Adacel TDAP and Milrinone Dextrose

• Generic Name: diphtheria toxoid / pertussis, acellular / tetanus toxoid
• Dosage Forms: injection, suspension
• Other Brand Names: Adacel, Boostrix

DTaP (Daptacel, Infanrix): Prevention of diphtheria, tetanus, and pertussis in infants and children 6 weeks through 6 years of age.

Tdap: Labeled by FDA for booster immunization against diphtheria, tetanus, and pertussis in adults and adolescents 10 through 64 years of age (Adacel) or adults and adolescents ≥10 years of age (Boostrix). Also recommended for use in children 7 through 10 years of age.

Diphtheria is caused by toxigenic strains of Corynebacterium diphtheriae or, rarely, C. ulcerans. Overall case-fatality rate is 5–10%; higher death rates (up to 20%) among individuals <5 years of age and >40 years of age. Diphtheria uncommon in US, but C. diphtheriae continues to circulate in US areas where the disease previously was endemic. Reported worldwide, particularly in tropical countries; endemic in many countries in Asia, the South Pacific, the Middle East, and Eastern Europe and in Haiti and Dominican Republic. Consult CDC Travelers' Health website for information regarding where diphtheria is endemic. During the 1920s (before widespread immunization against diphtheria was initiated), there were approximately 100,000–200,000 cases of diphtheria and 13,000–15,000 diphtheria-related deaths each year in US. Most diphtheria cases occur in individuals unvaccinated or incompletely vaccinated against diphtheria.

Tetanus is a potentially fatal disease caused by a neurotoxic exotoxin (tetanospasmin) produced by Clostridium tetani. C. tetani spores are ubiquitous in the environment worldwide; found in soil and in intestinal tracts of humans and animals (e.g., horses, sheep, cattle, dogs, cats, rats, guinea pigs, chickens). The spores can contaminate open wounds, especially puncture wounds or those with devitalized tissue; anaerobic wound conditions allow spores to germinate and produce exotoxins that disseminate through blood and lymphatic system. Neonatal tetanus (tetanus neonatorum) occurs in infants born under nonsterile conditions to inadequately vaccinated women; infection usually involves a contaminated umbilical stump and occurs because infant does not have passively acquired maternal antibodies against tetanus. Obstetric tetanus occurs within 6 weeks after delivery or termination of pregnancy because of contaminated wounds or abrasions or unclean deliveries or abortions. Generalized tetanus is characterized by rigidity and convulsive muscle spasms that usually involve the jaw (lockjaw) and neck and then become generalized. Tetanus occurs worldwide; reported most frequently in densely populated regions in hot, damp climates with soil rich in organic matter. Marked decrease in mortality from tetanus occurred in US from the early 1900s to the late 1940s when immunization against tetanus became part of routine childhood immunization. Average of 29 cases reported each year in US from 2001 through 2008 (case fatality rate 13%). Most US cases occur following an acute wound, usually a puncture or contaminated, infected, or devitalized wound. Almost all reported cases occur in individuals unvaccinated or inadequately vaccinated against the disease.

Pertussis (whooping cough) is an acute respiratory tract infection caused by Bordetella pertussis. Risk for severe pertussis and death highest among infants <1 year of age (especially those younger than 6 months of age). More than 1 million pertussis cases reported in US from 1940 through 1945 (average of 175,000 cases per year); incidence gradually declined in US after introduction of pertussis vaccine. Although average number of cases reported per year in US during 1980–1990 was 2900, pertussis incidence has been gradually increasing since early 1980s. During 2010, 27,550 pertussis cases and 27 pertussis-related deaths reported in US. B. pertussis infection in adults and adolescents may be asymptomatic or range from mild to severe. Adults and older siblings (including adolescents) with asymptomatic or mild pertussis are important sources of pertussis in unvaccinated or incompletely vaccinated infants and young children.

USPHS Advisory Committee on Immunization Practices (ACIP), AAP, and others recommend routine primary and booster immunization against diphtheria, tetanus, and pertussis in all individuals ≥6 weeks of age.

Combination preparation containing antigens for all 3 diseases (DTaP) preferred preparation for primary and booster immunization against these diseases in infants and children 6 weeks through 6 years of age, unless a component is contraindicated or should not be used.

ACIP, AAP, and others recommend that all adolescents who received primary immunization with DTaP, DTP (not commercially available in US), diphtheria and tetanus toxoids adsorbed (DT), or tetanus and diphtheria toxoids adsorbed (Td) receive a routine booster dose of Tdap (instead of Td) at 11 through 18 years of age (preferably at 11–12 years of age). If Tdap is unavailable or was administered previously, use Td for this adolescent booster dose.

Td usually preparation of choice for primary and booster immunization against diphtheria and tetanus in individuals ≥7 years of age. However, to reduce morbidity associated with pertussis, ACIP, AAP, and others recommend that a single dose of Tdap be used in place of a required primary or booster dose of Td in all adults, adolescents, and children 7 through 10 years of age who have not previously received Tdap, unless pertussis antigens contraindicated or should not be used. Use Td for all subsequent primary or booster doses.

ACIP recommends that all adults ≥65 years of age or older who have not previously received a dose of Tdap receive a single dose of Tdap, regardless of interval since last dose of vaccine containing tetanus or diphtheria toxoids. Use Td for all subsequent booster doses.

To ensure protection against pertussis, ACIP and others recommend that pregnant women receive a single dose of Tdap during each pregnancy (optimally between 27 and 36 weeks of gestation), regardless of prior vaccination history.

DTaP-IPV (Kinrix): Can be used in children 4 through 6 years of age to provide fifth dose of DTaP vaccination series and fourth dose of IPV vaccination series in those receiving primary immunization with Infanrix (DTaP) and/or Pediarix (DTaP-HepB-IPV) when there are no contraindications to any of the individual components.

DTaP-IPV (Quadracel): Can be used in children 4 through 6 years of age to provide fifth dose of DTaP vaccination series and fourth or fifth dose of IPV vaccination series in those receiving primary immunization with Pentacel (DTaP-IPV/Hib) and/or Daptacel (DTaP).

DTaP-HepB-IPV (Pediarix): Can be used as 3-dose primary series in infants and children 6 weeks through 6 years of age born to HBsAg-negative women when doses of DTaP, HepB, and IPV are indicated and there are no contraindications to any of the individual components. ACIP states also may be used to complete HBV vaccination series in infants 6 months through 6 years of age born to HBsAg-positive women. Should not be used for initial HepB dose indicated in neonates. For prevention of diphtheria, tetanus, and pertussis in infants and children 6 weeks through 6 years of age, may be used for initial 3 doses in DTaP series. Also may be used to complete first 3 doses of DTaP series in children who received 1 or 2 doses of Infanrix DTaP; data not available regarding safety and efficacy of Pediarix used following ≥1 dose of DTaP vaccine from a different manufacturer. Children who receive 3-dose series of Pediarix should complete DTaP and IPV series according to recommended childhood immunization schedule. To complete DTaP series, manufacturer recommends use of Infanrix for fourth dose of DTaP and either Infanrix DTaP or DTaP-IPV (Kinrix) for fifth dose of DTaP (these vaccines contain same pertussis antigens as Pediarix).

DTaP-IPV/Hib (Pentacel): Can be used as 4-dose series in infants and children 6 weeks through 4 years of age when doses of DTaP, IPV, and Hib vaccine are indicated and there are no contraindications to any of the individual components. To complete DTaP series, children who receive 4-dose series of Pentacel at 2, 4, 6, and 15 through 18 months of age should receive a dose of Daptacel at 4 through 6 years of age to provide fifth dose of DTaP. Pentacel also may be used in infants and children 6 weeks through 4 years of age who received ≥1 doses of Daptacel DTaP. Data not available on safety and immunogenicity of mixed sequences of Pentacel and Daptacel for successive doses in DTaP series or mixed sequences of Pentacel and DTaP from other manufacturers.

Combined active immunization with a preparation containing tetanus toxoid adsorbed (Td, DT, DTaP, Tdap) and passive immunization with tetanus immune globulin (TIG) is used for postexposure prophylaxis in individuals with tetanus-prone wounds who are inadequately immunized against tetanus or whose tetanus immunization history is uncertain.

DTaP and Tdap not indicated for treatment of diphtheria, tetanus, or pertussis.

Because diphtheria and tetanus infections may not confer immunity against the diseases, initiate or complete primary immunization against diphtheria and tetanus at time of recovery in any previously unvaccinated or incompletely vaccinated individual. Although pertussis is likely to confer short-term immunity against the disease, protection wanes over time (beginning as early as 5–7 years after infection); initiate or complete immunization against pertussis at time of recovery.

Preexposure Vaccination Against Tetanus, Diphtheria, and Pertussis in High-risk Groups

Pregnant women should be adequately immunized against tetanus, diphtheria, and pertussis; protection is conferred to infants through transplacental transfer of maternal antibody.

Ideally, complete primary immunization and administer appropriate booster doses prior to pregnancy. To ensure protection against tetanus (especially against maternal and neonatal tetanus), primary immunization or booster doses of Td can be given during second or third trimester of pregnancy (and before 36 weeks of gestation).

For previously unvaccinated or incompletely vaccinated pregnant women, ACIP and others recommend that a dose of Tdap be substituted for a required Td dose, preferably during third trimester (optimally between 27 and 36 weeks of gestation). In addition, to ensure protection against pertussis, these experts recommend give a dose of Tdap during each pregnancy, regardless of prior vaccination history.

Infants <12 months of age are at increased risk for pertussis (too young to be fully protected by initial DTaP doses given in early infancy). To reduce likelihood of pertussis transmission to such infants, ACIP and AAP recommend that adolescents and adults who have or anticipate having close contact with an infant <12 months of age (e.g., parents, siblings, grandparents, childcare providers, health-care personnel) receive a single dose of Tdap if they have not previously received a dose. Give Tdap dose at least 2 weeks before close contact with infant, regardless of interval since last Td dose.

Health-care personnel should have documentation of age-appropriate primary immunization with a preparation containing diphtheria and tetanus toxoids and booster doses of Td every 10 years. A single dose of Tdap also recommended for all health-care personnel (regardless of age) if they have not previously received a dose.

For health-care personnel without documentation of primary immunization, give 3-dose vaccination series using Tdap for first dose and Td for subsequent primary and booster doses. For previously vaccinated health-care personnel who have not received Tdap, give a single dose of Tdap as soon as feasible, regardless of interval since last Td dose; use Td for subsequent booster doses.

Travelers who are unvaccinated or incompletely vaccinated against diphtheria, tetanus, and pertussis should receive remaining recommended doses prior to travel.

Because tetanus, diphtheria, and pertussis occur worldwide, CDC recommends that travelers be adequately immunized against all 3 diseases before leaving US.

Adults, adolescents, and children 7 through 10 years of age who are unvaccinated or incompletely vaccinated should receive a single dose of Tdap followed by remaining recommended doses of Td according to usual age-appropriate catch-up vaccination schedule. Adults and adolescents ≥11 years of age who were previously vaccinated but have not received Tdap should receive a single dose of Tdap (instead of Td) for booster dose. When indicated to provide protection against pertussis before travel, Tdap may be administered regardless of interval since last Td dose.

If necessary to complete vaccination series before departure, adults, adolescents, and children can receive an accelerated immunization schedule using age-appropriate minimum intervals between doses.

Postexposure Prophylaxis of Diphtheria

Postexposure vaccination in household and other close contacts of an individual with culture-confirmed or suspected diphtheria.

Regardless of vaccination status, all household and other close contacts of an individual with culture-confirmed or suspected diphtheria should promptly receive anti-infective postexposure prophylaxis (single IM dose of penicillin G benzathine or oral erythromycin given for 7–10 days). Take samples for cultures prior to giving the anti-infective and continue to observe individual for 7 days for evidence of disease.

In addition, those who previously received <3 doses of a diphtheria toxoid-containing preparation or whose vaccination status is unknown should receive an immediate dose of an age-appropriate preparation containing diphtheria toxoid adsorbed and the primary vaccination series should be completed. Contacts who previously completed primary vaccination series should receive an immediate booster dose of age-appropriate preparation containing diphtheria toxoid adsorbed if it has been ≥5 years since last booster dose.

Diphtheria antitoxin (equine) (available in US only from CDC under an investigational new drug [IND] protocol) is no longer routinely recommended for postexposure prophylaxis of diphtheria in contacts, but may be recommended in exceptional circumstances for postexposure prophylaxis in individuals with known or suspected exposure to toxigenic Corynebacterium. To obtain diphtheria antitoxin (equine), contact CDC at 404-639-8257 from 8:00 a.m. to 4:30 p.m. EST Monday–Friday or CDC Emergency Operations Center at 770-488-7100 after hours, on weekends, and holidays.

Postexposure Prophylaxis of Tetanus

Postexposure prophylaxis of tetanus in individuals with tetanus-prone wounds who previously received <3 doses of a preparation containing tetanus toxoid adsorbed or whose tetanus vaccination status is uncertain.

Postexposure prophylaxis of tetanus involves active immunization with a tetanus toxoid-containing preparation with or without passive immunization with a dose of tetanus immune globulin (TIG).

Tetanus-prone wounds include (but are not limited to) wounds contaminated with dirt, feces, soil, or saliva; deep wounds; burns; crush injuries; and wounds containing devitalized or necrotic tissue. Tetanus also has been associated with apparently clean, superficial wounds, surgical procedures, insect bites, animal bites, dental infections, compound fractures, chronic sores and infections, and IV drug abuse.

In the event of injury and possible exposure to tetanus, the need for active immunization against tetanus with or without passive immunization with TIG depends on the individual’s vaccination status and the likelihood of contamination with tetanus bacilli (e.g., condition of wound, source of contamination).

Table 1 summarizes ACIP guidelines for active and passive immunization against tetanus in routine wound management.

A dose of Tdap preferred instead of a dose of Td in adults and adolescents ≥11 years of age who have not previously received a dose of Tdap. Use Td in individuals in this age group who previously received a dose of Tdap. Use Td in individuals in this age group who previously received a dose of Tdap.

Td used in adults, adolescents, and children ≥7 years of age. For children 6 weeks through 6 years of age, DTaP usually indicated, but DT can be used if pertussis antigens contraindicated. Single-antigen tetanus toxoid adsorbed not commercially available in US.

If only 3 doses of tetanus toxoid fluid (no longer commercially available in US) have been received previously, give a fourth dose as a preparation containing tetanus toxoid adsorbed.

Yes, if it has been >10 years since last dose of tetanus toxoid-containing preparation.

Yes, if it has been >5 years since last dose of tetanus toxoid-containing preparation; more frequent booster doses not needed and can accentuate adverse effects.

Adapted from the Recommendations of the Immunization Practices Advisory Committee (ACIP) on prevention of diphtheria, tetanus, and pertussis published in MMWR Recomm Rep. 2006; 55(RR-3):1-43 and MMWR Recomm Rep. 2006; 55(RR-17):1-37.

Any individual whose tetanus vaccination status is unknown or uncertain should be considered to have had no previous doses of tetanus toxoid adsorbed.

ACIP and others recommend that a single dose of Tdap be used in place of a dose of Td for postexposure prophylaxis in individuals ≥11 years of age (including those ≥65 years of age) who have not previously received a dose of Tdap. Those who previously received Tdap should receive Td for postexposure prophylaxis.

Anti-infectives not indicated for tetanus postexposure prophylaxis since they do not neutralize exotoxin already formed and cannot eradicate C. tetani spores, which may revert to toxin-producing vegetative forms.

Postexposure Prophylaxis of Pertussis

Postexposure vaccination in household and other close contacts of an individual with pertussis.

Regardless of vaccination status or age, all household and other close contacts of an individual with suspected pertussis should receive prophylaxis with an anti-infective active against B. pertussis (usually azithromycin, clarithromycin, erythromycin; alternatively, co-trimoxazole).

In addition, all close contacts <7 years of age who have not completed primary immunization with DTaP should complete the vaccination series with minimal intervals between doses. Those who received their third DTaP dose ≥6 months before the exposure should receive a fourth dose.

ACIP and AAP recommend a single dose of Tdap in all adults, adolescents, and children ≥7 years of age who have not previously received a dose and are at increased risk of pertussis during pertussis outbreaks or because they are close contacts of an individual with pertussis (e.g., in a family, residential facility, school, school-related activity); this includes children 7 through 10 years of age who did not complete DTaP vaccination series.

• Generic Name: milrinone
• Dosage Forms: injection, solution
• Other Brand Names: Primacor, Primacor IV.

Milrinone is a vasodilator that works by relaxing the muscles in your blood vessels to help them dilate (widen). This lowers blood pressure and allows blood to flow more easily through your veins and arteries.

Milrinone is used as a short-term treatment for life-threatening heart failure.

Milrinone may also be used for purposes not listed in this medication guide.