PRODUCT INFORMATION
`
`NABI/2297
`
`Table 3 Recommended Schedule of Hepatitis B lmmunoprophylaxis to Prfivent Perinatal Transmissio.n of ·Hepatitis B
`Virus Infection 19
`
`Age of Infant
`
`Infant born to mother known
`to be HBsAg-positive '
`
`Infant bar~ to mother not
`screened for HBsAg
`
`Administer
`
`First Vaccination*
`Hepatitis B Immune
`Globulin (Human)'
`
`Birth (within 12 hours)
`Birth (within 12 hours)
`
`Birth (within 12 hourR)
`If mother is found to be HBsAg
`positive, administer dose to
`infant as soon as possible, not
`later than 1 week after birth
`1-2 months ·
`.
`6 monthst
`
`!'month
`Second Vaccination*
`Third Vaccination*
`6 months*
`* See manufacturers' recornme;ndations for appropriate dose.
`t 0.5 mL administered IM at a site different from that used for the vaccirie.
`* See ACIP recommendation.
`sexual contact with the infected person will continue. Ad~
`ministering the vaccine with Hepatitis B Immune Globu(cid:173)
`lin (Human) may improve the efficacy of pOst-exposure
`treatment. The vaccine has the added advantage of con(cid:173)
`ferring long-lastng protection. 19
`• Household Exposure to Persons With Acute HBV Infec(cid:173)
`tion
`Prophylaxis of an infant less than 12 months of age with
`0.5 mL Hepatitis B Immune Globulin (Human) and Hep(cid:173)
`atitis B Vaccine is indicated if the mother or primary~ar­
`egiver has acute· HBV infection. Prophylaxis of other
`household contacts of persons with acute HBV infection is
`not indicated unless they had an identifiable blood expo(cid:173)
`sure to the index patient. such 'as by sharing toothbrushes
`or razors. Such exposures should be treated like sexual
`exposures. If the index patient becomes an HBV carrier,
`all household contacts should receive Hepatitis B Vac(cid:173)
`cine.19
`HOW SUPPLIED
`Nabi-HB™, Hepatitis B Immune Globulin (Human), is sup(cid:173)
`plied as:
`NDC Number Contents
`a carton containing a 1.0 mL single dose
`59730-4402-1
`vial (>312 IU) and package insert
`a carton containing a 5.0 mL single dose
`vial (>1560 IU) and package insert
`
`59730-4403-1
`
`16. Poovorawan Y, et al.: Long term hepatitis B vaccine in
`infants born to hepatitis B e antigen positive mothers.
`Archives of Diseases in Childhood 1997; 77:F47-F51.
`17. Stevens CE, et al.: Perinatal Hepatitis B virus transmis(cid:173)
`sion in the United States: Prevention by passive-active
`immunization. JAMA 1985; 253:1740-1145,
`18. Jhaveri R, et al.: High titer multiple dose therapy with
`HBIG in newborn infants of HBsAg positive mothers. J
`Pediatr 1980; 97:305-308.
`19. Centers for Disease 8ontrol: Hepatitis B virus: A com(cid:173)
`prehensive strategy for eliminating transmiSsion in the
`United States through universal childhood vaccination.
`Recommendations of the Immunization Practices Advi(cid:173)
`sory Committee (ACIP). MMWR 1991; 40(13):1-25,
`20. Data on file, Nabi®,
`21. Scheiermann N, Kuwert ER: Uptake and elimination of
`hepatitis B immunoglobulins after intramuscular appli~
`cation in man. Develop Biol Standard 1983; 54:347_
`22. Centers for Disease Control: General recommendations
`on immunization. Recomm·endations of "the Advisory
`Committee on Immunization Practices (ACIP). MM"WR
`1994; 1:6.
`23. Ellis EF artd Henney CS: Adverse reactions following
`administ~ation of human gamma globulin. J Allerg
`1969; 43:45-54,
`Manufactured by:
`Nabi®
`Boca Raton, FL 33487
`U.S, License No. 1022
`Part No, 07,0210.01
`June, 2000
`
`WinRho SOfTM
`[win' ro s d tl
`Rh 0 (0) Immune Globulin Intravenous (Human)
`
`~
`
`DESCRIPTION
`Rh,(D) Immune Globulin Intravenous (Human) (Rh,(D)
`IGIV)-WinRho SDFTM_is a sterile, freeze-dried gamma
`globulin (IgG) fraction containing antibodies to the Rh,(D)
`antigen (D antigen). WinRho SDF™ is prepared from hu(cid:173)
`man plasma by an anion-exchange column chromatography
`method. 1- 3 The manufacturing process includes a solvent
`detergent treatment step (using tri-n-butyl phosphate-and
`Triton X-100) that is effective in inactivating lipid enveloped
`viruses such as hepatitis B, hepatitis C, and HIV. 4
`WinRho SDFTM is filtered using a Planova 35 nm Virus Fil(cid:173)
`ter which has been validated to be effective in the removal
`of some nonlipid enveloped viruses. 5-6 These two processes
`are designed to increase product safety by reducing the risk
`of transmission of enveloped and nonenv~loped viruses, re(cid:173)
`spectively .
`The product potency is expressed in international units by
`comparison to the World Health Organization (WHO) stan(cid:173)
`dard_ A300 ~g (1,500 International Unit [IU]*) vial contains
`sufficient anti-Rh0(D) to effectively suppress the immuniz(cid:173)
`ing potential of approximately "17 mL of Rh0(D) (D·positive)
`red blood cells (RBCs). This product contains approximately
`5 ~glp>L IgA per 120 )lg (600 IU) viaL
`The Product iS stabilized with 0.1.M glycine, 0.04 M sodium
`chloride, and 0.01% polysorbate 80. It contains no presezva(cid:173)
`tive.
`Treatment oflTP
`For use in the treatment of immune thrombocytopenic pur·
`pura (ITP), WinRho SDFTM must be administered intrave~
`nously.
`Suppression of RH Isoimmunization
`For use in the suppression of· Rh isoimmunization,
`WinRho SDFTM may be administered either intramuscu(cid:173)
`larly or intravenously.
`
`*In the past, a full dose of Rh,(D) Immune Globulin (Hu(cid:173)
`man) has traditionally been referred to as a "300 p.g" dose.
`Potency .and dosing recommendations are nOw expressed in
`IU by comparison to the WHO anti-Rh,(D) standard, T_he
`conversion of "11g" to "IU" is 1 Jlg :::: 5 IU.
`CLINICAL PHARMACOLOGY
`Treat~nt o{ITP_
`WinRh.o SDFTM, Rh0(D) Immune Globulin Intravenous (Hu(cid:173)
`man), has been shown to increase platelet counts in non(cid:173)
`splenectomized, Rh 0(D) positive patients with ITP. Platelet
`counts usually rise within one to two days and peak within
`
`STORAGE
`Refrigerate between 2 to 8 "C (36 to 46 "F). Do not freeze_ Do
`not use after expiration date. Use within 6 hours after the
`vial has been entered.
`REFERENCES
`1. Bowman JM, et al.: WinRho: Rh immune globulin pre(cid:173)
`pared by ion exchange for intravenous use. Canadian
`Med Assoc J 1980; 123:1121-1125,
`2. Friesen AD, et al.: Column ion-exchange preparation
`and characterization of an Rh immune globulin (Win(cid:173)
`Rho) for intravenous use. Journal of Applied Biochem
`1981; 3:164-175.
`3. Horowitz B: Investigators into the application of tri(n(cid:173)
`butyl)phosphate/detergent mixtures to blood deriva(cid:173)
`tives. Morgenthaler J (ed): Virus Inactivation in Plasma
`Products, Curr Stud Hematol Blood Transfus 1989; 56:
`83--96.
`4. Burnouf T: Value of virus fi1tration as method for im(cid:173)
`proving the safety of plasma products. Vox Sang 1996;
`70:235-236,
`5. Unpublished data on file, Viral Validation Study Re(cid:173)
`ports, Cangene Corporation.
`6. Grady GF, and Lee VA: Hepatitis B Immune globulin(cid:173)
`prevention of hepatftis from accidental exposure among
`medical personnel. N Engl J Med 1975; 293:1067-1070.
`7. Seeff LB, et al.: Type B hepatitis after needle-stick ex(cid:173)
`posure: Prevention with hepatitis B immune globulin.
`. 4nn Int Med 1978; 88:285-293.
`8. Krugman S, and Giles JP: Viral hepatitis, type B (MS-
`2-strain). Further observations on natural history and
`prevention. N Engl J Med 1973; 288:755-760.
`9. Hoofnagle JH, et al.: Passive-active immunity from
`hepatitis B immune globulin. Ann Int Med 1979; 91:
`813-818.
`10. Beasley RP, et al.: Efficacy of hepatitis B immune glob(cid:173)
`ulin for prevention of perinatal transmission of the hep·
`atitis B virus carrier state: Final report of a randomized
`double-blind, placebo-controlled trial. Hepatology 1983;
`3:135-14L
`11. Szmuness W, et al.: PaSsive active immunisation against
`hepatitis B: Immunogenicity studies in adult Ameri(cid:173)
`cans, Lancet 1981; 1:575-577.
`12. Centers for .Disease Control: Recommendations for pro(cid:173)
`tection against viral hepatitis. Recommendations of the
`Immunization Practices Advisory Committee (ACIP).
`MMWR 1985; 34(22):313-335.
`13. Shiraki Y, et al.: Hepatitis B surface antigen and chronic
`hepatitis in infants born to asymptomatic carrier moth(cid:173)
`ers, Am J Dis Child 1977; 131:644-647.
`14. Beasley RP, et al.: The e antigen a.I).d vertical transmis(cid:173)
`sion of hepatitis B surface antigen. Am J Epidemiol
`1977; 105:94-98,
`15. Wong VCW, et al.: Prevention of the HBsAg carrier state
`in newborn infants of mothers who are chronic carriers
`of HBsAg and HBeAg by administration of hepatitis B
`vaccine and hepatitis B immunoglobulin: .Oouble-blind
`randomized placebo-controlled study. Lancet 1984;
`1:921-926.
`
`seven to 14 days after initiation of therapy. The duratioq of
`response is variable; however, the average 'duration is ap(cid:173)
`proximately 30 days. The mechanism of action is not com(cid:173)
`pletely understood, but is thought to be due to the formation
`of anti-Rh,(D) (anti-D)-coated RBC- complexes resulting in
`Fe receptor blockade 1 thus sparing antibody·coated plate(cid:173)
`lets.7-e
`Suplf[ession o' Rh Isoimmunization
`WUlho SDF' 1
`ts used to suppreS:Sthe immune response of
`non-sensitized Rh0 (D) negative individual~ following expo·
`sure to Rh0 (D) positive RBCs by fetomaternal hemorrhage
`during delivery of an Rh 0(D) positive infant, abortion (span·
`taneous or induced), amniocentesis, abdominal trauma·, ·or
`mismatched transfusion.g....n 'l'he mechanism of action is not
`completely understood.
`.
`WinRho SDFT:-t, when administered within 72 hours of a
`full-term delivery of an Rh,(D) positive infant by an Rh,(D)
`negative mother, will.reduce the incidence of Rh isoimmu(cid:173)
`nization from 12-13% to 1-2% .. The 1-2% is, .for the most
`part~ due to isoimmunization during the last trimester of
`pregnancy. When treatment is given both antenatally at 28
`weeks gestation and Rostpartum, the Rh immunization rate
`drops to about 0.1%. 2- 15
`When' 120 ~g (600 IU) of Rh,(D) IGN is administered to
`pregnant women, passive anti·Rh0(D) antibodies are not de(cid:173)
`tectable in the circulation fQr more than six weeks and
`therefore a dose of 300 ~g (1,500 IU) should be used for an(cid:173)
`tenatal administration.
`In a clinical study with Rh0(D) negative Volunteers (nine
`males and one female), Rh 0(D) positive red ce11s were com(cid:173)
`pletely cleared from the circulation within eight hours of in·
`travenous administration of Rh 0(0) IGIV There was· no in·
`dication of Rh isoimmunization of these subjects at six
`months after the clearance of the Rh0(D) positive red cells.
`Pharmacokinetics~M versus IV Administration
`In a clinical study involving Rh0(D) negative volunteers, two
`subjects received 120 )lg (600 IU) Rh,(D) IGN by intrave(cid:173)
`nous (IV) administration and two subjects received this dose
`by intramuscular (IM) administration. Peak levels (36 to 48
`ng/mL) were reached within two hours of IV administration
`and peak levels (18 to 19 ng!mL) were reached at five to 10
`days after IM administratjon. The calculated areas under
`the curve were the same for both routes of administration.
`The t 112 for anti-Rh,(D) was about 24 days following N ad(cid:173)
`ministration and about 30 days following IM administra(cid:173)
`tion.
`INDICATIONS AND CLINICAL USE
`Treatment o~ ITP,
`WmRho SD tM,~(D) Immune Globulin Intravenous (Hu(cid:173)
`man), is recommended for the treatment of non·splenecto(cid:173)
`mized, Rh0(0) positive
`• children with chronic or acute ITP,
`• adults with chronic ITP, or
`• children and adults with ITP secondary to HIV infec-
`tion
`in clinical situations requiring an ·increase in platelet count
`to prevent excessive hemorrhage. The safety and efficacy of
`WinRho have not been evaluated in clinical trials for pa·
`tients with non-ITP causes of thrombocytopenia or in previ(cid:173)
`ously splenectomized patients.
`Suppression of Rh Isoimmunization
`Pregnancy a~d Other Obstetric Conditions
`WinRho SDF™ is recommended for the ·suppression of Rh
`isoimmunization in non-sensitized~ Rho(D) negative (0·
`negative) women within 72 hours after spontaneous or in(cid:173)
`duced abortions~ amniocentesis, chorionic villus sampling,
`ruptured tubal pregnancy, abdominal trauma or transpla(cid:173)
`cental hemorrhage or in the normal course of pregnancy un(cid:173)
`less the blood type of the fetus or father is known to be
`Rh 0(D) negative. In the case of materrial bleeding due to
`threatened abortion, WinRho SDF™ should. be adminis·
`tered as soon as possible. Suppression of Rh isoimmuniza(cid:173)
`tion reduces the likelihood of hemolytic disease in an Rh0(D)
`positive fetus in present and future pregnancies.
`The criteria for an Rh-incompati}Jle pregnancy requiring ad(cid:173)
`ministration of WinRho SDF™ at 28 weeks gestation and
`within 72 hours after delivery are:
`• the mother must be Rh0 (D) negative,
`• the mother is carrying a child whose father is either
`Rh0(D) positive or Rh0(D) unknown,
`• the baby· is either Rh0 (D) positive or Rh0 (D) unknown,
`and
`• the mother must not be previously sensitized to the
`Rh,(DJ factor.
`Transfusion
`WinRho SDF™, Rh0 (0) Immune Globulin Intravenous (Hu(cid:173)
`man}, is recommended for the suppression of Rh isoimmu(cid:173)
`nization ·in Rh0(D) negative female children and female
`adults in their childbearing years transfused with Rho(D)
`positive RBCs or blood components containing Rh0 (D) posi(cid:173)
`tive RBCs. Treatment should be initiated within 72 hours of
`exposure .. Treatment should be given (without preceding e~­
`change transfusion) only if tp.e transfused Rh0(D) positive
`b~ood Tgpreserlts less than 20% of the total circulating fed
`cejls, A 300 )lg (1,500 IU) dose will suppressthe immunizing
`potential of approxi~ately 17n:iL of Rh,(D). positive RBCs,
`CLINICAL TRIALS
`Jieatmen_0!llJf
`Efficacy was documented in four subgroups of patients with
`ITP:
`Childhood Chronic ITP
`In an open~Iabel, single acrn, multicenter study, 24 non(cid:173)
`splenectomized, Rh0(0) positive children with. ITP of greater
`than six months duration Wf.'-re treated initially with 50
`r•g/kg l250 !U/kg) Rh,(D) Immune Globulin Intravenous
`
`Continued on next page
`
`Consult 2 0 0 2 POR® supplements and future editions for revisions
`
`Ex. 2026-0001
`
`

`
`2298/NABI
`
`WinRho SDF-Cont.
`
`(Human) (25 )lg/kg (125 IU/kg) on days 1 and 2, with sub(cid:173)
`sequent doses ranging from 25 to 55 )lg/kg (125 to 275 IU/
`kg)). Response was defined as a platelet increase to at least
`50,000/mm3 and a doubling of the baseline. Nineteen of 24
`patients responded for .an overall response Tate o(79%, and
`overall mean peak platelet count of 229,400/mm3 (range
`43,300 to 456,000), and a mean duration of response of 36.5
`days (range 6 to 84). 1&-17
`Childhood Acute ITP
`A multicenter, randomiz~d. ··controlled trial comparing
`Rh.(D) IGIV to high dose and low dose Immune Globulin
`Intravenous (Human) and prednisone was cOnducted in 146
`non-splenectomized, Rh 0(D) positive children with acute
`ITP and platelet counts less than 20,000/mm3. Of 38 pa(cid:173)
`tients receiving Rh0(D) IGIV (25 )lg/kg (125 IU/kg) on days 1
`and 2), 32 patients (84%) responded (platelet count ;;,
`50,000 mm3
`) with a mean peak platelet count of 319;500/
`mm3 (range 61,000 to 892,000), with no statistically signif(cid:173)
`icant differenc~s compared to other treatment arms. The
`mean times to achieving ~ 20,000/mm3 or 2: 50,000/mm3
`platelets for patients receiving Rho(D) IGIV were 1.9 aod
`2.8 days, respectively. When Comparing the different. thera~
`pies for time to platelet count 2: 20,000/mm3 or 2: 56,000/
`mm3 , no statistically significant differences among treat~
`ment groups were detected, with a range of 1.3 to 1.9 days
`and 2.0 to "3.2 days, respectively. 18-19
`Adult Chronit ITP
`'I\venty~four nonMsplenectomized, Rh 0(D) positive adults
`with ITP of greater than six months duration and platelet
`counts < 30,000/mm3 or requiring therapy were enrolled in
`a single~arm, open~lab-el trial and treated with 20 to 75
`)lg/kg (100 to 375 IU/kg) Rh 0(D) IGIV (mean dose 46.2 pg/kg
`(231 !Uikg)). '1\venty-one of 24 patients responded (increase
`2: 20,000/mm3) during the first two courses of therapy for an
`overall response rate of 88% with a mean peak platelet
`21
`count of92,300/mm3 (range B,OOO.to 229,000). 2
`"'
`ITP Secondary to HIV Infection
`Eleven children and 52 adults, who were non-splenecto(cid:173)
`mized and Rh0(D} positive, with all Walter Reed classes of
`HIV infection and ITP, with initial platelet counts of :$:
`30,000/mm3 or requiring therapy, were treated with 20 to 75
`)lg/kg (100 to 375 IU/kg) Rh0(D) IGIV in an open label trial.
`Rh 0(D) IGIV was administered for an average of7.3 cours.es
`(range 1 to 57) over a mean period of 407 days (range 6 to
`1,952). Fifty-seven of 63 patients responded (increase 2.
`20,000/mm3) during the first six courses of therapy for an
`overall response rate of 90%. The- overall mean change in
`platelet count for six courses was 60,900/mm3 (range -2,000
`to 565,000), and the mean peak glatelet count was 81,700/
`mm3 (range 16,000 to 593,000).2 · 23
`§!:.I!.P.!!!.2!!ion o Rh Isoimmunization
`The pivotal stud
`supporting this indication was con(cid:173)
`ducted in 1,186 non·sensitized, Rh0 (D) negative pregnant"
`women in cases in which the blood types of the fathers were
`either Rh,(D) positive or unknown. Rh0(D) IGIV was admin(cid:173)
`istered according to one of three regimens: 1) 93 wome:p.. re·
`ceived 120 )lg (600 !U) at 28 weeks; 2) 131 women received
`240 )lg (1200 !U) each at 28 and 34 weeks; 3) 962 women
`received 240 )lg (1200 IU) at 28 weeks. All women received
`a postnatal administration of 120 )lg (600 !U) if the newborn
`was found to he Rh 0(D) positive. Of 1,186 women who re(cid:173)
`ceived antenatal Rh0(Dl IGIV, 806 were given Rli,(D) IGIV
`postnatally following the delivery of an Rh0 (D) positive in(cid:173)
`fant, of which 325 women underwent testing at six months
`after delivery for evidence of Rh isoimmunization. Of these
`325 women, 23 would have been expected to display siglls of
`Rh isoimmunization; however, none was observed (p <
`0.001 in a Chi-square test of significance of difference be(cid:173)
`tween observed and expected isoimmunization in the ab~
`sence of Rh.(D) IGIV).
`CONTRAINDICATIONS
`Treatment of ITP and Suppression of Rh Isoimmunization
`Individuals known to have .had an anaphylactic or.severe
`systemic· reaction to human globulin should not receive
`WinRho SOFTM, Rh0(D} Immune Globulin Intravenous (Hu(cid:173)
`man), or any other
`Immune Globulin
`(Human).
`WinRho SDFTM contains trace amounts ofigA (appioximate(cid:173)
`ly 5 pg!mL per I20 )lg [600 IU] vial). Individuals who are
`deficient in IgA may have the potential for developing IgA
`antibodies and have anaphylactic reactions. The physician
`must weigh the potential benefit of treatment with
`WinRho SDFTM .against the potential for hypersensitivity re~
`actions.
`WARNINGS
`WinRho SOPM, Rh 0 {D) Immune Globulin Intravenous (HU(cid:173)
`man), is made from human plasma. Products mad8 from
`human Plasma may carry a risk of transmitting i~fectiou"S
`agents, e.g., viruses and theoretically, the Cr8~tzfeldt-Ja­
`kob disease (CJO) agent. The risk that such Products will
`transmit an infectious agent has beefl' reduced by screen(cid:173)
`ing plasma donors for prior exposure to certain vi_ruses, by
`testing for the presence of certain current virus infections,
`and by inactivating and/or removing certain viruses. The
`WinRho SDF™ manufacturing process includes ·a ·solvent
`detergent treatment step (using tri-n-butyl phosphate and
`Triton XM100) that iS effective in inactivating lipid enveloped
`viruses such as hepatitis B. hepatitis C, and HIV.
`Win Rho SDF™ is filtered using a Planova 35 nm VirUs Filter
`that is effective in reducing the level of some non·lipid en~
`veloped viruses such as hepatitis A. These two processes
`
`are designed to increase product safety by reducing the
`risk of transmission of lipid enveloped and non-lipid envel(cid:173)
`oped viruses, respectively. Despite these measures, such
`products can still potentially transmit disease. ·There is also
`the possibility that u_nknown infectious agents may be pre(cid:173)
`sent in such products. All infections thought bY a physi(cid:173)
`cian possibly to have been transmitted by this product
`should be reported by the physician or other healthcare
`provider to the distributor, Nabi® ·at 1-800-4WINRHO (1-
`800-494-6746}. The physician should discuss the risks and
`benefits of this prodUct with the patierit.
`Treatment ofl'fE_
`WinRho SDFTM must·be administered via the intravenous
`route for the treatment of ITP as its efficacy has not been
`established by the intramuscular or subcutaneous routes.
`WinRho SDFTM should not be administered to Rh,(D) nega(cid:173)
`tive or splenectomized individuals as its efficacy in these pa(cid:173)
`tients has not been demonstrated.
`Suppression of Rh Isoimmunization
`For the suppression :of Rh isoimmunization in the mother,
`do not administer to .the infant.
`PRECAUTIONS
`WinRho SDF™, Rh0(D) Immune Globulin Intravenous (Hu·
`man), should not be administered as immunoglobulin re(cid:173)
`placement therapy for immune globulin deficiency syn(cid:173)
`dromes.
`..
`Treatment of ITP
`Following administration ofWinRho SDF™, Rho(D) positive
`ITP patients should be monitored for signs and/or symp(cid:173)
`toms of intravascular hemolysis (!VH), clinically compro(cid:173)
`mising anemia, and renal insufficiency.
`If patients are to be transfused, Rho(D) negative red blood
`cells (PRBCs) should be used so as not to exacerbate ongo(cid:173)
`ing IVH. Platelet products may contain up to 5.0 mL of
`RBCs, th_us caution should likewise be exercised if platelets
`from Rh0 (D) positive donors are trarisfused.
`If the patient has a lower than normal_hemoglobin level
`(less than 10 g/dL), a reduced dose of 25 to 40 )lg/kg (125 to
`200 IU/kg) should be given to minimize the· risk of increas~
`ing the severity of anemia in the patient. WinRho SDFTM
`must be used. with extreiJ?.e caution in patients with a he(cid:173)
`moglobin leVel that is less than 8 g/dL due to the risk of
`increasing the severity of the anemia (See DOSAGE AND
`ADMINISTRATION, Treatment of ITP).
`~~ssion of Rh Iso"IrnrnunTzatio~
`WinRho SDFTM should not be administered to Rh0(D) nega(cid:173)
`tive individuals who are Rh immunized ·as evidenced by an
`indirect antiglobulin (Coombs') test revealing the presence
`of anti-Rh,(D) (anti-D) antibody.
`A large fetomaternal hemorrhage late in pregnancy or fol(cid:173)
`lowing delivery may cause a weak mixed field positive nu
`test result. Such an individual should be assessed for a
`large
`fetomaternal hemorrhage and
`the dose of
`WinRho SDfTM adjusted accordingly. WinRho SDFTM should
`be admin~stered if there is any doubt about the mother's
`blood type.
`·
`Laboratory Tests
`In addition to anti-D, WinRho SDFTM contains· traCe
`amounts of anti-A, anti-B, anti-C and anti~E antibodies.
`Treatment of IT['
`Passively acquired anti-A) anti·B, anti-C, and anti-E blood
`group antibodies may be detectable in direct and indirect
`antiglobulin
`(Coombs')
`tests
`obtained
`following
`WinRho SDF™, Rh 0(D) Immune Globulin Intravenous (Hu(cid:173)
`man), administration. Interpretation of direct and indirect
`antiglobulin tests must be made in the context of the pa~
`tient's underlying clinical condition and supporting labora~
`tory data.
`Suppression of Rh Isoimmunization.
`The presence of passively administered anti-Rh0 (D) in ma(cid:173)
`ternal or fetal blood can lead to a positive direct antiglobulin
`(Coombs') test. If there is an uncertainty about the mother's
`Rh group or immune status, WinRho SD:FT"M" should be adM
`ministered to the mother. "
`Drug Interactions
`TI-eatment of IT£ and Su.E.P!!!!_sion o~soimmunization
`Administration· of WinRho SDFTM concomitantly with other
`drugs has not been evaluated. Other antibodies contained in
`WirtRho SDf'TM may interfere with the response to live virus
`va6cines such as measles, mumps, polio or rubella. 'J.'here(cid:173)
`fore, immunization with live vaccines should not be given
`within·3 months after WmRho SDF1 administration.
`Refer to Dosage and Administration section for information
`on drug compatibility.
`Pregnancy Category C
`'[reatme!E_f!f I'fP and Suppression of Rh Isoimm'!:!l:.i:!ation
`Animal reproduction studies have not been conduct.E~d with
`WinRho, SDF'M. It is not known whether WinRho SDFTM
`can cause fetal harm wh~n administered to a pregnant
`woman or can affect reproductive capacity. WinR4o SDF™
`should be given to a pregnant woman only if clearly needed.
`
`ADVERSE REACTIONS
`~tof!TP ·
`In clinical trials of subjects (n:161) with childhood acute
`ITP, adults aod children with chronic ITP, and adults and
`children with ITP secondary to HN, 60/848 (7%) of infusions
`were associated with at least one· adverse event. that· Was
`considered to be related to the study medication. The .most
`common adverse events were headache (19 infusions; 2%),
`chills (14 infusions; <2%), and fever (nine infusions; 1%).
`All are exp"ected adverse events associated with infusions of
`immunoglobulins.
`
`PHYSICIANS' DESK REFERENCE®
`
`WinRho SDFT!'d r Rho(D) Immune Globulin Intravenous (Hu~
`man), is administered to Rh0(D) positive patients with ITP.
`Therefore, side effects related to the destruction ·of Rh,(D)
`positive red blood cells, most notably a decreased hemoglo~
`bin, can be expected. In four clinical trials of patients
`treated with. the recommended initial intravenous dose of
`50 )lg/kg (250 IU/kg), the mean maximum decrease .in he(cid:173)
`moglobin was 1.70 g/dL (range: +0.40 to -6.1 g/dL). At are(cid:173)
`duced dose, ranging from 25 to 40 pg/kg (125 to 200 IU!kg),
`the mean maximum decrease in hemoglobin was 0.81 g/dL
`(range: +0.65 to -1.9 gidL). Only 5/137 (3.7%) of patients had
`a maximum decrease in hemoglobin of greater than 4 g/dL
`(range 4.2 to 6.1 g/dL).
`In most cases, the RBC destruction is believed to occur in
`the spleen. However, signs and symptoms consistent with
`IVH, including back pain, shaking chilJs, ancVor hemoglo(cid:173)
`binuria, have. been reported, occurring within 4 hours of
`WinRho administration. IVH-related complications that
`have been reported include dea~h (fo_ur ~ases reported be(cid:173)
`tween May 1996 and April 1999), acute onset or exacerba(cid:173)
`tion of anemia, and act,tte onset or exacerbation of renal in(cid:173)
`su~ciency. One patient died froiD .complications secondary
`to !VI-I -induced exacerbation of anemia after administration
`of WinRho fOr treatment ofiTP. Although the primary cause
`of death .in the other three I'l'P patients treated with Win·
`Rho was related to underlying disease, the extent to which
`lVH·related clinical complications exacerbated their condi(cid:173)
`tions and contributed to their deaths in unknown. ·'
`The mean maximum decrease in hemoglObin in pS:tients
`who were not traosfused with PRBCs was 3. 7 g/dL (range:
`0.0-7.6 g/dL). Transfusions for treatment-associated aneM
`mia were administered withiD. hours to days of the onset of
`IVH and consisted of between 1-6 units of PRBCs. Acute
`renal insufficiency was noted within 2 to 48 hours of the on(cid:173)
`set of IVH. The mean maximum increase in serum CJ'eati(cid:173)
`nine was 3.5 mg/dL (range: 0.8-10.3 mg/dL) and occurred
`within 2-9 days~ The renal insufficiency in all surviving pa(cid:173)
`lients resolved with medical management, including dialy(cid:173)
`sis, within 4-23 days.
`The etiology of IVH following WinRho administration is un·
`known. No known risk factors associated with this adverse
`event have yet been identified from among those examined,
`which included age, gender, preMtreatment renal function,
`pretreatment hemoglobin, concomitantly administered
`PRBCs, or WinRho dose.
`§.':!l!I!!!ssion of.!!d.L_. Isoimmunization
`Adverse reactions to Rh0(D) Immune Globulin Intravenous
`(Human) are infreauent in Rh0 (D) negative individuals. In
`the clinical trial2 of 1,186 Rh0(D) negative pregnant
`women, no adverse events were attributed to Rho(D} IGIV.
`Discomfort and slight swelling at the site of injection and
`slight elevation in t~mperature have been reported in a
`small number of cases. A post-marketing survey conducted
`since the Canadian licensure of Rh,(D) IGIV in 1980 for this
`indication included data obt~ined from 31,059 injections
`(25,068 for routine Rh prophylaxis and 5,991 following abor·
`tions, amniocentesis, chorionic villus sampling and antepar(cid:173)
`tum hemorrhage). There were 9,905 Rh 0(D) nega~ive women
`who ~elivered Rh0(D) positive infants, almost all of whom
`had received antenatal as well as postnatal prophylaxis. Of
`the patients followed in this 'survey, there were 26 reported
`treatment failures that resulted in the development of
`Rh 0(D) antibodies. There were no adverse experiences re(cid:173)
`lat~d to Rh,(D) IGIV reported in this survey.
`General Adverse Reactions
`111 addition to the aaversel-eactions described above, the fol(cid:173)
`lowing have been reported infreq~ently in clinical trials
`ancVor postmarketing experience, in patients treated for
`ITP or the suppression of Rh isoimmunization, and are
`thought to be. te.mpora~ly associated with WinRho SDFTM,
`Rh 0(D) Immune Globulm. Intravenous (Human), use: asthe~
`nia, abdominal or back pain, hypotension, pallor, diarrhea,
`increased LDH, arthralgia, myalgia, dizziness, hyperkine(cid:173)
`sia, somnolence, vasodilation, pruritus, rash, and sweating.
`As is the case with all drugs of this na~ure, there is a remote
`chance of an idiosyncratic or anaphylactic reaction with
`WinRho SDFTM in individuals with hypersensitivity to blood
`products.
`SYMPTOMS AND TREATMENT OF OVERDOSE
`'.!!.!!.~!!}ent of ITP ani!_ Suppression of Rh Isoimmunization
`There are no report~ of kpown overdoses in patients being
`treated for Rh isoimmunization or ITP. In clinical studies
`with nonpregnant Rh 0(D) positive patients with ITP
`(n=141) treated with 120 to 6,500 )lg (600 to 32,500 !U) of
`Rh 0(D) IGIV, there were no signs or symptoms that war(cid:173)
`ranted medical intervention. However, these same doses
`were associated with a mild, transient hemolytic anemia.
`DOSAGE AND ADMINISTRATION
`!!~f:!l .. t!tent of ITP and SupPression !!f...!lh Isoimmunization
`WinRho SDF™, Rh0(D) Immune Globulin Intravenous (H.U~
`man), should be reconstituted only with the accompanying
`vial of 0.9% Sodium Chloride Injection. It should not·be ad(cid:173)
`ministered concurrently with other products.
`Reconstitution
`Intravenous Administration
`Ar;eptically reconstitute the product shortly before use with
`2.5 mL of 0.9% Sodium Chloride Injection for 120 11g (600
`!U) and 300 )lg (1,500 !U) and 8.5 mL of0.9% Sodium Chlo(cid:173)
`ride Injection for 1,000 )lg (5,000 IU) (see the next table).
`Inject the diluent slowly onto-the inside wall of the vial and
`gently swirl until dissolved. Do not shake.
`Intramuscular Administratio-n ___ _
`Aseptically reconstitute the product shortly before use with
`1.25 mL of 0.9% Sodium Chloride Injection for 120 )lg (600
`
`Information will be superseded by supplements and subsequent editions
`
`Ex. 2026-0002
`
`

`
`PRODUCT INFORMATION
`
`IV) and 300 ~g (1,500 IU) and 8.5 mL of 0.9% Sodium Chlo(cid:173)
`ride Injection for 1,000 ~g (5,000 IU) (see the next table),
`Inject the diluent slowly onto the inside wall of the vial and
`gently swirl until dissolved. Do not shake.
`
`Reconstitution of WinRho SDFTM
`
`Vial Size
`
`Volume of Diluent
`to be Added to Vial
`
`Intravenous Injection
`
`120 }lg (600 IU)
`
`300 }lg ( 1,500 IU)
`
`1,000 Jlg (5,000 !Ul
`
`Intramuscular Injection
`
`120 }lg (600 !U)
`
`300 Jlg (1,500 IU)
`
`!,000 Jlg (5,000 IU)
`
`-
`
`2.5 mL
`
`2.5 mL
`
`8.5 mL
`
`-
`
`1.25 mL
`
`1.25 mL
`
`8.5 mL*
`
`* To be admm1stered mto several s1tes
`
`Injection
`Parenteral products such as WinRho SDF™ should be in~
`spected for particulate matter and discoloration prior to ad·
`ministration. Use the product within 12 hour:s of reconsti(cid:173)
`tution. Discard any unused portion.
`Intravenous Administration
`Infuse the entire dose into a suitable vein over three to five
`minutes. WinRho SDFTM should be administered separately
`from other drugs.
`Intramuscular Administration
`Administer into the deltoid muscle of the upper arm or the
`anterolateral aspects of the upper thigh. Due to the risk of
`sciatic nerve injury, the gluteal region should not be used as
`a routine injection site. If the gluteal region is used, use
`only the upper, outer quadrant.
`1}:eatment o[ITP_
`WinRho SDF™, Rh0(D) Immune Globulin Intravenous (Hu~
`man), must be given by ln'traVenous administration for the
`treatment of ITP.
`Initial Dosing: After confirming that the patient is Rh0 (0)
`positive, an