Pharmacy Guide
Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
Pharmacy Guide
Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
Atovaquone/Proguanil Hydrochloride 62.5 mg/25 mg film-coated tablets
⚠ This medicine appears to have been discontinued
The electronic medicines compendium (emc) no longer publishes a Summary of Product Characteristics for this product, which usually means it is no longer marketed in the UK. The patient leaflet below is kept for reference, but the product may not be available.
If you were prescribed this medicine, other products containing Atovaquone, Proguanil hydrochloride may still be available. Do not stop your treatment — ask your pharmacist or GP what to use instead.
What it is and what it is used for
for 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 (for children weighing between 11kg and 40kg)
- to treat malaria (for children weighing between 5kg and 11kg) Dosage instructions for each use are in Section 3, How to give Atovaquone/Proguanil Hydrochloride. Although this medicine is usually used for children and teenagers, it can be prescribed for adults weighing less than 40kg. 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 your child from catching malaria People of any age can get malaria. It is a serious disease, but is preventable.
As well as giving 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 your child gets symptoms after returning from abroad, such as high temperature, headache, shivering and tiredness.
What you need to know before you take it
e Atovaquone/Proguanil Hydrochloride Do not take Atovaquone/Proguanil Hydrochloride: •
if your child is allergic to atovaquone, proguanil hydrochloride or any of the other ingredients of this medicine (listed in section 6).
•
for preventing malaria, if your child has severe kidney disease.
Tell your doctor if either of these apply to your child. Take special care with Atovaquone/Proguanil Hydrochloride Talk to your doctor or pharmacist before you give Atovaquone/Proguanil Hydrochloride to your child if: • •
your child has severe kidney disease your child is being treated for Malaria and weighs less than 5 kg or is given Atovaquone/Proguanil Hydrochloride to prevent Malaria and weighs less than 11 kg.
Tell your doctor or pharmacist if any of these applies to your child. If any of the above applies to your child, talk to your doctor, before your child starts taking this medicine. Other medicines and Atovaquone/Proguanil Hydrochloride Tell your doctor or pharmacist if your child is taking, has recently taken or might take any other medicine, including medicines bought without prescription.
Some medicines can affect the way Atovaquone/Proguanil Hydrochloride works, or Atovaquone/Proguanil Hydrochloride itself 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 warfarin and other medicines that stop blood clotting etoposide used to treat cancer.
Tell your doctor if your child is taking any of these. Your doctor may decide that Atovaquone/Proguanil Hydrochloride isn't suitable for them, or that they need extra check ups whilst taking it. Remember to tell your doctor if your child starts taking any other medicines while they're taking Atovaquone/Proguanil Hydrochloride. Atovaquone/Proguanil Hydrochloride with food and drink Give Atovaquone/Proguanil Hydrochloride with food or a milky drink, where possible. This will increase the amount of Atovaquone/Proguanil Hydrochloride your child's body can absorb, and make the treatment more effective. Pregnancy, breast-feeding and fertility If you or your child is pregnant, do not take Atovaquone/Proguanil Hydrochloride unless your doctor recommends it. Do not breast feed while taking Atovaquone/Proguanil Hydrochloride, as the ingredients may pass into breast milk and may harm the 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'.
How to take it
Atovaquone/Proguanil Hydrochloride Always give this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. Give Atovaquone/Proguanil Hydrochloride with food or a milky drink, where possible. The tablets should be swallowed whole. However, for children who find them difficult to swallow, they may be crushed just before being taken and mixed with food or a milky drink. It is best to give Atovaquone/Proguanil Hydrochloride at the same time each day. To prevent malaria: The recommended dose to prevent malaria depends on your child's weight.
11-20 kg – 1 tablet once a day 21-30 kg – 2 tablets once a day (as a single dose) 31-40 kg – 3 tablets once a day (as a single dose) • • •
Start giving Atovaquone/Proguanil Hydrochloride 1 to 2 days before travelling to an area which has malaria. Continue giving it every day during the stay. Continue giving it for another 7 days after your return to a malaria-free area
For maximum protection your child must take the full course of treatment. To treat malaria: The recommended dose to treat malaria depends on your child's weight. 5-8 kg – 2 tablets once a day for 3 consecutive days 9-10 kg – 3 tablets once a day for 3 consecutive days If your child is sick (vomits) For preventing Malaria:
- if your child is sick (vomits) within 1 hour of taking Atovaquone/Proguanil Hydrochloride, give another dose straight away
- it is important to take the full course of Atovaquone/Proguanil Hydrochloride. If your child has to take extra tablets due to sickness, they may need another prescription.
- if your child has 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 your child has vomiting and diarrhea tell your doctor. Your child 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 their blood. If your child takes more Atovaquone/Proguanil Hydrochloride than they should have Contact a doctor or a pharmacist for advice. If possible show them the Atovaquone/Proguanil Hydrochloride pack. If you forget to give Atovaquone/Proguanil Hydrochloride It is very important that your child takes the full course of Atovaquone/Proguanil Hydrochloride. If you forget to give your child a dose, don't worry. Just give the next dose as soon as you remember. Then continue the treatment as before. Don`t take extra tablets to make up for a missed dose. Just take your next dose at the usual time. Don't stop giving Atovaquone/Proguanil Hydrochloride without advice Keep giving Atovaquone/Proguanil Hydrochloride for 7 days after you return to a malariafree area. Give the full course of tablets for maximum protection. Stopping early puts your child 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.
4. Possible side effects 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 your child gets any of these symptoms. Stop using 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 pains
- 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 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 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 problem 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 blood tests:
- A decrease in all types of blood cells (pancytopenia). Reporting of side effects If your child gets 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 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.
How to store it
Atovaquone/Proguanil Hydrochloride 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 label and carton after EXP. The expiry date refers to the last day of that month. Atovaquone/Proguanil Hydrochloride 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. This will help protect the environment.
Contents of the pack and other information
What Atovaquone/Proguanil Hydrochloride contains The active ingredients are atovaquone and proguanil hydrochloride. Each tablet contains 62.5 mg of atovaquone and 25 mg of proguanil hydrochloride. The other ingredients are: Tablet core: Poloxamer 188, microcrystalline cellulose (E460), low-substituted hydroxypropyl cellulose (E463), sodium starch glycolate (Type A), silica colloidal anhydrous (E551), povidone (E2101), magnesium stearate (E572) Tablet coating: hypromellose (E464), titanium dioxide (E171), macrogol (E1521), iron oxide red (E172). Tell your doctor, before giving Atovaquone/Proguanil Hydrochloride to your child, if you think your child may be allergic to any of these ingredients. What Atovaquone/Proguanil Hydrochloride looks like and contents of the pack Atovaquone/Proguanil Hydrochloride film coated tablets are round, pink, biconvex film coated tablets debossed with 'I' on one side and '11' on the other side. Atovaquone/Proguanil Hydrochloride is available in blister packs and HDPE containers Pack sizes Alu-Alu Blister: 1, 12, 21, 24, 28, 36 film-coated tablets Alu-PVC Blister: 1, 12, 21, 24, 28, 36 film-coated tablets HDPE containers: 30, 100 film-coated tablets Not all pack sizes may be marketed. Marketing Authorisation Holder Amarox Limited Congress House, 14 Lyon Road Harrow, Middlesex HA1 2EN United Kingdom Manufacturer Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park Paola, PLA 3000 Malta Amarox Limited Congress House, 14 Lyon Road Harrow, Middlesex HA1 2EN United Kingdom Amarox Pharma B.V. Rouboslaan 32 2252 TR Voorschoten Netherlands This leaflet was last revised in 03/2023.
Frequently asked questions about Atovaquone/Proguanil Hydrochloride 62.5 mg/25 mg film-coated tablets
How do I take Atovaquone/Proguanil Hydrochloride 62.5 mg/25 mg film-coated tablets?
Atovaquone/Proguanil Hydrochloride 62.5 mg/25 mg film-coated tablets comes as tablet containing 62.5mg / 25mg. Always follow the dose your doctor or pharmacist has given you, and read the leaflet that comes with the medicine.
What is the active substance in Atovaquone/Proguanil Hydrochloride 62.5 mg/25 mg film-coated tablets?
The active substance in Atovaquone/Proguanil Hydrochloride 62.5 mg/25 mg film-coated tablets is atovaquone, proguanil hydrochloride.
Are there equivalent medicines to Atovaquone/Proguanil Hydrochloride 62.5 mg/25 mg film-coated tablets?
Medicines with the same active substance, strength and form include: Malarone paediatric 62.5 mg/25 mg film-coated tablets. They are interchangeable only if your prescriber or pharmacist says so.
Where does this information come from?
This leaflet reproduces the patient information leaflet approved for Atovaquone/Proguanil Hydrochloride 62.5 mg/25 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.
Can I get Atovaquone/Proguanil Hydrochloride 62.5 mg/25 mg film-coated tablets without a prescription?
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.
About this leaflet
The text above reproduces the patient information leaflet approved for this medicine, restructured for easier reading.
- Source: electronic medicines compendium (emc), Datapharm
- Active substance: atovaquone, proguanil hydrochloride
- Official document: view the original leaflet on emc →
⚕For healthcare professionals — Summary of Product Characteristics (SmPC)Full SmPC: dosage, interactions, contraindications, warnings+
4.1. Therapeutic indications
Prophylaxis of Plasmodium falciparum malaria in adults and children weighing 11-40 kg.
Treatment of acute, uncomplicated Plasmodium falciparum malaria in adults and in children weighing ≥5 kg and <11 kg.
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.
4.2. Posology and method of administration
Posology
The dosage for the prophylaxis and treatment of acute, uncomplicated P. falciparum malaria in children is based on body weight.
Prophylaxis
Dosage in individuals weighing 11-40 kg
Dosage/ day
Body Weight Range (kg)
Atovaquone
(mg)
Proguanil
(mg)
No of Tablets
11-20
62.5
25
One Atovaquone/Proguanil
Hydrochloride paediatric tablet
21-30
125
50
Two Atovaquone/Proguanil
Hydrochloride paediatric tablets
31-40
187.5
75
Three Atovaquone/Proguanil
Hydrochloride paediatric tablet
>40
250
100
Subjects of >40 kg should receive ONE Atovaquone/Proguanil Hydrochloride 250/100 mg tablet daily
The safety and effectiveness of atovaquone/proguanil paediatric tablets for prophylaxis of malaria in children who weigh less than 11 kg has not been established.
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.
The safety and effectiveness of atovaquone/proguanil paediatric tablets have been established in studies of up to 12 weeks in residents (semi-immune) of endemic areas. (see section 5.1).
In non-immune subjects, the average duration of exposure in clinical studies was 27 days.
Treatment
Dosage in individuals weighing 5-11 kg
Dosage /day
Body Weight Range (kg
Atovaquone
(mg)
Proguanil
(mg)
No of Tablets
5-8
125
50
Two Atovaquone/Proguanil
Hydrochloride paediatric tablets daily for 3 consecutive days
9-10
187.5
75
Three Atovaquone/Proguanil Hydrochloride paediatric tablets daily for 3 consecutive days.
≥ 11
Refer to Atovaquone/Proguanil Hydrochloride 250/100 mg tablets SmPC
The safety and effectiveness of atovaquone/proguanil paediatric tablets for the treatment of malaria in children who weigh less than 5 kg has not been established.
For individuals whom weight 11 kg or more, the first choice for the treatment of acute, uncomplicated P. falciparum malaria is Atovaquone/Proguanil Hydrochloride tablets (250/100 mg). Please consult the Atovaquone/Proguanil Hydrochloride tablets SmPC for the recommended dosage for this weight range. Atovaquone/Proguanil Hydrochloride tablets are four-times the strength of Atovaquone/Proguanil Hydrochloride paediatric tablets.
In circumstances when sufficient Atovaquone/Proguanil Hydrochloride tablets are not available, then Atovaquone/Proguanil Hydrochloride paediatric tablets may be used.
Hepatic Impairment
There are no studies in children with hepatic impairment. However, a pharmacokinetic study in adults 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).
Renal Impairment
There are no studies in children with renal impairment. However, pharmacokinetic studies in adults indicate that no dosage adjustments are needed in those with mild to moderate renal impairment. Due to the lack of information regarding appropriate dosing, Atovaquone/Proguanil Hydrochloride is contraindicated for the prophylaxis of malaria in adults and children with severe renal impairment (creatinine clearance <30 mL/min; see sections 4.3 and 5.2).
Method of administration
The daily dose should be taken once daily 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 paediatric 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.
Atovaquone/Proguanil Hydrochloride paediatric tablets should preferably be swallowed whole. If difficulties are encountered when dosing young children, the tablets may be crushed and mixed with food or a milky drink just prior to administration.
4.3. Contraindications
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).
4.4. Special warnings and precautions for use
The safety and effectiveness of atovaquone/proguanil paediatric tablets for the prophylaxis of malaria in children who weigh less than 11 kg and the treatment of malaria in children who weigh less than 5 kg have not been established.
Persons taking Atovaquone/Proguanil Hydrochloride paediatric tablets for prophylaxis or treatment of malaria should take a repeat dose if they vomit within 1hour of dosing. In the event of diarrhoea, normal dosing should be continued.
Absorption of atovaquone may be reduced in individuals 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. 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, or failure of chemoprophylaxis with Atovaquone/Proguanil Hydrochloride paediatric 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 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).
Atovaquone/Proguanil Hydrochloride paediatric tablets are not indicated for the treatment of acute uncomplicated P. falciparum malaria in individuals weighing 11- 40 kg. Atovaquone/Proguanil Hydrochloride tablets (atovaquone 250mg/proguanil hydrochloride 100mg tablets) should be used in these individuals (see section 4.2).
4.5. Interaction with other medicinal products and other forms of interaction
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.
Although some children have received concomitant Atovaquone/Proguanil Hydrochloride and metoclopramide in clinical trials without any evidence of decreased protection against malaria, the possibility of a clinically significant drug interaction cannot be ruled out.
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 anticoagulant 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 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).
4.6. Fertility, pregnancy and lactation
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 only 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.
Proguanil 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 paediatric 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 paediatric tablets 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.
4.7. Effects on ability to drive and use machines
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.
4.8. Undesirable effects
In clinical trials of atovaquone/proguanil paediatric tablets for prophylaxis of malaria, 357 children or adolescents 11 to ≤ 40 kg body weight received atovaquone/proguanil paediatric tablets. Most of these were residents of endemic areas and took atovaquone/proguanil paediatric tablets for about 12 weeks. The rest were travelling to endemic areas, and most took atovaquone/proguanil paediatric tablets for 2-4 weeks.
Open label clinical studies investigating the treatment of children weighing between ≥ 5 kg and <11 kg have indicated that the safety profile is similar to that in children weighing between 11 kg and 40 kg, and adults.
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.
In clinical trials of atovaquone/proguanil for 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).
System Organ Class
Very Common
Common
Uncommon
Rare
Not known2
Blood and lymphatic disorders
Anaemia Neutropenia 1
Pancytopenia
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
Palpitations
Tachycardia
Gastrointestinal disorders
Nausea1
Vomiting
Diarrhoea
Abdominal pain
Stomatitis
Gastric intolerance3
Oral ulceration3
Hepatobiliary disorders
Elevated liver enzymes1
Hepatitis Cholestasis3
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.
4.9. Overdose
There is insufficient experience to predict the consequences or suggest specific management of Atovaquone/Proguanil Hydrochloride 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.
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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.