Pharmacy Guide. to Non-Prescription Atovaquone/Proguanil Once Daily 250 mg/100 mg (Maloff Protect)

Transcription

1 250 mg/100 mg Tablets atovaquone/proguanil hydrochloride Pharmacy Guide to Non-Prescription Atovaquone/Proguanil Once Daily 250 mg/100 mg (Maloff Protect) Maloff Protect pharmacy guide Date of preparation July 2017

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3 Maloff Protect is indicated for chemoprophylaxis of Plasmodium falciparum (P. falciparum) malaria in adults Contents Page About this guide 5 Introduction to malaria and Maloff Protect 6 Who is Maloff Protect for? 8 Advice for customers who purchase Maloff Protect: 9 - How many tablets will be required? 9 - Which pack size is recommended? 9 - Are there any storage requirements? 9 - How and when should Maloff Protect be taken? 10 - Possible side effects and when to seek medical advice 12 - What symptoms can indicate malaria? 13 Key considerations when a customer requests antimalarial prevention 14 Posologies, contraindications/warnings and common adverse events for other available antimalarials 16 Useful resources 22 References 23

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5 About this guide This guide has been developed to provide information to pharmacists and pharmacy assistants on the correct choice and usage of malaria chemoprophylaxis, and in doing so manage the risks related to atovaquone/proguanil once daily 250 mg/100 mg (Maloff Protect) and promote its safe supply and use. It summarises key information to help you identify whether or not it would be appropriate to supply Maloff Protect to a customer, and the advice you should give to help them use Maloff Protect appropriately. A toolkit has been developed which contains: - This guide - A checklist summarising the actions that need to be completed prior to the provision of Maloff Protect - A screening questionnaire to help you determine a customer s suitability for Maloff Protect - A pack size calculator to help you determine the appropriate Maloff Protect pack size for the customer s need - A user reminder card you can provide to the customer, containing a medication reminder calendar and a section for you to complete with recommendations to seek additional travel advice - A reminder app to help customers remember to take their Maloff Protect at the right time and complete the course of Maloff Protect For full information, including all contraindications and possible side effects, please refer to the Summary of Product Characteristics (SmPC) (available online at emc/medicine/33700) and the patient information leaflet (PIL) that comes in the package with Maloff Protect. 5

6 Introduction to malaria and Maloff Protect Malaria is a serious tropical illness spread by mosquitoes. It causes fevers, and patients may suffer from raised temperature, chills, sweats, uncontrollable shivering, dizziness, headache, diarrhoea and abdominal pain, cough, muscular aching and weakness, vomiting, general malaise and body aches. It is one of the major causes of illness and/or death in the tropical regions of the world, where it is transmitted through the bites of infected Anopheles mosquitoes. Malaria prevention is important for travellers, as anyone who spends time in a malarial region is at risk of being infected with malaria. This includes: Someone travelling to a malarial region Someone born in a malarial region returning to visit friends or family. Any natural resistance they might have had disappears when they live outside the country Through their bites, the mosquitoes infect red blood cells with a parasite called Plasmodium, and it is this that causes malaria it only takes one bite for someone to become infected. Symptoms of malaria infection can take a long time to develop so travellers may not know they have malaria until they have returned home 1. The most common form of human malaria is caused by Plasmodium falciparum (P. falciparum): Worldwide, it is believed that approximately 2.4 billion people are at risk of being infected with P. falciparum 2 In 2015, 76% (1068/1400) of the total reported cases of malaria in the UK were caused by P. falciparum 3 Understanding how Maloff Protect works Maloff Protect contains atovaquone/proguanil in the ratio 250 mg/100 mg. Both work in slightly different ways to stop the reproduction of the P. falciparum parasite once it is in the blood stream. Proguanil hydrochloride blocks the action of a compound that is found in the parasite Atovaquone interferes with the production of substances needed by the malarial parasites to reproduce 6

7 Selecting the right malaria chemoprophylaxis 1 There are a number of antimalarials available that should be considered when providing advice to customers about malaria chemoprophylaxis. Table 1: Available options for malaria chemoprophylaxis Generic name Brand name Status Atovaquone/proguanil Maloff Protect Pharmacy Atovaquone/proguanil Malarone Prescription only Chloroquine Avloclor Pharmacy Chloroquine/proguanil Avloclor/Paludrine Pharmacy Doxycycline Vibramycin-D Prescription only Mefloquine Lariam Prescription only Proguanil Paludrine Pharmacy For a full list of contraindications, warnings/precautions and common adverse events for each of the other antimalarials, please refer to the tables towards the end of this guide. Selecting the right antimalarial depends on the region(s) the customer intends to travel to and the prevalence of resistance to antimalarial drugs in those regions. Before advising the customer, check the latest recommendations about malaria chemoprophylaxis at: (for Scottish healthcare professionals) Malaria chemoprophylaxis works by killing the parasite spread by an infected mosquito. If visiting more than one country, malaria may be caused by a different parasite. The malaria chemoprophylaxis selected should offer protection for all locations to be visited. Remember to complete the section in the user reminder card detailing the malaria prevention advice you have given the customer so that they can pass this on to their GP. This is recommended in guidelines from the UK Advisory Committee on Malaria Prevention (ACMP) and Public Health England (PHE) 3 Ensure the customer has had a full travel consultation. If they have not, remind them of the need to undertake an overall risk assessment-based package of travel health advice including advice on vaccinations. Provide the address to a facility they can receive this in the space provided on the patient reminder card. Malaria prophylaxis is only one of the aspects of pre-travel advice. 7

8 Who is Maloff Protect for? Atovaquone/proguanil 250 mg/100 mg (Maloff Protect) is now reclassified as a pharmacy medicine available without prescription for chemoprophylaxis of P. falciparum malaria in adults. See the Maloff Protect SmPC for further information. Maloff Protect is suitable for people who 1,4 : are aged 18 years or over weigh 40 kg (6 st 4 lbs) or more Do not supply Maloff Protect for the following people; instead advise them to see their doctor about malaria prevention 1,4 : children and adolescents adults weighing less than 40 kg people allergic to atovaquone and/or proguanil hydrochloride people allergic to any other ingredients in Maloff Protect (see SmPC for full list) breastfeeding women pregnant women women who are trying to become pregnant or think they may be pregnant People who: have a history of depression have kidney disease or renal impairment of any severity have ever had epilepsy, convulsions or fits have hepatic impairment of any severity have tuberculosis People who are taking: metoclopramide (for nausea and vomiting) the antibiotics: tetracycline rifampicin rifabutin indinavir, efavirenz, zidovudine or boosted protease inhibitors (used to treat HIV) further information on interactions with drugs to treat HIV, including an HIV drug interaction checker, is available at the University of Liverpool HIV Drug Interactions website ( warfarin, other coumarin-based anticoagulants, or new oral anticoagulants (NOACs) such as dabigatran etexilate, rivaroxaban and apixaban etoposide (used to treat cancer) 8

9 Advice for customers who purchase Maloff Protect How many tablets will be required? Advise customers to take some additional tablets with them in case of food poisoning or other illness causing vomiting. Which pack size is recommended? Maloff Protect is available as a pack size of 24 or 36 tablets. Refer to the pack size calculator for recommended pack sizes. Please note, customers should seek medical advice if they vomit repeatedly for more than a day or two for any reason. 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. Are there any storage requirements? There are no special storage conditions for Maloff Protect. As with all medicines, Maloff Protect should be kept out of the sight and reach of children 1,4. Remind customers to return any remaining Maloff Protect tablets to the pharmacy for destruction once the course has been completed. 9

10 Advice for customers who purchase Maloff Protect How and when should Maloff Protect be taken? To ensure that your customers receive the maximum prophylactic protection from Maloff Protect, you should advise them of the following: 1. The maximum prophylactic benefit of Maloff Protect will be achieved by1,4: starting one to two days prior to entering a malaria-endemic area continuing during the period of the stay continuing for seven days after returning to a malaria-free area Ensure the customer understands the importance of taking the full course of Maloff Protect for maximum protection Taking tablets for one to two days before travelling to a malaria area will ensure the customer is protected from malaria as soon as they arrive1,4 Stopping early increases the risk of malaria, as it takes seven days to ensure that any parasites in the blood are killed following a bite from an infected mosquito1 Ensure the customer understands that Maloff Protect must be taken once every 24 hours and it is preferable to take it at the same time every day1,4. Remind them to bear this in mind when travelling through different time zones 2. The dosage is one tablet daily4 If a tablet is missed for any reason, advise the customer that they should not take two tablets together. They should take their missed dose as soon as they remember or, if it is nearly time for their next dose, skip the missed dose altogether 10 Tablets should not be crushed Tablets should be taken with food or a milky drink (to ensure absorption) at the same time each day1

11 3. In the event of vomiting within one hour of dosing, advise the customer that they will need to take another dose straight away 1,4 Ensure the customer understands why, if they vomit for any reason within one hour of dosing, they should: take another dose straight away take other practical steps to avoid being bitten (see page 14) This is to avoid the possible risk associated with a lower than expected level of absorption of Maloff Protect 4 4. Maloff Protect should always be taken alongside other malaria prevention techniques Explain the importance of bite avoidance Ensure the customer understands that they must take other practical steps to avoid being bitten as well as taking their malaria chemoprophylaxis (see page 14) 11

12 Advice for customers who purchase Maloff Protect Possible side effects and when to seek medical advice Atovaquone/proguanil 250 mg/100 mg has been available on prescription since A full list of side effects experienced with Maloff Protect over the past 20 years can be found in the SmPC 4. For malaria prevention, the dosage of Maloff Protect is only one tablet, once daily 4. Advise customers to tell a doctor or pharmacist if any side effects become serious, or if they notice any side effects not listed in the PIL. The most commonly reported side effects in the use of Maloff Protect as prophylaxis are 1 : A small number of people (exact frequency cannot be estimated from available data) 1 have experienced severe allergic reactions or severe skin reactions following treatment with Maloff Protect headache nausea and vomiting abdominal pain diarrhoea Advise customers to stop taking Maloff Protect and seek medical assistance immediately if they experience a severe allergic or skin reaction Customers can find further information on signs and symptoms in the User Guide and PIL 1 Despite possible side effects that might occur, it is important to ensure that the customer is protected against malaria In the case of severe side effects customers should stop taking Maloff Protect and seek medical assistance immediately Advise customers to limit the risk of malaria by continuing to take practical steps to avoid being bitten (listed on page 14) Please read the SmPC or PIL for full details of contraindications, special warnings and precautions. Remind every customer to read the PIL and User Guide carefully before taking Maloff Protect. 12

13 Advice for customers who purchase Maloff Protect What symptoms can indicate malaria? Advise customers that if they experience the symptoms below they should immediately seek medical assistance, even if they have been taking malaria chemoprophylaxis and using bite avoidance measures. Maloff Protect is not a treatment for malaria. The early symptoms of malaria are nonspecific and it is difficult to distinguish them from those of other common illnesses, such as acute respiratory infections (colds or flu) 5. Symptoms include 5 : fever chills headache muscular aching and weakness vomiting cough diarrhoea and abdominal pain general malaise Some types of malaria infection take a long time to cause symptoms days, weeks or even months after returning from abroad 1. The possibility of P. falciparum malaria should be considered for any unexplained fever starting at any time between seven days after the first possible exposure to malaria and three months (or, rarely, later) after the last possible exposure 3 Anybody who is/has been in a malarial region and experiences a fever in this time period should immediately seek medical assistance, advising the doctor of the possible exposure to malaria infection 3,5. P. falciparum malaria may be fatal if treatment is delayed beyond 24 hours after the onset of clinical symptoms 5. 13

14 Key considerations when a customer requests antimalarial prevention You should discuss all of the following with any customer planning to travel to a malarial region: 1. How malaria is transmitted 1 : Malaria is spread by the bite of an infected mosquito The infected mosquito passes the malaria parasite into the bloodstream 2. How to avoid mosquito bites 1 (you should highlight to the customer that the bite avoidance measures should be used in combination for maximum effectiveness): Use DEET-based insect repellent with a concentration of over 20% on exposed areas of the skin Wear clothing that covers most of the body, especially at dawn and after sunset as this is the time when mosquitoes are most active Sleep in a room with screened windows and doors or under a mosquito net (it is preferable to sleep under a mosquito net treated with insecticide, if possible) Close windows/doors after sunset (unless in a screened room) Sleep in a room with air-conditioning or a fan, as mosquitoes are less active in cooler temperatures Consider using an insecticide to clear a room of insects or to stop mosquitoes from entering the room The use of natural or homeopathic remedies is strongly advised against, as there is no scientific proof that these remedies are effective in either the prevention or the treatment of malaria 3. The importance of taking the medicine as instructed for malaria chemoprophylaxis 1,4 : Selecting the right antimalarial depends on the region(s) the customer intends to travel to and the prevalence of resistance to antimalarial drugs in those regions Maximum prophylaxis from Maloff Protect will only be achieved by following the instructions for use. This includes taking Maloff Protect one to two days before arrival in the malaria region and completing the entire course of tablets after leaving the region Using Maloff Protect incorrectly places others at risk of malaria in the future, as the parasite that causes malaria can become resistant to the drug. 14

15 4. Malaria prevention is only one aspect of healthy travel. You can play an important role in supporting healthy travel: Ensure the customer has had a full travel consultation. If they have not, remind them of the need to undertake an overall risk assessment-based package of travel health advice including advice on vaccinations. Provide the address to a facility they can receive this in the space provided on the patient reminder card. Malaria prophylaxis is only one of the aspects of pre-travel advice Advise customers to read the latest health and safety advice for the country they are travelling to. A good source of up to date information is: Provide advice on staying healthy when on holiday: Use of sunscreen Drinking water Basic travel health kit 5. Advise customers on symptoms of malaria and the need to seek medical attention immediately if they experience these symptoms 6. Advise the customer that if their travel plans change, they will need to seek updated travel advice The NHS provides a comprehensive checklist of advice for safe travel through Supply customer with User Reminder Card and inform them about the Reminder App. 15

16 Posologies, contraindications/warnings and common adverse events for other available antimalarials Atovaquone/proguanil (POM) 6 Posology Prior: h Post: 7 days 1 x 250 mg/100 mg tablet daily Contraindications Patients with hypersensitivity to the active substance or any excipients, severe renal impairment Warnings/ precautions Can cause: severe allergic reaction, including anaphylaxis Interactions Efavirenz or boosted protease inhibitors, etoposide, metoclopramide, rifampicin or rifabutin, tetracycline, warfarin and other coumarin-based anticoagulants Very common and common adverse events Abdominal pain, abnormal dreams, allergic reactions, anaemia, anorexia, cough, depression, diarrhoea, dizziness, elevated liver enzymes, fever, headache, hyponatraemia, insomnia, nausea, neutropenia, pruritus, rash, vomiting 16

17 Chloroquine (P) 7 Posology Prior: 1 week Post: 4 weeks 2 x 250 mg tablets once weekly after food (same day each week) Contraindications Concomitant use with amiodarone, patients with hypersensitivity to the active substance or any excipients Warnings/ precautions Can cause: acute extrapyramidal disorders, bone marrow suppression with long-term use, cardiomyopathy, diffuse parenchymal lung disease, drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, irreversible retinal damage and corneal change with long-term use, prolongation of QTc interval, severe hypoglycaemia Use with caution in patients with: congenital or documented acquired QT prolongation and/or known risk factors for QT prolongation, glucose-6-phosphate dehydrogenase deficiency, history of epilepsy, impaired hepatic and/or renal function, porphyria, psoriasis Interactions Agalsidase, antacids, antiepileptics, ciclosporin, cimetidine, digoxin, drugs known to prolong QT interval, halofantrine, mefloquine, multidrug and toxin extrusion protein (MATE1) inhibitors, neostigmine and pyridostigmine, praziquantel, rabies vaccine, thyroid medications Very common and common adverse events Not reported 17

18 Chloroquine/proguanil (P) 8 Posology Prior: 1 week Post: 4 weeks 2 x 100 mg proguanil tablets daily 2 x 250 mg chloroquine tablets once weekly (same day each week) Contraindications Concomitant use with amiodarone, patients with hypersensitivity to the active substance or any excipients Warnings/ precautions Can cause: acute extrapyramidal disorders, bone marrow suppression with long-term use, cardiomyopathy, diffuse parenchymal lung disease, DRESS syndrome, irreversible retinal damage and corneal change with long-term use, prolongation of QTc interval, severe hypoglycaemia Use with caution in patients with: congenital or documented acquired QT prolongation and/or known risk factors for QT prolongation, glucose-6-phosphate dehydrogenase deficiency, history of epilepsy, impaired hepatic and/or renal function, porphyria, psoriasis Interactions Agalsidase, antacids, anticoagulants, antiepileptics, boosted protease inhibitors, ciclosporin, cimetidine, digoxin, drugs known to prolong QT interval, live oral typhoid vaccine, mefloquine, multidrug and toxin extrusion protein (MATE1) inhibitors, neostigmine, pyridostigmine, praziquantel, rabies vaccine, thyroid medications Very common and common adverse events Not reported 18

19 Doxycycline (POM) 9 Posology Prior: 1-2 days Post: 4 weeks 1 x 100 mg tablet daily Contraindications Pregnancy, breastfeeding, children under 12 years of age, patients with hypersensitivity to the active substance or any excipients Warnings/ precautions Can cause: benign intracranial hypertension, Clostridium difficile - associated diarrhoea, microbiological overgrowth, oesophagitis, photosensitivity, porphyria, pseudomembranous colitis Use with caution in patients with: impaired hepatic and/ or renal function, myasthenia gravis, systemic lupus erythematosus Interactions Alcohol, antacids, barbiturates, carbamazepine or phenytoin, ciclosporine, isotretinoin or other systemic retinoids, methoxyflurane, oral contraceptives, penicillin, warfarin and other anticoagulants Very common and common adverse events Anaphylactic reaction, headache, nausea/vomiting, photosensitivity reaction, rash including maculopapular and erythematous rashes 19

20 Mefloquine (POM) 10 Posology Prior: 10 days Post: 4 weeks 1 x 250 mg tablet once weekly (same day each week) Contraindications Galactose intolerance, patients with active/history of psychiatric disorders or convulsions, patients with a history of Blackwater fever, patients with hypersensitivity to the active substance or any excipients, severe hepatic impairment, use with halofantrine Warnings/ precautions Can cause: arrhythmia or palpitations, blood and lymphatic system disorders, eye disorders, hypersensitivity reactions, neuropathy, neuropsychiatric symptoms, pneumonitis Use with caution in patients with: cardiac conduction disorders, congenital hyperinsulinaemic hypoglycaemia, epilepsy, impaired hepatic and/or renal function Interactions Anticonvulsants, CYP3A4 inhibitors and inducers, drugs that lower the epileptogenic threshold (antidepressants such as tricyclic or selective serotonin reuptake inhibitors [SSRIs], bupropion, antipsychotics, tramadol, chloroquine or some antibiotics), drugs that prolong QTc interval, halofantrine, ketoconazole, vaccines, mefloquine and other related compounds (e.g. quinine, quinidine and chloroquine) Very common and common adverse events Abdominal pain, abnormal dreams, insomnia, diarrhoea, dizziness, headache, nausea/vomiting, pruritus, vertigo, visual impairment 20

21 Proguanil (P) 11 Posology Prior: 1 week Post: 4 weeks 2 x 100 mg tablets daily Contraindications Patients with hypersensitivity to the active substance or any excipients Warnings/ precautions Use with caution in patients with: severe renal impairment Interactions Antacids, anticoagulants, boosted protease inhibitors, live oral typhoid vaccine (Ty21a strain) Very common and common adverse events Not reported 21

22 Useful resources TRAVEL HEALTH PRO Advice line for health professionals: Website: Access up-to-date country and disease information from the National Travel Health Network and Centre (NaTHNaC) TRAVAX Website: For Scottish travellers: up-to-date health information for Scottish healthcare professionals WORLD HEALTH ORGANISATION Website: Access one-page country profiles for all malaria-endemic countries of the world. The profiles contain key data about the countries malaria burden, as well as a summary of the main malaria interventions used, and information about the adoption of WHO-recommended policies NHS Check whether your customer will need to take preventative malaria treatment for the countries they intend to visit Find general information about malaria, symptoms, causes and prevention LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE Telephone number: Website: malaria.lshtm.ac.uk The Malaria Centre at the London School of Hygiene and Tropical Medicine houses the largest number of malaria researchers, students and support staff in Europe These links are provided as a useful resource. Glenmark accepts no liability for the accuracy or completeness of any of the information contained on these websites. 22

23 All adverse drug reactions should be reported. Reporting forms and information can be found at Date of preparation July 2017 Version 1 MHRA approval date: 3 July 2017 References 1. PIL for non prescription atovaquone/proguanil 250 mg/100 mg. Accessed July Guerra CA, Gikandi PW, Tatem AJ, et al. The limits and intensity of Plasmodium falciparum transmission: implications for malaria control and elimination worldwide. PLoS Med. 2008;5(2):e38. article?id= /journal.pmed Accessed July Public Health England. Guidelines for malaria prevention in travellers from the UK file/585695/2016_acmp_guidelines_final_-_updated_ethiopia_2_.pdf. Accessed March SmPC for non-prescription atovaquone/proguanil 250 mg/100 mg. Accessed July WHO. International Travel and Health. Chapter Accessed July GlaxoSmithKline. Malarone SmPC. Available at: medicine/756. Accessed February Alliance Pharmaceuticals. Avloclor SmPC. Available at: uk/emc/medicine/2272. Accessed February Alliance Pharmaceuticals. Paludrine/Avloclor SmPC. Available at: medicines.org.uk/emc/medicine/2294. Accessed February Pfizer Limited. Vibramycin-D SmPC. Available at: emc/medicine/ Accessed February Roche Products Limited. Lariam SmPC. Available at: emc/medicine/1701. Accessed February Alliance Pharmaceuticals. Paludrine SmPC. Available at: uk/emc/medicine/2293. Accessed February

24 Date of preparation July 2017