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
Amerge Side Effects, and Drug Interactions - Naratriptan
Amerge Side Effects, and Drug Interactions - Naratriptan
SIDE EFFECTS
Serious cardiac events,
including some that have been fatal,
have occurred following the use of 5-HT1 agonists. These events
are extremely rare and most have been reported in patients with
risk factors predictive
of CAD. Events reported have included coronary
artery vasospasm,
transient myocardial
ischemia, myocardial
infarction, ventricular
tachycardia, and
ventricular fibrillation (see CONTRAINDICATIONS,
WARNINGS, and
PRECAUTIONS).
Incidence in Controlled Clinical Trials
The most common adverse events were paresthesias, dizziness,
drowsiness, malaise/fatigue, and throat/ neck
symptoms, which occurred at a rate
of 2% and at least two times placebo
rate. Since patients treated only one to three headaches in the
controlled clinical
trials, the opportunity for discontinuation of therapy
in response to an adverse
event was limited. In a long-term, open
label study where patients
were allowed to treat multiple migraine attacks for up to 1 year,
15 patients (3. 6%) discontinued treatment due to adverse events.
Table 2 lists adverse events that occurred in five placebo-controlled
clinical trials of
approximately 1752 exposures to placebo and AMERGE Tablets in adult
migraine patients.
The events cited reflect experience gained under closely monitored
conditions of clinical
trials in a highly selected patient
population. In actual
clinical practice
or in other clinical
trials, these frequency
estimates may not apply, as the conditions of use, reporting behavior,
and the kinds of patients treated may differ.
Only events that occurred at a frequency
of 2% or more in the AMERGE Tablets 2.5-mg treatment
group and were more frequent
in that group than in
the placebo group are
included in Table 2. From this table, it appears that many of these
adverse events are dose
related.
Table 2:
Treatment-Emergent Adverse Events Reported by at Least 2%
of Patients in Placebo-Controlled Migraine Trials
|
Adverse Event Type
|
Placebo
(n = 498)
|
AMERGE 1 mg
(n = 627)
|
AMERGE 2. 5 mg
(n = 627)
|
| Atypical sensation
Paresthesias (all types)
|
1%
<1%
|
2%
1%
|
4%
2%
|
| Gastrointestinal
Nausea
|
5%
4%
|
6%
4%
|
7%
5%
|
| Neurological
Dizziness
Drowsiness
Malaise/ fatigue
|
3%
1%
<1%
1%
|
4%
1%
1%
2%
|
7%
2%
2%
2%
|
| Pain and pressure
sensation
Throat/ neck
symptoms
|
2%
1%
|
2%
1%
|
4%
2%
|
One event present in
more than 1% of patients receiving AMERGE Tablets (vomiting) occurred
more frequently on placebo
than on naratriptan 2.5 mg. AMERGE Tablets are generally well tolerated.
Most adverse reactions were mild and transient. The incidence
of adverse events in placebo-controlled clinical trials was not
affected by age or weight
of the patients, duration of headache
prior to treatment,
presence of aura, use of prophylactic
medications, or tobacco
use. There was insufficient data to assess the impact of race on
the incidence of adverse
events.
Other Events Observed in Association With the Administration
of AMERGE Tablets
In the paragraphs that follow, the frequencies of less commonly
reported adverse clinical
events are presented. Because the reports include events observed
in open and uncontrolled
studies, the role of AMERGE
Tablets in their causation cannot be reliably determined. Furthermore,
variability associated with adverse event reporting, the terminology
used to describe adverse events, etc. limit
the value of the quantitative
frequency estimates
provided. Event frequencies are calculated as the number
of patients reporting an event divided by the total number
of patients (n = 3557) exposed to oral naratriptan doses up to 10
mg. All reported events are included except those already listed
in the previous table, those too general to be informative, and
those not reasonably associated with the use of the drug. Events
are further classified within body
system categories and
enumerated in order of decreasing frequency
using the following definitions: frequent adverse events are those
occurring in at least 1/100 patients, infrequent adverse events
are those occurring in 1/100 to 1/1000 patients, and rare adverse
events are those occurring in fewer than 1/1000 patients.
Atypical Sensations: Frequent were warm/cold temperature
sensations. Infrequent were feeling
strange and burning/ stinging sensation.
Cardiovascular: Infrequent were palpitations, increased
blood pressure, tachyarrhythmias,
and abnormal ECG
(PR prolongation, QTc prolongation, ST/T wave
abnormalities, premature
ventricular contractions,
atrial flutter, or atrial
fibrillation), and syncope. Rare were bradycardia, varicosities,
hypotension, and
heart murmurs.
Ear, Nose, and Throat: Frequent were ear, nose, and
throat infections. Infrequent were phonophobia, sinusitis,
upper respiratory
inflammation, and tinnitus. Rare were allergic
rhinitis; labyrinthitis; ear, nose, and throat hemorrhage; and hearing
difficulty.
Endocrine and Metabolic: Infrequent were thirst
and polydipsia, dehydration, and fluid
retention. Rare were hyperlipidemia,
hypercholesterolemia, hypothyroidism, hyperglycemia,
glycosuria and ketonuria,
and parathyroid neoplasm.
Eye: Frequent was photophobia. Infrequent was blurred
vision. Rare were eye pain
and discomfort, sensation
of eye pressure,
eye hemorrhage, dry eyes, difficulty focusing, and scotoma.
Gastrointestinal: Frequent were hyposalivation
and vomiting. Infrequent were dyspeptic
symptoms, diarrhea,
gastrointestinal
discomfort and pain, gastroenteritis,
and constipation. Rare were abnormal
liver function tests,
abnormal bilirubin
levels, hemorrhoids, gastritis,
esophagitis, salivary gland
inflammation, oral
itching and irritation, regurgitation and reflux,
and gastric ulcers.
Hematological Disorders: Infrequent was increased
white cells. Rare were thrombocytopenia,
quantitative red
cell or hemoglobin defects,
anemia, and purpura.
Lower Respiratory Tract: Infrequent were bronchitis,
cough, and pneumonia. Rare were tracheitis, asthma,
pleuritis, and airway
constriction and obstruction.
Musculoskeletal: Infrequent were muscle
pain, arthralgia and articular
rheumatism, muscle cramps
and spasms, joint and
muscle stiffness, tightness,
and rigidity. Rare were bone
and skeletal pain.
Neurological: Frequent was vertigo. Infrequent were
tremors, cognitive function
disorders, sleep disorders,
and disorders of equilibrium. Rare were compressed nerve
syndromes, confusion,
sedation, hyperesthesia,
coordination disorders, paralysis
of cranial nerves, decreased
consciousness, dreams, altered sense
of taste, neuralgia,
neuritis, aphasia,
hypoesthesia, motor retardation, muscle
twitching and fasciculation,
psychomotor restlessness,
and convulsions.
Non-Site Specific: Infrequent were chills and/or
fever, descriptions of odor
or taste, edema and swelling,
allergies, and allergic reactions. Rare were spasms and mobility
disorders.
Pain and Pressure Sensations: Frequent were pressure/tightness/heaviness
sensations.
Psychiatry: Infrequent were anxiety,
depressive disorders, and detachment. Rare were aggression
and hostility, agitation,
hallucinations, panic, and hyperactivity.
Reproduction: Rare were lumps of female
reproductive tract,
breast inflammation,
inflammation of
vagina, inflammation
of fallopian tube, breast
discharge, endometrium
disorders, decreased libido,
and lumps of breast.
Skin: Infrequent were sweating, skin
rashes, pruritus, and urticaria. Rare were skin
erythema, dermatitis
and dermatosis, hair loss and alopecia,
pruritic skin rashes, acne
and folliculitis,
allergic skin reactions, macular skin/rashes, skin
photosensitivity,
photodermatitis, skin flakiness, and dry skin.
Urology: Infrequent were bladder
inflammation and
polyuria and diuresis. Rare were urinary
tract hemorrhage,
urinary urgency, pyelitis,
and urinary incontinence.
DRUG ABUSE AND DEPENDENCE
In one clinical study
enrolling 12 subjects, all of whom had experience using oral
opiates and other psychoactive
drugs, AMERGE Tablets produced less intense subjective
responses ordinarily associated with many drugs of abuse
than did codeine (30
to 90 mg).
DRUG INTERACTIONS
Ergot-containing drugs have been reported to cause
prolonged vasospastic reactions. Because there is a theoretical
basis that these effects
may be additive, use of ergotamine-containing or ergot-type medications
(like dihydroergotamine or methysergide) and naratriptan within
24 hours is contraindicated (see CONTRAINDICATIONS).
The administration of naratriptan with other 5-HT1 agonists
has not been evaluated in migraine
patients. Because their vasospastic
effects may be additive, coadministration
of naratriptan and other 5-HT1 agonists within 24 hours
of each other is not recommended (see CONTRAINDICATIONS).
Selective serotonin
reuptake inhibitors (SSRIs) (e.g., fluoxetine, fluvoxamine, paroxetine,
sertraline) have been reported, rarely, to cause
weakness, hyperreflexia, and incoordination
when coadministered with 5-HTv agonists. If concomitant
treatment with naratriptan
and an SSRI is clinically warranted, appropriate observation of
the patient is advised.
In normal volunteers,
coadministration
of single doses of naratriptan tablets and alcohol
did not result in substantial modification
of naratriptan pharmacokinetic parameters. From population
pharmacokinetic analyses, coadministration of naratriptan and fluoxetine,
beta-blockers, or tricyclic antidepressants did not affect
the clearance of naratriptan.
Naratriptan does not inhibit monoamine oxidase
(MAO) enzymes and is a p.o.
inhibitor of P450;
metabolic interactions between naratriptan and drugs metabolized
by P450 or MAO are therefore
unlikely.
Oral Contraceptives
Oral contraceptives reduced clearance
by 32% and volume of
distribution by 22%, resulting in slightly higher concentrations
of naratriptan. Hormone replacement therapy
had no effect
on pharmacokinetics
in older female patients.
Smoking increased the clearance
of naratriptan by 30%.
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