Maloff Protect 250mg/100mg tablets Atovaquone/proguanil hydrochloride

Business Reply Plus Licence Number RSHT-SUUC-GTXB MALOFF PROTECT CPD Module Kamal Kovac Maloff Protect CPD Module UBM EMEA Chemist Druggist 240 Blackfriars Road London SE1 8BF Malaria prevention Maloff Protect 250mg/100mg tablets Atovaquone/proguanil hydrochloride For the prevention of malaria in adults Can be recommended by pharmacy staff without a PGD or a prescription Maloff Protect is for adults aged 18 and over only. It is not recommended for those who are pregnant, breastfeeding, or likely to become pregnant Once-daily oral formulation to be taken for one to two days before travel, throughout the trip, and for seven days following return from a malariaaffected area Suitable for use in areas where malaria parasites have shown resistance to chloroquine or mefloquine Available in 24 and 36-tablet packs Risk Management Materials are provided by Glenmark Pharma and are a mandatory condition of the Marketing Authorisation to support the recommendation, sale or supply of Maloff Protect these are available via the EMC website and maloff@glenmarkpharma.com. Travellers must be reminded of the need for a full travel consultation, not just malaria prophylaxis. This CPD module will help you: Develop your knowledge of malaria Learn how to assess a traveller s risk of contracting malaria Provide risk-reduction advice Understand the malaria chemoprophylactic medications that you can recommend to customers without requiring a PGD or a prescription, including a product recently reclassified as a P product, Maloff Protect. (1) For further training and materials to support the safe use of Maloff Protect, please visit www.maloffprotect.co.uk NP-UK-MLF-0035 Date of Preparation: July 2017 Glenmark has paid for this piece and has been involved in its creation and editing

OVERVIEW Malaria cycle (4,5) 1. MOSQUITO BITE A female mosquito infected with P. falciparum bites the host and injects the sporozoite (immature) form of the parasite into the blood. 2. THE BLOOD STREAM The sporozoites travel in the blood to the liver and enter hepatocytes. 3. THE LIVER Sporozoites multiply their DNA and mature into schizonts. 4. CELL RUPTURE The schizonts burst and release numerous merozoites into the blood. Malaria is a serious disease that can be life-threatening. It can affect anyone who travels to a region where infected mosquitoes are found In 2015, the World Health Organisation estimated that there were 212 million cases of malaria worldwide, contributing to over 429,000 deaths. (2) The burden of malaria is felt most strongly in sub-saharan Africa, where numerous initiatives are aiming to improve disease prevention or treatment. Despite reductions in the number of people affected by malaria each year, progress is threatened by the rapid spread of resistance to insecticides and antimalarial drugs. (2) Malaria therefore remains a significant risk for international travellers from the UK. But malaria shouldn t ruin anyone s trip abroad. Mosquito bite prevention is an important way to reduce the risk of getting malaria; however, for many destinations, travellers are also advised to take malaria chemoprophylaxis. In the pharmacy, you are well placed to advise travellers about the potential risk of malaria and how they can protect themselves against infection. Types of malaria There are four main types of malaria parasites (Plasmodium or P.) that infect humans; of these, P. falciparum is the most deadly. (2) Malaria is spread by the bite of an infected female Anopheles mosquito, which passes the Plasmodium parasite into the bloodstream of a human when taking a blood meal. (3) 5. TROPHOZOITE FORMATION Merozoites infect red blood cells, forming trophozoites. 6. PARASITE MULTIPLICATION The trophozoites develop, multiply their DNA and mature into schizonts. 7. RED BLOOD CELL BURSTS The schizonts burst releasing numerous merozoites into the blood stream. 8. INFECTION SPREADS THROUGHOUT THE BODY The free merozoites infect more red blood cells. 9. DISEASE SPREADS After several asexual cycles, the trophozoites can mature into male and female gametocytes. When a mosquito bites the infected host, they take up these gametocytes. These can reproduce sexually inside the mosquito and lead to the formation of new sporozoites. These can spread the infection to new hosts and the whole process starts again. Sporozoites Merozoites Red blood cell Trophozoite Blood schizont Liver schizont 2 C+D CPD Module Malaria prevention Malaria prevention C+D CPD Module 3

SYMPTOMS RISKS OF MALARIA What are the symptoms of malaria? The initial symptoms of malaria resemble flu symptoms, such as: SWEATS & CHILLS The risk to UK travellers All travellers who visit areas with infected mosquitoes are at risk of malaria. In 2015, 1,400 travellers brought malaria back to the UK with them. (9) Of these, 1,068 cases were caused by P. falciparum infection, 1,143 were acquired in Africa, and six cases resulted in death. Travellers to areas of Asia, (9, 10) South and Central America, or Oceania can also be at risk of malaria. Public Health England (PHE) provides guidance to adults intending to travel to a malaria-endemic area. (6) The data from 2015 shows that 42.5% of imported malaria cases were individuals who had visited family in their country of origin, suggesting that information about malaria is not reaching all travellers. (11) ABCD VOMITING Other symptoms, such as diarrhoea, shivering, general malaise, and body aches can also occur. In some cases, flu-like symptoms can be mild or diarrhoea alone may be present this can make it difficult to diagnose the disease correctly. (6) Malaria can develop within seven days of being bitten by an infected mosquito. However, P. falciparum malaria can take up to three months to develop, while other types of malaria can lie dormant for up to a year. (3,6) A patient with malaria may seek over-the-counter cold or flu remedies. If this occurs within one year (but especially in the first three months) of their return from a malaria-endemic country, then malaria should be considered. You should ask the patient if they have had any fever or shivering, as these are classic symptoms to look out for. (7) With some types of malaria, the symptoms can occur in cycles of shivering or chills, followed by high fever. The fever in turn is accompanied by severe sweating and fatigue. These symptoms can last between six and 12 hours. (8) Malaria can quickly become life-threatening. All patients with suspected malaria should be immediately referred to a hospital. Malaria prevention advice involves a combination of preventive measures. It can be remembered using the mnemonic ABCD. (12) Awareness of risk Risk is specific to the region of travel, and the specific time of year. The risk of serious malaria will also be increased for some individuals, eg those who are very young, elderly, pregnant, or who have had a splenectomy. Each travel consultation by a pharmacist is unique and requires individualised advice. Some settled UK immigrants mistakenly assume they have full or partial immunity to malaria because they used to live in an endemic area. It is important to educate patients that no one has complete immunity, and any level of immunity quickly diminishes after moving out of the malaria-endemic region. Bite prevention Effective bite prevention (see next page) is the first line of defence against malaria. Stopping bites before they occur also reduces the traveller s risk of contracting other diseases transmitted via mosquitoes. Chemoprophylaxis Recommendations for malaria prophylaxis medication should be tailored to the individual and the destination of travel. You can check the latest recommendations about malaria chemoprophylaxis at travelhealthpro.org.uk/countries or travax.nhs.uk (NHS Scotland). Before recommending an antimalarial, screen the traveller for suitability using information in the Summary of Product Characteristics (SPC) or the British National Formulary (BNF). Diagnose malaria promptly and treat without delay Suspected malaria is a medical emergency. Consider the possibility of malaria for every traveller who has been to a malaria-endemic area in the past year and presents with fever. When diagnosed and treated promptly, most patients will make a full recovery. It is important to remember that while malaria can initially appear similar to several common viral illnesses, it can quickly become life-threatening. The importance of malaria prevention should be highlighted for all travellers who might be at risk. 4 C+D CPD Module Malaria prevention Malaria prevention C+D CPD Module 5

PREVENTION PREVENTION Bite prevention Mosquitoes can bite at any time of the day, so protection should be considered throughout a trip to an affected area. In all cases, bite prevention is the first line of defence against malaria and other mosquito-borne infections. For some destinations, this might be considered to be sufficient for protection alone, and chemoprophylaxis will not be required. Key recommendations for bite prevention from PHE include: (6) Insect repellents Several insect repellents are available, but those with 20% DEET are recommended on exposed areas of skin for those over the age of two months (unless allergic). Higher concentrations of DEET provide longer protection (20% for up to three hours protection; 30% for up to six hours; 50% for up to 12 hours). DEET has been widely used as an insect repellent for more than 50 years and poses a low risk of adverse events when applied topically. DEET should be applied on top of sunscreen that itself is preferably an SPF of between 30 and 50. Insecticide-treated mosquito nets Specially designed mosquito nets impregnated with insecticide should be used around the bed when sleeping. Travellers should ensure that there are no access points for mosquitoes and that exposed areas of skin do not touch the net, enabling biting. Customers should be aware that an impregnated net has a life span and the insecticide will be removed with washing. Clothing that covers the skin Covering the skin with clothing is a good way to reduce mosquito bites. This is important at dawn and after sunset, when the female Anopheles mosquito is most active. A long-sleeved t-shirt and trousers are therefore good options. Some clothing can be impregnated or sprayed with insecticide/insect repellent to reduce biting. Room protection with air conditioning and insecticide clearance Indoor areas should be screened to prevent the entry of mosquitoes. If this is not possible, windows and doors should be closed after sunset. Insecticide (such as permethrin or other synthetic pyrethroid) can have a rapid knock-down effect on mosquitoes resting in a room. The activity of any remaining mosquitoes can be reduced with the use of air conditioning or fans. Alternative methods are NOT recommended Herbal remedies, homeopathy, buzzers, vitamin B1 and B12 supplements, garlic, tea tree oil and other alternatives are not recommended as a method to prevent or treat malaria, as they have no robust scientific evidence to support their use. Malaria chemoprophylaxis Medications that help prevent infection with malaria-causing Plasmodium are highly recommended for travellers to areas where infected mosquitoes reside. In every case, the latest travel health recommendations should be checked during each consultation at: travelhealthpro.org.uk/countries or www.travax.nhs.uk. These websites are regularly updated with advice to reflect seasonal changes, the spread of antimalarial resistance, and other local factors. Chemoprophylaxis that can be recommended by pharmacy staff A variety of malaria chemoprophylaxis medications can now be recommended by pharmacy staff, directly to appropriate travellers. Proguanil and chloroquine (13, 14) Proguanil is taken once daily, while chloroquine is taken once a week. Both are used for one week before travel, throughout the trip, and for four weeks following return from a malaria-affected area. Proguanil works by inhibiting dihydrophosphate reductase, which is an enzyme required for DNA synthesis and parasite replication. Chloroquine binds and alters the properties of DNA, killing the parasite. There are very few areas where P. falciparum is fully sensitive to proguanil, so the agent is rarely recommended alone. (6) Proguanil and chloroquine have increased efficacy when used together, but as nearly all regions with P. falciparum have shown evidence of resistance to chloroquine, this combination is not recommended for travellers to regions where P. falciparum is endemic. It remains useful for travellers visiting areas affected by other types of Plasmodium. Chloroquine can be recommended alone to travellers visiting applicable areas. Recommendations should be checked at: travelhealthpro.org.uk/countries or www.travax.nhs.uk. 6 C+D CPD Module Malaria prevention Malaria prevention C+D CPD Module 7

PREVENTION PREVENTION Maloff Protect is now available to purchase without a prescription Atovaquone and proguanil hydrochloride have previously only been available with a prescription or PGD. (15) As Maloff Protect, this antimalarial combination can now be recommended as a malaria chemoprophylactic to adults without requiring a prescription or PGD. Maloff Protect (atovaquone 250mg/proguanil hydrochloride 100mg) should be taken once daily for one to two days before travel, during the trip, and for seven days following return from a malaria-affected area. (1) The active ingredients have complementary mechanisms of action that block parasitic replication and kill the parasite. Maloff Protect is suitable for use in areas where P. falciparum resistance to chloroquine or mefloquine has been reported. (1) Marketing authorisation holder Glenmark claims it adds a significant new tool to the pharmacy travel toolkit and increases the number of customers who can benefit from pharmacy-direct malaria chemoprophylaxis. Chemoprophylaxis that requires a PGD or prescription If the currently available P medicines are not appropriate for your customer, alternative forms of malaria chemoprophylaxis can be offered with a PGD or prescription. This includes other atovaquone/proguanil hydrochloride products, doxycycline, and mefloquine. These medicines can only be recommended by an authorised prescriber. Atovaquone and proguanil hydrochloride (15) should be taken once daily for one to two days before travel, throughout the trip, and for seven days following return from a malaria-affected area. Prescribed atovaquone and proguanil works in the same way as described for Maloff Protect. The most common adverse events reported after taking atovaquone and proguanil chemoprophylaxis are headaches, and gastrointestinal disturbances such as nausea, vomiting, diarrhoea or pain. Doxycycline (16) should be taken once daily for one to two days before travel, throughout the trip, and for four weeks following return from a malaria-affected area. Doxycycline kills parasites in red blood cells and is suitable for use in areas where P. falciparum resistance to chloroquine or mefloquine has been reported. The most common adverse events reported after taking doxycycline are anaphylactic reactions, headache, nausea, vomiting, rashes, and photosensitivity reactions (an exaggerated reaction to the sun). Mefloquine (17) (Lariam) should be taken once weekly from 10 days before travel, throughout the trip, and for four weeks following return from a malaria-affected area. It works by killing parasites in red blood cells. In some regions, Plasmodium have resistance to mefloquine. (18) The safety profile of mefloquine is characterised by a predominance of neuropsychiatric adverse reactions, but the most common adverse events reported after taking mefloquine are nausea, vomiting, and dizziness. The role of the pharmacist As a community pharmacist, you are highly accessible and have an important role in providing travel advice to patients. A significant number of cases of malaria are preventable, so your advice is crucial. As with all medicines, it is vital that any recommendations are made based on clinical screening of the customer, up-to-date travel health information, and individual product SPCs. You may not have a medication that is right for every customer. Use any screening questionnaires that are available, and if in doubt, refer the customer to their GP or nearest travel clinic. To ensure maximum protection, advise patients to take their malaria chemoprophylaxis as directed. Daily doses should be taken at the same time each day, and weekly doses must be taken on the same day each week. You should explain that the course should be started before travelling to the endemic area and continued after returning even if they believe they were not bitten. The length of time depends on the chosen medication. It is also important to ask patients about the entire trip they are taking, as they could be visiting more than one malaria zone. This should be a consideration when selecting the most appropriate malaria chemoprophylaxis. If the patient is a settled immigrant in the UK, inform them that they may have lost any immunity they gained while living in a malaria-endemic region. Malaria prevention is only one aspect of healthy travel. You can play an important role in supporting the health of travellers. Consider the following points when offering travel advice to your customer: 1. Engage the customer and ask where they are going. 2. Check the latest travel health advice at travelhealthpro.org.uk/countries or www.travax.nhs.uk. 3. Advise the customer about products and medicines you think could keep them safer while abroad. This conversation should cover antimalarials; vaccinations; ensuring they have a sufficient supply of any usual medicines to last the trip; recommending any medical supplies they may need while abroad (eg insect repellents, travel sickness tablets, pain killers, first aid supplies, travel-sized toiletries, sunscreen); and providing appropriate practical travel advice or directing them to the nearest travel clinic to obtain this information (eg whether it is safe to drink the tap water, how to seek medical advice abroad). You may find that you stock many of the items that they require to keep them safe on their travels. 8 C+D CPD Module Malaria prevention Malaria prevention C+D CPD Module 9

Maloff Protect 250mg/100mg tablets List of actives: atovaquone, proguanil. PL number: PL 25258/0166. Name and address of PL holder: Glenmark Pharmaceuticals Europe Limited, Laxmi House, 2 B Draycott Avenue, Kenton, Middlesex, HA3 0BU. Supply classification (P/GSL): P. Indication(s): Chemoprophylaxis of Plasmodium falciparum (P. Falciparum) malaria in adults. Check official guidelines (e.g. World Health Organisation (WHO) and public health authorities guidelines) before dispensing. Contraindications, precautions, side effects: Contraindications: hypersensitivity to atovaquone, proguanil or excipients, renal disease, hepatic impairment, children and adolescents. Precautions: if vomiting occurs within one hour of dosing repeat dose. If allergic reaction develops, discontinue use promptly and seek medical treatment. Refer the following patients to a doctor or other qualified prescriber: those taking etoposide, rifampicin, rifabutin, metoclopramide, warfarin and other anticoagulants, tetracycline, indinavir, efavirenz, zidovudine, boosted protease inhibitors, those with a history of depression or seizures, those with TB, patients who are pregnant, planning to become pregnant or those breast feeding. Safety and effectiveness has not been established in References 1. Glenmark Pharmaceuticals. Maloff Protect (Atovaquone 250 mg and Proguanil Hydrochloride 100 mg) tablets. Summary of Product Characteristics. 2017. Available from: https://www.medicines.org.uk/emc/medicine/33700. Accessed 2. World Health Organisation. World Malaria Report 2016. Available from: http://apps.who.int/iris/bitstre am/10665/252038/1/9789241511711-eng.pdf?ua=1. Accessed 3. Center for Disease Prevention and Control. About Malaria. Frequently Asked Questions. 2017. Available from: https://www.cdc.gov/malaria/about/faqs.html. Accessed 4. Kakkilaya BS. Pathophysiology. Updated Feb 2015. Available from: http://www.malariasite.com/pathophysiology/. Accessed 12th Apr 2017 5. Centers for Disease Control and Prevention. Malaria Biology. Updated Mar 2016. Available from: www. cdc.gov/malaria/about/biology/index.html. Accessed 10th Mar 2017. 6. Public Health England. Guidelines for malaria prevention in travellers from the UK 2016. 2016. Available from: https:// www.gov.uk/government/uploads/system/uploads/ attachment_data/file/585695/2016_acmp_guidelines_ Final_-_Updated_Ethiopia 2_.pdf. 7. Glenmark Pharmaceuticals. Maloff Protect (Atovaquone 250 mg and Proguanil Hydrochloride 100 mg) tablets. Product Information. 2017. Available from: https://www. medicines.org.uk/emc/medicine/33700. Accessed 8. National Health Service Choices. Malaria - Symptoms. Updated Nov 2015. Available from: http://www.nhs.uk/ Conditions/Malaria/Pages/Symptoms.aspx. Accessed 9. Public Health England. Imported malaria in the UK: statistics 2016. Available from: https://www.gov.uk/ government/uploads/system/uploads/attachment_data/ file/539448/imported_malaria_cases_deaths_1996_ to_2015.xlsx. Accessed patients <40kg. Remind travellers of the need for a full travel consultation. Side effects: The most common side effects are headache, abdominal pain and diarrhoea. Other important reactions reported are severe allergic reactions, pancytopenia in patients with severe renal impairment, severe skin reactions, seizure, hallucinations, liver inflammation, depression. Dosage and method used: One tablet daily with food or a milky drink at the same time each day. Commence 1-2 days prior to entering malaria-endemic area, continue for the duration of the stay plus seven days after leaving the area. The maximum duration of travel for which Maloff Protect can be supplied without prescription is 12 weeks (93 tablets). For longer durations of travel, advice should be sought from a doctor or other qualified prescriber. Adverse Event Reporting: Adverse events should be reported. Reporting forms and information can be found at yellowcard.mhra.gov.uk. Cost: RRP (excluding VAT): 24 Tablet Pack = 39.00, 36 Tablet Pack = 56.16. Date of EI creation: 4 July 2017. 10. Public Health England. Imported malaria in the UK: statistics 2016. Available from: https://www.gov.uk/government/ uploads/system/uploads/attachment_data/file/539449/ Imported_malaria_cases_by_species_and_region_of_travel United_Kingdom_2015.xlsx. Accessed 11. Public Health England. Imported malaria in the UK: statistics 2016. Available from: https://www.gov.uk/government/ uploads/system/uploads/attachment_data/file/539451/ Imported_malaria_cases_by_species_and_reason_for_ travel_uk_2015.xlsx. Accessed 12. National Health Service Choices. Malaria - Prevention. Updated Nov 2015. Available from: http://www.nhs.uk/ Conditions/Malaria/Pages/Symptoms.aspx. Accessed 13. Alliance Pharmaceuticals. Avloclor (Chloroquine Phosphate) 250 mg tablets. Summary of Product Characteristics 2016. Available from: https://www.medicines.org.uk/emc/ medicine/2272. Accessed 14. Alliance Pharmaceuticals. Paludrine (Proguanil Hydrochloride) and Avloclor (Chloroquine Phosphate) Antimalarial Travel Pack. Summary of Product Characteristics. 2016. Available from: https://www.medicines.org.uk/emc/ medicine/2294. Accessed 15. GlaxoSmithKline UK. Malarone (atovaquone 250 mg and proguanil hydrochlride 100 mg) film-coated tablets. Summary of Product Characteristics. 2016. Available from: https://www.medicines.org.uk/emc/medicine/756. Accessed 16. Pfizer Ltd. Vibramycin-D (Doxycycline dispersible tablets 100mg). Summary of Product Characteristics. 2016. Available from: https://www.medicines.org.uk/emc/medicine/20879. Accessed 17. Roche Products Ltd. Lariam (Mefloquine 250 mg) tablets. Summary of Product Characteristics 2017. Available from: https://www.medicines.org.uk/emc/medicine/1701. Accessed 18. Bloland P. World Health Organisation. Drug resistance in malaria. 2001. Available from: http://www.who.int/csr/ resources/publications/drugresist/malaria.pdf. Accessed Tips for your CPD entry on preventing malaria Reflect What is malaria and what are the symptoms? How many UK travellers bring back malaria from trips abroad? What travel advice can you give customers? What malaria chemoprophylaxis can you recommend? Plan This module provides information on what malaria is, what the risks are for UK travellers, and what pharmacy staff can do to manage this risk. Malaria prevention medicines that can be provided by pharmacy staff without a PGD or prescription are discussed, including a new product, Maloff Protect. Act Get the latest travel advice from travelhealthpro.org.uk/countries or www.travax.nhs.uk. Remind yourself of the medicines available for malaria chemoprophylaxis using the BNF some of these can be recommended by pharmacy staff without a PGD or prescription. Familiarise yourself with these medications using the individual SPCs. Evaluate Are you confident in your knowledge of malaria and malaria chemoprophylaxis? Would you be able to comprehensively advise a customer on travel health? Take the 5-minute test To receive your logsheet and certificate by email, complete the test below, add your details, then fold and freepost to C+D. Alternatively visit bit.ly/maloffprotectcpd to complete the test and receive your certificate and logsheet 1. Any UK traveller can catch malaria in an endemic region 7. Maloff Protect (atovaquone/ proguanil) can be recommended to adults without requiring a PGD or prescription 2. Infection of red blood cells by plasmodium parasites causes malaria 8. Maloff Protect can be recommended to travellers visiting regions where chloroquine or mefloquine-resistant 3. Malaria is a serious disease that can quickly become life-threatening malaria parasites have been reported 4. Vomiting is an early symptom of malaria 9. Maloff Protect can be recommended to children, women who are pregnant, breastfeeding, or could become pregnant 5. The symptoms of malaria always occur immediately 10. All malaria chemoprophylactic agents need to be taken daily 6. Effective malaria chemoprophylatic agents always require a prescription First name: Last name: Email: 10 C+D CPD Module Malaria prevention Malaria prevention C+D CPD Module 11