Atovaquone

drugbox
IUPAC_name = 2- [4-(4-chlorophenyl)cyclohexyl] - 3-hydroxynaphthalene-1,4-dione

---

CAS_number = 95233-18-4
ATC_prefix = P01
ATC_suffix = AX06
ATC_supplemental =
PubChem = 74989
DrugBank = APRD00805
C=22 | H=19 | Cl=1 | O=3
molecular_weight = 366.837 g/mol
bioavailability =
protein_bound =
metabolism =
elimination_half-life = 2.2 to 3.2 days
pregnancy_category =
legal_status = PoM (UK), Rx [US]
routes_of_administration = oral only

Atovaquone (alternative spelling: atavaquone) is a chemical compound that belongs to the class of naphthalenes. Atovaquone is a hydroxy-1,4-naphthoquinone, an analog of ubiquinone, with antipneumocystic activity. Its average wholesale price is about $2.13 per standard 250 mg. tablet. [ [http://www.aegis.com/pubs/atn/1992/ATN16401.html (ATN) Atovaquone (Mepron; 566C80) Approved for Pneumocystis; Drug Development, Activism Success] ] It is also manufactured in the US in the liquid form, or oral suspension, under the brand name Mepron. [ [http://www.drugs.com/pro/mepron.html Mepron] ]

Atovaquone is a medication used to treat or prevent:
# Pneumocystis pneumonia (PCP), although it is not approved for treatment of severe PCP.
# Toxoplasmosis. The medication has antiparasitic and therapeutic effects.
# Malaria. It is one of the two components (along with proguanil) in the drug Malarone. Malarone has fewer side effects and is more expensive than mefloquine. [ [http://healthlink.mcw.edu/article/979237802.html Malarone: New Malaria Medication With Fewer Side-effects] ]

Trimethoprim-sulfamethoxazole (TMP-SMX, Bactrim) is generally considered first line therapy for PCP or toxoplasmosis. However, atovaquone may be used in patients who cannot tolerate, or are allergic to, TMP-SMX. In addition, atovaquone has the advantage of not causing myelosuppression, which is an important issue in patients who have undergone bone marrow transplantation.

Malaria

Atovaquone is only available as a fixed preparation with proguanil that has been commercially available from GlaxoSmithKline since 2000 as Malarone (sometimes abbreviated A+P). It can be used both to treat and to prevent malaria.

A "standard" tablet of Malarone contains 100 mg of proguanil hydrochloride and 250 mg of atovaquone. A "pediatric" tablet of Malarone contains 25 mg of proguanil hydrochloride and 62.5 mg of atovaquone.

Treatment

The adult treatment dose is four "standard" tablets once a day for three days. In children, the drug is prescribed by body weight:
*11 to 20 kg: 1 "standard" tablet once daily for 3 days;
*21 to 30 kg: 2 "standard" tablets once daily for 3 days;
*31 to 40 kg: 3 "standard" tablets once daily for 3 days;
*41 kg and above: use adult dose.Malarone is not licensed for use in children weighing 10 kg or less. The "pediatric" tablets are "not" used in malaria treatment.

The advice of a specialist should always be sought when starting malaria treatment. Malarone should not be used to treat severe malaria, when an injectable drug (quinine or artesunate in the UK; quinidine in the US) should be used instead.

Prevention

Medical advice should always be taken before choosing a drug for malaria prevention. Because some strains of malaria are resistant, Malarone is not effective for malaria prevention in all parts of the world. It must be taken with a fatty meal or at least some milk to be absorbed adequately.

The adult dose is one "standard" tablet daily starting one or two days before traveling into a malaria-endemic area, and continuing throughout the stay and then for another 7 days after returning from the malarious area.

The child dose is prescribed according to body weight:
*11–20 kg: 1 "pediatric" tablet once daily;
*21–30 kg: 2 "pediatric" tablets once daily;
*31–40 kg: 3 "pediatric" tablets once daily;
*41 kg and above use adult dose.The duration of treatment is the same as for adults.

Resistance

Proguanil acts as a mitochondrial sensitiser and synergizes with atovaquone; also, there is a high natural frequency of cytochrome B mutants which leads to a high failure rate if atovaquone is used on its own to treat malaria. Specific mutations (Y268S, Y268C) have been shown to confer resistance "in vivo," [cite journal | author=Färnet A, Lindberg J, Gil P, "et al." | title=Evidence of "Plasmodium falciparum" malaria resistant to atovaquone and proguoanil hydrochloride: case reports | year=2003 | journal=Brit Med J | volume=326 | pages=628–29 | doi=10.1136/bmj.326.7390.628 | pmid=12649236 ] [cite journal | author=Fivelman QL, Butcher GA, Adagu IS, "et al." | title=Malarone treatment failure and in-vitro confirmation of resistance of "Plasmodium falciparum" isolate from Lagos, Nigeria | year=2002 | journal=Malaria J | volume=1 | pages=1 | doi=10.1186/1475-2875-1-1 ] [cite journal | author=Schwartz E, Bujanover S, Kain KC | title=Genetic confirmation of atovaquone-proguanil-resistant "Plasmodium falciparum" malaria acquired by a nonimmune traveller to east Africa | year=2003 | journal=Clin Infect Dis | volume=37 | pages=450–51 | doi=10.1086/375599 ] but there are other mechanisms of resistance that remain unknown. [cite journal | author=Wichmann O, Muehlen M, Gruss H, "et al." | title=Malarone treatment failure not associated with previously described mutations in the cytochrome b gene | year=2004 | journal=Malaria J | volume=3 | pages=14 | doi=10.1186/1475-2875-3-14 ]

References

External links

* [http://www.dartmouth.edu/~blt/Publications/JBC279,2817.pdf#search='Atovaquone' Molecular Basis for Atovaquone Resistance in Pneumocystis jirovecii]
* [http://www.lymenet.de/literatur/atovaquone.htm Atovaquone (Meprone)]
* [http://www.bnf.org British National Formulary]