Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1452
Predicate | Object |
---|---|
rdf:type | |
rdfs:label |
HALFAN (Tablet)
|
dailymed-instance:dosage |
(See INDICATIONS AND USAGE.) HALFAN should be given on an empty stomach at
least 1 hour before or 2 hours after food. (See WARNINGS.) The recommended
dosage regimen to treat adults able to tolerate oral medications, who have
mild to moderate malaria caused by P. falciparum or P. vivax is:<br/>Non-immune Patients: Patients with no previous
exposure or minimal exposure to malaria should be considered���non-immune.���These patients should receive 500 mg (2 x 250 mg tablets) of halofantrine
hydrochloride every 6 hours for 3 doses (total first course dosage 1,500 mg).
This course of therapy should be repeated 7 days after the first course.<br/>Semi-immune Patients: Patients with a history
of life-long residence in endemic areas and a clear history of recent previous
malaria caused by the same Plasmodium species
may be considered semi-immune. In these patients, omitting the second course
of therapy may be considered. Clinical trials in semi-immune patients have
utilized this one-course regimen with satisfactory efficacy and safety.<br/>Hepatic or Renally Impaired Patients: There is no information
on dosing alterations needed because of hepatic or renal impairment.
|
dailymed-instance:descripti... |
HALFAN (halofantrine hydrochloride) is an antimalarial drug
available as tablets containing 250 mg of halofantrine hydrochloride (equivalent
to 233 mg of the free base) for oral administration. The
chemical name of halofantrine hydrochloride is 1,3-dichloro-��-[2-(dibutylamino)
ethyl]-6-(trifluoromethyl)-9-phenanthrene-methanol hydrochloride. The
drug, a white to off-white crystalline compound, is practically insoluble
in water. Halofantrine hydrochloride has a calculated molecular weight of
536.89. The empirical formula is CHClFNO���HCl
and the structural formula is<br/>Inactive Ingredients: Inactive ingredients
are magnesium stearate, microcrystalline cellulose, povidone, pregelatinized
starch, sodium starch glycolate, and talc.
|
dailymed-instance:clinicalP... |
The interindividual variability in the pharmacokinetic parameters
of halofantrine is very wide and has led to great difficulty in precisely
determining the pharmacokinetic characteristics of this product. Following
administration of halofantrine hydrochloride tablets in single oral doses
of 250 mg to 1,000 mg to healthy volunteers, peak plasma levels were reached
in 5 to 7 hours. High variability in the peak plasma levels was observed in
all studies, suggesting erratic absorption from the gastrointestinal tract.
An approximately 7-fold increase in peak plasma concentration and a 3-fold
increase in area under the curve (AUC) of halofantrine were obtained when
a single 250-mg tablet was administered with high-fat food to healthy subjects. Healthy
volunteers who were given 3 oral doses of 500 mg of halofantrine hydrochloride
(500 mg every 6 hours), when fed 2 hours before the second and third
doses, had similar 3- to 5-fold increases in absorption. A mean Cof
3,200 ng/mL (range 1,555 to 4,920 ng/mL) with a corresponding Tof
9 to 17 hours was attained following this multiple-dose regimen. Halofantrine
has a relatively long distribution phase with a half-life of 16 hours and
a variable terminal elimination half-life of 6 to 10 days. The half-life of
halofantrine varies considerably among individuals. The
primary metabolite of halofantrine is n-desbutyl halofantrine. Cvaluesranging from 310 to 410 ng/mL were observed to occur between 32 and 56 hours
following oral administration of multiple doses of 500 mg halofantrine q6h
for 3 doses. The apparent terminal elimination half-life of the metabolite
is 3 to 4 days. Based on animal studies, hepatobiliary
clearance with fecal elimination of halofantrine parent compound and metabolite
predominates. The extent to which halofantrine is bound to plasma proteins
and the extent to which halofantrine is taken up into red blood cells are
unknown. The pharmacokinetics of halofantrine in patients
with compromised renal or hepatic function has not been investigated. The
course of the anemia developed by a few malaria patients treated with halofantrine
whose red blood cells were deficient in glucose-6-phosphate dehydrogenase
(G6PD) was not different from that in malaria patients with normal G6PD values.<br/>Microbiology: Halofantrine is a blood
schizonticidal antimalarial agent with no apparent action on the sporozoite,
gametocyte, or hepatic stages of the infection. The exact mechanism of its
action is unknown. The primary metabolite, n-desbutyl halofantrine, and the
parent compound are equally active in vitro. While in vitro studies indicate that there
may be cross-resistance between halofantrine and mefloquine, the clinical
data do not support this view. No significant correlation between halofantrine
and mefloquine resistance was observed in clinical trials.<br/>Clinical Trials: In controlled clinical
trials involving 90 non-immune patients with malaria due to Plasmodium
falciparum, treatment with HALFAN (500 mg every 6 hours for 3 doses
on days 0 and 7) had a cure rate of 99%. Patients were followed for 28 days
or more after initiation of treatment. In trials involving
583 acute malaria patients, the majority of whom were semi-immune, treatment
with HALFAN (500 mg every 6 hours for 3 doses) produced a cure rate of 90%
against Plasmodium falciparum infection
(n=512), and a cure rate of 99% against Plasmodium
vivax (n=71).
|
dailymed-instance:activeIng... | |
dailymed-instance:contraind... |
HALFANis contraindicated in patients with a known family history of congenital
QTc prolongation. (See BOXED WARNING.) Use of this drug is contraindicated
in patients with a known hypersensitivity to halofantrine.
|
dailymed-instance:supply |
HALFAN is available
as a white to off-white, capsule-shaped tablet containing 250 mg of halofantrine
hydrochloride in bottles of 60 tablets. The tablets are imprinted HALFAN on
1 side. Store at controlled room temperature between
20��to 25��C (68��to 77��F) and protect from light. 250
mg 60's: NDC 0007-4195-18
|
dailymed-instance:boxedWarn... |
WARNING: HALFAN HAS BEEN SHOWN TO PROLONG
QTc INTERVAL AT THE RECOMMENDED THERAPEUTIC DOSE. THERE HAVE BEEN RARE REPORTS
OF SERIOUS VENTRICULAR DYSRHYTHMIAS SOMETIMES ASSOCIATED WITH DEATH, WHICH
MAY BE SUDDEN. HALFAN IS THEREFORE NOT RECOMMENDED FOR USE IN COMBINATION
WITH DRUGS OR CLINICAL CONDITIONS KNOWN TO PROLONG QTc INTERVAL, OR IN PATIENTS
WHO HAVE PREVIOUSLY RECEIVED MEFLOQUINE, OR IN PATIENTS WITH KNOWN OR SUSPECTED
VENTRICULAR DYSRHYTHMIAS, A-V CONDUCTION DISORDERS OR UNEXPLAINED SYNCOPAL
ATTACKS. HALFAN SHOULD BEPRESCRIBED ONLY BY PHYSICIANS WHO HAVE SPECIAL COMPETENCE
IN THE DIAGNOSIS AND TREATMENT OF MALARIA, AND WHO ARE EXPERIENCED IN THE
USE OF ANTIMALARIAL DRUGS. PHYSICIANS SHOULD THOROUGHLY FAMILIARIZE THEMSELVES
WITH THE COMPLETE CONTENTS OF THIS LEAFLET BEFORE PRESCRIBING HALFAN.
|
dailymed-instance:activeMoi... | |
dailymed-instance:inactiveI... | |
dailymed-instance:precautio... |
General: A phototoxic potential
cannot be ruled out on the basis of the chemical moiety of halofantrine and
the results of animal tests. (See ANIMAL TOXICOLOGY.) However, there is no
evidence for this effect in humans.<br/>Drug Interactions: Although no drug interaction
studies have been conducted, HALFAN should not be administered with drugs
known to prolong the QTc interval. In clinical use, an interaction with mefloquine
has been reported to lead to further prolongation of the QTc interval.The
prolongation may be significant and potentially fatal; therefore, HALFAN should
not be given simultaneously with or subsequent to mefloquine. There have been
no drug interactions reported when halofantrine is coadministered with chloroquine. In vitro studies have shown that drugs which
inhibit hepatic CYP3A4, e.g., ketoconazole, lead to an inhibition of halofantrine
metabolism. Further, in dogs orally administered ketoconazole, the metabolism
of halofantrine was decreased (SEE WARNINGS).<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term studies of
halofantrine hydrochloride in animals have not been performed to evaluate
carcinogenic potential. Genotoxicity of halofantrine
hydrochloride was evaluated in 5 assay test systems including an Ames test,
a gene mutation test in Chinese hamster ovary cells, a chromosomal aberration
analysis in Chinese hamster ovary cells, a micronucleus test in mice, and
a dominant lethal assay. No mutagenic potential was demonstrated in any of
these test systems. Halofantrine hydrochloride did
not adversely affect male or female fertility in the rat at an oral dose of
30 mg/kg (1/6 of the maximum recommended human dose based on mg/m).<br/>Pregnancy:<br/>Teratogenic Effects: Pregnancy Category C: In pregnant rabbits, maternal-lethal doses (decremental
dose schedule of 360 to 120 mg/kg, equivalent to 3.6 times to 1.2 times the
maximum recommended human dose, respectively, based on mg/m) were
associated with abortion and an increased incidence of skeletal malformations,
but oral doses up to 60 mg/kg (6/10 of the maximum recommended human dose
based on mg/m) did not produce maternal or fetal developmental
toxicity.<br/>Non-teratogenic Effects: In reproduction
teratology studies in the rat, oral doses���30 g/kg (1/6 of the
maximum recommended human dose based on mg/m) produced postimplantation
embryonic death and reduced fetal weight and viability. Halofantrine hydrochloride
at doses of 15 mg/kg/day (1/10 of the maximum recommended human dose based
on mg/m) had no embryotoxicity or teratogenicity. These effects
occurred at and below doses that produced overt maternal toxicity in the rats. Halofantrine
has been shown to be embryocidal in rats. There are no adequate and well-controlled
studies in pregnant women. HALFAN should be used during pregnancy only if
the potential benefit justifies the potential risk to the fetus.<br/>Nursing Mothers: In lactation studies
performed in rats, dose-related decreases in offspring body weight were observed
at a dose of 25 mg/kg/day and above (1/8 of the maximum recommended human
dose based on mg/m). Control pups breast-fed by high-dosed mothers
had significant decreases in body weight and survival at doses of 50 and 100
mg/kg/day (1/4 to 1/2 of the maximum recommended human dose based on mg/m). It
is not known whether this drug is excreted in human milk. Because many drugs
are excreted in human milk and because of the potential for serious adverse
reactions in nursing infants from halofantrine hydrochloride, a decision should
be made whether to discontinue nursing or to discontinue the drug, taking
into account the importance of the drug to the mother.<br/>Pediatric Use: Safety and effectiveness
of halofantrine hydrochloride tablets in the pediatric population have not
been established.<br/>Geriatric Use: There are no studies
on the use of halofantrine hydrochloride in elderly individuals.
|
dailymed-instance:overdosag... |
In case of overdosage, vomiting should be induced, in conjunction
with appropriate supportive measures, which should include ECG monitoring.
The possibility of neurologic toxicity, especially decreased consciousness
and seizures, should be evaluated. Dehydration secondary to gastrointestinal
toxicity with diarrhea and vomiting may require treatment with intravenous
fluid therapy. Gastrointestinal distress with abdominal
pain, vomiting, cramping, and diarrhea occurs at doses higher than the recommended
therapeutic regimen. Palpitations have also been reported at these higher
doses.
|
dailymed-instance:genericMe... |
halofantrine hydrochloride
|
dailymed-instance:fullName |
HALFAN (Tablet)
|
dailymed-instance:adverseRe... |
Normal Subjects: The following adverse
events were reported in normal subjects given HALFAN 1,000 mg to 1,500 mg
in a single dosing course.<br/>Gastrointestinal: Abdominal pain (10%), anorexia (5%), diarrhea (5%), nausea
(10%), vomiting (10%).<br/>Central Nervous System: Dizziness (5%), headache (5%).<br/>Clinical Trials: In clinical trials involving
933 patients treated with three 500 mg doses (500 mg every 6 hours), the following
clinical adverse events were reported. There were
no deaths or permanent disabilities thought related to drug toxicity. Five
patients discontinued medication due to adverse events. Three patients vomited
medicine repeatedly. Though temporally related to
drug administration, the relationship of the following serious adverse events
to malaria or underlying illness as opposed to drug toxicity could not be
established. Two patients had decreased consciousness; other serious adverse
events reported during clinical trials included convulsions (3 cases), stomatitis
(3 cases), moderately severe diarrhea (2 cases), pulmonary edema (1 case),
tetany (1 case), hypertensive crisis (1 case), cerebrovascular accident (1
case). The most frequently reported adverse events
thought possibly���or probably���related to halofantrine were:
Abdominal pain (8.5%), diarrhea (6.0%), dizziness (4.5%), vomiting (4.3%),
nausea (3.4%), cough (3.0%), headache (3.0%), pruritus (2.6%), rigors (1.7%),
and myalgias (1.3%). These events are also characteristic of malaria. Pruritus
was reported in a higher proportion of highly pigmented patients than in other
patients. Adverse events thought possibly���or
probably���related to halofantrine affecting<1% of patients studied
in the clinical trials included:<br/>Body as a Whole: Fatigue, malaise.<br/>Cardiovascular: Chest pain, palpitations, postural hypotension.<br/>Dermatologic: Rash.<br/>Gastrointestinal: Abdominal distention, anorexia, constipation, dyspepsia.<br/>Mucous Membrane: Stomatitis.<br/>Musculoskeletal: Arthralgia, back pain.<br/>Central Nervous System: Asthenia, confusion, convulsions, depression, paresthesia,
sleep disorder.<br/>Renal: Urinary frequency.<br/>Special Senses: Abnormal vision, tinnitus.<br/>Laboratory: The most frequently noted
laboratory abnormalities that occurred following drug administration in the
clinical trials were decreased hematocrit, elevated hepatic transaminases,
decreased and increased white blood cell counts, and decreased platelet counts.
These alterations returned to normal limits within 2 to 3 weeks post-infection.
The causal relationship of these changes to HALFAN is unclear, as these laboratory
abnormalities can also occur with acute malaria.<br/>Postmarketing Experience: Halofantrine was marketed
in Europe starting in 1988. The following additional adverse experiences have
been reported in postmarketing surveillance outside the United States: Facial
edema and urticaria (allergic/anaphylactic reactions) in rare cases. Hemolysis/hemolytic
anemia (including immune hemolytic anemia) which may compromise renal function
have been reported in patients with malaria who have been treated with halofantrine.
Hemolytic reactions may also be observed in patients with malaria in the absence
of halofantrine. Prolongation of QT interval has been
reported. There have been rare reports of serious ventricular dysrhythmias
sometimes associated with death. These cases have occurred particularly under
certain conditions which include uses of doses higher than recommended, recent
or concomitant treatment with mefloquine, or presence of pre-existing prolongation
of QT interval.
|
dailymed-instance:warning |
In life-threatening, severe, or overwhelming malarial infections,
patients should be treated immediately with an appropriate parenteral antimalarial
drug. The safety and efficacy of HALFAN in the treatment of patients with
cerebral malaria or other forms of complicated malaria have not been established. HALFAN has been shown to prolong QTc interval
at the recommended therapeutic dose. There have been rare reports of serious
ventricular dysrhythmias sometimes associated with death, which may be sudden.
HALFAN is therefore not recommended in combination with drugs, or clinical
conditions, known to prolong QTc interval, or in patients with known or suspectedventricular dysrhythmias, A-V conduction disorders, or unexplained syncopal
attacks. Physicians should perform an ECG prior to dosing to ensure that the
patient's baseline QTc interval is within normal limits. Cardiac rhythm
should be monitored during and for 8 to 12 hours following completion of therapy. Caution
should be used with concomitant intake of drugs which are known to significantly
inhibit the hepatic cytochrome P450 enzyme, CYP3A4. HALFAN should be taken on an empty stomach as
increased absorption and, thus, increased toxicity may result from dosing
in association with food. Do not exceed recommended doses, as higher than
recommended doses of HALFAN have been shown to further prolong QTc interval. Data
on the use of HALFAN subsequent to administration of mefloquine suggest a
significant, potentially fatal, prolongation of the QTc interval.Therefore,
HALFAN should not be given simultaneously with, or subsequent to, mefloquine.
(See PRECAUTIONS���Drug Interactions.) Halofantrine
has been shown to be embryotoxic in animal tests. Use in women of childbearing
potential only with due caution regarding the potential effect on the fetus
if the patient is pregnant. (See PRECAUTIONS���Pregnancy subsection.)
|
dailymed-instance:indicatio... |
HALFAN tablets are
indicated for the treatment of adults who can tolerate oral medication and
who have mild to moderate malaria (equal to or less than 100,000 parasites/mm)
caused by Plasmodium falciparum or Plasmodium vivax. NOTE:
Patients with acute P. vivax malaria
treated with HALFAN are at risk of relapse because halofantrine does not eliminate
the exoerythrocytic (hepatic phase) parasites. To avoid relapse after initial
treatment of the acute P. vivax infection
with HALFAN, patients should subsequently be treated with an 8-aminoquinoline
to eradicate the exoerythrocytic parasites. NOTE: THE
EFFICACY OF HALFAN IN THE PROPHYLAXIS OF MALARIA HAS NOT BEEN ESTABLISHED.
|
dailymed-instance:represent... | |
dailymed-instance:routeOfAd... | |
dailymed-instance:name |
HALFAN
|