Proguanil

Oral
Prophylaxis of malaria

CrCl (mL/min)	Dosage
<10	50 mg once weekly.
10-19	50 mg every other day.
20-59	100 mg once daily.

Should be taken with food. Tab may be crushed & mixed w/ milk, honey or jam just before swallowing.

Refer to local medical recommendations on the appropriate prophylactic regimen to use in areas known or suspected to have drug-resistant malaria; prophylactic use of proguanil alone may not be sufficient. Renal impairment. Children. Pregnancy; ensure adequate folic acid supplementation in pregnant women. Lactation.

Significant: Increased risk of haematological changes (e.g. aplastic anaemia, megaloblastic anaemia, pancytopenia), particularly in patients with severe renal impairment.
Gastrointestinal disorders: Diarrhoea, constipation, mouth ulceration, stomatitis.
General disorders and administration site conditions: Pyrexia.
Hepatobiliary disorders: Cholestasis.
Immune system disorders: Hypersensitivity reactions (e.g. urticaria, angioedema).
Skin and subcutaneous tissue disorders: Skin exfoliation, rash, pruritus, reversible alopecia.
Vascular disorders: Vasculitis.

Symptoms: Epigastric discomfort, vomiting, and renal irritation resulting in haematuria. Management: May administer activated charcoal within 1 hour in patients who have ingested ≥30 mg/kg. Assess urea and electrolytes, LFTs and FBC in all patients. Check FBC again after 3 days, then 1 week following the overdose or if any new symptoms appear.

Absorption may be reduced with antacids. May potentiate the anticoagulant effect of warfarin and similar anticoagulants. Reduced proguanil exposure with boosted protease inhibitors. May diminish the effect of live oral typhoid vaccine (Ty21a strain).

Description:
Mechanism of Action: Proguanil is a biguanide derivative that has minimal antimalarial activity until metabolised to its active metabolite, cycloguanil. Cycloguanil inhibits plasmodial dihydrofolate reductase, thereby disrupting nucleic acid synthesis in the parasite. It is highly active against the primary exoerythrocytic forms of Plasmodium falciparum but has little inhibitory action against exoerythrocytic forms of Plasmodium vivax.
Pharmacokinetics:
Absorption: Rapidly absorbed from the gastrointestinal tract. Time to peak plasma concentration: 3-4 hours (proguanil); 4-9 hours (cycloguanil).
Distribution: Enters breast milk (small amounts). Plasma protein binding: Approx 75%.
Metabolism: Metabolised in the liver mainly by CYP2C19 isoenzyme and to a lesser extent by CYP3A4 isoenzyme into cycloguanil (active metabolite).
Excretion: Mainly via urine (approx 40-60%; 60% as unchanged drug, 30% as cycloguanil); faeces. Elimination half-life: 14-20 hours (proguanil); 20 hours (cycloguanil).

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 6178111, Proguanil. https://pubchem.ncbi.nlm.nih.gov/compound/Proguanil. Accessed Feb. 27, 2023.

Store below 30°C.

Antimalarials

P01BB01 - proguanil ; Belongs to the class of biguanide antimalarials.

Anon. Proguanil. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 27/12/2022.

Buckingham R (ed). Proguanil Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 27/12/2022.

Joint Formulary Committee. Proguanil Hydrochloride. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 27/12/2022.

Paludrine 100 mg Tablets (Alliance Pharmaceuticals Limited). MHRA. https://products.mhra.gov.uk. Accessed 27/12/2022.