Therapeutic Indications For active primary immunization against diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenza type b disease in infants 6 weeks of age.

Arapenta™ is for intramuscular use only.
Recommended for administration of 3 doses (1 dose = 0.5 mL) at 6, 10, 14 weeks of age by intramuscular injection.
The liquid vaccine vial should be shaken before use to homogenize the suspension. The vaccine should be injected intramuscularly. The anterolateral aspect of the upper thigh is the preferred site of injection. An injection into a child’s buttocks may cause injury to the sciatic nerve and is not recommended. It must not be injected into the skin as this may give rise to local reaction. One pediatric dose is 0.5mL. A sterile syringe and sterile needle must be used for each injection.

Known hypersensitivity to any component of the vaccine, or a 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. There are few contraindications to the first dose of DTwP – fits or abnormal cerebral signs in the newborn period or other serious neurological abnormality are contraindications to the pertussis component. In this case, the vaccines should not be given as a combination vaccine but DT should be given instead of DTwP and HepB and Hib vaccines given separately. The vaccine will not harm individuals currently or previously infected with the hepatitis B virus. Individuals infected with the human immune-deficiency virus (HIV), both asymptomatic and symptomatic, should be immunized with combined vaccine according to standard schedules.

Arapenta™ inj. should be administered in the gluteal region, and it must not be administered intravenously.
Thimerosal (an organomercuric compound) has been used in the manufacturing process of this medicinal product and residues of it are present in the final product. Therefore, sensitization reactions may occur.
As with any injectable vaccine, appropriate medical supervision and treatment should always be readily available in case of immediate allergic reactions, such as anaphylactic shock or anaphylactic reaction, following administration of the vaccine. Before administering the vaccine, precautions should be taken to avoid undesirable reactions.
These precautions include: review of the individual’s medical history, particularly regarding hypersensitivity reactions to previous administration of any type of vaccine, as well as the individual’s history of recent health disorders and any previous vaccinations.

The administration of any subsequent dose of a vaccine containing the whole-cell pertussis component should be carefully considered if, in connection with the administration of DTP vaccine, one or more of the following effects have been observed:
-40.0℃ temperature within 48 hours following vaccination (not due to other identifiable causes);
-collapse or shock (hypotonic hyporesponsive episodes) within 48 hoursfollowing vaccination;
-persistent crying lasting more than 3 hours during the 48 hours followingvaccination;
-convulsions, with or without fever, within 3 days following vaccination.There may be circumstances, such as high incidence of pertussis, when potential benefits outweigh possible risks.
HIV seropositivity does not represent a contraindication to vaccination. Patients with an immunodeficiency disorder or receiving immunosuppressive therapy may have a reduced immunological response. Individuals infected with the human immuno-deficiency virus(HIV), both asymptomatic and symptomatic, should be immunized with combined vaccine according to standard schedules.
The vaccination must not be injected into a blood vessel.
Arapenta™ inj. (DTwP-HepB-Hib fully liquid combined vaccine) should be administered with caution to subjects with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration to these subjects. A fine needle should be used for the vaccination and firm pressure applied to the site (without rubbing) for at least two minutes following administration.

4.5 Interactions with other medicinal products and other forms of interaction
The Arapenta inj. can be given safely and effectively at the same times as BCG, measles, polio(OPV, or IPV), and yellow fever vaccines and vitamin A supplementation. If Arapenta inj. is given at the same time as other vaccines, it should be administered at a separate site. It should not be mixed in the vial or syringe with any other vaccine unless it is licensed for use as a combined product.

Not applicable. This vaccine is intended only for pediatric use.

Not applicable.

The type and rate of adverse reactions of the DTwP-HepB-Hib fully liquid combination vaccine do not differ significantly from the DTwP, HepB, and Hib vaccine reactions described separately.
For DTwP, mild local or systemic reactions are common. Some temporary swelling tenderness and redness at the site of injection together with fever occur in a large proportion of cases. Occasionally severe reactions of high fever, irritability and screaming develop within 24 hours of administration. Hypotonic- hyporesponsive episodes have been reported. Febrile convulsions have been reported at a rate of one per 12500 doses administered. Administration of acetaminophen at the time and 4-8 hours after immunization decreases the subsequent incidence of febrile reactions. The national childhood encephalopathy study in the United Kingdom showed a small increased risk of encephalopathy (Primarily seizure) following DTP immunization. However subsequent detailed review of all available studies by a number of groups, including the United States Institute of Medicine, the Advisory Committee on Immunization Practices, and the pediatric associations of Australia, Canada, the United Kingdom and 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. (In weekly Epidemiological Record, No. 18, 7 May 1999. Page 139).

Hepatitis B vaccine is very well tolerated. In placebo-controlled studies, with the exception of local pain, reported events such as myalgia and transient fever have not been more frequent than in the placebo group. Reports of severe anaphylactic reactions are very rare. Available data do not indicate a causal association between hepatitis B vaccine and Guilain-Barre syndrome, or demyelinating disorders including multiple sclerosis, nor is there any epidemiological data to support a causal association between hepatitis B vaccination and chronic fatigue syndrome, arthritis, autoimmune disorders, asthma, sudden infant death syndrome, or diabetes.
Hib vaccine is very well tolerated. Localized reactions may occur within 24 hours of vaccination, when recipients may experience pain and tenderness at the injection site. These reactions are generally mild and transient. In most cases, they spontaneously resolve within two to three days and further medical attention is not required. Mild systemic reactions, including fever, rarely occur following administration of Hib vaccines. More serious reactions are very rare; a causal relationship between more serious reactions and the vaccine has been established.

Data from clinical studies:

Cardiac disorders
Cardio-respiratory arrest.
Eye disorders
Dacryostenosis acquired, Eye discharge.
Gastrointestinal disorders
Abdominal pain, Constipation, Diarrhea, Infantile colic, Mouth ulceration, Stomatitis, Vomiting.
General disorders and administration site conditions
Decreased activity, Injection site reaction, Pyrexia, Injection site erythema, Injection site swelling, Injection site induration, Injection site rash (Injection Site Skin Flare).
Hepatobiliary disorders
Neonatal cholestasis.

Immune system disorders
Hypersensitivity.
Infections and infestations
Acarodernatitis, Amoebiasis, Atypical pneumonia, Bacterial sepsis, Body tinea, Bronchiolitis, Bronchitis, Carbuncle, Conjunctivitis bacterial, Exanthema subitum, External ear cellulitis, Foliculitis, Fungal skin infection, Furuncle, Gastroenteritis, Impetigo, Meningitis bacterial, Nail infection, Nasopharyngitis, Omphalitis, Oral candidiasis, Otitis externa, Otitis media, Otitis media acute, Pneumonia, Pneumonia bacterial, Pneumonia viral, Rhinitis, Sepsis, Septic shock, Skin bacterial infection, Tinea versicolour, Upper respiratory tract infection, Urinary tract infection, Varicella, Viral infection, Viral rash, Viral rhinitis, Wound infection.
Injury, poisoning and procedural complications
Arthropod bite, Chest injury, Post procedural contusion, Thermal burn.
Metabolism and nutrition disorders
Loss of appetite.

Musculoskeletal and connective tissue disorders
Myalgia, Neoplasms benign, Malignant and unspecified (Incl cysts and polyps), Haemangiama.
Nervous system disorders
Generalised tonic-clonic seizure, Sleepiness.
Psychiatric disorders
Irritability, Restlessness.
Reproductive system and breast disorders
Testicular swelling.
Respiratory, thoracic and mediastinal disorders
Allergic pharyngitis, Aspiration, Bronchial hyperactivity, Cough, Nasal congestion, Rhinitis allergic, Sneezing, Upper-airway cough syndrome.

Skin and subcutaneous tissue disorders
Dermatitis allergic, Dermatitis atopic, Dermatitis contact, Dermatitis diaper, Generalised erythema, Miliaria, Rash, Rash vesicular, Seborrheoic dermatitis.

-To reports any side effect(s):

Saudi Arabia:

-The National Pharmacovigilance and Drug Safety Centre (NPC)
Fax: +966-11-205-7662
Call NPC at +966-11-2038222, Exts:2317-2356-2353-2354-2334-2340.
Toll gree phone: 8002490000
E-mail: npc.drug@sfda.gov.sa
Website: www.sfda.gov.sa/npc

In other countries, please contact the relevant competent authority.

Not applicable.

Not Applicable.

Not Applicable.

Single and repeated dose toxicity studies in which rats were administered clinical route showed no systemic toxicity or target organ toxicity, providing overall evidence that the vaccine was safe and well tolerated in the studied animal species. A local inflammatory response at injection site was observed which tended to diminish over time with no long-term muscle damage or impairment being observed, consistent with other vaccines containing aluminum-adjuvant (Goto et al., 1982).

Adjuvant              :Aluminum Hydroxide Gel (as aluminum) -----0.39 mg

Buffering agent : Sodium phosphate, heptahydrate ---------------0.08 mg

                              : Sodium phosphate, dihydrate ---------------------0.733 mg

Tonicity agent    : Sodium Chloride ----------------------------------------4.25 mg

Stabilizer             :Polysorbate 80 -------------------------------------------5 μg

Preservative       : Thimerosal -----------------------------------------------0.01 w/v%

Diluent                :Water for injection ----------------------------------  q.s.

None known

-36 months when stored at 2 ℃ to 8℃ . -In-use stability after 1st opening (for multi-dose vials): 4 weeks if all the following conditions are met. The expiry date has not passed. The vaccines are stored under appropriate cold chain conditions. The vaccine vial septum has not been submerged in water. Aseptic technique has been used to withdraw all doses. The vaccine vial monitor (VVM), if attached, has not reached the discard point.

Arapenta™ is stable for 36 months at 2 ℃ to 8 ℃ . It can be used safely for 36 months when stored at 2 ℃ to 8 ℃ [36-46℉] in a refrigerator. It should not be frozen.

Elastomeric closures and glass container (vial) for Injections
The containers are colorless and transparent, and have no bubbles.
Packs contain;
•Single-dose: 0.5 mL x 10 vials
•Multi-dose: 5.0 mL x 10 vials

It should not be frozen.
It should be well shaken before use.
And it must be administered by intramuscular injection