Acrivastine; Pseudoephedrine Hydrochloride (3163)
[ a'-kri-vas-teen; soo-doe-e-fed'-rin hye-droe-klor'-ide ]
| Ingredients: |
Acrivastine; Pseudoephedrine Hydrochloride |
| Indications: |
Rhinitis, allergic |
| Pregnancy Category: |
B |
| FDA Approved: |
1994- 03- 01 |
| Classes: |
Antihistamines, H1; Decongestants, nasal |
| Brand Names: |
Duact
-
Austria
;
Semprex-D
-
US
;
|
| DEA schedules: |
(none)
|
DESCRIPTION
|
| |
Semprex- D capsules (acrivastine and pseudoephedrine hydrochloride), are a fixed combination product formulation for oral
administration. Acrivastine is an antihistamine and pseudoephedrine is a decongestant. Each capsule contains 8 mg acrivastine
and 60 mg pseudoephedrine hydrochloride and the inactive ingredients: lactose, magnesium stearate and sodium starch glycolate.
The green and white capsule shell consists of gelatin, D&C yellow no. 10, FD&C green no. 3, and titanium dioxide. The yellow
band around the capsule consists of gelatin and D&C yellow no. 10. The capsules may contain one or more parabens and are printed
with edible black and white inks.
The chemical name of acrivastine is ( E, E ), - 3- [6- [1- (4- methylphenyl)- 3- (1- pyrrolidinyl)- 1- propenyl]- 2- propenoic acid; the molecular formula is C22 H24 N2 O2 . As an analog of triprolidine hydrochloride, acrivastine is classified as an alkylamine antihistamine. Acrivastine is an
odorless, white to pale cream crystalline powder that is soluble in chloroform and alcohol and slightly soluble in water.
The chemical name of pseudoephedrine hydrochloride is [ S - (R*, R*)]- α- [1- (methylamino)ethyl]benzenemethanol hydrochloride; the molecular formula is C10 H15 NO·HCl. Pseudoephedrine is one of the naturally occurring dextrorotatory diastereoisomers of ephedrine and is classified as
an indirect sympathomimetic amine. Pseudoephedrine hydrochloride occurs as odorless, fine white to off- white crystals or
powder; the drug is soluble in water, alcohol and chloroform.
|
CLINICAL PHARMACOLOGY
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| |
Acrivastine a structural analog of triprolidine HCl, exhibits H1 - antihistamine activity in isolated tissues, animals, and humans, and has sedative effects in humans (see PRECAUTIONS ). The propionic acid derivative of acrivastine is a metabolite in several animal species (as well as in man) and also exhibits
H1 - antihistamine activity.
Pseudoephedrine HCl is an indirect sympathomimetic agent; that is, it releases norepinephrine from adrenergic nerves.
In vitro tests and in vivo studies in animals of acrivastine and pseudoephedrine in combination failed to demonstrate evidence of any beneficial or deleterious
pharmacologic interaction between the two agents.
Pharmacokinetics and Metabolism
|
| |
Acrivastine was absorbed rapidly from combination capsule following oral administration and was bioavailable as a solution
of acrivastine. After administration of acrivastine and pseudoephedrine HCl capsules, maximum plasma acrivastine concentrations
were achieved at 1.14 ± 0.23 hours. A mass balance study in 7 healthy volunteers showed that acrivastine is primarily eliminated
by the kidneys. Over a 72 hour collection period, about 84% of the administered total radioactivity was recovered in urine
and about 13% in feces, for a combined recovery of about 97%. Further, 67% of the administered radioactive dose was recovered
in urine and the unchanged drug, 11% as the propionic acid metabolite, and 6% as other unknown metabolites.
Acrivastine exhibits linear kinetics over dosages ranging from 2- 32 mg tid. The mean ±SD terminal half- life for acrivastine
was 1.9 ± 0.3 hours following single oral doses and increased to 3.5 ± 1.9 hours at steady state. The terminal half- life
for the propionic acid metabolite was 3.8 ± 1.4 hours. Because of the short half lives of both acrivastine and its metabolites,
accumulation in the plasma following multiple dosing is not expected.
The steady- state maximum acrivastine plasma concentration was 227 ± 47 ng/ ml. The oral clearance and apparent volume of
distribution were 2.9± 0.7 ml/ min/ kg and 0.46 ± 0.05 L/ kg, respectively, following a single oral dose; oral clearance did
not change at steady state (2.86 ± 0.75 ml/ min/ kg). The apparent volume of distribution increased to 0.82 ± 0.6 L/ kg to
parallel the increase in the elimination half- life of the drug.
Acrivastine binding to human plasma proteins was 50 ± 2.0% and was concentration- independent over the range of 5- 1000 ng/
ml. The main binding protein was serum albumin although the drug was slightly bound to α 1- acid glycoprotein. No displacement
interaction was observed between acrivastine and either phenytoin or theophylline. The binding of acrivastine was not affected
by the presence of pseudoephedrine.
Pseudoephedrine HCl was also rapidly absorbed from the combination capsule, and the capsule was as bioavailable as a solution
of pseudoephedrine. Steady state maximum plasma concentration for pseudoephedrine was 498 ± 129 ng/ ml. The terminal half-
life, oral clearance and apparent volume of distribution were 6.2 ± 1.8 hours, 5.9 ± 1.7 ml/ min/ kg, and 3.0 ± 0.4 l/ kg,
respectively. Elimination of pseudoephedrine is primarily through the renal route as 55- 75% of an administered dose appears
unchanged in the urine. Pseudoephedrine elimination, however, is highly dependent upon urine pH; the plasma half- life decreased
to about 4 hours at pH 5 and increased to 13 hours at pH 8.
Pseudoephedrine did not bind to human plasma proteins over the concentration range of 50- 2000 ng/ ml.
Acrivastine and pseudoephedrine do not influence the pharmacokinetics of the other drug when administered concomitantly.
|
Special Populations
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A single dose pharmacokinetic study showed that the elimination half- lives of acrivastine, the propionic acid metabolite
of acrivastine, and pseudoephedrine were prolonged in patients with chronic renal insufficiency. Compared to normal volunteers,
the elimination half- life of acrivastine was about 50% increased in patients with mild renal insufficiency (creatinine clearance
= 26- 48 ml/ min) and was increased by about 130% in patients with moderate (creatinine clearance = 12- 17 ml/ min) or severe
(creatinine clearance 6- 10 ml/ min) renal insufficiency. Oral clearance of acrivastine was diminished by the same magnitude
as the half- life was prolonged in each of the three renally impaired groups. The elimination half- life of the propionic
acid metabolite of acrivastine was about 140% increased in patients with mild renal insufficiency and about 5 times increased
in patients with moderate or severe renal insufficiency.
Compared to normal volunteers, the elimination half- life of pseudoephedrine was about 3 times increased in patients with
mild renal insufficiency, about 7 times increased in patients with moderate renal insufficiency, and about 10 times increased
in patients with severe renal insufficiency. Oral clearance of pseudoephedrine was diminished by about the same magnitude
as the half- life was prolonged in each of the three renally impaired groups (see PRECAUTIONS, Impaired Renal Function .)
The total body load removed by dialysis is approximately 20%, 27%, and 38% for acrivastine, the propionic acid metabolite
of acrivastine, and pseudoephedrine, respectively, and therefore, a supplemental dose after a dialysis session is not required.
Based on a multiple dose cross study comparison, the apparent volume of distribution for acrivastine was 44% lower in elderly
(n=36, 65- 75 years) than in young volunteers (n=16, 19- 33 years). This difference could be attributed to the decrease in
total body water that occurs with aging. Despite this difference, no appreciable differences in plasma acrivastine concentrations
were seen in the elderly compared to the young, and no appreciable accumulation of acrivastine occurred in plasma at steady-
state. The elimination half- life for pseudoephedrine was 18% longer in elderly (7.9 hours) than in younger subjects (6.7
hours), presumably due to the deadline in average renal function that occurs with aging. Despite the difference, clearance
of pseudoephedrine was not appreciably different in elderly and younger subjects. Elderly patients should therefore be given
the same dosage as younger patients. Acrivastine and pseudoephedrine HCl capsules are not recommended, however, in patients
with renal impairment (see PRECAUTIONS, Impaired Renal Function .)
The effect of age and sex on the pharmacokinetics parameters of acrivastine and pseudoephedrine was determined in 93 healthy
volunteers who participated in various studies. All of the 93 volunteers were Caucasian (81 males and 12 females); 57 were
between the ages of 18 and 38 years and 36 were between the ages of 65 and 75 years. There were no age- or sex- related differences
in the pharmacokinetic parameters of either acrivastine or pseudoephedrine.
The effect of race on acrivastine and pseudoephedrine pharmacokinetics was examined by screening data obtained from 1035 patients,
age 12- 71 years, who participate in the 8 safety and efficacy studies. No race- related differences were observed in the
pharmacokinetics of either acrivastine or pseudoephedrine.
|
|
CLINICAL STUDIES
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In healthy volunteers, histamine- induced wheal and flare areas were significantly reduced relative to placebo at 30 minutes
after administration of a single dose of acrivastine 8 mg. Maximum reductions of wheal and flare occurred by 1- 2 hours and
significant reductions relative to placebo persisted for up to 6 hours a single oral dose of acrivastine 8 mg. No additional
reductions of wheal and flare were observed following single doses of acrivastine up to 24 mg. The exact correlation between
responses on skin testing and clinical efficacy is not established.
Five randomized, placebo- and or active- controlled trials compared acrivastine and pseudoephedrine HCl with its acrivastine
and pseudoephedrine components for the symptomatic relief of seasonal allergic rhinitis. In these studies, 696 patients received
4 daily doses of acrivastine 8 mg plus pseudoephedrine HCl 60 mg ( i.e., acrivastine and pseudoephedrine HCl capsules or bioequivalent formulations administered concurrently) or the same doses of
the components for 14 days. The combination reduced the intensity of sneezing, rhinorrhea, pruritus, and lacrimation more
than pseudoephedrine and reduced the intensity of nasal congestion more than acrivastine, demonstrating a contribution of
each of the components. The onset of antihistaminic and nasal decongestant actions occurred within 1 or 2 hours after the
first dose of acrivastine and pseudoephedrine HCl capsules. Somnolence occurred in about 12% of patients given acrivastine
and pseudoephedrine HCl compared with about 6% on placebo.
|
INDICATIONS AND USAGE
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Acrivastine and pseudoephedrine HCl capsules are indicated for relief of symptoms associated with seasonal allergic rhinitis
such as sneezing, rhinorrhea, pruritus, lacrimation, and nasal congestion. Acrivastine and pseudoephedrine HCl capsules should
be administered when both antihistaminic activity of acrivastine and the nasal decongestant activity of pseudoephedrine are
desired (see CLINICAL PHARMACOLOGY ). The efficacy of acrivastine and pseudoephedrine HCl capsules beyond 14 days of continuous treatment in patients with seasonal
allergic rhinitis has not been adequately investigated in clinical trials.
Acrivastine and pseudoephedrine HCl capsules have not been adequately studied for effectiveness in relieving the symptoms
of the common cold.
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CONTRAINDICATIONS
|
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Acrivastine and pseudoephedrine HCl capsules are contraindicated in patients with a known sensitivity to acrivastine, other
alkylamine antihistamines ( e.g., triprolidine), pseudoephedrine, other sympathomimetic amines ( e.g., phenylpropanolamine), or to any other components of the formulation. Acrivastine and pseudoephedrine HCl capsules are contraindicated
in patients with severe hypertension or severe coronary artery disease. Acrivastine and pseudoephedrine HCl capsules are contraindicated
in patients taking monoamine oxidase (MAO) inhibitors and for 2 weeks after stopping use of an MAO inhibitor (see DRUG INTERACTIONS ).
|
WARNINGS
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Acrivastine and pseudoephedrine HCl capsules should be used with caution in patients with hypertension, diabetes mellitus,
ischemic heart disease, increased intraocular pressure, hyperthyroidism, prostatic hypertrophy, stenosing peptic ulcer, or
pyloroduodenal obstruction. Overdose of sympathomimetic amines may produce CNS stimulation with convulsions or cardiovascular
collapse with accompanying hypotension. The elderly are more likely to have adverse reactions to sympathomimetic amines.
|
PRECAUTIONS
|
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General
|
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Acrivastine is sedating in some patients. In controlled clinical trials, somnolence ( i.e., drowsiness, sedation, sleepiness) was more common with acrivastine and pseudoephedrine HCl capsules (by an average of 6%)
than with placebo (see ADVERSE REACTIONS ).
Patients should be advised to assess their individual responses to acrivastine and pseudoephedrine HCl capsules before engaging
in any activity requiring mental alertness, such as driving a motor vehicle or operating machinery. Concurrent use of acrivastine
and pseudoephedrine HCl capsules with alcohol or other CNS depressants may cause additional reductions in alertness and impairment
of CNS performance and should be avoided (see DRUG INTERACTIONS ).
|
Impaired Renal Function
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Acrivastine and pseudoephedrine are excreted primarily through the kidneys. Both compounds therefore accumulate in patients
with impaired renal function. Due to the differential effects of renal failure on the serum half- life and clearance of acrivastine
and pseudoephedrine, use of acrivastine and pseudoephedrine HCl capsules, a fixed combination product, in patients with renal
impairment (creatinine clearance ≤48 ml/ min) is not recommended (see OVERDOSAGE and CLINICAL PHARMACOLOGY ).
|
Geriatric Use (Approximately 60 Years or Older)
|
| |
Elderly patients who participate in clinical trials did not differ in effectiveness or adverse effects from younger patients.
Antihistamines, however, as a pharmaceutical class, are more likely to cause dizziness, sedation, bladder- neck obstruction,
and hypotension in elderly patients. The elderly are also more likely to have adverse reactions to sympathomimetics such as
pseudoephedrine (see CLINICAL PHARMACOLOGY and WARNINGS ).
|
Information for the Patient
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Patients taking acrivastine and pseudoephedrine HCl capsules should receive the following information. acrivastine and pseudoephedrine
HCl capsules are prescribed to reduce symptoms associated with seasonal allergic rhinitis. Patients should be instructed to
take acrivastine and pseudoephedrine HCl capsules only as prescribed and not to exceed the prescribed dose. Patients should
be advised against the concurrent use of acrivastine and pseudoephedrine HCl with over- the- counter antihistamines and decongestants.
Patients who are or may become pregnant should be told that this product should be used in pregnancy or during lactation only
if the potential benefit justifies the potential risks to the fetus or nursing infant. Due to the risk of hypertensive crisis,
patients should be instructed not to take acrivastine and pseudoephedrine HCl capsules if they are presently taking a monoamine
oxidase inhibitor or for 2 weeks after stopping use of MAO inhibitor. Patients should be advised to assess their individual
responses to acrivastine and pseudoephedrine HCl capsules before engaging in any activity requiring mental alertness, such
as driving a car or operating machinery. Patients should be advised that the concurrent use of acrivastine and pseudoephedrine
HCl capsules with alcohol and other CNS depressants may lead to additional reductions in alertness and impairment of CNS performance
and should be avoided.
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Carcinogenesis, Mutagenesis, and Impairment of Fertility
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Carcinogenicity studies with the combination of acrivastine and pseudoephedrine have not been performed. Oral doses of acrivastine
alone at levels up to 40 mg/ kg/ day (236 mg/ m2/ day or 10 times the recommended human daily dose) for 20- 22 months in rats and up to 250 mg/ kg/ day (750 mg/ m2/ day or 32 times the recommended human daily dose) for 20- 24 months in mice revealed no evidence of carcinogenic potential.
No evidence of mutagenicity (with or without metabolic activation) was observed in the Ames Salmonella mutagenicity assay
or in the L5178Y/ tk+/ -lymphoma assay. In an in vitro cytogenetic study performed in cultured human lymphocytes, acrivastine induced structural chromosomal abnormalities in the
absence of metabolic activation, but not in its presence. In an in vivo cytogenic study in rats given single oral doses of acrivastine up to 1000 mg/ kg (5900 mg/ m2or 249 times the recommended human daily dose) there were no structural chromosomal alterations.
Reproduction- fertility studies in rats given acrivastine alone at levels up to 200 mg/ kg/ day (1180 mg/ m2/ day 50 times the recommended human daily dose) had no effect on male or female fertility. Similarly, no effect on fertility
was seen in male rats given acrivastine 20 mg/ kg/ day and pseudoephedrine 100 mg/ kg/ day (118 and 590 mg/ m2/ day or 5 and 3 times the recommended human daily dose, respectively) or in female rats given acrivastine 4 mg/ kg/ day and
pseudoephedrine 20 mg/ kg/ day (23.6 and 118 mg/ m2/ day or 1 and 0.7 times the recommended human daily doses, respectively).
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Pregnancy Category B
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Teratogenic Effects
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No evidence of teratogenicity was seen in rats and rabbits given acrivastine 1000 and 400 mg/ kg/ day, respectively (5900
and 4720 mg/ m2/ day or 249 and 200 times the recommended human daily dose). No evidence of teratogenicity was seen in rats given a combination
of acrivastine 30 mg/ kg/ day and pseudoephedrine 150 mg/ kg/ day (177 and 885 mg/ m2/ day or 8 and 5 times the recommended human daily dose respectively). Similarly, no evidence of teratogenicity was observed
in rabbits given acrivastine 20 mg/ kg/ day and pseudoephedrine 100 mg/ kg/ day (236 and 1180 mg/ m2/ day or 10 and 7 times the recommended human daily doses, respectively). There are, however, no adequate and well- controlled
studies in pregnant women. Because animal teratology studies are not always predictive of human responses, acrivastine and
pseudoephedrine HCl capsules should be used during pregnancy only if the potential benefit justifies the potential risks to
the fetus.
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Nonteratogenic Effects
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In a perinatal- postnatal study in rats, acrivastine given alone at levels up to 500 mg/ kg/ day (2950 mg/ m2/ day or 124 times the recommended human daily dose) was associated with maternal and neonatal morality at the maximum dose
level. Neonatal survival was decreased in rats given a combination of acrivastine 20 mg/ kg/ day and pseudoephedrine 100 mg/
kg/ day (118 and 590 mg/ m25 and 3 times the human dose, respectively).
|
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Nursing Mothers
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It is not know whether acrivastine is excreted in human milk. Acrivastine and pseudoephedrine HCl capsules should only be
used in nursing mothers when the potential benefit justifies the potential risks to the nursing infant.
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Pediatric Use
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Safety and effectiveness of acrivastine and pseudoephedrine HCl capsules in children under the age of 12 years have not been
established.
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DRUG INTERACTIONS
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MAO inhibitors and beta- adrenergic agonists increase the effects of sympathomimetic amines. Concomitant use of sympathomimetic
amines with MAO inhibitors can result in a hypertensive crisis (see CONTRAINDICATIONS ). Because MAO inhibitors are long- acting, acrivastine and pseudoephedrine HCl capsules should not be taken with MAO inhibitors
or for 2 weeks after stopping use of a MAO inhibitor.
Because of their pseudoephedrine content, acrivastine and pseudoephedrine HCl capsules may reduce the antihypertensive effects
of drugs that interfere with sympathetic activity. Care should be taken in the administration of acrivastine and pseudoephedrine
HCl capsules concomitantly with other sympathomimetic amines because the combined effects on the cardiovascular system may
be harmful to the patient.
Concomitant administration of acrivastine and pseudoephedrine HCl capsules with alcohol and other CNS depressants may result
in additional reductions in alertness and impairment of CNS performance and should be avoided.
No formal drug interaction studies between acrivastine and pseudoephedrine HCl capsules and other possible co- administered
drugs have been performed.
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ADVERSE REACTIONS
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Information on the incident of adverse events in clinical investigations conducted in the US was obtained from 33 controlled
and 15 uncontrolled clinical studies in which 2499 patients received acrivastine and 2631 patients received acrivastine plus
pseudoephedrine HCl for treatment periods ranging from 1 day to 1 year. The majority of patients in clinical trials were exposed
to acrivastine or acrivastine plus pseudoephedrine for less than 90 days. Acrivastine dosages ranged from 3- 96 mg/ day; 1336
patients received dosages equal to or greater than acrivastine 24 mg/ day. Acrivastine plus pseudoephedrine HCl dosages ranged
from acrivastine 8- 48 mg/ day plus pseudoephedrine HCl 60- 240 mg/ day. A total of 2335 patients received 3 of 4 daily doses
of acrivastine 8 mg plus pseudoephedrine HCl 60 mg.
In controlled clinical trials, only 12 spontaneously elicited adverse events were reported with frequencies greater than 1%
in the acrivastine plus pseudoephedrine HCl treatment group (see TABLE 1 ).
| TABLE 1
Adverse Event Reported in Clinical Trials*†
|
| |
|
Placebo |
ACR |
PSE |
ACR plus PSE |
| |
|
(n=1767) |
(n=1935) |
(n=887) |
(n=1650) |
| CNS
|
| |
Somnolence‡ |
6% |
12% |
8% |
12% |
| |
Headache |
18% |
19% |
19% |
19% |
| |
Dizziness |
2% |
3% |
3% |
3% |
| |
Nervousness‡ |
1% |
2% |
4% |
3% |
| |
Insomnia‡ |
1% |
1% |
6% |
4% |
| Miscellaneous
|
| |
Nausea |
2% |
3% |
3% |
2% |
| |
Dry mouth‡ |
2% |
3% |
5% |
7% |
| |
Asthenia |
2% |
3% |
2% |
2% |
| |
Dyspepsia |
1% |
1% |
2% |
2% |
| |
Pharyngitis |
2% |
1% |
1% |
3% |
| |
Cough increase |
1% |
2% |
1% |
2% |
| |
Dysmenorrhea |
1% |
2% |
3% |
2% |
|
| *
|
Includes all events regardless of causal relationship to treatment. |
| †
|
Includes all adverse events with reported frequency of >1% for the acrivastine plus pseudoephedrine treatment group. |
| ‡
|
Semprex- D demonstrates a statistically higher frequency of events than placebo, p ≤0.05. |
|
ACR = Acrivastine; PSE = Pseudoephedrine. |
|
The nature and overall frequency of adverse events from international clinical trials (35 studies involving approximately
1600 patients) were similar to the results obtained in the US studies.
Post- marketing clinical experience reports with acrivastine and acrivastine plus pseudoephedrine have included rare serious
hypersensitivity reactions manifested by anaphylaxis, angioedema, bronchospasm, and erythema multiforme. No deaths associated
with use of acrivastine or acrivastine plus pseudoephedrine have been reported.
Pseudoephedrine may cause ephedrine- like reactions such as tachycardia, palpitations, headache, dizziness, or nausea (see WARNINGS and OVERDOSAGE ).
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OVERDOSAGE
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There have been no reports of overdosage with acrivastine and pseudoephedrine HCl capsules. In the clinical trial program
and in international post- marketing experience, there have been two reported overdoses with acrivastine. Doses were 72 and
322 mg. Both patients recovered without sequelae. Adverse events included trembling, stridor loss of consciousness and possible
convulsions in the first patient and somnolence in the second.
Since acrivastine and pseudoephedrine have pharmacologically different actions, it is difficult to predict how an individual
will respond to overdosage with acrivastine and pseudoephedrine HCl capsules. However, acute overdosage with acrivastine and
pseudoephedrine HCl capsules may produce clinical signs of either CNS stimulation or depression. Overdosage of sympathomimetics
has been associated with the following events: fear, anxiety, tenseness, restlessness, tremor, weakness, pallor, respiratory
difficulty, dysuria, insomnia, hallucinations, convulsions, CNS depression, arrhythmias, and cardiovascular collapse with
hypotension. Treatment for overdosage with acrivastine and pseudoephedrine HCl capsules should follow general symptomatic
and supportive principles.
In a placebo- controlled, double- blind clinical trial in 18 healthy male subjects, single doses of acrivastine up to 400
mg (50 times the recommended antihistaminic dose) produced only a weak vagolytic effect, manifested as an increase in heart
rate, and did not cause cardiac repolarization delays ( i.e., increased QTc). Daily doses of acrivastine up to 2400 mg (75 times the recommended antihistamine dose) in an uncontrolled
study in 38 cancer patients produced a 15 beats per minute increase in mean heart rate and occasional episodes of nausea and
vomiting. The effects of acrivastine plus pseudoephedrine at single or multiple doses higher than the recommended daily dose
of acrivastine and pseudoephedrine HCl capsules ( i.e., 32 mg acrivastine plus 240 mg pseudoephedrine) on heart rate and cardiac repolarization have not been investigated in clinical
trials.
The mean LD50 (single, oral dose) of acrivastine is greater than 4000 mg/ kg (23600 mg/ m2or 1000 times the recommended human daily dose) in rats and greater than 1200 mg/ kg (3600 mg/ m2or 153 times the recommended human daily dose) in mice. The mean LD50 (single, oral dose) of pseudoephedrine HCl is 2206 mg/ kg (13, 015 mg/ m2or 73 times the recommended human daily dose in rats 726 mg/ kg (2178 mg/ m212 times the recommended human daily dose) in mice. The toxic and lethal concentrations of acrivastine and pseudoephedrine
in human biologic fluids are not known. Based upon pharmacokinetic screening data from clinical trials, the maximum plasma
acrivastine concentration after dosing with acrivastine 8 mg was 393 ng/ ml and the maximum plasma pseudoephedrine concentration
after dosing with pseudoephedrine HCl 60 mg was 1308 ng/ ml.
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DOSAGE AND ADMINISTRATION
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The recommended dosage for adults and children 12 years and older is 1 capsule administered orally, every 4- 6 hours four
times a day.
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HOW SUPPLIED
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Semprex- D capsules (dark green opaque cap and white opaque body with a yellow band) contain acrivastine 8 mg and pseudoephedrine
HCl 60 mg. The cap is printed with "Wellcome" and the unicorn logo in white ink, and the body is printed with "Semprex- D"
in black ink.
Storage: Store at 15- 25°C (59- 77°F) in a dry place and protected from light.
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PRODUCT LISTING - EQUIVALENTS NOT AVAILABLE
|
| |
| capsule - oral - 8 mg- 60 mg -
|
| 100.0 |
$118.67 |
Semprex- D
Celltech Pharmaceuticals Inc
|
53014040410 |
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|