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For the use of a Registered Medical Practitioner or a Hospital or Laboratory COVID-19 Vaccine [Ad26.COV2-S (recombinant)] NAME OF THE MEDICINAL PRODUCT Janssen COVID-19 Vaccine QUALITATIVE AND QUANTITATIVE COMPOSITION This is a multi-dose vial which contains 5 doses of 0.5 mL. One dose (0.5 mL) contains Adenovirus type 26 encoding the SARS-CoV-2 spike glycoprotein* (Ad26.COV2-S), not less than 2.5×1010 virus particles (VP) corresponding to not less than 8.92 log infectious units (Inf.U). 10 * Produced in the PER.C6 TetR Cell Line and by recombinant DNA technology. The product contains genetically modified organisms (GMOs). Excipients with known effect Each dose (0.5 mL) contains approximately 2 mg of ethanol. For the full list of excipients, see section on List of Excipients. PHARMACEUTICAL FORM Suspension for injection (injection). Colourless to slightly yellow, clear to very opalescent suspension (pH 6-6.4). CLINICAL PARTICULARS Therapeutic indications Janssen COVID-19 Vaccine is indicated for active immunisation to prevent COVID-19 caused by SARS-CoV-2 in individuals 18 years of age and older. The use of this vaccine should be in accordance with official recommendations. Posology and method of administration Posology Individuals 18 years of age and older Janssen COVID-19 Vaccine is administered as a single-dose of 0.5 mL by intramuscular injection only. Paediatric population The safety and efficacy of Janssen COVID-19 Vaccine in children and adolescents (less than 18 years of age) have not yet been established. No data is available. 1Elderly No dose adjustment is required in elderly individuals ≥ 65 years of age. See also sections Undesirable effects and Pharmacodynamic properties. Method of administration Janssen COVID-19 Vaccine is for intramuscular injection only, preferably in the deltoid muscle of the upper arm. Do not inject the vaccine intravascularly, intravenously, subcutaneously or intradermally. The vaccine should not be mixed in the same syringe with any other vaccines or medicinal products. For precautions to be taken before administering the vaccine, see section Special warnings and precautions for use. For instructions on handling and disposal of the vaccine, see section Special precautions for disposal and other handling. Contraindications Hypersensitivity to the active substance or to any of the excipients listed in section on List of Excipients. Individuals who have previously experienced episodes of capillary leak syndrome (CLS) (see also section Special warnings and precautions for use. Special warnings and precautions for use 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. Hypersensitivity and anaphylaxis Events of anaphylaxis have been reported. Appropriate medical treatment and supervision should always be readily available in case of an anaphylactic reaction following the administration of the vaccine. Close observation for at least 15 minutes is recommended following vaccination. Anxiety-related reactions Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation or stress‐related reactions may occur in association with vaccination as a psychogenic response to the needle injection. It is important that precautions are in place to avoid injury from fainting. Concurrent illness Vaccination should be postponed in individuals suffering from an acute severe febrile illness or acute infection. However, the presence of a minor infection and/or low-grade fever should not delay vaccination. Thrombosis with thrombocytopenia syndrome A combination of thrombosis and thrombocytopenia, in some cases accompanied by bleeding, has been observed very rarely following vaccination with Janssen COVID-19 Vaccine. This includes severe cases of venous thrombosis at unusual sites such as cerebral venous sinus thrombosis (CVST), 2splanchnic vein thrombosis as well as arterial thrombosis concomitant with thrombocytopenia. Fatal outcome has been reported. These cases occurred within the first three weeks following vaccination, and mostly in women under 60 years of age. Healthcare professionals should be alert to the signs and symptoms of thromboembolism and/or thrombocytopenia. Those vaccinated should be instructed to seek immediate medical attention if they develop symptoms such as shortness of breath, chest pain, leg pain, leg swelling, or persistent abdominal pain following vaccination. Additionally, anyone with neurological symptoms including severe or persistent headaches, seizures, mental status changes or blurred vision after vaccination, or who experiences skin bruising (petechia) beyond the site of vaccination after a few days, should seek prompt medical attention. Thrombosis in combination with thrombocytopenia requires specialised clinical management. Healthcare professionals should consult applicable guidance and/or consult specialists (e.g., haematologists, specialists in coagulation) to diagnose and treat this condition. Individuals diagnosed with thrombocytopenia within 3 weeks after vaccination with Janssen COVID- 19 Vaccine should be actively investigated for signs of thrombosis. Similarly, individuals who present with thrombosis within 3 weeks of vaccination should be evaluated for thrombocytopenia. Risk of bleeding with intramuscular administration As with other intramuscular injections, the vaccine should be given with caution in individuals receiving anticoagulant therapy or those with thrombocytopenia or any coagulation disorder (such as haemophilia) because bleeding or bruising may occur following an intramuscular administration in these individuals. Capillary leak syndrome Very rare cases of capillary leak syndrome (CLS) have been reported in the first days after vaccination with Janssen COVID-19 Vaccine, in some cases with a fatal outcome. A history of CLS has been reported. CLS is a rare disorder characterised by acute episodes of oedema mainly affecting the limbs, hypotension, haemoconcentration and hypoalbuminaemia. Patients with an acute episode of CLS following vaccination require prompt recognition and treatment. Intensive supportive therapy is usually warranted. Individuals with a known history of CLS should not be vaccinated with this vaccine. See also section Contraindications. Guillain-Barré syndrome Guillain-Barré syndrome (GBS) has been reported very rarely following vaccination with Janssen COVID-19 Vaccine. Healthcare professionals should be alert of GBS signs and symptoms to ensure correct diagnosis, in order to initiate adequate supportive care and treatment and to rule out other causes. Immunocompromised individuals The efficacy, safety and immunogenicity of the vaccine have not been assessed in immunocompromised individuals, including those receiving immunosuppressant therapy. The efficacy of Janssen COVID-19 Vaccine may be lower in immunosuppressed individuals. Duration of protection The duration of protection afforded by the vaccine is unknown as it is still being determined by ongoing clinical trials. Limitations of vaccine effectiveness Protection starts around 14 days after vaccination. As with all vaccines, vaccination with Janssen COVID-19 Vaccine may not protect all vaccine recipients (see section Pharmacodynamic properties). 3Excipients Sodium This medicinal product contains less than 1 mmol sodium (23 mg) per 0.5 mL dose, that is to say essentially ‘sodium-free’. Ethanol This medicinal product contains 2 mg of alcohol (ethanol) per 0.5 mL dose. The small amount of alcohol in this medicinal product will not have any noticeable effects. Interaction with other medicinal products and other forms of interaction No interaction studies have been performed. Concomitant administration of Janssen COVID-19 Vaccine with other vaccines has not been studied. Fertility, pregnancy and lactation Pregnancy There is limited experience with the use of Janssen COVID-19 Vaccine in pregnant women. Animal studies with Janssen COVID-19 Vaccine do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/foetal development, parturition or postnatal development (see section Preclinical safety data). Administration of Janssen COVID-19 Vaccine in pregnancy should only be considered when the potential benefits outweigh any potential risks to the mother and foetus. Breast-feeding It is unknown whether Janssen COVID-19 Vaccine is excreted in human milk. Fertility Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section Preclinical safety data). Effects on ability to drive and use machines Janssen COVID-19 Vaccine has no or negligible influence on the ability to drive and use machines. However, some of the adverse reactions mentioned under section Undesirable effects may temporarily affect the ability to drive or use machines. Undesirable effects Summary of safety profile The safety of Janssen COVID-19 Vaccine was evaluated in an ongoing phase 3 study (COV3001). A total of 21 895 adults aged 18 years and older received Janssen COVID-19 Vaccine. The median age of individuals was 52 years (range 18-100 years). The safety analysis was performed once the median follow-up duration of 2 months after vaccination was reached. Longer safety follow-up of > 2 months is available for 11 948 adults who received Janssen COVID-19 Vaccine. In study COV3001, the most common local adverse reactions reported was injection site pain (48.6%). The most common systemic adverse reactions were headache (38.9%), fatigue (38.2%), myalgia (33.2%) and nausea (14.2%). Pyrexia (defined as body temperature ≥ 38.0°C) was observed in 9% of participants. Most adverse reactions occurred within 1–2 days following vaccination and were mild to moderate in severity and of short duration (1–2 days). 4Reactogenicity was generally milder and reported less frequently in older adults (763 adults ≥ 65 years old). The safety profile was generally consistent across participants with or without prior evidence of SARS-CoV-2 infection at baseline; a total of 2 151 adults seropositive at baseline received Janssen COVID-19 Vaccine (9.8%). Tabulated list of adverse reactions Adverse drug reactions observed during study COV3001 are organised by MedDRA System Organ Class (SOC). Frequency categories are defined as follows: 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 the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Table 1: Adverse reactions reported following vaccination with Janssen COVID-19 Vaccine Not known (cannot be estimated Very Common Uncommon Rare from the System Organ common (≥ 1/100 to (≥ 1/1 000 to (≥ 1/10 000 to Very Rare available Class (≥ 1/10) < 1/10) < 1/100) < 1/1 000) (< 1/10 000) data) Immune system Hypersensitivitya; Anaphylaxis disorders urticaria b Nervous system Headache Tremor Guillain- disorders Barré syndrome Vascular Thrombosis Capillary disorders in leak combination syndrome with thrombo- cytopenia* Respiratory, Cough Sneezing; thoracic and oropharyngeal mediastinal pain disorders Gastrointestinal Nausea disorders Skin and Rash; subcutaneous hyperhidrosis tissue disorders Musculoskeletal Myalgia Arthralgia Muscular and connective weakness; pain tissue disorders in extremity; back pain General Fatigue; Pyrexia; Asthenia; disorders and injection injection malaise administration site pain site site conditions erythema; injection site swelling; chills 5a Hypersensitivity refers to allergic reactions of the skin and subcutaneous tissue. b Cases received from an ongoing open-label study in South Africa. * Severe and very rare cases of thrombosis in combination with thrombocytopenia have been reported post-marketing. These included venous thrombosis such as cerebral venous sinus thrombosis, splanchnic vein thrombosis, as well as arterial thrombosis (see section Special warnings and precautions for use) Overdose No case of overdose has been reported. In phase 1/2 studies where a higher dose (up to 2-fold) was administered Janssen COVID-19 Vaccine remained well-tolerated, however vaccinated individuals reported an increase in reactogenicity (increased vaccination site pain, fatigue, headache, myalgia, nausea and pyrexia). In the event of overdose, monitoring of vital functions and possible symptomatic treatment is recommended. PHARMACOLOGICAL PROPERTIES Pharmacodynamic properties Pharmacotherapeutic group: Vaccines, other viral vaccines, ATC code: J07BX03 Mechanism of action Janssen COVID-19 Vaccine is a monovalent vaccine composed of a recombinant, replication- incompetent human adenovirus type 26 vector that encodes a SARS-CoV-2 full-length spike (S) glycoprotein in a stabilised conformation. Following administration, the S glycoprotein of SARS-CoV-2 is transiently expressed, stimulating both neutralising and other functional S-specific antibodies, as well as cellular immune responses directed against the S antigen, which may contribute to protection against COVID-19. Clinical efficacy An ongoing, multicentre, randomised, double-blind, placebo-controlled phase 3 study (COV3001) is being conducted in the United States, South Africa and Latin American countries to assess the efficacy, safety, and immunogenicity of a single-dose of Janssen COVID-19 Vaccine for the prevention of COVID-19 in adults aged 18 years and older. The study excluded individuals with abnormal function of the immune system resulting from a clinical condition, individuals who are under immunosuppressive therapies within 6 months, as well as pregnant women. Participants with stable HIV infection under treatment were not excluded. Licensed vaccines, excluding live vaccines, could be administered more than 14 days before or more than 14 days after the vaccination in the study. Licensed live attenuated vaccines could be administered more than 28 days before or more than 28 days after the vaccination in the study. A total of 44 325 individuals were randomised in parallel in a 1:1 ratio to receive an intramuscular injection of Janssen COVID-19 Vaccine or placebo. A total of 21 895 adults received Janssen COVID-19 Vaccine and 21 888 adults received placebo. Participants were followed for a median of 58 days (range: 1-124 days) after vaccination. The primary efficacy analysis population of 39 321 individuals included 38 059 SARS-CoV-2 seronegative individuals at baseline and 1 262 individuals with an unknown serostatus. Demographic and baseline characteristics were similar among individuals who received the Janssen COVID-19 Vaccine and those who received placebo. In the primary efficacy analysis population, among the individuals who received Janssen COVID-19 Vaccine, the median age was 52.0 years (range: 18 to 100 years); 79.7% (N=15 646) of individuals were 18 to 64 years old [with 20.3% 6(N=3 984) aged 65 or older and 3.8% (N=755) aged 75 or older]; 44.3% of individuals were female; 46.8% were from Northern America (United States), 40.6% were from Latin America and 12.6% were from Southern Africa (South Africa). A total of 7 830 (39.9%) individuals had at least one pre-existing comorbidity associated with increased risk of progression to severe COVID-19 at baseline (comorbidities included: obesity defined as BMI ≥ 30 kg/m2 (27.5%), hypertension (10.3%), type 2 diabetes (7.2%), stable/well-controlled HIV infection (2.5%), serious heart conditions (2.4%) and asthma (1.3%)). Other comorbidities were present in ≤ 1% of the individuals. COVID-19 cases were confirmed by a central laboratory based on a positive SARS-CoV-2 viral RNA result using a polymerase chain reaction (PCR)-based test. Vaccine efficacy overall and by key age groups are presented in Table 2. Table 2: Analysis of vaccine efficacy against COVID-19b in SARS-CoV-2 seronegative adults - primary efficacy analysis population Janssen COVID-19 Vaccine Placebo N=19 630 N=19 691 % Vaccine COVID-19 Person- COVID-19 Person- Efficacy Subgroup Cases (n) Years Cases (n) Years (95% CI)c 14 days post-vaccination All subjectsa 116 3 116.57 348 3 096.12 66.9 (59.03; 73.40) 18 to 64 years of age 107 2 530.27 297 2 511.23 64.2 (55.26; 71.61) 65 years and older 9 586.31 51 584.89 82.4 (63.90; 92.38) 75 years and older 0 107.37 8 99.15 100 (45.90; 100.00) 28 days post-vaccination All subjectsa 66 3 102.00 193 3 070.65 66.1 (55.01; 74.80) 18 to 64 years of age 60 2 518.73 170 2 490.11 65.1 (52.91; 74.45) 65 years and older 6 583.27 23 580.54 74.0 (34.40; 91.35) 75 years and older 0 106.42 3 98.06 – a Co-primary endpoint as defined in the protocol. b Symptomatic COVID-19 requiring positive RT-PCR result and at least 1 respiratory sign or symptom or 2 other systemic signs or symptoms, as defined in the protocol. c Confidence intervals for ‘All Subjects’ were adjusted to implement type I error control for multiple testing. Confidence intervals for age groups are presented unadjusted. Vaccine efficacy against severe COVID-19 is presented in Table 3 below. Table 3: Analyses of vaccine efficacy against severe COVID-19a in SARS-CoV-2 seronegative adults - primary efficacy analysis population Janssen COVID-19 Vaccine Placebo N=19 630 N=19 691 % Vaccine COVID-19 Person- COVID-19 Person- Efficacy Subgroup Cases (n) Years Cases (n) Years (95% CI)b 14 days post-vaccination Severe 76.7 14 3 125.05 60 3 122.03 (54.56; 89.09) 28 days post-vaccination Severe 85.4 5 3 106.15 34 3 082.58 (54.15; 96.90) 7a Final determination of severe COVID-19 cases was made by an independent adjudication committee, who also assigned disease severity according to the definition per FDA guidance. b Confidence intervals were adjusted to implement type I error control for multiple testing. Of the 14 vs. 60 severe cases with onset at least 14 days after vaccination in the Janssen COVID-19 Vaccine group vs. placebo group, 2 vs. 6 were hospitalised. Three individuals died (all in the placebo group). The majority of the remaining severe cases fulfilled only the oxygen saturation (SpO ) 2 criterion for severe disease (≤ 93% on room air). Prior to unblinding, supplementary analyses, considered post-hoc, of positive cases using PCR-based tests regardless of confirmation by the central laboratory generally support the results of the primary analysis. Beyond 14 days after vaccination, 2 vs. 8 cases of molecularly confirmed COVID-19 were hospitalised, respectively in the Janssen COVID-19 Vaccine vs. placebo group. One case in the placebo group required Intensive Care Unit (ICU) admission and mechanical ventilation. The finding was supported by post-hoc analysis of all COVID-19 related hospitalisations implementing a broader search based on all available information from any source (2 vs. 29 cases in the extended data set). Subgroup analyses of the primary efficacy endpoint showed similar efficacy point estimates for male and female participants, as well as for participants with and without medical comorbidities associated with high risk of severe COVID-19. Exploratory subgroup analyses of vaccine efficacy against COVID-19 and severe COVID-19 for Brazil, South Africa, and the United States were conducted (see Table 4). For the subgroup analyses, all COVID-19 cases accrued up to the primary efficacy analysis data cut-off date, including cases confirmed by the central laboratory and cases with documented positive SARS-CoV-2 PCR from a local laboratory which are still awaiting confirmation by the central laboratory, were included. Table 4: Summary of vaccine efficacy against COVID-19 and severe COVID-19 for countries with > 100 reported cases Severity COVID-19 Severe COVID-19 Onset point estimate (95% CI) point estimate (95% CI) US at least 14 days after vaccination 74.4% (65.00; 81.57) 78.0% (33.13; 94.58) at least 28 days after vaccination 72.0% (58.19; 81.71) 85.9% (-9.38; 99.69) Brazil at least 14 days after vaccination 66.2% (51.01; 77.14) 81.9% (17.01; 98.05) at least 28 days after vaccination 68.1% (48.81; 80.74) 87.6% (7.84; 99.72) South at least 14 days after vaccination 52.0% (30.26; 67.44) 73.1% (40.03; 89.36) Africa at least 28 days after vaccination 64.0% (41.19; 78.66) 81.7% (46.18; 95.42) Samples from 71.7% of central laboratory confirmed primary analysis cases had been sequenced [United States (73.5%), South Africa (66.9%) and Brazil (69.3%)]. Of the sequenced samples there is an imbalance in the completeness of the dataset between Janssen COVID-19 Vaccine and placebo. In the United States, 96.4% of strains were identified as the Wuhan-H1 variant D614G; in South Africa, 94.5% of strains were identified as the 20H/501Y.V2 variant (B.1.351 lineage); in Brazil, 69.4% of strains were identified to be a variant of the P.2 lineage and 30.6% of strains were identified as the Wuhan-H1 variant D614G. Elderly population Janssen COVID-19 Vaccine was assessed in individuals 18 years of age and older. The efficacy of Janssen COVID-19 Vaccine was consistent between elderly (≥ 65 years) and younger individuals (18-64 years). 8Paediatric population See section Posology and method of administration for information on paediatric use. Conditional approval This medicinal product has been authorised for restricted use in Emergency situation as per the provisions of New Drugs and Clinical Trials Rules, 2019 under Drugs & Cosmetics Act, 1940. Pharmacokinetic properties Not applicable. Preclinical safety data Non-clinical data reveal no special hazards for humans based on conventional studies of repeat-dose toxicity and local tolerance, and reproductive and developmental toxicity. Genotoxicity and carcinogenicity Janssen COVID-19 Vaccine has not been evaluated for its genotoxic or carcinogenic potential. The components of the vaccine are not expected to have genotoxic or carcinogenic potential. Reproductive toxicity and fertility Female reproductive toxicity and fertility were assessed in a combined embryo-foetal and pre- and post-natal development study in the rabbit. In this study a first vaccination of Janssen COVID-19 Vaccine was administered intramuscularly to female rabbits 7 days prior to mating, at a dose equivalent to 2-fold above the recommended human dose, followed by two vaccinations at the same dose during the gestation period (i.e., at gestational days 6 and 20). There were no vaccine-related effects on female fertility, pregnancy, or embryo-foetal or offspring development. The parental females as well as their foetuses and offspring exhibited SARS-CoV-2 S protein-specific antibody titers, indicating that maternal antibodies were transferred to the foetuses during gestation. No Janssen COVID-19 Vaccine data are available on vaccine excretion in milk. In addition, a conventional (repeat-dose) toxicity study in rabbits with Janssen COVID-19 Vaccine did not reveal any effects on male sex organs that would impair male fertility. PHARMACEUTICAL PARTICULARS List of excipients 10 vial pack 2-hydroxypropyl-β-cyclodextrin (HBCD) Citric acid monohydrate Ethanol Hydrochloric acid Polysorbate-80 Sodium chloride Sodium hydroxide Trisodium citrate dihydrate Water for injections Incompatibilities This medicinal product must not be mixed with other medicinal products or diluted. 9Shelf life Unopened vial The unopened vaccine may be stored refrigerated at 2°C to 8°C, protected from light, for a single period not exceeding the printed expiry date. Once thawed the vaccine should not be re-frozen. For special precautions for storage, see section Special precautions for storage. Opened vial (after first puncture of the vial) Chemical and physical in-use stability of the vaccine has been demonstrated for 6 hours at 2°C to 25°C. From a microbiological point of view, the product should preferably be used immediately after first puncture of the vial; however, the product can be stored between 2°C to 8°C for a maximum of 6 hours or remain at room temperature (maximally 25°C) up to 3 hours after first puncture of the vial. Beyond these times, in-use storage is the responsibility of the user. Special precautions for storage The vaccine can be stored in a refrigerator at 2°C to 8°C for a single period of up to 6 months, not exceeding the original expiry date.. The vaccine can also be transported at 2°C to 8°C as long as the appropriate storage conditions (temperature, time) are applied. Keep the vials in the original carton in order to protect from light. Nature and contents of container A 2.5 mL suspension in a multi-dose vial (type I glass) with a rubber stopper (chlorobutyl with fluoropolymer coated surface), aluminium crimp and blue plastic cap. Each vial contains 5 doses of 0.5 mL. Pack sizes of 10 multi-dose vials. Special precautions for disposal and other handling Handling instructions and administration This vaccine should be handled by a healthcare professional using aseptic technique to ensure the sterility of each dose. • Keep the vials in the original carton in order to protect from light and to record the expiry for the different storage conditions, if applicable. 10a. Storage upon receipt of vaccine IF YOU RECEIVE YOUR VACCINE THAWED AT 2°C to 8°C you should store in a refrigerator: 2°C to 8°C Do not re-freeze if the product is received already thawed at 2°C to 8°C. b. Inspect vial and vaccine • Janssen COVID-19 Vaccine is a colorless to slightly yellow, clear to very opalescent suspension (pH 6-6.4). • The vaccine should be inspected visually for particulate matter and discoloration prior to administration. • The vial should be inspected visually for cracks or any abnormalities, such as evidence of tampering prior to administration. If any of these should exist, do not administer the vaccine. c. Prepare and administer vaccine 10 SEC Swirl the vial gently Withdraw 0.5 mL Inject 0.5 mL • Before administering a dose • Use a sterile needle and • Administer by of vaccine, swirl the vial sterile syringe to extract a intramuscular injection gently in an upright single-dose of 0.5 mL from only into the deltoid muscle position for 10 seconds. the multi-dose vial (see of the upper arm (see • Do not shake. section Posology and section Posology and Method of Administration). Method of Administration). A maximum of 5 doses can be withdrawn from the multi-dose vial. Discard any remaining vaccine in the vial after 5 doses have been extracted. 11d. Storage after first puncture 2°C to 8°C Maximally 25°C Store up to 6 hours Store up to 3 hours OR Record date and time the • After the first puncture of • After the first puncture of vial should be discarded the vial, the vaccine can the vial, the vaccine can • After first puncture of the be held at 2°C to 8°C for be held at room vial record the date and up to 6 hours. temperature (maximally time the vial should be • Discard if vaccine is not 25°C) for a single period discarded on each vial used within this time. of up to 3 hours. (see label. section Shelf Life). • Discard if vaccine is not Preferably, use used within this time. immediately after first puncture. e. Disposal Any unused vaccine or waste material should be disposed of in compliance with local guidance for pharmaceutical waste. Potential spills should be disinfected with agents with viricidal activity against adenovirus. Patient Counseling Information Blood disorders A combination of blood clots and low levels of ‘platelets’ in the blood has been observed very rarely following vaccination with Janssen COVID-19 Vaccine. This includes severe cases with blood clots, including in unusual locations, such as the brain, liver, bowel and spleen in some cases in combination with bleeding. These cases occurred within the first three weeks following vaccination and occurred mostly in women below 60 years of age. Fatal outcome has been reported. Seek immediate medical attention, if you experience severe or persistent headaches, seizures (fits), mental status changes or blurred vision, unexplained skin bruising beyond the site of vaccination which appear a few days after vaccination, pinpoint round spots beyond the site of vaccination, develop shortness of breath, chest pain, leg pain, leg swelling, or persistent abdominal pain. Inform your healthcare provider that you have recently received Janssen COVID-19 Vaccine. Capillary leak syndrome Very rare cases of capillary leak syndrome (CLS) have been reported following vaccination with Janssen COVID-19 Vaccine. At least one affected patient had a previous diagnosis of CLS. CLS is a serious, potentially fatal condition causing fluid leakage from small blood vessels (capillaries) resulting in rapid swelling of the arms and legs, sudden weight gain and feeling faint (low blood pressure). Seek immediate medical attention if you develop these symptoms in the days following vaccination. Guillain-Barré syndrome 12Seek immediate medical attention if you develop weakness and paralysis in the extremities that can progress to the chest and face (Guillain-Barré syndrome). This has been reported very rarely after vaccination with Janssen COVID-19 Vaccine. Children and adolescents Janssen COVID-19 Vaccine is not recommended for children aged below 18 years. Currently there is not enough information available on the use of Janssen COVID-19 Vaccine in children and adolescents younger than 18 years of age. Other medicines and Janssen COVID-19 Vaccine Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines or vaccines. Pregnancy and breast-feeding If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor, pharmacist or nurse for advice before you receive this vaccine. Driving and using machines Some of the side effects of Janssen COVID-19 Vaccine listed in section Special warnings and precautions for use (Possible side effects) may temporarily affect your ability to drive or use machines. Wait until these effects have worn off before you drive or use machines. Janssen COVID-19 Vaccine contains sodium This medicine contains less than 1 mmol sodium (23 mg) per dose of 0.5 mL, that is to say essentially ‘sodium-free’. Janssen COVID-19 Vaccine contains ethanol This medicine contains 2 mg of alcohol (ethanol) in each dose of 0.5 mL. The amount of ethanol in this medicine is equivalent to less than 1 mL beer or wine. The small amount of alcohol in this medicine will not have any noticeable effects. Possible side effects Like all vaccines, Janssen COVID-19 Vaccine can cause side effects, although not everybody gets them. Most of the side effects occur in the 1 or 2 days of getting the vaccination. Get medical attention immediately if within 3 weeks of vaccination you get any of the following symptoms: • experience severe or persistent headaches, blurred vision, mental status changes or seizures (fits); • develop shortness of breath, chest pain, leg swelling, leg pain or persistent abdominal pain; • notice unusual skin bruising or pinpoint round spots beyond the site of vaccination. Get urgent medical attention if you get symptoms of a severe allergic reaction. Such reactions may include a combination of any of the following symptoms: • feeling faint or light-headed • changes in your heartbeat • shortness of breath • wheezing • swelling of your lips, face, or throat • hives or rash • nausea or vomiting • stomach pain. The following side effects can happen with this vaccine. 13Very common: may affect more than 1 in 10 people • headache • nausea • muscle aches • pain where the injection is given • feeling very tired Common: may affect up to 1 in 10 people • redness where the injection is given • swelling where the injection is given • chills • joint pain • cough • fever Uncommon: may affect up to 1 in 100 people • rash • muscle weakness • arm or leg pain • feeling weak • feeling generally unwell • sneezing • sore throat • back pain • tremor • excessive sweating Rare: may affect up to 1 in 1 000 people • allergic reaction • hives Very Rare: may affect up to 1 in 10 000 people • blood clots often in unusual locations (e.g., brain, liver, bowel, spleen) in combination with low level of blood platelets • serious nerve inflammation, which may cause paralysis and difficulty breathing (Guillain-Barré syndrome (GBS)) Unknown (cannot be estimated from the available data) • severe allergic reaction • capillary leak syndrome (a condition causing fluid leakage from small blood vessels). Tell your doctor, pharmacist or nurse if you have any side effects that bother you or do not go away. Manufactured by: Janssen Pharmaceutica N.V., Turnhoutseweg 30, 2340 Beerse, Belgium Imported by: Johnson & Johnson Private Limited Gala no. 3, BULDG No. B-2, Citylink Warehousing Complex, S.No. 120-121, Mumbai Nashik Highway, Village Vadpe, Bhiwandi, Maharashtra, India- 421302. 14Marketed in India by: Johnson & Johnson Private Limited L.B.S. Marg, Mulund (West), Mumbai 400 080. Permission no.: IMP/BIO/21/000048 dated 06-Aug-2021 DATE OF REVISION OF THE TEXT 16 Sep 2021 based on EU Summary of Product Characteristics (SmPC) dated 23 Jul 2021 15Janssen COVID-19 Vaccine suspension for injection Janssen COVID-19 Vaccine [Ad26.COV2-S (recombinant)] FACT SHEET FOR VACCINE RECIPIENT APPROVED FOR RESTRICTED USE IN EMERGENCY FOR Janssen COVID-19 Vaccine IN PREVENTION OF COVID-19 DISEASE IN INDIVIDUALS 18 YEARS OF AGE AND OLDER This vaccine has been given restricted use license for emergency situation. It does not have a marketing authorization, however, this approval for the restricted use in emergency situation grants permission for the vaccine to be used for active immunisation to prevent COVID-19 caused by SARS-CoV-2 in individuals 18 years of age and older when given in single dose (0.5 mL). Reporting of side effects As with any new medicine, this vaccine will be closely monitored to allow quick identification of new safety information. You can help by reporting any side effects you may get after vaccination to Johnson and Johnson Private Limited at vaccinemedinfoap@its.jnj.com. For more information read this fact sheet carefully. Read all of this leaflet carefully before you are vaccinated because it contains important information for you. • Keep this leaflet. You may need to read it again. • If you have any further questions, ask your doctor, pharmacist or nurse. • If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section on Possible side effects. What is in this leaflet 1. What Janssen COVID-19 Vaccine is and what it is used for 2. What you need to know before you receive Janssen COVID-19 Vaccine 3. How Janssen COVID-19 Vaccine is given 4. Possible side effects 5. How to store Janssen COVID-19 Vaccine 6. Contents of the pack and other information 1. What Janssen COVID-19 Vaccine is and what it is used for Janssen COVID-19 Vaccine is a vaccine used to protect people aged 18 years and older against coronavirus disease-2019 (COVID-19). COVID-19 is caused by a virus called coronavirus (SARS-CoV-2). How the vaccine works Janssen COVID-19 Vaccine stimulates the body’s natural defenses (immune system). It causes the body to produce its own protection (antibodies) against the virus. This will help to protect you against COVID-19 in the future. None of the ingredients in this vaccine can cause COVID-19. 1What is COVID-19? COVID-19 is caused by a coronavirus called SARS-CoV-2. This type of coronavirus has not been seen before. You can get COVID-19 through contact with another person who has the virus. It is predominantly a respiratory illness that can affect other organs. People with COVID-19 have had a wide range of symptoms reported, ranging from mild symptoms to severe illness. Symptoms may appear 2 to 14 days after exposure to the virus. Common symptoms may include: fever or chills, cough, shortness of breath, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, a congested or runny nose, nausea or vomiting, diarrhea. 2. What you need to know before you receive Janssen COVID-19 Vaccine Do not have the vaccine if: • you have previously had a severe allergic reaction to any of the active substance(s) or any of the other ingredients of Janssen COVID-19 Vaccine (listed in section on Contents of the pack and other information), • you have ever had a severe allergic reaction after a dose of any other ‘adenovirus-based vaccine’. • you have ever had a diagnosis of capillary leak syndrome, a very rare, serious condition where fluid (plasma) leaks out of the small blood vessels into the body tissues. If you are not sure, talk to your doctor, pharmacist or nurse before you are given the vaccine. Warnings and precautions Talk to your doctor, pharmacist or nurse before you are given Janssen COVID-19 Vaccine if: • you have ever had a severe allergic reaction after any type of injectable vaccine, • you have a weak or compromised immune system, • you have previously had a blood clot in the brain (venous sinus thrombosis) with low platelets, blood cells that help your body stop bleeding, (thrombocytopenia), or have had a heparin-induced thrombocytopenia (HIT), • you have ever fainted following any needle injection. If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before you are given Janssen COVID-19 Vaccine. Janssen COVID-19 Vaccine may not protect everyone from COVID-19. Blood disorders Blood clots involving blood vessels in the brain, abdomen, and legs along with low levels of platelets, have occurred in some people who have received Janssen COVID-19 Vaccine. In people who developed these blood clots and low levels of platelets, symptoms began mostly within 3 weeks of vaccination. The chance of having this occur is remote. You should seek medical attention right away if you have any of the following symptoms after receiving Janssen COVID-19 Vaccine: • Shortness of breath • Chest pain • Leg pain or swelling • Persistent abdominal pain • Severe and persistent headaches or blurred vision • Unexplained skin bruising or tiny blood spots under the skin beyond the site of the injection 2Neurological events Seek immediate medical attention if you develop weakness and paralysis in the extremities that can progress to the chest and face (Guillain-Barré syndrome). This has been reported very rarely after vaccination with Janssen COVID-19 Vaccine. Children younger than 18 years of age No information are currently available on the use of Janssen COVID-19 Vaccine in children younger than 18 years of age. Other medicines and Janssen COVID-19 Vaccine Tell your doctor or pharmacist if you are taking, have recently taken or might take, any other medicines or vaccines. Pregnancy and breastfeeding If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, tell your doctor, pharmacist or nurse. Your doctor, pharmacist or nurse will discuss with you whether you can be given the vaccine. Driving and using machines Do not drive or use machines if you are feeling unwell after vaccination. 3. How Janssen COVID-19 Vaccine is given Your doctor, pharmacist or nurse will inject the vaccine into the muscle - usually in the upper arm. How much vaccine will you receive A single dose (0.5 mL) of Janssen COVID-19 Vaccine (blue cap vial) vaccine should be administered. During and after the injection of the vaccine, you will be observed. Your doctor, pharmacist or nurse will decide how long to observe you. If you have any further questions on the use of this vaccine, ask your doctor, pharmacist or nurse. Instructions for preparing the vaccine – intended for medical and healthcare professionals – are included at the end of the leaflet. 4. Possible side effects Like all vaccines, Janssen COVID-19 Vaccine can cause side effects, although not everybody gets them. Most of the side effects happened within 1-2 days of getting the injection. The following side effects may happen with this vaccine: Very common (may affect more than 1 in 10 people): • headache • nausea • muscle aches • pain where the injection is given • feeling very tired 3Common (may affect up to 1 in 10 people): • fever • redness where the injection is given • swelling where the injection is given • chills • joint pain Uncommon (may affect up to 1 in 100 people): • rash • muscle weakness • arm or leg pain • feeling weak • feeling generally unwell Rare (may affect up to 1 in 1000 people): • allergic reaction • hives Very rare (may affect up to 1 in 10000 people): • blood clots often in unusual locations (e.g., brain, liver) in combination with low level of blood platelets • persistent ringing in the ears (tinnitus) • diarrhea • unusual feeling in the skin, such as tingling or a crawling feeling (paresthesia) • swollen lymph nodes (lymphadenopathy) • vomiting • decreased feeling or sensitivity, especially in the skin (hypoesthesia) • serious nerve inflammation, which may cause paralysis and difficulty breathing (Guillain-Barré syndrome) Not known (cannot be estimated from the available data): • severe allergic reaction Most of these side effects are mild to moderate in intensity and resolved within 1-2 days. These may not be all the possible side effects of Janssen COVID-19 Vaccine. Tell your doctor, pharmacist or nurse if you have any side effects that bother you or do not go away. 5. How to store Janssen COVID-19 Vaccine Information about storage, expiry, and use and handling are described in the section intended for healthcare professionals only at the end of the leaflet. Your doctor, pharmacist or nurse is responsible for storing this vaccine and disposing of any unused product correctly. 46. Contents of the pack and other information What Janssen COVID-19 Vaccine contains One dose (0.5 mL) contains: • The active substance is a recombinant, replication-incompetent adenovirus type 26 (Ad26) vectored COVID-19 vaccine encoding the SARS-CoV-2 spike (S) protein, not less than 2.5×1010 virus particles (VP) corresponding to not less than 8.92 log infectious units (Inf.U)* 10 * Produced in the PER.C6® TetR Cell Line and by recombinant DNA technology. The Product contains genetically modified organisms (GMOs). The other ingredients (excipients) are 2-hydroxypropyl-β-cyclodextrin (HBCD), citric acid monohydrate, ethanol, hydrochloric acid, polysorbate-80, sodium chloride, sodium hydroxide, trisodium citrate dihydrate, water for injections. What Janssen COVID-19 Vaccine looks like and contents of the pack Janssen COVID-19 Vaccine is a 2.5 mL suspension in a multi-dose Type I glass vial with a latex-free rubber stopper, aluminum crimp and blue plastic cap. A maximum of 5 doses can be withdrawn from the multi- dose vial. Colorless to slightly yellow, clear to very opalescent suspension. Janssen COVID-19 Vaccine is available in a pack containing 10 multi-dose vials. --------------------------------------------------------------------------------------------------------------------------- The following information is intended for healthcare professionals only: • As with all injectable vaccines, appropriate medical treatment and supervision must always be readily available in the event of an anaphylactic reaction following the administration of Janssen COVID-19 Vaccine. Individuals should be monitored by a healthcare professional after vaccination based on clinical judgement. • Janssen COVID-19 Vaccine must not be mixed with other medicinal products in the same syringe. • Janssen COVID-19 Vaccine must not be administered by intravascular injection under any circumstances. • Immunization should be carried out by intramuscularly (IM) injection only. • Healthcare professionals should be alert to the signs and symptoms of thromboembolism and/or thrombocytopenia. Those vaccinated should be instructed to seek immediate medical attention if they develop symptoms such as shortness of breath, chest pain, leg pain or swelling, or progressive abdominal pain following vaccination. Additionally, anyone with neurological symptoms including severe or persistent headaches or blurred vision after vaccination, or who experiences skin bruising (petechia) beyond the site of vaccination after a few days, should seek prompt medical attention. Since management may be different than usual medical practice for thromboembolic events if patients present with concomitant thrombocytopenia, healthcare professionals should consult applicable guidance (e.g., from local health authorities or expert groups) and/or consult specialists (e.g., hematologists) to diagnose and treat this condition. Instructions for administration and handling: Janssen COVID-19 Vaccine is a colorless to slightly yellow, clear to very opalescent suspension. The vaccine should be inspected visually for particulate matter and discoloration prior to administration. The 5vial should be inspected visually for cracks or any abnormalities, such as evidence of tampering prior to administration. If any of these should exist, do not administer the vaccine. Before administering a dose of vaccine, carefully mix the contents of the multi-dose vial by swirling gently in an upright position for 10 seconds. Do not shake. Use a sterile needle and sterile syringe to extract a single dose of 0.5 mL from the multi-dose vial and administer by intramuscular injection only. Changing needles between extracting vaccine from a vial and injecting it into an individual is not necessary unless the needle has been damaged or contaminated. Discard any remaining vaccine in the vial after 5 doses have been extracted. See Storage Conditions section in the full prescribing information for instructions regarding storage after the first dose has been withdrawn. Any unused product and waste material should be disposed of in accordance with local requirements. Manufactured by: Janssen Pharmaceutica N.V., Turnhoutseweg 30, 2340 Beerse, Belgium Imported by: Johnson & Johnson Private Limited Gala no. 3, BULDG No. B-2, Citylink Warehousing Complex, S.No. 120-121, Mumbai Nashik Highway, Village Vadpe, Bhiwandi, Maharashtra, India- 421302. Marketed in India by: Johnson & Johnson Private Limited L.B.S. Marg, Mulund (West), Mumbai 400 080. 6