Proguanil with atovaquone oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of proguanil hydrochloride with atovaquone.
Drugs List
Therapeutic Indications
Uses
Malaria - prophylaxis of P falciparum malaria
Treatment of acute,uncomplicated Plasmodium falciparum malaria
Prophylaxis of Plasmodium falciparum malaria.
Treatment of acute, uncomplicated Plasmodium falciparum malaria.
For up to date advice on geographical resistance patterns and appropriate prophylaxis, current guidelines should be consulted.
Guidelines for Malaria Prevention from Public Health England specifically developed for travellers from the United Kingdom may be obtained from:
https://www.gov.uk/government/publications/malaria-prevention-guidelines-for-travellers-from-the-uk
Unlicensed Uses
Treatment of non-falciparum malaria
Treatment of non-falciparum malaria.
Dosage
Doses have been expressed as proguanil hydrochloride/atovaquone.
Adults
Prophylaxis of Plasmodium falciparum malaria
Start course 24 or 48 hours prior to entering a malaria endemic area, continue during the period of the stay and continue for seven days after leaving the area.
Over 40kg bodyweight
Take one 100mg/250mg tablet daily for three consecutive days.
Under 40kg bodyweight
(See Dosage; Children).
Treatment of acute, uncomplicated Plasmodium falciparum malaria and treatment of non-falciparum malaria (unlicensed)
Over 40kg bodyweight
Four 100mg/250mg tablets as a single dose daily for three consecutive days.
Under 40kg bodyweight
(See Dosage; Children).
Children
Prophylaxis of Plasmodium falciparum malaria
Start course 24 or 48 hours prior to entering a malaria endemic area, continue during the period of the stay and continue for seven days after leaving the area.
Over 40kg bodyweight: Take one 100mg/250mg tablet daily.
31kg to 40kg: Three 25mg/62.5mg tablets daily, as a single dose.
21kg to 30kg: Two 25mg/62.5mg tablets daily, as a single dose.
11kg to 20kg: One 25mg/62.5mg tablet daily.
9kg to 10kg (unlicensed): Three quarters of a 25mg/62.5mg tablet daily.
5kg to 8kg (unlicensed): Half a 25mg/62.5mg tablet daily.
Treatment of acute, uncomplicated Plasmodium falciparum malaria and treatment of non-falciparum malaria (unlicensed)
Over 40kg bodyweight: Four 100mg/250mg tablets as a single dose daily for three consecutive days.
31kg to 40kg: Three 100mg/250mg tablets as a single dose daily for three consecutive days.
21kg to 30kg: Two 100mg/250mg tablets as a single dose daily for three consecutive days.
11kg to 20kg: One 100mg/250mg tablet daily for three consecutive days.
9kg to 10kg: Three 25mg/62.5mg tablets as a single daily dose for three consecutive days.
5kg to 8kg: Two 25mg/62.5mg tablets as a single daily dose for three consecutive days.
Contraindications
Children weighing less than 5kg
Renal impairment - creatinine clearance <30ml/min (for malaria prophylaxis)
Precautions and Warnings
Children weighing between 5kg-11kg
Chronic infection
Diarrhoea
Vomiting
Breastfeeding
Pregnancy
Renal impairment - creatinine clearance <30ml/min (for malaria treatment)
Advise ability to drive/operate machinery may be affected by side effects
Consult national/regional policy on the use of anti-infectives
Drugs for malaria prophylaxis are not prescribable on the NHS
Not all available products are recommended for all age groups/body weights
Use different drug for treatment if this agent was used for prophylaxis
Advise patients to take with food or milky drink, at the same time each day
Monitor patients presenting with diarrhoea or vomiting for parasitaemia
Discontinue if serious allergic or anaphylactic reaction occurs
Absorption may be reduced by diarrhoea or vomiting
Advise of importance of avoiding mosquito bites
Advise patients on the importance of taking treatment regularly
Consult Dr. if illness occurs within 1 year of return from malarious area
Take another dose if vomiting occurs within one hour
Pregnancy and Lactation
Pregnancy
Use proguanil with atovaquone tablets with caution in pregnancy.
The manufacturers suggest proguanil and atovaquone should only be considered if the expected benefit to the mother outweighs any potential risk to the foetus. Briggs suggests that for atovaquone, the maternal benefit appears to exceed the embryo/foetal risk, and so the agent should not be withheld because of pregnancy. At the time of writing, animal studies have shown no evidence for teratogenicity. Individually, proguanil and atovaquone, have not shown effects on parturition or pre- and post-natal development. However, maternal toxicity was shown in an animal study.
Proguanil acts by inhibiting parasitic dihydrofolate reductase. There is no 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 proguanil and atovaquone tablets.
Lactation
Use proguanil with atovaquone with caution in breastfeeding.
The manufacturer does not recommend proguanil and atovaquone during breastfeeding. LactMed (2018) suggests proguanil and atovaquone may be used to treat women who are breastfeeding infants of any weight when the potential benefit outweighs the potential risk to the infant. Proguanil is excreted into human milk at low levels. It is unknown whether atovaquone is excreted into human milk. Due to the potential severe adverse effects in the infant such as gastrointestinal symptoms, hepatic toxicity or carcinogenicity, Briggs (2015) does not recommend the use of proguanil and atovaquone during breastfeeding.
Side Effects
Abdominal pain
Allergic reaction
Anaemia
Anaphylaxis
Angioedema
Anorexia
Anxiety
Blistering
Blood disorders
Cholestasis
Cough
Crying
Depression
Diarrhoea
Dizziness
Dream abnormalities
Elevated amylase levels
Elevation of liver enzymes
Erythema multiforme
Fever
Gastrointestinal intolerance
Hair loss
Hallucinations
Headache
Hepatitis
Hyponatraemia
Insomnia
Mouth ulcers
Nausea
Neutropenia
Nightmares
Palpitations
Pancytopenia
Panic attack
Photosensitivity
Pruritus
Psychotic disorder
Rash
Seizures
Skin exfoliation
Stevens-Johnson syndrome
Stomatitis
Tachycardia
Urticaria
Vasculitis
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: June 2019
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Summary of Product Characteristics: Atovaquone/Proguanil Hydrochloride 250mg/100mg tablets. Glenmark Pharmaceuticals Europe Ltd. Revised July 2017.
Summary of Product Characteristics: Mafamoz 62.5 mg/25 mg tablets. Teva UK. Revised July 2014.
Summary of Product Characteristics: Mafamoz 250 mg/100 mg. Teva UK. Revised July 2014.
Summary of Product Characteristics: Malarone tablets. GlaxoSmithKline UK. Revised March 2016.
Summary of Product Characteristics: Malarone Paediatric tablets. GlaxoSmithKline UK. Revised October 2017.
Summary of Product Characteristics: Maloff Protect tablets. Glenmark Pharmaceuticals Europe Ltd. Revised July 2017.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 20 June 2019
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Atovaquone and proguanil. Last revised: October 31, 2018
Last accessed: 20 June 2019
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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