www.archive.org
`415.561.6767
`41 5.840 -0391 e-fax
`
`Internet A rchive
`300 Funston Avenue
`San Francisco, CA 94118
`
`AFFIDAVIT OF CHRISTOPHER BUTLER
`
`1. I am the Office Manager at the Internet Archive, located in San Francisco,
`California. I make this declaration of my own personal knowledge.
`
`2. The Internet Archive is a website that provides access to a digital library of
`Internet sites and other cultural artifacts in digital form. Like a paper library, we provide
`free access to researchers, historians, scholars, and the general public. The Internet
`Archive has partnered with and receives support from various institutions, including the
`Library of Congress.
`
`3. The Internet Archive has created a service known as the Wayback Machine. The
`Wayback Machine makes it possible to surf more than 450 billion pages stored in the
`Internet Archive's web archive. Visitors to the Wayback Machine can search archives
`by URL (i.e., a website address). If archived records for a URL are available, the visitor
`will be presented with a list of available dates. The visitor may select one of those
`dates, and then begin surfing on an archived version of the Web. The links on the
`archived files, when served by the W ayback Machine, point to other archived files
`(whether HTML pages or images). If a visitor clicks on a link on an archived page, the
`Wayback Machine will serve the archived file with the closest available date to the page
`upon which the link appeared and was clicked.
`
`4. The archived data made viewable and browseable by the Wayback Machine is
`compiled using software programs known as crawlers, which surf the Web and
`automatically store copies of web files, preserving these files as they exist at the point of
`time of capture.
`
`5. The Internet Archive assigns a URL on its site to the archived files in the format
`http://web.archive.org/web/[Year in yyyy][Month in mm][Day in dd][Time code in
`hh:mm:ss]/[Archived URL]. Thus, the Internet Archive URL
`http://web.archive.org/web/19970126045828/http://www.archive.org/ would be the
`URL for the record of the Internet Archive home page HTML file
`(http://www.archive.org/) archived on January 26, 1997 at 4:58 a.m. and 28 seconds
`(1997/01/26 at 04:58:28). A web browser may be set such that a printout from it will
`display the URL of a web page in the printout's footer. The date assigned by the Internet
`Archive applies to the HTML file but not to image files linked therein. Thus images that
`appear on a page may not have been archived on the same date as the HTML file.
`Likewise, if a website is designed with "frames," the date assigned by the Internet
`Archive applies to the frameset as a whole, and not the individual pages within each
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`
`6. Attached hereto as Exhibit A are true and accurate copies of printouts of the
`Internet Archive's records of the HTML files or PDF files for the URLs and the dates
`specified in the attached coversheet of each printout.
`
`Nexus Ex. 1004
`Page 1 of 14
`
`

`

`7. I declare that all statements made herein of my own knowledge are true
`and that all statements made on information and belief are believed to be true;
`and that these statements were made with the knowledge that willful false
`statements and the like so made are punishable by fine or imprisonment, under
`Section 1001 of Title 18 of the United States Code.
`
`DATE: S[i /1,,u
`
`Christopher Butler
`
`Nexus Ex. 1004
`Page 2 of 14
`
`

`

`
`
`
`
`
`
`Exhibit A
`Exhibit A
`
`Nexus Ex. 1004
`Page 3 of 14
`
`Nexus Ex. 1004
`Page 3 of 14
`
`

`

`https://web.archive.org/web/20170403170533/http://www.drugsdb.eu/drug.php?d=L-
`cysteine%20Hydrochloride&m=Sandoz%20Inc&id=083366d6-0437-4ee0-90d4-
`440a5b5d03b5.xml
`
`
`Nexus Ex. 1004
`Page 4 of 14
`
`

`

`5/1/2020
`
`L-CYSTEINE HYDROCHLORIDE - cysteine hydrochloride injection, solution  - Prescription (RX) Marketed Drugs Encyclopedia
`
`r
`
`I
`
`r· ~ ,
`
`\Vith permission of
`U.S. ~atimrnl Library
`of l\kdicinc
`
`
`
`You are here: HomeHome > Prescription(RX) DrugsPrescription(RX) Drugs > LL > L-cysteine Hydrochloride
`L-cysteine Hydrochloride (Sandoz Inc)
`
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`Name:
`
`L-cysteine Hydrochloride
`
`Manufacturer: Sandoz Inc
`
`Category: Prescription Marketed Drugs
`
`L-CYSTEINE HYDROCHLORIDE - cysteine
`hydrochloride injection, solution
`Sandoz Inc
`Disclaimer: This drug has not been found by FDA to be safe and
`effective, and this labeling has not been approved by FDA. ForFor
`further information about unapproved drugs, click here.
`further information about unapproved drugs, click here.
`----------
`L-Cysteine
`Hydrochloride Injection, USP
`0.5 g/10 mL (50 mg/mL)
`
`PHARMACY BULK PACKAGE
`NOT FOR DIRECT INFUSION
`
`DESCRIPTION
`L-Cysteine Hydrochloride Injection, USP, 50 mg/mL, is a sterile, nonpyrogenic solution. Each mL
`contains: 50 mg of L-Cysteine Hydrochloride Monohydrate USP; Water for Injection, USP q.s.; Air
`replaced with Nitrogen. pH 1.0-2.5
`L-Cysteine is a sulfur-containing amino acid. In premixed solutions of crystalline amino acids, cysteine
`is relatively unstable over time, eventually converting to insoluble cystine. To avoid such precipitation,
`L-Cysteine Hydrochloride Injection USP is intended to be used as an additive with crystalline Amino
`Acid Injections immediately prior to administration to the patient.
`The structural formula of Cysteine Hydrochloride Monohydrate USP is:
`
`H
`I
`HSCH2 - C - C00H •HC l•H20
`I
`NH2
`
`Molecular Weight
`175.63
`
`Molecular Formula
`C H NO S•HCl•H O
`3 7
`2
`2
`
`CLINICAL PHARMACOLOGY
`L-Cysteine is synthesized from methionine via the trans-sulfuration pathway in the adult, but newborn
`infants lack the enzyme necessary to effect this conversion. Therefore, L-Cysteine is generally
`considered to be an essential amino acid in infants.
`
`INDICATIONS AND USAGE
`
`https://web.archive.org/web/20170403170533/http://www.drugsdb.eu/drug.php?d=L-cysteine Hydrochloride&m=Sandoz Inc&id=083366d6-0437-4ee0-90d4-440a5b… 1/5
`
`Nexus Ex. 1004
`Page 5 of 14
`
`

`

`L-CYSTEINE HYDROCHLORIDE - cysteine hydrochloride injection, solution  - Prescription (RX) Marketed Drugs Encyclopedia
`5/1/2020
`L-Cysteine Hydrochloride Injection, USP is intended for use only after dilution as an additive to
`Crystalline Amino Acid Injections to meet the intravenous amino acid nutritional requirements of infants
`receiving total parenteral nutrition.
`
`CONTRAINDICATIONS
`This preparation should not be used in patients with hepatic coma or metabolic disorders involving
`impaired nitrogen utilization.
`
`WARNINGS
`Peripheral intravenous infusion of amino acids may induce a rise in blood urea nitrogen (BUN)
`especially in patients with impaired hepatic or renal function. Appropriate laboratory tests should be
`performed periodically and infusion discontinued if BUN levels exceed normal postprandial limits and
`continue to rise. It should be noted that a modest rise in BUN normally occurs as a result of increased
`protein intake.
`Administration of amino acid solutions to a patient with hepatic insufficiency may result in serum amino
`acid imbalances, metabolic alkalosis, prerenal azotemia, hyperammonemia, stupor and coma.
`Administration of amino acid solutions in the presence of impaired renal function may augment an
`increasing BUN, as does any protein dietary component.
`Solutions containing sodium ion should be used with great care, if at all, in patients with congestive
`heart failure, severe renal insufficiency, and in clinical states in which there exists edema with sodium
`retention.
`Solutions which contain potassium ion should be used with great care, if at all, in patients with
`hyperkalemia, severe renal failure and in conditions in which potassium retention is present.
`Solutions containing acetate ion should be used with great care in patients with metabolic or
`respiratory alkalosis. Acetate should be administered with great care in those conditions in which there
`is an increased level or an impaired utilization of this ion such as severe hepatic insufficiency.
`Hyperammonemia is of special significance in infants, as it can result in mental retardation. Therefore
`it is essential that blood ammonia levels be measured frequently in infants.
`Instances of asymptomatic hyperammonemia have been reported in patients without overt liver
`dysfunction. The mechanisms of this reaction are not clearly defined but may involve genetic defects
`and immature or subclinically impaired liver function.
`Frequent Clinical Evaluation and Laboratory Determinations are Necessary for Proper
`Monitoring During Administration. Blood studies should include glucose, urea nitrogen, serum
`electrolytes, ammonia, cholesterol, acid-base balance, serum proteins, kidney and liver function tests,
`osmolarity and hemogram. White blood count and blood cultures are to be determined if indicated.
`Urinary osmolarity and glucose should be determined frequently.
`Safe use during pregnancy has not been established, therefore, infusion of amino acids should be
`undertaken during pregnancy only when this is deemed essential to the patients' welfare, as judged by
`the physician.
`WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with
`prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly
`at risk because their kidneys are immature, and they require large amounts of calcium and phosphate
`solutions, which contain aluminum.
`Research indicates that patients with impaired kidney function, including premature neonates, who
`receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels
`associated with central nervous system and bone toxicity. Tissue loading may occur at even lower
`rates of administration
`
`PRECAUTIONS
`Special care must be taken when administering hypertonic glucose to provide calories in diabetic or
`prediabetic patients.
`Because of its antianabolic activity, concurrent administration of tetracycline may reduce the nitrogen
`sparing effects of infused amino acids.
`Do not withdraw venous blood for blood chemistries through the peripheral infusion site, as
`interference with estimations of nitrogen containing substances may occur.
`Intravenous feeding regimens which include amino acids should be used with caution in patients with a
`history of renal disease, pulmonary disease, or with cardiac insufficiency so as to avoid excessive fluid
`accumulation.
`The effect of infusion of amino acids, without dextrose, upon carbohydrate metabolism of children is
`not known at this time.
`Nitrogen intake should be carefully monitored in patients with impaired renal function. For long-term
`total nutrition, or if a patient has inadequate fat stores, it is essential to provide adequate exogenous
`calories concurrently with the amino acids. Concentrated dextrose solutions are an effective source of
`such calories. Such strongly hypertonic nutrient solutions should be administered through an
`indwelling intravenous catheter with the tip located in the superior vena cava.
`
`ADVERSE REACTIONS
`Local reactions consisting of a warm sensation, erythema, phlebitis and thrombosis at the infusion site
`have occurred with peripheral intravenous infusion of amino acids, particularly if the other substances,
`such as antibiotics, are also administered through the same site. In such cases the infusion site should
`be changed promptly to another vein. Use of large peripheral veins, inline filters, and slowing the rate
`of infusion may reduce the incidence of local venous irritation. Electrolyte additives should be spread
`throughout the day. Irritating additive medications may need to be injected at another venous site.
`Generalized flushing, fever and nausea also have been reported during peripheral infusions of amino
`acid solutions.
`https://web.archive.org/web/20170403170533/http://www.drugsdb.eu/drug.php?d=L-cysteine Hydrochloride&m=Sandoz Inc&id=083366d6-0437-4ee0-90d4-440a5b… 2/5
`
`Nexus Ex. 1004
`Page 6 of 14
`
`

`

`L-CYSTEINE HYDROCHLORIDE - cysteine hydrochloride injection, solution  - Prescription (RX) Marketed Drugs Encyclopedia
`5/1/2020
`Drug Abuse and Dependence
`None known.
`
`DOSAGE AND ADMINISTRATION
`L-Cysteine Hydrochloride Injection USP is intended for use only after dilution in Crystalline Amino Acid
`Injection. Each 0.5 gram of L-Cysteine Hydrochloride Monohydrate should be combined aseptically
`with 12.5 grams of Crystalline Amino Acid Injection, such as that present in 250 mL of 5% Crystalline
`Amino Acid Injection. The admixture is then diluted with 250 mL of dextrose 50% or such lesser
`volume as indicated. Equal volumes of 5% Crystalline Amino Acid Injection and dextrose 50% produce
`a final solution which contains Crystalline Amino Acid Injection 2.5% in dextrose 25%, which is suitable
`for administration by central venous infusion. Administration of the final admixture should begin within
`one hour of mixing. Otherwise, the admixture should be refrigerated immediately and used within 24
`hours of the time of mixing. For the recommended rate of administration, see the Crystalline Amino
`Acid Injection package insert.
`Parenteral drug products should be inspected visually for particulate matter and discoloration prior to
`administration, whenever solution and container permit.
`
`DIRECTIONS FOR PROPER USE OF PHARMACY BULK PACKAGE
`The pharmacy bulk package is for use in a Pharmacy Admixture Service only.
`Use of this product is restricted to a suitable work area, such as a laminar flow hood. Prior to entering
`the vial, remove the flip-off seal and cleanse the rubber closure with a suitable antiseptic agent.
`The container closure may be penetrated only one time, utilizing a suitable sterile transfer device or
`dispensing set which allows measured distribution of the contents. The date and time the vial was
`initially opened should be recorded in the space provided on the label. Transfer individual doses(s) to
`appropriate intravenous infusion solutions. Use of a syringe with needle is not recommended. Multiple
`entries increase the potential of microbial and particulate contamination.
`The withdrawal of container contents should be accomplished without delay using aseptic technique.
`However, should this not be possible, a maximum time of 4 hours from initial closure entry is permitted
`to complete fluid transfer operations.
`
`RECOMMENDED STORAGE CONDITIONS AFTER OPENING
`Keep under laminar flow hood at room temperature. Any unused portion of the vial must be discarded
`within 4 hours after initial entry.
`
`HOW SUPPLIED
`L-Cysteine Hydrochloride Injection, USP (50 mg/mL) is supplied as follows:
`
`PHARMACY BULK
`PACKAGE
`NDC Number Volume
`66758-005-01 50 mL
`66758-005-02 5 × 50
`mL
`
`Also available as:
`
`SINGLE DOSE VIAL
`NDC Number
`Volume
`66758-004-01
`10 mL
`66758-004-02
`10 × 10 mL
`
`Store at controlled room temperature 15°-30°C (59°-86°F) Do not freeze.
`For Sandoz Inc. Customer Service, call 1-800-525-8747
`Rx only
`Manufactured for:
`SANDOZ
`Princeton, NJ 08540
`Revised: November 2009
`L-028-00
`
`Package Label - Principal Display Panel - 50 mL Vial
`SANDOZ
`Rx only NDC 66758-005-01
`L-Cysteine
`Hydrochloride Injection, USP
`PHARMACY BULK PACKAGE
`NOT FOR DIRECT INFUSION
`50 mg/mL
`For IV Use Only After Dilution
`Do Not Dispense As A Unit
`50 mL
`
`https://web.archive.org/web/20170403170533/http://www.drugsdb.eu/drug.php?d=L-cysteine Hydrochloride&m=Sandoz Inc&id=083366d6-0437-4ee0-90d4-440a5b… 3/5
`
`Nexus Ex. 1004
`Page 7 of 14
`
`

`

`5/1/2020
`L-018-00
`PHARMACY BULK PACKAGE
`
`L-CYSTEINE HYDROCHLORIDE - cysteine hydrochloride injection, solution  - Prescription (RX) Marketed Drugs Encyclopedia
`
`~ SANDOZ
`booly
`NOC 667511oO0,-o 1
`L-Cysteine
`Hydroc~lorlde fnjec1100, USP
`,w,R.W.CYBULI( P,1 KAU
`""nr r nuun tNtll'-ION
`SO mg/ml
`For IV Ule Only Aflet Dilution
`Du Nut O&pcme ,u A Uplr
`50 mL
`L-01HD
`~4tlrTIA.7~1UlA
`
`Each ml conU11n,: sc, mg L-C1~teme H•drochlond<,
`"1Cnoh'ltird11,, USP; W~,
`for lnJealon' USP, q.>.; Ail
`replaced with Nlrog•n. pH 1.0-2.S
`Direct QnS for U,e: S,., p.c""'o ln;ert.
`Warning: h r IV IDC only M .. I be diluted l.dorce u,..
`Co,,tmtf hoold be ci,pen,o:d promptlv •fter lnlllal cltl<lure
`puncture. Oisc~rd ur,uwd ctlllltn!J ~ft•r 4 houn.
`tor• al oontrolltd r.om t.mp~ture
`1S'..JO' C (S!"-86' F). Do not rttze
`L01ta1ns no more INn 1>,tlUIJ "'cg,l of aluminun,.
`lvbnuf.v1urr-tf (n,· S;incfo? fnr.
`P~ncir.on, J 08540
`
`Package Label - Principal Display Panel - 50 mL Vial Carton
`SANDOZ
`5 × 50 mL Vials NDC 66758-005-02
`L-Cysteine Hydrochloride
`Injection, USP
`50 mg/mL
`Pharmacy Bulk Package
`Not For Direct Infusion
`For IV Use Only After Dilution
`Rx only
`
`~ SANDOZ
`SxSO mlVilo1-
`L-Cysteine l-l ydrochloride
`lnjt'ction, USP
`50 mg/ml
`
`.
`
`.
`I
`r
`Nat
`For IV U... Only Aftot DllubOn
`
`NOC 66758--00S.02
`
`L-CYSTEINE HYDROCHLORIDE
`l-cysteine hydrochloride injection, solution
`
`Product Information
`Product Type
`Route of Administration
`
`HUMAN PRESCRIPTION DRUG
`INTRAVENOUS
`
`Item Code (Source)
`DEA Schedule
`
`NDC:66758-005
`
`
`Active Ingredient/Active Moiety
`Ingredient Name
`CYSTEINE HYDROCHLORIDE (CYSTEINE)
`
`Basis of Strength
`CYSTEINE HYDROCHLORIDE
`
`Strength
`50 mg in 1 mL
`
`Inactive Ingredients
`Ingredient Name
`WATER
`
`Product Characteristics
`Color
`Shape
`Flavor
`Contains
`
`Strength
`
`
`
`
`
`
`Score
`Size
`Imprint Code
`
`
`
`Packaging
`# Item Code
`1 NDC:66758-005-
`02
`1 NDC:66758-005-
`01
`
`Package Description
`5 VIAL, PHARMACY BULK PACKAGE ( VIAL) in 1
`CARTON
`50 mL in 1 VIAL, PHARMACY BULK PACKAGE
`
`Multilevel Packaging
`contains a VIAL, PHARMACY BULK PACKAGE (66758-005-
`01)
`This package is contained within the CARTON (66758-005-02)
`
`Marketing Information
`https://web.archive.org/web/20170403170533/http://www.drugsdb.eu/drug.php?d=L-cysteine Hydrochloride&m=Sandoz Inc&id=083366d6-0437-4ee0-90d4-440a5b… 4/5
`
`Nexus Ex. 1004
`Page 8 of 14
`
`

`

`5/1/2020
`Marketing Category
`Unapproved drug other
`
`L-CYSTEINE HYDROCHLORIDE - cysteine hydrochloride injection, solution  - Prescription (RX) Marketed Drugs Encyclopedia
`Application Number or Monograph Citation
`Marketing Start Date
`Marketing End Date
`12/01/2008
`
`Labeler - Sandoz Inc (005387188)
`
`Revised: 06/2010
`
`
`
`Sandoz Inc
`
`Source: http://dailymed.nlm.nih.gov
`Reproduced with permission of U.S. National Library of MedicineU.S. National Library of Medicine
`
`
`
`
`
`
`
`
`Terms of Use Copyright © 2017 Drugsdb.euDrugsdb.eu by Dionisios FentasDionisios Fentas || Terms of Use
`
`https://web.archive.org/web/20170403170533/http://www.drugsdb.eu/drug.php?d=L-cysteine Hydrochloride&m=Sandoz Inc&id=083366d6-0437-4ee0-90d4-440a5b… 5/5
`
`Nexus Ex. 1004
`Page 9 of 14
`
`

`

`https://web.archive.org/web/20160824090050/http://www.drugsdb.eu/drug.php?d=L-
`cysteine%20Hydrochloride&m=Sandoz%20Inc&id=083366d6-0437-4ee0-90d4-
`440a5b5d03b5.xml
`
`
`Nexus Ex. 1004
`Page 10 of 14
`
`

`

`5/1/2020
`
`L-CYSTEINE HYDROCHLORIDE - cysteine hydrochloride injection, solution  - Prescription (RX) Marketed Drugs Encyclopedia
`
`T\DTT,--. ~
`
`,~ ..-,~ 1> ,~~.I\
`
`"" \\,dr11!!,DB.t·11
`
`r
`
`I
`
`t·
`
`'-,,,,
`
`\
`
`\Vith permission of
`U.S. ~ational Lihrar~:
`of l\kdkinl'
`
`You are here: HomeHome > Prescription(RX) DrugsPrescription(RX) Drugs > LL > L-cysteine Hydrochloride
`
`L-cysteine Hydrochloride (Sandoz Inc)
`- - - - - - - - -
`- - - - - - - -
`
`Loading
`
`Name:
`
`L-cysteine Hydrochloride
`
`Manufacturer: Sandoz Inc
`
`Category: Prescription Marketed Drugs
`
`Prescription Marketed Drugs Alphabetically
`AA| BB| CC| DD| EE| FF| GG| HH| II| JJ| KK| LL| MM| NN| OO| PP| QQ| RR| SS|
`TT| UU| VV| WW| XX| YY| ZZ| 0-90-9
`
`Categories:
`Prescription(RX) Drugs
`Prescription(RX) Drugs
`Over-the-counter (OTC) Drugs
`Over-the-counter (OTC) Drugs
`Homeopathic Drugs
`Homeopathic Drugs
`Animal Drugs
`Animal Drugs
`Feedback
`Feedback
`
`L-CYSTEINE HYDROCHLORIDE - cysteine
`hydrochloride injection, solution
`Sandoz Inc
`Disclaimer: This drug has not been found by FDA to be safe and
`effective, and this labeling has not been approved by FDA. ForFor
`further information about unapproved drugs, click here.
`further information about unapproved drugs, click here.
`----------
`L-Cysteine
`Hydrochloride Injection, USP
`0.5 g/10 mL (50 mg/mL)
`PHARMACY BULK PACKAGE
`NOT FOR DIRECT INFUSION
`DESCRIPTION
`L-Cysteine Hydrochloride Injection, USP, 50 mg/mL, is a sterile,
`nonpyrogenic solution. Each mL contains: 50 mg of L-Cysteine
`Hydrochloride Monohydrate USP; Water for Injection, USP q.s.; Air replaced with Nitrogen. pH 1.0-2.5
`L-Cysteine is a sulfur-containing amino acid. In premixed solutions of crystalline amino acids, cysteine
`is relatively unstable over time, eventually converting to insoluble cystine. To avoid such precipitation,
`L-Cysteine Hydrochloride Injection USP is intended to be used as an additive with crystalline Amino
`Acid Injections immediately prior to administration to the patient.
`The structural formula of Cysteine Hydrochloride Monohydrate USP is:
`H
`I
`HSCH2 - C - C00H•HC l•H20
`I
`NH2
`Molecular Formula
`Molecular Weight
`C3H7NO2S•HCl•H2O
`175.63
`CLINICAL PHARMACOLOGY
`L-Cysteine is synthesized from methionine via the trans-sulfuration pathway in the adult, but newborn
`infants lack the enzyme necessary to effect this conversion. Therefore, L-Cysteine is generally
`considered to be an essential amino acid in infants.
`INDICATIONS AND USAGE
`L-Cysteine Hydrochloride Injection, USP is intended for use only after dilution as an additive to
`Crystalline Amino Acid Injections to meet the intravenous amino acid nutritional requirements of infants
`receiving total parenteral nutrition.
`CONTRAINDICATIONS
`This preparation should not be used in patients with hepatic coma or metabolic disorders involving
`impaired nitrogen utilization.
`WARNINGS
`Peripheral intravenous infusion of amino acids may induce a rise in blood urea nitrogen (BUN)
`especially in patients with impaired hepatic or renal function. Appropriate laboratory tests should be
`performed periodically and infusion discontinued if BUN levels exceed normal postprandial limits and
`continue to rise. It should be noted that a modest rise in BUN normally occurs as a result of increased
`protein intake.
`Administration of amino acid solutions to a patient with hepatic insufficiency may result in serum amino
`acid imbalances, metabolic alkalosis, prerenal azotemia, hyperammonemia, stupor and coma.
`Administration of amino acid solutions in the presence of impaired renal function may augment an
`increasing BUN, as does any protein dietary component.
`Solutions containing sodium ion should be used with great care, if at all, in patients with congestive
`heart failure, severe renal insufficiency, and in clinical states in which there exists edema with sodium
`https://web.archive.org/web/20160824090050/http://www.drugsdb.eu/drug.php?d=L-cysteine Hydrochloride&m=Sandoz Inc&id=083366d6-0437-4ee0-90d4-440a5b… 1/4
`
`Nexus Ex. 1004
`Page 11 of 14
`
`

`

`L-CYSTEINE HYDROCHLORIDE - cysteine hydrochloride injection, solution  - Prescription (RX) Marketed Drugs Encyclopedia
`
`5/1/2020
`retention.
`Solutions which contain potassium ion should be used with great care, if at all, in patients with
`hyperkalemia, severe renal failure and in conditions in which potassium retention is present.
`Solutions containing acetate ion should be used with great care in patients with metabolic or
`respiratory alkalosis. Acetate should be administered with great care in those conditions in which there
`is an increased level or an impaired utilization of this ion such as severe hepatic insufficiency.
`Hyperammonemia is of special significance in infants, as it can result in mental retardation. Therefore
`it is essential that blood ammonia levels be measured frequently in infants.
`Instances of asymptomatic hyperammonemia have been reported in patients without overt liver
`dysfunction. The mechanisms of this reaction are not clearly defined but may involve genetic defects
`and immature or subclinically impaired liver function.
`Frequent Clinical Evaluation and Laboratory Determinations are Necessary for Proper Monitoring
`During Administration. Blood studies should include glucose, urea nitrogen, serum electrolytes,
`ammonia, cholesterol, acid-base balance, serum proteins, kidney and liver function tests, osmolarity
`and hemogram. White blood count and blood cultures are to be determined if indicated. Urinary
`osmolarity and glucose should be determined frequently.
`Safe use during pregnancy has not been established, therefore, infusion of amino acids should be
`undertaken during pregnancy only when this is deemed essential to the patients' welfare, as judged by
`the physician.
`WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with
`prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly
`at risk because their kidneys are immature, and they require large amounts of calcium and phosphate
`solutions, which contain aluminum.
`Research indicates that patients with impaired kidney function, including premature neonates, who
`receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels
`associated with central nervous system and bone toxicity. Tissue loading may occur at even lower
`rates of administration
`PRECAUTIONS
`Special care must be taken when administering hypertonic glucose to provide calories in diabetic or
`prediabetic patients.
`Because of its antianabolic activity, concurrent administration of tetracycline may reduce the nitrogen
`sparing effects of infused amino acids.
`Do not withdraw venous blood for blood chemistries through the peripheral infusion site, as
`interference with estimations of nitrogen containing substances may occur.
`Intravenous feeding regimens which include amino acids should be used with caution in patients with a
`history of renal disease, pulmonary disease, or with cardiac insufficiency so as to avoid excessive fluid
`accumulation.
`The effect of infusion of amino acids, without dextrose, upon carbohydrate metabolism of children is
`not known at this time.
`Nitrogen intake should be carefully monitored in patients with impaired renal function. For long-term
`total nutrition, or if a patient has inadequate fat stores, it is essential to provide adequate exogenous
`calories concurrently with the amino acids. Concentrated dextrose solutions are an effective source of
`such calories. Such strongly hypertonic nutrient solutions should be administered through an
`indwelling intravenous catheter with the tip located in the superior vena cava.
`ADVERSE REACTIONS
`Local reactions consisting of a warm sensation, erythema, phlebitis and thrombosis at the infusion site
`have occurred with peripheral intravenous infusion of amino acids, particularly if the other substances,
`such as antibiotics, are also administered through the same site. In such cases the infusion site should
`be changed promptly to another vein. Use of large peripheral veins, inline filters, and slowing the rate
`of infusion may reduce the incidence of local venous irritation. Electrolyte additives should be spread
`throughout the day. Irritating additive medications may need to be injected at another venous site.
`Generalized flushing, fever and nausea also have been reported during peripheral infusions of amino
`acid solutions.
`Drug Abuse and Dependence
`None known.
`DOSAGE AND ADMINISTRATION
`L-Cysteine Hydrochloride Injection USP is intended for use only after dilution in Crystalline Amino Acid
`Injection. Each 0.5 gram of L-Cysteine Hydrochloride Monohydrate should be combined aseptically
`with 12.5 grams of Crystalline Amino Acid Injection, such as that present in 250 mL of 5% Crystalline
`Amino Acid Injection. The admixture is then diluted with 250 mL of dextrose 50% or such lesser
`volume as indicated. Equal volumes of 5% Crystalline Amino Acid Injection and dextrose 50% produce
`a final solution which contains Crystalline Amino Acid Injection 2.5% in dextrose 25%, which is suitable
`for administration by central venous infusion. Administration of the final admixture should begin within
`one hour of mixing. Otherwise, the admixture should be refrigerated immediately and used within 24
`hours of the time of mixing. For the recommended rate of administration, see the Crystalline Amino
`Acid Injection package insert.
`Parenteral drug products should be inspected visually for particulate matter and discoloration prior to
`administration, whenever solution and container permit.
`DIRECTIONS FOR PROPER USE OF PHARMACY BULK PACKAGE
`The pharmacy bulk package is for use in a Pharmacy Admixture Service only.
`Use of this product is restricted to a suitable work area, such as a laminar flow hood. Prior to entering
`the vial, remove the flip-off seal and cleanse the rubber closure with a suitable antiseptic agent.
`The container closure may be penetrated only one time, utilizing a suitable sterile transfer device or
`dispensing set which allows measured distribution of the contents. The date and time the vial was
`initially opened should be recorded in the space provided on the label. Transfer individual doses(s) to
`https://web.archive.org/web/20160824090050/http://www.drugsdb.eu/drug.php?d=L-cysteine Hydrochloride&m=Sandoz Inc&id=083366d6-0437-4ee0-90d4-440a5b… 2/4
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`L-CYSTEINE HYDROCHLORIDE - cysteine hydrochloride injection, solution  - Prescription (RX) Marketed Drugs Encyclopedia
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`appropriate intravenous infusion solutions. Use of a syringe with needle is not recommended. Multiple
`entries increase the potential of microbial and particulate contamination.
`The withdrawal of container contents should be accomplished without delay using aseptic technique.
`However, should this not be possible, a maximum time of 4 hours from initial closure entry is permitted
`to complete fluid transfer operations.
`RECOMMENDED STORAGE CONDITIONS AFTER OPENING
`Keep under laminar flow hood at room temperature. Any unused portion of the vial must be discarded
`within 4 hours after initial entry.
`HOW SUPPLIED
`L-Cysteine Hydrochloride Injection, USP (50 mg/mL) is supplied as follows:
`PHARMACY BULK
`PACKAGE
`NDC Number Volume
`66758-005-01 50 mL
`66758-005-02 5 × 50 mL
`Also available as:
`SINGLE DOSE VIAL
`NDC Number
`Volume
`66758-004-01
`10 mL
`66758-004-02
`10 × 10
`mL
`Store at controlled room temperature 15°-30°C (59°-86°F) Do not freeze.
`For Sandoz Inc. Customer Service, call 1-800-525-8747
`Rx only
`Manufactured for:
`SANDOZ
`Princeton, NJ 08540
`Revised: November 2009
`L-028-00
`Package Label - Principal Display Panel - 50 mL Vial
`SANDOZ
`Rx only NDC 66758-005-01
`L-Cysteine
`Hydrochloride Injection, USP
`PHARMACY BULK PACKAGE
`NOT FOR DIRECT INFUSION
`50 mg/mL
`For IV Use Only After Dilution
`Do Not Dispense As A Unit
`50 mL
`L-018-00
`PHARMACY BULK PACKAGE
`
`Each ml conu,,ns: 5C• mg L-C1·steme H•drochlonde
`IV\Cnoh'/drau,, USP; W~,
`(or lnJealon' USP, cp.; Ai
`replaced wilh Nlrog•n. pH 1.0-2.S
`Direct ons ror U,e: S.., pzc~c ln;e,t.
`Warning: h r IV ,ue only M .. I be diluted bdor,e u,..
`Cootentf htwld be ci,pen,o:d prompdv •fter lnlllal cl01ure
`punc:lutc. Discard IA'!UR<l coolen ~ft•r 4 hoUJ'L
`tor• ill oontrolltd reom llffflp@r..lure
`1s•-ao·c (5!"-116' F). Do not rteze
`L01ta1ns no nlOII! lNn ;,,~uu ""'g,l of alun,n,'"'·
`lvbn.ufonurr-rl fn ,· .S.incfot fnr.
`P~ncir.on, "11 08540
`
`L-Cysteine
`Hydrcc~lorldc lnjt!Ct1on, USP
`
`50 mg/ml
`For IV Ule Only After Dilution
`Du Nat Ohpome A>' A Uplt
`SO mL
`L-01.CO
`
`Package Label - Principal Display Panel - 50 mL Vial Carton
`SANDOZ
`5 × 50 mL Vials NDC 66758-005-02
`L-Cysteine Hydrochloride
`Injection, USP
`50 mg/mL
`Pharmacy Bulk Package
`Not For Direct Infusion
`For IV Use Only After Dilution
`Rx only
`
`~ SANDOZ
`5Jt50 mLViaoi.
`L-Cysteine l-l yclrochloride
`lnj(>ction, USP
`.
`50 mg/ml ..
`.
`FOi IV Use, Only After DllullOn
`
`NOC 6675~5-42
`
`L-CYSTEINE HYDROCHLORIDE
`https://web.archive.org/web/20160824090050/http://www.drugsdb.eu/drug.php?d=L-cysteine Hydrochloride&m=Sandoz Inc&id=083366d6-0437-4ee0-90d4-440a5b… 3/4
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`Nexus Ex. 1004
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`L-CYSTEINE HYDROCHLORIDE - cysteine hydrochloride injection, solution  - Prescription (RX) Marketed Drugs Encyclopedia
`5/1/2020
`l-cysteine hydrochloride injection, solution
`Product Information
`Product Type
`
`Item Code (Source)
`
`DEA Schedule
`
`Basis of Strength
`CYSTEINE HYDROCHLORIDE
`
`Strength
`
`
`NDC:66758-
`005
`
`
`Strength
`50 mg in 1 mL
`
`
`
`HUMAN PRESCRIPTION
`DRUG
`INTRAVENOUS
`Route of Administration
`Active Ingredient/Active Moiety
`Ingredient Name
`CYSTEINE HYDROCHLORIDE (CYSTEINE)
`Inactive Ingredients
`Ingredient Name
`WATER
`Product Characteristics
`Color
`Shape
`Fla