Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/4241
| Predicate | Object |
|---|---|
| rdf:type | |
| rdfs:label |
MALARONE (Tablet)
|
| dailymed-instance:dosage |
The daily dose should be taken at the same time
each day with food or a milky drink. In the event of vomiting within
1 hour after dosing, a repeat dose should be taken.<br/>Prevention of Malaria: Prophylactic treatment with MALARONE should be started
1 or 2 days before entering a malaria-endemic area and continued
daily during the stay and for 7 days after return.<br/>Adults: One MALARONE Tablet (adult strength = 250 mg
atovaquone/100 mg proguanil hydrochloride) per day.<br/>Pediatric Patients: The dosage for prevention of malaria in pediatric
patients is based upon body weight (Table 5).<br/>Treatment of Acute Malaria:<br/>Adults: Four MALARONE Tablets (adult strength; total daily
dose 1 g atovaquone/400 mg proguanil hydrochloride) as a
single dose daily for 3 consecutive days.<br/>Pediatric Patients: The dosage for treatment of acute malaria in pediatric
patients is based upon body weight (Table 6). MALARONE Tablets may be crushed and mixed with
condensed milk just prior to administration for children who may have
difficulty swallowing tablets.<br/>Patients With Renal Impairment: MALARONE should not be used for malaria prophylaxis
in patients with severe renal impairment (creatinine clearance<30 mL/min).
MALARONE may be used with caution for the treatment of malaria in
patients with severe renal impairment (creatinine clearance<30 mL/min),
only if the benefits of the 3-day treatment regimen outweigh the potential
risks associated with increased drug exposure (see CLINICAL PHARMACOLOGY:
Special Populations: Renal Impairment). No dosage adjustments are
needed in patients with mild (creatinine clearance 50 to 80 mL/min)
and moderate (creatinine clearance 30 to 50 mL/min) renal impairment
(see CLINICAL PHARMACOLOGY: Special Populations).<br/>Patients With Hepatic Impairment: No dosage adjustments are needed in patients with
mild to moderate hepatic impairment. No studies have been conducted
in patients with severe hepatic impairment (see CLINICAL PHARMACOLOGY:
Special Populations: Hepatic Impairment).
|
| dailymed-instance:descripti... |
MALARONE (atovaquone and proguanil hydrochloride)
is a fixed-dose combination of the antimalarial agents atovaquone
and proguanil hydrochloride. The chemical name of atovaquone is trans-2-[4-(4-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthalenedione.
Atovaquone is a yellow crystalline solid that is practically insoluble
in water. It has a molecular weight of 366.84 and the molecular formula
CHClO. The compound has the
following structural formula: The chemical name of proguanil hydrochloride is 1-(4-chlorophenyl)-5-isopropyl-biguanide
hydrochloride. Proguanil hydrochloride is a white crystalline solid
that is sparingly soluble in water. It has a molecular weight of 290.22
and the molecular formula CHClN���HCl. The compound has the following structural formula: MALARONE Tablets and MALARONE Pediatric
Tablets are for oral administration. Each MALARONE Tablet contains
250 mg of atovaquone and 100 mg of proguanil hydrochloride
and each MALARONE Pediatric Tablet contains 62.5 mg of atovaquone
and 25 mg of proguanil hydrochloride. The inactive ingredients
in both tablets are low-substituted hydroxypropyl cellulose, magnesium
stearate, microcrystalline cellulose, poloxamer 188, povidone K30,
and sodium starch glycolate. The tablet coating contains hypromellose,
polyethylene glycol 400, polyethylene glycol 8000, red iron
oxide, and titanium dioxide.
|
| dailymed-instance:clinicalP... |
Microbiology:<br/>Mechanism of Action: The constituents of MALARONE, atovaquone and proguanil
hydrochloride, interfere with 2 different pathways involved in
the biosynthesis of pyrimidines required for nucleic acid replication.
Atovaquone is a selective inhibitor of parasite mitochondrial electron
transport. Proguanil hydrochloride primarily exerts its effect by
means of the metabolite cycloguanil, a dihydrofolate reductase inhibitor.
Inhibition of dihydrofolate reductase in the malaria parasite disrupts
deoxythymidylate synthesis.<br/>Activity In Vitro and In
Vivo: Atovaquone and cycloguanil (an active metabolite
of proguanil) are active against the erythrocytic and exoerythrocytic
stages of Plasmodium spp. Enhanced efficacy of the combination compared
to either atovaquone or proguanil hydrochloride alone was demonstrated
in clinical studies in both immune and non-immune patients (see CLINICAL STUDIES).<br/>Drug Resistance: Strains of P. falciparum with decreased susceptibility to atovaquone or proguanil/cycloguanil
alone can be selected in vitro or in vivo. The combination of atovaquone
and proguanil hydrochloride may not be effective for treatment of
recrudescent malaria that develops after prior therapy with the combination.<br/>Pharmacokinetics:<br/>Absorption: Atovaquone is a highly lipophilic compound with
low aqueous solubility. The bioavailability of atovaquone shows considerable
inter-individual variability. Dietary fat taken
with atovaquone increases the rate and extent of absorption, increasing
AUC 2 to 3 times and C5 times over fasting.
The absolute bioavailability of the tablet formulation of atovaquone
when taken with food is 23%. MALARONE Tablets should be taken with
food or a milky drink. Proguanil hydrochloride
is extensively absorbed regardless of food intake.<br/>Distribution: Atovaquone is highly protein bound (>99%) over the
concentration range of 1 to 90 mcg/mL. A population pharmacokinetic
analysis demonstrated that the apparent volume of distribution of
atovaquone (V/F) in adult and pediatric patients after oral administration
is approximately 8.8 L/kg. Proguanil is
75% protein bound. A population pharmacokinetic analysis demonstrated
that the apparent V/F of proguanil in adult and pediatric patients>15 years of age with body weights from 31 to 110 kg ranged
from 1,617 to 2,502 L. In pediatric patients���15 years
of age with body weights from 11 to 56 kg, the V/F of proguanil
ranged from 462 to 966 L. In human plasma,
the binding of atovaquone and proguanil was unaffected by the presence
of the other.<br/>Metabolism: In a study whereC-labeled atovaquone
was administered to healthy volunteers, greater than 94% of the dose
was recovered as unchanged atovaquone in the feces over 21 days.
There was little or no excretion of atovaquone in the urine (less
than 0.6%). There is indirect evidence that atovaquone may undergo
limited metabolism; however, a specific metabolite has not been identified.
Between 40% to 60% of proguanil is excreted by the kidneys. Proguanil
is metabolized to cycloguanil (primarily via CYP2C19) and 4-chlorophenylbiguanide.
The main routes of elimination are hepatic biotransformation and renal
excretion.<br/>Elimination: The elimination half-life of atovaquone is about
2 to 3 days in adult patients. The elimination
half-life of proguanil is 12 to 21 hours in both adult patients
and pediatric patients, but may be longer in individuals who are slow
metabolizers. A population pharmacokinetic
analysis in adult and pediatric patients showed that the apparent
clearance (CL/F) of both atovaquone and proguanil are related to the
body weight. The values CL/F for both atovaquone and proguanil in
subjects with body weight���11 kg are shown in Table 1. The pharmacokinetics of atovaquone and proguanil
in patients with body weight below 11 kg have not been adequately
characterized.<br/>Special Populations:<br/>Pediatrics: The pharmacokinetics of proguanil and cycloguanil
are similar in adult patients and pediatric patients. However, the
elimination half-life of atovaquone is shorter in pediatric patients
(1 to 2 days) than in adult patients (2 to 3 days). In clinical
trials, plasma trough levels of atovaquone and proguanil in pediatric
patients weighing 5 to 40 kg were within the range observed in
adults after dosing by body weight.<br/>Geriatrics: In a single-dose study, the pharmacokinetics of
atovaquone, proguanil, and cycloguanil were compared in 13 elderly
subjects (age 65 to 79 years) to 13 younger subjects (age
30 to 45 years). In the elderly subjects, the extent of systemic
exposure (AUC) of cycloguanil was increased (point estimate = 2.36,
CI = 1.70, 3.28). Twas longer in elderly
subjects (median 8 hours) compared with younger subjects (median
4 hours) and average elimination half-life was longer in elderly
subjects (mean 14.9 hours) compared with younger subjects (mean
8.3 hours).<br/>Hepatic Impairment: In a single-dose study, the pharmacokinetics of
atovaquone, proguanil, and cycloguanil were compared in 13 subjects
with hepatic impairment (9 mild, 4 moderate, as indicated
by the Child-Pugh method) to 13 subjects with normal hepatic function.
In subjects with mild or moderate hepatic impairment as compared to
healthy subjects, there were no marked differences (<50%) in the
rate or extent of systemic exposure of atovaquone. However, in subjects
with moderate hepatic impairment, the elimination half-life of atovaquone
was increased (point estimate = 1.28, 90% CI = 1.00
to 1.63). Proguanil AUC, C, and its tincreased in subjects with mild hepatic impairment when compared
to healthy subjects (Table 2). Also, the proguanil AUC and its tincreased in subjects with moderate hepatic impairment
when compared to healthy subjects. Consistent with the increase in
proguanil AUC, there were marked decreases in the systemic exposure
of cycloguanil (Cand AUC) and an increase in its elimination
half-life in subjects with mild hepatic impairment when compared to
healthy volunteers (Table 2). There were few measurable cycloguanil
concentrations in subjects with moderate hepatic impairment (see DOSAGE
AND ADMINISTRATION). The pharmacokinetics of atovaquone, proguanil,
and cycloguanil after administration of MALARONE have not been studied
in patients with severe hepatic impairment.<br/>Renal Impairment: In patients with mild renal impairment (creatinine
clearance 50 to 80 mL/min), oral clearance and/or AUC data for
atovaquone, proguanil, and cycloguanil are within the range of values
observed in patients with normal renal function (creatinine clearance>80 mL/min). In patients with moderate renal impairment (creatinine
clearance 30 to 50 mL/min), mean oral clearance for proguanil
was reduced by approximately 35% compared with patients with normal
renal function (creatinine clearance>80 mL/min) and the oral
clearance of atovaquone was comparable between patients with normal
renal function and mild renal impairment. No data exist on the use
of MALARONE for long-term prophylaxis (over 2 months) in individuals
with moderate renal failure. In patients with severe renal impairment
(creatinine clearance<30 mL/min), atovaquone Cand AUC are reduced but the elimination half-lives for proguanil
and cycloguanil are prolonged, with corresponding increases in AUC,
resulting in the potential of drug accumulation and toxicity with
repeated dosing (see CONTRAINDICATIONS).<br/>Drug Interactions: There are no pharmacokinetic interactions between
atovaquone and proguanil at the recommended dose. Concomitant treatment with tetracycline has been associated with approximately a 40% reduction in plasma
concentrations of atovaquone. Concomitant treatment
with metoclopramide has also been
associated with decreased bioavailability of atovaquone. Concomitant administration of rifampin or rifabutin is known to reduce atovaquone levels by approximately 50% and 34%,
respectively (see PRECAUTIONS: Drug Interactions). The mechanisms
of these interactions are unknown. Concomitant
administration of atovaquone (750 mg BID with food for 14 days)
and indinavir (800 mg TID without food for 14 days) did
not result in any change in the steady-state AUC and Cof indinavir but resulted in a decrease in the Cof indinavir (23% decrease [90% CI 8%, 35%]). Caution should be exercised
when prescribing atovaquone with indinavir due to the decrease in
trough levels of indinavir. Atovaquone is highly
protein bound (>99%) but does not displace other highly protein-bound
drugs in vitro, indicating significant drug interactions arising from
displacement are unlikely (see PRECAUTIONS: Drug Interactions). Proguanil
is metabolized primarily by CYP2C19. Potential pharmacokinetic interactions
with other substrates or inhibitors of this pathway are unknown.
|
| dailymed-instance:activeIng... | |
| dailymed-instance:contraind... |
MALARONE is contraindicated in individuals with
known hypersensitivity to atovaquone or proguanil hydrochloride or
any component of the formulation. Rare cases of anaphylaxis following
treatment with atovaquone/proguanil have been reported. MALARONE is contraindicated for prophylaxis of P. falciparum malaria in patients with
severe renal impairment (creatinine clearance<30 mL/min)
(see CLINICAL PHARMACOLOGY: Special Populations: Renal Impairment).
|
| dailymed-instance:supply |
MALARONE Tablets, containing 250 mg atovaquone
and 100 mg proguanil hydrochloride, are pink, film-coated, round,
biconvex tablets engraved with���GX CM3���on one side. Bottle of 100 tablets with child-resistant closure (NDC
0173-0675-01). Unit Dose Pack of 24 (NDC 0173-0675-02). MALARONE Pediatric Tablets, containing 62.5 mg atovaquone
and 25 mg proguanil hydrochloride, are pink, film-coated, round,
biconvex tablets engraved with���GX CG7���on one side. Bottle of 100 tablets with child-resistant closure (NDC
0173-0676-01). Store
at 25��C (77��F); excursions permitted to 15��to 30��C
(59��to 86��F) (see USP Controlled Room Temperature).
|
| dailymed-instance:activeMoi... | |
| dailymed-instance:inactiveI... |
dailymed-ingredient:hypromellose,
dailymed-ingredient:low-substituted_hydroxypropylcellulose,
dailymed-ingredient:magnesium_stearate,
dailymed-ingredient:microcrystalline_cellulose,
dailymed-ingredient:poloxamer_188,
dailymed-ingredient:polyethylene_glycol_400,
dailymed-ingredient:polyethylene_glycol_8000,
dailymed-ingredient:povidone_K30,
dailymed-ingredient:red_iron_oxide,
dailymed-ingredient:sodium_starch_glycolate,
dailymed-ingredient:titanium_dioxide
|
| dailymed-instance:precautio... |
General: MALARONE has not been evaluated for the treatment
of cerebral malaria or other severe manifestations of complicated
malaria, including hyperparasitemia, pulmonary edema, or renal failure.
Patients with severe malaria are not candidates for oral therapy. Elevated liver function tests and rare cases of hepatitis
have been reported with prophylactic use of MALARONE. A single case
of hepatic failure requiring liver transplantation has also been reported
with prophylactic use. Absorption of atovaquone
may be reduced in patients with diarrhea or vomiting. If MALARONE
is used in patients who are vomiting (see DOSAGE AND ADMINISTRATION),
parasitemia should be closely monitored and the use of an antiemetic
considered. Vomiting occurred in up to 19% of pediatric patients given
treatment doses of MALARONE. In the controlled clinical trials of
MALARONE, 15.3% of adults who were treated with atovaquone/proguanil
received an antiemetic drug during that part of the trial when they
received atovaquone/proguanil. Of these patients, 98.3% were successfully
treated. In patients with severe or persistent diarrhea or vomiting,
alternative antimalarial therapy may be required. Parasite relapse occurred commonly when P. vivax malaria was treated with MALARONE alone. In the event of recrudescent P. falciparum infections after treatment with MALARONE
or failure of chemoprophylaxis with MALARONE, patients should be treated
with a different blood schizonticide.<br/>Information for Patients: Patients should be instructed:<br/>Drug Interactions: Concomitant treatment with tetracycline has been associated with approximately a 40%
reduction in plasma concentrations of atovaquone. Parasitemia should
be closely monitored in patients receiving tetracycline. While antiemetics
may be indicated for patients receiving MALARONE, metoclopramide may reduce the bioavailability
of atovaquone and should be used only if other antiemetics are not
available. Concomitant administration of rifampin or rifabutin is known to reduce atovaquone levels by approximately 50% and 34%,
respectively. The concomitant administration of MALARONE and rifampin
or rifabutin is not recommended. Proguanil
may potentiate the anticoagulant effect of warfarin and other coumarin-based
anticoagulants. The mechanism of this potential drug interaction has
not been established. Caution is advised when initiating or withdrawing
malaria prophylaxis or treatment with MALARONE in patients on continuous
treatment with coumarin-based anticoagulants. When these products
are administered concomitantly, suitable coagulation tests should
be closely monitored. Atovaquone is highly
protein bound (>99%) but does not displace other highly protein-bound
drugs in vitro, indicating significant drug interactions arising from
displacement are unlikely. Potential interactions
between proguanil or cycloguanil and other drugs that are CYP2C19
substrates or inhibitors are unknown. Carcinogenesis, Mutagenesis, Impairment of Fertility:<br/>Atovaquone: Carcinogenicity studies in rats were negative; 24-month
studies in mice showed treatment-related increases in incidence of
hepatocellular adenoma and hepatocellular carcinoma at all doses tested
which ranged from approximately 5 to 8 times the average steady-state
plasma concentrations in humans during prophylaxis of malaria. Atovaquone
was negative with or without metabolic activation in the Ames Salmonella mutagenicity assay, the Mouse
Lymphoma mutagenesis assay, and the Cultured Human Lymphocyte cytogenetic
assay. No evidence of genotoxicity was observed in the in vivo
Mouse Micronucleus assay.<br/>Proguanil: No evidence of a carcinogenic effect was observed
in 24-month studies conducted in CD-1 mice (doses up to 1.5 times
the average systemic human exposure based on AUC) and in Wistar Hannover
rats (doses up to 1.1 times the average systemic human exposure). Proguanil was negative with or without metabolic activation
in the Ames Salmonella mutagenicity
assay and the Mouse Lymphoma mutagenesis assay. No evidence of genotoxicity
was observed in the in vivo Mouse Micronucleus assay. Cycloguanil, the active metabolite of proguanil, was
also negative in the Ames test, but was positive in the Mouse Lymphoma
assay and the Mouse Micronucleus assay. These positive effects with
cycloguanil, a dihydrofolate reductase inhibitor, were significantly
reduced or abolished with folinic acid supplementation. Genotoxicity studies have not been performed with atovaquone
in combination with proguanil. Effects of MALARONE on male and female
reproductive performance are unknown.<br/>Pregnancy: Pregnancy Category C. Falciparum malaria carries
a higher risk of morbidity and mortality in pregnant women than in
the general population. Maternal death and fetal loss are both known
complications of falciparum malaria in pregnancy. In pregnant women
who must travel to malaria-endemic areas, personal protection against
mosquito bites should always be employed (see Information for Patients)
in addition to antimalarials. Atovaquone was
not teratogenic and did not cause reproductive toxicity in rats at
maternal plasma concentrations up to 5 to 6.5 times the estimated
human exposure during treatment of malaria. Following single-dose
administration ofC-labeled atovaquone to pregnant rats,
concentrations of radiolabel in rat fetuses were 18% (mid-gestation)
and 60% (late gestation) of concurrent maternal plasma concentrations.
In rabbits, atovaquone caused maternal toxicity at plasma concentrations
that were approximately 0.6 to 1.3 times the estimated human
exposure during treatment of malaria. Adverse fetal effects in rabbits,
including decreased fetal body lengths and increased early resorptions
and post-implantation losses, were observed only in the presence of
maternal toxicity. Concentrations of atovaquone in rabbit fetuses
averaged 30% of the concurrent maternal plasma concentrations. The combination of atovaquone and proguanil hydrochloride
was not teratogenic in rats at plasma concentrations up to 1.7 and
0.10 times, respectively, the estimated human exposure during
treatment of malaria. In rabbits, the combination of atovaquone and
proguanil hydrochloride was not teratogenic or embryotoxic to rabbit
fetuses at plasma concentrations up to 0.34 and 0.82 times, respectively,
the estimated human exposure during treatment of malaria. While there are no adequate and well-controlled studies
of atovaquone and/or proguanil hydrochloride in pregnant women, MALARONE
may be used if the potential benefit justifies the potential risk
to the fetus. The proguanil component of MALARONE acts by inhibiting
the parasitic dihydrofolate reductase (see CLINICAL PHARMACOLOGY:
Microbiology: Mechanism of Action). However, there are no clinical
data indicating that folate supplementation diminishes drug efficacy,
and for women of childbearing age receiving folate supplements to
prevent neural tube birth defects, such supplements may be continued
while taking MALARONE.<br/>Nursing Mothers: It is not known whether atovaquone is excreted into
human milk. In a rat study, atovaquone concentrations in the milk
were 30% of the concurrent atovaquone concentrations in the maternal
plasma. Proguanil is excreted into human milk
in small quantities. Caution should be exercised
when MALARONE is administered to a nursing woman.<br/>Pediatric Use:<br/>Treatment of Malaria: The efficacy and safety of MALARONE for the treatment
of malaria have been established in controlled studies involving pediatric
patients weighing 5 kg or more (see CLINICAL STUDIES). Safety
and effectiveness have not been established in pediatric patients
who weigh less than 5 kg.<br/>Prophylaxis of Malaria: The efficacy and safety of MALARONE have been established
for the prophylaxis of malaria in controlled studies involving pediatric
patients weighing 11 kg or more (see CLINICAL STUDIES). Safety
and effectiveness have not been established in pediatric patients
who weigh less than 11 kg.<br/>Geriatric Use: Clinical studies of MALARONE did not include sufficient
numbers of subjects aged 65 and over to determine whether they respond
differently from younger subjects. In general, dose selection for
an elderly patient should be cautious, reflecting the greater frequency
of decreased hepatic, renal, or cardiac function, the higher systemic
exposure to cycloguanil (see CLINICAL PHARMACOLOGY: Special Populations:
Geriatrics), and the greater frequency of concomitant disease or other
drug therapy.
|
| dailymed-instance:overdosag... |
There is no information on overdoses of MALARONE
substantially higher than the doses recommended for treatment. There is no known antidote for atovaquone, and it is
currently unknown if atovaquone is dialyzable. The median lethal dose
is higher than the maximum oral dose tested in mice and rats (1,825 mg/kg/day).
Overdoses up to 31,500 mg of atovaquone have been reported. In
one such patient who also took an unspecified dose of dapsone, methemoglobinemia
occurred. Rash has also been reported after overdose. Overdoses of proguanil hydrochloride as large as 1,500 mg have
been followed by complete recovery, and doses as high as 700 mg
twice daily have been taken for over 2 weeks without serious
toxicity. Adverse experiences occasionally associated with proguanil
hydrochloride doses of 100 to 200 mg/day, such as epigastric
discomfort and vomiting, would be likely to occur with overdose. There
are also reports of reversible hair loss and scaling of the skin on
the palms and/or soles, reversible aphthous ulceration, and hematologic
side effects.
|
| dailymed-instance:genericMe... |
atovaquone and proguanil hydrochloride
|
| dailymed-instance:fullName |
MALARONE (Tablet)
|
| dailymed-instance:adverseRe... |
Because MALARONE contains atovaquone and proguanil
hydrochloride, the type and severity of adverse reactions associated
with each of the compounds may be expected. The higher treatment doses
of MALARONE were less well tolerated than the lower prophylactic doses. Among adults who received MALARONE for treatment of malaria,
attributable adverse experiences that occurred in���5% of patients
were abdominal pain (17%), nausea (12%), vomiting (12%), headache
(10%), diarrhea (8%), asthenia (8%), anorexia (5%), and dizziness
(5%). Treatment was discontinued prematurely due to an adverse experience
in 4 of 436 adults treated with MALARONE. Among pediatric patients (weighing 11 to 40 kg) who received
MALARONE for the treatment of malaria, attributable adverse experiences
that occurred in���5% of patients were vomiting (10%) and pruritus
(6%). Vomiting occurred in 43 of 319 (13%) pediatric patients who
did not have symptomatic malaria but were given treatment doses of
MALARONE for 3 days in a clinical trial. The design of this clinical
trial required that any patient who vomited be withdrawn from the
trial. Among pediatric patients with symptomatic malaria treated with
MALARONE, treatment was discontinued prematurely due to an adverse
experience in 1 of 116 (0.9%). In a study of
100 pediatric patients (5 to<11 kg body weight) who
received MALARONE for the treatment of uncomplicated P. falciparum malaria, only diarrhea
(6%) occurred in���5% of patients as an adverse experience attributable
to MALARONE. In 3 patients (3%), treatment was discontinued prematurely
due to an adverse experience. Abnormalities
in laboratory tests reported in clinical trials were limited to elevations
of transaminases in malaria patients being treated with MALARONE.
The frequency of these abnormalities varied substantially across studies
of treatment and were not observed in the randomized portions of the
prophylaxis trials. In one phase III trial
of malaria treatment in Thai adults, early elevations of ALT and AST
were observed to occur more frequently in patients treated with MALARONE
compared to patients treated with an active control drug. Rates for
patients who had normal baseline levels of these clinical laboratory
parameters were: Day 7: ALT 26.7% vs. 15.6%; AST 16.9% vs. 8.6%. By
day 14 of this 28-day study, the frequency of transaminase elevations
equalized across the 2 groups. In this
and other studies in which transaminase elevations occurred, they
were noted to persist for up to 4 weeks following treatment with
MALARONE for malaria. None were associated with untoward clinical
events. Among subjects who received MALARONE
for prophylaxis of malaria in placebo-controlled trials, adverse experiences
occurred in similar proportions of subjects receiving MALARONE or
placebo (Table 3). The most commonly reported adverse experiences
possibly attributable to MALARONE or placebo were headache and abdominal
pain. Prophylaxis with MALARONE was discontinued prematurely due to
a treatment-related adverse experience in 3 of 381 adults and
0 of 125 pediatric patients. In an additional placebo-controlled study of
malaria prophylaxis with MALARONE involving 330 pediatric patients
in a malaria-endemic area (see CLINICAL STUDIES), the safety profile
of MALARONE was consistent with that described above. The most common
treatment-emergent adverse events with MALARONE were abdominal pain
(13%), headache (13%), and cough (10%). Abdominal pain (13% vs. 8%)
and vomiting (5% vs. 3%) were reported more often with MALARONE than
with placebo, while fever (5% vs. 12%) and diarrhea (1% vs. 5%) were
more common with placebo. No patient withdrew from the study due to
an adverse experience with MALARONE. No routine laboratory data were
obtained during this study. Among subjects
who received MALARONE for prophylaxis of malaria in clinical trials
with an active comparator, adverse experiences occurred in a similar
or lower proportion of subjects receiving MALARONE than an active
comparator (Table 4). The mean durations of dosing and the periods
for which the adverse experiences are summarized in Table 4, were
28 days (Study 1) and 26 days (Study 2) for MALARONE, 53 days
for mefloquine, and 49 days for chloroquine plus proguanil (reflecting
the different recommended dosing regimens). Fewer neuropsychiatric
adverse experiences occurred in subjects who received MALARONE than
mefloquine. Fewer gastrointestinal adverse experiences occurred in
subjects receiving MALARONE than chloroquine/proguanil. Compared with
active comparator drugs, subjects receiving MALARONE had fewer adverse
experiences overall that were attributed to prophylactic therapy (Table
4). Prophylaxis with MALARONE was discontinued prematurely due to
a treatment-related adverse experience in 7 of 1,004 travelers. In a third active-controlled study, MALARONE (n = 110)
was compared with chloroquine/proguanil (n = 111) for the
prophylaxis of malaria in 221 non-immune pediatric patients (see
CLINICAL STUDIES). The mean duration of exposure was 23 days
for MALARONE, 46 days for chloroquine, and 43 days for proguanil,
reflecting the differentrecommended dosage regimens for these products.
Fewer patients treated with MALARONE reported abdominal pain (2% vs.
7%) or nausea (<1% vs. 7%) than children who received chloroquine/proguanil.
Oral ulceration (2% vs. 2%), vivid dreams (2% vs.<1%), and blurred
vision (0% vs. 2%) occurred in similar proportions of patients receiving
either MALARONE or chloroquine/proguanil, respectively. Two patients
discontinued prophylaxis with chloroquine/proguanil due to adverse
events, while none of those receiving MALARONE discontinued due to
adverse events.<br/>Post-Marketing Adverse Reactions: In addition to adverse events reported
from clinical trials, the following events have been identified during
world-wide post-approval use of MALARONE. Because they are
reported voluntarily from a population of unknown size, estimates
of frequency cannot be made. These events have been chosen for inclusion
due to a combination of their seriousness, frequency of reporting,
or potential causal connection to MALARONE.<br/>Blood and Lymphatic System
Disorders: Neutropenia and rarely anemia. Pancytopenia in patients
with severe renal impairment treated with proguanil.<br/>Immune System Disorders: Allergic reactions including angioedema, urticaria,
and rare cases of anaphylaxis and vasculitis.<br/>Nervous System Disorders: Rare cases of seizures and psychotic events (such
as hallucinations); however, a causal relationship has not been established.<br/>Gastrointestinal Disorders: Stomatitis.<br/>Hepatobiliary Disorders: Elevated liver function tests and rare cases of
hepatitis, cholestasis; a single case of hepatic failure requiring
transplant has been reported.<br/>Skin and Subcutaneous Tissue
Disorders: Photosensitivity, rash, and rare cases of erythema
multiforme and Stevens-Johnson syndrome.
|
| dailymed-instance:indicatio... |
Prevention of Malaria: MALARONE is indicated for the prophylaxis of P. falciparum malaria, including
in areas where chloroquine resistance has been reported (see CLINICAL
STUDIES).<br/>Treatment of Malaria: MALARONE is indicated for the treatment of acute,
uncomplicated P. falciparum malaria. MALARONE has been shown to be effective in regions where
the drugs chloroquine, halofantrine, mefloquine, and amodiaquine may
have unacceptable failure rates, presumably due to drug resistance.
|
| dailymed-instance:represent... | |
| dailymed-instance:routeOfAd... | |
| dailymed-instance:name |
MALARONE
|