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Hexaxim (DTaP-IPV-HB-Hib) is a vaccine used to protect against infectious diseases.
Hexaxim helps to protect against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and serious diseases caused by Haemophilus influenzae type b. Hexaxim is given to children from six weeks of age.
The vaccine works by causing the body to produce its own protection (antibodies) against the bacteria and viruses that cause these different infections:
· Diphtheria is an infectious disease that usually first affects the throat. In the throat, the infection causes pain and swelling that can lead to suffocation. The bacterium that causes the disease also makes a toxin (poison) that can damage the heart, kidneys, and nerves.
· Tetanus (often called lock jaw) is usually caused by the tetanus bacterium entering a deep wound. The bacterium makes a toxin (poison) that causes spasms of the muscles leading to inability to breathe and the possibility of suffocation.
· Pertussis (often called whooping cough) is a highly infectious illness that affects the airways. It causes severe coughing that may lead to problems with breathing. The coughing often has a “whooping” sound. The cough may last for one to two months or longer. Whooping cough can also cause ear infections, chest infections (bronchitis) that may last a long time, lung infections (pneumonia), fits, brain damage, and even death.
· Hepatitis B is caused by the hepatitis B virus. It causes the liver to become swollen (inflamed). In some people, the virus can stay in the body for a long time and can eventually lead to serious liver problems, including liver cancer.
· Poliomyelitis (often just called polio) is caused by viruses that affect the nerves. It can lead to paralysis or muscle weakness most commonly of the legs. Paralysis of the muscles that control breathing and swallowing can be fatal.
· Haemophilus influenzae type b infections (often just called Hib) are serious bacterial infections and can cause meningitis (inflammation of the outer covering of the brain), which can lead to brain damage, deafness, epilepsy, or partial blindness. Infection can also cause inflammation and swelling of the throat leading to difficulties in swallowing and breathing. The infection can affect other parts of the body such as the blood, lungs, skin, bones, and joints.
Important information about the protection provided
- Hexaxim will only help to prevent these diseases if they are caused by the bacteria or viruses targeted by the vaccine. Your child could get diseases with similar symptoms if they are caused by other bacteria or viruses.
- The vaccine does not contain any live bacteria or viruses and it cannot cause any of the infectious diseases against which it protects.
- This vaccine does not protect against infections caused by other types of Haemophilus influenzae nor against meningitis due to other micro-organisms.
- Hexaxim will not protect against hepatitis infection caused by other agents such as hepatitis A, hepatitis C, and hepatitis E.
- Because symptoms of hepatitis B take a long time to develop, it is possible for unrecognised hepatitis B infection to be present at the time of vaccination. The vaccine may not prevent hepatitis B infection in such cases.
- As with any vaccine, Hexaxim may not protect 100% of children who receive the vaccine
To make sure that Hexaxim is suitable for your child, it is important to talk to your doctor or nurse if any of the points below apply to your child. If there is anything you do not understand, ask your doctor, pharmacist, or nurse to explain.
Do not use Hexaxim if your child:
· has had respiratory disorder or swelling of the face (anaphylactic reaction) after administration of Hexaxim
· has had an allergic reaction
- to the active substances,
- to any of the excipients listed in section 6,
- to glutaraldehyde, formaldehyde, neomycin, streptomycin or polymyxin B, as these substances are used during the manufacturing process
- after previous administration of Hexaxim or any other diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, or Hib containing vaccines.
· suffered from a severe reaction affecting the brain (encephalopathy) within 7 days of a prior dose of a pertussis vaccine (acellular or whole cell pertussis).
· has an uncontrolled condition or severe illness affecting the brain and nervous system (uncontrolled neurologic disorder), or uncontrolled epilepsy.
Warnings and precautions
Talk to your doctor, pharmacist or nurse before vaccination if your child:
· has a moderate or high temperature or an acute illness (e.g. fever, sore throat, cough, cold, or flu). Vaccination with Hexaxim may need to be delayed until your child is better.
· has had any of the following events after receiving a pertussis vaccine, as the decision to give further doses of pertussis containing vaccine will need to be carefully considered:
- fever of 40°C or above within 48 hours of vaccination not due to another identifiable cause.
- collapse or shock-like state with hypotonic-hyporesponsive episode (drop in energy) within 48 hours of vaccination.
- persistent, inconsolable crying lasting 3 hours or more, occurring within 48 hours of vaccination.
- fits (convulsions) with or without fever, occurring within 3 days of vaccination.
· previously had Guillain-Barré syndrome (temporary inflammation of nerves causing pain, paralysis, and sensitivity disorders) or brachial neuritis (severe pain and decreased mobility of arm and shoulder) after being given a vaccine containing tetanus toxoid (an inactivated form of tetanus toxin). In this case, the decision to give any further vaccine containing tetanus toxoid should be evaluated by your doctor.
· is having a treatment that suppresses her/his immune system (the body’s natural defenses) or has any disease that causes the weakness of the immune system. In these cases the immune response to the vaccine may be decreased. It is normally recommended to wait until the end of the treatment or disease before vaccinating. However children with long standing problems with their immune system such as HIV infection (AIDS) may still be given Hexaxim, but the protection may not be as good as in children whose immune system is healthy.
· suffers from an acute or chronic illness including chronic renal insufficiency or failure (inability of the kidneys to work properly).
· suffers from any undiagnosed illness of the brain or epilepsy that is not controlled. Your doctor will assess the potential benefit offered by vaccination.
· has any problems with the blood that cause easy bruising or bleeding for a long time after minor cuts. Your doctor will advise you whether your child should have Hexaxim.
Fainting can occur following, or even before, any needle injection. Therefore, tell your doctor or nurse your child fainted with a previous injection.
Other medicines or vaccines and Hexaxim
Tell your doctor or nurse if your child is taking, has recently taken, or might take any other medicines or vaccines.
Hexaxim can be given at the same time as other vaccines such as pneumococcal vaccines, measles, mumps, rubella vaccines, varicella vaccines, rotavirus vaccines or meningococcal vaccines.
When given at the same time with other vaccines, Hexaxim will be given at different injection sites.
Hexaxim contains phenylalanine, potassium and sodium
Hexaxim contains 85 micrograms phenylalanine in each 0.5-mL dose. Phenylalanine may be harmful if you have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body cannot remove it properly.
Hexaxim contains less than 1 mmol potassium (39 mg) and less than 1 mmol sodium (23 mg) per dose, that is to say essentially “potassium-free” and “sodium-free”.
Hexaxim will be given to your child by a doctor or nurse trained in the use of vaccines and who are equipped to deal with any uncommon severe allergic reaction to the injection (see section 4 Possible side effects).
Hexaxim is given as an injection into a muscle (intramuscular route IM) in the upper part of your child’s leg or upper arm. The vaccine will never be given into a blood vessel or into or under the skin.
The recommended dose is as follows:
First course of vaccination (primary vaccination)
Your child will receive either two injections given at an interval of two months, or three injections given at an interval of one to two months (at least four weeks apart). This vaccine should be used according to the local vaccination programme.
Additional injections (booster)
After the first course of injections, your child will receive a booster dose, in accordance with local recommendations, at least 6 months after the last dose of the first course. Your doctor will tell you when this dose should be given.
If you forget one dose of Hexaxim
If your child misses a scheduled injection, it is important that you discuss with your doctor or nurse who will decide when to give the missed dose.
It is important to follow the instructions from the doctor or nurse that your child completes the course of injections. If not, your child may not be fully protected against the diseases.
If you have any further questions on the use of this vaccine, ask your doctor, pharmacist, or nurse.
Like all medicines, this vaccine can cause side effects, although not everybody gets them.
Serious allergic reactions (anaphylactic reaction)
If any of these symptoms occur after leaving the place where your child received his/her injection, you must consult a doctor IMMEDIATELY:
- difficulty in breathing
- blueness of the tongue or lips
- a rash
- swelling of the face or throat
- sudden and serious malaise with drop in blood pressure causing dizziness and loss of consciousness, accelerated heart rate associated with respiratory disorders.
When these signs or symptoms (signs or symptoms of anaphylactic reaction) occur they usually develop quickly after the injection is given and while the child is still in the clinic or doctor’s surgery.
Serious allergic reactions are a rare possibility (may affect up to 1 in 1,000 people) after receiving this vaccine.
Other side effects
If your child experiences any of the following side effects, please tell your doctor, nurse, or pharmacist.
- Very common side effects (may affect more than 1 in 10 people) are:
- loss of appetite (anorexia)
- crying
- sleepiness (somnolence)
- vomiting
- pain, redness, or swelling at the injection site
- irritability
- fever (temperature 38°C or higher)
- Common side effects (may affect up to 1 in 10 people) are:
- abnormal crying (prolonged crying)
- diarrhoea
- injection site hardness (induration)
- Uncommon side effects (may affect up to 1 in 100 people) are:
- allergic reaction
- lump (nodule) at the injection site
- high fever (temperature 39.6°C or higher)
- Rare side effects (may affect up to 1 in 1,000 people) are:
- rash
- large reactions at the injection site (larger than 5 cm), including extensive limb swelling from the injection site beyond one or both joints. These reactions start within 24-72 hours after vaccination, may be associated with redness, warmth, tenderness, or pain at the injection site, and get better within 3-5 days without the need for treatment.
- fits (convulsions) with or without fever
- Very rare side effects (may affect up to 1 in 10,000 people) are:
- episodes when your child goes into a shock-like state or is pale, floppy and unresponsive for a period of time (hypotonic reactions or hypotonic hyporesponsive episodes HHE).
Potential side effects
Other side effects not listed above have been reported occasionally with other diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, or Hib-containing vaccines and not directly with Hexaxim:
- Temporary inflammation of nerves causing pain, paralysis and sensitivity disorders (Guillain-Barré syndrome), and severe pain and decreased mobility of arm and shoulder (brachial neuritis) have been reported after administration of a tetanus containing vaccine.
- Inflammation of several nerves causing sensory disorders or weakness of limbs (polyradiculoneuritis), facial paralysis, visual disturbances, sudden dimming or loss of vision (optic neuritis), inflammatory disease of brain and spinal cord (central nervous system demyelination, multiple sclerosis) have been reported after administration of a hepatitis B antigen containing vaccine.
- Swelling or inflammation of the brain (encephalopathy/encephalitis).
- In babies born very prematurely (at or before 28 weeks of gestation) longer gaps than normal between breaths may occur for 2 - 3 days after vaccination.
· Swelling of one or both feet and lower limbs which may occur along with bluish discoloration of the skin (cyanosis), redness, small areas of bleeding under the skin (transient purpura), and severe crying following vaccination with Haemophilus influenzae type b containing vaccines. If this reaction occurs, it is mainly after first injections and within the first few hours following vaccination. All symptoms should disappear completely within 24 hours without need for treatment.
Reporting of side effects
If your child gets any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. By reporting side effects you can help provide more information on the safety of this medicine.
Keep this vaccine out of the sight and reach of children.
Do not use this vaccine after the expiry date which is stated on the carton and the label after EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C - 8°C).
Do not freeze.
Keep the vaccine in the outer carton in order to protect it from the light.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.
What Hexaxim contains
The active substances are per dose (0.5 mL)1:
Diphtheria Toxoid not less than 20 IU2,4 (30 Lf)
Tetanus Toxoid not less than 40 IU3,4 (10 Lf)
Bordetella pertussis antigens
Pertussis Toxoid 25 micrograms
Filamentous Haemagglutinin 25 micrograms
Poliovirus (Inactivated)5
Type 1 (Mahoney) 40 D-antigen units6
Type 2 (MEF-1) 8 D-antigen units6
Type 3 (Saukett) 32 D-antigen units6
Hepatitis B surface antigen7 10 micrograms
Haemophilus influenzae type b polysaccharide 12 micrograms
(Polyribosylribitol Phosphate)
conjugated to Tetanus protein 22-36 micrograms
1 Adsorbed on aluminium hydroxide, hydrated (0.6 mg Al3+)
2 As lower confidence limit (p= 0.95) and not less than 30 IU as mean value
3 As lower confidence limit (p= 0.95)
4 Or equivalent activity determined by an immunogenicity evaluation
5 Produced on Vero cells
6 Or equivalent antigenic quantity determined by a suitable immunochemical method
7 Produced in yeast Hansenula polymorpha cells by recombinant DNA technology
The other ingredients are:
Disodium hydrogen phosphate, potassium dihydrogen phosphate, trometamol, saccharose, essential amino acids including L-phenylalanine, sodium hydroxide and/or acetic acid and/or hydrochloric acid (for pH adjustment), and water for injections.
The vaccine may contain traces of glutaraldehyde, formaldehyde, neomycin, streptomycin, and polymyxin B.
Marketing Authorisation Holder:
Sanofi Pasteur, 14 Espace Henry Vallée, 69007 Lyon, France
Manufacturer:
Sanofi Pasteur, Marcy l'Etoile, France
Sanofi Pasteur, Val de Reuil, France
Secondary Packaging:
Arab Company for Pharmaceutical Products (ARABIO), Makkah, Kingdome of Saudi Arabia
هيكساكزيم (DTaP-IPV-HB-Hib) هو لقاح يُستخدم للحماية من الأمراض المعدية.
يساعد هيكساكزيم على الحماية من الإصابة بالأمراض التالية: الدفتيريا "الخناق" والكزاز والسعال الديكي "الشاهوق" والتهاب الكبد ب وشلل الأطفال والأمراض الخطيرة التي تسببها المستديمة النزليّة من النمط باء. يُعطى هيكساكزيم للأطفال من عمر ستة أسابيع.
يعمل اللقاح عن طريق تحفيز الجسم على إنتاج الحماية الخاصة به (الأجسام المضادة) ضد البكتيريا والفيروسات التي تسبب الأمراض المختلفة التالية:
· الدفتيريا "الخناق" مرض معدٍ يصيب عادة الحلق أوّلاً. تسبّب العدوى الألم والتورّم في الحلق مما قد يؤدّي إلى الاختناق. كما تفرز البكتيريا المسببة للمرض سمًّا يمكن أن يُلحق الضرر بالقلب والكلى والأعصاب.
· الكزاز (غالبًا ما يُسمّى كزاز الفك) يحدث عادة بسبب دخول بكتيريا الكزاز عبر جرح عميق. تفرز البكتيريا سمًّا يسبّب التشنّجات في العضلات، مما يؤدّي إلى عدم القدرة على التنفّس واحتماليّة الاختناق.
· الشاهوق (يُطلق عليه غالبًا السعال الديكي) هو مرض شديد العدوى يُصيب الجهاز التنفسي. يسبّب سعالاً شديدًا قد يؤدي إلى مشاكل في التنفّس. غالبًا ما يكون للسعال صوت يشبه "صوت الديك". قد يستمرّ السعال لمدّة شهر إلى شهرين أو أكثر. يمكن أن يسبب السعال الديكي أيضًا التهابات الأذن والتهابات الصدر (التهاب الشعب الهوائيّة) التي قد تستمرّ لفترة طويلة، والتهابات الرئة (الالتهاب الرئوي)، وتشنّجات وتلف في الدماغ وحتّى الوفاة.
· التهاب الكبد الوبائي (ب) ناجم عن فيروس التهاب الكبد (ب) وهو يؤدّي إلى تورّم الكبد (التهاب). يمكن أن يبقى الفيروس في الجسم لفترة طويلة عند بعض الأشخاص، ويمكن أن يؤدّي في النهاية إلى مشاكل خطيرة في الكبد، بما في ذلك سرطان الكبد.
· التهاب سنجابية النخاع (غالبًا ما يُطلق عليه شلل الأطفال فقط) يحدث بسبب فيروسات تصيب الأعصاب. يمكن أن تؤدّي الإصابة إلى الشلل أو ضعف العضلات الذي يكون أكثر شيوعًا في الساقين. كما يمكن أن يكون شلل العضلات التي تتحكّم في التنفّس والبلع قاتلاً.
· عدوى المستديمة النزليّة من النوع (ب) (التي تُسمّى غالبًا Hib) هي عدوى بكتيريّة خطيرة يمكن أن تسبّب التهاب السحايا (التهاب الغطاء الخارجي للدماغ)، مما قد يؤدي إلى تلف الدماغ أو الصمم أو الصرع أو العمى الجزئي. يمكن أن تسبّب العدوى أيضًا التهاب الحلق وتورّمه، مما يؤدي إلى صعوبات في البلع والتنفّس. ويمكن أن تؤثّر العدوى على أجزاء أخرى من الجسم مثل الدم والرئتين والجلد والعظام والمفاصل.
معلومات مهمّة حول الحماية التي يوفّرها اللقاح
· سوف يساعد هيكساكزيم على منع هذه الأمراض فقط إذا كانت ناجمة عن البكتيريا أو الفيروسات المستهدفة باللقاح. قد يُصاب طفلك بأعراض مشابهة إذا كانت ناجمة عن بكتيريا أو فيروسات أخرى.
· لا يحتوي اللقاح على أيّ بكتيريا أو فيروسات حيّة ولا يمكن أن يسبّب أيًا من الأمراض المعدية التي أُعدّ للحماية منها.
· لا يحمي هذا اللقاح من الالتهابات التي تسببها أنواع أخرى من المستديمة النزليّة أو ضد التهاب السحايا الذي تسبّبه كائنات حيّة دقيقة أخرى.
· لن يحمي هيكساكزيم من عدوى التهاب الكبد الناتج عن عوامل أخرى مثل التهاب الكبد A والتهاب الكبد C والتهاب الكبد E.
· نظرًا لأنّ أعراض التهاب الكبد ب B تستغرق وقتًا طويلاً لتتطوّر، فمن الممكن أن تكون عدوى التهاب الكبد ب B غير الظاهرة موجودة وقت التطعيم. قد لا يمنع اللقاح عدوى التهاب الكبد ب في مثل هذه الحالات.
· كما هو الحال مع أيّ لقاح، لا يمنح هيكساكزيم الحماية 100% للأطفال الذين يتلقون اللقاح.
للتأكّد من أنّ هيكساكزيم مناسب لطفلك، من المهمّ التحدّث مع طبيبك أو ممرّضتك إذا كانت أيّ من النقاط أدناه تنطبق على طفلك. إذا استعصى عليك فهم أيّ شيء، فاطلب من طبيبك أو الصيدلي أو الممرّض(ة) توضيحه لك.
لا تستخدمِ هيكساكزيم إذا كان طفلك:
· لديه اضطراب في الجهاز التنفّسي أو تورّم في الوجه (ردّ فعل تأقي) بعد تلقّي هيكساكزيم.
· لديه ردّ فعل تحسسي:
- تجاه المواد الفعالة،
- تجاه أيّ من المواد غير الفعالة المدرجة في الفقرة رقم 6،
- تجاه الغلوتارالدهيد أو الفورمالديهايد أو النيومايسين أو الستربتومايسين أو البوليميكسين ب، لأنّه يتمّ استخدام هذه المواد أثناء عملية التصنيع،
- بعد تلقي لقاح هيكساكزيم في السابق أو أي لقاحات أخرى تحتوي على الدفتيريا أو الكزاز أو السعال الديكي أو شلل الأطفال أو التهاب الكبد ب أو Hib.
· قد عانى من رد فعل شديد يؤثر على الدماغ (اعتلال الدماغ) في غضون 7 أيام من جرعة سابقة من لقاح السعال الديكي (السعال الديكي اللاخلوي أو الخلوي الكامل).
· يعاني من حالة غير منضبطة أو مرض شديد يؤثر على الدماغ والجهاز العصبي (اضطراب عصبي غير منضبط) أو الصرع غير المنضبط.
التحذيرات والاحتياطات
تحدّث إلى طبيبك أو الصيدلي أو الممرّض (ة) قبل التطعيم إذا كان طفلك:
· يعاني من حمى معتدلة أو مرتفعة أو مرض حاد (مثل الحمى أو التهاب الحلق أو السعال أو الزكام أو الأنفلونزا). قد يلزم تأخير التطعيم بهيكساكزيم حتى يتحسّن طفلك.
· تعرّض لأيّ من الأحداث التالية بعد تلقّي لقاح السعال الديكي، وذلك لأنّ قرار إعطاء جرعات إضافيّة من لقاح السعال الديكي سيحتاج حينها إلى دراسة متأنيّة:
- حمى تصل إلى 40 درجة مئوية أو أعلى في غضون 48 ساعة من التطعيم بدون سبب آخر واضح.
- الانهيار أو حالة شبيهة بالصدمة مع حالة ارتخاء وانخفاض رد الفعل (انخفاض في الطاقة) في غضون 48 ساعة من التطعيم.
- بكاء مستمر لا يستجيب للتهدئة لمدة 3 ساعات أو أكثر، يحدث في غضون 48 ساعة من التطعيم.
- نوبات (تشنّجات) مع أو بدون حمى، تحدث في غضون 3 أيام من التطعيم.
· عانى من متلازمة غيلان باريه (التهاب مؤقت في الأعصاب يسبب الألم والشلل واضطرابات حسيّة) أو التهاب الأعصاب العضديّة (ألم شديد وتناقص حركة الذراع والكتف) بعد تلقي لقاح يحتوي على تكسُيد الكزاز (شكل غير نشط من ذيفان الكزاز). في هذه الحالة، يجب على طبيبك تقييم قرار إعطاء أي لقاح آخر يحتوي على ذوفان الكزاز.
· يخضع لعلاج مثبّط للمناعة (الدفاعات الطبيعيّة للجسم) أو يعاني من أي مرض يسبب ضعف الجهاز المناعي. في هذه الحالات قد تنخفض الاستجابة المناعيّة للقاح. يوصى عادة بالانتظار حتى نهاية العلاج أو المرض قبل التطعيم. ومع ذلك، يمكن إعطاء هيكساكزيم للأطفال الذين يعانون من مشاكل طويلة الأمد في جهاز المناعة مثل عدوى فيروس نقص المناعة البشرية (الإيدز)، ولكن قد لا يحظون بحماية جيدة كما هو الحال لدى الأطفال الذين يتمتعون بنظام مناعة طبيعي.
· يعاني من مرض حاد أو مزمن بما في ذلك القصور أو الفشل الكلوي المزمن (عجز الكلى عن العمل بشكل صحيح).
· يعاني من أي مرض غير مشخّص في الدماغ أو الصرع غير المنضبط. سيقوم الطبيب بتقييم الفوائد المحتملة التي يوفّرها التطعيم.
· يعاني من أيّ مشاكل في الدم تسبب سهولة حدوث الكدمات أو النزيف الذي يستمرّ لفترة طويلة بعد جروح طفيفة. سوف ينصحك طبيبك إذا كان يمكن إعطاء هيكساكزيم لطفلك.
يمكن أن يحدث إغماء بعد، أو حتى قبل، أيّ حقن إبرة. لذلك، أخبر الطبيب أو الممرّض(ة) أنّ طفلك أغميَ عليه مع حقنة سابقة.
أدوية أو لقاحات أخرى وهيكساكزيم
أخبر طبيبك أو ممرضك عما إذا كان طفلك يتناول أو تناول مؤخرًا أو قد يتناول أي أدوية أو لقاحات أخرى.
يمكن إعطاء هيكساكزيم في الوقت ذاته مع لقاحات أخرى مثل لقاحات المكورات الرئوية أو اللقاح الثلاثي "الحصبة – النكاف- الحصبة الألمانيّة" أو لقاحات الحماق أو لقاحات فيروس الروتا أو لقاحات المكورات السحائية.
عندما يتم إعطاء هيكساكزيم في الوقت نفسه مع لقاحات أخرى، سوف يُعطى في مواقع حقن مختلفة.
يحتوي هيكساكزيم على الفينيل ألانين والبوتاسيوم والصوديوم
يحتوي هيكساكزيم على 85 ميكروغرام من الفينيل ألانين في كل جرعة من 0.5 مل. قد يكون الفينيل ألانين ضارًا إذا كنت تعاني من بيلة الفينيل كيتون، وهو اضطراب وراثي نادر يتراكم فيه الفينيل ألانين لأنّ الجسم لا يستطيع إزالته بشكل صحيح.
يحتوي هيكساكزيم على أقلّ من 1 مليمول من البوتاسيوم (39 ملغ) وأقل من 1 مليمول من الصوديوم (23 ملغ) لكلّ جرعة، وهذا يعني بشكل أساسي أنّه "خالٍ من البوتاسيوم" و"خالٍ من الصوديوم".
سيتم إعطاء هيكساكزيم لطفلك من قبل طبيب أو ممرض(ة) مدرّب(ة) على استخدام اللقاحات ولديهما استعداد للتعامل مع أي رد فعل تحسسي شديد غير شائع ينجم عن الحقن (انظر الفقرة 4 - الأعراض الجانبيّة المحتملة).
يتم إعطاء هيكساكزيم عن طريق الحقن في العضلات في الجزء العلوي من ساق طفلك أو الجزء العلوي من ذراعه. لن يتم إعطاء اللقاح في وعاء دموي أو داخل الجلد أو تحته.
الجرعة الموصى بها هي كما يلي:
الدورة الأولى للتطعيم (التطعيم الأولي)
سوف يتلقى طفلك إما حقنتين بينهما فاصل زمني مدّته شهران أو ثلاث حقن بين كلّ حقنة وأخرى فاصل زمني يتراوح من شهر إلى شهرين (أربعة أسابيع على الأقل). يجب استخدام هذا اللقاح وفقًا لبرنامج التطعيم المحلي.
حقن إضافيّة (معززة)
سيتلقى طفلك جرعة معززة بعد دورة التطعيم الأولى، وفقًا للتوصيات المحلية، بعد 6 أشهرعلى الأقل من آخر جرعة في الدورة الأولى. سيخبرك طبيبك بموعد إعطاء هذه الجرعة.
إذا نسيت جرعة واحدة من هيكساكزيم
إذا فات طفلك تلقّي حقنة مقررة، فمن المهم أن تناقش مع طبيبك أو ممرضك الذي سقرر وقت إعطاء الجرعة الفائتة.
من المهم اتباع إرشادات الطبيب أو الممرض بشأن إكمال الحقن المقررة لطفلك.
إذا لم تلتزم بذلك، فقد لا يتمتع طفلك بالحماية الكاملة من الأمراض.
إذا كان لديك أي أسئلة أخرى حول استخدام هذا اللقاح، اسأل طبيبك أو الصيدلي أو الممرض(ة).
كما هو الحال مع سائر الأدوية، يمكن أن يسبب هذا اللقاح أعراضًا جانبية، مع أنّها لا تحدث لدى جميع من يستخدمه.
تفاعلات حساسية خطيرة (رد الفعل التأقي)
في حالة حدوث أي من الأعراض التالية بعد مغادرة المكان الذي تلقى فيه طفلك اللقاح، يجب عليك استشارة الطبيب فورًا:
· صعوبة في التنفّس
· ازرقاق اللسان أو الشفتين
· طفح جلدي
· تورّم في الوجه أو الحلق
· الشعور بتوعّك مفاجئ وخطير مع انخفاض في ضغط الدم بسبب الدوخة وفقدان الوعي، وتسارع معدّل ضربات القلب المرتبط باضطرابات الجهاز التنفّسي.
عندما تحدث هذه العلامات أو الأعراض (علامات أو أعراض رد الفعل التحسسي) فإنها عادة ما تتطور بسرعة بعد إعطاء الحقن بينما لا يزال الطفل في عيادة الطبيب.
الحساسية الخطيرة هي احتمال نادر (قد تؤثر على ما يصل إلى 1 من كل 1000 شخص) بعد تلقي هذا اللقاح.
أعراض جانبيّة أخرى
إذا تعرّض طفلك لأيّ من الأعراض الجانبية التالية، يرجى إخبار الطبيب أو الممرض(ة) أو الصيدلي.
· الأعراض الجانبية الشائعة جدًا (قد تؤثر على أكثر من 1 من كل 10 أشخاص) هي:
- فقدان الشهية
- بكاء
- نعاس
- قيء
- ألم أو احمرار أو تورّم في موقع الحقن
- هيجان
- حمى (درجة حرارة 38 درجة مئوية أو أعلى)
· الأعراض الجانبية الشائعة (قد تؤثر على ما يصل إلى 1 من كل 10 أشخاص) هي:
- بكاء غير طبيعي (بكاء مُطوّل)
- إسهال
- تيبّس موقع الحقن (تصلّب)
· الأعراض الجانبية غير الشائعة (قد تؤثر على ما يصل إلى 1 من كل 100 أشخاص) هي:
- رد فعل تحسسي
- ظهور كتلة (عُقيدة) في موقع الحقن
- ارتفاع في درجة الحرارة (درجة الحرارة تصل إلى 39.6 درجة مئوية أو أعلى).
· الأعراض الجانبية النادرة (قد تؤثر على ما يصل إلى 1 من كل 1000 أشخاص) هي:
- طفح جلدي
- ردود فعل واسعة في موقع الحقن (تتجاوز 5 سم)، بما في ذلك تورم واسع النطاق للطرف الذي تمّ الحقن فيه يتجاوز واحد أو كلا المفصلين. تبدأ ردود الفعل هذه في غضون 24-72 ساعة بعد التطعيم، وقد تترافق مع احمرار أو دفء أو إيلام أو ألم في موقع الحقن، وتتحسن في غضون 3-5 أيام دون الحاجة إلى العلاج.
- نوبات (تشنّجات) مع أو بدون حمى.
· الأعراض الجانبية النادرة جدًا (قد تؤثر على ما يصل إلى 1 من كل 10000 أشخاص) هي:
- فترات يدخل طفلك فيها في حالة تشبه الصدمة أو يصبح شاحبًا ومرتخيًا ولا يستجيب لفترة من الزمن (ردود فعل منخفضة التوتّر أو نوبات ارتخاء وانخفاض ردّ الفعل HHE).
الأعراض الجانبيّة المحتملة
تمّ الإبلاغ عن أعراض جانبية أخرى غير مذكورة أعلاه من حين لآخر مع لقاحات الدفتيريا، والكزاز، والسعال الديكي، وشلل الأطفال، والتهاب الكبد ب الأخرى، أو لقاحات محتوية على Hib وليس مع هيكساكزيم مباشرة:
· تم الإبلاغ عن التهاب مؤقت في الأعصاب يسبب الألم والشلل واضطرابات حسيّة (متلازمة غيلان باريه) وألم شديد وتدني القدرة في حركة الذراع والكتف (التهاب الأعصاب العضدية) بعد تناول لقاح يحتوي على الكزاز.
· تمّ الإبلاغ عن حدوث التهاب عدّة أعصاب مما يسبب اضطرابات حسيّة أو ضعف الأطراف (التهاب الأعصاب والجذور)، وشلل الوجه، الاضطرابات البصريّة، غباش العين المفاجئ أو فقدان الرؤية (التهاب العصب البصري)، مرض التهاب الدماغ والحبل الشوكي (فقدان الميالين بالجهاز العصبي المركزي، التصلب المتعدد) بعد إعطاء لقاح يحتوي على مستضد التهاب الكبد ب.
· تورّم أو التهاب الدماغ (اعتلال الدماغ/التهاب الدماغ).
· قد تحدث فجوات أطول من المعتاد بين الأنفاس لدى الأطفال المولودين قبل الأوان "الخدّج" (عند أو قبل 28 أسبوعًا من الحمل) لمدة يومين إلى ثلاثة أيام بعد التطعيم.
· قد يحدث تورّم في إحدى القدمين أو كلتيهما والأطراف السفلية مع احتمال تغيّر لون الجلد إلى الأزرق (زرقة)، واحمرار، ونزيف تحت الجلد في مناطق صغيرة (فرفرية عابرة)، والبكاء الشديد بعد التطعيم بلقاحات المستدمية النزلية من النوع ب. إذا حدث رد الفعل هذا، فإنّه يحدث بشكل أساسي بعد الحقن الأولي وخلال الساعات القليلة الأولى بعد التطعيم. يجب أن تختفي جميع الأعراض تمامًا خلال 24 ساعة دون الحاجة إلى علاج.
التبليغ عن الأعراض الجانبيّة
إذا أصيب طفلك بأيّ أعراض جانبيّة، تحدّث إلى طبيبك أو الصيدلي أو الممرّض(ة). يتضمّن ذلك أي أعراض جانبيّة محتملة غير مذكورة في هذه النشرة. من خلال الإبلاغ عن الأعراض الجانبيّة، يمكنك المساعدة في توفير مزيد من المعلومات حول سلامة هذا الدواء.
للإبلاغ عن أيّ عارض (أعراض) جانبيّ (ة):
· المملكة العربية السعودية:
· المركز الوطني للتّيقُّظ والسلامة الدوائية: - مركز اتصال الهيئة العامة للغذاء والدواء: 19999 - البريد الإلكتروني: npc.drug@sfda.gov.sa - الموقع الإلكتروني: https://ade.sfda.gov.sa/ · سانوفي للتّيقُّظ والسلامة الدوائية: - +966-54-428-4797 - KSA_Pharmacovigilance@sanofi.com |
إحفظ هذا اللقاح بعيدًا عن نظر الأطفال ومتناولهم.
لا تستعمل هذا اللقاح بعد تاريخ انتهاء الصلاحية المدوّن على علبة الكرتون والملصق بعد EXP. يشير تاريخ انتهاء الصلاحية إلى اليوم الأخير من الشهر المذكور.
يُحفظ في البرّاد (بين درجتين مئويّتين و8 درجات مئويّة). لا تجمّده.
إحفظ اللقاح داخل علبة الكرتون الخارجيّة لحمايته من الضوء.
لا تتخلّص من أيّ أدوية عن طريق مياه الصرف الصحي أو النفايات المنزليّة. إسأل الصيدلي عن كيفيّة التخلّص من الأدوية التي لم تعد تستعملها. فمن شأن هذه التدابير أن تساعد في حماية البيئة.
محتويات هيكساكزيم
المواد الفعالة في كلّ جرعة مكوّنة من 0.5 مل 1:
توكسُيد الدفتيريا لا يقلّ عن 20 وحدة دوليّة2,4 (30 Lf)
توكسُيد التيتانوس "الكزاز" لا يقلّ عن 40 وحدة دوليّة3,4 (10 Lf)
مستضدّات البورديتيلا الشاهوقيّة
ذوفان الشاهوق 25 ميكروجرام
الراص الدموي الخيطي 25 ميكروجرام
فيروس شلل الأطفال (المُعطل)5
النوع 1 (ماهوني) 40 دي وحدات مستضد6
النوع 2 (إم إي إف-1) 8 دي وحدات مستضد6
النوع 3 (سوكيت) 32 دي وحدات مستضد6
مستضد السطح لفيروس التهاب الكبد الوبائي ب7 10 ميكروجرام
المستديمة النزلية نوع ب عديد السكريد 12 ميكروجرام
(فوسفات بوليريبوسيلريبوتيل)
مقترن ببروتين الكزاز 22-36 ميكروجرام
1 ممتزّ على هيدروكسيد الألمنيوم المائي (0.6 ملغ Al3+)
2 كحد أدنى للثقة (p= 0.95) ولا يقل عن 30 وحدة دولية كقيمة متوسطة
3 كحد أدنى للثقة (p= 0.95)
4 أو نشاط مكافئ يحدده تقييم الاستمناع
5 أُنتجت في خلايا فيرو
6 أو كمية مستضدية مكافئة محددة بواسطة طريقة كيميائية مناعية مناسبة
7 أُنتجت في خلايا خميرة هانسينولا بوليمورفا باستخدام تقنيّة الهندسة الوراثيّة.
المحتويات الأخرى:
فوسفات الهيدروجين ثنائي الصوديوم، فوسفات البوتاسيوم ثنائي الهيدروجين، تروميتامول، سكروز، أحماض أمينيّة أساسيّة بما في ذلك إل-فينيل ألانين، هيدروكسيد الصوديوم و/أو حمض الأسيتيك و/أو حمض الهيدروكلوريك (لتعديل الرقم الهيدروجيني)، والماء المخصص للحقن.
قد يحتوي اللقاح على آثار من الغلوتارالدهيد والفورمالديهايد والنيومايسين والستربتومايسين والبوليمكسين ب.
الشكل الصيدلاني لهيكساكزيم ومحتويات العبوة
يتوفّر هيكساكزيم على شكل معلّق معدّ للحقن في محقنة مسبقة التعبئة (0.5 مل).
يتوفر هيكساكزيم في علبة تحتوي على محقنة مسبقة التعبئة أو علبة تحتوي على 10 محاقن مسبقة التعبئة مع إبرتين منفصلتين.
قد لا تكون أحجام العبوات كلّها مسوّقة.
يظهر اللقاح بعد رجّه على شكل معلّق عَكِر ضارب إلى البياض.
حامل رخصة التسويق
شركة سانوفي باستير، 14 ايسبيس هينري فالي، 69007 ليون، فرنسا
الشركة المصنعة:
شركة سانوفي باستير، ميرسيلتو، فرنسا
شركة سانوفي باستير، فالدي روي، فرنسا
مصنع التغليف الثانوي:
الشركة العربية للمستحضرات الدوائية (ARABIO)، مكة المكرمة، المملكة العربية السعودية
Hexaxim (DTaP-IPV-HB-Hib) is indicated for primary and booster vaccination of infants and toddlers from six weeks of age against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive diseases caused by Haemophilus influenzae type b (Hib).
The use of this vaccine should be in accordance with official recommendations.
Posology
Primary vaccination:
The primary vaccination consists of 2 doses (with an interval of at least 8 weeks) or 3 doses (with an interval of at least 4 weeks) in accordance with the official recommendations.
All vaccination schedules including the WHO Expanded Program on Immunisation (EPI) at 6, 10, 14 weeks of age can be used whether or not a dose of hepatitis B vaccine has been given at birth.
Where a dose of hepatitis B vaccine is given at birth;
- Hexaxim can be used for supplementary doses of hepatitis B vaccine from the age of 6 weeks. If a second dose of hepatitis B vaccine is required before this age, monovalent hepatitis B vaccine should be used.
- Hexaxim can be used for a mixed hexavalent/pentavalent/hexavalent combined vaccine immunisation schedule in accordance with official recommendations.
Booster vaccination:
After a 2-dose primary vaccination with Hexaxim, a booster dose must be given.
After a 3-dose primary vaccination with Hexaxim, a booster dose should be given.
Booster doses should be given at least 6 months after the last priming dose and in accordance with the official recommendations. As a minimum, a dose of Hib vaccine must be administered.
In addition:
In the absence of hepatitis B vaccination at birth, it is necessary to give a hepatitis B vaccine booster dose. Hexaxim can be considered for the booster.
When a hepatitis B vaccine is given at birth, after a 3-dose primary vaccination, Hexaxim or a pentavalent DTaP-IPV/Hib vaccine can be administered for the booster.
Hexaxim may be used as a booster in individuals who have previously been vaccinated with another hexavalent vaccine or a pentavalent DTaP-IPV/Hib vaccine associated with a monovalent hepatitis B vaccine.
WHO-EPI schedule (6, 10, 14 weeks):
After a WHO-EPI schedule, a booster dose should be given
- As a minimum, a booster dose of polio vaccine should be given
- In absence of hepatitis B vaccine at birth, a hepatitis B vaccine booster must be given
- Hexaxim can be considered for the booster
Other paediatric population
The safety and efficacy of Hexaxim in infants less than 6 weeks of age have not been established. No data are available.
No data are available in older children (see sections 4.8 and 5.1).
Method of administration
Immunisation must be carried out by intramuscular (IM) injection. The recommended injection sites are the antero-lateral area of the upper thigh (preferred site) or the deltoid muscle in older children (possibly from 15 months of age).
For instructions on handling, see section 6.6.
Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Hexaxim will not prevent disease caused by pathogens other than Corynebacterium diphtheriae,
Clostridium tetani, Bordetella pertussis, hepatitis B virus, poliovirus or Haemophilus influenzae type b. However, it can be expected that hepatitis D will be prevented by immunisation as hepatitis D (caused by the delta agent) does not occur in the absence of hepatitis B infection.
Hexaxim will not protect against hepatitis infection caused by other agents such as hepatitis A, hepatitis C and hepatitis E or by other liver pathogens.
Because of the long incubation period of hepatitis B, it is possible for unrecognised hepatitis B infection to be present at the time of vaccination. The vaccine may not prevent hepatitis B infection in such cases.
Hexaxim does not protect against infectious diseases caused by other types of Haemophilus influenzae or against meningitis of other origins.
Prior to immunisation
Immunisation should be postponed in individuals suffering from moderate to severe acute febrile illness or infection. The presence of a minor infection and/or low-grade fever should not result in the deferral of vaccination.
Vaccination should be preceded by a review of the person’s medical history (in particular previous vaccinations and possible adverse reactions). The administration of Hexaxim must be carefully considered in individuals who have a history of serious or severe reactions within 48 hours following administration of a vaccine containing similar components.
Before the injection of any biological medicinal product, the person responsible for administration must take all precautions known for the prevention of allergic or any other reactions. As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of an anaphylactic reaction following administration of the vaccine.
If any of the following events are known to have occurred after receiving any pertussis containing vaccine, the decision to give further doses of pertussis containing vaccine should be carefully considered:
• Temperature of ≥40°C within 48 hours of vaccination not due to another identifiable cause;
• Collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours of vaccination;
• Persistent, inconsolable crying lasting ≥3 hours, occurring within 48 hours of vaccination;
• Convulsions with or without fever, occurring within 3 days of vaccination.
There may be some circumstances, such as high incidence of pertussis, when the potential benefits outweigh possible risks.
A history of febrile convulsions, a family history of convulsions or Sudden Infant Death Syndrome (SIDS) do not constitute a contraindication for the use of Hexaxim. Individuals with a history of febrile convulsions should be closely followed up as such adverse events may occur within 2 to 3 days post vaccination.
If Guillain-Barré syndrome or brachial neuritis has occurred following receipt of prior vaccine containing tetanus toxoid, the decision to give any vaccine containing tetanus toxoid should be based on careful consideration of the potential benefits and possible risks, such as whether or not the primary vaccination has been completed. Vaccination is usually justified for individuals whose primary vaccination is incomplete (i.e. fewer than three doses have been received).
The immunogenicity of the vaccine may be reduced by immunosuppressive treatment or immunodeficiency. It is recommended to postpone vaccination until the end of such treatment or disease. Nevertheless, vaccination of individuals with chronic immunodeficiency such as HIV infection is recommended even if the antibody response may be limited.
Special populations
Immunogenicity data are available for 105 preterm infants. These data support the use of Hexaxim in preterm infants. As expected in preterm infants, lower immune response has been observed for some antigens, when indirectly compared to term infants, although seroprotective levels have been achieved (see section 5.1). No safety data were collected in preterm infants (born ≤37 weeks of gestation) in clinical trials.
The potential risk of apnoea and the need for respiratory monitoring for 48 to 72 hours should be considered when administering the primary immunisation series to very premature infants (born ≤28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity. As the benefit of vaccination is high in this group of infants, vaccination should not be withheld or delayed.
Immune responses to the vaccine have not been studied in the context of genetic polymorphism.
In individuals with chronic renal failure, an impaired hepatitis B response is observed and administration of additional doses of hepatitis B vaccine should be considered according to the antibody level against hepatitis B virus surface antigen (anti-HBsAg).
Immunogenicity data in HIV-exposed infants (infected and uninfected) showed that Hexaxim is immunogenic in the potentially immunodeficient population of HIV-exposed infants whatever their HIV status at birth (see section 5.1). No specific safety concern was observed in this population.
Precautions for use
Do not administer by intravascular, intradermal or subcutaneous injection.
As with all injectable vaccines, the vaccine must be administered with caution to individuals with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration.
Syncope can occur following, or even before, any vaccination as a psychogenic response to the needle injection. Procedures should be in place to prevent falling and injury and to manage syncope.
Interference with laboratory testing
Since the Hib capsular polysaccharide antigen is excreted in the urine, a positive urine test can be observed within 1 to 2 weeks following vaccination. Other tests should be performed in order to confirm Hib infection during this period.
Hexaxim contains phenylalanine, potassium and sodium
Hexaxim contains 85 micrograms phenylalanine in each 0.5-mL dose. Phenylalanine may be harmful for individuals with phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body cannot remove it properly.
Hexaxim contains less than 1 mmol potassium (39 mg) and less than 1 mmol sodium (23 mg) per dose, that is to say essentially “potassium-free” and “sodium-free”.
Hexaxim can be administered simultaneously with a pneumococcal polysaccharide conjugate vaccine, measles, mumps, rubella (MMR) and varicella-containing vaccines, rotavirus vaccines, a meningococcal C conjugate vaccine or a meningococcal group A, C, W-135 and Y conjugate vaccine, as no clinically relevant interference in the antibody response to each of the antigens has been shown.
If co-administration with another vaccine is considered, immunisation should be carried out on separate injection sites.
Hexaxim must not be mixed with any other vaccines or other parenterally administered medicinal products.
No significant clinical interaction with other treatments or biological products has been reported except in the case of immunosuppressive therapy (see section 4.4).
Interference with laboratory testing: see section 4.4.
Not applicable. This vaccine is not intended for administration to women of child-bearing age.
Not applicable.
a- Summary of the safety profile
In clinical studies in individuals who received Hexaxim, the most frequently reported reactions include injection-site pain, irritability, crying, and injection-site erythema.
Slightly higher solicited reactogenicity was observed after the first dose compared to subsequent doses.
The safety of Hexaxim in children over 24 months of age has not been studied in clinical trials.
b- Tabulated list of adverse reactions
The following convention has been used for the classification of adverse reactions;
Very common (≥1/10)
Common (≥1/100 to <1/10)
Uncommon (≥1/1,000 to <1/100)
Rare (≥1/10,000 to <1/1,000)
Very rare (<1/10,000)
Not known (cannot be estimated from available data)
Table 1: Adverse Reactions from clinical trials and post marketing surveillance
* Adverse reactions from spontaneous reporting.
† See section c.
c- Description of selected adverse reactions
Extensive limb swelling: Large injection-site reactions (>50 mm), including extensive limb swelling from the injection site beyond one or both joints, have been reported in children. These reactions start within 24-72 hours after vaccination, may be associated with erythema, warmth, tenderness or pain at the injection site and resolve spontaneously within 3-5 days. The risk appears to be dependent on the number of prior doses of acellular pertussis containing vaccine, with a greater risk following the 4th dose.
d- Potential adverse events (i.e. adverse events that have been reported with other vaccines containing one or more of the components or constituents of Hexaxim and not directly with Hexaxim).
Nervous system disorders
- Brachial neuritis and Guillain-Barré Syndrome have been reported after administration of a tetanus toxoid-containing vaccine
- Peripheral neuropathy (polyradiculoneuritis, facial paralysis), optic neuritis, central nervous system demyelination (multiple sclerosis) have been reported after administration of a hepatitis B antigen-containing vaccine
- Encephalopathy/encephalitis
Respiratory, thoracic and mediastinal disorders
Apnoea in very premature infants (≤28 weeks of gestation) (see section 4.4)
General disorders and administration site conditions
Oedematous reaction affecting one or both lower limbs may occur following vaccination with Haemophilus influenzae type b-containing vaccines. If this reaction occurs, it is mainly after primary injections and within the first few hours following vaccination. Associated symptoms may include cyanosis, redness, transient purpura, and severe crying. All events should resolve spontaneously without sequel within 24 hours.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.
To reports any side effect(s):
Saudi Arabia:
· The National Pharmacovigilance Centre (NPC):
- SFDA Call Center: 19999
- E-mail: npc.drug@sfda.gov.sa
- Website: https://ade.sfda.gov.sa/
Other GCC States:
- Please contact the relevant competent authority.
Sanofi Pharmacovigilance:
- KSA_Pharmacovigilance@sanofi.com
For any other medical inquiry:
- KSA.Medicalenquiry@sanofi.com
No cases of overdose have been reported.
Pharmaco-therapeutic group: Vaccines, Bacterial and viral vaccines combined, ATC code: J07CA09
The immunogenicity of Hexaxim in children over 24 months of age has not been studied in clinical trials.
Results obtained for each of the components are summarised in the tables below:
Table 1: Seroprotection/Seroconversion rates* one month after primary vaccination with 2 or 3 doses of Hexaxim
Antibody Thresholds | Two doses | Three doses | |||
3-5 Months | 6-10-14 Weeks | 2-3-4 Months | 2-4-6 Months | ||
N=249** | N=123 to 220† | N=322†† | N=934 to 1270‡ | ||
% | % | % | % | ||
Anti-diphtheria (³0.01 IU/mL) | 99.6 | 97.6 | 99.7 | 97.1 | |
Anti-tetanus (³0.01 IU/mL) | 100.0 | 100.0 | 100.0 | 100.0 | |
Anti-PT (Seroconversion ‡‡) (Vaccine response§) |
93.4 98.4 |
93.6 100.0 |
88.3 99.4 |
96.0 99.7 | |
Anti-FHA (Seroconversion ‡‡) (Vaccine response§) |
92.5 99.6 |
93.1 100.0 |
90.6 99.7 |
97.0 99.9 | |
Anti-HBs (³10 mIU/mL) | With hepatitis B vaccination at birth | / | 99.0 | / | 99.7 |
Without hepatitis B vaccination at birth | 97.2 | 95.7 | 96.8 | 98.8 | |
Anti-Polio type 1 (³8 (1/dilution)) | 90.8 | 100.0 | 99.4 | 99.9 | |
Anti-Polio type 2 (³8 (1/dilution)) | 95.0 | 98.5 | 100.0 | 100.0 | |
Anti-Polio type 3 (³8 (1/dilution)) | 96.7 | 100.0 | 99.7 | 99.9 | |
Anti-PRP (³0.15 µg/mL) | 71.5 | 95.4 | 96.2 | 98.0 | |
* Generally accepted surrogates (PT, FHA) or correlates of protection (other components)
N = Number of individuals analysed (per protocol set)
** 3, 5 months without hepatitis B vaccination at birth (Finland, Sweden)
† 6, 10, 14 weeks with and without hepatitis B vaccination at birth (Republic of South Africa)
†† 2, 3, 4 months without hepatitis B vaccination at birth (Finland)
‡ 2, 4, 6 months without hepatitis B vaccination at birth (Argentina, Mexico, Peru) and with hepatitis B vaccination at birth (Costa Rica and Colombia)
‡‡ Seroconversion: minimum 4-fold increase compared to pre-vaccination level (pre-dose 1)
§ Vaccine response: If pre-vaccination antibody concentration <8 EU/mL, then the post-vaccination antibody concentration should be ≥8 EU/mL. Otherwise, post-vaccination antibody concentration should be ≥ pre-immunisation level
Table 2: Seroprotection/Seroconversion rates* one month after booster vaccination with Hexaxim
Antibody Thresholds | Booster vaccination at 11-12 months of age after a two-dose primary course | Booster vaccination during the second year of life following a three-dose primary course | |||
3-5 | 6-10-14 | 2-3-4 | 2-4-6 | ||
N=249** | N=204† | N=178†† | N=177 to 396‡ | ||
% | % | % | % | ||
Anti-diphtheria (³0.1 IU/mL) | 100.0 | 100.0 | 100.0 | 97.2 | |
Anti-tetanus (³0.1 IU/mL) | 100.0 | 100.0 | 100.0 | 100.0 | |
Anti-PT (Seroconversion‡‡) (Vaccine response§) |
94.3 98.0 |
94.4 100.0 |
86.0 98.8 |
96.2 100.0 | |
Anti-FHA (Seroconversion‡‡) (Vaccine response§) |
97.6 100.0 |
99.4 100.0 |
94.3 100.0 |
98.4 100.0 | |
Anti-HBs (³10 mIU/mL) | With hepatitis B vaccination at birth | / | 100.0 | / | 99.7 |
Without hepatitis B vaccination at birth | 96.4 | 98.5 | 98.9 | 99.4 | |
Anti-Polio type 1 (³8 (1/dilution)) | 100.0 | 100.0 | 98.9 | 100.0 | |
Anti-Polio type 2 (³8 (1/dilution)) | 100.0 | 100.0 | 100.0 | 100.0 | |
Anti-Polio type 3 (³8 (1/dilution)) | 99.6 | 100.0 | 100.0 | 100.0 | |
Anti-PRP (³1.0 µg/mL) | 93.5 | 98.5 | 98.9 | 98.3 | |
* Generally accepted surrogates (PT, FHA) or correlates of protection (other components)
N = Number of individuals analysed (per protocol set)
** 3, 5 months without hepatitis B vaccination at birth (Finland, Sweden)
† 6, 10, 14 weeks with and without hepatitis B vaccination at birth (Republic of South Africa)
†† 2, 3, 4 months without hepatitis B vaccination at birth (Finland)
‡ 2, 4, 6 months without hepatitis B vaccination at birth (Mexico) and with hepatitis B vaccination at birth (Costa Rica and Colombia)
‡‡ Seroconversion: minimum 4-fold increase compared to pre-vaccination level (pre-dose 1)
§ Vaccine response: If pre-vaccination antibody concentration (pre-dose 1) <8 EU/mL, then the post-booster antibody concentration should be ≥8 EU/mL. Otherwise, post-booster antibody concentration should be ≥ pre-immunisation level (pre-dose 1)
Immune responses to Hib and pertussis antigens after 2 doses at 2 and 4 months of age
The immune responses to Hib (PRP) and pertussis antigens (PT and FHA) were evaluated after 2 doses in a subset of subjects receiving Hexaxim (N=148) at 2, 4, 6 months of age. The immune responses to PRP, PT and FHA antigens one month after 2 doses given at 2 and 4 months of age were similar to those observed one month after a 2-dose priming given at 3 and 5 months of age:
- anti-PRP titers ≥0.15 µg/mL were observed in 73.0% of individuals,
- anti-PT vaccine response in 97.9% of individuals,
- anti-FHA vaccine response in 98.6% of individuals.
Persistence of immune response
Studies on long-term persistence of vaccine induced antibodies following varying infant / toddler primary series and following Hepatitis B vaccine given at birth or not have shown maintenance of levels above the recognized protective levels or antibody thresholds for the vaccine antigens (see Table 3).
Table 3: Seroprotection ratesa at the age of 4.5 years old after vaccination with Hexaxim
Antibody Thresholds | Primary 6-10-14 weeks and booster at | Primary 2-4-6 months and booster at 12–24 months | |
Without hepatitis B at birth | With hepatitis B at birth | With hepatitis B at birth | |
N=173b | N=103b | N=220c | |
% | % | % | |
Anti-diphtheria (³0.01 IU/mL) (³0.1 IU/mL) |
98.2 75.3 |
97 64.4 |
100 57.2 |
Anti-tetanus (³0.01 IU/mL) (³0.1 IU/mL) |
100 89.5 |
100 82.8 |
100 80.8 |
Anti-PTe (³8 EU/mL) |
42.5 |
23.7 |
22.2 |
Anti-FHAe (³8 EU/mL) |
93.8 |
89.0 |
85.6 |
Anti-HBs (³10 mIU/mL) |
73.3 |
96.1 |
92.3 |
Anti-Polio type 1 (³8 (1/dilution)) |
NAd |
NAd |
99.5 |
Anti-Polio type 2 (³8 (1/dilution)) |
NAd |
NAd |
100 |
Anti-Polio type 3 (³8 (1/dilution)) |
NAd |
NAd |
100 |
Anti-PRP (³0.15 µg/mL) |
98.8 |
100 |
100 |
N = Number of individuals analysed (per protocol set)
a Generally accepted surrogates (PT, FHA) or correlates of protection (other components)
b 6, 10, 14 weeks with and without hepatitis B vaccination at birth (Republic of South Africa)
c 2, 4, 6 months with hepatitis B vaccination at birth (Colombia)
d Due to an OPV National Immunisation Days in the country, Polio results have not been analysed
e 8 EU/mL corresponds to 4 LLOQ (Lower Limit Of Quantification in enzyme-linked immunosorbent assay ELISA).
LLOQ value for anti-PT and anti-FHA is 2 EU/mL
The persistence of the immune responses against the hepatitis B component of Hexaxim was evaluated in infants primed from two different schedules.
For a 2-dose primary infant series at 3 and 5 months of age without hepatitis B at birth, followed by a toddler booster at 11-12 months of age, 53.8% of children were seroprotected (anti-HBsAg ≥10 mIU/mL) at 6 years of age, and 96.7% presented an anamnestic response after a challenge dose with a standalone Hepatitis B vaccine.
For a primary series consisting of one dose of hepatitis B vaccine given at birth followed by a 3-dose infant series at 2, 4, and 6 months of age without a toddler booster, 49.3% of children were seroprotected (anti-HBsAg ≥10 mIU/mL) at 9 years of age, and 92.8% presented an anamnestic response after a challenge dose with a standalone Hepatitis B vaccine.
These data support persisting immune memory induced in infants primed with Hexaxim.
Immune responses to Hexaxim in preterm infants
Immune responses to Hexaxim antigens in preterm (105) infants (born after a gestation period of 28 to 36 weeks), including 90 infants born to women vaccinated with Tdap vaccine during pregnancy and 15 to women not vaccinated during pregnancy, were evaluated following a 3-dose primary vaccination course at 2, 3, and 4 months of age, and a booster dose at 13 months of age.
One month after primary vaccination, all subjects were seroprotected against diphtheria (≥0.01 IU/mL), tetanus (≥0.01 IU/mL), and poliovirus types 1, 2 and 3 (≥8 (1/dilution)); 89.8% of subjects were seroprotected against hepatitis B (≥10 IU/mL) and 79.4% were seroprotected against Hib invasive diseases (≥0.15 µg/mL).
One month after the booster dose, all subjects were seroprotected against diphtheria (≥0.1 IU/mL), tetanus (≥0.1 IU/mL), and poliovirus types 1, 2 and 3 (≥8 (1/dilution)); 94.6% of subjects were seroprotected against hepatitis B (≥10 IU/mL) and 90.6% were seroprotected against Hib invasive diseases (≥1 µg/mL).
Regarding pertussis, one month after primary vaccination 98.7% and 100% of subjects developed antibodies ≥8 EU/mL against PT and FHA antigens, respectively. One month after the booster dose, 98.8% of subjects developed antibodies ≥8 EU/mL against both PT and FHA antigens. Pertussis antibody concentrations increased by 13-fold after primary vaccination and by 6- to 14-fold after the booster dose.
Immune responses to Hexaxim in infants born to women vaccinated with Tdap during pregnancy
Immune responses to Hexaxim antigens in term (109) and preterm (90) infants born to women vaccinated with Tdap vaccine during pregnancy (between 24 and 36 weeks of gestation) were evaluated following a 3-dose primary vaccination course at 2, 3, and 4 months of age, and a booster dose at 13 (preterm infants) or 15 (term infants) months of age.
One month after primary vaccination, all subjects were seroprotected against diphtheria (≥0.01 IU/mL), tetanus (≥0.01 IU/mL), and poliovirus types 1 and 3 (≥8 (1/dilution)); 97.3% of subjects were seroprotected against poliovirus type 2 (≥8 (1/dilution)); 94.6% of subjects were seroprotected against hepatitis B (≥10 IU/mL) and 88.0% were seroprotected against Hib invasive diseases (≥0.15 µg/mL).
One month after the booster dose, all subjects were seroprotected against diphtheria (≥0.1 IU/mL), tetanus (≥0.1 IU/mL), and poliovirus types 1, 2 and 3 (≥8 (1/dilution)); 93.9% of subjects were seroprotected against hepatitis B (≥10 IU/mL) and 94.0% were seroprotected against Hib invasive diseases (≥1 µg/mL).
Regarding pertussis, one month after primary vaccination 99.4% and 100% of subjects developed antibodies ≥8 EU/mL against PT and FHA antigens, respectively. One month after the booster dose, 99.4% of subjects developed antibodies ≥8 EU/mL against both PT and FHA antigens. Pertussis antibody concentrations were increased by 5- to 9-fold after primary vaccination, and by 8- to 19-fold after the booster dose.
Immune responses to Hexaxim in HIV-exposed infants
Immune responses to Hexaxim antigens in 51 HIV-exposed infants (9 infected and 42 uninfected) were evaluated following a 3-dose primary vaccination course at 6, 10, and 14 weeks of age, and a booster dose at 15 to 18 months of age.
One month after primary vaccination, all infants were seroprotected against diphtheria (≥0.01 IU/mL), tetanus (≥0.01 IU/mL), poliovirus types 1, 2, and 3 (≥8 (1/dilution), hepatitis B (≥10 IU/mL), and more than 97.6% for Hib invasive diseases (≥0.15 µg/mL).
One month after the booster dose, all subjects were seroprotected against diphtheria (≥0.1 IU/mL), tetanus (≥0.1 IU/mL), poliovirus types 1, 2 and 3 (≥8 (1/dilution), hepatitis B (≥10 IU/mL), and more than 96.6% for Hib invasive diseases (≥1 µg/mL).
Regarding pertussis, one month after primary vaccination, 100% of subjects developed antibodies ≥8 EU/mL against both PT and FHA antigens. One month after the booster dose, 100% of subjects developed antibodies ≥8 EU/mL against both PT and FHA antigens. Seroconversion rates defined as minimum 4-fold increase compared to pre-vaccination level (pre-dose 1) were 100% in the HIV-
exposed and infected group for anti-PT and anti-FHA; and 96.6% for anti-PT and 89.7% for anti-FHA in the HIV-exposed and uninfected group.
Efficacy and effectiveness in protecting against pertussis
Vaccine efficacy of the acellular pertussis (aP) antigens contained in Hexaxim against the most severe WHO-defined typical pertussis (³21 days of paroxysmal cough) is documented in a randomised double-blind study among infants with a 3 dose primary series using a DTaP vaccine in a highly endemic country (Senegal). The need for a toddler booster dose was seen in this study.
The long-term capability of the acellular pertussis (aP) antigens contained in Hexaxim to reduce pertussis incidence and control pertussis disease in childhood has been demonstrated in a 10-year national pertussis surveillance on pertussis disease in Sweden with the pentavalent DTaP-IPV/Hib vaccine using a 3, 5, 12 months schedule. Results of long-term follow-up demonstrated a dramatic reduction of the pertussis incidence following the second dose regardless of the vaccine used.
Effectiveness in protecting against Hib invasive disease
The vaccine effectiveness against Hib invasive disease of DTaP and Hib combination vaccines (pentavalent and hexavalent including vaccines containing the Hib antigen from Hexaxim) has been demonstrated in Germany via an extensive (over five years follow-up period) post-marketing surveillance study. The vaccine effectiveness was of 96.7% for the full primary series, and 98.5% for the booster dose (irrespective of priming).
No pharmacokinetic studies have been performed.
Non-clinical data reveal no special hazard for humans based on conventional repeat dose toxicity and local tolerance studies.
At the injection sites, chronic histological inflammatory changes were observed that are expected to have a slow recovery.
Disodium hydrogen phosphate
Potassium dihydrogen phosphate
Trometamol
Saccharose
Essential amino acids including L-phenylalanine
Sodium hydroxide, acetic acid or hydrochloric acid (for pH adjustment)
Water for injections.
For adsorbent: see section 2.
In the absence of compatibility studies, this vaccine must not be mixed with other vaccines or medicinal products.
Store in a refrigerator (2°C – 8°C).
Do not freeze.
Keep the container in the outer carton in order to protect it from the light.
Stability data indicate that the vaccine components are stable at temperatures up to 25°C for 72 hours. At the end of this period, Hexaxim should be used or discarded. These data are intended to guide healthcare professionals in case of temporary temperature excursion only.
Hexaxim in pre-filled syringes
0.5 mL suspension in pre-filled syringe (type I glass) with plunger stopper (halobutyl) and tip cap (halobutyl), with 2 separate needles.
Pack size of 1 or 10.
Hexaxim in vials
0.5 mL suspension in vial (type I glass) with a stopper (halobutyl).
Pack size of 10.
Not all pack sizes may be marketed.
Hexaxim in pre-filled syringes
Prior to administration, the pre-filled syringe should be shaken in order to obtain a homogeneous, whitish, cloudy suspension.
The suspension should be visually inspected prior to administration. In the event of any foreign particulate matter and/or variation of physical aspect being observed, discard the pre-filled syringe.
For syringes without an attached needle, the needle must be fitted firmly to the syringe, rotating it by a one-quarter turn.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Hexaxim in vials
Prior to administration, the vial should be shaken in order to obtain a homogeneous, whitish, cloudy suspension.
The suspension should be visually inspected prior to administration. In the event of any foreign particulate matter and/or variation of physical aspect being observed, discard the vial.
A dose of 0.5 mL is withdrawn using a syringe for injection.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
