KAM-RHO D I.M.

העדוה העדוה

לע לע

הרמחה הרמחה

(

(

עדימ עדימ

ןולעב )תוחיטב ןולעב )תוחיטב

ל

ל

אפור אפור ןכדועמ( ןכדועמ(

05.2013

05.2013

ךיראת

__________

14-7-13

_____________

םש

רישכת

תילגנאב

רפסמו

םושירה

KAM-RHO D I.M., 108-73-28991

םש

לעב

םושירה

__________

Kamada Ltd

ספוט

הז

דעוימ

טורפל

תורמחהה

דבלב

תורמחהה

תושקובמה קרפ

ןולעב טסקט

יחכונ טסקט

שדח

WARNINGS

Recommendations Regarding Thrombosis

Care should be used when immune globulin products

are given to individuals determined to be at increased

risk of thrombosis.

Patients at increased risk of thrombosis include those

with acquired or hereditary hypercoagulable states,

prolonged immobilization, in-dwelling vascular

catheters, advanced age, estrogen use, a history of

venous or arterial thrombosis, cardiovascular risk

factors (including history of atherosclerosis and/or

impaired cardiac output), and hyperviscosity

(including cryoglobulins, fasting chylomicronemia

and/or high triglyceride levels, and monoclonal

gammopathies).

As noted in product labeling, patients at risk for

thrombosis should receive immune globulin products

at the slowest rate practicable, and these individuals

should be monitored for thrombotic complications.

Consideration should also be given to measurement

of baseline blood viscosity in individuals at risk for

hyperviscosity.

Recommendations Regarding Hemolysis

Heightened awareness of the potential for hemolysis

is recommended in individuals receiving immune

globulin

products,

particularly

those

determined to be at increased risk.

Patients

increased

risk

hemolysis

following treatment with immune globulins include

those with non-O blood group types, those who have

underlying associated inflammatory conditions, and

those receiving high cumulative doses of immune

globulins over the course of several days.

As noted in product labeling, patients receiving

immune globulin products should be monitored for

hemolysis, particularly those at increased risk.

Clinical symptoms and signs of hemolysis include

fever, chills and dark urine. If these occur,

appropriate laboratory testing should be obtained.

(D) Immune Globulin (Human) for intramuscular

use only.

DESCRIPTION

KamRh

o

-D I.M. is a sterile non-pyrogenic aqueous

solution, containing 150

g/ml of immune globulin

anti-D. It is prepared from pooled Human venous plasma

with a high content of anti-D antibodies. Each unit of

plasma and each plasma pool used in the manufacture

of this product has been tested and found to be non-

reactive to Hepatitis B Surface Antigen (HBsAg), anti

HIV I-II and anti-HCV. Kamada’s manufacturing process includes

a Solvent/Detergent step, that is, treatment with tri-(n-butyl)

phosphate and Triton X-100, a step designed to increase the

safety of the product by eliminating the risk of transmission of

lipid enveloped viruses. In addition the process includes heat-

treatment at 60°C for 10 hours, a process long-known to inactivate

viruses. Finally the purification process itself has been found to be

capable of reducing the concentration of a non-enveloped type

virus by several logs.

The product is stabilized with 0.3 M Glycine and is preservative

free.

Composition

Each vial of KamRh

o

-D I.M. contains:

(D) Immune Globulin 150

g/ml

Glycine 2.25% W/V = 0.3 M.

ACTIONS AND CLINICAL PHARMACOLOGY

Pharmacology

KamRh

o

-D I.M. is a sterile non-pyrogenic purified gamma globulin

(IgG) solution, manufactured from human plasma containing

high titers of anti-Rh

(D). The manufacturing process includes

a solvent/detergent treatment and heat - treatment at 60°C for

10 hours, steps that are effective in inactivating viruses such as

hepatitis B, hepatitis C, HIV and others. These steps are designed to

increase product safety by reducing the risk of virus transmission.

KamRh

o

-D immune globulin is prepared from human plasma by

an ion-exchange column chromatography method.

KamRh

o

-D I.M. is used to suppress the immune response of

non-sensitized Rh

(D) antigen-negative individuals following

(D) antigen-positive red blood cell exposure by fetomaternal

hemorrhage during delivery of a Rh

(D) antigen-positive infant,

abortion (spontaneous or induced), amniocentesis, abdominal

trauma or mismatched transfusion.

The mechanism of action is not completely understood. Rh

(D) immune globulin, when administered within 72 hours of a

full-term delivery of a Rh

(D) antigen-positive infant by a Rh

(D) antigen-negative mother, will reduce the incidence of Rh

isoimmunization from between 12% and 13% to between 1%

and 2%. The 1% to 2% treatment failures are due, for the most

part, to isoimmunization during the last trimester of pregnancy.

Thus, when treatment is given both antenatally at 28 weeks

gestation and postpartum, the Rh immunization rate drops to

approximately 0.1%.

INDICATIONS

Pregnancy/Other Obstetric Conditions:

Suppression of Rh immunization in non-sensitized Rh

(D) negative

women delivering a Rh

positive baby, or when the baby’s Rh type

is unknown

[1,2]

. Suppression of Rh immunization after spontaneous

or induced abortions, threatened abortion associated with maternal

bleeding, amniocentesis, chorionic villus sampling, ruptured tubal

pregnancy, and significant abdominal trauma. KamRh

o

-D I.M.

should be given within 72 hours of the event. It may be given

even after up to one month although efficacy may be somewhat

reduced

Transfusion

Suppression of Rh isoimmunization in Rh

(D) antigen-negative

patients transfused with Rh

(D) antigen-positive RBCs or blood

components containing Rh

(D) antigen-positive RBCs. Initiate

treatment within 72 hours of exposure.

CONTRAINDICATIONS

Individuals known to have an anaphylactic or severe systemic

reaction to human globulin or other plasma proteins. KamRh

o

-D

I.M. contains trace amounts of IgA (<2

g per 1500 IU [300

g]).

Individuals who are deficient in IgA may have the

potential for developing IgA antibodies and have

anaphylactic reactions. Evaluate the potential benefit

of treatment with Rh

(D) immune globulin against

the potential for hypersensitivity reactions.

WARNINGS

Route of Administration

KamRh

o

-D I.M. must be administered intramuscularly.

For the suppression of Rh isoimmunization in the mother.

Do not administer to the infant.

Criteria for KamRh

o

-D I.M. Administration to Prevent

Alloimmunization

The criteria for an Rh-incompatible pregnancy requiring

administration of Rh

(D) immune globulin at 28 weeks gestation

and within 72 hours after delivery are: The mother is Rh

antigen-negative; the mother is bearing a child whose father is

either Rh

(D) antigen-positive or Rh

(D) unknown; the infant is

either Rh

(D) antigen-positive or Rh

(D) unknown; the mother

was not previously sensitized to the Rh

(D) antigen (and thus

does not carry anti-Rh

(D) antibodies).

Pregnancy: Category C

It is not known whether Rh

(D) immune globulin can cause fetal

harm when administered to a pregnant woman or can affect

reproductive capacity.

Infants

KamRh

o

-D I.M. is for the suppression of Rh Isoimmunization in the

mother. Do not administer to the infant. (See Warnings).

Recommendations Regarding Thrombosis

Care should be used when immune globulin products are given to

individuals determined to be at increased risk of thrombosis.

Patients at increased risk of thrombosis include those with acquired

or hereditary hypercoagulable states, prolonged immobilization,

in-dwelling vascular catheters, advanced age, estrogen use, a

history of venous or arterial thrombosis, cardiovascular risk

factors (including history of atherosclerosis and/or impaired

cardiac output), and hyperviscosity (including cryoglobulins,

fasting chylomicronemia and/or high triglyceride levels, and

monoclonal gammopathies).

As noted in product labeling, patients at risk for thrombosis

should receive immune globulin products at the slowest rate

practicable, and these individuals should be monitored for

thrombotic complications.

Consideration should also be given to measurement of baseline

blood viscosity in individuals at risk for hyperviscosity.

Recommendations Regarding Hemolysis

Heightened awareness of the potential for hemolysis is

recommended in individuals receiving immune globulin products,

particularly those who are determined to be at increased risk.

Patients at increased risk for hemolysis following treatment with

immune globulins include those with non-O blood group types,

those who have underlying associated inflammatory conditions,

and those receiving high cumulative doses of immune globulins

over the course of several days.

As noted in product labeling, patients receiving immune globulin

products should be monitored for hemolysis, particularly those

at increased risk.

Clinical symptoms and signs of hemolysis include fever, chills

and dark urine. If these occur, appropriate laboratory testing

should be obtained.

PRECAUTIONS

General

Plasma used in manufacturing KamRh

o

-D I.M. has been extensively

tested in accordance with the Pharmacopoeal and FDA regulations.

The process includes Solvent/Detergent treatment to inactivate

lipid enveloped viruses and heat treatment at 60°C for 10 hours,

a well established technique for inactivating viral pathogens.

However, the possibility of transmission of infectious disease

cannot be excluded. As with all preparations administered by the

I.M. route, bleeding complications may be encountered in patients

with thrombocytopenia or other bleeding disorders.

KamRh

o

-D I.M. should not be administered to Rh

(D) negative

individuals who are Rh immunized as evidenced by standard

manual Rh antibody screening tests.

A large fetomaternal hemorrhage late in pregnancy or following

delivery may cause a weak mixed field positive D

test result. Such an

individual should be assessed for a large fetomaternal hemorrhage

and the dose of KamRh

o

-D I.M. adjusted accordingly.

KamRh

o

-D I.M. should be administered if there is any doubt

about the mother’s blood type.

Drug Interactions

It is recommended that KamRh

o

-D I.M. be administered

independently of other drugs.

Other antibodies in the KamRh

o

-D I.M. preparation may interfere

with the response to live vaccines such as measles, mumps,

polio or rubella. Therefore, immunization with live vaccines

should not be given within three months after KamRh

o

-D I.M.

administration.

ADMINISTRATION AND DOSAGE

KamRh

o

-D I.M. must be administered intramuscularly only.

Pregnancy

A 1,500 IU (300

g) dose of KamRh

o

-D I.M. should be administered

at 28 weeks gestation. If KamRh

o

-D I.M. is administered early

in the pregnancy, it is recommended that KamRh

o

-D I.M. be

administered at 12-week intervals in order to maintain an adequate

level of passively acquired anti-Rh. A 600 IU (120

g) dose should

be administered as soon as possible after delivery of a confirmed

(D) positive baby and normally no later than 72 hours after

delivery. In the event that the Rh status of the baby is not known at

72 hours, KamRh

o

-D I.M. should be administered to the mother

at 72 hours after delivery. If more than 72 hours have elapsed,

KamRh

o

-D I.M. should not be withheld, but administered as

soon as possible up to 28 days after delivery.

Other Obstetric Conditions

A 600 IU (120

g) dose of KamRh

o

-D I.M. should be administered

immediately after abortion, amniocentesis (after 34 weeks gestation)

or any other manipulation late in pregnancy (after 34 weeks

gestation) associated with increased risk of Rh isoimmunization.

Administration should take place within 72 hours after the

event.

A 1,500 IU (300

g) dose of KamRh

o

-D I.M. should be administered

immediately after amniocentesis before 34 weeks gestation or after

chorionic villus sampling. This dose should be repeated every 12

weeks while the woman is pregnant. In case of threatened abortion,

KamRh

o

-D I.M. should be administered as soon as possible.

Transfusion

KamRh

o

-D I.M. should be administered within 72 hours after

exposure to treatment of incompatible blood transfusions or massive

fetal hemorrhage as outlined in the table below:

Route of

Administration

Dose and

Frequency

KamRh

o

-D I.M. Dosage

Rh+ Blood

Rh+ Red Cell

Intramuscular

6,000 IU

(1,200

every 12

hours until

total dose

administered

60 IU (12

ml blood

120 IU (24

g)/ml cells

Injection

Parenteral products such as KamRh

o

-D I.M. should be

inspected for foreign particulate matter and coloration prior to

administration.

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.

Laboratory Test

The intrapartum administration of KamRh

o

-D I.M. may result

in a positive direct antiglobulin test in the baby after delivery. In

rare cases, this may also put into question the true status of the

infant’s Rh blood type. Appropriate laboratory tests should be

performed to resolve such problems. The presence of administered

KamRh

o

-D I.M. in the maternal circulation may cause a positive

indirect antiglobulin test. If there is uncertainty about mother’s Rh

group or immune status, KamRh

o

-D I.M. should be administered

to the mother.

The occurrence of a large fetomaternal hemorrhage late in pregnancy

or at delivery may cause spurious mixed field agglutination reactions

in a Rh

(D) negative mother, and may result in her being mistyped

as Rh

(D) positive or D

. Such instances may indicate the need

for a larger than normal dose of KamRh

o

-D I.M.

ADVERSE REACTIONS

Rh Isoimmunization Suppression

Adverse reactions to Rh

(D) immune globulin are infrequent in

(D) antigen-negative individuals. Discomfort and swelling at

the site of injection and slight elevation in temperature might

occur in a small number of cases. As is the case with all drugs of

this nature, there is a remote chance of an anaphylactic reaction in

individuals with hypersensitivity to blood products. In the event of

an immediate reaction (anaphylaxis) characterized by collapse, rapid

pulse, shallow respiration, pallor, cyanosis, edema or generalized

urticaria, subcutaneous injection of epinephrine hydrochloride 0.3

ml 1:1000 aqueous solution should be immediately instituted,

followed by intravenous administration of hydrocortisone, 50 to

100 mg, if necessary.

Elevated bilirubin levels have been reported in some individuals

receiving multiple doses of Rh

(D) Immune Globulin (Human),

following mismatched transfusions. This is believed to be due to

a relatively rapid rate of foreign red cell destruction.

OVERDOSAGE

Symptoms and Treatment of Overdosage

A Rh

(D) positive individual treated with large doses of KamRh

o

-D

I.M. may develop a mild anemia. However this condition is normally

compensated for by elevated red cell production. In most cases,

medical intervention other than discontinuation of KamRh

o

-D

I.M. treatment would not be required.

STORAGE

Store at 2°-8°C. Do not freeze.

Do not use after expiration date.

Discard any unused portion.

PRESENTATION

Vials of 1 or 2 ml of Rh

(D) Immune Globulin containing 150

g/ml, for I.M. use.

CAUTION

This product may not be dispensed without a doctor’s

prescription.

REFERENCES

(1) Pollack W., Gorman J.G., Freda V.J., et al. Results of Clinical

Trials of RhoGAM in Women. Transfusion 8:151, 1968.

(2) Freda V.J., Gorman J.G., Pollack W. et al. Prevention of Rh

Isoimmunization. Progress Report of the Clinical Trials in Mothers.

JAMA 199:390, 1967.

(3) Samson D., Mollison P.L. Effect on Primary Rh Immunization

of Delayed Administration of anti-Rh. Immunology 28:349,

1975.

License No.: 108732899100

Manufactured by:

Kamada Ltd.

Beit Kama

ISRAEL

The format of the leaflet has been determined by the Ministry

of Health and its content thereof was checked and approved

in July 2014.

3200007380-02