Diazepam Oral Solution Concentrate and Diphtheria and Tetanus Toxoids Adsorbed, Tetanus and Diphtheria Toxoids Adsorbed

• Generic Name: diazepam
• Dosage Forms: solution, concentrate
• Other Brand Names: Valium, Diastat, Diastat AcuDial, Diastat Pediatric, Diazepam Intensol, Zetran

Diazepam is a benzodiazepine (ben-zoe-dye-AZE-eh-peens). It affects chemicals in the brain that may be unbalanced in people with anxiety.

Diazepam is used to treat anxiety disorders, alcohol withdrawal symptoms, or muscle spasms.

Diazepam is sometimes used with other medications to treat seizures.

• Generic Name: diphtheria toxoid / tetanus toxoid
• Dosage Forms: n.a.
• Other Brand Names:

  Diphtheria-Tetanus Toxoids, Pediatric, Decavac, Tenivac

DT: Prevention of diphtheria and tetanus in infants and children 6 weeks through 6 years of age. Use only when diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed (DTaP) cannot be used (i.e., when pertussis antigens contraindicated or should not be used).

Td: Prevention of diphtheria and tetanus in adults, adolescents, and children ≥7 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 the US. Most diphtheria cases occur in individuals unvaccinated or incompletely vaccinated against the disease.

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.

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 for primary and booster immunization against these diseases in infants and children 6 weeks through 6 years of age, unless pertussis antigens contraindicated or should not be used. Use DT for primary or booster immunization against diphtheria and tetanus only when DTaP cannot be used.

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 tetanus toxoid and reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap) be used in place of a required primary or booster dose of Td in all individuals ≥7 years of age who have not previously received Tdap, unless pertussis antigens contraindicated or should not be used. Use Td for subsequent primary or booster doses.

Combined active immunization with a preparation containing tetanus toxoid adsorbed and passive immunization with tetanus immune globulin (TIG) is used to prevent tetanus in individuals with tetanus-prone wounds who are inadequately vaccinated against tetanus or whose tetanus vaccination status is uncertain.

DT and Td not indicated for treatment of diphtheria or tetanus.

Because diphtheria and tetanus infections may not confer immunity against the diseases, initiate or complete primary immunization against diphtheria and tetanus at the time of recovery in any previously unvaccinated or incompletely vaccinated individual.

Preexposure Vaccination Against Tetanus and Diphtheria in High-risk Groups

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

Ideally, complete primary immunization and administer appropriate booster doses prior to pregnancy. To ensure protection (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.

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 and tetanus 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 the 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 dose of Td.

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 the primary vaccination series should receive an immediate booster dose of an age-appropriate preparation containing diphtheria toxoid adsorbed if it has been >5 years since their last booster dose.

Diphtheria antitoxin (equine) (available in the 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 the 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 unknown or 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.

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 a single dose of 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.