Declomycin

Generic Name: Demeclocycline Hydrochloride
Class: Tetracyclines
VA Class: AM250
CAS Number: 64-73-3  

Introduction

Antibacterial; tetracycline antibiotic derived from Streptomyces aureofaciens.¹⁰⁰

Uses for Declomycin

Respiratory Tract Infections

Treatment of respiratory tract infections caused by Mycoplasma pneumoniae.¹⁰⁰

Treatment of respiratory tract infections caused by Haemophilus influenzae, Streptococcus pneumoniae, or Klebsiella.¹⁰⁰ Should only be used for treatment of infections caused by these bacteria when in vitro susceptibility tests indicate the organism is susceptible.^{100 a}

Acinetobacter Infections

Treatment of infections caused by Acinetobacter;¹⁰⁰ minocycline may be the preferred tetracycline for use as an alternative to imipenem or meropenem.^e

Acne

Adjunctive treatment of moderate to severe inflammatory acne.¹⁰⁰ Not indicated for treatment of noninflammatory acne.^a

Actinomycosis

Treatment of actinomycosis caused by Actinomyces israelii;¹⁰⁰ oral tetracyclines used as follow-up after initial parenteral treatment with penicillin G.^d

Amebiasis

Adjunct to amebicides for treatment of acute intestinal amebiasis.¹⁰⁰ Tetracyclines generally not recommended for treatment of amebiasis caused by Entamoeba.^d

Anthrax

Alternative to doxycycline for treatment of inhalational anthrax when a parenteral regimen is not available (e.g., when there are supply or logistic problems because large numbers of individuals require treatment in a mass casualty setting).¹⁰⁰ A multiple-drug parenteral regimen (ciprofloxacin or doxycycline and 1 or 2 other anti-infectives predicted to be effective) is preferred for treatment of inhalational anthrax that occurs as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism.^f

Bartonella Infections

Treatment of infections caused by Bartonella bacilliformis.¹⁰⁰

Brucellosis

Treatment of brucellosis;¹⁰⁰ tetracyclines considered drugs of choice.^{d e} Used in conjunction with other anti-infectives (e.g., streptomycin or gentamicin and/or rifampin),^{100 d e} especially for severe infections or when there are complications (e.g., endocarditis, meningitis, osteomyelitis).^d

Campylobacter Infections

Treatment of infections caused by Campylobacter.¹⁰⁰ Tetracyclines are alternatives, not drugs of choice.^{d e}

Chancroid

Treatment of chancroid caused by Haemophilus ducreyi.¹⁰⁰ Not included in CDC recommendations for treatment of chancroid.¹⁰¹

Chlamydial Infections

Treatment of uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia trachomatis.¹⁰⁰ Doxycycline is the preferred tetracycline for treatment of these infections, including presumptive treatment of chlamydial infections in patients with gonorrhea.¹⁰¹

Treatment of trachoma and inclusion conjunctivitis caused by C. trachomatis.¹⁰⁰ Consider that anti-infectives may not eliminate C. trachomatis in all cases of chronic trachoma.¹⁰⁰

Treatment of lymphogranuloma venereum (genital, inguinal, or anorectal infections) caused by C. trachomatis.¹⁰⁰ Doxycycline is the preferred tetracycline for these infections.^{101 d}

Treatment of psittacosis (ornithosis) caused by C. psittaci.¹⁰⁰ Doxycycline and tetracycline are drugs of choice.^{a d} For initial treatment of severely ill patients, use IV doxycycline.^a

Clostridium Infections

Alternative for treatment of infections caused by Clostridium.¹⁰⁰ Tetracyclines are alternatives to metronidazole or penicillin G for adjunctive treatment of C. tetani infections.^e

Enterobacteriaceae Infections

Treatment of infections caused by susceptible Escherichia coli, Enterobacter aerogenes, Klebsiella, or Shigella.¹⁰⁰ Should only be used for treatment of infections caused by these common gram-negative bacteria when other appropriate anti-infectives are contraindicated or ineffective^a and when in vitro susceptibility tests indicate the organism is susceptible.^{100 a}

Fusobacterium Infections

Alternative to penicillin G for the treatment of infections caused by Fusobacterium fusiforme (Vincent's infection).¹⁰⁰

Gonorrhea and Associated Infections

Alternative for treatment of uncomplicated gonorrhea (including urethritis) caused by susceptible Neisseria gonorrhoeae.¹⁰⁰ However, tetracyclines are considered inadequate therapy and are not recommended by CDC for treatment of gonorrhea.^{101 a}

Granuloma Inguinale (Donovanosis)

Treatment of granuloma inguinale (donovanosis) caused by Calymmatobacterium granulomatis.¹⁰⁰ Doxycycline is the tetracycline recommended as drug of choice by CDC.¹⁰¹

Listeria Infections

Alternative for treatment of listeriosis caused by Listeria monocytogenes.¹⁰⁰ Not usually considered a drug of choice or alternative for these infections.^{d e}

Nongonococcal Urethritis

Treatment of nongonococcal urethritis (NGU) caused by Ureaplasma urealyticum, C. trachomatis, or Mycoplasma.¹⁰⁰ Doxycycline usually is the tetracycline of choice for NGU.¹⁰¹

Consider that some cases of recurrent urethritis following treatment may be caused by tetracycline-resistant U. urealyticum.¹⁰¹

Plague

Treatment of plague caused by Yersinia pestis.¹⁰⁰ Regimen of choice is streptomycin or gentamicin (with or without doxycycline).^{d e}

Relapsing Fever

Treatment of relapsing fever caused by Borrelia recurrentis.¹⁰⁰ Tetracyclines are drugs of choice.^e

Rickettsial Infections

Treatment of rickettsial infections including Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, and tick fevers caused by Rickettsiae.¹⁰⁰ Tetracyclines are drugs of choice for treatment of most rickettsial infections; doxycycline usually is the preferred tetracycline.^{a d}

Syndrome of Inappropriate Antidiuretic Hormone Secretion

Treatment of syndrome of inappropriate antidiuretic hormone secretion† (SIADH).^a Only limited value in patients with acute water intoxication caused by excess ADH secretion, but may be effective in inhibiting the action of ADH in patients with chronic form of the disease.^a

Also has been used to treat hyponatremia and water retention† in patients with congestive heart failure or cirrhosis, but a high incidence of renal failure has been reported and the drug probably should not be used in these patients.^a

Syphilis

Alternative to penicillin G for treatment of primary, secondary, latent, or tertiary syphilis (not neurosyphilis) in nonpregnant adults and adolescents hypersensitive to penicillins.¹⁰⁰ Doxycycline and tetracycline are the preferred tetracyclines in patients hypersensitive to penicillins.¹⁰¹ Use tetracyclines only if compliance and follow-up can be ensured since efficacy not well documented.¹⁰¹

Tularemia

Treatment of tularemia caused by Francisella tularensis.¹⁰⁰ Tetracyclines considered alternatives to streptomycin (or gentamicin);^{d e g} risk of relapse and primary treatment failure may be higher than with aminoglycosides.^g

Vibrio Infections

Treatment of cholera caused by Vibrio cholerae.¹⁰⁰ Doxycycline and tetracycline are drugs of choice; used as an adjunct to fluid and electrolyte replacement in moderate to severe disease.^{d e}

Yaws

Alternative to penicillin G for treatment of yaws caused by Treponema pertenue.¹⁰⁰

Declomycin Dosage and Administration

Administration

Oral Administration

Administer orally 1 hour before or 2 hours after meals and/or milk.¹⁰⁰

Administer with adequate amounts of fluid to reduce the risk of esophageal irritation and ulceration.¹⁰⁰

Dosage

Pediatric Patients

General Pediatric Dosage

Oral

Children >8 years of age: 7–13 mg/kg daily given in 2–4 divided doses.^c

Adults

General Adult Dosage

Oral

150 mg 4 times daily or 300 mg 2 times daily.^c

Gonorrhea and Associated Infections

Oral

600 mg initially followed by 300 mg every 12 hours for 4 days for a total of 3 g.¹⁰⁰

No longer recommended for gonorrhea by CDC or other experts.¹⁰¹

Syndrome of Inappropriate Antidiuretic Hormone Secretion†

Oral

600 mg to 1.2 g daily in 3 or 4 divided doses.^b Diuresis usually occurs within 5 days after initiation of therapy and reverses within 2–6 days after drug discontinued.^b

Prescribing Limits

Pediatric Patients

Maximum 600 mg daily.^c

Special Populations

Hepatic Impairment

Adjust dosage by decreasing doses or increasing dosing interval.¹⁰⁰

Use with caution.¹⁰⁰

Renal Impairment

Adjust dosage by decreasing doses or increasing dosing interval.¹⁰⁰

Use with caution.¹⁰⁰

Cautions for Declomycin

Contraindications

• 
  

  Known hypersensitivity to demeclocycline, other tetracyclines, or any ingredient in the formulation.¹⁰⁰

  
  

Warnings/Precautions

Warnings

Adverse Dental and Bone Effects

Use during tooth development (e.g., pregnancy, children <8 years of age) may cause permanent yellow-gray to brown discoloration of teeth and enamel hypoplasia¹⁰⁰ Effects are most common following long-term use, but may occur following repeated short-term use.¹⁰⁰

Tetracyclines form a stable calcium complex in any bone-forming tissue.¹⁰⁰ Reversible decrease in fibula growth rate has occurred in prematures receiving tetracycline.¹⁰⁰

Use not recommended in children <8 years of age unless other appropriate drugs are ineffective or are contraindicated or unless the benefits in certain indications (e.g., anthrax) outweigh the risks.¹⁰⁰ (See Pediatric Use under Cautions.)

Fetal/Neonatal Morbidity

Animal studies indicate possible fetal toxicity (e.g., retardation of skeletal development) and embryotoxicity.¹⁰⁰ If used during pregnancy or if patient becomes pregnant while receiving demeclocycline, patient should be apprised of the potential hazard to the fetus.¹⁰⁰ (See Pregnancy under Cautions.)

Nervous System Effects

Possibility of adverse CNS effects (light-headedness, dizziness, vertigo) that may impair ability to drive vehicles or operate hazardous machinery.¹⁰⁰

Benign intracranial hypertension (pseudotumor cerebri) in adults reported with tetracyclines; usually manifested as headache and blurred vision.¹⁰⁰ Bulging fontanels reported in infants.¹⁰⁰ Effects usually resolve when drug discontinued, but possibility for permanent sequelae exists.¹⁰⁰

Renal Effects

Tetracyclines have antianabolic effects and may increase BUN.¹⁰⁰

In patients with impaired renal function, high serum demeclocycline concentrations may result in azotemia, hyperphosphatemia, and acidosis.¹⁰⁰ Excessive drug accumulation and possible liver toxicity may occur if usual dosage is used patients with renal impairment.¹⁰⁰ (See Renal Impairment under Dosage and Administration.)

Diabetes Insipidus Syndrome

Diabetes insipidus syndrome (polyuria, polydipsia and weakness) reported with long-term demeclocycline therapy.¹⁰⁰ Syndrome is nephrogenic, dose-dependent, and reversible when drug discontinued.¹⁰⁰

Laboratory Monitoring

Periodically assess organ system function, including renal, hepatic and hematopoietic, during long-term therapy.¹⁰⁰

Sensitivity Reactions

Photosensitivity Reactions

Photosensitivity, manifested by an exaggerated sunburn reaction, reported with tetracyclines.¹⁰⁰

Photosensitivity reactions may develop within a few minutes to several hours after sun exposure and usually persist 1–2 days after discontinuance of the drug.^a Most reactions result from accumulation of tetracyclines in skin and are phototoxic in nature; photoallergic reactions may also occur.^a

Discontinue drug at first evidence of skin erythema.¹⁰⁰

General Precautions

Superinfection

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.¹⁰⁰ Discontinue drug and institute appropriate therapy if superinfection occurs.¹⁰⁰

Selection and Use of Anti-infectives

Because many strains of Acinetobacter, Bacteroides, Enterobacter, E. coli, Klebsiella, Shigella, S. pyogenes (group A β-hemolytic streptococci), S. pneumoniae, enterococci, and α-hemolytic streptococci are resistant to tetracyclines (including demeclocycline), in vitro susceptibility tests should be performed if the drug is used for treatment of infections caused by these bacteria.¹⁰⁰

Incision and drainage or other surgical procedures should be performed in conjunction with demeclocycline therapy when indicated.¹⁰⁰

Specific Populations

Pregnancy

Category D.¹⁰⁰ (See Fetal/Neonatal Morbidity under Cautions.)

Lactation

Distributed into milk;¹⁰⁰ discontinue nursing or the drug.¹⁰⁰

AAP states maternal use of tetracyclines usually is compatible with breast-feeding since absorption of the drugs by nursing infants is negligible.^d

Pediatric Use

Should not be used in children <8 years of age unless benefits outweigh the risks.¹⁰⁰ (See Adverse Dental and Bone Effects under Cautions.)

Hepatic Impairment

Use with caution.¹⁰⁰ Reduce dosage.¹⁰⁰

Renal Impairment

Use with caution.¹⁰⁰ Reduce dosage.¹⁰⁰

Because usual dosage of doxycycline can be used in patients with impaired renal function, it may preferred when a tetracycline is indicated in a patient with impaired renal function.^b

Common Adverse Effects

GI effects (anorexia, nausea, vomiting, diarrhea); maculopapular and erythematous rash; dose-related BUN increase; hypersensitivity reactions.¹⁰⁰

Interactions for Declomycin

Specific Drugs

Drug	Interaction	Comments
Antacids (aluminum-, calcium-, or magnesium-containing)	Decreased demeclocycline absorption100	Administer antacids containing aluminum, calcium, or magnesium 1–2 hours before or after demeclocyclinea
Anticoagulants, oral	Possible increased anticoagulant effect;100 tetracyclines may impair utilization of prothrombin or decrease vitamin K production by intestinal bacteriaa	Monitor PT carefully; adjust anticoagulant dosage as neededa 100
Hormonal contraceptives	Possible decreased effectiveness of oral contraceptives100	Use alternative nonhormonal contraceptivesa
Iron-containing preparations	Possible decreased absorption of demeclocycline100	Administer demeclocycline 2 hours before or 3 hours after an oral iron preparationa
Methoxyflurane	Possible fatal nephrotoxicity100	Concomitant use not recommendeda
Penicillins	Possible antagonism100	Concomitant use not recommendeda

Declomycin Pharmacokinetics

Absorption

Bioavailability

Approximately 60–80% of a dose absorbed from the GI tract in fasting adults.^b Peak serum concentrations attained within 2–4 hours.^{b c}

Food

Food and/or milk decrease GI absorption by ≥50%.^{b c}

Distribution

Extent

Well distributed into body tissues and fluids.^c

Plasma Protein Binding

36–91%.^{a c}

Elimination

Metabolism

Does not appear to be metabolized.^a

Elimination Route

Excreted into the GI tract via bile and by nonbiliary routes.^a Excreted in urine by glomerular filtration.^{a c}

44% of a 150-mg oral dose excreted in urine and 13–46% excreted in feces as unchanged drug.^{b c}

Half-life

Adults with normal renal function: 10–17 hours.^{b c}

Special Populations

Patients with severe renal impairment: half-life 42–68 hours.^b

Stability

Storage

Oral

Tablets

20–25°C.¹⁰⁰

Actions and SpectrumActions

• 
  

  Usually bacteriostatic,^{100 a} but may be bactericidal in high concentrations or against highly susceptible organisms.^a

  
  


• 
  

  Inhibits protein synthesis¹⁰⁰ in susceptible organisms by reversibly binding to 30S and 50S ribosomal subunits.^a

  
  


• 
  

  The complete mechanisms by which tetracyclines reduce acne lesions have not been fully elucidated.^a The effects appear to result in part from the antibacterial activity of the drugs, but other mechanisms also are involved.^a

  
  


• 
  

  Spectrum of activity includes many gram-positive and -negative bacteria and various other organisms (e.g., Rickettsia, Chlamydia, Mycoplasma, spirochetes).^{a c} Inactive against fungi and viruses.^a

  
  


• 
  

  Gram-positive aerobes and anaerobes: active against Actinomyces israelii, Bacillus anthracis, Clostridium, Propionibacterium acnes, and some staphylococci and streptococci.^{a c} Many strains of S. pyogenes and Enterococci are resistant.^a

  
  


• 
  

  Gram-negative aerobes and anaerobes: active against Bartonella bacilliformis, Brucella, Calymmatobacterium granulomatis, Francisella tularensis, Haemophilus ducreyi, H. influenzae, Neisseria gonorrhoeae, Vibrio cholerae, and Y. pestis.¹⁰⁰ Many strains of Acinetobacter, E. aerogenes, E. coli, Klebsiella, and Shigella and nearly all strains of Proteus and Pseudomonas are resistant.^{a c}

  
  


• 
  

  Other organisms: active against Rickettsia, Coxiella burnetii, Chlamydia psittaci, C. trachomatis, Mycoplasma hominis, M. pneumoniae, Ureoplasma urealyticum, B. recurrentis, Leptospira, Treponema pallidum, and T. pertenue.^{a c}

  
  


• 
  

  Complete cross-resistance usually occurs between demeclocycline and other tetracyclines (doxycycline, minocycline, oxytetracycline, tetracycline).^{a c}

  
  

Advice to Patients

• 
  

  Importance of drinking sufficient quantities of fluids when taking tablets to reduce the risk of esophageal irritation and ulceration.¹⁰⁰

  
  


• 
  

  Advise patients that absorption of demeclocycline may be reduced when taken with foods, especially those containing calcium, and that tablets should be taken at least 1 hour before or 2 hours after meals and/or milk.¹⁰⁰

  
  


• 
  

  Advise patients that adverse CNS effects (light-headedness, dizziness, vertigo) may occur and caution should be used when driving vehicles or operating hazardous machinery.¹⁰⁰

  
  


• 
  

  Advise patients to avoid excessive sunlight or artificial UV light and to discontinue the drug at the first sign of skin erythema;¹⁰⁰ consider use of sunscreen or sunblock.^a

  
  


• 
  

  Advise patients that demeclocycline may decrease effectiveness of oral contraceptives and that alternative nonhormonal contraceptive measures should be used.¹⁰⁰

  
  


• 
  

  Advise patients that unused supplies of demeclocycline should be discarded by the expiration date.¹⁰⁰

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹⁰⁰ (See Fetal/Neonatal Morbidity under Cautions.)

  
  


• 
  

  Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs.¹⁰⁰

  
  


• 
  

  Importance of informing patients of other important precautionary information. (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Demeclocycline Hydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Bulk	Powder*
Oral	Tablets, film-coated	150 mg*	Declomycin	Glades
			Demeclocycline Tablets	Barr, Impax
		300 mg*	Declomycin	Glades
			Demeclocycline Tablets	Barr, Impax

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions July 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

100. Lederle Pharmaceuticals. Declomycin (demeclocycline hydrochloride) for oral use prescribing information. Pearl River, NY. 2002 Mar 14.

101. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2002. MMWR Morb Mortal Wkly Rep. 2002; 51(No. RR-6):1-78.

a. AHFS Drug Information 2004. McEvoy GK, ed. Tetracyclines General Statement. American Society of Health-System Pharmacists; 2004:433-49.

b. AHFS Drug Information 2004. McEvoy GK, ed. Demeclocycline hydrochloride. Bethesda, MD: American Society of Health-System Pharmacists; 2004:449.

c. Lederle Pharmaceuticals. Declomycin (demeclocycline hydrochloride) tablets prescribing information. Pearl River, NY. 2003 Jun.

d. Committee on Infectious Diseases, American Academy of Pediatrics. 2000 Red book: report of the Committee on Infectious Diseases. 25th ed. Elk Grove Village, IL: American Academy of Pediatrics: 2000:187-8,192-3,374-9,547-59.

e. Anon. The choice of antibacterial drugs. Med Lett Drugs Ther. 2001; 43:69-78. [PubMed 11518876]

f. Inglesby TV, O’Toole T, Henderson DA et al for the Working Group on Civilian Biodefense. Anthrax as a biological weapon, 2002. Updated recommendations for management. JAMA. 2002; 287:2236-52. [IDIS 480001] [PubMed 11980524]

g. Dennis DT, Inglesby TV, Henderson DA et al for the Working Group on Civilian Biodefense. Tularemia as a biological weapon: medical and public health management. JAMA. 2001; 285:2763-73. [IDIS 465175] [PubMed 11386933]

More Declomycin resources

• Declomycin Side Effects (in more detail)
• Declomycin Use in Pregnancy & Breastfeeding
• Drug Images
• Declomycin Drug Interactions
• Declomycin Support Group
• 2 Reviews for Declomycin - Add your own review/rating

• Declomycin MedFacts Consumer Leaflet (Wolters Kluwer)


• Declomycin Concise Consumer Information (Cerner Multum)


• Demeclocycline Prescribing Information (FDA)


• Demeclocycline Professional Patient Advice (Wolters Kluwer)

Compare Declomycin with other medications

• SIADH

RhoGAM Ultra-Filtered PLUS

Dosage Form: injection, solution
FULL PRESCRIBING INFORMATION

Rho(D) Immune Globulin (Human)

RhoGAM® Ultra-Filtered PLUS

(300 μg) (1500 IU)

MICRhoGAM® Ultra-Filtered PLUS (50 μg) (250 IU)

Rx Only

For Intramuscular Injection Only

Prefilled syringes, preservative-free (thimerosal free), latex-free delivery system

Indications and Usage for RhoGAM Ultra-Filtered PLUS

. Pregnancy and other obstetrical conditions

For administration to Rh-negative women not previously sensitized to the Rho(D) factor, unless the father or baby are conclusively Rh-negative.

• Delivery of an Rh-positive baby irrespective of the ABO groups of the mother and baby


• Antepartum prophylaxis at 26 to 28 weeks gestation


• Antepartum fetal-maternal hemorrhage (suspected or proven) as a result of placenta previa, amniocentesis, chorionic villus sampling, percutaneous umbilical blood sampling, other obstetrical manipulative procedure (e.g., version) or abdominal trauma


• Actual or threatened pregnancy loss at any stage of gestation


• Ectopic pregnancy

. Transfusion of Rh-incompatible blood or blood products

• Prevention of Rh immunization in any Rh-negative person after incompatible transfusion of Rh-positive blood or blood products (e.g., red blood cells, platelet concentrates, granulocyte concentrates)

RhoGAM Ultra-Filtered PLUS Dosage and Administration

For intramuscular use only. Do not inject RhoGAM Ultra-Filtered PLUS (RhoGAM) or MICRhoGAM Ultra-Filtered PLUS (MICRhoGAM) intravenously. In the case of postpartum use, the product is intended for maternal administration. Do not inject the newborn infant. Inject the entire contents of the syringe(s). For single use only. (See WARNINGS AND PRECAUTIONS)

RhoGAM or MICRhoGAM should be administered within 72 hours of delivery or known or suspected exposure to Rh-positive red blood cells. There is little information concerning the effectiveness of Rho(D) Immune Globulin (Human) when given beyond this 72 hour period. In one study, Rho(D) Immune Globulin (Human) provided protection against Rh immunization in about 50% of subjects when given 13 days after exposure to Rh-positive red blood cells.1 Administer every 12 weeks starting from first injection to maintain a level of passively acquired anti-D. If delivery occurs within three weeks after the last antepartum dose, the postpartum dose may be withheld, but a test for fetal-maternal hemorrhage should be performed to determine if exposure to > 15 mL of red blood cells has occurred.2

Parenteral drug products should be inspected visually for particulate matter, discoloration and syringe damage prior to administration. Do not use if particulate matter and / or discoloration are observed. The solution should appear clear or slightly opalescent.

Indications and Recommended Dosage

Indication	Dose	Notes
Postpartum (if the newborn is Rh-positive)	RhoGAM (300 μg) (1500 IU)	Additional doses of RhoGAM are indicated when the patient has been exposed to > 15 mL of Rh-positive red blood cells. This may be determined by use of qualitative or quantitative tests for fetal-maternal hemorrhage.
Administer within 72 hours of delivery.
Antepartum:
Prophylaxis at 26 to 28 weeks gestation Administer within 72 hours of suspected or proven exposure to Rh-positive red blood cells resulting from: Amniocentesis, chorionic villus sampling (CVS) and percutaneous umbilical blood sampling (PUBS) Abdominal trauma or obstetrical manipulation Ectopic pregnancy Threatened pregnancy loss after 12 weeks gestation with continuation of pregnancy Pregnancy termination (spontaneous or induced) beyond 12 weeks gestation		If antepartum prophylaxis is indicated, it is essential that the mother receive a postpartum dose if the infant is Rh-positive.
		If RhoGAM is administered early in pregnancy (before 26 to 28 weeks), there is an obligation to maintain a level of passively acquired anti-D by administration of RhoGAM at 12-week intervals.
Actual or threatened termination of pregnancy (spontaneous or induced) up to and including 12 weeks gestation Administer within 72 hours	MICRhoGAM (50 μg) (250 IU)	RhoGAM may be administered if MICRhoGAM is not available.
Transfusion of Rh-incompatible blood or blood products		Administer within 72 hours of suspected or proven exposure to Rh-positive red blood cells.
< 2.5 mL Rh-positive red blood cells	MICRhoGAM (50 μg) (250 IU)	RhoGAM may be administered if MICRhoGAM is not available.
2.5 - 15.0 mL Rh-positive red blood cells	RhoGAM (300 μg) (1500 IU)
> 15.0 mL Rh-positive red blood cells	RhoGAM (300 μg) (1500 IU) (multiple syringes)	Additional doses of RhoGAM are indicated when the patient has been exposed to > 15 mL of Rh-positive red blood cells. Administer 20 μg of RhoGAM per mL of Rh-positive red blood cell exposure.   Multiple doses may be administered at the same time or at spaced intervals, as long as the total dose is administered within three days of exposure.

RhoGAM Administration

Each single dose prefilled syringe of RhoGAM contains 300 μg (1500 IU) of Rho(D) Immune Globulin (Human). This is the dose for the indications associated with pregnancy at or beyond 13 weeks unless there is clinical or laboratory evidence of a fetal-maternal hemorrhage (FMH) in excess of 15 mL of Rh-positive red blood cells.

MICRhoGAM Administration

Each single dose prefilled syringe of MICRhoGAM contains 50 μg (250 IU) of Rho(D) Immune Globulin (Human). This dose will suppress the immune response to up to 2.5 mL of Rh-positive red blood cells. MICRhoGAM is indicated within 72 hours after termination of pregnancy up to and including 12 weeks gestation. At or beyond 13 weeks gestation, RhoGAM should be administered instead of MICRhoGAM.

Multiple Dosage

Multiple doses of RhoGAM are required if a FMH exceeds 15 mL, an event that is possible but unlikely prior to the third trimester of pregnancy and is most likely at delivery. Patients known or suspected to be at increased risk of FMH should be tested for FMH by qualitative or quantitative methods.3 In efficacy studies, RhoGAM was shown to suppress Rh immunization in all subjects when given at a dose of ≥ 20 μg per mL of Rh-positive red blood cells.4 Thus, a single dose of RhoGAM will suppress the immune response after exposure to≤ 15 mL of Rh-positive red blood cells. However, in clinical practice, laboratory methods used to determine the amount of exposure (volume of transfusion or FMH) to Rh-positive red blood cells are imprecise.5,6 Therefore, administration of more than 20 μg of RhoGAM per mL of Rh-positive red blood cells should be considered whenever a large FMH or red blood cell exposure is suspected or documented.6 Multiple doses may be administered at the same time or at spaced intervals, as long as the total dose is administered within three days of exposure.7

Dosage Frequency

To maintain an adequate level of anti-D, RhoGAM should be administered every 12 weeks. The exact timing for the injection is based on 12 week intervals starting from the administration of the first injection. If delivery of the baby does not occur 12 weeks after the administration of the standard antepartum dose (at 26 to 28 weeks), a second dose is recommended to maximize protection antepartum. If delivery occurs within three weeks after the last antepartum dose, the postpartum dose may be withheld, but a test for FMH should be performed to determine if exposure to > 15 mL of red blood cells has occurred.2

Administration

Administer injection per standard protocol.
Note: When administering an intramuscular injection, place fingers in contact with syringe barrel through windows in shield to prevent possible premature activation of safety guard.

	Slide safety guard over needle.
	After injection, use free hand to slide safety guard over needle. An audible "click" indicates proper activation. Keep hands behind needle at all times. Dispose of the syringe in accordance with local regulations.

Dosage Forms and Strengths

• RhoGAM® Ultra-Filtered PLUS - 300 μg (1500 IU)1 – Prefilled Syringes


• MICRhoGAM® Ultra-Filtered PLUS - 50 μg (250 IU)1 – Prefilled Syringes

1

The anti-D content of RhoGAM / MICRhoGAM is expressed as μg per dose or as International Units (IU) per dose. The conversion factor is 1 μg = 5 IU.8

Contraindications

The use of RhoGAM and MICRhoGAM is contraindicated in Rh-positive individuals.

Warnings and Precautions

Warnings

• For intramuscular use only, do not inject intravenously.


• In the case of postpartum use, the product is intended for maternal administration.


• Do not inject the newborn infant.


• Patients should be observed for at least 20 minutes after administration.


• Administer with caution to patients who have had prior severe systemic allergic reactions to human immune globulin.


• RhoGAM / MICRhoGAM contain a small quantity og IgA. There is a potential risk of hypersensitivity in IgA deficient individuals.


• Patients treated for Rh-incompatible transfusion should be monitored by clinical and laboratory means for signs and symptoms of a hemolytic reaction.


• Store at 2 to 8°C. Do not store frozen.


• Do not use after the expiration date printed on the syringe.

Use of Plasma Derived Products

RhoGAM and MICRhoGAM are made from human plasma and may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically the Creutzfeldt-Jakob disease (CJD) agent. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing plasma for the presence of certain current virus infections and by using pathogen removal and inactivation techniques during the manufacturing process. All of the above steps are designed to increase product safety by reducing the risk of pathogen transmission. Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products. All infections thought by a physician possibly to have been transmitted by these products should be reported by the physician or other healthcare provider in the United States to Ortho-Clinical Diagnostics, Inc. at 1-800-421-3311. Outside the United States, the company distributing these products should be contacted. The physician should discuss the risks and benefits of these products with the patient.

Laboratory Tests

Recovery of anti-D in plasma or serum after injection of RhoGAM or other Rho(D) Immune Globulin (Human) products is highly variable among individuals. Anti-D detection in a patient's plasma is dependent on assay sensitivity and time of sample collection post-injection. Currently there are no requirements or practice standards to test for the presence of anti-D in order to determine adequacy or efficacy of dose following an injection of RhoGAM.

The presence of passively acquired anti-D in the maternal serum may cause a positive antibody screening test. This does not preclude further antepartum or postpartum prophylaxis.

Some babies born to women given Rho(D) Immune Globulin (Human) antepartum have weakly positive direct antiglobulin (Coombs) tests at birth.

Fetal-maternal hemorrhage may cause false blood typing results in the mother. Late in pregnancy or following delivery, there may be sufficient fetal Rh-positive red blood cells in the circulation of the Rh-negative mother to cause a positive antiglobulin test for weak D (Du). In this instance if there is any doubt as to the patient's Rh type, RhoGAM or MICRhoGAM should be administered.9

Adverse Reactions

Adverse events (AE) after administration of RhoGAM and MICRhoGAM are rare.

The most frequently reported AEs are anti-D formation and injection site reactions, such as swelling, induration, redness and mild pain or warmth. Possible systemic reactions are skin rash, body aches or a slight elevation in temperature. Severe systemic allergic reactions are extremely rare. Patients should be observed for at least 20 minutes after administration. There have been no reported fatalities due to anaphylaxis or any other cause related to RhoGAM or MICRhoGAM administration.

As with any Rho(D) Immune Globulin (Human), administration to patients who are Rh-positive or have received Rh-positive red blood cells may result in signs and symptoms of a hemolytic reaction, including fever, back pain, nausea and vomiting, hypo- or hypertension, hemoglobinuria/emia, elevated bilirubin and creatinine and decreased haptoglobin.

RhoGAM and MICRhoGAM contain a small quantity of IgA (less than 15 μg per dose).10 Although high doses of intravenous immune globulin containing IgA at levels of 270-720 μg/mL have been given without incident during treatment of patients with high-titered antibodies to IgA,11 the attending physician must weigh the benefit against the potential risks of hypersensitivity reactions.

Drug Interactions

Immune globulin preparations including Rho(D) Immune Globulin (Human) may impair the efficacy of live vaccines such as measles, mumps and varicella. Administration of live vaccines should generally be delayed until 12 weeks after the final dose of immune globulin. If an immune globulin is administered within 14 days after administration of a live vaccine, the immune response to the vaccination may be inhibited.12

Because of the importance of rubella immunity among women of childbearing age, the postpartum vaccination of rubella-susceptible women with rubella or MMR vaccine should not be delayed because of the receipt of Rho(D) Immune Globulin (Human) during the last trimester of pregnancy or at delivery. Vaccination should occur immediately after delivery and if possible, testing should be performed after 3 or more months to ensure immunity to rubella and if necessary, to measles.12

USE IN SPECIFIC POPULATIONS

Pregnancy

Pregnancy Category C

Animal reproduction studies have not been conducted with RhoGAM or MICRhoGAM. The available evidence suggests that Rho(D) Immune Globulin (Human) does not harm the fetus or affect future pregnancies or the reproduction capacity of the maternal recipient.13,14

Rh Blood Type

RhoGAM or MICRhoGAM Rho(D) Immune Globulin (Human) should only be administered to Rh-negative patients exposed or potentially exposed to Rh-positive red blood cells to prevent Rh immunization.

Overdosage

Repeated administration or increased dosage in Rh-negative individuals should not cause more severe or more frequent adverse reactions than the normal dose. Patients who receive RhoGAM or MICRhoGAM for Rh-incompatible transfusion should be monitored by clinical and laboratory means due to the risk of a hemolytic reaction.

RhoGAM Ultra-Filtered PLUS Description

RhoGAM and MICRhoGAM Rho(D) Immune Globulin (Human) are sterile solutions containing immunoglobulin G (IgG) anti-D (anti-Rh) for use in preventing Rh immunization. They are manufactured from human plasma containing anti-D. A single dose of RhoGAM contains sufficient anti-D (300 μg or 1500 IU) to suppress the immune response to up to 15 mL of Rh-positive red blood cells.4,15 A single dose of MICRhoGAM contains sufficient anti-D (50 μg or 250 IU) to suppress the immune response to up to 2.5 mL of Rh-positive red blood cells. The anti-D dose is measured by comparison to the RhoGAM in-house reference standard, the potency of which is established relative to the U.S./World Health Organization/European Pharmacopoeia Standard Anti-D Immunoglobulin Rho(D) Immune Globulin (Human) CBER Lot 4: NIBSC Lot 01/572 (285 IU/ampoule).16

Plasma for RhoGAM is typically sourced from a donor center owned and operated by Ortho-Clinical Diagnostics. All donors are carefully screened by history and laboratory testing to reduce the risk of transmitting blood-borne pathogens from infected donors. Each plasma donation is tested and found to be non-reactive for the presence of hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C (HCV) and human immunodeficiency viruses (HIV) 1 and 2. Additionally, plasma is tested by FDA licensed Nucleic Acid Testing (NAT) for HCV and HIV-1 and the results must be negative. Plasma is also tested by investigational NAT for hepatitis B (HBV) and must be non-reactive. However, the significance of a negative result has not been established. Plasma is tested by in-process NAT procedures for hepatitis A virus (HAV) and parvovirus B19 (B19) in a minipool format. Only plasma that has passed virus screening is used for production. The procedure for B19 detects all three genotypes based upon sequence alignment of known virus isolates. The limit of B19 DNA in the manufacturing pool is set not to exceed 104 IU per mL.

Fractionation of the plasma is performed by a modification of the cold alcohol procedure that has been shown to significantly lower viral titers.10 Following plasma fractionation, a viral clearance filtration step and a viral inactivation step are performed. The viral filtration step removes viruses via a size-exclusion mechanism utilizing a patented Viresolve 180 ultrafiltration membrane with defined pore-size distribution of 12-18 nanometers to remove enveloped and non-enveloped viruses. Following viral filtration, quality control tests (CorrTest and diffusion test) are performed on the Viresolve 180 ultrafiltration membrane to insure filter integrity.17 The viral inactivation step utilizes Triton X-100 and tri-n-butyl phosphate (TNBP) to inactivate enveloped viruses such as HCV, HIV and West Nile Virus (WNV)10,18 (Patent Pending).

The donor selection process, the fractionation process, the viral filtration step and the viral inactivation process increase product safety by reducing the risk of transmission of enveloped and non-enveloped viruses. Rho(D) Immune Globulin (Human) intended for intramuscular use and prepared by cold alcohol fractionation has not been shown to transmit hepatitis or other infectious diseases.19 There have been no documented cases of infectious disease transmission by RhoGAM or MICRhoGAM.

Laboratory spiking studies10,20 have shown that the cumulative viral removal and inactivation capability of the RhoGAM / MICRhoGAM manufacturing process is as follows:

Virus	HIV	BVDV	PRV	PPV	EMC	WNV	HAV
Units = log10 reduction HIV Human Immunodeficiency Virus, Model for HIV-1 and 2 and Human T-cell Lymphotropic Virus (HTLV) 1 and 2 BVDV Bovine Viral Diarrhea Virus, Model for Hepatitis C Virus PRV Pseudorabies Virus, Model for Herpes Viruses PPV Porcine Parvovirus, Model for Parvovirus B19 EMC Encephalomyocarditis Virus, Model for Hepatitis A Virus WNV West Nile Virus HAV Hepatitis A Virus ND Not Determined N/A Not Applicable
Lipid Enveloped	Yes	Yes	Yes	No	No	Yes	No
Size (nm)	80-120	40-70	120-200	18-24	25-30	40-60	27-32
Genome	SS-RNA	SS-RNA	DS-DNA	SS-DNA	SS-RNA	SS-RNA	SS-RNA
Fractionation	≥ 7.98	7.29	≥ 11.74	8.30	ND	ND	ND
Viral Filtration	≥ 5.60	5.40	≥ 6.20	3.30	4.16	ND	≥ 5.07
Viral Inactivation	≥ 4.28	≥ 4.90	≥ 5.58	N/A	N/A	≥ 7.05	N/A
Total Viral Reduction	≥ 17.86	≥ 17.59	≥ 23.52	11.60	4.16	≥ 7.05	≥ 5.07

The safety of Rho(D) Immune Globulin (Human) has been further shown in an empirical study of viral marker rates in female blood donors in the United States.21 This study revealed that Rh-negative donors, of whom an estimated 55-60% had received Rho(D) Immune Globulin (Human) for pregnancy-related indications, had prevalence and incidence viral marker rates similar to those of Rh-positive female donors who had not received Rho(D) Immune Globulin (Human).

The final product contains 5 ± 1% IgG, 2.9 mg/mL sodium chloride, 0.01% Polysorbate 80 (non-animal derived) and 15 mg/mL glycine. Small amounts of IgA, typically less than 15 μg per dose, are present.10 The pH range is 6.20 - 6.55 and IgG purity is ≥ 98%. The product contains no added human serum albumin (HSA), no thimerosal or other preservatives and utilizes a latex-free delivery system.

RhoGAM Ultra-Filtered PLUS and MICRhoGAM Ultra-Filtered PLUS are manufactured and distributed by Ortho-Clinical Diagnostics, Inc., Raritan, NJ 08869.

RhoGAM Ultra-Filtered PLUS - Clinical Pharmacology

Mechanism of Action

RhoGAM and MICRhoGAM act by suppressing the immune response of Rh-negative individuals to Rh-positive red blood cells. The mechanism of action is unknown. RhoGAM, MICRhoGAM and other Rho(D) Immune Globulin (Human) products are not effective in altering the course or consequences of Rh immunization once it has occurred.

Pharmacokinetic Properties

Pharmacokinetic studies after intramuscular injection were performed on sixteen Rh-negative subjects receiving a single dose of (368 μg or 1840 IU) RhoGAM.10 Plasma anti-D levels were monitored for thirteen weeks using a validated Automated Quantitative Hemagglutination method with sensitivity of approximately 1 ng/mL. The following mean pharmacokinetic parameters were obtained from data collected over the first ten weeks of a thirteen-week study:

Parameter	Mean	SD	Units
Maximum plasma concentration obtained (Cmax)	54.0	13.0	ng/mL
Time to attain Cmax (Tmax)	4		days
Elimination half-life (T1/2)	30.9	13.8	days
Volume of distribution (Vd)	7.3	1.5	liters
Clearance (CL)	150.4	53.3	mL/day

Obstetrical Use

The Rh-negative obstetrical patient may be exposed to red blood cells from her Rh-positive fetus during the normal course of pregnancy or after obstetrical procedures or abdominal trauma.

Use after Rh-Incompatible Transfusion

An Rh-negative individual transfused with one unit of Rh-positive red blood cells has about an 80% likelihood of producing anti-D.4 However, Rh immunization can occur after exposure to < 1 mL of Rh-positive red blood cells. Protection from Rh immunization is accomplished by administering ≥ 20 μg of RhoGAM or MICRhoGAM per mL of Rh-positive red blood cells within 72 hours of transfusion of incompatible red blood cells.13,22

Clinical Studies

Rho(D) Immune Globulin (Human) administered at 28 weeks, as well as within 72 hours of delivery, has been shown to reduce the Rh immunization rate to about 0.1-0.2%.23,24 Clinical studies demonstrated that administration of MICRhoGAM within three hours following pregnancy termination was 100% effective in preventing Rh immunization.25

Multiple studies have been performed that prove the safety and efficacy of RhoGAM in both the obstetrical and post transfusion settings.

Freda, Gorman and colleagues26, 27 studied the efficacy of RhoGAM in the postpartum setting in a randomized, controlled study completed in 1967. The control group received no immunoglobulin therapy after delivery, while the test group received 300 μg of RhoGAM intramuscularly within 72 hours of delivery of an Rh-positive infant. Six months after delivery, the incidence of Rh immunization in the control group was 6.4% (32/499) versus 0.13% (1/781) in the RhoGAM group (p < 0.001).

Pollack et al. performed two randomized, placebo-controlled studies in the post transfusion setting that were designed to establish the dose response relationship of RhoGAM. In the first study,15 178 (176 males, 2 females) Rh-negative volunteers received varying volumes of Rh- positive red cells; 92 subjects then received RhoGAM. A single dose of RhoGAM (1.1 mL @ 267 μg/mL) was shown to suppress anti-D formation after injection of up to 15.1 mL of Rh-positive red cells. In a companion study,4 Pollack administered 500 mL of Rh-positive whole blood to 44 Rh-negative male volunteers. Twenty-two (22) subjects received 20 μg RhoGAM per mL of Rh-positive red cells and 22 received no RhoGAM. None of the RhoGAM-treated subjects developed anti-D; 18/22 control arm subjects developed anti-D (p < 0.0001).

Human clinical studies10 were subsequently performed to prove the efficacy of MICRhoGAM and the low protein (5%) formulations. In the MICRhoGAM study, 81 Rh-negative male volunteers received an initial injection of 2.5 mL Rh-positive red cells, followed by a booster injection (0.1 mL) of red cells at 26 weeks; 40 subjects received an injection of MICRhoGAM after the initial red cell injection. None of the subjects who received MICRhoGAM developed anti-D, both before and after the booster red cell injection. A similar study was performed in 1985 using the low protein formulation of RhoGAM. None of the 30 Rh-negative male volunteers who received RhoGAM after injection of 15 mL of Rh-positive red cells developed anti-D.

REFERENCES

 1

Samson D, Mollison PL. Effect on primary Rh immunization of delayed administration of anti-Rh. Immunol 1975;28:349-57.

 2

Garratty G, ed. Hemolytic disease of the newborn. Arlington, VA: American Association of Blood Banks, 1984:78.

 3

Urbaniak SJ. Statement from the Consensus Conference on Anti-D Prophylaxis, The Royal College of Physicians of Edinburgh & The Royal College of Obstetricians and Gynaecologists, UK. Vox Sang 1998;74:127-28.

 4

Pollack W, Ascari WQ, Crispen JF, O'Connor RR, Ho TY. Studies on Rh prophylaxis. II. Rh immune prophylaxis after transfusion with Rh-positive blood. Transfusion 1971;11:340-44.

 5

Bayliss KM, Kueck DB, Johnson ST, Fueger JT, McFadden PW, Mikulski D, Gottschall JL. Detecting fetomaternal hemorrhage: a comparison of five methods. Transfusion 1991;31:303-7.

 6

Kumpel BM. Quantification of anti-D and fetomaternal hemorrhage by flow cytometry (editorial). Transfusion 2000;40:6-9.

 7

AABB Technical Manual. 15th ed. Bethesda, Maryland: AABB, 2005.

 8

HH, Bowell PJ, Kirkwood TBL. Collaborative study to recalibrate the International Reference Preparation of anti-D immunoglobulin. J Clin Pathol 1980;33:249-53.

 9

ACOG practice bulletin. Prevention of Rh D alloimmunization. Number 4, May 1999 (replaces educational bulletin Number 147, October 1990). Clinical management guidelines for obstetrician-gynecologists. American College of Obstetrics and Gynecology. Int J Gynaecol Obstet. 1999; 66(1):63-70.

10

Data on file at Ortho-Clinical Diagnostics, Inc.

11

Cunningham-Rundles C, Zhuo Z, Mankarious S, Courter S. Long-term use of IgA-depleted intravenous immunoglobulin in immunodeficient subjects with anti-IgA antibodies. J Clin Immunol 1993;13:272-78.

12

Centers for Disease Control and Prevention. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices and the American Academy of Family Physicians. MMWR 2002;51 (No. RR-2):6-7.

13

Zipursky A, Israels LG. The pathogenesis and prevention of Rh immunization. Can Med Assoc J 1967;97:1245-56.

14

Thornton JG, Page C, Foote G, Arthur GR, Tovey LAD, Scott JS. Efficacy and long term effects of antenatal prophylaxis with anti-D immunoglobulin. Brit Med J 1989;298:1671-73.

15

Pollack W, Ascari WQ, Kochesky RJ, O'Connor RR, Ho TY, Tripodi D. Studies on Rh prophylaxis. I. Relationship between doses of anti-Rh and size of antigenic stimulus. Transfusion 1971;11:333-39.

16

Thorpe SJ, Sands D, Fox B, Behr-Gross ME, Schaffner G, Yu MW. A global standard for anti-D immunoglobulin: international collaborative study to evaluate a candidate preparation. Vox Sang 2003;85:313-21.

17

Phillips MW, DiLeo AJ. A Validatible Porosimetric Technique for verifying the integrity of virus-retentive membranes. Biologicals 1996;24:243-53.

18

Horowitz B, Wiebe ME, Lippin A, Stryker MH. Inactivation of viruses in labile blood derivatives. I. Disruption of lipid-enveloped viruses by tri (n-butyl) phosphate detergent combinations. Transfusion 1985; 25(6):516-22.

19

Tabor E. The epidemiology of virus transmission by plasma derivatives: clinical studies verifying the lack of transmission of hepatitis B and C viruses and HIV type 1. Transfusion 1999;39:1160-68.

20

Van Holten RW, Ciavarella D, Oulundsen G, Harmon F, Riester S. Incorporation of an additional viral-clearance step into a human immunoglobulin manufacturing process. Vox Sang 2002;83:227-33.

21

Watanabe KK, Busch MP, Schreiber GB, Zuck TF. Evaluation of the safety of Rh Immunoglobulin by monitoring viral markers among Rh-negative female blood donors. Vox Sang 2000;8:1-6.

22

Crispen J. Immunosuppression of small quantities of Rh-positive blood with MICRhoGAM in Rh-negative male volunteers. In: Proceedings of a symposium on Rh antibody mediated immunosuppression. Raritan, NJ: Ortho Research Institute of Medical Sciences, 1975:51-54.

23

Bowman JM, Chown B, Lewis M, Pollock JM. Rh isoimmunization during pregnancy: antenatal prophylaxis. Can Med Assoc J 1978;118:623-27.

24

Bowman JM, Pollock JM. Antenatal prophylaxis of Rh isoimmunization: 28-weeks' gestation service program. Can Med Assoc J 1978;118:627-30.

25

Stewart FH, Burnhill MS, Bozorgi N. Reduced dose of Rh immunoglobulin following first trimester pregnancy termination. Obstet Gynecol 1978;51:318-22.

26

Pollack W, Gorman JG, Freda VJ, Ascari WQ, Allen AE, Baker WJ. Results of clinical trials of RhoGAM in women. Transfusion 1968;8:151-53.

27

Freda VJ, Gorman JG, Pollack W, Bowe E. Prevention of Rh hemolytic disease – ten years' clinical experience with Rh immune globulin. New Engl J Med 1975; 292:1014-16.

HOW SUPPLIED / STORAGE AND HANDLING

RhoGAM Ultra-Filtered PLUS package sizes

• 1 prefilled single-dose syringe of RhoGAM (Product Code 780501)
  
  NDC 0562-7805-01
  
  1 package insert, 1 control form, 1 patient identification card


• 5 prefilled single-dose syringes of RhoGAM (Product Code 780505)
  
  NDC 0562-7805-05
  
  5 package inserts, 5 control forms, 5 patient identification cards


• 25 prefilled single-dose syringes of RhoGAM (Product Code 780525)
  
  NDC 0562-7805-25
  
  25 package inserts, 25 control forms, 25 patient identification cards

MICRhoGAM Ultra-Filtered PLUS package sizes

• 1 prefilled single-dose syringe of MICRhoGAM (Product Code 780601)
  
  NDC 0562-7806-01
  
  1 package insert, 1 control form, 1 patient identification card


• 5 prefilled single-dose syringes of MICRhoGAM (Product Code 780605)
  
  NDC 0562-7806-05
  
  5 package inserts, 5 control forms, 5 patient identification cards


• 25 prefilled single-dose syringes of MICRhoGAM (Product Code 780625)
  
  NDC 0562-7806-25
  
  25 package inserts, 25 control forms, 25 patient identification cards

Store at 2 to 8°C. Do not store frozen. Do not use after the expiration date printed on the syringe.

Patient Counseling Information

As with all immune globulin preparations, the physician should discuss the risks and benefits with the patient. The most common adverse reactions are local reactions including swelling, induration, redness and mild pain at the site of injection, and a small number of patients have noted a slight elevation in temperature.

Systemic reactions to RhoGAM or MICRhoGAM are extremely rare, however allergic responses to RhoGAM or MICRhoGAM may occur. Patients should be observed for at least 20 minutes after administration. Patients should be informed of the early signs of hypersensitivity reactions including hives, generalized urticaria, tightness of the chest, wheezing, hypotension and anaphylaxis.

The physician should provide the patient with a completed RhoGAM Patient Identification Card and advise the patient to retain the card and present it to other health care providers when appropriate.

SUMMARY OF REVISIONS

Section	Revision
10 DESCRIPTION	Modified parvovirus and hepatitis A virus testing.

U.S. LICENSE 1236

Ortho-Clinical Diagnostics, Inc.

a Johnson&Johnson company

Raritan, New Jersey 08869

© OCD 2007

Printed in U.S.A.

Made by methods of

U.S. Pat. 6,096,872

Patent Pending

Revised February 2008

631203003

PATIENT IDENTIFICATION CARD

Name _____________________________________________________________________________________________________________

Address _____________________________________________________________________________________________________________

I AM Rh NEGATIVE. I have received a protective injection of RhoGAM® or MICRhoGAM® Rho(D) Immune Globulin (Human) Ultra-Filtered PLUS.

IMPORTANT: Anti-Rh antibody (also called anti-D) will be present in my blood for several weeks after the injection, and may be detectable by laboratory testing. The presence of this passive anti-Rh antibody does not disqualify me from receiving additional injections of RhoGAM or MICRhoGAM as indicated and prescribed by my physician.

©Ortho-Clinical Diagnostics, Inc. 2007

Rho(D) Immune Globulin (Human)

RhoGAM® and MICRhoGAM®

Ultra-Filtered PLUS

This 3-part form contains:

• Directions for Use


• Patient Control Form


• Patient Identification Card

U.S. LICENSE 1236

Ortho-Clinical Diagnostics, Inc.

a Johnson&Johnson company

Raritan, New Jersey 08869

631203003

Date of Injection of RhoGAM or MICRhoGAM

Principal Display Panel - 300 ug Carton

Rho(D) Immune Globulin (Human)

RhoGAM®

Ultra-Filtered PLUS – 300 µg Dose (1500 IU*)

Thimerosal-Free

*International Units

Do not store frozen

See Directions for Use

Package Contains:

• 1 prefilled syringe containing a
  
  single dose of RhoGAM


• 1 control form


• 1 package insert


• 1 patient identification card

1 single dose

Active Ingredients

Anti-D Rho Immune Globulin (300 µg), the potency of

which is determined relative to the US/WHO/EP Standard

Anti-D Immunoglobulin Rho(D) Immune Globulin (Human)

CBER Lot 4: NIBSC Lot 01/572 (285 IU/ampoule)

Inactive ingredients

2.9 mg/mL sodium chloride

0.01% polysorbate 80

15 mg/mL glycine

ORTHO

Product Code

780501

Principal Display Panel - 50 µg Carton

Rho(D) Immune Globulin (Human)

MICRhoGAM®

Ultra-Filtered PLUS – 50 µg Dose (250 IU*)

Thimerosal-Free

*International Units

Do not store frozen

See Directions for Use

Package Contains:

• 1 prefilled syringe containing a
  
  single dose of MICRhoGAM


• 1 control form


• 1 package insert


• 1 patient identification card

1 single dose

Active Ingredients

Anti-D Rho Immune Globulin (50 µg), the potency of

which is determined relative to the US/WHO/EP Standard

Anti-D Immunoglobulin Rho(D) Immune Globulin (Human)

CBER Lot 4: NIBSC Lot 01/572 (285 IU/ampoule)

Inactive ingredients

2.9 mg/mL sodium chloride

0.01% polysorbate 80

15 mg/mL glycine

ORTHO

Product Code

780601

RhoGAM Ultra-Filtered PLUS  human rho(d) immune globulin  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0562-7805 Route of Administration INTRAMUSCULAR DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength HUMAN RHO(D) IMMUNE GLOBULIN (HUMAN IMMUNOGLOBULIN G) HUMAN RHO(D) IMMUNE GLOBULIN 300 ug

Inactive Ingredients Ingredient Name Strength SODIUM CHLORIDE   GLYCINE   POLYSORBATE 80

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0562-7805-01 1 POUCH In 1 CARTON contains a POUCH 1 1 SYRINGE In 1 POUCH This package is contained within the CARTON (0562-7805-01) 2 0562-7805-05 5 POUCH In 1 CARTON contains a POUCH 2 1 SYRINGE In 1 POUCH This package is contained within the CARTON (0562-7805-05) 3 0562-7805-25 25 POUCH In 1 CARTON contains a POUCH 3 1 SYRINGE In 1 POUCH This package is contained within the CARTON (0562-7805-25)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
BLA	BLA103777	03/09/2007

MICRhoGAM Ultra-Filtered PLUS  human rho(d) immune globulin  i

Danium

Danium may be available in the countries listed below.

Ingredient matches for Danium

Calcium Dobesilate

Calcium Dobesilate is reported as an ingredient of Danium in the following countries:

• Czech Republic


• Slovakia

Clobazam

Clobazam is reported as an ingredient of Danium in the following countries:

• Bangladesh

International Drug Name Search

Pro Vit A

Pro Vit A may be available in the countries listed below.

In some countries, this medicine may only be approved for veterinary use.

Ingredient matches for Pro Vit A

Retinol

Retinol is reported as an ingredient of Pro Vit A in the following countries:

• South Africa

Tocopherol, α-

Tocopherol, α- is reported as an ingredient of Pro Vit A in the following countries:

• South Africa

International Drug Name Search

Lorazepam Induquimica

Lorazepam Induquimica may be available in the countries listed below.

Ingredient matches for Lorazepam Induquimica

Lorazepam

Lorazepam is reported as an ingredient of Lorazepam Induquimica in the following countries:

• Peru

International Drug Name Search

Oprelvekin

Pronunciation: oh-PREL-ve-kin
Generic Name: Oprelvekin
Brand Name: Neumega

Oprelvekin may cause allergic reactions, including severe allergic reactions. Do not use any more of Oprelvekin and seek immediate medical help if you develop symptoms of an allergic reaction, such as rash; hives; itching; trouble breathing; tightness in your chest; or swelling of the mouth, face, lips, or tongue.

Oprelvekin is used for:

Prevention of severe reductions in the number of blood clotting cells (platelets) caused by some chemotherapy. It may also be used for other conditions as determined by your doctor.

Oprelvekin is an interleukin. It works by stimulating certain body chemicals to produce platelets that function normally and have a normal life span.

Do NOT use Oprelvekin if:

• you are allergic to any ingredient in Oprelvekin

Contact your doctor or health care provider right away if any of these apply to you.

Before using Oprelvekin:

Some medical conditions may interact with Oprelvekin. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have a history of leukemia, multiple myeloma (disease of the bone marrow), bone marrow transplant, brain tumors, or other tumors involving the central nervous system


• if you consume 3 or more alcohol-containing beverages a day


• if you have a history of irregular heart rhythm, high blood pressure, stroke, congestive heart failure, other heart disease, or lung problems


• if you have kidney problems, are taking diuretics ("water pills") to decrease the amount of fluid in your body, have a history of fluid retention, or have low potassium levels in your blood


• if you have a history of swelling of the eye or have an eye disease (eg, papilledema)

Some MEDICINES MAY INTERACT with Oprelvekin. However, no specific interactions with Oprelvekin are known at this time.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Oprelvekin may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Oprelvekin:

Use Oprelvekin as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Oprelvekin comes with an additional patient leaflet. Read it carefully and reread it each time you get Oprelvekin refilled.


• Oprelvekin is usually administered as an injection at your doctor's office, hospital, or clinic. If you are using Oprelvekin at home, carefully follow the injection procedures taught to you by your health care provider.


• If Oprelvekin contains particles or is discolored, or if the vial is cracked or damaged in any way, do not use it.


• Oprelvekin should be injected in the stomach, hip, or thigh. It may be injected into the upper arm if it is given by another qualified individual. Oprelvekin must be injected under the skin not in the muscle.


• When drawing a dose into a syringe, be sure to follow the procedure demonstrated to you to prevent contamination of the vial, syringe, or medicine. Never touch the rubber stopper of the vial or needle of the syringe with your fingers.


• Carefully check that you have drawn the correct dose before administration.


• Do not shake Oprelvekin.


• Oprelvekin works best if it is taken at the same time each day.


• Continue using Oprelvekin for the full course of treatment even if you feel better in a few days.


• You should stop using Oprelvekin at least 2 days before starting the next planned cycle of cancer chemotherapy.


• Keep this product, as well as syringes and needles, out of the reach of children. Do not reuse needles, syringes, or other materials. Dispose of properly after use. Ask your doctor, nurse, or pharmacist to explain local regulations for proper disposal.


• If you miss a dose of Oprelvekin, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once. If more than one dose is missed, contact your doctor or pharmacist.

Ask your health care provider any questions you may have about how to use Oprelvekin.

Important safety information:

• Oprelvekin may cause dizziness or fainting. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Oprelvekin. Using Oprelvekin alone, with certain other medicines, or with alcohol may lessen your ability to drive or to perform other potentially dangerous tasks.


• Serious eye problems (papilledema) may occur more often in children.


• Contact your health care provider if shortness of breath or irregular heartbeat occurs or worsens while using Oprelvekin.


• LAB TESTS, including complete blood cell count, platelet count, and electrolyte levels, may be performed to monitor your progress or to check for side effects. Be sure to keep all doctor and lab appointments.


• Use Oprelvekin with extreme caution in CHILDREN younger than 12 years of age. Safety and effectiveness in this age group have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, discuss with your doctor the benefits and risks of using Oprelvekin during pregnancy. It is unknown if Oprelvekin is excreted in breast milk. Do not breast-feed while taking Oprelvekin.

Possible side effects of Oprelvekin:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Chills; constipation; cough; diarrhea; dizziness; fever; flushing; hair loss; headache; increased cough; indigestion; inflammation or sores of the mouth or lips; joint pain; loss of appetite; mild swelling of the arms and legs; muscle pain; nausea; nervousness; pain; runny nose; shortness of breath when moving; sleeplessness; sore throat; stomach pain; vomiting; weakness.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); eye infection; eye pain; fainting; heart flutter; irregular or fast heartbeat; pain, redness, or swelling at the injection site; pounding in the chest; severe headache, dizziness, or one-sided weakness; unusual bruising; unusual or severe swelling; vision changes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Oprelvekin side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include continuing irregular or fast heartbeat.

Proper storage of Oprelvekin:

Store powder and the dilution solution in the refrigerator, between 36 and 46 degrees F (2 and 8 degrees C). Protect from light. Do not freeze. Mixed solution must be used within 3 hours and be stored in the vial at 36 to 46 degrees F (2 and 8 degrees C) or at room temperature, up to 77 degrees F (25 degrees C). Do not freeze or shake Oprelvekin after it is mixed. Do not store in the bathroom. Keep Oprelvekin out of the reach of children and away from pets.

General information:

• If you have any questions about Oprelvekin, please talk with your doctor, pharmacist, or other health care provider.


• Oprelvekin is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Oprelvekin. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Oprelvekin resources

• Oprelvekin Side Effects (in more detail)
• Oprelvekin Use in Pregnancy & Breastfeeding
• Oprelvekin Drug Interactions
• Oprelvekin Support Group
• 0 Reviews for Oprelvekin - Add your own review/rating

• Oprelvekin Monograph (AHFS DI)


• Oprelvekin Professional Patient Advice (Wolters Kluwer)


• oprelvekin injectable Concise Consumer Information (Cerner Multum)


• oprelvekin Subcutaneous Advanced Consumer (Micromedex) - Includes Dosage Information


• Neumega Prescribing Information (FDA)

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