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Tetanus vaccine

1. NAME
   1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS number
      1.4.2 Other numbers
   1.5 Brand names, Trade names
   1.6 Manufacturers, Importers
2. SUMMARY
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First aid measures and management principles
3. PHYSICO-CHEMICAL PROPERTIES
   3.1 Origin of the substance
   3.2 Chemical structure
   3.3 Physical properties
      3.3.1 Properties of the substance
      3.3.2 Properties of the locally available formulation
   3.4 Other characteristics
      3.4.1 Shelf-life of the substance
      3.4.2 Shelf-life of the locally available formulation
      3.4.3 Storage conditions
      3.4.4 Bioavailability
      3.4.5 Specific properties and composition
4. USES
   4.1 Indications
   4.2 Therapeutic dosage
      4.2.1 Adults
      4.2.2 Children
   4.3 Contraindications
5. ROUTES OF ENTRY
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Other
6. KINETICS
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination by route of exposure
7. PHARMACOLOGY AND TOXICOLOGY
   7.1 Mode of action
      7.1.1 Toxicodynamics
      7.1.2 Pharmacodynamics
   7.2 Toxicity
      7.2.1 Human data
         7.2.1.1 Adults
         7.2.1.2 Children
      7.2.2 Relevant animal data
      7.2.3 Relevant in vitro data
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
   7.7 Main adverse effects
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection
         8.1.1.1 Toxicological analyses
         8.1.1.2 Biomedical analyses
         8.1.1.3 Arterial blood gas analysis
         8.1.1.4 Haematological analyses
         8.1.1.5 Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens
         8.1.2.1 Toxicological analyses
         8.1.2.2 Biomedical analyses
         8.1.2.3 Arterial blood gas analysis
         8.1.2.4 Haematological analyses
         8.1.2.5 Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens
         8.1.3.1 Toxicological analyses
         8.1.3.2 Biomedical analyses
         8.1.3.3 Arterial blood gas analysis
         8.1.3.4 Haematological analyses
         8.1.3.5 Other (unspecified) analyses
   8.2 Toxicological Analyses and Their Interpretation
      8.2.1 Tests on toxic ingredient(s) of material
         8.2.1.1 Simple Qualitative Test(s)
         8.2.1.2 Advanced Qualitative Confirmation Test(s)
         8.2.1.3 Simple Quantitative Method(s)
         8.2.1.4 Advanced Quantitative Method(s)
      8.2.2 Tests for biological specimens
         8.2.2.1 Simple Qualitative Test(s)
         8.2.2.2 Advanced Qualitative Confirmation Test(s)
         8.2.2.3 Simple Quantitative Method(s)
         8.2.2.4 Advanced Quantitative Method(s)
         8.2.2.5 Other Dedicated Method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis
         8.3.1.1 Blood, plasma or serum
         8.3.1.2 Urine
         8.3.1.3 Other fluids
      8.3.2 Arterial blood gas analyses
      8.3.3 Haematological analyses
      8.3.4 Interpretation of biomedical investigations
   8.4 Other biomedical (diagnostic) investigations and their interpretation
   8.5 Overall Interpretation of all toxicological analyses and toxicological investigations
   8.6 References
9. CLINICAL EFFECTS
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systematic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological
         9.4.3.1 CNS
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic nervous system
         9.4.3.4 Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 Other
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ear, nose, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      9.4.12 Metabolic
         9.4.12.1 Acid-base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Other
   9.6 Summary
10. MANAGEMENT
   10.1 General principles
   10.2 Relevant laboratory analyses
      10.2.1 Sample collection
      10.2.2 Biomedical analysis
      10.2.3 Toxicological analysis
      10.2.4 Other investigations
   10.3 Life supportive procedures and symptomatic/specific treatment
   10.4 Decontamination
   10.5 Elimination
   10.6 Antidote treatment
      10.6.1 Adults
      10.6.2 Children
   10.7 Management discussion
11. ILLUSTRATIVE CASES
   11.1 Case reports from literature
   11.2 Internally extracted data on cases
   11.3 Internal cases
12. Additional information
   12.1 Availability of antidotes
   12.2 Specific preventive measures
   12.3 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)
    PHARMACEUTICALS
    1. NAME
     1.1 Substance
       Tetanus vaccine
     1.2 Group
       Biological immunological agent.
     1.3 Synonyms
       Adsorbed Tetanus vaccine (BP)
       Pasteur Tetanus vaccine (France)
       Tetanol (France, Germany)
       Tetanus Toxoid (USP) and Tetanus Toxoid adsorbed (USP)
       Tetanus vaccine (BP)
     1.4 Identification numbers
       1.4.1 CAS number
       1.4.2 Other numbers
     1.5 Brand names, Trade names
       Tetanol (Germany)
       Tetavax (UK)
       Te Anatoxin Berne (Switzerland)
       Tetanus toxoid adsorbed puragated (USA)
     1.6 Manufacturers, Importers
       Behring        (Germany)
       Merieux        (UK)
       Wellcome       (UK)
       Servier        (UK)
       Slavo          (USA)
       Lederle        (USA)
       Wyeth-Ayerst   (USA)
    2. SUMMARY
     2.1 Main risks and target organs
       Main risk is adverse reactions which may be local or involve 
       multiple organs.
     2.2 Summary of clinical effects
       Local effects:  Local reactions at injection site include 
       tenderness, erythema, induration, warmth and oedema.  Rarely, 
       the local reactions may become extensive as a result of 
       hypersensitivity. The incidence of reactions increases with 
       the 2nd and 3rd injections, but the reactions are generally 
       not severe.
       
       Systemic effects: transient fever, malaise, generalized aches 
       and pains, rash, generalized urticaria or pruritus, 
       lymphadenopathy, tachycardia and hypotension.  More rarely, a 
       severe anaphylactic reaction may occur. Neurological disorders 
       include cochlear lesions, brachial plexus neuropathies, 
       paralysis of radial or recurrent nerves, accommodation paresis,
        EEG disturbances. Dysphagia and polyradiculoneuropathy have 
       been reported.
     2.3 Diagnosis
       Diagnosis is based on occurrence of local and/or systemic 
       reactions following the parenteral administration of the 
       vaccine.
     2.4 First aid measures and management principles
       Immediate allergic reactions should be controlled with 
       antihistamines, and anaphylaxis with the administration of 
       epinephrine 1:1000 (see Treatment protocol).

    3. PHYSICO-CHEMICAL PROPERTIES
     3.1 Origin of the substance
       Tetanus vaccine is prepared from tetanus toxin produced by the 
       growth of the bacterium Clostridium tetani.  The toxin is 
       converted to tetanus formol toxoid by treatment with 
       formaldehyde solution. In addition, for tetanus toxoid 
       adsorbed or adsorbed tetanus vaccine, aluminium phosphate or 
       aluminium potassium sulphate is used as a mineral adjuvant to 
       adsorb the tetanus antigens.  This prolongs and enhances the 
       antigenic properties by retarding the rate of absorption of 
       the injected toxoid into the body. [There are slight 
       variations of the production methods used by different 
       manufacturers but all products must meet the established 
       potency of 5 to 7.5 Lf units/0.5 ml dose].
     3.2 Chemical structure
       Not relevant.
     3.3 Physical properties
       3.3.1 Properties of the substance
             Tetanus vaccine is a clear, colourless to 
             brownish yellow or slightly turbid liquid, free from 
             evident lumps or particles, having a characteristic 
             odour or an odour of formaldehyde.
             
             Tetanus toxoid adsorbed (USP) or Adsorbed tetanus vaccine 
             (BP): Turbid, white, slightly grey or slightly pink 
             suspension, free from evident lumps after shaking.
       3.3.2 Properties of the locally available formulation
             Pasteur tetanus vaccine is a preparation containing 
             purified tetanus toxoid adsorbed onto aluminium 
             hydroxide.  Each 0.5 ml dose  contains: purified tetanus 
             toxoid (1 vaccination dose q.s. 0.5 ml);  aluminium 
             hydroxide (expressed as aluminium) (2.25 mg maximum);  
             thiomersal (preservative) (0.05 mg maximum); isotonic 
             sodium  chloride solution corresponding to at least 40 
             immunizing international units.
             
             One dose (0.5 ml) of Behring Preparation contains 
             adsorbed tetanus vaccine (tetanol) (75 IU); aluminium 
             hydroxide (1.5 mg) and sodium p-ethyl-mercuri-mercapto-
             benzol-sulphate (0.025 mg) as preservative.
     3.4 Other characteristics
       3.4.1 Shelf-life of the substance
             The expiry date of tetanus toxoid and tetanus toxoid 
             adsorbed is not later than 5 years after the date of 
             issue from the manufacturers cold storage or one year 
             when the manufacturer's cold  storage was at 5C.
       3.4.2 Shelf-life of the locally available formulation
             Not less than 5 years from the date on which the potency 
             test was begun.
       3.4.3 Storage conditions
             Tetanus vaccine or adsorbed tetanus vaccine should be 
             stored in a refrigerator at a temperature ranging 
             between +2 and +8 C; it  should be used on or before 
             the date of expiry given on the pack.   It must not be 
             frozen and should be protected from light.
       3.4.4 Bioavailability

             One hundred percent.
       3.4.5 Specific properties and composition
             Not relevant.
    4. USES
     4.1 Indications
       Tetanus vaccines are used for active immunization 
       against tetanus. The main objective of tetanus 
       immunization is to prevent the severe complications (or 
       death), which arise from the potent exotoxin elaborated 
       by Clostridium tetanus.  Unless otherwise 
       contraindicated, all infants of 6 to 8 weeks of age or 
       older, all children, and all adults should be immunized 
       against tetanus with the primary series of tetanus 
       vaccine and a booster injection every 10 years 
       throughout their lives, including:
       
       -  Adults: Especially those of 50 years of age and 
       older.  In recent years, approximately two-thirds of persons
       contracting tetanus have been in this age group.

       -  Persons with uncertain histories of complete primary courses 
       of vaccination with tetanus vaccine or immunizing agents 
       containing tetanus toxoid.
       
       -  Travellers
       
       -  Persons at increased risk of receiving lacerations and 
       abrasions through their occupation or recreational activities.
       
       -  Persons with known hypersensitivity to horse serum or with
       asthma or other allergies.  This is to minimize the possible 
       need for passive immunization with tetanus antitoxin (TAT) of 
       animal origin (usually horse) if a wound is received.  Although 
       human tetanus immune globulin (TIG) is usually used for passive 
       immunization, TAT of animal origin may still be used in certain 
       areas of the world and risks causing adverse reactions in
       hypersensitive patients.
       
       -  Pregnant women who are not immunized or inadequately immunized 
       and who may deliver their infants in conditions of poor hygiene 
       thereby exposing their infants to neonatal tetanus.
       
       -  Those recovering from tetanus.  Since an injection of TAT or 
       TIG does not confer immunity, immunization with tetanus vaccine 
       should be initiated or continued at the time of recovery from the 
       illness.
       
       -  Persons who are injured may require emergency tetanus 
       prophylaxis depending on the number of primary immunizations, 
       the timing of any boosters, and the type of wound received.
       
       The active immunization of children is not discussed 
       further in this monograph.
       
       When a single entity vaccine is used, adsorbed tetanus 
       vaccine (BP) or tetanus toxoid adsorbed (USP) are the 

       vaccines of choice for primary immunization because 
       greater antigenic stimulation and longer lasting 
       immunity are achieved than with the tetanus toxoid (USP) 
       or tetanus vaccine (BP).  For wounds, tetanus toxoid 
       (fluid) USP may be used as emergency prophylaxis of 
       tetanus. 
     4.2 Therapeutic dosage
       4.2.1 Adults
             The dosage of tetanus vaccine/tetanus toxoid is the same 
             for all persons, infants, children and adults.
       4.2.2 Children
             (See 4.2.1)
             
             - Tetanus toxoid adsorbed (injection)
             
             A primary vaccination course of tetanus toxoid adsorbed 
             consists of 3 doses each of 0.5 ml (not less than 40 
             units for adsorbed vaccine  or not less than 14 Lf for 
             non-adsorbed vaccine).
             
             Usual adult and adolescent dose: Intramuscular, 0.5 ml.
             
             First dose:    at initial visit
             Second dose:   4 to 8 weeks after the first dose
             Third dose:    6 to 14 months after the second dose
             Booster doses: every 10 years.
             
             - Tetanus Vaccine/Toxoid (Fluid) (Injection)
             
             Usual adult and adolescent dose: Intramuscular or 
             subcutaneous 0.5 ml (US, UK, Zimbabwe) or 1 ml (Canada).
             
             First dose:    at initial visit
             Second dose:   4 to 8 weeks after the first dose
             Third dose:    4 to 8 weeks after the second dose
             Fourth dose:   6 to 12 months after the third dose
             Booster doses: every 10 years.
             
             N.B. In other countries the strength of the vaccine, 
             dosages and schedules may differ slightly from that 
             outlined above. Immunization against tetanus forms part 
             of the World Health Organization's Expanded Programme on 
             Immunization, which recommends the treatment schedules.
     4.3 Contraindications
       Tetanus vaccine and adsorbed tetanus vaccine are 
       contraindicated in individuals who have had a prior systemic 
       hypersensitivity reaction to either vaccine.
       
       -  The US Public Health Service Immunizations Practices
          Advisory Committee states that tetanus toxoid and tetanus
          toxoid adsorbed are contraindicated in individuals who
          experienced a neurological reaction after a previous dose
          of a tetanus toxoid-containing preparation.
       
       -  Routine administration of the vaccines is contraindicated
          in patients having acute respiratory disease because

          routine primary or booster immunization should not be
          administered until the symptoms of the patient's illness
          have abated;  however, emergency tetanus prophylaxis for
          wounds should be administered as usual.  Minor illness,
          such as upper respiratory tract infection, does not
          preclude administration of tetanus toxoid.
       
       -  The vaccine should not be administered during an outbreak
          of poliomyelitis; elective immunization of patients over
          the age of 6 months with tetanus toxoid should be deferred
          during an outbreak of poliomyelitis.
       
       -  Tetanus vaccine is contraindicated in individuals with
          tetanus infection.  Tetanus toxoid should not be used to
          treat a tetanus infection, for which tetanus antitoxin,
          preferably tetanus immune globulin (TIG), should be used
          instead; vaccination with tetanus toxoid should begin
          after recovery.
    5. ROUTES OF ENTRY
     5.1 Oral
       No data available.
     5.2 Inhalation
       No data available.
     5.3 Dermal
       During sensitivity testing and desensitization
     5.4 Eye
       Conjunctival test.
     5.5 Parenteral
       Intramuscular, subcutaneous and intravenous injection. 
     5.6 Other
       No data available.
    6. KINETICS
     6.1 Absorption by route of exposure
       Not relevant.
     6.2 Distribution by route of exposure
       Not relevant.
     6.3 Biological half-life by route of exposure
       Not relevant.
     6.4 Metabolism
       Not relevant.
     6.5 Elimination by route of exposure
       Not relevant.
    7. PHARMACOLOGY AND TOXICOLOGY
     7.1 Mode of action
       7.1.1 Toxicodynamics
             Not relevant.
       7.1.2 Pharmacodynamics
             Following intramuscular injection of tetanus toxoid 
             adsorbed or either intramuscular or subcutaneous 
             injection of tetanus toxoid,  an antigen response is 
             induced in the immunized patient causing  the formation 
             of antibodies to tetanus toxins (USP DI 1990).
     7.2 Toxicity
       7.2.1 Human data
             7.2.1.1 Adults
                     Local reactions are more common in adults than 

                     in children and an incidence in adults of 1 - 2% 
                     has been reported (Martindale, 1982).
             7.2.1.2 Children
                     Local reactions are more common in adults than 
                     in children and an incidence in adults of 1 - 2% 
                     has been reported (Martindale, 1982).
       7.2.2 Relevant animal data
             Not relevant.
       7.2.3 Relevant in vitro data
             Not relevant.
     7.3 Carcinogenicity
       No data available.
     7.4 Teratogenicity
       There is no evidence that tetanus toxin is teratogenic.  In 
       general, waiting until the second trimester is a reasonable 
       precaution to minimise any theoretical concern (PDR, 1992).
     7.5 Mutagenicity
       No data available. 
     7.6 Interactions
       No data available. 
     7.7 Main adverse effects
       Common adverse effects include redness or hard lump at 
       injection site, which may persist for a few days.
       
       Hypersensitivity to reinforcing doses of tetanus toxoid has 
       been described (Dittmann, 1988), especially in individuals who 
       are sensitive to the mercury in thiomersal.  Slight local 
       reactions such as induration, erythema and tenderness seem to 
       be more common with the adsorbed type of vaccine.  If 
       aluminium adsorbed toxoid is given subcutaneously, a small 
       granuloma may occur due to deposition of material at the 
       injection site.  Intramuscular injection of tetanus toxoid is 
       generally better tolerated and the product can best be 
       injected into a large muscle (gluteal) (Dittmann, 1988).
       
       Anaphylactic reactions may occur rarely and can be sudden and 
       severe.  These include difficulty in breathing or swallowing; 
       hives and itching, especially  of the soles or palms; 
       reddening of skin, especially around the ears,  swelling of 
       the eyes, the face, of the inside of the nose; unusual 
       tiredness  or weakness.  Adverse neurological effects include 
       confusion, fever over  39.4C (103 F), severe or continuing 
       headache, seizures, excessive  sleepiness, unusual 
       irritability and severe or continuing vomiting.   
       Lymphadenopathy (swelling of glands and armpit).  Swelling, 
       blistering, or  pain at injection site, which may be severe 
       and extensive.
       
       Allergic reactions of the delayed and the cell-mediated type 
       occur occasionally and include pain, tenderness, itching, or 
       swelling at injection site, chills, fever, irritability or 
       unusual tiredness.
       
       A nodule or sterile abscess at the injection site, probably 
       caused by the aluminium content of tetanus toxoid adsorbed, 
       may persist for several weeks. Skin rash has also been 

       reported (McEvoy, 1988; USP DI 1990).
     8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
     8.1 Material sampling plan
       8.1.1 Sampling and specimen collection
             8.1.1.1 Toxicological analyses
             8.1.1.2 Biomedical analyses
             8.1.1.3 Arterial blood gas analysis
             8.1.1.4 Haematological analyses
             8.1.1.5 Other (unspecified) analyses
       8.1.2 Storage of laboratory samples and specimens
             8.1.2.1 Toxicological analyses
             8.1.2.2 Biomedical analyses
             8.1.2.3 Arterial blood gas analysis
             8.1.2.4 Haematological analyses
             8.1.2.5 Other (unspecified) analyses
       8.1.3 Transport of laboratory samples and specimens
             8.1.3.1 Toxicological analyses
             8.1.3.2 Biomedical analyses
             8.1.3.3 Arterial blood gas analysis
             8.1.3.4 Haematological analyses
             8.1.3.5 Other (unspecified) analyses
     8.2 Toxicological Analyses and Their Interpretation
       8.2.1 Tests on toxic ingredient(s) of material
             8.2.1.1 Simple Qualitative Test(s)
             8.2.1.2 Advanced Qualitative Confirmation Test(s)
             8.2.1.3 Simple Quantitative Method(s)
             8.2.1.4 Advanced Quantitative Method(s)
       8.2.2 Tests for biological specimens
             8.2.2.1 Simple Qualitative Test(s)
             8.2.2.2 Advanced Qualitative Confirmation Test(s)
             8.2.2.3 Simple Quantitative Method(s)
             8.2.2.4 Advanced Quantitative Method(s)
             8.2.2.5 Other Dedicated Method(s)
       8.2.3 Interpretation of toxicological analyses
     8.3 Biomedical investigations and their interpretation
       8.3.1 Biochemical analysis
             8.3.1.1 Blood, plasma or serum
             8.3.1.2 Urine
             8.3.1.3 Other fluids
       8.3.2 Arterial blood gas analyses
       8.3.3 Haematological analyses
       8.3.4 Interpretation of biomedical investigations
     8.4 Other biomedical (diagnostic) investigations and their 
       interpretation
     8.5 Overall Interpretation of all toxicological analyses and >
       toxicological investigations     8.6 References
    9. CLINICAL EFFECTS
     9.1 Acute poisoning
       9.1.1 Ingestion
             Not relevant
       9.1.2 Inhalation
             No data available.
       9.1.3 Skin exposure
             Not relevant.
       9.1.4 Eye contact

             Not relevant.
       9.1.5 Parenteral exposure
             Local and systemic reactions may occur after 
             ultramuscular administration.
       9.1.6 Other
             No data available.
     9.2 Chronic poisoning
       9.2.1 Ingestion
             Not relevant.
       9.2.2 Inhalation
             No data available.
       9.2.3 Skin exposure
             No data available.
       9.2.4 Eye contact
             No data available.
       9.2.5 Parenteral exposure
             No data available.
       9.2.6 Other
             No data available.
     9.3 Course, prognosis, cause of death
       Local reactions such as erythema, induration, oedema and 
       redness are usually self-limiting and need no special 
       treatment.  Nodules or sterile abcesses may eventually appear 
       at the site of administration.  In case of severe adverse 
       reactions, e.g. anaphylaxis, appropriate emergency treatment 
       is imperative as it constitutes a life-threatening effect.
     9.4 Systematic description of clinical effects
       9.4.1 Cardiovascular
             Tachycardia and hypotension 
       9.4.2 Respiratory
             Respiratory manifestations of anaphylaxis, for example 
             bronchospasm, have been reported as a manifestation of 
             anaphylaxis.
       9.4.3 Neurological
             9.4.3.1 CNS
                     Neurological disorders reported include 
                     convulsions, cochlear lesions, paralysis of 
                     radial or recurrent nerves, accommodation 
                     paresis and EEG disturbances.
             9.4.3.2 Peripheral nervous system
                     A case of peripheral neuropathy with paralysis 
                     of the right radial nerve has been reported in a 
                     medical student a few hours after administration 
                     of tetanus vaccine.  Various mono
                     - and polyneuropathies including Gillain-Barre 
                     Syndrome have been reported following the 
                     administration of tetanus  antigens (PDR 1992).
             9.4.3.3 Autonomic nervous system
                     No data available.
             9.4.3.4 Skeletal and smooth muscle
                     No data available.
       9.4.4 Gastrointestinal
             Dysphagia may occur 
       9.4.5 Hepatic
             No data available.
       9.4.6 Urinary

             9.4.6.1 Renal
                     No data available.
             9.4.6.2 Other
                     No data available.
       9.4.7 Endocrine and reproductive systems
             No data available.
       9.4.8 Dermatological
             Skin rash, generalized urticaria or pruritus as 
             manifestations of allergic reactions.
       9.4.9 Eye, ear, nose, throat: local effects
             Reddening and swelling as manifestations of allergic  
             reactions.
       9.4.10 Haematological
              No data available.
       9.4.11 Immunological
              No data available.
       9.4.12 Metabolic
              9.4.12.1 Acid-base disturbances
                       No data available.
              9.4.12.2 Fluid and electrolyte disturbances
                       No data available.
              9.4.12.3 Others
                       No data available.
       9.4.13 Allergic reactions
              Allergic and anaphylactoid reactions have been reported 
              (US  DI 1990) [see section 7.7].
       9.4.14 Other clinical effects
              No data available
       9.4.15 Special risks
              Pregnancy:          No data available.
              Breast feeding:     No problems have been documented.
              Enzyme deficiency:  No data available.
     9.5 Other
       No data available.
     9.6 Summary
    10. MANAGEMENT
      10.1 General principles
         Management principles consist of the control of anaphylactic 
         reactions and its life-threatening effects.  Minor reactions 
         to the vaccine are usually self-limiting and do not require 
         special treatment.  Anti-histamines may be used is required.
      10.2 Relevant laboratory analyses
         10.2.1 Sample collection
                Not relevant
         10.2.2 Biomedical analysis
                Not relevant
         10.2.3 Toxicological analysis
                Not relevant
         10.2.4 Other investigations
                Not relevant
      10.3 Life supportive procedures and symptomatic/specific 
         treatmentAn antihistamine may be indicated for mild allergic 
         reactions. For anaphylactic reactions, adrenaline 
         (epinephrine) with maintenance of vital functions is 
         necessary.

         
         Adult dosage: If anaphylaxis occurs, give 0.2 to 0.5 mg of 
         adrenaline intramuscularly or subcutaneously; the dose 
         should be repeated every 10 to 15 min as needed and if 
         necessary increased up to a maximum of 1 mg per dose. If 
         anaphylactic shock occurs, give 0.5 mg of adrenaline 
         intramuscularly or subcutaneously, followed by slow 
         intravenous administration of adrenaline or 0.0025 to 0.005 
         mg. The dose may be repeated every 5 to 15 min as needed.
         
         Children's dosage: If anaphylaxis occurs, give adrenaline 
         0.01 mg per kg body weight or 0.3 mg per square metre of 
         body surface, up to a maximum of 0.5 mg per dose, by 
         subcutaneous injection; repeat every 15 min for two doses, 
         then every 4 h as needed.  If anaphylactic shock occurs, 
         give 0.3 mg adrenaline intramuscularly or intravenously; 
         repeat every 15 min for 3 or 4 doses, if necessary.
      10.4 Decontamination
         Not relevant
      10.5 Elimination
         Not relevant
      10.6 Antidote treatment
         10.6.1 Adults
         10.6.2 Children
      10.7 Management discussion
         Not relevant
    11. ILLUSTRATIVE CASES
      11.1 Case reports from literature
         A 24-year-old woman developed anaphylactic shock and died 30 
         min after an injection of tetanus vaccine.  Previous 
         injections with the vaccine had been well tolerated 
         (Martindale, 1989).
      11.2 Internally extracted data on cases
         To be completed by the centre
      11.3 Internal cases
         To be completed by the centre
    12. Additional information
      12.1 Availability of antidotes
         Not relevant
      12.2 Specific preventive measures
         The existence of any contraindication to immunization should 
         be determined prior to administration of the vaccine
      12.3 Other
         No data available
    13. REFERENCES
    Briggs CG, Freeman RK, Yaffe SJ (1986). Tetanus/Diphtheria 
    toxoids (adult). Drugs in pregnancy and lactation.  A reference 
    guide to foetal and neonatal risk. Second edition.  Williams & 
    Wilkins, Baltimore, 423 t.
    
    Dittman S (1988)  Immunological preparations.  In: Dukes MNG. 
    Meyler's side effects of drugs, 11th edition, Elsevier, Amsterdam,
     668-692.
    
    McEvoy GK (1988)  Serums, Toxoids and Vaccines: Tetanus 
    antitoxin.  American Hospital Formulary Service Drug Information 

    88. The American Society of the Hospital Pharmacists, Montgomery 
    Avenue, Bethesda, 1871-1969.
    
    PDR Physician's Desk Reference (1993), 46th Edition Medical 
    Economics Data, USA.
    
    Reynolds JEF (1989)  Immunological agents: Tetanus antitoxins. 
    Martindale, the Extra Pharmacopoeia. The Pharmaceutical Press, 
    London, 1155-1183.
    
    The United States Pharmacopoeial Convention Inc. (1990)  Tetanus 
    toxoid.  USP Drug Information for Health Care Professionals.  
    Vol. IB, 2580-2583.
    
    Zink GL (1990)  Immunizing agents and diagnostic antigens.  In: 
    Osol Arthur, Remington's Pharmaceutical Sciences, 16th Edition, 
    Mack Publishing Company, Easton, Pennsylvania, 1324-1340.
    14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE 
    ADDRESS(ES)

    Author:   Dr O.J. Kasilo
              Drug and Toxicology Information Service (DaTIS),
              Department of Pharmacy
              University of Zimbabwe Medical School
              P.O.Box A178
              Avondale
              Harare
              Zimbabwe.
    
    Author:   Dr C.F.B. Nhachi
              Department of Clinical Pharmacology and Toxicology
              University of Zimbabwe Medical School
              P.O.Box A178
              Avondale
              Harare
              Zimbabwe.
              Tel:      263-4-790233/791631, Ext. 228
              Telex:    265801 UNIV ZW
              Fax:      263-4-303-292
    
    Reviewer:
    
    Finalized and updated at the IPCS, May 1994.



    See Also:
       Toxicological Abbreviations