Reference ID:3536446 INJECTION, USP SODIUM PHOSPHATE DEXAMETHASONE 45799G/Revised: May 2014 45799G/Revised: related derivativesofhydrocortisone. retaining property of hydrocortisone and closely closely and hydrocortisone of property retaining methasone almost completely lacks the sodium- the lacks completely almost methasone immune responsestodiversestimuli. bolic effects. In addition, they modify the body’s body’s the modify they addition, In effects. bolic disorders ofmanyorgansystems. used for their potent anti-inflammatory effects in in effects anti-inflammatory potent their for used primarily are dexamethasone, including analogs, adrenocortical deficiency states. Their synthetic synthetic Their states. deficiency adrenocortical properties, are used as replacement therapy in in therapy replacement as used are properties, sone and cortisone), which also have salt-retaining sive toadrenocorticalsteroidtherapy. suitable for the treatment of acute disorders respon- with less soluble preparations. Because of this, it is onset but short duration of action when compared Dexamethasone sodium phosphate has a rapid rapid a has phosphate sodium Dexamethasone ment (7.0 to 8.5). Air in the container is displaced is container the in Air 8.5). to (7.0 ment CLINICAL PHARMACOLOGY: hydroxide may have been added for pH adjust- pH for added been have may hydroxide by nitrogen. Water for Injection q.s. Citric acid and/or sodium sodium and/or acid Citric q.s. Injection for Water drate 11 mg; sodium sulfite 1 mg as an antioxidant; 10 mg added as preservative; sodium citrate dihy- 5 4 mg or dexamethasone 3.33 mg; benzyl alcohol alcohol benzyl mg; 3.33 dexamethasone or mg 4 phate equivalent to dexamethasone phosphate phosphate dexamethasone to equivalent phate nous or intramuscular use are indicated as follows: 4-diene-3,20-dione 21-(dihydrogen phosphate) phosphate) 21-(dihydrogen 4-diene-3,20-dione the condition, those products labeled for intrave- for labeled products those condition, the or intralesionaluse. reasonably lend the preparation to the treatment of (IV), intramuscular (IM), intra-articular, soft-tissue soft-tissue intra-articular, (IM), intramuscular (IV), 9-Fluoro-11 cortical steroidanti-inflammatorydrug. dosage form, and route of administration of the drug phosphate in water for injection for intravenous intravenous for injection for water in phosphate ingly hygroscopicandisfreelysolubleinwater. odorless or has a slight odor of alcohol, is exceed- 5 When oral therapy is not feasible and the strength, USP is a sterile solution of dexamethasone sodium as a white or slightly yellow crystalline powder, is is powder, crystalline yellow slightly or white a as soluble inorganic ester of dexamethasone. It occurs 5 Intravenous orIntramuscularInjection disodium salt and has the following structural formula: water- a is phosphate sodium Dexamethasone DESCRIPTION: C

INDICATIONS ANDUSAGE:

Endocrine Disorders Rheumatic Disorders Collagen Diseases 22 Glucocorticoids cause profound and varied meta- Chemically, dexamethasone sodium phosphate is Dexamethasone sodium phosphate is an adreno- Each mL contains dexamethasone sodium phos- Naturally occurring glucocorticoids (hydrocorti- glucocorticoids occurring Naturally At equipotent anti-inflammatory doses, dexa- doses, anti-inflammatory equipotent At Dexamethasone Sodium Phosphate Injection, Injection, Phosphate Sodium Dexamethasone

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Primary or secondary adrenocortical insuffi- adrenocortical secondary or Primary ciency (hydrocortisone or cortisone is the drug As adjunctive therapy for short-term administra- tion (to tide the patient over an acute episode acute an over patient the tide (to tion or exacerbation)in: Acute rheumaticcarditis Systemic lupuserythematosus Hypercalcemia associatedwithcancer Post-traumatic osteoarthritis Epicondylitis rheu- juvenile including arthritis, Rheumatoid Synovitis ofosteoarthritis Acute nonspecifictenosynovitis Psoriatic arthritis Acute goutyarthritis Ankylosing spondylitis therapy inselectedcasesof: During anexacerbationorasmaintenance cortisone or cortisone is the drug of choice; choice; of drug the is cortisone or cortisone mineralocorticoid supplementation may be be may supplementation mineralocorticoid (hydro- insufficiency adrenocortical Acute plementation isofparticularimportance) sup- mineralocorticoid infancy, in applicable; necessary, particularlynecessary, when synthetic analogs are used) Preoperatively, and in the event of serious serious of event the in and Preoperatively, trauma or illness, in patientsadre-knownillness,within or trauma if adrenocortical insufficiency exists or is is or exists insufficiency suspected adrenocortical if therapy conventional to unresponsive Shock is doubtful nal insufficiency or when adrenocortical reserve Nonsuppurative thyroiditis Congenital adrenalhyperplasia Acute andsubacutebursitis low-dose maintenancetherapy) require may cases (selected arthritis matoid

of choice; synthetic analogs may be used in in used be may analogs synthetic choice; of conjunction with mineralocorticoids where where mineralocorticoids with conjunction

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5 5 5 5 5 5 Systemic fungal infections (see (see infections regarding amphotericin B). Hypersensitivity to any fungal Systemic By IntralesionalInjection CONTRAINDICATIONS: 5 5 5 5 By Intra-articularorSoftTissueInjection 5

Neoplastic Diseases Hematologic Disorders Respiratory Diseases Gastrointestinal Diseases Miscellaneous Allergic States Edematous States Dermatologic Diseases Ophthalmic Diseases Cerebral Edema associated with primary or or primary with associated Edema Cerebral igotc etn o arncria hyper- adrenocortical of testing Diagnostic Leukemias andlymphomasinadults For palliativemanagementof: Congenital (erythroid)hypoplasticanemia Erythroblastopenia (RBCanemia) Secondary thrombocytopeniainadults (IV only;IMadministrationiscontraindicated) Idiopathic thrombocytopenic purpura in adults Acquired (autoimmune) hemolytic anemia anemia hemolytic (autoimmune) Acquired syndrome not manageable by other means means Aspiration pneumonitis other by manageable not syndrome priate appro- antituberculous chemotherapy with Loeffler’s concurrently used when culosis Fulminating or disseminated pulmonary tuber­ Berylliosis Symptomatic sarcoidosis Regional enteritis(Systemictherapy) To tide the patient over a critical period of the of period critical a over patient the tide To disease in: Ulcerative colitis(Systemictherapy) Allergic cornealmarginalulcers block or impending block when used concur- used when block impending or block rently with appropriate antituberculous che- antituberculous appropriate with rently Keratitis Tuberculous meningitis with subarachnoid subarachnoid with meningitis Tuberculous Allergic conjunctivitis Anterior segmentinflammation Sympathetic ophthalmia thematosus Optic neuritis Control of severe or incapacitating allergic allergic incapacitating or severe of Control the idiopathic type, or that due to lupus ery- lupus to due that or type, idiopathic the Diffuse posterioruveitisandchoroiditis Mycosis fungoides Severe psoriasis in the nephrotic syndrome, without uremia, of uremia, without syndrome, nephrotic the in Chorioretinitis Severe seborrheicdermatitis Bullous dermatitisherpetiformis Exfoliative dermatitis Rheumatoid arthritis Acute andsubacutebursitis Acute goutyarthritis Epicondylitis To induce diuresis or remission of proteinuria of remission or diuresis induce To Iritis, iridocyclitis Johnson syndrome) Severe erythemamultiforme(Stevens- Synovitis ofosteoarthritis Acute nonspecifictenosynovitis Post-traumatic osteoarthritis granuloma annulare and lichen simplex chroni- cus (neurodermatitis) Necrobiosis lipoidicadiabeticorum Discoid lupuserythematosus Alopecia areata aponeurosis ortendon(ganglia) May alsobeusefulincystictumorsofan Herpes zosterophthalmicus Pemphigus function involvement metastatic brain tumor, craniotomy, or head head or craniotomy, tumor, brain metastatic injury. Use in cerebral edema is not a substitute for for substitute a not is edema cerebral in Use careful neurosurgical evaluation and definitive and evaluation neurosurgical careful As adjunctive therapy for short-term administra- specific therapy. other or neurosurgery as such management or exacerbation)in: episode acute an over patient the tide (to tion tory lesions of: lichen inflamma- planus, psoriaticinfiltrated, plaques, hypertrophic, Localized Keloids inflam- and allergic chronic and acute Severe Acute leukemiaofchildhood matory processesinvolvingtheeye,suchas:

motherapy Trichinosis with neurologic or myocardial myocardial or neurologic with Trichinosis Contact dermatitis Atopic dermatitis Serum sickness Seasonal orperennialallergicrhinitis Drug hypersensitivityreactions Urticarial transfusionreactions rine is thedrugoffirstchoice) Acute noninfectious laryngeal edema (epineph- conditions intractable to adequate trials of of trials adequate to intractable conditions conventional treatmentin: Bronchial asthma

WARNINGS WARNINGS

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the tropics or any patient with unexplained diarrhea. steroid therapy in any patient who has spent time in amebiasis be ruled out before initiating cortico- initiating before out ruled be amebiasis Therefore, it is recommended that latent or active active or latent that recommended is it Therefore, pneumonia andgastrointestinalbleeding. prolongation of coma and a higher incidence of of incidence higher a and coma of prolongation that the use of corticosteroids is associated with with associated is corticosteroids of use the that produce falsenegativeresults. nitroblue-tetrazolium test for bacterial infection and use. There may be decreased resistance and and are used. Moreover, corticosteroids may affect the resistance corticosteroids when infection localize to decreased inability be may There use. their during appear may infections new and tion, tered concurrently. salt and/or a mineralocorticoid should be adminis- Since mineralocorticoid secretion may be impaired, steroids already, dosage may have to be increased. tion of therapy; therefore, in any situation of stress of situation any in therefore, therapy; of tion occurring during that period, hormone therapy therapy hormone period, that during occurring should be reinstituted. If the patient is receiving receiving is patient the If reinstituted. be should ficiency may persist for months after discontinua- after insuf- months for persist relative may ficiency of type This dosage. of reduction with the synthetic derivatives except when used in used when except derivatives synthetic the with large doses. Dietary salt restriction and potassium and restriction salt Dietary doses. large corticosteroids and may be minimized by gradual by minimized be may and corticosteroids of potassium. These effects are less likely to occur ficiency may result from too rapid withdrawal of of withdrawal rapid too from result may ficiency salt and water retention, and increased excretion excretion increased and retention, water and salt stressful situationisindicated. cortisone can cause elevation of blood pressure, pressure, blood of elevation cause can cortisone acting corticosteroids before, during, and after the reactions have been reported for dexamethasone dexamethasone for reported been have reactions sodium phosphate (see to any unusual stress, increased dosage of rapidly to any drug. Anaphylactoid and hypersensitivity hypersensitivity and Anaphylactoid drug. any to especially when the patient has a history of allergy infections duetofungiorviruses. measures should be taken prior to administration, to prior taken be should measures parenteral precautionary appropriate receiving therapy, corticosteroid patients in occurred have to avoid exposure. How the dose, route and dura- and route dose, the How exposure. avoid to tion of corticosteroid administration affects the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or disease underlying the of contribution The latent tuberculosis or tuberculin reactivity, close close reactivity, tuberculin or tuberculosis latent enhance the establishment of secondary ocular ocular secondary of establishment the enhance congestive failure. Because rare instances of anaphylactoid reactions WARNINGS: had these diseases, particular care should be taken prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be be may (VZIG) globulin immune zoster varicella If chickenpox develops, treatment with antiviral antiviral with treatment develops, chickenpox If agents maybeconsidered. in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculo- disseminated or fulminating of cases sis in which the corticosteroid is used for the the for used is corticosteroid management of the disease in conjunction with an the which in sis appropriate antituberculousregimen. possible damage to the optic nerves, and may may and nerves, optic the to damage possible tisone was followed by cardiac enlargement and and enlargement cardiac by followed was tisone component of this product, including sulfites (see observation is necessary as reactivation of the dis- patients should be observed closely for develop- for closely observed be should patients observation is necessary as reactivation of the dis- WARNINGS). (see sulfites including product, this of component If inactivated viral or bacterial vaccines are admin- are vaccines bacterial or viral inactivated If ing immunosuppressive doses of corticosteroids. corticosteroids. of doses immunosuppressive ing receiv- individuals in contraindicated is smallpox, istered to individuals receiving immunosuppres- receiving individuals to istered sive doses of corticosteroids, the expected serum expected the corticosteroids, of doses sive antibody response may not be obtained. However, immunization procedures may be undertaken in in undertaken be may procedures immunization patients who are receiving corticosteroids as as corticosteroids receiving are who patients immune system are more susceptible to infections for example, can have a more serious or even fatal than healthy individuals. Chickenpox and measles, replacement therapy,e.g.,forAddison’sdisease. costeroids. In such children or adults who have not corti- on adults or children non-immune in course indicated. If exposed to measles, prophylaxis with prophylaxis measles, to exposed If indicated. indicated. (See the respective package inserts for inserts package respective the (See indicated. pooled intramuscular immunoglobulin (IG) may be complete VZIG and IG prescribing information). information). prescribing IG and VZIG complete Moreover, there have been cases reported in which concomitant use of amphotericin B and hydrocor- and B amphotericin of use concomitant posterior subcapsular cataracts, glaucoma with with glaucoma cataracts, subcapsular posterior supplementation may be necessary. All cortico- All necessary. be may supplementation steroids increasecalciumexcretion. toms and life-threatening or less severe asthmatic severe less or life-threatening and toms episodes in certain susceptible people. The over- The people. susceptible certain in episodes all prevalence of sulfite sensitivity in the general general the in sensitivity sulfite of prevalence all population is unknown and probably low. Sulfite Sulfite low. probably and unknown is population sensitivity is seen more frequently in asthmatic than in non-asthmaticpeople. to control drug reactions due to amphotericin B. B. amphotericin to due reactions drug control to presence of such infections unless they are needed infections and therefore, should not be used in the contains sodium bisulfite, a sulfite that may cause may that sulfite a bisulfite, sodium contains allergic-type reactions including anaphylactic symp-

In cerebral malaria, a double-blind trial has shown Prolonged use of corticosteroids may produce produce may corticosteroids of use Prolonged Corticosteroids may mask some signs of infec- of signs some mask may Corticosteroids Average and large doses of cortisone or hydro- or cortisone of doses large and Average Corticosteroids may exacerbate systemic fungal Corticosteroids may activate latent amebiasis. amebiasis. latent activate may Corticosteroids Persons who are on drugs which suppress the the suppress which drugs on are who Persons In patients on corticosteroid therapy subjected subjected therapy corticosteroid on patients In The use of dexamethasone sodium phosphate phosphate sodium dexamethasone of use The If corticosteroids are indicated in patients with with patients in indicated are corticosteroids If Drug-induced secondary adrenocortical insuf­ adrenocortical secondary Drug-induced Administration of live virus vaccines, including including vaccines, virus live of Administration

Dexamethasone sodium phosphate injection injection phosphate sodium Dexamethasone

ADVERSE REACTIONS).

reduction mustbegradual. and when reduction in dosage is possible, the the possible, is dosage in reduction when and be used to control the condition under treatment, treatment, under condition the control to used be neal perforation. patients with ocular herpes simplex for fear of cor- of fear for simplex herpes ocular with patients rhosis. patients with hypothyroidism and in those with cir-patientshypothyroidismwiththosewith in and ficiency. steroid withdrawal syndrome including fever, fever, adrenalinsuf-withoutevidenceofpatients even in occur including may This malaise. and arthralgia, syndrome myalgia, withdrawal steroid ticosteroids may result in symptoms of the cortico- of thevial. exterior the sterilize to desirable is it when claved is sensitive to heat. Therefore, it should not be auto- This product, like many other steroid formulations, corticosteroids should be advised not to nurse. PRECAUTIONS: ticosteroid production, or cause other unwanted unwanted other cause or production, ticosteroid effects. Mothers taking pharmacologic doses of of doses pharmacologic taking Mothers effects. specific ulcerative colitis, if there is a probability probability a is there if colitis, ulcerative specific of impending perforation, abscess, or other pyo­ other or abscess, perforation, impending of cor­ endogenous with interfere growth, suppress signs ofhypoadrenalism. with corticosteroidsinhypoprothrombinemia. during pregnancy should be carefully observed for have received substantial doses of corticosteroids of doses substantial received have Serious Neurologic Adverse Reactions Reactions Adverse Neurologic Serious with Epidural Administration Administration Epidural with cies maybeaggravatedbycorticosteroids. and embryo or fetus. Infants born of mothers who mothers of born Infants fetus. or embryo and should be used with great caution in these patients. and malaise is suggestive of septic arthritis. If this If arthritis. septic of suggestive is malaise and should be used with great caution in these patients. existing emotional instability or psychotic tenden- psychotic or instability emotional existing weighed against the possible hazards to the mother rclrfe alrpueatrarcn ycril A marked increase in pain accompanied by local entisnecessarytoexcludeasepticprocess. myocardial recent a after rupture wall free tricular ven- left and corticosteroids of use between tion infarction; therefore, therapy with corticosteroids swelling, further restriction of joint motion, fever, fever, motion, joint of restriction further swelling, corticosteroids with therapy therefore, infarction; lessened physiologic activity, thus requiring adjust- ment in corticosteroid dosage. These interactions These dosage. corticosteroid in ment may interfere with dexamethasone suppression suppression dexamethasone with interfere may tests which should be interpreted with caution dur­ comitantly with potassium-depleting diuretics, diuretics, potassium-depleting with comitantly depression to frank psychotic manifestations. Also, potential requires that the anticipated benefits be be benefits anticipated the that requires potential apy, these patients should receive chemoprophy- Intra-articular injection of a corticosteroid may may corticosteroid a of injection Intra-articular chemoprophy- receive should patients these apy, laxis. steroids resulting in decreased blood levels and and levels blood decreased in resulting steroids ing administrationofthesedrugs. pression test (DST) in patients being treated with with treated being patients in (DST) test pression quently in patients who are receiving corticoste- receiving are who patients in quently roids and coumarin anticoagulants at the same time because of reports that corticosteroids have altered the response to these anticoagulants. Studies have rins, although there have been some conflicting conflicting some been have there although rins, couma- to response of inhibition is corticosteroids adding by produced effect usual the that shown reports of potentiation not substantiated by studies. mood swings, personality changes, and severe severe and changes, personality swings, mood drugs in pregnancy or in women of childbearing childbearing of women in or pregnancy in drugs aemyocr uigpoogdcriotri hr mentofhypokalemia. ease may occur. During prolonged corticosteroid ther- receiving large doses of corticosteroids may be be may corticosteroids of doses large receiving following gastrointestinal perforation in patients patients in perforation gastrointestinal irritation following peritoneal of and Signs gravis. osteoporosis, myasthenia hypertension, insufficiency, minimal or absent. Fat embolism has been reported as apossiblecomplicationofhypercortisonism. advise that antacids be administered between between administered be antacids that advise on prolonged corticosteroid therapy should be be should carefully followed. therapy corticosteroid prolonged on meals tohelppreventpepticulcer. number ofspermatozoainsomepatients. may enhance the metabolic clearance of cortico- of clearance metabolic the enhance may of the DST should be interpreted with caution in in these patients. caution with interpreted be should DST the of results Thus, reported. been have indomethacin Since adequate human reproduction studies have studies reproduction human adequate Since steroids are used, ranging from euphoria, insomnia, these of use corticosteroids, with done been not corticosteroids.Specific events reported include, but

genic infection, also in diverticulitis, fresh intestinal anastomoses, active or latent peptic ulcer, renal renal ulcer, peptic latent or active anastomoses, are not limited to, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke. These serious neurologic events have been reported with and without use of fluoroscopy. The safety and and safety The fluoroscopy. of use without and effectiveness of epidural administration or cortico­ or administration epidural of effectiveness Teratogenic Effects: Pregnancy Category C– C– Category Pregnancy Effects: Teratogenic corticoste- and established, been not has steroids roids arenotapprovedforthisuse. Pregnancy Serious neurologic events, some resulting in death, have been reported with epidural injection of of injection epidural with reported been have

Psychic derangements may appear when cortico- The lowest possible dose of corticosteroid should Phenytoin, phenobarbital, ephedrine, and rifampin There is an enhancedancorticosteroids effectThereisof in False negative results in the dexamethasone sup- Following prolonged therapy, withdrawal of cor- Followingwithdrawalprolongedtherapy,of Aspirin should be used cautiously in conjunction Corticosteroids appear in breast milk and could and milk breast in appear Corticosteroids ieauerprssgeta paetasca Appropriateexaminationofanyjointfluidpres- associa- apparent an suggest reports Literature Growth and development of infants and children Steroids may increase or decrease motility and motility decrease or increase may Steroids When large doses are given, some authorities authorities some given, are doses large When The prothrombin time should be checked fre- checked be should time prothrombin The Corticosteroids should be used cautiously in in cautiously used be should Corticosteroids Steroids should be used with caution in non- in caution with used be should Steroids hn otcseod ae diitrd con- administered are corticosteroids When

mm

Dermatologic: Gastrointestinal: Musculoskeletal: Neurologic: Fluid andelectrolytedisturbances: ADVERSE REACTIONS: complication occurs and the diagnosis of sepsis is confirmed, appropriate antimicrobial therapy should should besoughtwithoutdelay. advised that if they are exposed, medical advice advice medical exposed, are they if that advised to chickenpox or measles. Patients should also be produce systemicaswelllocaleffects. Metabolic: corticosteroids should be warned to avoid exposure Endocrine: Ophthalmic: Cardiovascular: Other: Information forPatients Persons who are on immunosuppressant doses of

unstable joints. importance of not overusing joints in which symp- which in joints overusing not of importance tomatic benefit has been obtained as long as the the as long as obtained been has benefit tomatic inflammatory processremainsactive. administration shouldberecognized. damage tojointtissues. be instituted. be avoided. Patients should be impressed strongly with the the with strongly impressed be should Patients The slower rate of absorption by intramuscular intramuscular by absorption of rate slower The Injection of a steroid into an infected site is to to is site infected an into steroid a of Injection Frequent intra-articular injection may result in in result may injection intra-articular Frequent Petechiae andecchymoses Thin fragileskin Impaired woundhealing Ulcerative esophagitis Abdominal distention Pancreatitis larly in patients with inflammatory bowel disease Perforation of the small and large bowel, particu- and hemorrhage Peptic ulcer with possible subsequent perforation Tendon rupture Aseptic necrosisoffemoralandhumeralheads Vertebral compressionfractures Pathologic fractureoflongbones Osteoporosis Loss ofmusclemass Steroid myopathy Muscle weakness Hypertension Hypokalemic alkalosis Congestive heartfailureinsusceptiblepatients Potassium loss Convulsions Fluid retention Sodium retention matitis, urticaria,angioneuroticedema Other cutaneous reactions, such as allergic der­ (after IVinjection) Burning or tingling, especially in the perineal area Increased intraocularpressure Glaucoma Exophthalmos related toparenteralcorticosteroidtherapy: Rare instances of blindness associated with with associated blindness of instances Rare May suppressreactionstoskintests Posterior subcapsularcataracts Negative nitrogen balance due to protein catabo­ lism Anaphylactoid orhypersensitivityreactions Thromboembolism Weight gain Increased appetite Hiccups Malaise Nausea The following following The Increased sweating Psychic disturbances Headache Menstrual irregularities Development ofcushingoidstate Suppression ofgrowthinchildren Secondary adrenocortical and pituitary unre­ pituitary and adrenocortical Secondary Manifestations oflatentdiabetesmellitus Decreased carbohydratetolerance as stress, of times in particularly sponsiveness, Increased requirements for insulin or oral hypo- oral or insulin for requirements Increased in trauma,surgery,orillness glycemic agentsindiabetics Hirsutism infarction (seeWARNINGS) myocardial recent following rupture Myocardial Erythema Increased intracranial pressure with papilledema (pseudotumor cerebri) usually after treatment treatment after usually cerebri) (pseudotumor Vertigo Corticosteroids should not be injected into into injected be not should Corticosteroids

additional additional

adverse reactions are are reactions adverse

CrossTech–74191–Proof A1 Form M01 Fresenius Kabi USA, LLC P.O. No. 4500143063–Job No. 45799G 4/29/14–hc–Indd4 m Fonts: Helvetica (A) Typesmiths Pi Font 5AV

intralesional therapy around the face and head within 12 to 24 hours and dosage may be reduced 2. Dietzman, R.H.; Ersek, R.A.; Bloch, J.M.; Lillehei, Hyperpigmentation or hypopigmentation after two to four days and gradually discontinued R.C.: High-output, low-resistance gram-negative Subcutaneous and cutaneous atrophy over a period of five to seven days. For palliative septic shock in man, Angiology 20: 691-700, Sterile abscess management of patients with recurrent or inoper­ Dec. 1969. Post-injection flare (following intra-articular use) able brain tumors, maintenance therapy with two 3. Frank, E.: Clinical observations in shock and Charcot-like arthropathy mg two or three times a day may be effective. management (In: Shields, T.F., ed.: Symposium Acute Allergic Disorders on current concepts and management of shock), OVERDOSAGE: J. Maine Med. Ass. 59: 195-200, Oct. 1968. Reports of acute toxicity and/or death following In acute, self-limited allergic disorders or acute exacerbations of chronic allergic disorders, the 4. Oaks, W. W.; Cohen, H.E.: Endotoxin shock in overdosage of glucocorticoids are rare. In the event the geriatric patient, Geriat. 22: 120-130, Mar. of overdosage, no specific antidote is available; following dosage schedule combining parenteral and oral therapy is suggested: 1967. treatment is supportive and symptomatic. 5. Schumer, W.; Nyhus, L.M.: Corticosteroid effect The oral LD of dexamethasone in female mice Dexamethasone sodium phosphate injection, 50 4 mg/mL: first day, 1 or 2 mL (4 or 8 mg), intra­ on biochemical parameters of human oligemic was 6.5 g/kg. The intravenous LD50 of dexameth­ shock, Arch. Surg. 100: 405-408, Apr. 1970. asone sodium phosphate in female mice was muscularly. 794 mg/kg. Dexamethasone tablets, 0.75 mg: second and third days, 4 tablets in two divided doses each day; DOSAGE AND ADMINISTRATION: fourth day, 2 tablets in two divided doses; fifth and Dexamethasone sodium phosphate injection, sixth days, 1 tablet each day; seventh day, no treat­ 4 mg/mL– For intravenous, intramuscular, intra- ment; eighth day, follow-up visit. articular, intralesional, and soft tissue injection. This schedule is designed to ensure adequate Dexamethasone sodium phosphate injection can therapy during acute episodes, while minimizing be given directly from the vial, or it can be added the risk of overdosage in chronic cases. to Sodium Chloride Injection or Dextrose Injection Intra-articular, Intralesional and Soft Tissue and administered by intravenous drip. Injection: Solutions used for intravenous administration or Intra-articular, intralesional, and soft tissue injections further dilution of this product should be preserva­ are generally employed when the affected joints or tive free when used in the neonate, especially the areas are limited to one or two sites. Dosage and premature infant. frequency of injection varies depending on the con­ When it is mixed with an infusion solution, sterile dition and the site of injection. The usual dose is precautions should be observed. Since infusion from 0.2 to 6 mg. The frequency usually ranges from solutions generally do not contain preservatives, once every three to five days to once every two to mixtures should be used within 24 hours. three weeks. Frequent intra-articular injection may result in damage to joint tissues. DOSAGE REQUIREMENTS ARE VARIABLE AND Some of the usual single doses are: MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE AND THE RESPONSE OF THE Amount of PATIENT. Site of Injection Dexamethasone Phosphate (mg) Intravenous and Intramuscular Injection: The initial dosage of dexamethasone sodium Large Joints 2 to 4 phosphate injection varies from 0.5 to 9 mg a day depending on the disease being treated. In less (e.g., Knee) severe diseases doses lower than 0.5 mg may suf­ Small Joints fice, while in severe diseases doses higher than (e.g., Interphalangeal, 9 mg may be required. Temporomandibular) 0.8 to 1 The initial dosage should be maintained or adjusted until the patient’s response is satisfac­ Bursae 2 to 3 m tory. If a satisfactory clinical response does not occur after a reasonable period of time, discontinue Tendon Sheaths 0.4 to 1 dexamethasone sodium phosphate injection and Soft Tissue Infiltration 2 to 6 transfer the patient to other therapy. After a favorable initial response, the proper Ganglia 1 to 2 maintenance dosage should be determined by decreasing the initial dosage in small amounts to Dexamethasone sodium phosphate injection is the lowest dosage that maintains an adequate clini­ particularly recommended for use in conjunction cal response. with one of the less soluble, longer-acting steroids Patients should be observed closely for signs for intra-articular and soft tissue injection. that might require dosage adjustment, including Parenteral drug products should be inspected changes in clinical status resulting from remissions visually for particulate matter and discoloration prior or exacerbations of the disease, individual drug to administration, whenever the solution and con­ responsiveness, and the effect of stress (e.g., sur­ tainer permit. gery, infection, trauma). During stress it may be HOW SUPPLIED: necessary to increase dosage temporarily. If the drug is to be stopped after more than a few Product NDC days of treatment, it usually should be withdrawn No. No. gradually. 16501 63323-165-01 Dexamethasone When the intravenous route of administration Sodium Phosphate is used, dosage usually should be the same as Injection, USP the oral dosage. In certain overwhelming, acute, (equivalent to life-threatening situations, however, administration 4 mg per mL in dosages exceeding the usual dosages may be dexamethasone justified and may be in multiples of the oral dos­ phosphate) ages. The slower rate of absorption by intramuscu­ 1 mL fill, in a 2 mL lar administration should be recognized. flip-top vial, packaged in 25. Shock 16505 63323-165-05 Dexamethasone There is a tendency in current medical practice to Sodium Phosphate use high (pharmacologic) doses of corticosteroids Injection, USP for the treatment of unresponsive shock. The follow­ (equivalent to ing dosages of dexamethasone sodium phosphate 20 mg/5 mL injection have been suggested by various authors: [4 mg/mL] Author Dosage dexamethasone

Cavanagh1 3 mg/kg of body weight per 24 phosphate) 5 mL hours by constant intravenous fill, in a 5 mL flip-top infusion after an initial intra­ vial, packaged venous injection of 20 mg in 25.

Dietzman2 2 to 6 mg/kg of body weight as a 16530 63323-165-30 Dexamethasone single intravenous injection Sodium Phosphate 3 Injection, USP Frank 40 mg initially followed by repeat (equivalent to intravenous injection every 4 to 6 120 mg per 30 mL hours while shock persists [4 mg per mL] Oaks4 40 mg initially followed by repeat dexamethasone intravenous injection every 2 to 6 phosphate) 30 mL hours while shock persists fill, in a 30 mL flip-top Schumer5 1 mg/kg of body weight as a vial, packaged single intravenous injection individually.

Administration of high dose corticosteroid therapy Store at 20° to 25°C (68° to 77°F) [see USP Con­

should be continued only until the patient’s condi­ trolled Room Temperature]. Protect from freezing. tion has stabilized and usually not longer than 48 Sensitive to heat. Do not autoclave. to 72 hours. Protect from light. Store container in carton until Although adverse reactions associated with high contents have been used. dose, short term corticosteroid therapy are uncom­ mon, peptic ulceration may occur. Do not use if precipitate is present. Cerebral Edema REFERENCES: Dexamethasone sodium phosphate injection is 1. Cavanagh, D.; Singh, K.B.: Endotoxin shock in Fresenius Kabi USA, LLC generally administered initially in a dosage of pregnancy and abortion, in: “Corticosteroids in Lake Zurich, IL 60047 10 mg intravenously followed by four mg every the Treatment of Shock”, Schumer, W.; Nyhus,

six hours intramuscularly until the symptoms of L.M., Editors, Urbana, University of Illinois Press, 45799G cerebral edema subside. Response is usually noted 1970, pp. 86-96. Revised: May 2014

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rsTc–49–ro A1 CrossTech–74191–Proof Form M02 Fresenius Kabi USA, LLC P.O. No. 4500143063–Job No. 45799G 4/29/14–hc–Indd4 (A) Helvetica Fonts: Reference ID: 3536446 Reference ID:3536446 Rx only For Intravenous or Intramuscular Use Only INJECTION, USP SODIUM PHOSPHATE DEXAMETHASONE May 2014 45955E/Revised: disodium salt, (11 ide, if necessary. pH: 7.0 to 8.5. q.s. properties, are used as replacement therapy in in therapy replacement as used are properties, 11,17­dihydroxy­16­methyl­21­(phosphonooxy)­, 11,17­dihydroxy­16­methyl­21­(phosphonooxy)­, sodium citrate, dihydrate; and Water for Injection, for Water and dihydrate; citrate, sodium sone and cortisone), which also have salt­retaining hmclyi Pregna­1,4­diene­3,20­dione, is 9­fluoro­ chemically to 10 mg dexamethasone phosphate; 24.75 mg mg 24.75 phosphate; dexamethasone mg 10 to eaehsn oimpopae S equivalent USP phosphate, dexamethasone sodium responsive to adrenocortical steroid therapy. a rapid onset but short duration of action when com­ when injected intramuscularly. dihydrate; 10 mg benzyl alcohol; and Water for for Water and alcohol; benzyl mg 10 dihydrate; 1. Endocrine Disorders INDICATIONS AND USAGE: derivatives of hydrocortisone. Injection, USP USP Injection, hs ti utbefrteteteto ct disorders acute of treatment the for suitable is it this, following structural formula: Dexamethasone sodium phosphate injection has injection phosphate sodium Dexamethasone citrate, sodium mg 13.5 dexamethasone phosphate; even response rapid a produces which ethasone disorders of in many organ systems. effects anti­inflammatory potent their for used oral therapy is not feasible: property of hydrocortisone and closely related related closely and hydrocortisone of property pared with less soluble preparations. Because of Because preparations. soluble less with pared CLINICAL PHARMACOLOGY: solutions have a pH between 7.0 and 8.5. It has the exceedingly hygroscopic, is soluble in water and its dexam­ of ester inorganic USP,water­soluble a is adrenocortical deficiency states. Their synthetic synthetic Their states. deficiency adrenocortical mg 10 to equivalent USP phosphate, sodium analogs, including dexamethasone, are primarily are dexamethasone, including analogs, By intravenous or intramuscular injection when sone almost completely lacks the sodium­ retaining

C DESCRIPTION:

hydroxide, if necessary. pH: 7.0 to 8.5. 3. 2. body’s the modify they addition, In effects. bolic Injection, q.s. pH adjusted with citric acid or sodium Injection, USP Dexamethasone Sodium Phosphate Injection, Injection, Phosphate Sodium Dexamethasone immune responses to diverse stimuli.

22

At equipotent anti­inflammatory doses, dexametha­ Glucocorticoids cause profound and varied meta­ Naturally occurring glucocorticoids (hydrocorti­ glucocorticoids occurring Naturally Each mL of Dexamethasone Sodium Phosphate Each mL Dexamethasone Sodium Phosphate Phosphate Sodium Dexamethasone mL Each It occurs as a white to creamy white powder, is powder, white creamy to white a as occurs It Dexamethasone Sodium Phosphate, USP USP Phosphate, Sodium Dexamethasone Collagen Diseases Rheumatic Disorders H

Ankylosing spondylitis Psoriatic arthritis Acute gouty arthritis Acute rheumatic carditis Acute nonspecific tenosynovitis Systemic lupus erythematosus are used). necessary, particularly when synthetic analogs Epicondylitis Acute and subacute bursitis therapy in selected cases of: Nonsuppurative thyroiditis is or Congenital adrenal hyperplasia exists suspected. insufficiency adrenocortical if therapy conventional to unresponsive Shock is doubtful. reserve adrenocortical when or insufficiency adrenal known with patients in illness, or trauma Hypercalcemia associated with cancer be may supplementation mineralocorticoid choice; of drug the is cortisone or cortisone supplementation is of particular importance). in used be may analogs synthetic choice; of applicable; in infancy, mineralocorticoid mineralocorticoid infancy, in where applicable; mineralocorticoids with conjunction ciency (hydrocortisone or insuffi­ cortisone is the adrenocortical drug secondary or Primary

low­dose maintenance therapy). As adjunctive therapy for short­term adminis­ short­term for therapy adjunctive As During an exacerbation or as maintenance tration (to tide the patient over an acute episode or exacerbation) in: matoid arthritis (selected cases may require require may cases (selected arthritis matoid rheu­ juvenile including arthritis, Rheumatoid Synovitis of osteoarthritis Post­traumatic osteoarthritis pH adjusted with citric acid or sodium hydrox­

28

Preoperatively, and in the event of serious of event the in and Preoperatively, ct arncria isfiiny (hydro­ insufficiency adrenocortical Acute

FNa

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(Preservative Free) Free) (Preservative b, 16a).

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tisone was followed by cardiac enlargement and enlargement cardiac by followed was tisone concomitant use of amphotericin B and hydrocor­ Moreover, there have been cases reported in which to control drug reactions due to amphotericin B. amphotericin to due reactions drug control to stressful situation is indicated. presence of such infections unless they are needed acting corticosteroids before, during, and after the infections and, therefore, should not be used in the to any unusual stress, increased dosage of rapidly REACTIONS). have occurred in patients receiving parenteral parenteral receiving patients in occurred have Because rare instances of anaphylactoid reactions WARNINGS:

corticosteroid therapy, appropriate precautionary appropriate therapy, corticosteroid measures should be taken prior to administration, 14. 13. 12. 11. 10. 9. 8. 7. 6. 5. 4. sodium phosphate injection (see (see injection phosphate sodium dexamethasone for reported been have reactions hypersensitivity and Anaphylactoid drug. any to congestive failure. ing amphotericin B). (see infections fungal Systemic CONTRAINDICATIONS: especially when the patient has a history of allergy (see

Hypersensitivity to any component of this product Corticosteroids may exacerbate systemic fungal In patients on corticosteroid therapy subjected therapy corticosteroid on patients In Hematologic Disorders Respiratory Diseases Gastrointestinal Diseases Ophthalmic Diseases Allergic States Dermatologic Diseases

Miscellaneous Edematous States Neoplastic Diseases Cerebral Edema Edema Cerebral igotc etn o arncria hyper- adrenocortical of testing Diagnostic Allergic corneal marginal ulcers Mycosis fungoides Keratitis Severe psoriasis Anterior segment inflammation Allergic conjunctivitis Aspiration pneumonitis Severe seborrheic dermatitis Sympathetic ophthalmia means. Bullous dermatitis herpetiformis Optic neuritis Loeffler’s syndrome not manageable by other by manageable not syndrome Loeffler’s Fulminating or disseminated pulmonary tuber­ Exfoliative dermatitis Ulcerative colitis (systemic therapy) matosus. Acute leukemia of childhood Diffuse posterior uveitis and choroiditis priate antituberculous chemotherapy. Berylliosis disease in: conventional treatment in: Johnson syndrome) (IV only; IM administration is contraindicated). Idiopathicthrombocytopenic purpura in adults the idiopathic type or that due to lupus erythe­ Leukemias and lymphomas in adults Chorioretinitis culosis when used concurrently with appro­ with concurrently used when culosis Symptomatic sarcoidosis the of period critical a over patient the tide To of trials adequate to intractable allergic conditions incapacitating or severe of Control Severe erythema multiforme (Stevens­ Acquired (autoimmune) hemolytic anemia. anemia. hemolytic (autoimmune) Acquired Secondary thrombocytopenia in adults in the nephrotic syndrome, without uremia, of uremia, without syndrome, nephrotic the in For palliative management of: injury. Use in cerebral edema is not a substi­ a not is edema cerebral in Use injury. head or craniotomy, tumor, brain metastatic Regional enteritis (systemic therapy)

Herpes zoster ophthalmicus Urticarial transfusion reactions Drug hypersensitivity reactions Seasonal or perennial allergic rhinitis Serum sickness Atopic dermatitis Contact dermatitis Bronchial asthma Iritis, iridocyclitis Acute noninfectious laryngeal edema (epineph­ rine is the drug of first choice).

or other specific therapy. neurosurgery as such management definitive and evaluation neurosurgical careful for tute Pemphigus Severe acute and chronic allergic and inflam­ and allergic chronic and acute Severe matory processes involving the eye, such as: involvement. concurrently used when block impending or ihappropriate antituberculouswith chemotherapy. To induce diuresis or remission of proteinuria of remission or diuresis induce To Tuberculousmeningitiswithsubarachnoidblock function. Congenital (erythroid) hypoplastic anemia Erythroblastopenia (RBC anemia) WARNINGS).

Trichinosis with neurologic or myocardial myocardial or neurologic with Trichinosis

associated with primary or or primary with associated

WARNINGS

ADVERSE ADVERSE

regard­

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mineralocorticoid secretion may be impaired, saltimpaired, be maysecretionmineralocorticoid cortisone can cause elevation of blood pressure, blood of elevation cause can cortisone have received substantial doses of corticosteroids already, dosage may have to be increased. Since increased. be to have may dosage already, and embryo or fetus. Infants born of mothers who mothers of born Infants fetus. or embryo and be reinstituted. If the patient is receiving steroids receiving is patient the If reinstituted. be enhance the establishment of secondary ocular ocular secondary of establishment the enhance infections due to fungi or viruses. weighed against the possible hazards to the mother who are receiving corticosteroids as replacement as corticosteroids receiving are who ring during that period, hormone therapy should therapy hormone period, that during ring possible damage to the optic nerves, and may may and nerves, optic the to damage possible potential requires that the anticipated benefits be benefits anticipated the that requires potential ticosteroid production, or cause other unwanted unwanted other cause or production, ticosteroid zation procedures may be undertaken in patients in undertaken be may procedures zation of therapy; therefore, in any situation of stress occur­ posterior subcapsular cataracts, glaucoma with with glaucoma cataracts, subcapsular posterior drugs in pregnancy or in women of childbearing of women in or pregnancy in drugs suppress growth, interfere with endogenous cor­ endogenous with interfere growth, suppress response may not be obtained. However, immuni­ ficiency may persist for months after discontinuation supplementation may be necessary. All cortico­ All necessary. be may supplementation large doses. Dietary salt restriction and potassium with varicella zoster immune globulin (VZIG) may be be indicated. (See the inserts may package respective (IG) for globulin immune with prophylaxis measles, lying disease. If exposed to chickenpox, corticosteroidprophylaxis administration as well as to the under­ Since adequate human reproduction studies have not been done with corticosteroids, use of these of use corticosteroids, with done been not and corticosteroids are not approved for this use. tration of corticosteroids has not been established,The safety and effectiveness of epidural adminis­ been reported with and without use of and fluoroscopy.stroke. These serious neurologic events have tion, paraplegia, quadriplegia, cortical blindness, infarc­ cord spinal to, limited not are but include, reported events Specific corticosteroids. of injec­ tion epidural in with reported resulting been have some death, events, neurologic Serious with Epidural Administration Reactions Adverse Neurologic Serious of corticosteroids, the expected serum antibody antibody serum expected the corticosteroids, of tion, and new infections may appear during their during appear may infections new and tion, immunosuppressive doses of corticosteroids. If If corticosteroids. of doses immunosuppressive with the synthetic derivatives except when used in insuf­ relative of type This dosage. of reduction than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal antiviral agents may be considered. If exposed to exposed If considered. be may agents antiviral and can be related to the dose, route and duration of diarrhea. Usage in Pregnancy signs of hypoadrenalism. to individuals receiving immunosuppressive doses concurrently. and/or a mineralocorticoid should be administered mlpx scnridctdi niiul receiving individuals in contraindicated is smallpox, of potassium. These effects are less likely to occur gradual by minimized be may and corticosteroids immune system are more susceptible to infections course in non­immune children or adults on cor­ on adults or children non­immune in course indicated. If chickenpox develops, treatment with treatment develops, chickenpox If indicated. disseminated infection varies among individuals individuals among varies infection disseminated easemayoccur.Duringprolongedcorticosteroidther­ observation is close necessary as reactivation of the reactivity, dis­ tuberculin or tuberculosis latent steroids increase calcium excretion. produce false negative results. the affect nitroblue may tetrazolium test for bacterial infection and corticosteroids Moreover, are used. corticosteroids when infection localize to ity use. There may be decreased resistance and inabil­ steroid therapy in any patient who has spent time spent has who patient any in therapy steroid with associated is corticosteroids of use the that in the tropics or in any patient with unexplained unexplained with patient any in or tropics the in of incidence higher a and coma of prolongation pneumonia and gastrointestinal bleeding. apy, these patients should receive chemoprophylaxis. inactivated viral or bacterial vaccines are administered

during pregnancy should be carefully observed for used with great caution in these patients. be should corticosteroids with therapy therefore, rewall free rupture after a recent myocardial infarction; corticosteroidsventricularleftof andbetweenuse therapy, e.g., for Addison’s disease. excretion increased and retention, water and salt corticosteroids should be advised not to nurse. of withdrawal rapid too from result may ficiency Therefore, it is recommended that latent or active or latent that recommended is it Therefore, amebiasis be ruled out before initiating cortico­ cortico­ initiating before out ruled be amebiasis the management of the disease in conjunction with injection in active tuberculosis should be restricted an appropriate antituberculous regimen. to those cases of fulminating or disseminated disseminated or tuberculosis in fulminating which the corticosteroid is used for of cases those to

taken to avoid exposure. The risk of developing a developing of risk The exposure. avoid to taken VZIG and IG for complete prescribing information). not had these diseases, particular care should be should care particular diseases, these had not ticosteroids. In such children or adults who have who adults or children such In ticosteroids.

ieauerprssgeta paetassociation apparent an suggest Literature reports In cerebral malaria, a double­blind trial has shown Average and large doses of cortisone or hydro­ or cortisone of doses large and Average Prolonged use of corticosteroids may produce may corticosteroids of use Prolonged Corticosteroids appear in breast milk and could Corticosteroids may mask some signs of infec­ of signs some mask may Corticosteroids Patients who are on drugs which suppress the suppress which drugs on are who Patients The use of dexamethasone sodium phosphate sodium dexamethasone of use The If corticosteroids are indicated in patients with with patients in indicated are corticosteroids If Administration of live virus vaccines, including including vaccines, virus live of Administration Corticosteroids may activate latent amebiasis. amebiasis. latent activate may Corticosteroids rgidcdscnayarncria nu­efcs ohr aigpamclgcdsso Dermatologic: of doses pharmacologic taking Mothers effects. insuf­ adrenocortical secondary Drug­induced

steroid withdrawal syndrome including fever, fever, including syndrome withdrawal steroid tomoses, active or latent peptic ulcer, renal insuffi­ ticosteroids may result in symptoms of the cortico­ infection, also in diverticulitis, fresh intestinal anas­ specific ulcerative colitis, if there is a probability of impending perforation, abscess, or other pyogenic Gastrointestinal: lessened physiologic activity, thus requiring adjust­ rior of the vial. steroids resulting in decreased blood levels and and levels blood decreased in resulting steroids autoclaved when it is desirable to sterilize the exte­ tion with corticosteroids in hypoprothrombinemia. may enhance the metabolic clearance of cortico­ of clearance metabolic the enhance may is sensitive to heat. Therefore, it should not be be not should it Therefore, heat. to sensitive is doses of corticosteroids may be minimal or absent. reports conflicting of potentiationsome notbeen substantiated have by there studies. although rins, time same the at anticoagulants coumarin and ficiency. to help prevent peptic ulcer. large receiving patients in perforation trointestinal This product, like many other steroid formulations, administration of these drugs. corticosteroids is inhibition of response to couma­ quently in patients who are receiving corticosteroids cies may be aggravated by corticosteroids. number of spermatozoa in some patients. in patientsin evenwithout evidence adrenalof insuf­ occur may This malaise. and arthralgia, myalgia, a nefr ihdexamethasone suppression with tests interfere may meals between administered be antacids that advise gas­ following irritation peritoneal of Signs gravis. PRECAUTIONS: which should be interpreted with caution during during caution with interpreted be should which shown that the usual effect produced by adding adding by produced effect usual the that shown should also be advised that if they are exposed, are they if that advised be also should avoid exposure to chickenpox or measles. Patients sant doses of corticosteroids should be warned to Fat embolism has been reported as a possible possible a as reported been has embolism Fat patients with ocular herpes simplex for fear of of fear for simplex corneal perforation. herpes ocular with patients cirrhosis. with those in andhypothyroidism with patients in depression to frank psychotic manifestations. Also, treatment, under condition the control to used be existing emotional instability or psychotic tenden­ psychotic or instability emotional existing the possible, is reduction must be dosage gradual. in reduction when and Musculoskeletal: Fluid and electrolyte disturbances: ADVERSE REACTIONS: be carefully followed. should therapy corticosteroid prolonged on patients medical advice should be sought without delay. Growth and development of infants and children and infants of development and Growth Pediatric Use

complication of hypercortisonism. ment in corticosteroid dosage. These interactions These dosage. corticosteroid in ment myasthenia hypertension, osteoporosis,ciency, and steroids are used, ranging from euphoria, insomnia, mood swings, personality changes, and severe severe and changes, personality swings, mood administration should be recognized. develop­ for closely observed be should patients ment of hypokalemia. comitantly with potassium­depleting diuretics, diuretics, potassium­depleting with comitantly the response to these anticoagulants. Studies have because of reports that corticosteroids have altered these patients. Information for Patients Susceptible patients who are on immunosuppres­ of the DST should be interpreted with caution in caution with interpreted be should DST the of ihidmtai aebe eotd hs results Thus, reported. been have indomethacin with suppression test (DST) in patients being treated treated being patients in (DST) test suppression

Phenytoin,phenobarbital,ephedrine,andrifampin sci eagmnsmyapa hncortico­ when appear may derangements Psychic Followingprolonged therapy, withdrawal cor­of The lowest possible dose of corticosteroid should Aspirin should be used within caution in conjunc­ Steroids may increase or decrease motility and motility decrease or increase may Steroids The slower rate of absorption by intramuscular by absorption of rate slower The There is an enhanced effect of corticosteroids corticosteroids of effect enhanced an is There When large doses are given, some authorities authorities some given, are doses large When The prothrombin time should be checked fre­ checked be should time prothrombin The tris hud e sd ih ato i non­ in caution with used be should Steroids Corticosteroids should be used cautiously in in cautiously used be should Corticosteroids False negative results in the dexamethasone dexamethasone the in results negative False hn otcseod ae diitrd con­ administered are corticosteroids When and hemorrhage etcucrwt osbesbeun perforation subsequent possible with ulcer Peptic Pathologic fracture of long bones Ulcerative esophagitis Tendon rupture Abdominal distention Aseptic necrosis of femoral and humeral heads Vertebral compression fractures Pancreatitis Osteoporosis Potassium loss larly in patients with inflammatory bowel disease Hypertension Loss of muscle mass Steroid myopathy Muscle weakness Hypokalemic alkalosis Congestive heart failure in susceptible patients Fluid retention Perforation of the small and large bowel; particu­ Sodium retention

mm

transfer the patient to other therapy. dexamethasone sodium phosphate injection and injection phosphate sodium dexamethasone Ophthalmic: after a reasonable period of time, discontinue discontinue time, of period reasonable a after If a satisfactory clinical response does not occur not does response clinical satisfactory a If clinical response. adjusted until the patient’s response is satisfactory. to the lowest dosage that maintains an adequate an maintains that dosage lowest the to Metabolic: OVERDOSAGE: may be required. decreasing the initial dosage in small amounts amounts small in dosage initial the decreasing Other: treatment is supportive and symptomatic. while in severe diseases doses higher than 9 mg 9 than higher doses diseases severe in while THE DISEASE AND THE RESPONSE OF THE THE OF RESPONSE THE AND DISEASE THE maintenance dosage should be determined by by determined be should dosage maintenance Neurologic: of overdosage, no specific antidote is available; available; is antidote specific no overdosage, of administered by intravenous drip. Sodium Chloride Injection or Dextrose Injection and be given directly from the vial, or it can be added to Endocrine: diseases doses lower than 0.5 mg may suffice, suffice, may mg 0.5 than lower doses diseases PATIENT. OF BASIS THE ON INDIVIDUALIZED BE MUST DOSAGE REQUIREMENTS ARE VARIABLE AND mixtures should be used within 24 hours. preservatives, contain not do generally solutions infusion Since observed. be should precautions further dilution of this product should be preserva­ premature infant. tive free when used in the neonate, especially the especially neonate, the in used when free tive Cardiovascular: 10 mg/mL– mg/mL– 10 Dexamethasone sodium phosphate injection, injection, phosphate sodium Dexamethasone DOSAGE AND ADMINISTRATION:

The following overdosage of glucocorticoids are rare. In the event thasone sodium phosphate in female mice was was 794 mg/kg. mice female in phosphate sodium thasone following death and/or toxicity acute of Reports was 6.5 g/kg. The intravenous LD intravenous The g/kg. 6.5 was injection only. to parenteral corticosteroid therapy: Intravenous and Intramuscular Injection ing on the disease being treated. In less severe severe less In treated. being disease the on depend­ ing day a mg 9 to 0.5 from varies injection phate The initial dosage of dexamethasone sodium phos­

Dexamethasone sodium phosphate injection can The oral LD When it is mixed with an infusion solution, sterile Solutions used for intravenous administration or After a favorable initial response, the proper proper the response, initial favorable a After The initial dosage should be maintained or or maintained be should dosage initial The

Other cutaneous reactions, such as allergic der­ Glaucoma (after IV injection) Increased intraocular pressure Burning or tingling, especially in the perineal area Posterior subcapsular cataracts Weight gain May suppress reactions to skin tests Thromboembolism Increased sweating Hirsutism Anaphylactoid or hypersensitivity reactions Erythema glycemic agents in diabetics Convulsions Hypertrophic cardiomyopathy in low birth weight Petechiae and ecchymoses Hiccups Charcot­like arthropathy Increased requirements for insulin or oral hypo­ matitis, urticaria, angioneurotic edema Nausea infarction (see Retinopathy of prematurity Thin fragile skin Malaise Psychic disturbances Headache Vertigo treatment after usually cerebri) (pseudotumor Increased intracranial pressure with papilledema Decreased carbohydrate tolerance Menstrual irregularities Manifestations of latent diabetes mellitus Suppression of growth in pediatric patients Development of cushingoid state infants Negative nitrogen balance due to protein catabolism Myocardial rupture following recent myocardial recent following rupture Myocardial Impaired wound healing eodr arncria ad iutr unre­ pituitary and adrenocortical Secondary Increased appetite Exophthalmos sponsiveness, particularly in times of stress, as in trauma, surgery, or illness Sterile abscess Subcutaneous and cutaneous atrophy Hyperpigmentation or hypopigmentation

For intravenous and intramuscular intramuscular and intravenous For additional

50

of dexamethasone in female mice

WARNINGS)

adverse reactions are related

50 50

of dexame­ of

CrossTech–74239–Proof 1 Form M01 Fresenius Kabi USA, LLC P.O. 4500139607–Job No. 45955E 4/30/14–hc–Indd4 m Fonts: Helvetica (A) Typesmiths Pi Font 5AV

Patients should be observed closely for signs Protect from light. that might require dosage adjustment, including Single dose vials–Store in container until time of changes in clinical status resulting from remis­ use. Discard unused portion. sions or exacerbations of the disease, individual drug responsiveness, and the effect of stress Multiple dose vials–Store in container until con­ (e.g., surgery, infection, trauma). During stress it tents are used. may be necessary to increase dosage temporarily. If the drug is to be stopped after more than a few REFERENCES: days of treatment, it usually should be withdrawn 1. Cavanagh, D.; Singh, K.B.: Endotoxin shock in gradually. pregnancy and abortion, in: “Corticosteroids in When the intravenous route of administration the Treatment of Shock”, Schumer, W.; Nyhus, is used, dosage usually should be the same as L.M., Editors, Urbana, University of Illinois Press, the oral dosage. In certain overwhelming, acute, 1970, pp. 86­96. life­threatening situations, however, administration 2. Dietzman, R.H.; Ersek, R.A.; Bloch, J.M.; Lilleheir, in dosages exceeding the usual dosages may be R.C.: High­output, low­resistance gram­negative justified and may be in multiples of the oral dosages. septic shock in man, Angiology 20: 691­700, The slower rate of absorption by intramuscular Dec. 1969. administration should be recognized. 3. Frank, E.: Clinical observations in shock and management (in: Shields, T.F., ed.: Symposium Shock on current concepts and management of shock), There is a tendency in current medical practice to J. Maine Med. Ass. 59: 195­200, Oct. 1968. use high (pharmacologic) doses of corticosteroids 4. Oaks, W. W.; Cohen, H.E.: Endotoxin shock in the for the treatment of unresponsive shock. The follow­ geriatric patient, Geriat. 22: 120­130, Mar. 1967. ing dosages of dexamethasone sodium phosphate 5. Schumer, W.; Nyhus, L.M.: Corticosteroid effect injection have been suggested by various authors: on biochemical parameters of human oligemic Author Dosage shock, Arch. Surg. 100: 405­408, Apr. 1970. Cavanagh1 3 mg/kg of body weight per 24 hours by constant intravenous infusion after an initial intra­ venous injection of 20 mg Dietzman2 2 to 6 mg/kg of body weight as a single intravenous injection Frank3 40 mg initially followed by repeat intravenous injection every 4 to 6 hours while shock persists Oaks4 40 mg initially followed by repeat intravenous injection every 2 to 6 hours while shock persists Schumer5 1 mg/kg of body weight as a single intravenous injection Administration of high dose corticosteroid therapy should be continued only until the patient’s condi­ tion has stabilized and usually not longer than 48 to 72 hours. Although adverse reactions associated with high dose, short­term corticosteroid therapy are uncom­ m mon, peptic ulceration may occur.

Cerebral Edema Dexamethasone sodium phosphate injection is generally administered initially in a dosage of 10 mg intravenously followed by four mg every six hours intramuscularly until the symptoms of cerebral edema subside. Response is usually noted within 12 to 24 hours and dosage may be reduced after two to four days and gradually discontinued over a period of five to seven days. For palliative manage­ ment of patients with recurrent or inoperable brain tumors, maintenance therapy with 2 mg two or three times a day may be effective. Acute Allergic Disorders In acute, self­limited allergic disorders or acute exacerbations of chronic allergic disorders, the following dosage schedule combining parenteral and oral therapy is suggested: Dexamethasone sodium phosphate injection, first day, 4 or 8 mg intramuscularly. Dexamethasone tablets, 0.75 mg: second and third days, 4 tablets in two divided doses each day; fourth day, 2 tablets in two divided doses; fifth and sixth days, 1 tablet each day; seventh day, no treat­ ment; eighth day, follow­up visit. This schedule is designed to ensure adequate therapy during acute episodes, while minimizing the risk of overdosage in chronic cases. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever the solution and container permit. HOW SUPPLIED: Dexamethasone Sodium Phosphate Injection, USP (Preservative Free) equivalent to 10 mg dexamethasone phosphate, is supplied in a single dose vial as follows: Product NDC No. No. Strength Vial Size 500601 63323­506­01 10 mg 1 mL vial, per mL packaged in twenty­ fives. Dexamethasone Sodium Phosphate Injection, USP (Preserved) equivalent to 10 mg dexametha­ sone phosphate, is supplied in a multiple dose vial as follows:

Product NDC No. No. Strength Vial Size 501610 63323­516­10 100 mg 10 mL vial, per 10 mL packaged (10 mg in tens. per mL) This container closure is not made with natural

rubber latex. Storage

Store at 20° to 25°C (68° to 77°F) [see USP Con­ Fresenius Kabi USA, LLC trolled Room Temperature]. Sensitive to heat. Do Lake Zurich, IL 60047 not autoclave. 45955E

Protect from freezing. Revised: May 2014 Font Pi Typesmiths

rsTc–43–ro 1 CrossTech–74239–Proof Form M02 Fresenius Kabi USA, LLC P.O. 4500139607–Job No. 45955E 4/30/14–hc–Indd4 (A) Helvetica Fonts:

Reference ID: 3536446