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 250 mg/100 mg Film-coated tablets belong to a group of medicines called antimalarials . It contains two active ingredients, atovaquone and proguanil hydrochloride.
Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets have two uses:
• to prevent malaria in adults and children who weigh more than 40 kg
• to treat malaria in adults and children who weigh more than 11 kg
Malaria is spread by the bite of an infected mosquito, which passes the malaria parasite (Plasmodium falciparum) into the bloodstream. Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets prevent malaria by killing this parasite. For people who are already infected with malaria, Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets 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 250 mg/100 mg Film-coated tablets, 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.
Do not take Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets: • if you are allergic to Atovaquone and/or proguanil hydrochloride or any of the ingredients of this medicine (listed in section 6).
• for preventing malaria, if you have severe kidney disease.
Warnings and precautions When preventing malaria:
• if you are sick (vomit) within 1 hour of taking your Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablet, take another dose straight away
• it is important to take the full course of Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets. 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 250 mg/100 mg Film-coated tablets may not be as effective, as the amount absorbed will be reduced.
When treating malaria:
• if you have vomiting and diarrhoea tell your doctor, you will need regular blood tests. Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets 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 have severe kidney disease, your doctor may want to prescribe a different medicine
• if you get a certain type of infection whilst being treated with Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets, your doctor may prescribe another type of medicine instead of Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets
• if the malaria is treated but then comes back repeatedly or if the malaria is caused by a certain type of parasite, your doctor may prescribe another medicine to be taken as well as Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets
Other medicines and Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Some medicines can affect the way Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets works, or Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets themselves can strengthen or weaken the effectiveness of other medicines taken at the same time. These include:
• metoclopramide, used to treat nausea and vomiting
• the antibiotics tetracycline, rifampicin and rifabutin
• efavirenz or certain highly active protease-inhibitors used to treat HIV
• indinavir, used to treat HIV
• warfarin and other medicines that stop blood clotting
• etoposide used to treat cancer.
Tell your doctor if you are taking any of these. Your doctor may decide that Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets aren't suitable for you, or that you need extra check ups while you're taking it.
REMEMBER to tell your doctor if you start taking any other medicines while you're taking Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets.
Atovaquone/Proguanil Hydrochloride with food and drink Take Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets with food or a milky drink, where possible. This will increase the amount of Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets your body can absorb, and make your treatment more effective.
The tablets should preferably not be crushed.
Pregnancy and breast-feeding If you are pregnant or if you have the intention to get pregnant, do not take Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets unless your doctor recommends it.
Ask your doctor or pharmacist for advice before taking Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets.
Do not breast feed while taking Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets, as the ingredients of Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets may pass into breast milk and may harm your baby.
Driving and using machines If you feel dizzy, do not drive. Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets make 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.
Always take Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.
Take Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets with food or a milky drink, where possible.
It is best to take Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets at the same time each day.
For preventing malaria The usual dose for adults and adolescents weighing more than 40 kg is 1 tablet once a day, taken as below.
For children, talk to your doctor.
Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets is not recommended for preventing malaria in children, or in adults or adolescents who weigh less than 40 kg.
There may be a different type of Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets available for children in your country.
To prevent malaria in adults:
• start taking Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets 1 to 2 days before travelling to an area which has malaria
• continue taking it every day during your stay and then continue taking it for another 7 days after your return to a malaria-free area. Take the full course of Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets 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.
For treating malaria: The usual dose for adults is 4 tablets once a day for 3 days.
For children weighing 11 kg or more:
• ≥11 to <20 kg – 1 tablet once a day for 3 days
• ≥ 21 to <30 kg – 2 tablets once a day for 3 days
• ≥ 31 to <40 kg – 3 tablets once a day for 3 days
• Over 40 kg – dose as for adults.
Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets is 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 Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablet available in your country
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 250 mg/100 mg Film-coated tablets pack.
If you forget to take Atovaquone/Proguanil Hydrochloride It is very important that you take the full course of Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets. 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 a double dose to make up for a missed dose.
Don't stop taking Atovaquone/Proguanil Hydrochloride without advice Keep taking Atovaquone/Proguanil Hydrochloride for 7 days after you return to a malaria-free 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.
Please talk to your doctor or pharmacist if you need any advice.
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 250 mg/100 mg Film-coated tablets. 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: affects more than 1 user in 10
• headache
• feeling sick and being sick (nausea and vomiting)
• stomach pain
• diarrhoea
Common: affects 1 to 10 users in 100
• dizziness
• sleeping problems (insomnia)
• strange dreams
• depression
• loss of appetite
• fever
• rash
• cough
• allergic reactions
• itching (pruritus)
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: affects 1 to 10 users in 1,000
These 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
• red swollen patches on the skin (hives)
• hair loss.
Uncommon side effects that may show up in your blood tests:
• an increase in amylase (an enzyme produced in the pancreas) .
Rare: affects 1 to 10 users in 10,000
• 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 (seizure)
• panic attacks, crying
• nightmares
• severe mental health problem in which the person loses contact with reality and is unable to think and judge clearly
• mouth ulcers
• blisters
• peeling skin
• increased sensitivity of the skin to sunlight
• effects on your stomach (gastric intolerance).
Other side effects that may show up in your blood tests:
• Adecrease 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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and the blister after EXP. The expiry date refers to the last day of that month.
This medicinal product does not require any special storage conditions.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
What Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets contain The active substances are atovaquone and proguanil hydrochloride.
Each tablet contains 250 mg atovaquone and 100 mg proguanil hydrochloride.
The other ingredients are:
Core
Poloxamer 188 , Microcrystalline Cellulose, Low-substituted Hydroxypropyl Cellulose, Povidone K30, Sodium Starch Glycolate Type A, Silica Colloidal anhydrous, Magnesium Stearate
Coating
Hypromellose, Titanium Dioxide (E171), Iron Oxide Red (E172), Macrogol 400, Macrogol 8000
What Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets looks like and contents of the pack Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets are Pinkish brown to brown coloured, circular, biconvex beveled edge Film-coated tablets with '404' debossed on one side and 'G' debossed on the other side.
Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated are supplied in PVC/PVDC (clear) and hard tempered PVC/PVDC-Aluminium foil blister packs containing 12 tablets
Pack size: 12, 24, 36, 60
Not all pack sizes may be marketed.
Marketing Authorisation Holder Glenmark Pharmaceuticals Europe Limited
Laxmi House
2 B Draycott Avenue
Kenton
Middlesex
HA3 0BU
United Kingdom
Manufacturer Glenmark Pharmaceuticals Europe Limited
Building 2
Croxley Green Business Park Croxley Green
Hertfordshire
WD 18 8YA
United Kingdom
Glenmark Pharmaceuticals s.r.o.
Hvězdova 1716/2b
140 78 Prague 4
Czech Republic
This medicinal product is authorised in the Member States under the following names:
Denmark Atovaquon/Proguanilhydrochlorid Glenmark 250 mg /100 mg Filmovertrukne tabletter
Germany Atovaquon/Proguanilhydrochlorid Glenmark 250 mg /100 mg Filmtabletten
France Atovaquone/Proguanil Alfasigma 250 mg /100 mg comprimé pelliculé
United Kingdom Atovaquone/Proguanil Hydrochloride 250 mg /100 mg Film-coated tablets
The Netherlands Atovaquon/Proguanilhydrochloride Glenmark 250 mg /100 mg Filmomhulde Tabletten
Belgium Atovaquone/Proguanil Glenmark 250mg/100mg filmomhulde tabletten/comprimés pellicullés/Filmtabletten
Sweden Atovakvon / Proguanil Glenmark 250/100 mg filmdragerade tabletter
Spain Malaway 250 mg/100 mg Comprimidos recubiertos con película
Ireland Atovaquone/Proguanil Hydrochloride 250 mg /100 mg Film-coated tablets
Poland Falcimar
Iceland Atóvakón/Prógúanílhýdróklóríð Glenmark 250mg/100mg filmuhúðaðar töflur
Norway Atovakon/proguanil Glenmark
Austria Atovaquon/Proguanil-Hydrochlorid Glenmark 250 mg/100 mg Filmtabletten
Finland Atovaquone/Proguanil Glenmark 250 mg/100 mg kalvopäällysteinen tabletti
This leaflet was last revised in 02/2018.
Glenmark Pharmaceuticals Europe Ltd
Address
Building 2, Croxley Park, Watford, WD18 8YA
Telephone
+44 (0)1923 202 950
Fax
+44 (0)1923 251137
Medical Information Direct Line
0800 458 0383
E-mail
[email protected]
Stock Availability
+44 (0)1923 202 950
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www.glenmarkpharma.com
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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.
Atovaquone/Proguanil Hydrochloride is a fixed dose combination of atovaquone and proguanil hydrochloride which acts as a blood schizonticide and also has activity against hepatic schizonts of Plasmodium falciparum.
It is indicated for:
• 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.
Because Atovaquone/Proguanil Hydrochloride is effective against drug sensitive and drug resistant P.falciparum it is especially recommended for prophylaxis and treatment of P. falciparum malaria where the pathogen may be resistant to other antimalarials.
Official guidelines and local information on the prevalence of resistance to antimalarial drugs should be taken into consideration. Official guidelines will normally include World Health Organisation (WHO)and public health authorities' guidelines.
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.
The tablets should preferably not be crushed.
If patients are unable to tolerate food, Atovaquone/Proguanil Hydrochloride 250 mg/100 mg film-coated tablets 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.
Posology
Prophylaxis:
Prophylaxis should:
• commence 24 to 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 Hydrochloride 250 mg/100 mg film-coated tablets 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 adolescents more than 40 kg bodyweight:
One Atovaquone/Proguanil Hydrochloride 250 mg/100 mg film-coated tablet daily.
Atovaquone/Proguanil Hydrochloride 250 mg/100 mg film-coated tablets are not recommended for malaria prophylaxis in persons under 40 kg bodyweight.
Treatment:
Dosage in adults
Four Atovaquone/Proguanil Hydrochloride 250 mg/100 mg film-coated tablets as a single dose for three consecutive days.
Dosage in Children weighing 11 kg or more
≥ 11 to <21 kg bodyweight. One tablet daily for three consecutive days.
≥ 21 to <31 kg bodyweight. Two tablets as a single dose for three consecutive days.
≥ 31 to <40 kg bodyweight. Three tablets as a single does 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 250 mg/100 mg film-coated tablets 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
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.
Atovaquone/Proguanil Hydrochloride 250 mg/100 mg film-coated tablets is contraindicated for prophylaxis of P. falciparum malaria in patients with severe renal impairment (creatinine clearance <30 mL/min)
Persons taking Atovaquone/Proguanil Hydrochloride 250 mg/100 mg film-coated tablets 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 Hydrochloride 250 mg/100 mg film-coated tablets for malaria prophylaxis. However, as with other antimalarial agents, subjects with diarrhoea or vomiting should be advised to continue with malaria 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 250 mg/100 mg film-coated tablets are used to treat malaria in these patients, parasitaemia and the patient's clinical condiion should be closely monitored.
Atovaquone/Proguanil Hydrochloride 250 mg/100 mg film-coated tablets have 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 Hydrochloride 250 mg/100 mg film-coated tablets. If patients experience an allergic reaction (see section 4.8) Atovaquone/Proguanil Hydrochloride 250 mg/100 mg film-coated tablets should be discontinued promptly and appropriate treatment initiated.
Atovaquone/Proguanil Hydrochloride 250 mg/100 mg film-coated tablets 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 Hydrochloride 250 mg/100 mg film-coated tablets alone. Travellers 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 250 mg/100 mg film-coated tablets, or failure of to chemoprophylaxis with Atovaquone/Proguanil Hydrochloride 250 mg/100 mg film-coated tablets, 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 250 mg/100 mg film-coated tablets and efavirenz or boosted protease-inhibitors should be avoided whenever possible (see section 4.5).
The concomitant administration of Atovaquone/Proguanil Hydrochloride 250 mg/100 mg film-coated tablets 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 250 mg/100 mg film-coated tablets 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 250 mg/100 mg film-coated tablets for treatment of acute P. falciparum malaria should be recommended whenever possible (see sections 4.2, 4.3 and 5.2)
The safety and effectiveness of Atovaquone/Proguanil Hydrochloride 250 mg/100 mg film-coated tablets has not been established for prophylaxis of malaria in patients who weigh less than 40kg, or in the treatment of malaria in paediatric patients who weigh less than 11kg.
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 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 250 mg/100 mg film-coated tablets treatment or after its withdrawal, based on INR results.
Concomitant treatment with tetracycline has been associated with decreases in plasma concentrations of atovaquone.
Concomitant administration of atovaquone and indinavir results in a decrease in the Cmin of indinavir (23% decrease; 90% CI 8-35%). Caution should be exercised when prescribing atovaquone with indinavir due to the decrease in the trough levels of indinavir.
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).
Atovaquone is highly protein bound (>99%) but does not displace other highly protein bound drugs in vitro, indicating significant drug interactions arising from displacement are unlikely.
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. Maternal toxicity was seen in pregnant rabbits during a teratogenicity study (see section 5.3). The use of Atovaquone/Proguanil Hydrochloride 250 mg/100 mg film-coated tablets 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 250 mg/100 mg film-coated tablets acts by inhibiting parasitic dihydrofolate reductase. There are no clinical data indicating that folate supplementation diminishes drug efficacy.
For women of child bearing age receiving folate supplements to prevent neural tube birth defects, such supplements should be continued while taking Atovaquone/Proguanil Hydrochloride 250 mg/100 mg film-coated tablets.
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 250 mg/100 mg film-coated tablets should not be taken by breast-feeding women.
Fertility
None or insufficient data regarding male and female 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); 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 Hydrochloride 250 mg/100 mg film-coated tablets on growth, puberty and general development have not been studied.
System Organ Class
Very Common
Common
Uncommon
Rare
Not known2
Blood and lymphatic disorders
Anaemia
Neutropenia1
Pancytopenia in patients with severe renal impairment3
Immune system disorders
Allergic reactions
Angioedema3
Anaphylaxis (see section 4.4)
Vasculitis3
Metabolism and nutrition disorders
Hyponatraemia1
Anorexia
Elevated amylase levels1
Psychiatric disorders
Abnormal dreams
Depression
Anxiety
Hallucinations
Panic attack
Crying
Nightmares
Psychotic disorder
Nervous system disorders
Headache
Insomnia
Dizziness
Seizure
Cardiac disorders
Palpitations1
Tachycardia
Gastrointestinal disorders
Nausea1
Vomiting
Diarrhoea
Abdominal pain
Stomatitis
Gastric intolerance3
Oral ulceration3
Hepatobiliary disorders
Elevated liver enzymes1
Hepatitis
Cholestasis
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 advance Human Immunodeficiency Virus (HIV) disease. Therefore, the causal relationship between the adverse experiences and atovaquone is difficult to evaluate. 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. The frequency is unknown
3. Observed with proguanil.
4. Clinical trial data for atovaquone-proguanil indicated that abnormalities in liver function tests were reversible and not associated with untoward clinical events.
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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
There is insufficient experience to predict the consequences or suggest specific management of Atovaquone/Proguanil Hydrochloride 250 mg/100 mg film-coated tablets 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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