Per 0.5 mL Diphtheria toxoid 25 Lf (not <30 IU), tetanus toxoid 5.5 Lf (not <60 IU), B. pertussis (whole cell) 16 IOU (not <4 IU), r-HBsAg 12.5 mcg, purified capsular polysaccharide of Hib (PRP) covalently linked to 20-36.7 mcg of tetanus toxoid 11 mcg, Al phosphate not >1.25 mg.
Diphtheria, Tetanus, Pertussis (Whole Cell), Hepatitis-B (rDNA) and Haemophilus influenzae Type b Conjugate Vaccine (Adsorbed) is a sterile suspension for injection which contains diphtheria (D), tetanus (T) toxoids, whole cell inactivated pertussis bacteria (wP), purified major surface antigen of the hepatitis B virus (HBV), adsorbed on aluminium salts and conjugated Haemophilus influenzae type b polysaccharide.
The Diphtheria and Tetanus toxoids are prepared from the toxins of cultures of Corynebacterium diphtheriae and Clostridium tetani by formalin inactivation using established technology. The Pw component is obtained by heat inactivation of phase I culture of Bordetella pertussis bacteria.
The surface antigen of HBV (HBsAg) is produced from genetically-engineered yeast cells (Pichia pastoris) which carry the gene coding for the major surface antigen of the HBV. This HBsAg expressed in yeast cells is purified by several physico-chemical steps.
The capsular polysaccharide is produced from cultures of Haemophilus influenzae type b and purified. Purified polysaccharide (PRP) is covalently bound to tetanus toxoid (T) to produce PRP-T conjugate.
1 dose (0.5 mL) contains Diphtheria Toxoid 25 Lf (not less than 30 IU), Tetanus Toxoid 5.5 Lf (not less than 60 IU*), B. Pertussis (Whole cell) 16 IOU (not less than 4 IU**), r-HBsAg 12.5 micrograms, Purified capsular polysaccharide of Hib (PRP) covalently linked to 20-36.7 micrograms of tetanus toxoid 11 micrograms, Al+++ (as AlPO4) not more than 1.25 mg. Preservative: Thiomersal BP/Ph. Eur 0.01% w/v.
* Not less than 40 IU when tested in guinea pigs and not less than 60 IU when tested in mice.
** The lower fiducial limit (p=0.95) of the estimated potency is not less than 2.0 IU.
The product is a whitish turbid liquid in which the mineral carriers, tends to settle down slowly on keeping and disperse uniformly upon shaking.
Excipients/Inactive Ingredients: Al+++ (as AlPO4) (Adjuvant), Thiomersal BP/Ph. Eur (Preservative), Sodium Chloride (Isotonic agent), Sodium Hydroxide (For pH adjustment), Hydrochloric Acid (For pH adjustment), Water for Injection (q.s.).
Pharmacotherapeutic group: Bacterial and viral vaccines, combined. ATC code: J07CA11.
Pharmacology: Pharmacodynamics: In a phase-III clinical trial involving 6-8 week old healthy infants the combined liquid pentavalent DTwP-rHepB-Hib vaccine manufactured by Biological E. Limited has demonstrated a comparable safety and immunogenicity in comparison with a licensed, WHO prequalified vaccine marketed in India. The primary immunogenicity analysis showed seroprotection rates of 98.25%, 100%, 96.49%, 94.74% and 89.47% against Diphtheria, Tetanus, Pertussis, Hepatitis-B and Haemophilus influenzae type b antigen components respectively.
Pharmacokinetics: Not applicable.
Toxicology: Preclinical safety data: Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity.
Uni 5 is indicated for active immunization against diphtheria, tetanus, pertussis, hepatitis B (HB) and Haemophilus influenzae type b disease in infants from 6 weeks of age.
The primary vaccination schedule consists of three doses of 0.5 mL each given intramuscularly within the first six months of life. Three vaccine doses at 6-10-14 weeks of age must be administered at intervals of at least 4 weeks.
Where HBV vaccine is not given at birth, the combined vaccine must be administered beginning as early as 6 weeks of age. Where there is a high endemicity of HBV, the practice to administer HBV vaccine at birth may be continued.
In the case of children born to known HBV carrier mothers, the immuno-prophylactic measures for hepatitis B should not to be modified. This may require separate vaccination with HBV and DTwP vaccines and also include the administration of HBIg at birth.
Method of administration: Uni 5 vial should be shaken well to get a uniform suspension. This pentavalent vaccine is for deep intramuscular injection, preferably in the anterolateral aspect of the thigh. As with all parenteral drug products, aseptic procedures should be followed during the administration of this vaccine.
Parenteral drug products should be inspected visually for extraneous particulate matter and or discoloration prior to administration whenever solution and container permit. If these conditions exist, the vaccine should not be administered.
Hypersensitivity to the active substances or to any of the excipients listed in Description.
Severe reaction to a previous dose of the combination vaccine or any of its constituents is an absolute contraindication to subsequent doses of the combination vaccine or the specific vaccine known to have provoked an adverse reaction.
Convulsions/seizures or abnormal cerebral signs in the newborn period or other serious neurological abnormalities are contraindications to the pertussis component. In these cases, the vaccine should not be given as a combination vaccine but DT should be given instead of DTwP and Hep B and Hib vaccine given separately. The vaccine will not harm individuals currently or previously infected with the hepatitis B virus.
Vaccination should be preceded by a review of the medical history (especially with regard to previous vaccination and possible occurrence of undesirable events) and a clinical examination by a qualified physician.
If any of the following events occur in temporal relation to receipt of this vaccine, the decision to give subsequent doses of vaccine containing the pertussis component should be carefully considered: Temperature ≥ 40°C within 48 hours, not due to another identifiable cause; Collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours; Persistent crying lasting ≥ 3 hours, occurring within 48 hours; Convulsions with or without fever, occurring within 3 days.
There may be circumstances, such as a high incidence of pertussis, when the potential benefits outweigh possible risks.
A history of febrile convulsions, a family history of convulsions, a family history of SIDS (Sudden Infant Death Syndrome) and a family history of an adverse event following DTwP-rHepB-Hib vaccination do not constitute contraindications.
HIV infection is not considered as a contraindication for diphtheria, tetanus, pertussis, Hepatitis-B and Hib vaccination. The expected immunological response may not be obtained after vaccination of immunosuppressed patients, e.g. patient on immunosuppressive therapy.
Uni 5 should be administered with caution to subjects with thrombocytopenia, a bleeding disorder since bleeding may occur following intramuscular administration of vaccine to these subjects.
As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine, 1:1000 adrenaline should be available for immediate treatment if such reaction occurs. For this reason the vaccinee should remain under medical supervision for at least 30 minutes after immunization.
As with other vaccines, the administration of Uni 5 should be postponed in subjects suffering from acute severe febrile illness. The presence of minor infection, however, is not a contraindication for vaccination.
Uni 5 should under no circumstances be administered intravenously.
The vaccine is NOT to be used for the treatment of Diphtheria, Tetanus, Pertussis, Hepatitis-B or Haemophilus influenzae type b infection.
Effects on ability to drive and use machines: Not applicable.
Summary of the safety profile:
The type and rate of severe adverse reactions do not differ significantly from the DTwP, rHepB and Hib vaccine reactions described separately.
In an earlier phase 3 clinical trial, 35% of the subjects reported at least one adverse event, out of which commonly reported local adverse events were pain (13%) and swelling (4%) and systemic adverse event was fever (28%).
Description of selected adverse reactions:
For this vaccine, mild local or systemic reactions are common. Some temporary swelling, tenderness and redness at the site of injection together with fever may occur in a small number of cases. With similar pentavalent vaccines occasional severe reactions of high fever, irritability and screaming may develop within 24 hours of administration. Hypotonic-hyporesponsive episodes have been reported. Febrile convulsions have been reported at a rate of one per 12,500 doses administered. Administration of acetaminophen at the time and 4-8 hours after vaccination decreases the subsequent incidence of febrile reactions.
The national childhood encephalopathy study in the United Kingdom showed a small increased risk of acute encephalopathy (primary seizures) following DTwP immunization.
However subsequent detailed reviews of all available studies by a number of groups, including the United States Institute of Medicine, the Advisory Committee on Immunization Practices, and the paediatric association of Australia, Canada, the United Kingdom and the United States, concluded that the data did not demonstrate a causal relationship between DTwP and chronic nervous system dysfunction in children. Thus there is no scientific evidence that these reactions have any permanent consequences for the children.
As with other intramuscular injections, use with caution in patients on anticoagulant therapy.
Immunosuppressive therapies, including irradiations, anti-metabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiological doses), may reduce the immune response to vaccines. Short-term (< 2 weeks) corticosteroids therapy or intra-articular, bursa, or tendon injections with corticosteroids would not be immunosuppressive. (See Precautions.)
Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Special precautions for disposal and other handling: Uni 5 is available as a suspension. Upon storage, a white deposit and clear supernatant may be observed. The vaccine should be shaken well in order to obtain a homogenous turbid white suspension and visually inspected for any foreign particulate matter and/or variation of physical aspect prior to administration. In the event of either of the above being observed, discard the vaccine.
Vaccine Vial Monitor (VVM) is part of the label. The colour dot that appears on the label of the vial, is a VVM. This is a time-temperature sensitive dot that provides an indication of the cumulative heat to which the vial has been exposed. It warns the end user when exposure to heat is likely to have degraded the vaccine beyond an acceptable level.
The interpretation of the VVM is simple. Focus on the central square. Its colour will change progressively. As long as the colour of this square is lighter than the colour of the ring, then the vaccine can be used. As soon as the colour of the central square is the same colour as the ring or of a darker colour than the ring, then the vial should be discarded.
Any unused medicinal product or waste material should be discarded as Biomedical waste.
Special precautions for storage: Uni 5 should be stored between 2°C - 8°C throughout their use.
Do not freeze. Discard if the vaccine has been frozen.
Once opened, multi dose vials of Uni 5 from which one or more doses of vaccine have been removed during an immunization session may be used in subsequent immunization sessions for up to a maximum of 4 weeks, provided that all of the following conditions are met: 1. The expiry date has not passed.
2. The vaccines are stored under appropriate cold chain conditions.
3. The vaccine vial septum has not been submerged in water.
4. Aseptic technique has been used to withdraw all doses.
5. The vaccine vial monitor (VVM) has not reached the discard point.
Shelf-life: 30 months from the date of manufacture.
J07AG52 - haemophilus influenzae B, combinations with pertussis and toxoids ; Belongs to the class of hemophilus influenzae B bacterial vaccines.
Susp for inj (vial) (whitish turbid liquid) 10's.