspected:
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include cold or blue skin; confusion; diarrhea; excessive sweating; fainting; fast, slow, or irregular heartbeat; persistent throbbing headache; seizures; trouble breathing; vision problems.
Proper storage of Nitroglycerin:
Store Nitroglycerin at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Nitroglycerin out of the reach of children and away from pets.
General information:
- If you have any questions about Nitroglycerin, please talk with your doctor, pharmacist, or other health care provider.
- Nitroglycerin is to be used only by the patient for whom it is prescribed. Do not share it with other people.
- If your symptoms do not improve or if they become worse, check with your doctor.
- Check with your pharmacist about how to dispose of unused medicine.
This information is a summary only. It does not contain all information about Nitroglycerin. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Issue Date: February 1, 2012
Database Edition 12.1.1.002
Copyright © 2012 Wolters Kluwer Health, Inc.
More Nitroglycerin resources
- Nitroglycerin Side Effects (in more detail)
- Nitroglycerin Use in Pregnancy & Breastfeeding
- Drug Images
- Nitroglycerin Drug Interactions
- Nitroglycerin Support Group
- 6 Reviews for Nitroglycerin - Add your own review/rating
- Nitroglycerin Monograph (AHFS DI)
- Nitroglycerin Professional Patient Advice (Wolters Kluwer)
- nitroglycerin Intravenous Advanced Consumer (Micromedex) - Includes Dosage Information
- Minitran Advanced Consumer (Micromedex) - Includes Dosage Information
- Minitran Prescribing Information (FDA)
- Nitro-Bid Prescribing Information (FDA)
- Nitro-Dur Prescribing Information (FDA)
- Nitro-Time Prescribing Information (FDA)
- Nitro-Time Advanced Consumer (Micromedex) - Includes Dosage Information
- NitroMist Consumer Overview
- NitroMist Prescribing Information (FDA)
- Nitrolingual Prescribing Information (FDA)
- Nitrostat Prescribing Information (FDA)
- Rectiv Consumer Overview
- Rectiv Advanced Consumer (Micromedex) - Includes Dosage Information
Compare Nitroglycerin with other medications
- Anal Fissure and Fistula
- Angina
- Angina Pectoris Prophylaxis
- Heart Attack
- Heart Failure
- High Blood Pressure
- Raynaud's Syndrome
Hibitane 5% Concentrate (Molnlycke Health Care )
1. Name Of The Medicinal Product
Hibitane 5% Concentrate.
2. Qualitative And Quantitative Composition
Chlorhexidine gluconate 5.0% w/v (incorporated as Chlorhexidine Gluconate Solution Ph.Eur.).
3. Pharmaceutical Form
Liquid.
4. Clinical Particulars
4.1 Therapeutic Indications
Hibitane 5% Concentrate is an antimicrobial agent for general antiseptic purposes. A surface active agent is present to inhibit precipitation when dilutions are made with hard water.
4.2 Posology And Method Of Administration
For external (topical) use only. No special dosages or indications are specified for use of this product for children or the elderly.
Dilute before use with fresh distilled water, tap water of an acceptable bacteriological standard or alcohol (ethanol, industrial methylated spirit or isopropanol).
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* sterilise the dilution by autoclaving at 115º– 116ºC for 30 minutes or 121º– 123ºC for 15 minutes
4.3 Contraindications
Hibitane preparations are contraindicated for patients who have previously shown a hypersensitivity reaction to chlorhexidine. However, such reactions are extremely rare.
4.4 Special Warnings And Precautions For Use
For external use. Dilute before use. Solutions applied to wounds, burns or broken skin should be sterile. Syringes, needles or instruments which have been immersed in Hibitane solutions should be thoroughly rinsed in sterile water or saline before use. Avoid contact with the brain, meninges and middle ear. Not for injection. Do not use in body cavities. The concentrated solution is irritant to eyes and mucous membranes. Keep all solutions out of the eyes. If chlorhexidine solutions come into contact with the eyes, rinse promptly and thoroughly with water. Prolonged skin contact with alcoholic solutions should be avoided. Allow to dry before proceeding.
As with any other antiseptic agent, antimicrobial activity may be diminished through incompatibility or in the presence of significant quantities of organic matter.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Hibitane 5% Concentrate contains a surfactant and therefore instruments containing cemented glass components should not be disinfected with solutions prepared from Hibitane 5% concentrate.
The low solubility of inorganic salts of chlorhexidine may cause precipitation and consequent loss of activity if Hibitane 5% concentrate is diluted with a solution containing inorganic anions, for example saline or peritoneal dialysis fluid. This precipitation may occur when Hibitane 5% concentrate is used to disinfect catheters intended for use in peritoneal dialysis. Inadvertent repeated exposure of peritoneal membranes to precipitated material has been claimed as a possible predisposing factor for peritoneal fibrosis.
4.6 Pregnancy And Lactation
There is no evidence of any adverse effects from the use of Hibitane 5% Concentrate during pregnancy and lactation therefore no special precautions are recommended.
4.7 Effects On Ability To Drive And Use Machines
None have been reported or are known.
4.8 Undesirable Effects
Irritative skin reactions can occasionally occur. Generalised allergic reactions to chlorhexidine have also been reported but are extremely rare.
4.9 Overdose
This has not been reported.
Accidental ingestion:
Chlorhexidine taken orally is poorly absorbed. Treat with gastric lavage with milk, raw egg, gelatin or mild soap. Employ supportive measures as appropriate.
Accidental intravenous infusion:
Blood transfusion may be necessary to counteract haemolysis.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Chlorhexidine is effective against a wide range of gram-negative and gram-positive vegetative bacteria, yeasts, dermatophyte fungi and lipophilic viruses. It is inactive against bacterial spores except at elevated temperatures.
5.2 Pharmacokinetic Properties
Because of its cationic nature, chlorhexidine binds strongly to skin, mucosa and other tissues and is thus very poorly absorbed. No detectable blood levels have been found in man following oral use and percutaneous absorption, if it occurs at all, is insignificant.
5.3 Preclinical Safety Data
Chlorhexidine is a drug on which extensive clinical experience has been obtained. All relevant information for the prescriber is provided elsewhere in the Summary of Product Characteristics.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Carmoisine E122; d-gluconolactone; isopropyl alcohol; linalyl acetate; nonylphenol/ethylene oxide condensate; purified water.
6.2 Incompatibilities
Hypochlorite bleaches may cause brown stains to develop in fabrics which have previously been in contact with preparations containing chlorhexidine. Chlorhexidine is incompatible with soap and other anionic agents.
6.3 Shelf Life
4 years.
6.4 Special Precautions For Storage
Do not store above 30ºC.
6.5 Nature And Contents Of Container
White HDPE bottle with tamper evident HDPE screw cap (5 litres)
6.6 Special Precautions For Disposal And Other Handling
As cork may protect certain gram-negative organisms from the action of antiseptics, Hibitane solutions must be stored in bottles with glass, plastic or rubber closures.
As a precaution against bacterial contamination, aqueous stock solutions should contain at least 4% v/v of isopropanol or 7% v/v of ethanol which may be denatured (ie industrial methylated spirit).
Aqueous dilutions of Hibitane used for instrument storage should contain 0.1% w/v sodium nitrite to inhibit metal corrosion. Such solutions must be changed every 7 days.
See also section 4.4.
7. Marketing Authorisation Holder
Regent Medical Overseas Limited, Two Omega Drive, River Bend Technology Centre, Irlam, Manchester, M44 5BJ, United Kingdom.
8. Marketing Authorisation Number(S)
PL 21855/0004.
9. Date Of First Authorisation/Renewal Of The Authorisation
30th December 2004.
10. Date Of Revision Of The Text
December 2004.
Sunday, 8 July 2012
Refolinon Tablets
1. Name Of The Medicinal Product
Refolinon Tablets
2. Qualitative And Quantitative Composition
Leucovorin calcium equivalent to
leucovorin (folinic acid) 15.0 mg
3. Pharmaceutical Form
Uncoated tablet for oral use
4. Clinical Particulars
4.1 Therapeutic Indications
Leucovorin (folinic acid) is the formyl derivative of tetrahydrofolic acid and is an intermediate product of the metabolism of folic acid. Leucovorin is used in cytotoxic therapy as an antidote to folic acid antagonists such as methotrexate. Leucovorin is effective in the treatment of megaloblastic anaemia.
4.2 Posology And Method Of Administration
To be given orally.
Although leucovorin calcium may also be available as a solution for injection, leucovorin calcium should not be administered intrathecally.
Adults and children:
Leucovorin rescue: Depending upon the dose of methotrexate administered, dosage regimens of leucovorin calcium vary. Up to 120 mg leucovorin calcium are generally given, usually in divided doses over 12-24 hours by intramuscular injection, bolus intravenous injection or intravenous infusion in normal saline. This is followed by 12-15 mg intramuscularly or 15 mg orally every 6 hours for 48 hours. Rescue therapy is usually started 24 hours after the commencement of methotrexate administration.
If overdosage of methotrexate is suspected, the dose of leucovorin calcium should be equal to or greater than the dose of methotrexate and should be administered within one hour of the methotrexate administration.
Megaloblastic anaemia (folate deficiency): 15 mg (one tablet) leucovorin per day.
4.3 Contraindications
Leucovorin calcium should not be used in patients who have a known hypersensitivity to any of the constituents of the product.
Calcium folinate should not be used for the treatment of pernicious anaemia or other megaloblastic anaemia where vitamin B12 is deficient.
4.4 Special Warnings And Precautions For Use
Calcium folinate should only be used with methotrexate and 5-fluorouracil by clinicians experienced in the use of cancer chemotherapeutic agents.
Patients with rare hereditary problems of galacatose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Leucovorin should not be given simultaneously with a folic acid antagonist, for the purpose of reducing or preventing clinical toxicity, as the therapeutic effect of the antagonist may be nullified.
Folic acid in large amounts may counteract the antiepileptic effect of phenobarbital, phenytoin, as well as primidone and increase the frequency of seizures.
Concurrent administration of chloramphenicol and folic acid in folate-deficient patients may result in antagonism of the haematopoietic response to folic acid.
Calcium folinate may enhance the toxicity of fluorouracil.
4.6 Pregnancy And Lactation
Pregnancy
There are no adequate and well-controlled clinical studies conducted in pregnant or breast feeding women. No formal animal reproductive toxicity studies with calcium folinate have been conducted. There are no indications that folic acid induces harmful effects if administered during pregnancy. During pregnancy, methotrexate should only be administered on strict indications, where the benefits of the drug to the mother should be weighed against possible hazards to the foetus. Should treatment with methotrexate or other folate antagonists take place despite pregnancy or lactation, there are no limitations as to the use of calcium folinate to diminish toxicity or counteract the effects.
5-fluorouracil use is generally contraindicated during pregnancy and contraindicated during breastfeeding; this applies also to the combined use of calcium folinate with 5-fluorouracil.
Please refer to the SPC for methotrexate, other folate antagonists (and 5-fluorouracil) containing medicinal products.
Lactation
It is not known whether calcium folinate is excreted into human breast milk. Calcium folinate can be used during breast feeding when considered necessary according to the therapeutic indications.
4.7 Effects On Ability To Drive And Use Machines
None known.
4.8 Undesirable Effects
Adverse reactions to leucovorin calcium are rare, but following intravenous and intramuscular administration occasional pyrexial reactions have been reported.
The most common dose-limiting adverse reaction occurring in patients receiving combination of calcium folinate and 5-fluorouracil are stomatitis and diarrhoea. In addition, haematological adverse reactions, such as leucocytopenia and thrombocytopenia, may occur. These adverse reactions are dose-dependent and their occurrence can usually be decreased by reducing the dosage of cytotoxic drugs. These adverse reactions can be controlled by close monitoring of haematological values, e.g. blood leucocyte and thrombocyte levels, and serum electrolyte (e.g. Na, K, Ca) and creatinine levels.
Anaphylactoid and urticaria allergic reactions have also been reported with the use of leucovorin.
4.9 Overdose
There have been no reported sequelae in patients who have received significantly more calcium folinate then the recommended dosage. However, excessive amounts of calcium folinate may nullify the chemotherapeutic effect of folic acid antagonists.
Should overdosage of the combination of 5-fluorouracil and calcium folinate occur, the overdosage instructions for 5-FU should be followed.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Methotrexate rescue: Leucovorin (5-formyltetrahydrofolinate) acts partly by providing a fresh supply of tetrahydrofolate and also by competitively displacing methotrexate from dihydrofolate reductase so that its excretion is accelerated (methotrexate binds to the enzyme dihydrofolate reductase which is responsible for reducing dietary folic acid to dihydrofolate and tetrahydrofolate thus inhibiting its action.
Megaloblastic anaemia: Leucovorin is an active folic acid derivative and it can therefore relieve pathological conditions associated with folic acid deficiency e.g. megaloblastic anaemia.
5.2 Pharmacokinetic Properties
The bioavailability of leucovorin following administration of both tablet and parenteral formulations is comparable. After 30 minutes approximately 90% of the total reduced folates were assayed as 5-methyltetrahydrofolate following oral administration compared with only 72% following i.m. administration. The half-life of leucovorin after reaching peak plasma levels was 35-45 minutes by both routes. Peak serum tetrahydrofolate levels were reached 2 hours after oral administration and approximately 40 minutes after i.m administration.
5.3 Preclinical Safety Data
None stated.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Avicel PH101 NF
Magnesium stearate Ph. Eur
Lactose Ph. Eur
6.2 Incompatibilities
None known.
6.3 Shelf Life
60 months.
6.4 Special Precautions For Storage
Store below 25 °C. Do not refrigerate or freeze. Keep out of the reach and sight of children.
6.5 Nature And Contents Of Container
The tablets are contained in white high density polyethylene containers with polyethylene screw closures. The bottles contain 30 or 100 tablets.
6.6 Special Precautions For Disposal And Other Handling
The tablets are contained in white high density polyethylene containers with polyethylene screw closures. The bottles contain 30 or 100 tablets.
7. Marketing Authorisation Holder
Pharmacia Ltd
Ramsgate Road
Sandwich
Kent
CT13 9NJ
8. Marketing Authorisation Number(S)
PL 00032/0347
9. Date Of First Authorisation/Renewal Of The Authorisation
02/12/2005
10. Date Of Revision Of The Text
August 2009
V6.0
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