A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Adderall XR Side Effects, and Drug Interactions - Amphetamine
Adderall XR Side Effects, and Drug Interactions - Amphetamine
SIDE EFFECTS
The premarketing development program for ADDERALL XR
included exposures in a total of 685 participants n clinical trials (615 patients,
70 healthy adult subjects). These participants i received ADDERALL XR
at daily doses up to 30 mg. The 615 patients (ages 6 to 12) were evaluated in
two controlled clinical studies, one open- l clinical study, and one single-dose
clinical pharmacology study (N=20). Safety data on all patients are included
in the discussion that follows. Adverse reactions were assessed by collecting
adverse events, results of physical examinations, vital signs, weights, laboratory
analyses, and ECGs.
Adverse events during exposure were obtained primarily by general
inquiry and recorded by clinical investigators using terminology of their own
choosing. Consequently, it is not possible to provide a meaningful estimate
of the proportion of individuals experiencing adverse events without first grouping
similar types of events into a smaller number of standardized event categories.
In the tables and listings that follow, COSTART terminology has been used to
classify reported adverse events.
The stated frequencies of adverse events represent the proportion
of individuals who experienced, at least once, a treatment-emergent adverse
event of the type listed.
Adverse events associated with discontinuation of treatment:
In two placebo-controlled studies of up to 5 weeks duration, 2.4% (10/425)
of ADDERALL XR treated patients discontinued due to adverse events
(including 3 patients with loss of appetite, one of whom also reported insomnia)
compared to 2.7% (7/359) receiving placebo. The most frequent adverse events
associated with discontinuation of ADDERALL XR in controlled and
uncontrolled, multiple-dose clinical trials (N=595) are presented below. Over
half of these patients wero exposed to ADDERALL XR for 12 months
or more.
|
Adverse event
|
of patient % s discontinuing (N=595)
|
|
Anorexia (lass of appetite)
|
2.9
|
|
Insomnia
|
1.5
|
|
Weight loss
|
1.2
|
|
Emotional lability
|
1.0
|
|
Depression
|
0.7
|
Adverse events occurring in a controlled trial: Adverse
events reported in a 3-week clinical trial of pediatric patients treated with
ADDERALL XR or placebo are presented in the table below.
The preserver should be aware mat these figures cannot be used
to predict the incidence of adverse events in the course of usual medical practice
where patient characteristics and other factors differ from those which prevailed
in the clinical trials. Similarly, the cited frequencies cannot be compared
with figures obtained from other clinical investigations involving different
treatments, uses, and investigators. The cited figures, however, do provide
the prescribing physician with some basis for estimating the relative contribution
of drug and non-drug factors to the adverse event incidence rate in the population
studied.
|
Table 1 Adverse Events Reported by More Than 1% of Patients
Receiving ADDERALL XR with Higher incidence man cm Placebo
in a 584 patient Clinical Study
|
|
Body System
|
Preferred Term
|
ADDERAILL XR (N=374)
|
Placebo (N-210)
|
|
General
|
Abdominal Pain (stomachache)
|
14%
|
10%
|
| |
Accidental Injury
|
3%
|
2%
|
| |
Asthenia (fallout)
|
2%
|
0%
|
| |
Fever
|
5%
|
2%
|
| |
Infection
|
4%
|
2%
|
| |
Viral Infection
|
2%
|
0%
|
|
Digestive System
|
Loss of Appetite
|
22%
|
2%
|
| |
Diarrhea
|
2%
|
1%
|
| |
Dyspepsia
|
2%
|
1%
|
| |
Nausea
|
5%
|
3%
|
| |
Vomiting
|
7%
|
! %
|
|
Nervous System
|
Dizziness
|
2%
|
0%
|
| |
Emotional Lability
|
9%
|
2%
|
| |
Insomnia
|
17%
|
2%
|
| |
Nervousness
|
6%
|
2%
|
|
Metabolic/Nutritional
|
Weight Loss
|
4%
|
0%
|
The following adverse reactions have been associated with amphetamine
use:
Cardiovascular: Palpitations, tachycaidia, elevation of blood
pressure. There have been isolated reports of cardiomyopathy associated with
chronic amphetamine use.
Central Nervous System: Psychotic episodes at recommended doses,
overstimulation , restlessness, dizziness, insomnia, euphoria, dyskinesia, dysphoria
, tremor, headache, exacerbation of motor and phonic tics and Tourette's syndrome.
Gastrointestinal: Dryness of the mouth, unpleasant taste, diarrhea,
constipation, other gastrointestinal disturbances. Anorexia and weight loss
may occur as undesirable effects.
Allergic: Urticaria.
Endocrine: Impotence, changes in libido.
DRUG ABUSE AND DEPENDENCE
ADDERALL XR is a Schedule II controlled substance.
Amphetamines have been extensively abused. Tolerance, extreme
psychological dependence, and severe social disability have occurred. There
are reports of patients who have increased the dosage to many times that recommended.
Abrupt cessation following prolonged high dosage administration results in extreme
fatigue and mental depression; changes are also noted on the sleep EEC. Manifestations
of chronic intoxication with amphetamines may include severe dermatoses, marked
insomnia, irritability, hyperactivity, and personality changes. The most severe
manifestation of chronic intoxication is psychosis, often clinically indistinguishable
from schizophrenia.
DRUG INTERACTIONS
Acidifying agents—Gastrointestinal acidifying agents
(guanethidine reserpins, glutamic acid HCI. ascorbic acid, etc.) lower absorption
of amphetamines.
Urinary acidifying agents—These agents (ammonium chloride,
sodium acid phosphate, etc.) increase the concentration of the ionized species
of the amphetamine molecule, thereby increasing urinary excretion. Both groups
of agents lower blood levels and efficacy of amphetamines.
Adrenergic blockers—Adrenergic blockers are inhibited
by amphetamines.
Alkalinizing agents—Gastrointestinal alkalinizing agents (sodium
bicarbonate. etc.) increase absorption of amphetamines. Co-administration of
ADDERALL XR and gastrointestinal alxalinizing agents, such as antacids,
should be avoided. Urinary alkalinizing agents (acetazolamide. some thiazides)
increase the concentration of the non-ionized species of the amphetamine molecule,
thereby decreasing urinary excretion. Both groups of agents increase blood levels
and therefore potentiate the actions of amphetamines.
Antidepressants, tricyclio—Amphetamines may enhance
the activity of tricyclic antidepressants or sympathomimetic agents; d-amphetamine
with desipramine or protriptyline and possibly other tricyclics cause striking
and sustained increases in the concentration of d-amphetamine in the brain;
cardiovascular effects can be potentiated .
MAO inhibitors—MAOI antidepressants, as well as a metebolite
of furazolidone, slow amphetamine metabolism. This slowing potentiates amphetamines,
increasing their effect on the release of norepinephrine and other monoamines
from adrenergic nerve endings; this csn cause headaches and other signs of hypertensive
crisis. A variety of toxic neurological effects and malignant hyperpyrexia can
occur, somatimes with fatal results.
Antihistamines—Amphetamines may counteract the sedative effect
of antihistamines.
Antihypertensives—Amphetamines may antagonize the hypotensive
effects of antihypertensives.
Chlorpromazine—Chlorpromazine blocks dopamine and norepinephrine
receptors, thus inhibiting the central stimulant affects of amphstaminas, and
can be used to treat amphetamine poisoning.
Ethosuximide—Amphetamines may delay intestinal absorption
of ethosuximide.
Haloperidol—Haloperidol blocks dopamine receptors, thus
inhibiting the central stimulant effects of amphetamines.
Lithium carbonate—The anorectic and stimulatory effects
of amphetamines may be inhibited by lithium carbonate.
Meperidine—Amphetamines potentiate the analgesic effect
of meperidine.
Methenamine therapy—Urinary excretion of amphetamines
is increased, and efficacy is reduced, by acidifying agents used in methenamine
therapy.
Norepinephrine—Amphetamines enhance the adrenergic effect
of norepinephrine.
Phenobarbital—Amphetamines may delay intestinal absorption
of phenobarbital; co-administration of phenobarbital may produce a synergistic
anticonvulsant action .
Phenytoin—Amphetamines may delay intestinal absorption
of phenytoin; co-administration of phenytoin may produce a synergistic anticonvulsant
action.
Propoxyptiene—In cases of propoxyphene overdosage, amphetamine
CNS stimulation is potentiated and fatal convulsions can occur.
Veratrum alkaloids—Amphetamines inhibit the hypotensive
effect of veratrum alkaloids.
Drug/Laboratory Test Interactions
Amphetamines can cause a significant elevation in plasma corticosteroid
levels. This increase is greatest in the evening.
Amphetamines may interfere with urinary steroid determinations.
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