Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/3288
Predicate | Object |
---|---|
rdf:type | |
rdfs:label |
DARAPRIM (Tablet)
|
dailymed-instance:dosage |
For Treatment of Toxoplasmosis: The dosage of DARAPRIM for the treatment of toxoplasmosis
must be carefully adjusted so as to provide maximum therapeutic effect and
a minimum of side effects. At the dosage required, there is a marked variation
in the tolerance to the drug. Young patients may tolerate higher doses than
older individuals. Concurrent administration of folinic acid is strongly recommended
in all patients. The adult starting dose is 50 to 75 mg of the drug daily, together with 1 to
4 g daily of a sulfonamide of the sulfapyrimidine type, e.g., sulfadoxine.
This dosage is ordinarily continued for 1 to 3 weeks, depending on the
response of the patient and tolerance to therapy. The dosage may then be reduced
to about one half that previously given for each drug and continued for an
additional 4 to 5 weeks. The pediatric dosage
of DARAPRIM is 1 mg/kg/day divided into 2 equal daily doses; after
2 to 4 days this dose may be reduced to one half and continued for approximately
1 month. The usual pediatric sulfonamide dosage is used in conjunction
with DARAPRIM.<br/>For Treatment of Acute Malaria: DARAPRIM is NOT recommended alone in the treatment of acute
malaria. Fast-acting schizonticides, such as chloroquine or quinine, are indicated
for treatment of acute malaria. However, DARAPRIM at a dosage of 25 mg
daily for 2 days with a sulfonamide will initiate transmission control
and suppression of non-falciparum malaria. DARAPRIM
is only recommended for patients infected in areas where susceptible plasmodia
exist. Should circumstances arise wherein DARAPRIM must be used alone in semi-immune
persons, the adult dosage for acute malaria is 50 mg for 2 days;
children 4 through 10 years old may be given 25 mg daily for 2 days.
In any event, clinical cure should be followed by the once-weekly regimen
described below for chemoprophylaxis. Regimens which include suppression should
be extended through any characteristic periods of early recrudescence and
late relapse, i.e., for at least 10 weeks in each case.<br/>For Chemoprophylaxis of Malaria: Adults and pediatric patients over
10 years���25 mg (1 tablet) once weekly Children
4 through 10 years���12.5 mg (/2 tablet) once
weekly Infants and children under 4 years���6.25 mg (/4 tablet) once weekly
|
dailymed-instance:descripti... |
DARAPRIM (pyrimethamine) is an antiparasitic compound available
in tablet form for oral administration. Each scored tablet contains 25 mg
pyrimethamine and the inactive ingredients corn and potato starch, lactose,
and magnesium stearate. Pyrimethamine, known chemically
as 5-(4-chlorophenyl)-6-ethyl-2,4-pyrimidinediamine, has the following structural
formula: CHClN Mol.
Wt 248.71
|
dailymed-instance:clinicalP... |
Pyrimethamine is well absorbed with peak levels occurring
between 2 to 6 hours following administration. It is eliminated slowly
and has a plasma half-life of approximately 96 hours. Pyrimethamine is
87% bound to human plasma proteins.<br/>Microbiology: Pyrimethamine is a folic acid antagonist and the rationale
for its therapeutic action is based on the differential requirement between
host and parasite for nucleic acid precursors involved in growth. This activity
is highly selective against plasmodia and Toxoplasma
gondii. Pyrimethamine possesses blood schizonticidal
and some tissue schizonticidal activity against malaria parasites of humans.
However, the 4-amino-quinoline compounds are more effective against the erythrocytic
schizonts. It does not destroy gametocytes, but arrests sporogony in the mosquito. The
action of pyrimethamine against Toxoplasma gondii is greatly enhanced when used in conjunction with sulfonamides.
This was demonstrated by Eyles and Colemanin the treatment of
experimental toxoplasmosis in the mouse. Jacobs et aldemonstrated
that combination of the 2 drugs effectively prevented the development
of severe uveitis in most rabbits following the inoculation of the anterior
chamber of the eye with toxoplasma.
|
dailymed-instance:activeIng... | |
dailymed-instance:contraind... |
Use of DARAPRIM is contraindicated in patients with known
hypersensitivity to pyrimethamine or to any component of the formulation.
Use of the drug is also contraindicated in patients with documented megaloblastic
anemia due to folate deficiency.
|
dailymed-instance:supply |
White, scored tablets containing 25 mg pyrimethamine,
imprinted with���DARAPRIM���and���A3A���in bottles
of 100 (NDC 0173-0201-55). Store
at 15��to 25��C (59��to 77��F) in a dry place and protect
from light.
|
dailymed-instance:genericDr... | |
dailymed-instance:activeMoi... | |
dailymed-instance:inactiveI... | |
dailymed-instance:precautio... |
General: The recommended dosage for chemoprophylaxis of malaria should
not be exceeded. A small���starting���dose for toxoplasmosis is
recommended in patients with convulsive disorders to avoid the potential nervous
system toxicity of pyrimethamine. DARAPRIM should be used with caution in
patients with impaired renal or hepatic function or in patients with possible
folate deficiency, such as individuals with malabsorption syndrome, alcoholism,
or pregnancy, and those receiving therapy, such as phenytoin, affecting folate
levels (see Pregnancy subsection).<br/>Information for Patients: Patients should be warned that at the first appearance of
a skin rash they should stop use of DARAPRIM and seek medical attention immediately.
Patients should also be warned that the appearance of sore throat, pallor,
purpura, or glossitis may be early indications of serious disorders which
require treatment with DARAPRIM to be stopped and medical treatment to be
sought. Women of childbearing potential who are taking
DARAPRIM should be warned against becoming pregnant. Patients should be warned
to keep DARAPRIM out of the reach of children. Patients should be advised
not to exceed recommended doses. Patients should be warned that if anorexia
and vomiting occur, they may be minimized by taking the drug with meals. Concurrent
administration of folinic acid is strongly recommended when used for the treatment
of toxoplasmosis in all patients.<br/>Laboratory Tests: In patients receiving high dosage, as for the treatment
of toxoplasmosis, semiweekly blood counts, including platelet counts, should
be performed.<br/>Drug Interactions: Pyrimethamine may be used with sulfonamides, quinine and
other antimalarials, and with other antibiotics. However, the concomitant
use of other antifolic drugs or agents associated with myelosuppression including
sulfonamides or trimethoprim-sulfamethoxazole combinations, proguanil, zidovudine,
or cytostatic agents (e.g., methotrexate), while the patient is receiving
pyrimethamine, mayincrease the risk of bone marrow suppression. If signs
of folate deficiency develop, pyrimethamine should be discontinued. Folinic
acid (leucovorin) should be administered until normal hematopoiesis is restored
(see WARNINGS). Mild hepatotoxicity has been reported in some patients when
lorazepam and pyrimethamine were administered concomitantly.<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility: See WARNINGS section for information on carcinogenesis.<br/>Mutagenesis: Pyrimethamine has been shown to be nonmutagenic in the following
in vitro assays: the Ames point mutation assay, the Rec assay, and the E. coli WP2 assay. It was positive in the L5178Y/TK
+/- mouse lymphoma assay in the absence of exogenous metabolic activation.Human
blood lymphocytes cultured in vitro had structural chromosome aberrations
induced by pyrimethamine. In vivo, chromosomes analyzed
from the bone marrow of rats dosed with pyrimethamine showed an increased
number of structural and numerical aberrations.<br/>Pregnancy:<br/>Teratogenic Effects: Pregnancy Category C. Pyrimethamine has been shown to be
teratogenic in rats when given in oral doses 7 times the human dose for
chemoprophylaxis of malaria or 2.5 times the human dose for treatment
of toxoplasmosis. At these doses in rats, there was a significant increase
in abnormalities such as cleft palate, brachygnathia, oligodactyly, and microphthalmia.
Pyrimethamine has also been shown to produce terata such as meningocele in
hamsters and cleft palate in miniature pigs when given in oral doses 170 and
5 times the human dose, respectively, for chemoprophylaxis of malaria
or for treatment of toxoplasmosis. There are no adequate
and well-controlled studies in pregnant women. DARAPRIM should be used during
pregnancy only if the potential benefit justifies the potential risk to the
fetus. Concurrent administration of folinic acid is strongly recommended
when used for the treatment of toxoplasmosis during pregnancy.<br/>Nursing Mothers: Pyrimethamine is excreted in human milk. Because of the
potential for serious adverse reactions in nursing infants from pyrimethamine
and from concurrent use of a sulfonamide with DARAPRIM for treatment of some
patients with toxoplasmosis, 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 (see WARNINGS and PRECAUTIONS: Pregnancy ).<br/>Pediatric Use: See DOSAGE AND ADMINISTRATION section.<br/>Geriatric Use: Clinical studies of DARAPRIM did not include sufficient
numbers of subjects aged 65 and over to determine whether they respond differently
from younger subjects. Other reported clinical experience has not identified
differences in responses between the elderly and younger patients. In general,
dose selection for an elderly patient should be cautious, usually starting
at thelow end of the dosing range, reflecting the greater frequency of decreased
hepatic, renal, or cardiac function, and of concomitant disease or other drug
therapy.
|
dailymed-instance:overdosag... |
Following the ingestion of 300 mg or more of pyrimethamine,
gastrointestinal and/or central nervous system signs may be present, including
convulsions. The initial symptoms are usually gastrointestinal and may include
abdominal pain, nausea, severe and repeated vomiting, possibly including hematemesis.
Central nervous system toxicity may be manifest by initial excitability, generalized
and prolonged convulsions which may be followed by respiratory depression,
circulatory collapse, and death within a few hours. Neurological symptoms
appear rapidly (30 minutes to 2 hours after drug ingestion), suggesting
that in gross overdosage pyrimethamine has a direct toxic effect on the central
nervous system. The fatal dose is variable, with the
smallest reported fatal single dose being 375 mg. There are, however,
reports of pediatric patients who have recovered after taking 375 to 625 mg. There
is no specific antidote to acute pyrimethamine poisoning. In the event of
overdosage, symptomatic and supportive measures should be employed. Gastric
lavage is recommended and is effective if carried out very soon after drug
ingestion. Parenteral diazepam may be used to control convulsions. Folinic
acid should also be administered within 2 hours of drug ingestion to
be most effective in counteracting the effects on the hematopoietic system
(see WARNINGS). Due to the long half-life of pyrimethamine, daily monitoring
of peripheral blood counts is recommended for up to several weeks after the
overdose until normal hematologic values are restored.
|
dailymed-instance:genericMe... |
pyrimethamine
|
dailymed-instance:fullName |
DARAPRIM (Tablet)
|
dailymed-instance:adverseRe... |
Hypersensitivity reactions, occasionally severe (such as
Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme,
and anaphylaxis), and hyperphenylalaninemia, can occur particularly when pyrimethamine
is administered concomitantly with a sulfonamide. Consult the complete prescribing
information for the relevant sulfonamide for sulfonamide-associated adverse
events. With doses of pyrimethamine used for the treatment of toxoplasmosis,
anorexia and vomiting may occur. Vomiting may beminimized by giving the medication
with meals; it usually disappears promptly upon reduction of dosage. Doses
used in toxoplasmosis may produce megaloblastic anemia, leukopenia, thrombocytopenia,
pancytopenia, atrophic glossitis, hematuria, and disorders of cardiac rhythm.
Hematologic effects, however, may also occur at low doses in certain individuals
(see PRECAUTIONS: General). Pulmonary eosinophilia
has been reported rarely.
|
dailymed-instance:warning |
The dosage of pyrimethamine required for the treatment of
toxoplasmosis is 10 to 20 times the recommended antimalaria dosage and
approaches the toxic level. If signs of folate deficiency develop (see ADVERSE
REACTIONS), reduce the dosage or discontinue the drug according to the response
of the patient. Folinic acid (leucovorin) should be administered in a dosage
of 5 to 15 mg daily (orally, IV, or IM) until normal hematopoiesis is
restored. Data in 2 humans indicate that pyrimethamine
may be carcinogenic: a 51-year-old female who developed chronic granulocytic
leukemia after taking pyrimethamine for 2 years for toxoplasmosis,and
a 56-year-old patient who developed reticulum cell sarcoma after 14 months
of pyrimethamine for toxoplasmosis. Pyrimethamine
has been reported to produce a significant increase in the number of lung
tumors in mice when given intraperitoneally at doses of 25 mg/kg. DARAPRIM
should be kept out of the reach of infants and children as they are extremely
susceptible to adverse effects from an overdose. Deaths in pediatric patients
have been reported after accidental ingestion.
|
dailymed-instance:indicatio... |
Treatment of Toxoplasmosis: DARAPRIM is indicated for the treatment of toxoplasmosis
when used conjointly with a sulfonamide, since synergism exists with this
combination.<br/>Treatment of Acute Malaria: DARAPRIM is also indicated for the treatment of acute malaria.
It should not be used alone to treat acute malaria. Fast-acting schizonticides
such as chloroquine or quinine are indicated and preferable for the treatment
of acute malaria. However, conjoint use of DARAPRIM with a sulfonamide (e.g.,
sulfadoxine) will initiate transmission control and suppression of susceptible
strains of plasmodia.<br/>Chemoprophylaxis of Malaria: DARAPRIM is indicated for the chemoprophylaxis of malaria
due to susceptible strains of plasmodia. However, resistance to pyrimethamine
is prevalent worldwide. It is not suitable as a prophylactic agent for travelers
to most areas.
|
dailymed-instance:represent... | |
dailymed-instance:routeOfAd... | |
dailymed-instance:name |
DARAPRIM
|