P&T News: March 1997
Joan M. Murhammer, R.Ph., Clinical Pharmacist
Peer Review Status: Internally Peer Reviewed by Ellen A.
Link, M.D., Clinical Assistant Professor, Department of Pediatrics
and Jody R. Murph, M.D., Associate Professor, Department of
Pediatrics
Polio Vaccine
The recommendations for routine immunization of children against
polio has changed because wild-virus-associated polio has been
eliminated from the Western Hemisphere, as well as a reduced threat
of poliovirus importation into the United States due to progress in
world polio eradication efforts. The last reported case of
indigenously acquired poliomyelitis in the U.S. caused by wild
poliovirus was in 1979.3 Since that time, an average of eight to nine
cases of vaccine-associated paralytic poliomyelitis (VAPP) have been
reported annually in the U.S. from the live-attenuated oral polio
vaccine (OPV), and VAPP has been the only indigenous paralytic
polio.3 Unless polio is eliminated entirely from the world (like
smallpox), the need for vaccination against polio will continue.
Therefore, a new polio vaccination policy placing a greater reliance
on the inactivated polio vaccine (IPV) to reduce the incidence of
VAPP has been recommended.1
OPV is a trivalent, live-attenuated vaccine. OPV induces intestinal immunity against poliovirus reinfection, explaining its effectiveness in controlling wild-virus circulation. OPV persists in the pharynx for one to two weeks and is excreted in the feces for several weeks after administration; therefore, the vaccine virus can be transmitted to contacts and results in their immunization. In rare cases, VAPP can occur in these contacts as well as those vaccinated.3 In addition to intestinal immunity, advantages of OPV are ease of administration and lower costs compared to IPV.2 The only well documented adverse effect associated with OPV is VAPP, which occurs in approximately one case per 750,000 children receiving their first dose of OPV.3 The risk of acquiring VAPP is substantially lower with subsequent doses for both recipients and contacts.2
IPV has three types of polio virus which are completely inactivated with formaldehyde. VAPP is not associated with IPV use. Enhanced-potency IPV has been available since the late 1980s and results in high titers to the three poliovirus types in 99 to 100% of recipients after three doses.3 Mucosal immunity is induced by enhanced-potency IPV, but to a lesser extent than with OPV. IPV has the additional disadvantages of requiring additional injections and being more costly than OPV. No serious adverse effects have been associated with the use of the currently available IPV.2
The revised vaccination schedule now recommends the sequential immunization (see Table 1 and Table 2).1,2 The rationale for the sequential schedule is that two doses of IPV induce sufficient humoral immunity m most recipients to prevent development of VAPP from subsequent administration of OPV.3 The OPV will then induce optimal intestinal immunity as well as sustain humoral immunity. Universal application of this sequential schedule would be expected to reduce the number of cases of VAPP by 50 to 75% per year.3 However, all three acceptable poliomyelitis vaccine schedules (sequential IPV/OPV, OPV-only, and IPV-only) are highly effective in protecting against poliomyelitis from wild-type polioviruses. Each regimen has advantages and disadvantages; depending on the patient, one may be preferred or recommended (see Table 3).3
Diphtheria, Tetanus, and Acellular-Pertussis (DTaP)
Vaccine
The whole-cell pertussis vaccine is effective in the prevention of
pertussis disease, but concerns about local and systemic reactions
have stimulated efforts to produce a less reactogenic vaccine.
Acellular-pertussis vaccines contain only the parts of the pertussis
bacteria thought to be important for immunity, while whole-cell
vaccines contain whole, killed bacteria and multiple antigens. The
protective efficacy of acellular-pertussis is similar to the expected
range for most whole-cell vaccines (70 to 90%).5 DTaP has been shown
to have significantly less frequent and less severe local reactions
(e.g., redness, swelling) and systemic reactions (e.g., fever,
drowsiness, irritability, or prolonged high-pitch crying) than those
associated with the whole-cell product.6
Since 1991, DTaP vaccines have been FDA approved for the fourth and fifth doses of the pertussis series in children aged 15 months up to seven years. Recent studies have demonstrated the efficacy of DTaP vaccines when administered as the primary immunization (initial three-dose series) in infancy.5,6 Based on these clinical studies, the FDA has approved three DTaP vaccines for use in infants starting at six weeks of age: Tripedia[R], Acel- Imune[R], and Infanrix[R].7-9
Because of the decreased frequency of side effects and high immunogenicity, DTaP is now recommended for all doses of the pertussis vaccination series.4 Diphtheria, tetanus, and whole-cell pertussis (DTP) remains an acceptable alternative. Children routinely receive a series of five doses of vaccine against diphtheria, tetanus, and pertussis disease before the age of seven years. As with the whole-cell DTP, the first three doses of DTaP are recommended at ages 2, 4, and 6 months; the fourth dose at 15 to 18 months; and the fifth dose at 4 to 6 years of age.' The fourth dose may be given as early as 12 months of age if six months have elapsed since the third dose. The fifth dose of DTaP is not necessary if the fourth dose was administered on or after the fourth birthday. Once children reach their seventh birthday, they should not be immunized against pertussis.
DTaP is also recommended for all remaining doses of the schedule in children who have started the vaccination series with one, two, three, or four doses of DTP.5 Whenever feasible, the same DTaP vaccine should be used throughout the entire vaccination series. No data are available on the safety, immunogenicity, or efficacy of different DTaP vaccines when administered interchangeably. However, if original product identity is unknown or not available, any DTaP vaccine may be used to complete the series. All three DTaP vaccines are considered safe, effective, and acceptable for pertussis immunization.22 Direct comparative studies among the vaccines have not been conducted; currently the ACIP states that all three vaccines are efficacious.22
Haemophilus b Conjugate and Hepatitis B Combination
Vaccine
A new combination product, Comvax[R], containing haemophilus b
conjugate (Hib) vaccine (Pedvax[R].-HIB] and hepatitis B vaccine was
approved by the FDA in October 1996. Comvax[R] is approved for the
immunization of infants at 2, 4, and 12 to 15 months of age,
constituting a complete series of Hib and hepatitis B vaccination.10
A dose at six months of age is not required for Pedvax[R]-HIB. For
complete protection against invasive Hib disease, infants should
receive the first dose of Hib vaccine at two months of age and should
complete the series by 12 to 15 months of age.1 If the series is
started late, the required number of doses of Hib vaccine depends on
the child's age at the start of vaccination. It is important to note
that three doses of hepatitis B vaccine are required regardless of
the child's age when they start the series.4 Infants born to
HBsAG-positive mothers, should not receive Comvax[R] at birth. They
should receive a passive-active regimen of hepatitis B immune
globulin and hepatitis B vaccine.10 Infants who have received a
previous dose of hepatitis B vaccine at birth may receive three doses
of Comvax[R] at 2, 4, and 12 to 15 months.10 Comvax[R]. should not be
administered to children less than six weeks old. The Hib component
administered at less than six weeks of age is not adequately
immunogenic and has the potential for suppression of the immune
response to Hib with subsequent doses administered at older ages.4
The primary advantage of Comvax[R] is that it may reduce the number
of injections required at a single visit.
Diphtheria, Tetanus, and Acellular-Pertussis and Haemophilus b
Conjugate (Hib) Combination Vaccine
A new combination vaccine (TriHIBIT[R]) containing DTaP and Hib was
approved by the FDA in September 1996. The Hib conjugate vaccine
powder is reconstituted with the DTaP component. TriHIBIT[R]. is only
FDA-labeled for the fourth dose of the childhood DTP/DTaP and Hib
series at 15 to 18 months of age.8,11 It is not currently licensed
for the primary three-dose series at 2, 4, and 6 months. The primary
series should consist of simultaneous administration of DTaP and Hib
vaccines given at different sites or the administration of the
combination vaccine DTP/Hib (Tetramune[R]). The primary advantage of
TriHIBIT[R] is that it will reduce the number of injections required
at 15 to 18 months.
Varicella Vaccine
Varicella-zoster virus (VZV) is the cause of chickenpox (primary
infection) and herpes zoster or shingles (secondary infection caused
by reactivation of latent VZV). Varicella is one of the most
contagious diseases.12 Eighty to 90% of exposed susceptible contacts
within households will develop varicella.12 About 3.9 million cases
of varicella are estimated to occur annually in the U.S., typically
in children under ten years of age. Most cases that occur in healthy
children are self-limited and free of complications.
Live-attenuated varicella vaccine was approved by the FDA in March 1995 for vaccination against varicella in individuals 12 months of age and older.13 The American Academy of Pediatrics recommends the routine use of varicella vaccine in children who do not have a history of varicella.12 It should be given as part of the routine immunization schedule at 12 to 18 months of age (see Table 1).1
Vaccination may be given at any time during childhood before the 13th birthday; after this age, natural varicella is more severe, complications more frequent, and two doses of vaccine are needed.14 Patients 13 years of age and older who have not been immunized previously and have no history of varicella infection should be immunized against varicella by administration of two doses of vaccine four to eight weeks apart. 13
A single dose of vaccine results in seroconversion rates of over 95% in children 12 months to 12 years of age. 12 Adolescents over the age of 12 years and adults have shown an age-related decrease in the ability of the immune system to mount and maintain a primary response to the vaccine. After two doses of vaccine, seroconversion rates of 94% have been reported.12 Long-term immunity to varicella may wane after vaccination; however, no evidence of loss of immunity has been noted in the six to ten years of follow-up of healthy children. It is unknown if booster doses may be needed.12,14
Universal vaccination in early childhood and immunization in susceptible older children and adolescents are recommended based on the frequency of serious complications and deaths after infection with wild varicella, the excess cost to the family and society, and the efficacy and safety of the varicella vaccine. 12
Hepatitis A Vaccine
Hepatitis A vaccines (Havrix[R] and Vaqta[R]) have been FDA approved
since February 1995 and March 1996, respectively.15,16 Hepatitis A
vaccine is approved for the active immunization of persons two years
of age and older against hepatitis A virus (HAV)15,16 It is not
currently part of the recommended childhood vaccination schedule.'
Before hepatitis A vaccines were available, the primary methods used
for prevention of hepatitis A were passive immunization with immune
globulin (IG) to provide short-term preexposure or postexposure
protection and hygienic measures. 17
HAV infection is acquired primarily by the fecal-oral route by either person-to-person contact or ingestion of contaminated food or water. 17 In the U.S. during the past several decades, a decline in the overall incidence of hepatitis A has occurred primarily as a result of better hygienic and sanitary conditions.18 However, high rates of disease among many segments of the U.S. population and the continued occurrence of extensive community outbreaks indicate that hepatitis A remains a major public health problem.17 The CDC estimates that 80,000 cases and 134,000 infections occurred in 1994. 17 The highest rates of hepatitis A are among children five to 14 years of age. 17 Many more children presumably have unrecognized, asymptomatic infection and can be a source of infection for others.
Hepatitis A immunization is likely to substantially lower the incidence of disease because HAV does not produce a chronic infection, and humans are the only natural reservoir of the virus.18 Hepatitis A vaccines have been shown to be highly immunogenic. Ninety-five to 100% of children had protective levels of anti-HAV one month after the first dose of either vaccine.15,16 A booster dose is recommended to provide long-term immunity. Havrix[R] and Vaqta[R] have different dosage strengths and dosage schedules (see Table 2). They should not be used interchangeably for hepatitis A vaccination.15,16
Until hepatitis A vaccine is licensed for use among children less than two years of age, the interim strategy to prevent and control hepatitis A should focus on preexposure vaccination of the following patient populations: a) persons at increase risk for HAV infection or its consequences (e.g., travelers and persons who have chronic liver disease); b) children living in communities that have high rates of hepatitis A to help prevent recurrent epidemics; and, if indicated, c) children and young adults in communities that have intermediate rates of hepatitis A to help control ongoing and prevent future epidemics.18 In addition, contacts of case-patients should be administered postexposure prophylaxis (i.e., immune globulin [IG] or, when appropriate, IG and hepatitis A vaccine)." A substantial reduction in the incidence of disease cannot be expected until hepatitis A vaccine is included in the routine childhood immunizations schedule and a sufficient number of children are vaccinated.
Summary
Vaccines have been very effective in reducing the incidence of
diseases such as measles, mumps, rubella, pertussis, tetanus
diphtheria, H. influenzae type b, poliomyelitis, and hepatitis B in
children.19,20 With the new recommendations for childhood
vaccination, a reduction in varicella infections will potentially be
achieved as well.12 The new polio vaccination guidelines will produce
fewer cases of VAPP associated with OPV.2 The use of DTaP for the
full pertussis series will provide a safer adverse effect profile
without compromising efficacy as compared to the whole-cell pertussis
vaccine.1 New combination products will enhance the efficacy of the
vaccination process by reducing the number of injections required per
visit and increasing compliance with the growing complexity of the
immunization schedules.1
Additional information on recommendations about the use of the vaccines including dosages, administration, contraindications, and precautions is available in the 1994 Red Book, the vaccine-specific ACIP statements, or the manufacturer's package inserts (see Table 2).
Table 3: Selection Criteria for Various Polio Regimens3
Sequential IPV/OPV Regimen
IPV-only Regimen
OPV-only Regimen
References
PHARMACY AND THERAPEUTICS SUBCOMMITTEE ACTIONS
DRUGS ADDED TO STOCK
ALPROSTADIL
Urethral Suppositories: 125 mcg, 250 mcg, S00 mcg, 1000 mcg
Alprostadil urethral suppositories (MUSE - Vivus) are indicated for
the management of erectile dysfunction.
BENAZEPRIL
Tablets: 5 mg, 10 mg, 20 mg, 40 mg Benazepril (Lotensin - Novartis)
is an angiotensin converting enzyme inhibitor indicated for the
treatment of hypertension.
DONEPEZIL
Tablets: 5 ma, 10 mg Donepezil (Aricept. - Eisai/Pfizer) is a
reversible inhibitor of acetylcholinesterase indicated for the
treatment of mild to moderate dementia of the Alzheimer's type. NOTE:
The prescribing of donepezil is restricted to the Department of
Neurology and the Division of Geriatrics.
FEXOFENADINE Capsules: 60 mg Fexofenadine (Allege. - Hoechst Marion Roussel) is a nonsedating antihistamine indicated for the relief of seasonal allergic rhinitis.
FLUTICASONE
Oral Inhaler: 44 mcg, 110 mcg, and 220 mcg per actuation; 13 g
canbter. Fluticasone oral inhaler (Flovent. - Glaxo Wellcome) is
indicated for the prophylactic maintenance treatment of asthma.
LORATADINE
Tableb: 10 mg Oral Syrup: 1 mg/ml Loratadine (Claritin. - Schering)
is a nonsedating antihistamine indicated for the management of the
symptoms of seasonal allergic rhinitis.
LORATADINE WITH PSEUDOEPHEDRINE Tablets: Loratadine 10 mg with Pseudoephedrine 240 mg Loratadine with pseudoephedrine (Claritin-D 24 hours. - Schering) is indicated for the management of the symptoms of seasonal allergic rhinitis.
PEGASPARGASE Injection: 7S0 unih per ml, S ml vial Pegaspargase (Oncaspar. - Rhone-Poulenc Rorer) is indicated for the treatment of acute Iymphoblastic leukemia in patients who have developed a hypersensitivity to l-asparaginase.
PERGOLIDE
Tablets: 0.05 ma, 0.25 ma, 1 mg Pergolide (Permax. - Athena) is
indicated as adjunctive treatment to levodopa/carbidopa in the
management of the signs and symptoms of Parkinson's disease.
ZIDOVUDINE Injection: 20 mg per ml, 20 ml vial Zidovudine injection (Retrovir. - Glaxo Wellcome) is part of a treatment regimen to prevent maternal-fetal HIV transmission.
ADDITIONAL ACTIONS
ALBUMIN S% INJECTION, 50 ml VIAL
A smaller size vial was added to stock to decrease the potential for
waste.
FOLIC ACID 0.4 mg TABLETS
This strength was added to stock due to the periodic unavailability
of the 1 mg tablets.
DRUGS DELETED FROM STOCK
ASPIRIN WITH CODEINE TABLETS (EMPIRIN #3) Discontinued due to low use. Individual components are available.
AURANOFIN CAPSULES (RIDAURA.) Discontinued due to low use. Aurothioglucose Injection is available.
CALCIUM LACTATE TABLETS Discontinued due to low use. Calcium Carbonate, Calcium Citrate, and Calcium Gluconate Tablets are available.
COLLAGEN, BOVINE CROSSLINKED INJECTION (ZYPLAST. IMPLANT) Discontinued due to low use. Collagen Bovine Injection (Zyderm2 11 Implant) is available.
COLLODION, FLEXIBLE TOPICAL Discontinued due to low use. Collodion Topical is available.
CYCLOSERINE CAPSULES (SEROMYCIN.) Discontinued due to low use. Ethambutol, Isoniazid, Pyrazinamide, and Rifampin are available.
DEXAMETHASONE 24 mg per ml INJECTION Discontinued due to comparatively high cost. Dexamethasone 4 mg per ml and 10 mg per ml injections are available.
DEXTROSE 10% INJECTION 3 ml AMPUL Discontinued due to low use. Dextrose 10% Injection 500 ml and 100 ml are available.
DL\ZOXIDE CAPSULES (PRoGLYCEM9 Discontinued due to low use. Diazoxide Oral Suspension is available.
DIETHYLS=LBESTEROL TABLETS Discontinued due to low use. Leuprolide and Goserelin Injections are available.
ENFLURANE INHALATION SOLUTION Discontinued due to low use. Desflurane, Halothane, and Isoflurane Inhalation Solutions are available.
FLUOXYMESTERONE 10 mg TABLETS (HALOTESTIN0) Discontinued due to low use. Fluoxymesterone 5 mg Tablets are available.
FOSINOPRIL TABLETS (MONOPRIL.) Discontinued due to the availability of benazopril, captopril, and enalapril.
HOMATROPINE 4% OPHTHALMIC SOLUTION Discontinued due to low use. Homatropine 2% Ophthalmic Solution is available.
MEPHENYTOIN TABLETS (MESANTOIN.) Discontinued due to low use. Phenytoin Capsules are available.
NYSTATIN TABLETS 500,000 UNITS Discontinued due to low use. Nystatin Oral Suspension is available.
PENICILLAMINE 12S mg CAPSULES Discontinued due to low use. Penicillamine 250 mg capsules are available.
PENICILLIN G PROCAINE INJECTION 600,000uniVml AND 1.2 MILLION uniV2 ml INJECTION Discontinued due to low use. Penicillin G Procaine Injection 2.4 million uniV4 ml is available.
PERITONEAL DIALYSIS SOLUTION - LOW CALCIUM (1.5% AND 2.5% DEXTROSE) Discontinued due to low use. Peritoneal Dialysis Solution (1.5%, 2.5%, and 4.25% Dextrose) is available.
PROCAINE INJECTION Discontinued due to low use. Lidocaine, Tetracaine, and Mepivacaine Injections are available.
PROCYCLIDINE TABLETS (KEMADRIN.) Discontinued due to low use. Benztropine Tablets are available.
SCARLET RED GAUZE Discontinued due to low use.
SODIUM SULFATE 4S% ORAL SOLUTION Discontinued due to low use. Magnesium Citrate Oral Solution is available.
TERFENADINE TABLETS (SELDANE.) Discontinued due to the availability of fexofenadine, cetirizine, and loratadine.
TERFENADINE WITH PSEUDOEPHEDRINE TABLETS (SELDANE -D.) Discontinued due to the availability of triprolidine with pseudoophedrine (Actifed.) and loratadine with pseudoephedri ne (C l arit in-D 24 Hour.) .
TETRACYCLINE ORAL SUSPENSION Discontinued due to low use. Tetracycline Oral Capsules are available.