Patient leaflets and SmPCs, drug interaction checker, official and paediatric dosages, pregnancy and breastfeeding guidance, and NHS pharmacy opening hours — all in one place.
Patient leaflets and SmPCs, drug interaction checker, official and paediatric dosages, pregnancy and breastfeeding guidance, and NHS pharmacy opening hours — all in one place.
Atovaquone/Proguanil Hydrochloride belongs to a group of medicines called antimalarials. It contains two active ingredients, atovaquone and proguanil hydrochloride Atovaquone/Proguanil Hydrochloride has two uses: • to prevent malaria • to treat malaria Dosage instructions for each use are in Section 3, How to take Atovaquone/Proguanil Hydrochloride. Malaria is spread by the bite of an infected mosquito, which passes the malaria parasite (Plasmodium falciparum) into the bloodstream. Atovaquone/Proguanil Hydrochloride prevents malaria by killing this parasite. For people who are already infected with malaria, Atovaquone/Proguanil Hydrochloride also kills these parasites. Protect yourself from catching malaria People of any age can get malaria. It is a serious disease, but is preventable. As well as taking Atovaquone/Proguanil Hydrochloride, it is very important that you also take steps to avoid being bitten by mosquitoes. • Use insect repellent on exposed areas of the skin
• Wear light coloured clothing that covers most of the body, especially after sunset as this is the time when mosquitoes are most active • Sleep in a screened room or under a mosquito net impregnated with insecticide • Close windows and doors at sunset, if they are not screened • Consider using an insecticide (mats, spray, plug-ins) to clear a room of insects or to deter mosquitoes from entering the room. If you need further advice, talk to your doctor or pharmacist. It is still possible to get malaria after taking the necessary precautions. Some types of malaria infection take a long time to cause symptoms, so the illness may not start until several days, weeks or even months after returning from abroad. See a doctor immediately if you get symptoms such as high temperature, headache, shivering and tiredness after returning home.
Take Atovaquone/Proguanil Hydrochloride with food or a milky drink, where possible. This will increase the amount of Atovaquone/Proguanil Hydrochloride your body can absorb, and make your treatment more effective. Pregnancy and breast feeding If you are pregnant, do not take Atovaquone/Proguanil Hydrochloride unless your doctor recommends it. Ask your doctor or pharmacist for advice before taking Atovaquone/Proguanil Hydrochloride. Do not breast feed while taking Atovaquone/Proguanil Hydrochloride, as the ingredients of Atovaquone/Proguanil Hydrochloride may pass into breast milk and may harm your baby. Driving and using machines If you feel dizzy, do not drive. Atovaquone/Proguanil Hydrochloride makes some people feel dizzy. If this happens to you, do not drive, use machines or take part in activities where you may put yourself or others at risk. Atovaquone/Proguanil Hydrochloride contains sodium This medicine contains less than 1 mmol sodium (23mg) per film-coated tablet, that is so to say essentially 'sodium-free'.
• over 40 kg – dose as for adults. Not recommended for treating malaria in children who weigh less than 11 kg. For children who weigh less than 11 kg talk to your doctor. There may be a different type of tablets available in your country. If you are sick (vomit) For preventing malaria: • if you are sick (vomit) within 1 hour of taking your Atovaquone/Proguanil Hydrochloride tablet, take another dose straight away • it is important to take the full course of Atovaquone/Proguanil Hydrochloride. If you have to take extra tablets due to sickness, you may need another prescription. • if you have been vomiting, it is especially important to use extra protection, such as repellents and bednets. Atovaquone/Proguanil Hydrochloride may not be as effective, as the amount absorbed will be reduced. For treating malaria: • if you have vomiting or diarrhoea tell your doctor, you Will need regular blood tests. Atovaquone/Proguanil Hydrochloride will not be as effective, as the amount absorbed will be reduced. The tests will check whether the malaria parasite is being cleared from your blood. If you take more Atovaquone/Proguanil Hydrochloride than you should Contact a doctor or pharmacist for advice. If possible show them the Atovaquone/Proguanil Hydrochloride pack. If you forget to take Atovaquone/Proguanil Hydrochloride It is very important that you take the full course of Atovaquone/Proguanil Hydrochloride. If you forget to take a dose, don't worry. Just take your next dose as soon as you remember. Then continue your treatment as before. Don't take extra tablets to make up for a missed dose. Just take your next dose at the usual time. If you stop taking Atovaquone/Proguanil Hydrochloride Do not stop taking Atovaquone/Proguanil Hydrochloride without advice. Keep taking Atovaquone/Proguanil Hydrochloride for 7 days after you return to a malariafree area. Take the full course of Atovaquone/Proguanil Hydrochloride for maximum protection. Stopping early puts you at risk of getting malaria, as it takes 7 days to ensure that any parasites that may be in your blood following a bite from an infected mosquito are killed. If you have any further questions on the use of this product, ask your doctor or pharmacist.
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Look out for the following severe reactions. They have occurred in a small number of people, but their exact frequency is unknown. Severe allergic reactions - signs include: • rash and itching • sudden wheezing, tightness of the chest or throat, or difficulty breathing • swollen eyelids, face, lips, tongue or other part of the body. Contact a doctor immediately if you get any of these symptoms. Stop taking Atovaquone/Proguanil Hydrochloride. Severe skin reactions • skin rash, which may blister and looks like small targets (central dark spots, surrounded by paler area with a dark ring around the edge) (erythema multiforme) • severe widespread rash with blisters and peeling skin, particularly occurring around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome). If you notice any of these symptoms contact a doctor urgently. Most of the other side effects reported have been mild and have not lasted very long. Very common side effects (may affect more than 1 in 10 people) • headache • feeling sick and being sick (nausea and vomiting) • stomach pain • diarrhoea. Common side effects (may affect up to 1 in 10 people): • dizziness • sleeping problems (insomnia) • strange dreams • depression • loss of appetite • fever • rash which may be itchy • cough. Common side effects, which may show up in your blood tests are: • reduced numbers of red blood cells (anaemia) which can cause tiredness, headaches and shortness of breath • reduced numbers of white blood cells (neutropenia) which may make you more likely to catch infections • low levels of sodium in the blood (hyponatraemia) • an increase in liver enzymes. Uncommon side effects (may affect up to 1 in 100 people) • anxiety • an unusual awareness of abnormal beating of the heart (palpitations) • swelling and redness of the mouth • hair loss
• itchy, bumpy rash (hives) Uncommon side effects that may show up in your blood tests: • an increase in amylase (an enzyme produced in the pancreas). Rare side effects (may affect up to 1 in 1,000 people): • seeing or hearing things that are not there (hallucinations) Other side effects Other side effects have occurred in a small number of people but their exact frequency is unknown. • Inflammation of the liver (hepatitis) • blockage of the bile ducts (cholestatis) • increase in heart rate (tachycardia) • inflammation of the blood vessels (vasculitis) which may be visible as red or purple raised spots on the skin but can affect other parts of the body • fits (seizures) • panic attacks, crying • nightmares • severe mental health problems in which the person loses contact with reality and is unable to think and judge clearly • indigestion • mouth ulcers • blisters • peeling skin • increased sensitivity of the skin to sunlight. Other side effects that may show up in your blood tests: • A decrease in all types of blood cells (pancytopenia). Reporting of side effects If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme website www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.
Amarox Pharma B.V. Rouboslaan 32 2252 TR Voorschoten Netherlands This leaflet was last revised in 03/2023.
Atovaquone/Proguanil Hydrochloride 250 mg/100 mg film-coated tablets comes as tablet containing 250mg / 100mg. Always follow the dose your doctor or pharmacist has given you, and read the leaflet that comes with the medicine.
The active substance in Atovaquone/Proguanil Hydrochloride 250 mg/100 mg film-coated tablets is atovaquone, proguanil hydrochloride.
Medicines with the same active substance, strength and form include: Malarone 250 mg/100 mg film-coated tablets, Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets, Atovaquone/Proguanil Hydrochloride 250 mg/100 mg film-coated tablets. They are interchangeable only if your prescriber or pharmacist says so.
This leaflet reproduces the patient information leaflet approved for Atovaquone/Proguanil Hydrochloride 250 mg/100 mg film-coated tablets, as published on the electronic medicines compendium (emc). The version printed inside your medicine’s packaging is the one that applies to you.
Whether a medicine is available over the counter or on prescription only depends on its licence. Check the leaflet, or ask your pharmacist — they can tell you straight away.
The text above reproduces the patient information leaflet approved for this medicine, restructured for easier reading.
Prophylaxis of Plasmodium falciparum malaria in adults and in children weighing more than 40 kg.
Treatment of acute, uncomplicated Plasmodium falciparum malaria in adults and in children weighing 11 kg or more.
Official guidelines and local information on the prevalence of resistance to antimalarial drugs should be taken into consideration. Official guidelines will normally include WHO and public health authorities' guidelines.
Posology Prophylaxis: Prophylaxis should • commence 24 or 48 hours prior to entering a malaria-endemic area, • continue during the period of the stay, • continue for 7 days after leaving the area. In residents (semi-immune subjects) of endemic areas, the safety and effectiveness of atovaquone/proguanil has been established in studies of up to 12 weeks. In non-immune subjects, the average duration of exposure in clinical studies was 27 days. Dosage in Adults and children weighing at least 40 kg One Atovaquone/Proguanil Hydrochloride tablet daily. Atovaquone/Proguanil Hydrochloride tablets are not recommended for malaria prophylaxis in persons under 40 kg bodyweight. Atovaquone/Proguanil Hydrochloride paediatric tablets are recommended for malaria prophylaxis in persons weighing <40 kg Treatment Dosage in Adults Four Atovaquone/Proguanil Hydrochloride tablets as a single dose for three consecutive days. Dosage in Children weighing 11 kg or more 11-20 kg bodyweight One tablet daily for three consecutive days. 21-30 kg bodyweight Two tablets as a single dose for three consecutive days. 31-40 kg bodyweight Three tablets as a single dose for three consecutive days. >40 kg bodyweight Dose as for adults. Dosage in the Elderly A pharmacokinetic study indicates that no dosage adjustments are needed in the elderly (See Section 5.2). Dosage in Hepatic Impairment A pharmacokinetic study indicates that no dosage adjustments are needed in patients with mild to moderate hepatic impairment. Although no studies have been conducted in patients with severe hepatic impairment, no special precautions or dosage adjustment are anticipated (See Section 5.2). Dosage in Renal Impairment Pharmacokinetic studies indicate that no dosage adjustments are needed in patients with mild to moderate renal impairment. In patients with severe renal impairment (creatine clearance <30 mL/min) alternatives to Atovaquone/Proguanil Hydrochloride for treatment of acute P. falciparum malaria should be recommended whenever possible (See Sections 4.4 and 5.2). For prophylaxis of P. falciparum malaria in patients with several renal impairments see Section 4.3. Method of administration The daily dose should be taken with food or a milky drink (to ensure maximum absorption) at the same time each day. If patients are unable to tolerate food, Atovaquone/Proguanil Hydrochloride should be administered, but systemic exposure of atovaquone will be reduced. In the event of vomiting within 1 hour of dosing a repeat dose should be taken. <summary id="CONTRAINDICATIONS" data-evt="smpcSectionOpen"
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. Atovaquone/Proguanil Hydrochloride is contra-indicated for prophylaxis of P. falciparum malaria in patients with severe renal impairment (creatinine clearance < 30 mL/min). <summary id="CLINICAL_PRECAUTIONS" data-evt="smpcSectionOpen"
The safety and effectiveness of atovaquone 250mg/proguanil hydrochloride 100mg tablets has not been established for propyhlaxis of malaria in patients who weigh less than 40kg, or in the treatment of malaria in paediatric patients who weigh less than 11kg. Persons taking Atovaquone/Proguanil Hydrochloride for prophylaxis or treatment of malaria should take a repeat dose if they vomit within 1 hour of dosing. In the event of diarrhoea, normal dosing should be continued. Absorption of atovaquone may be reduced in patients with diarrhoea or vomiting, but diarrhoea or vomiting was not associated with reduced efficacy in clinical trials of atovaquone/proguanil for malaria prophylaxis. However, as with other antimalarial agents, subjects with diarrhoea or vomiting should be advised to continue with malaria prevention measures by complying with personal protection measures (repellants, bednets). In patients with acute malaria who present with diarrhoea or vomiting, alternative therapy should be considered. If Atovaquone/Proguanil Hydrochloride is used to treat malaria in these patients, parasitaemia and the patient's clinical condition should be closely monitored. Atovaquone/proguanil has not been evaluated for the treatment of cerebral malaria or other severe manifestations of complicated malaria including hyperparasitaemia, pulmonary oedema or renal failure. Occasionally, severe allergic reactions (including anaphylaxis) have been reported in patients taking atovaquone/proguanil. If patients experience an allergic reaction (see section 4.8) Atovaquone/Proguanil Hydrochloride should be discontinued promptly and appropriate treatment initiated. Atovaquone/proguanil has been shown to have no efficacy against hypnozoites of Plasmodium vivax as parasite relapse occurred commonly when P. vivax malaria was treated with atovaquone/proguanil alone. Travelers with intense exposure to P. vivax or P. ovale , and those who develop malaria caused by either of these parasites, will require additional treatment with a drug that is active against hypnozoites. In the event of recrudescent infections due to P. falciparum after treatment with Atovaquone/Proguanil Hydrochloride, or failure of chemoprophylaxis with Atovaquone/Proguanil Hydrochloride, patients should be treated with a different blood schizonticide as such events can reflect a resistance of the parasite. Parasitaemia should be closely monitored in patients receiving concurrent tetracycline (see section 4.5). The concomitant administration of Atovaquone/Proguanil Hydrochloride and efavirenz or boosted protease-inhibitors should be avoided whenever possible (see section 4.5). The concomitant administration of Atovaquone/Proguanil Hydrochloride and rifampicin or rifabutin is not recommended (see section 4.5). Concurrent use of metoclopramide is not recommended. Another antiemetic treatment should be given (see section 4.5). Caution is advised when initiating or withdrawing malaria prophylaxis or treatment with Atovaquone/Proguanil Hydrochloride in patients on continuous treatment with warfarin and other coumarin based anticoagulants (see section 4.5). Atovaquone can increase the levels of etoposide and its metabolite (see section 4.5). In patients with severe renal impairment (creatinine clearance <30 mL/min) alternatives to Atovaquone/Proguanil Hydrochloride for treatment of acute P. falciparum malaria should be recommended whenever possible (see sections 4.2, 4.3 and 5.2). <summary id="INTERACTIONS" data-evt="smpcSectionOpen"
Concomitant administration of rifampicin or rifabutin is not recommended as it is known to reduce plasma concentrations of atovaquone levels by approximately 50% and 34%, respectively (see section 4.4). Concomitant treatment with metoclopramide has been associated with a significant decrease (about 50 %) in plasma concentrations of atovaquone (see section 4.4). Another antiemetic treatment should be given. When given with efavirenz or boosted protease-inhibitors, atovaquone concentrations have been observed to decrease as much as 75%. This combination should be avoided whenever possible (see section 4.4) Proguanil may potentiate the effect of warfarin and other coumarin based anticoagulants which may lead to an increase in the risk of haemorrhage. The mechanism of this potential drug interaction has not been established. Caution is advised when initiating or withdrawing malaria prophylaxis or treatment with atovaquone-proguanil in patients on continuous treatment with oral anticoagulants. The dose of the oral anticoagulant may need to be adjusted during Atovaquone/Proguanil Hydrochloride treatment or after its withdrawal, based on INR results. Concomitant treatment with tetracycline has been associated with decreases in plasma concentrations of atovaquone. The co-administration of atovaquone at doses of 45mg/kg/day in children (n=9) with acute lymphoblastic leukaemia for prophylaxis of PCP was found to increase the plasma concentrations (AUC) of etoposide and its metabolite etoposide catechol by a median of 8.6% (P=0.055) and 28.4% (P=0.031) (respectively compared to the co- administration of etoposide and sulfamethoxazole-trimethoprim). Caution should be advised in patients receiving concomitant therapy with etoposide (see section 4.4). Proguanil is primarily metabolised by CYP2C19. However, potential pharmacokinetic interactions with other substrates, inhibitors (e.g. moclobemide, fluvoxamine) or inducers (e.g. artemisinin, carbamazepine) of CYP2C19 are unknown (see section 5.2). <summary id="PREGNANCY" data-evt="smpcSectionOpen"
Pregnancy
The safety of atovaquone and proguanil hydrochloride when administered concurrently for use in human pregnancy has not been established and the potential risk is unknown.
Animal studies showed no evidence for teratogenicity of the combination. The individual components have shown no effects on parturition or pre- and post- natal development. In rabbits treated with atovaquone during pregnancy, embryotoxicity was observed in the presence of maternal toxicity (see section 5.3).
The use of Atovaquone/Proguanil Hydrochloride in pregnancy should only be considered if the expected benefit to the mother outweighs any potential risk to the foetus.
The proguanil component of Atovaquone/Proguanil Hydrochloride acts by inhibiting parasitic dihydrofolate reductase. There are no clinical data indicating that folate supplementation diminishes drug efficacy. For women of childbearing age receiving folate supplements to prevent neural tube birth defects, such supplements should be continued while taking Atovaquone/Proguanil Hydrochloride.
Breast-feeding
The atovaquone concentrations in milk, in a rat study, were 30% of the concurrent atovaquone concentrations in maternal plasma. It is not known whether atovaquone is excreted in human milk.
Proguanil is excreted in human milk in small quantities.
Atovaquone/Proguanil Hydrochloride should not be taken by breast-feeding women.
Fertility
Proguanil hydrochloride did not cause effects on fertility in rats at exposures below the human therapeutic exposure. Otherwise, there are no data regarding potential effects of atovaquone and proguanil hydrochloride on fertility.
Dizziness has been reported. Patients should be warned that if affected they should not drive, operate machinery or take part in activities where this may put themselves or others at risk.
In clinical trials of atovaquone/proguanil in the treatment of malaria the most commonly reported adverse reactions were abdominal pain, headache, anorexia, nausea, vomiting, diarrhoea and coughing. In clinical trials of atovaquone/proguanil for prophylaxis of malaria, the most commonly reported adverse reactions were headache, abdominal pain and diarrhoea. The following table provides a summary of adverse reactions that have been reported to have a suspected (at least possible) causal relationship to treatment with atovaquone-proguanil in clinical trials and spontaneous post-marketing reports. The following convention is used for the classification of frequency: 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); not known (cannot be estimated from the available data). There are limited long term safety data in children. In particular, the long-term effects of atovaquone/proguanil on growth, puberty and general development have not been studied. System Organ Class Very Common Common Uncommon Rare Not known 2 Blood and lymphatic disorders Anaemia Neutropenia 1 Pancytopenia Immune system disorders Allergic reactions Angioedema 3 Anaphylaxis (see section 4.4) Vasculitis 3 Metabolism and nutrition disorders Hyponatraemia 1 Anorexia Elevated amylase levels 1 Psychiatric disorders Abnormal dreams Depression Anxiety Hallucinations Panic attack Crying Nightmares Psychotic disorder Nervous system disorders Headache Insomnia Dizziness Seizure Cardiac disorders Palpitations Tachycardia Gastrointestinal disorders Nausea 1 Vomiting Diarrhoea Abdominal pain Stomatitis Gastric intolerance 3 Oral ulceration 3 Hepatobiliary disorders Elevated liver enzymes 1 Hepatitis Cholestasis 3 Skin and subcutaneous tissue disorders Pruritus Rash Hair loss Urticaria Stevens- Johnson syndrome Erythema multiforme Blister Skin exfoliation Photosensitivity reactions General disorders and administration site conditions Fever Respiratory, thoracic and mediastinal disorders Cough 1. Frequency taken from atovaquone label. Patients participating in clinical trials with atovaquone have received higher doses and have often had complications of advanced Human Immunodeficiency Virus (HIV) disease. These events may have been seen at a lower frequency or not at all in clinical trials with atovaquone-proguanil. 2. Observed from post-marketing spontaneous reports and the frequency is therefore unknown 3. Observed with proguanil. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. <summary id="OVERDOSE" data-evt="smpcSectionOpen"
There is insufficient experience to predict the consequences or suggest specific management of atovaquone/proguanil overdose. However, in the reported cases of atovaquone overdose, the observed effects were consistent with known undesirable effects of the drug. If overdose occurs, the patient should be monitored, and standard supportive treatment applied.
Ask anything about Atovaquone/Proguanil Hydrochloride 250 mg/100 mg film-coated tablets. The assistant answers only from this leaflet — if the leaflet does not cover it, it will say so. It does not give medical advice.
Answers come from the patient leaflet published on the electronic medicines compendium (emc). They are not medical advice. Ask a pharmacist or your GP if you are unsure. For urgent help call NHS 111, or 999 in an emergency.
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