proguanil


Also found in: Dictionary, Wikipedia.
Related to proguanil: mefloquine

atovaquone/proguanil

(a-toe-va-kwone/pro-gwa-nil),

Malarone

(trade name)

Classification

Therapeutic: antimalarials
Pregnancy Category: C

Indications

Prevention of malaria caused by Plasmodium falciparum, including chloroquine-resistant strains.Treatment of acute, uncomplicated P. falciparum malaria; effective for many drug-resistant strains.

Action

Atovaquone is a selective inhibitor of parasite mitochondrial transport.
Proguanil's metabolite, cycloguanil, is a dihydrofolate reductase inhibitor.
Both interfere with pyrimidine synthesis required for nucleic acids and replication are active against both erthrythrocytic and exoerythrocytic stages of Plasmodiumspp.

Therapeutic effects

Prevention/treatment of malarial illness and its sequelae.

Pharmacokinetics

Absorption: Atovaquone—variably absorbed following oral administration, food enhances absorption; Proguanil—well absorbed following oral administration.
Distribution: Proguanil— enters breast milk in small quantities.
Protein Binding: Atovaquone—>99%.
Metabolism and Excretion: Atovaquone—undergoes enterohepatic recycling, >94% eliminated unchanged in feces; Proguanil— metabolized mostly by the CYP2C19 enzyme system and is converted to cycloguanil, the pharmacologically active metabolite.
Half-life: Atovaquone—adults: 2–3 days, children: 1–2 days Cycloguanil—Adults: 8.3 hr, elderly: 14.9 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
atovaquone POunknown1–8 hr; 24–96 hr†24 hr
proguanil POunknownunknown24 hr
† Two peaks are due to enterohepatic recycling.

Contraindications/Precautions

Contraindicated in: Hypersensitivity to atovaquone or proguanil; Severe renal impairment (CCr <30 mL/min.
Use Cautiously in: Nausea or vomiting; may require repeat dosing and/or prophylactic use of anti-emetics; Severe malaria; oral agents are insufficient; Geriatric: Dose carefully, considering age-realated decrease in body mass, hepatic/renal/cardiac function, concurrent disease states and drug therapy; Obstetric: Pregnancy; malaria is a more serious illness, consider risk/benefit of travel to endemic areas, use only if potential benefit outweighs risk to the fetus.; Lactation: Use cautiously; proguanil enters breast milk; Pediatric: Safe and effective use in children <5 kg has not been established.

Adverse Reactions/Side Effects

Prophylaxis of Malaria

Central nervous system

  • dizziness
  • dreams
  • headache
  • insomnia

Ear, Eye, Nose, Throat

  • visual difficulties

Gastrointestinal

  • abdominal pain
  • oral ulcers

Treatment of Malaria

Central nervous system

  • headache (most frequent)
  • dizziness
  • weakness

Gastrointestinal

  • abdominal pain (most frequent)
  • diarrhea (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)
  • anorexia
  • ↑ liver enzymes

Dermatologic

  • pruritus (↑ in children)
  • photosensitivity

Hematologic

  • neutropenias

Miscellaneous

  • allergic reactions including anaphylaxis

Interactions

Drug-Drug interaction

Rifampin, rifabutin, metoclopramide and tetracylcine ↓ atovaquone levels.Atovaquone ↓ trough levels of indinavir ; use cautiously.

Route/Dosage

Prevention of Malaria
Oral (Adults and Children > 40 kg) One adult strength tablet (atovaquone 250 mg/proguanil 100 mg) once daily 1–2 days prior to entering endemic area and continued for seven days following return.
Oral (Children 31–40 kg) Three pediatric tablets (atovaquone 187.5 mg/proguanil 75 mg) once daily 1–2 days prior to entering endemic area and continued for seven days following return.
Oral (Children 21–30 kg) Two pediatric tablets (atovaquone 125 mg/proguanil 50 mg) once daily 1–2 days prior to entering endemic area and continued for seven days following return.
Oral (Children 11–20 kg) One pediatric tablet (atovaquone 62.5 mg/proguanil 25 mg) once daily 1–2 days prior to entering endemic area and continued for seven days following return.
Treatment of Malaria
Oral (Adults and Children 40) Four adult tablets (total daily dose atovaquone 1 g/proguanil 400 mg) as a single daily dose for 3 consecutive days.
Oral (Children 31–40 kg) Three adult tablets (total daily dose atovaquone 750 mg/proguanil 300 mg) once daily for 3 days.
Oral (Children 21–30 kg) Two adult tablets (total daily dose atovaquone 500 mg/proguanil 300 mg) once daily for 3 days.
Oral (Children 11–20 kg) One adult strength tablet (total daily dose atovaquone 250 mg/proguanil 150 mg) once daily for three days.
Oral (Children 9–10 kg) Three pediatric tablets (total daily dose atovaquone 187.5 mg/proguanil 75 mg once daily for three days.
Oral (Children 5–8 kg) Two pediatric tablets (total daily dose atovaquone 125 mg/proguanil 50 mg) once daily for three days.

Availability

Adult ablets : atovaquone 250 mg/proguanil 100 mg
Pediatric tablets : atovaquone 62.5 mg/proguanil 25 mg

Nursing implications

Nursing assessment

  • Malaria: Assess patient for improvement in signs and symptoms of condition daily throughout therapy.
  • Lab Test Considerations: Monitor CBC periodically throughout therapy. May cause neutropenia.
    • May cause ↑ AST and ALT. Monitor liver function tests periodically during therapy.

Potential Nursing Diagnoses

Risk for infection (Indications)
Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

  • For malaria prophylaxis, therapy should be started 1–2 days prior to potential exposures and continued for 7 days after leaving the area.
  • For treatment of malaria, take once daily for 3 days.
  • Oral: Administer with food or a milky drink to minimize GI distress. Tablets may be crushed and mixed with condensed milk just prior to administration for children with difficulty swallowing tablets.

Patient/Family Teaching

  • Instruct patient to take medication exactly as directed and continue full course of therapy, even if feeling better. If vomiting occurs within 1 hr of dose, may take a repeat dose. Take missed doses as soon as remembered, unless almost time for next dose. Do not double doses.
  • Review methods of minimizing exposure to mosquitoes with patients receiving atovaquone/proguanil prophylactically (use insect repellent, wear long-sleeved shirt and long trousers, use screen or netting).
  • Advise patient to wear protective clothing and sunscreen to avoid photosensitivity reactions.
  • Advise female patients to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Risk of death and serious complications is higher with Falciparum malaria. Advise pregnant women anticipating travel to malarious area to discuss risks with health care professional.

Evaluation/Desired Outcomes

  • Prevention of or improvement in signs and symptoms of malaria.

proguanil

(prō-gwä′nəl)
n.
A drug, C11H16ClN5, used in its hydrochloride form as an antimalarial, usually in combination with atovaquone.

proguanil

An antimalarial drug mainly used for prevention (as a prophylactic). A brand name is Paludrine. The drug is on the WHO official list. Formulated in conjunction with ATOVAQUONE, it is produced under the brand name Malarone.
References in periodicals archive ?
Antimalarial drug regimens prescribed n (%) Non-artemisinin monotherapies (NAMTs) 8 (2.4) Proguanil 5 (1.5) Sulphadoxine-Pyrimethamine 2 (0.6) Amodiaquine 1 (0.3) Artemisinin monotherapies (AMTs) 6 (1.8) Artesunate 2 (0.6) Arteether 2 (0.6) Artemether 1 (0.3) Dihydroartemisinin 1 (0.3) Artemisinin combination therapies (ACTs) 319 (95.8) Artemether/Lumefantrine 269 (80.8) Artesunate/ Meflo quine 20 (6.0) Dihydroartemisinin/Piperaquine 16 (4.8) Artesunate/Amo diaquine 8 (2.4) Artesunate/Piperaquine 4(1.2) Artemether/Lumefantrine + Sulphadoxine-Pyrimethamine 1 (0.3) Artesunate/Sulphadoxine-Pyrimethamine + Proguanil 1 (0.3) Table 3: Drug prescribing indicators.
La atovacuona, una hidroxinaftoquinona, y el proguanil, una biguanida (figura 3), componen esta combinacion de medicamentos que actua sobre trofozoitos de Plasmodium, tanto hepaticos como eritrociticos.
Proguanil plus sulfamethoxazole is not causally prophylactic in the Macaca mulatta-Plasmodium cynomolgi model.
In addition to metabolizing drugs and developing inactive metabolites, it is also activated in the activation process of some effective medications, including the conversion of proguanil anti-malaria drug into cycloguanil (13), conversion of tamoxifen to the two active metabolites including 4-hydroxy tamoxifen and 4-hydroxy methyl-N-dose tamoxifen (14) and the conversion of clopidogrel at first to its active form and then into 2-oxo-clopidogrel (15,16).
After laboratory confirmation of malaria diagnosis, the therapy was changed to a 3-day course of atovaquone and proguanil. The patient fully recovered, while no complications were observed.
Atovaquone/Proguanil (Malarone) is a combination of the atovaquone mentioned above (Mepron) in a tablet form combined with proguanil. (37) This is primarily the only way for most physicians to prescribe proguanil.
Los demas tratamientos antimalaricos evaluados se administraron en un porcentaje inferior a 10%, estos resultados son similares a los reportados en estudios en la poblacion general, pero diferentes al manejo realizado en poblaciones militares en diferentes partes del mundo, donde hay mayor porcentaje de utilizacion de doxiciclina oral y atovaquona proguanil como primera linea de tratamiento (2).
Proguanil, 200mg daily, is recommended additionally in the high risk regions [26].
Chloroguanil and cycloguanil both were derived from proguanil. The most important antifolate is pyrimethamine which belongs to the 2 4- diaminopyrimidine families.
Drug hypersensitivity may result from agents such as verapamil, quinacrine, etodolac, mepacrine, proguanil, mexiletine, methyldopa, lithium, venlafaxine, gold, fluorouracil, bleomycin, hydroxyurea, practolol and doxorubicin.