Nutriflex Lipid Plus ohne Elektrolyte

Arginine:

• Nutriflex Lipid Plus ohne Elektrolyte (Arginine) reviews

Nutritive Wound - Skin Cream

For Minor Cuts and Wounds

- Eases Discomfort

- Soothing Cream

CONTAINS:

Nutriflex Lipid Plus ohne Elektrolyte (Arginine) Aminobenzoate 2.5% Patent # 5734080

In a cream base with Safflower Oil, Apricot Kernel Oil, Mixed Tocopherols, Glycerin, Coconut Oil, Borage Oil, Tea Tree Oil, Camphor, Thymine, Lecithin, Grapefruit Extract, Lemon Oil and Aloe Vera.

DIRECTIONS:

Apply topically as needed to superficial wounds and abrasions.

INDICATIONS FOR USE:

FelineAid can be used on minor cuts, abrasions and irritations as well as superficial wounds and skin lesions on cats.

CAUTIONS:

Avoid contact with eyes. If contact occurs, flush with copious amounts of water. If condition persists or worsens discontinue use.

Shake Well

Store at room temperature.

For Veterinary Use Only

Glycine:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• Im-1453
• Nutriflex Lipid Plus ohne Elektrolyte (Glycine) reviews

INDICATIONS AND USAGE

1.5% Nutriflex Lipid Plus ohne Elektrolyte (Glycine) Irrigation, USP is indicated for use as irrigating fluid during transurethral prostatic resection and other transurethral surgical procedures.

CONTRAINDICATIONS

NOT FOR INJECTION BY USUAL PARENTERAL ROUTES.

Do not use in patients with anuria.

WARNINGS

FOR UROLOGIC IRRIGATION ONLY.

Solutions for urologic irrigation must be used with caution in patients with severe cardiopulmonary or renal dysfunction. Irrigating fluids used during transurethral prostatectomy have been demonstrated to enter the systemic circulation in relatively large volumes. Thus, Nutriflex Lipid Plus ohne Elektrolyte (Glycine) irrigating solution must be regarded as a systemic drug. Absorption of large amounts of fluids containing Nutriflex Lipid Plus ohne Elektrolyte (Glycine) may significantly alter cardiopulmonary and renal dynamics.

Do not heat container over 66°C (150°F).

PRECAUTIONS

Cardiovascular status, especially of the patient with cardiac disease, should be carefully observed before and during transurethral resection of the prostate when using Nutriflex Lipid Plus ohne Elektrolyte (Glycine) irrigating solution, because the quantity of fluid absorbed into the systemic circulation by opened prostatic veins may produce significant expansion of the extracellular fluid and lead to fulminating congestive heart failure. Shift of sodium free intracellular fluid into the extracellular compartment following systemic absorption of solution may lower serum sodium concentration and aggravate pre-existing hyponatremia.

Care should be exercised if impaired liver function is known or suspected. Under such conditions, ammonia resulting from metabolism of Nutriflex Lipid Plus ohne Elektrolyte (Glycine) may accumulate in the blood.

Aseptic technique is essential with the use of sterile solutions for irrigation. The administration set should be attached promptly. Unused portions should be discarded and a fresh container of appropriate size used for the start-up of each cycle or repeat procedure.

Do not administer unless solution is clear, seal is intact and container is undamaged. Discard unused portion.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Studies with Nutriflex Lipid Plus ohne Elektrolyte (Glycine) Irrigation, USP have not been performed to evaluate carcinogenic potential, mutagenic potential, or effects on fertility.

Nursing Mothers: Caution should be exercised when Nutriflex Lipid Plus ohne Elektrolyte (Glycine) Irrigation, USP is administered to a nursing woman.

Pregnancy: Teratogenic Effects.

Pregnancy Category C. Animal reproduction studies have not been conducted with Nutriflex Lipid Plus ohne Elektrolyte (Glycine) Irrigation, USP. It is also not known whether Nutriflex Lipid Plus ohne Elektrolyte (Glycine) Irrigation, USP can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Nutriflex Lipid Plus ohne Elektrolyte (Glycine) Irrigation, USP should be given to a pregnant woman only if clearly needed.

Pediatric Use: The safety and effectiveness of Nutriflex Lipid Plus ohne Elektrolyte (Glycine) Irrigation have not been established. Its limited use in pediatric patients has been inadequate to fully define proper dosage and limitations for use.

ADVERSE REACTIONS

Adverse reactions may result from intravascular absorption of Nutriflex Lipid Plus ohne Elektrolyte (Glycine). Large intravenous doses of Nutriflex Lipid Plus ohne Elektrolyte (Glycine) are known to cause salivation, nausea and lightheadedness. Other consequences of absorption of urologic irrigating solutions include fluid and electrolyte disturbances such as acidosis, electrolyte loss, marked diuresis, urinary retention, edema, dryness of mouth, thirst, dehydration, coma from hyponatremia, secondary hyponatremia due to fluid overload, and hyper- ammonemia with resultant coma and/or encephalopathy; cardiovascular disorders such as hypotension, tachycardia, angina-like pains; pulmonary disorders such as pulmonary congestion; and other general reactions such as blurred vision, convulsions, nausea, vomiting, rhinitis, chills, vertigo, backache, transient blindness and urticaria. Allergic reactions from Nutriflex Lipid Plus ohne Elektrolyte (Glycine) are unknown or exceedingly rare.

Should any adverse reaction occur, discontinue the irrigant, evaluate the patient, institute appropriate therapeutic countermeasures and save the remainder of the fluid for examination if deemed necessary.

OVERDOSAGE

In the event of overhydration or solute overload, re-evaluate the patient and institute appropriate corrective measures. See WARNINGS, PRECAUTIONS and ADVERSE REACTIONS.

DOSAGE AND ADMINISTRATION

1.5% Nutriflex Lipid Plus ohne Elektrolyte (Glycine) Irrigation, USP should be administered only by transurethral instillation with appropriate urologic instrumentation. A disposable irrigation set should be used. The total volume of solution used for irrigation is solely at the discretion of the surgeon.

Height of container(s) above the operating table in excess of 60 cm (approx. 2 ft.) has been reported to increase intravascular absorption of the irrigating fluid.

Drug Interactions

Additives may be incompatible. Consult with pharmacist, if available. When introducing additives, use aseptic technique, mix thoroughly and do not store.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution container permits. See PRECAUTIONS.

HOW SUPPLIED

1.5% Nutriflex Lipid Plus ohne Elektrolyte (Glycine) Irrigation, USP is supplied in single-dose 3000 mL flexible irrigation container ( List No. 7974).

Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing. Store at 20 to 25°C (68 to 77°F).

Revised: October 2004

©Hospira 2004 EN-0577 Printed in USA

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

IM-1453

iv bag ndc 0409-7974-08

2

HDPE

TO OPEN TEAR AT NOTCH

DO NOT REMOVE FROM OVERWRAP UNTIL READY FOR USE. AFTER REMOVING

THE OVERWRAP, CHECK FOR MINUTE LEAKS BY SQUEEZING CONTAINER FIRMLY.

IF LEAKS ARE FOUND, DISCARD SOLUTION AS STERILITY MAY BE IMPAIRED.

RECOMMENDED STORAGE: ROOM TEMPERATURE (25°C). AVOID EXCESSIVE

HEAT. PROTECT FROM FREEZING. SEE INSERT.

98-4321-R14-3/98

Lysine Monohydrate:

• Boxed warning
• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate) reviews

BOXED WARNING

Pharmacy Bulk Package

Not For Direct Infusion

DESCRIPTION

Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15% Amino Acids Injection in a Pharmacy Bulk Package is a sterile, clear, nonpyrogenic solution of essential and nonessential amino acids for intravenous infusion in parenteral nutrition following appropriate dilution.

Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15% in a Pharmacy Bulk Package is not for direct infusion. It is a sterile dosage from which contains several single doses for use in a pharmacy admixture program in the preparation of intravenous parenteral fluids.

Each 100 mL contains:

Essential Amino Acids
Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate) (from Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate) Acetate, USP)……………………………………...1.18		g
Leucine, USP……………………………………………………………...1.04		g
Phenylalanine, USP……………………………………...1.04		g
Valine, USP……………………………………………………………...960		mg
Isoleucine, USP………………………………………...749		mg
Methionine, USP………………………………………...749		mg
Threonine, USP………………………………………...749		mg
Tryptophan, USP………………………………………...250		mg
Nonessential Amino Acids
Alanine, USP…………………………………………...2.17		g
Arginine, USP…………………………………………...1.47		g
Glycine, USP…………………………………………...1.04		g
Histidine, USP…………………………………………...894		mg
Proline, USP……………………………………………………………...894		mg
Glutamic Acid…………………………………………...749		mg
Serine, USP……………………………………………...592		mg
Aspartic Acid, USP……………………………………...434		mg
Tyrosine, USP…………………………………………...39		mg
Sodium Metabisulfite, NF added……………………………………………...30		mg
Water for Injection, USP……………………………………………………...		qs
Essential Amino Acids………………………………………………………...6.7		g
Nonessential Amino Acids…………………………………………………...8.3		g
Total Amino Acids…………………………………………………………...15.0		g
Total Nitrogen………………………………………………………………...2.37		g
Acetate*……………………………………………………...151		mEq/L
Osmolarity (calculated)……………………………………...1388		mOsmol/L
pH……………………………………………………………………………...5.6(5.2-6.0)
*Acetate from Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate) Acetate, USP and acetic acid used for pH adjustment.

The formulas for the individual amino acids are as follows:

Formulas for individual amino acids

CLINICAL PHARMACOLOGY

Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15% Amino Acids Injection providesseventeen crystalline amino acids. This completely utilizable substrate promotesprotein synthesis and wound healing and reduces the rate of protein catabolism.

A.Total Parenteral Nutrition (Central Infusion)

When enteralfeeding is inadvisable, Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15% given by central venousinfusion in combination with energy sources, vitamins, trace elements andelectrolytes, will completely satisfy the requirements for weight maintenanceor weight gain, depending upon the dose selected. The energy component inparenteral nutrition by central infusion may be derived solely from dextroseor may be provided by a combination of dextrose and intravenous fat emulsion. The addition of intravenous fat emulsion provides essential fatty acids andpermits a dietary balance of fat and carbohydrate, at the same time offeringthe option of reducing the dextrose load and/or increasing the total caloricinput. An adequate energy supply is essential for optimal utilization of aminoacids.

B. Total Parenteral Nutrition (Peripheral Infusion)

Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15%can also be administered as part of a total parenteral nutrition program byperipheral vein when the enteral route is inadvisable and use of the centralvenous catheter is contraindicated.

Reduction of proteinloss can be achieved by use of diluted Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15% in combinationwith dextrose or with dextrose and intravenous fat emulsion by peripheralinfusion. Complete peripheral intravenous nutrition can be achieved in patientswith low caloric requirements by a Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^®15%-dextrose-fatregimen.

INDICATIONS AND USAGE

Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15% is indicated as an amino acid(nitrogen) source in parenteral nutrition regimens. This use is appropriatewhen the enteral route is inadvisable, inadequate or not possible, as when:

-Gastrointestinal absorption is impaired by obstruction, inflammatory diseaseor its complications, or antineoplastic therapy;

-Bowel rest is needed because of gastrointestinal surgery or its complicationssuch as ileus, fistulae or anastomotic leaks;

-Tube feeding methods alone cannot provide adequate nutrition.

CONTRAINDICATIONS

This solution should not be used in patients in hepatic coma,severe renal failure, metabolic disorders involving impaired nitrogen utilizationor hypersensitivity to one or more amino acids.

WARNINGS

Administration of amino acids solutions at excessive ratesor to patients with hepatic insufficiency may result in plasma amino acidimbalances, hyperammonemia, prerenal azotemia, stupor and coma. Conservativedoses of amino acids should be given to these patients, dictated by the nutritionalstatus of the patient. Should symptoms of hyperammonemia develop, amino acidadministration should be discontinued and the patient’s clinical statusre-evaluated.

Contains sodium metabisulfite, a sulfitethat may cause allergic-type reactions including anaphylactic symptoms andlife-threatening or less severe asthmatic episodes in certain susceptiblepeople. The overall prevalence of sulfite sensitivity in the general populationis unknown and probably low.

Sulfite sensitivity isseen more frequently in asthmatic than in nonasthmatic people.

WARNING: This product contains aluminum that maybe toxic. Aluminum may reach toxic levels with prolonged parenteral administrationif kidney function is impaired. Premature neonates are particularly at riskbecause their kidneys are immature, and they require large amounts of calciumand phosphate solutions, which contain aluminum.

Researchindicates that patients with impaired kidney function, including prematureneonates, who receive parenteral levels of aluminum at greater than 4 to 5mcg/kg/day accumulate aluminum at levels associated with central nervous systemand bone toxicity. Tissue loading may occur at even lower rates of administration.

PRECAUTIONS

A. GENERAL

It is essential to provide adequate calories concurrently if parenterally administered amino acids are to be retained by the body and utilized for protein synthesis.

The administration of Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15% Amino Acids Injection as part of total parenteral nutrition (TPN) with large volumes of hyperosmotic fluids requires periodic monitoring of the patient for signs of hyperosmolarity, hyperglycemia, glycosuria and hypertriglyceridemia.

During parenteral nutrition with concentrated dextrose and amino acids solutions, essential fatty acid deficiency syndrome may develop but may not be clinically apparent. Early demonstration of this condition can only be accomplished by gas liquid chromatographic analysis of plasma lipids. The syndrome may be prevented or corrected by appropriate treatment with intravenous fat emulsions.

For complete nutritional support, TPN regimens must also include multiple vitamins and trace elements. Potentially incompatible ions such as calcium and phosphate may be added to alternate infusate bottles to avoid precipitation. Although the metabolizable acetate ion in Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15% diminishes the risk of acidosis, the physician must be alert to the potential appearance of this disorder.

Initiation and termination of infusions of TPN fluids must be gradual to permit adjustment of endogenous insulin release.

Undiluted Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15% should not be administered peripherally. When administered centrally, it should be diluted with appropriate diluents, e.g., dextrose, electrolytes and other nutrient components, to at least half strength. See DOSAGE AND ADMINISTRATION.

Caution against volume overload should be exercised.

Drug product contains no more than 25 mcg/L of aluminum.

B. Laboratory Tests

Infusion of Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15% without concomitant infusion of an adequate number of non-protein calories may result in elevated BUN. Monitoring of BUN is required and the balance between Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15% and the calorie source may require adjustment. Frequent clinical evaluations and laboratory determinations are required to prevent the complications which may occur during the administration of solutions used in TPN. Laboratory tests should include blood glucose, serum electrolytes, liver and kidney function, serum osmolarity, blood ammonia, serum protein, pH, hematocrit, WBC and urinary glucose. When Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15% is combined with electrolytes, care should be used in administering this solution to patients with congestive heart failure, renal failure, edema, adrenal hyperactivity, acid-base imbalance and those receiving diuretics or antihypertensive therapy. Total volume infused should be closely monitored. Serum electrolytes should be monitored daily in these patients.

C. Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies with Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15% have not been performed to evaluate carcinogenic potential, mutagenic potential, or effects on fertility.

D. Pregnancy Category C

Animal reproduction studies have not been conducted with Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15%. It is also not known whether Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15% can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15% should be given to a pregnant woman only if clearly needed.

E. Nursing Mothers

Caution should be exercised when Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15% is administered to a nursing woman.

F. Pediatric Use

Safety and effectiveness of Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15% Amino Acids Injection in pediatric patients have not been established by adequate and well-controlled studies. However, the use of amino acids injections in pediatric patients as an adjunct in the offsetting of nitrogen loss or in the treatment of negative nitrogen balance is referenced in the medical literature.

G. Special Precautions for Central Infusion

TPN delivered by indwelling catheter through a central or large peripheral vein is a special technique requiring a team effort by physician, nurse and pharmacist. The responsibility for administering this therapy should be confined to those trained in the procedures and alert to signs of complications. Complications known to occur from the placement of central venous catheter are pneumothorax, hemothorax, hydrothorax, artery puncture and transection, injury to the brachial plexus, malposition of the catheter, formation of arteriovenous fistula, phlebitis, thrombosis, and air/catheter emboli. The risk of sepsis is present during intravenous therapy, especially when using central venous catheters for prolonged periods. It is imperative that the preparation of admixtures and the placement and care of the catheters be accomplished under controlled aseptic conditions.

H. Admixtures

Admixtures should be prepared under a laminar flow hood using aseptic technique.

Admixtures should be stored under refrigeration and must be administered within 24 hours after removal from refrigerator.

Filters of less than 1.2 micron pore size must not be used with admixtures containing fat emulsion.

I. Do not administer unless solution is clear and the seal is intact.

IT IS ESSENTIAL THAT A CAREFULLY PREPARED PROTOCOL, BASED ON CURRENT MEDICAL PRACTICES, BE FOLLOWED, PREFERABLY BY AN EXPERIENCED TEAM.

ADVERSE REACTIONS

OVERDOSAGE

In the event of overhydration or solute overload, re-evaluatethe patient and institute appropriate corrective measures. See WARNINGS andPRECAUTIONS.

DOSAGE AND ADMINISTRATION

The appropriate daily dose of amino acids to be used withdextrose or with dextrose and intravenous fat emulsion will depend upon themetabolic status and clinical response of the patient as therapy proceeds. Doses which achieve nitrogen equilibrium or positive balance are the mostdesirable. The dosage on the first day should be approximately half the anticipatedoptimal dosage and should be increased gradually to minimize glycosuria; similarly,withdrawal should be accomplished gradually to avoid rebound hypoglycemia.

Fatemulsion coadministration should be considered when prolonged (more than 5days) parenteral nutrition is required in order to prevent essential fattyacid deficiency (EFAD). Serum lipids should be monitored for evidence of EFADin patients maintained on fat free TPN.

The amount administeredis dosed on the basis of amino acids/kg of body weight/day. In general, twoto three g/kg of body weight for neonates and infants with adequate caloriesare sufficient to satisfy protein needs and promote positive nitrogen balance. In pediatric patients, the final solution should not exceed twice normal serumosmolarity (718 mOsmol/L).

DIRECTIONSFOR PROPER USE OF PHARMACY BULK PACKAGE

Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15%in a Pharmacy Bulk Package is not intended for direct infusion. The containerclosure may be penetrated only once using a suitable sterile transfer deviceor dispensing set which allows measured dispensing of the contents. The PharmacyBulk Package is to be used only in a suitable work area such as a laminarflow hood (or an equivalent clean air compounding area). Once the closureis penetrated, the contents should be dispensed as soon as possible; the transferof contents must be completed within 4 hours of closure entry. The bottlemay be stored at room temperature (25°C) after the closure has been entered. Date and time of container entry should be noted in the area designated onthe container label.

When using Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15%in patients with a need for fluid volume restriction, it can be diluted asfollows:

	Volume	Amount	FinalConcentration
Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)® 15%	500 mL	75 g	7.5%
Dextrose 70%	250 mL	175 g	17.5%
Intralipid® 20%	250 mL	50 g	5.0%

This will provide 1395 kilocalories (kcal) per 1000 mLof admixture with a ratio of 118 non-protein calories per gram of nitrogenand an osmolarity of 1561 mOsmol/L.

In patients wherethe need for fluid restriction is not so marked, either of the following regimensmay be used dependent upon the energy needs of the patient.

	Volume	Amount	FinalConcentration
Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)® 15%	500 mL	75 g	3.75%
Dextrose 50%	1000 mL	500 g	25%
Intralipid® 20%	500 mL	100 g	5%

This will provide 1500 kcal per 1000 mL of admixture witha ratio of 228 non-protein calories per gram of nitrogen and an osmolarityof 1633 mOsmol/L.

	Volume	Amount	FinalConcentration
Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)® 15%	500 mL	75 g	3.75%
Dextrose 30%	1000 mL	300 g	15%
Intralipid® 10%	500 mL	50 g	2.5%

This will provide 935 kcal per 1000 mL of admixture witha ratio of 158 non-protein calories per gram of nitrogen and an osmolarityof 1128.5 mOsmol/L.

A. Total Parenteral Nutrition (CentralInfusion)

In unstressed adult patients with no unusualnitrogen losses, a minimum dosage of 0.1 gram nitrogen (4.2 mL of Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15%)plus 4.4 grams (15 calories) of dextrose per kilogram of body weight per dayare required to achieve nitrogen balance and weight stability. Intravenousfat emulsion may be used as a partial substitute for dextrose. This regimenprovides a ratio of 150 non-protein calories per gram of nitrogen.

Forpatients stressed by surgery, trauma or sepsis, and those with unusual nitrogenlosses, the dosage required for maintenance may be as high as 0.3 to 0.4 gramsof nitrogen (13 to 17 mL Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15%) per kilogram of bodyweight per day, with proportionate increases in non-protein calories. Periodicassessment of nitrogen balance of the individual patient is the best indicatorof proper dosage. Volume overload and glycosuria may be encountered at highdosage, and nitrogen balance may not be achieved in extremely hypermetabolicpatients under these constraints. Concomitant insulin administration may berequired to minimize glycosuria. Daily laboratory monitoring is essential.

Useof an infusion pump is advisable to maintain a steady infusion rate duringcentral venous infusion.

B. Peripheral Nutrition

Inpatients for whom central venous catheterization is not advisable, proteincatabolism can be reduced by peripheral use of diluted Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15%plus non-protein calorie sources. Dilution of 250 mL Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15%in 750 mL of 10% dextrose will reduce the osmolarity to a level (724 mOsmol/L)which is more favorable to the maintenance of the integrity of the walls ofthe veins. Intravenous fat emulsion can be infused separately or simultaneously;if infused simultaneously the fat emulsion will provide a dilution effectupon the osmolarity while increasing the energy supply.

Parenteraldrug products should be inspected visually for particulate matter and discolorationprior to administration, whenever solution and container permit.

Toreduce the risk of bacterial contamination, all intravenous administrationsets should be replaced at least every 24 hours. Usage of admixtures mustbe initiated within 24 hours after mixing. If storage is necessary duringthis 24 hour period, admixtures must be refrigerated and completely used within24 hours of beginning administration.

HOW SUPPLIED

Nutriflex Lipid Plus ohne Elektrolyte (Lysine Monohydrate)^® 15% Amino Acids Injection is suppliedas a Pharmacy Bulk Package in 500 mL containers.

500mL NDC 0409-0468-05

STORAGE

Store inthe closed carton; do not expose solution to light until ready for use. Exposureof pharmaceutical products to heat should be minimized. Avoid excessive heat. It is recommended that the product be stored at 20 to 25°C (68 to 77°F). Brief exposure to temperatures above25°C during transport and storage will not adversely affect the product. Solution that has been frozen must not be used.

©Hospira 2005	EN-1010

Hospira, Inc., Lake Forest, IL 60045 USA

RL-1450

Soybean Oil:

• Warnings
• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdose section
• Dosage and administration
• How supplied
• Storage and handling
• Limited warranty
• References
• Nutriflex Lipid Plus ohne Elektrolyte (Soybean Oil) reviews

WARNINGS

This product is intended for use only by licensed medical personnel experienced in administering allergenic extracts and trained to provide immediate emergency treatment in the event of a life-threatening reaction. Allergenic extracts may potentially elicit a severe life-threatening systemic reaction, rarely resulting in death.1

Therefore, emergency measures and personnel trained in their use must be available immediately in the event of such a reaction.

Patients should be instructed to recognize adverse reaction symptoms, be observed in the office for at least 30 minutes after skin testing or treatment, and be cautioned to contact the physician's office if symptoms occur. See ADVERSE REACTION section of this package insert regarding adverse event reporting.

Standardized glycerinated extracts may be more potent than regular extracts and therefore are not directly interchangeable with non-standardized extracts, or other manufacturers' products.

Patients with cardiovascular diseases and/or pulmonary diseases such as symptomatic unstable, steroid dependent asthma, and/or those who are receiving cardiovascular drugs such as beta blockers, may be at higher risk for severe adverse reactions. These patients may also be more refractory to the normal allergy treatment regimen. Patients should be treated only if the benefit of treatment outweighs the risks.1

Patients on beta blockers may be more reactive to allergens given for testing or treatment and may be unresponsive to the usual doses of epinephrine used to treat allergic reactions. 2

This product should never be injected intravenously.

Refer to the WARNINGS, PRECAUTIONS, ADVERSE REACTIONS and OVERDOSE Sections for further discussion.

DESCRIPTION

The allergenic extract in this vial is referred to as a "bulk" extract or stock concentrate since it is designed primarily for the physician equipped to prepare dilutions and mixtures as required. The extract is sterile and intended for subcutaneous injection for immunotherapy and scratch, prick or puncture for diagnosis. Unless specified otherwise, the concentration of extract supplied will in most cases be expressed in weight to volume (e.g., 1:10 or 1:20 w/v) and will be the strongest available. Where mixtures of pollens and non-pollens have been ordered, the mixed extract will be treated as a pollen mixture. To insure maximum potency for the entire dating period, all bulk concentrates will contain 50% volume to volume (v/v) glycerin unless otherwise requested. Dilutions will also be prepared with 50% (v/v) glycerin unless another diluent is specified.

Source materials utilized in allergenic extract products include pollens, molds, animal epidermals, insects, foods and environmental materials.

Pollens are collected using techniques such as waterset or vacuuming, cleaned and purified to greater than 99% single specie pollen (less than 1% foreign particle presence).

Molds are typically grown on synthetic nutrient medias and are derived from the surface growth (mycelia).

Animal source materials are collected from animals deemed to be healthy at the time of collection by a veterinarian or individual trained and certified by a veterinarian. Epidermals include feathers, hair and dander, or the whole epidermal (pelt) as described on product labeling.

Regular process epidermals are extractions of the source material without additional processing, except that certain materials are defatted. AP (acetone precipitated) epidermal source materials are derived from the precipitate formed when acetone is added to an aqueous extract. The resulting precipitate is dried, and becomes the source material for the AP product.

Insects are collected in whole body form. Extractions take place as whole body or ground insects.

Information on Foods and other Environmental source materials can be obtained by contacting our Customer Service Department.

The following is a brief summary of the six methods of describing allergenic product concentration.

1. Weight to volume (w/v). Weight to volume (w/v) describes the weight of allergenic source material added to a given volume of extracting fluid. A 1:10 w/v extract, e.g., indicates that the solution contains the extractable material from one gram of raw material added to each 10 mL Glycero-Coca's or 10 mL Coca's extracting fluid. The amount and composition of extracted materials will vary with the type of antigen, the extracting fluid, duration of extraction, pH, temperature, and other variables. Pollens are typically extracted at a 1:20 w/v ratio in Glycero-Coca's while Coca's extracts are 1:10 w/v. Epidermal, environmental, regular molds and insect products are typically extracted at 1:10 w/v. AP (acetone precipitated) epidermal products are prepared at a 1:50 w/v concentration (i.e., 1 gram of dried precipitate in 50 mL of reconstitution fluid). AP Dog Hair-Dander is prepared at 1:100 w/v concentration. (i.e., 1 gram of dried precipitate in 100 mL of reconstitution fluid.)

2. Protein Nitrogen Units per mL (PNU/mL). One protein nitrogen unit represents 0.00001 mg phosphotungstic acid precipitable protein nitrogen dissolved in one mL of antigen extract. The PNU content of extracts of the same antigen may vary according to the method of measuring the PNU. Thus, the PNU content of extracts from different manufacturers is not comparable unless the PNU method is known to be the same and is reproducible from lot to lot. The amount of protein nitrogen extracted from the source material is influenced by such factors as the type of antigen, the extracting fluid, duration of extraction, pH, temperature and other variables. Allergenic materials make up a variable proportion of the total protein of an extract. Most allergenic extracts are assayed for PNU. Specific PNU information is available upon request.

3. Amb a 1. Of the many allergens from Short Ragweed which have been purified and characterized [Amb a 1 3 (also known as Antigen E), Amb a 2 3 (also known as Antigen K), Ra3 4, Ra4 (BPA-R) 5, Ra5 6, Ra6, Ra7, Ra87, and cytochrome C 8], Amb a 1 is considered the most important and has been selected as the basis for standardization. Extracts of Short Ragweed containing Amb a 1 are diffused in agar against standard anti-serum to Amb a 1, and compared to the diffusion of standard Amb a 1 solutions. The amount of Amb a 1 is expressed as units of Amb a 1 per mL of extract. A Short Ragweed pollen extracted at 1:20 (w/v) usually assays within a range of 50,000 to 70,000 PNU/mL and 100 to 300 units of Amb a 1 per mL.

The Amb a 1 concentration of any Short Ragweed extract which is diluted with a diluent or other allergenic extracts is determined by calculation. The resulting Amb a 1 value does not reflect the total potency of the product if Short Ragweed extract is mixed with another allergenic extract.

4. Allergy Units per mL (AU/mL). The potency of extracts labeled in Allergy Units (AU)/mL is determined by in vitro comparison to a reference standard established by the Center for Biologics Evaluation and Research (CBER) of the Food and Drug Administration (FDA).

5. Bioequivalent Allergy Units per mL (BAU/mL). Other standardized allergenic extracts are labeled in Bioequivalent Allergy Units/mL (BAU/mL) based on their comparison (by in vitro assay or major allergen content) to CBER, FDA Reference Preparations. The FDA reference extracts have been assigned Bioequivalent Allergy Units based on the CBER ID₅₀EAL method.9 Briefly, highly sensitive patients are skin tested to the reference preparation using an intradermal technique employing 3-fold extract dilutions. Depending on the dilution which elicits a summation of erythema diameter of 50, Bioequivalent Allergy Units are assigned as follows:

BAU/mL	D50 Range
100,000	13.9 - 15.9
10,000	10.9 - 12.9
1,000	8.8 - 10.8
100	6.7 - 8.7

References labeled 10,000 BAU/mL can be diluted one to a half million fold, and references labeled 100,000 BAU/mL can be diluted one to 5 million fold and produce a sum of erythema diameter of 50 mm when Intradermal testing highly reactive subjects.

6. Concentrate. Concentrate label terminology applies to allergenic extract mixtures, where the individual allergens being combined vary in strength or the designation of strength.

e.g. Concentrate

50% Short Ragweed 1:20 w/v

25% Std. Cat Pelt 10,000 BAU/mL

25% Mite D. farinae 10,000 AU/mL

Should the physician choose to calculate the actual strength of each component in the "Concentrate" mixture, the following formulation may be used:

Actual Allergen Strength in Concentrate	=	Allergen Manufacturing Strength	X	% Allergen in Formulation (by volume or parts)

Ingredients: Active ingredients are the allergen(s) noted on the vial label. Preservative is 50% (v/v) glycerin, or 0.4% phenol, as indicated on the vial label. Additional ingredients are 0.5% sodium chloride, and 0.275% sodium bicarbonate.

CLINICAL PHARMACOLOGY

The mechanism by which hyposensitization is achieved is not known completely. It has been shown that repeated injections of appropriate allergenic extracts will ameliorate the intensity of allergic symptoms upon contact with the allergen.11, 12, 13, 14 Clinical studies which address the efficacy of immunotherapy are available. The allergens which have been studied are cat, mite, and some pollen extracts.10, 15, 16, 17, 18, 19

IgE antibodies bound to receptors on mast cell membranes are required for the allergic reaction, and their level is probably related to serum IgE concentrations. Immunotherapy has been associated with decreased levels of IgE, and also with increases in allergen specific IgG "blocking" antibody.

The histamine release response of circulating basophils to a specific allergen is reduced in some patients by immunotherapy, but the mechanism of this change is not clear.

Further study and clarification of the relationships among changes in blocking antibody, reaginic antibody, and mediator-releasing cells, and between these three factors and successful immunotherapy, is needed.

INDICATIONS AND USAGE

20,21,22,23

Allergenic extracts are indicated for use in diagnosis and immunotherapy of patients presenting symptoms of allergy (hay fever, rhinitis, etc.) to specific environmental allergens. The selection of allergenic extracts to be used should be based on a thorough and carefully taken history of hypersensitivity, and confirmed by skin testing.

The use of mixed or unrelated antigens for skin testing is not recommended since, in the case of a positive reaction, it does not indicate which component of the mix is responsible for the reaction, while, in the case of a negative reaction, it fails to indicate whether the individual antigens at full concentration would give a positive reaction. Utilization of such mixes for compounding a treatment may result, in the former case, in administering unnecessary antigens and, in the latter case, in the omission of a needed antigen.

Avoidance of allergens is to be advocated if possible, but cannot always be attained, e.g., allergy to dog dander in kennel owners and employees, dog breeders, research workers, veterinarians, etc.

Allergens to which a patient is extremely sensitive should not be included in treatment mixes with allergens to which there is much less sensitivity, but should be administered separately. This allows individualized and better control of dosage increases, including adjustments in dosage becoming necessary after severe reactions which may occur with the highly reactive allergen.

CONTRAINDICATIONS

There are no known absolute contraindications to immunotherapy. See PRECAUTIONS and WARNINGS.

Patients with cardiovascular diseases and/or pulmonary diseases such as symptomatic unstable, steroid-dependent asthma, and/or those who are receiving cardiovascular drugs such as beta blockers, may be at higher risk for severe adverse reactions. These patients may also be more refractory to the normal allergy treatment regimen. Patients should be treated only if the benefit of treatment outweighs the risks.1

Treat patients only with allergens to which they are allergic by skin test reaction, have a history of symptoms on exposure, and are likely to be exposed to again.

Any injections, including immunotherapy, should be avoided in patients with a bleeding tendency. Patients on beta blockers may be more reactive to allergens given for testing or treatment and may be unresponsive to the usual doses of epinephrine used to treat systemic reactions.2

Since there are differences of opinion concerning the possibility of routine immunizations exacerbating autoimmune diseases, immunotherapy should be given cautiously to patients with other immunologic diseases and only if the risk from exposure is greater than the risk of exacerbating the underlying disorder.

WARNINGS

Allergenic extracts must be temporarily withheld from patients or the dose adjusted downward if any of the following conditions exist: (1) severe symptoms of rhinitis and/or asthma; (2) infection or flu accompanied by fever; (3) any evidence of an excessively large local or any generalized reaction during the initial stages of immunotherapy or during maintenance therapy, and/or (4) exposure to excessive amounts of clinically relevant allergen prior to a scheduled injection. Do not administer immunotherapy during a period of symptoms due to exposure. Since the individual components of the extract are those to which the patient is allergic, and to which s/he will be exposed, typical allergic symptoms may follow shortly after the injection, particularly when the antigen load from exposure plus the injected antigen exceeds the patient's antigen tolerance.

THE CONCENTRATE MUST NOT BE INJECTED AT ANY TIME UNLESS TOLERANCE HAS BEEN ESTABLISHED. DILUTE CONCENTRATED EXTRACTS WITH STERILE DILUENT FOR SKIN TESTING AND IMMUNOTHERAPY.

INJECTIONS MUST NEVER BE GIVEN INTRAVENOUSLY. Subcutaneous injection is recommended. Intracutaneous or intramuscular injection may produce large local reactions or be excessively painful.

AFTER INSERTING NEEDLE SUBCUTANEOUSLY, BUT BEFORE INJECTING, ALWAYS WITHDRAW THE PLUNGER SLIGHTLY. IF BLOOD APPEARS IN THE SYRINGE, CHANGE NEEDLE AND GIVE THE INJECTION IN ANOTHER SITE.

IF CHANGING TO A DIFFERENT LOT OF EXTRACT: All extracts lose potency over time, and a fresh extract could have an effective potency that is substantially greater than that of the old extract. Even though it is the same formula and concentration, the first dose from the new vial should not exceed 50% of the previous dose.

IF THE EXTRACT PREVIOUSLY USED WAS FROM ANOTHER MANUFACTURER: Since manufacturing processes and sources of raw materials differ among manufacturers, the interchangeability of extracts from different manufacturers cannot be insured. The starting dose of the extract therefore should be greatly decreased even though the extract is the same formula and dilution. In general, a dose reduction to 50% of the previous product dose should be adequate, but each situation must be evaluated separately considering the patient's history of sensitivity, tolerance of previous injections, and other factors. If the patient tolerates a 50% decrease, the next dose could be raised to the previous dose amount. If the decrease is greater than 50%, the next dose would need to be determined by the allergist, depending on the situation. Dose intervals should not exceed one week when rebuilding dose. See DOSAGE AND ADMINISTRATION.

IF A PROLONGED PERIOD OF TIME HAS ELAPSED SINCE THE LAST INJECTION: Patients may lose tolerance for allergen injections during prolonged periods between doses. The duration of tolerance is an individual characteristic and varies from patient to patient. In general, the longer the lapse in the injection schedule, the greater dose reduction required. If the interval since last dose is over four weeks, perform skin tests to determine starting dose. See DOSAGE AND ADMINISTRATION.

IF THE PREVIOUS EXTRACT WAS OUTDATED: The dating period for allergenic extracts indicates the time that they can be expected to remain potent under refrigerated storage conditions (2° - 8°C). During the storage of extracts, even under ideal conditions, some loss of potency occurs. For this reason, extracts should not be used beyond their expiration date. If a patient has been receiving injections of an outdated extract, s/he may experience excessive local or systemic reactions when changed to a new and possibly more potent extract. In general, the longer the material has been outdated, the greater the dose reduction necessary for the fresh extract.

IF CHANGING FROM ALUM-ADSORBED TO AQUEOUS OR GLYCERINATED EXTRACTS: When the patient was previously receiving alum-adsorbed or alum-precipitated extract, the safest course is to start over as though the patient had not been receiving immunotherapy. See DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS.

IF ANY OTHER CHANGES HAVE BEEN MADE IN THE EXTRACT CONCENTRATE FORMULA: Changes other than those listed above may include situations such as a redistribution of component parts or percentages, a difference in extracting fluid (i.e., change from non-glycerin extracts to 50% glycerin extracts), combining two or more stock concentrates, or any other change. It should be recognized that any change in formula can affect a patient's tolerance of the treatment. The usual 1/2 of the previous dose for a new extract may produce an adverse reaction; extra dilutions are recommended whenever starting a revised formula. The greater the change, the greater the number of dilutions required.

Proper selection of the dose and careful injection should prevent most systemic reactions. It must be remembered that allergenic extracts are highly potent in sensitive individuals, and that systemic reactions of varying degrees of severity may occur, including urticaria, rhinitis, conjunctivitis, wheezing, coughing, angioedema, hypotension, bradycardia, pallor, laryngeal edema, fainting, or even anaphylactic shock and death, as described under ADVERSE REACTIONS. Patients should be informed of this, and the precautions should be discussed prior to immunotherapy. Severe systemic reactions should be treated as indicated in ADVERSE REACTIONS. Refer to WARNINGS box.

PRECAUTIONS

1. General

The presence of asthmatic signs and symptoms appear to be an indicator for severe reactions following allergy injections. An assessment of airway obstruction either by measurement of peak flow or an alternate procedure may provide a useful indicator as to the advisability of administering an allergy injection.1, 24, 25, 26, 27

Concentrated extracts must not be injected unless tolerance has been established. Concentrated extracts must be diluted prior to use: See DOSAGE and ADMINISTRATION for detailed instructions on the dilution of allergenic extracts.

Any evidence of a local or generalized reaction requires a reduction in dosage during the initial stages of immunotherapy, as well as during maintenance therapy.

Allergenic extracts diluted with sterile Albumin Saline with Phenol may be more potent than extracts diluted with diluents which do not contain stabilizers. When switching from non-stabilized to stabilized diluent, consider weaker initial dilutions for both intradermal testing and immunotherapy.

Sterile solutions, vials, syringes, etc. should be used and aseptic precautions observed in making dilutions.

To avoid cross-contamination, do not use the same needle to withdraw materials from vials of more than one extract, or extract followed by diluent.

A sterile tuberculin syringe graduated in 0.01 mL units and with a needle at least 5/8" long should be used to measure each dose from the appropriate dilution.

Aseptic techniques should always be employed when injections of allergenic extracts are being administered. A separate sterile syringe should be used for each patient to prevent transmission of hepatitis and other infectious agents from one person to another.

Patient reactions to previous injections should be reviewed before each new injection, so that dosage can be adjusted accordingly. See ADVERSE REACTIONS and WARNINGS.

Rarely, a patient is encountered who develops systemic reactions to minute doses of allergen and does not demonstrate increasing tolerance to injections after several months of treatment. If systemic reactions or excessive local responses occur persistently at very small doses, efforts at immunotherapy should be stopped.

PATIENTS SHOULD BE OBSERVED IN THE OFFICE FOR AT LEAST 30 MINUTES AFTER SKIN TESTING AND EACH TREATMENT INJECTION. Most severe reactions will occur within this time period, and rapid treatment measures should be instituted. See ADVERSE REACTIONS for such treatment measures.

In order to avoid darkening and possible precipitation, do not dilute the following extracts with solutions containing phenol: Privet pollen and food extracts of White Potato, Corn, Oat, Rye, and Wheat. Injections of such extracts discolored by reaction with phenol may produce a lasting tattoo-like discoloration of the skin.

2. Information for Patients

Patients should be instructed in the recognition of adverse reactions to immunotherapy, and in particular, to the symptoms of shock. Patients should be made to understand the importance of a 30 minute observation period, and be cautioned to return to the office promptly if symptoms occur after leaving. Patients should be instructed to report any symptoms of exposure to the allergen, so the physician can adjust the dosage appropriately.

3. Drug Interactions

Patientswith cardiovascular diseases and/or pulmonary diseases such assymptomatic unstable, steroid-dependent asthma, and/or those who arereceiving cardiovascular drugs such as beta blockers, may be at higherrisk for severe adverse reactions. These patients may also be morerefractory to the normal allergy treatment regimen. Patients should betreated only if the benefit of treatment outweighs the risks.1

Patientson beta blockers may be more reactive to allergens given for testing ortreatment and may be unresponsive to the usual doses of epinephrineused to treat allergic reactions.2. Certain medications may lessen the skin test wheal anderythema responses elicited by allergens and histamine for varying timeperiods. Conventional antihistamines should be discontinued at least 5days before skin testing. Long acting antihistamines should bediscontinued for at least 3 weeks prior to skin testing. 28 Topical steroids should be discontinued at the skin test site for at least 2-3 weeks before skin testing.28, 29

Tricyclic antidepressants such as Doxepin should be withheld for at least 7 days before skin testing. 30 Topical local anesthetics may suppress the flare responses and should be avoided in skin test sites.31

4. Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been conducted with allergenic extracts to determine their potential for carcinogenicity, mutagenicity or impairment of fertility.

5. Pregnancy

Pregnancy Category C. Animal reproduction studies have not been conducted with allergenic extracts. It is also not known whether allergenic extracts can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Allergenic extracts should be given to a pregnant woman only if clearly needed. The physician must carefully consider the benefit-to-risk ratio to both patient and fetus, of performing skin testing or continuing immunotherapy during pregnancy. The recommended precautions for preventing adverse reactions are especially important in the pregnant patient. Based on the physician's discretion, immunotherapy maintenance doses may be continued during pregnancy if the patient has not experienced adverse side effects. Immunotherapy is generally not initiated during pregnancy due to the risks associated with systemic reactions and their treatment. 33

6. Nursing Mothers

There are no current studies on the secretion of allergenic extract components in human milk or their effect on the nursing infant. Because many drugs are excreted in human milk, caution should be exercised when allergenic extracts are administered to a nursing woman.

7. Pediatric Use

Since dosage for the pediatric population is the same as for adults 34, 35 larger volumes of solution may produce excessive discomfort. Therefore, in order to achieve the total dose required, the volume of the dose may need to be divided into more than one injection per visit.

8. Geriatric Use

The reactions from immunotherapy can be expected to be the same in elderly patients as in younger ones. Elderly patients may be more likely to be on medication that could block the effect of epinephrine which could be used to treat serious reactions, or they could be more sensitive to the cardiovascular side effect of epinephrine because of pre-existing cardiovascular disease. 36

ADVERSE REACTIONS

Physicians administering allergenic extract testing or treatment materials should be experienced in the treatment of severe systemic reactions. See WARNINGS box at the beginning of this package insert.

1. Local Reactions

Some erythema, swelling or pruritus at the site of injection are common, the extent varying with the patient. Such reactions should not be considered significant unless they persist for at least 24 hours. Local reactions (erythema or swelling) which exceed 4-5 cm in diameter are not only uncomfortable, but also indicate the possibility of a systemic reaction if dosage is increased. In such cases the dosage should be reduced to the last level not causing the reaction and maintained at this level for two or three treatments before cautiously increasing again. Large persistent local reactions may be treated by local cold, wet dressings and/or the use of oral antihistamines. They should be considered a warning of possible severe systemic reactions and an indication of the need for temporarily reduced dosages. A mild burning immediately after the injection is to be expected. This usually subsides in 10 to 20 seconds.

2. Systemic Reactions

With careful attention to dosage and administration, systemic reactions occur infrequently, but it cannot be overemphasized that in sensitive individuals, any injection could result in anaphylactic shock. Therefore, it is imperative that physicians administering allergenic extracts understand and be prepared for the treatment of severe reactions.

Most severe systemic reactions will begin within a 30 minute time period, but systemic reactions may occur at any time after skin tests or immunotherapy. Symptoms may range from mild to life-threatening (due to anaphylaxis)as described below.

Other possible systemic reactions which may occur in varying degrees of severity are laryngeal edema, fainting, pallor, bradycardia, hypotension, angioedema, cough, wheezing, conjunctivitis, rhinitis, and urticaria. Adverse reaction frequency data for allergenic extract administration for testing and treatment show that risk is low. 1, 37

If a systemic or anaphylactic reaction does occur, apply a tourniquet above the site of injection and inject 1:1,000 epinephrine-hydrochloride intramuscularly or subcutaneously into the opposite arm. Loosen the tourniquet at least every 10 minutes. Do not obstruct arterial blood flow with the tourniquet.

EPINEPHRINE

Dosage:

ADULT: 0.3 to 0.5 mL should be injected. Repeat in 5 to 10 minutes if necessary.

PEDIATRIC: The usual initial dose is 0.01 mg (mL) per kg body weight or 0.3 mg (mL) per square meter of body surface area. Suggested dosage for infants to 2 years of age is 0.05 mL to 0.1 mL; for children 2 to 6 years, 0.15 mL; and children 6 to 12 years, 0.2 mL. Single pediatric doses should not exceed 0.3 mg (mL). Doses may be repeated as frequently as every 20 minutes, depending on the severity of the condition and the response of the patient. After administration of epinephrine, profound shock or vasomotor collapse should be treated with intravenous fluids, and possibly vasoactive drugs. Airway patency should be insured. Oxygen should be given by mask. Intravenous antihistamine, inhaled bronchodilators, theophylline and/or adrenal corticosteroids may be used if necessary after adequate epinephrine and circulatory support has been given. Emergency resuscitation measures and personnel trained in their use must be available immediately in the event of a serious systemic or anaphylactic reaction not responsive to the above measures [Ref. J. Allergy and Clinical Immunology, 77(2):p. 271-273, 1986].

Rarely are all of the above measures necessary; the tourniquet and epinephrine usually produce prompt responses. However, the physician should be prepared in advance for all contingencies. Promptness in beginning emergency treatment measures is of utmost importance.

Severe systemic reactions mandate a decrease of at least 50% in the next dose, followed by cautious increases. Repeated systemic reactions, even of a mild nature, are sufficient reason for the cessation of further attempts to increase the reaction-causing dose.

3. Adverse Event Reporting

Report all adverse events to Jubilant HollisterStier LLC, Customer Technical Services Department at 1 (800) 992-1120. A voluntary adverse event reporting system for health professionals is available through the FDA MEDWATCH program. Preprinted forms (FDA Form 3500) are available from the FDA by calling 1 (800) FDA-1088. Completed forms should be mailed to MEDWATCH, 5600 Fisher Lane, Rockville, MD 20852-9787 or Fax to: 1 (800) FDA-0178.

OVERDOSE SECTION

See ADVERSE REACTIONS.

DOSAGE AND ADMINISTRATION

1. General

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Dosage of allergenic extracts is a highly individualized matter and varies according to the degree of sensitivity of the patient, his clinical response, and tolerance to the extract administered during the early phases of an injection regimen.

Allergen extracts should be administered using a sterile syringe with 0.01 mL gradations and a 25-27 gauge x 1/2" to 5/8" needle. The injections are given subcutaneously. The most common sites of injection are the lateral aspect of the upper arm or thigh. Intracutaneous or intramuscular injections may produce large local reactions and may be very painful.

Sterile aqueous diluent containing human serum albumin [Albumin Saline with Phenol ] or diluent of 50% glycerin may be used when preparing dilutions of the concentrate for immunotherapy. Dilutions should be made accurately and aseptically, using sterile diluent, vials, syringes, etc. Mix thoroughly and gently by rocking or swirling. Maintain stock solutions and dilutions constantly at 2° - 8°C. To prepare dilutions for intradermal and therapeutic use, make a 1:10 dilution by adding 1.0 mL of the Concentrate to 9.0 mL of sterile aqueous diluent. Subsequent serial dilutions are made in a similar manner.

Following is a suggested schedule for average patients and will be satisfactory in most cases. However, the degree of sensitivity varies in many patients. The size of the dose should be adjusted according to the patient's tolerance and reaction. Decrease the size of the dose if the previous injection resulted in marked local or the slightest general reaction. Another dose should never be given until all reactions resulting from the previous dose have disappeared.

The starting dose should be based on skin tests of the extract to be used for immunotherapy. To determine the starting dose, begin intradermal testing with the most dilute extract preparation. Inject 0.02 mL and read the reaction after 15 minutes. Intradermal testing is continued with increasing concentrations of the extract until a reaction of 10-20 mm erythema ( ∑ E 0-40 mm) and/or a 5 mm wheal occurs. This concentration at a dose of 0.03 mL then can serve as a starting dose for immunotherapy. Subsequent doses can be increased by 0.03 mL to as high as 0.12 mL increments each time until 0.3 mL is reached, at which time a dilution 10 times as strong can be used, starting with 0.03 mL. Proceed in this way until a tolerance dose is reached or symptoms are controlled. Suggested maintenance dose for a pollen extract is 0.2 mL of the Concentrate, while for a non-pollen extract the maximum suggested dose is 0.5 mL of the Concentrate. Occasionally, higher doses are necessary to relieve symptoms. Special caution is required in administering doses greater than 0.2 mL. The interval between doses is normally 3 to 7 days during dose building regimen.

Normally immunotherapy can be started with a 1:100,000 dilution of extracts labeled in weight/volume. Certain therapeutic mixtures are labeled as Concentrate, (v/v) dilutions of Concentrate, Amb a 1, Allergy units/mL or Bioequivalent Allergy Units/mL. (See DESCRIPTION.) Strength of each antigen in the mixture is indicated in the product labeling. For beginning treatment, use at least a 1,000-fold dilution of the Concentrate extract for non-pollens, and at least a 10,000-fold dilution of the Concentrate extract for pollens.

In some patients, the dosage may be increased more rapidly than recommended above. In seasonal allergies, treatment should be started and the interval between doses regulated so that at least the first twenty doses will have been administered by the time symptoms are expected. Thus, the shorter the interval between the start of immunotherapy and the expected onset of symptoms, the shorter the interval between each dose. Some patients may even tolerate daily doses.

Should symptoms develop before the next injection is scheduled, the interval between doses should be decreased. Should allergic symptoms or local reactions develop shortly after the dose is administered, the size of the dose should be decreased. In seasonal allergies, it is often advisable to decrease the dose to one-half or one-quarter of the maximum dose previously attained if the patient has any seasonal symptoms.

A maintenance dose, the largest dose tolerated by the patient that relieves symptoms without producing undesirable local or general reactions, is recommended for most patients. The upper limits of dosage have not been established; however, doses larger than 0.2 mL of extract may be painful if glycerin is present. The dosage of allergenic extract does not vary significantly with the respiratory allergic disease under treatment. The size of this dose and the interval between doses will vary and can be adjusted as necessary.

The interval between maintenance doses can be increased gradually from one week to 10 days, to two weeks, to three weeks, or even to four weeks, if tolerated. Repeat the doses at a given interval three or four times to check for untoward reactions before further increasing the interval. Protection is lost rapidly if the interval between doses is more than four weeks. (See WARNINGS.)

The usual duration of treatment has not been established. A period of two or three years of injection therapy constitutes an average minimum course of treatment.

2. Pediatric Use

The dose for the pediatric population is the same as for adults.

3. Geriatric Use

The dose for elderly patients is the same as for adult patients under 65.36

HOW SUPPLIED

In 10 mL, 30 mL and 50 mL vials at the w/v, Concentrate, v/v dilution of Concentrate, AU/mL (Standardized Mite Extracts: D. farinae, D. pteronyssinus 10,000 and 30,000 AU/mL; Mite Mixtures: 5,000 AU/mL each species, or 15,000 AU/mL each species), BAU/mL (Standardized Cat Hair and Cat Pelt extracts: 10,000 BAU/mL; Standardized Grass extracts: 10,000 and 100,000 BAU/mL); Amb a 1 units/mL; or PNU/mL ordered by the physician. Please see the current Allergy Product Catalog.

STORAGE AND HANDLING

The expiration date is listed on the container label. To ensure the maximum potency, the extract and its dilutions should be stored at 2° - 8°C, and kept in this temperature range at all times, even during use. Dilutions are less stable than concentrates. If loss of potency is suspected, dilutions should be checked by skin testing with equal v/v dilutions of a freshly prepared dilution on individuals known to be allergic to the specific allergen.

LIMITED WARRANTY

A number of factors beyond our control could reduce the efficacy of this product or even result in an ill effect following its use. These include storage and handling of the product after it leaves our hands, diagnosis, dosage, method of administration and biological differences in individual patients. Because of these factors, it is important that this product be stored properly and that the directions be followed carefully during use. No warranty, express or implied, including any warranty of merchantability or fitness, is made. Representatives of the Company are not authorized to vary the terms or the contents of any printed labeling, including the package insert, for this product except by printed notice from the Company's headquarters. The prescriber and user of this product must accept the terms hereof.

REFERENCES

1. Lockey, R.F., L.M. Benedict, P.C. Turkletaub, S.C. Bukantz. Fatalities from immunotherapy (IT) and skin testing (ST). J. Allergy Clin. Immunol., 79 (4): 660-677, 1987.

2. Jacobs, R.L., G.W. Rake, Jr., et al. Potentiated anaphylaxis in patients with drug-induced beta-adrenergic blockade. J. Allergy Clin. Immunol., 68 (2): 125-127, August 1981.

3. Griffith, I.J., J. Pollock, D.G. Klapper, B.L. Rogers and A.K. Nault. Sequence Polymorphism of Amb a I and Amb a II, the Major Allergens in Ambrosia artemisiifolia (Short Ragweed). Int. Arch. Allergy Apply. Immunol., 96: 296-304, 1991.

4. Underdown, B. J. and L. Goodfriend. Isolation and characterization of an allergen from short ragweed pollen. Biochem. 8 (3): 980-989, 1969.

5. Griffiths, B. W and R. Brunet. Isolation of a basic protein antigen of low ragweed pollen. Can. J. Biochem. 49 (3): 396-400, 1971.

6. Lapkoff, C. B. and L. Goodfriend. Isolation of a low molecular weight ragweed allergen: Ra5. Int. Arch. Allergy Appl. Immunol. 46 (2): 215-229, 1974.

7. Hussain, R. and D. G. March. Characterization and allergenic activity of ragweed allergens Ra6, Ra7, Ra8. J. Allergy Clin. Immunol. 65 (3): 230, abstr. 218, 1980

8. Goodfriend, L., A. M. Choudhury, J. Del Carpio and T. P. King. Cytochrome C: New ragweed pollen allergen. Fed. Proc. 38 (3, part II): 1415, abstr. 6261, 1979.

9. Turkeltaub, P.C., MD, and S.C. Rastogi, PhD. Quantitative intradermal test procedure for evaluation of subject sensitivity to standardized allergenic extracts and for assignment of bioequivalent allergy units to reference preparations using the ID₅₀EAL method. Allergenics Products Testing Laboratory, Center for Biologics Evaluation and Research (CBER), FDA. Revised: November, 1994.

10. Norman, P. S. Postgraduate Course Presentation. An overview of immunotherapy, implications for the future. J. Allergy Clin. Immunol., 65 (2): 87-96, 1980.

11. Lowell, F. C. and W. Franklin. A "double-blind" study of treatment with aqueous allergenic extracts in cases of allergic rhinitis. J. Allergy, 34 (2):165-182, 1963.

12. Lowell, F. C. and W. Franklin. A double-blind study of the effectiveness and specificity of injection therapy in ragweed hay fever. N. Eng. J. Med. 273 (13): 675-679, 1965.

13. Zavazal, V. and A. Stajner. Immunologic changes during specific treatment of the atopic state. II. Acta. Allergol. 25 (1): 11-17, 1970.

14. Reisman, R. E., J. I. Wypych, and E. E. Arbesman. Relationship of immunotherapy, seasonal pollen exposure and clinical response to serum concentrations of total IgE and ragweed-specific IgE. Int. Arch. Allergy Appl. Immunol. 48 (6): 721-730, 1975.

15. Taylor, W. W., J. L. Ohman, F. C. Lowell. Immunotherapy in cat-induced asthma; double-blind trial with evaluation of bronchial responses to cat allergen and histamine. J. Allergy Clin. Immunol., 61 (5): 283-287, 1978.

16. Smith, A. P. Hyposensitization with Dermatophagoides pteronyssinus antigen: Trial in asthma induced by house dust. Br. Med. J., 4: 204-206, 1971.

17. Chapman, M. D., T. A. E. Platts-Mills, M. Gabriel, H. K. Ng, W. G. L. Allen, L. E.Hill, A. J. Nunn. Antibody response following prolonged hyposensitization with Dermatophagoides pteronyssinus extract. Int. Arch. Allergy Appl. Immunol., 61:431-440, 1980.

18. Norman, P. S., W. L. Winkenwerder. Maintenance immunotherapy in ragweed hay fever. J. Allergy, 74: 273-282, 1971.

19. Norman, P. S., W. L. Winkenwerder, L. M. Lichtenstein. Immunotherapy of hay fever with ragweed Antigen E; comparisons with whole pollen extract and placebos. J. Allergy, 42: 93-108, 1968.

20. Middleton, E., C. E. Reed and E. F. Ellis, editors. Allergy Principles and Practice. C. V. Mosby Co., St. Louis, 1978, pp. 877-898.

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23. Swineford, O. Asthma and Hay Fever. Charles C. Thomas. Springfield, IL, 1971, pp. 148-155.

24. Reid, M.J., R.F. Lockey, P.C. Turkletaub, T.A.E., Platts-Mills. Survey of fatalities from skin testing and immunotherapy. J. 0 Clin. Immunol. 92 (1): 6-15, July 1993.

25. Reid, M.J., G. Gurka. Deaths associated with skin testing and immunotherapy. J. Allergy Clin. Immunol. 97(1) Part 3:231, Abstract 195, January 1996.

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27. Malling, H.J., B. Weeke, et al, The European Academy of Allergology and Clinical Immunology. Position Papers. Allergy. 48 (Supplement 14): 9-82, 1993.

28. Pipkorn, U. Pharmacological influence of anti-allergic medication on In Vivo allergen testing. Allergy. 43: 81-86,1988.

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30. Rao, K.S., et al. Duration of suppressive effect of tricyclic anti-depressants on histamine induced wheal and flare reactions on human skin. J. Allergy Clin. Immunol. 82: 752-757, November 1988.

31. Pipkorn, U., and M. Andersson. Topical dermal anesthesia inhibits the flare but not the wheal response to allergen and histamine in the skin prick test. Clinical Allergy. 17: 307-311, 1987.

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34. Patterson, R., et al. Allergy Principles and Practice, 2nd ed. E. Middleton, Jr., C. E. Reed, E. F. Ellis, Ed., C. V. Mosby Co., 1983, St. Louis, MO, 1983, Chapter 52

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37. Turkeltaub, P.C., MD, and P.J. Gergen, MD. The risk of adverse reactions from percutaneous prick-puncture allergen skin testing, venipuncture, and body measurements: Data from the second National Health and Nutrition Examination Survey 1976-80 (NHANES II). J. Allergy Clin. Immunol. 84(6): 886-890, Dec. 1989.

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