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
Zomig Side Effects, and Drug Interactions - Zolmitriptan
Zomig Side Effects, and Drug Interactions - Zolmitriptan
SIDE EFFECTS
Although not reported with zolmitriptan in clinical
trials, serious cardiac events, including some that have been fatal,
have rarely occurred following use of 5-HT1 agonists.
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
Among 2,633 patients treated with ZOMIG in the active and placebo
controlled trials, no patients
withdrew for reasons related to adverse events, but as patients
treated a single headache
in these trials, the opportunity for discontinuation was limited.
In a long term, open
label study where patients
were allowed to treat multiple
migraine attacks for
up to 1 year, 8% (167 out of 2,058) withdrew from the trial because
of adverse experience. The most common events were paresthesia,
asthenia, nausea,
dizziness, pain, chest
or neck tightness or heaviness,
somnolence and warm
sensation.
Table 2 lists the adverse events that occurred in ³2%
of the 2,074 patients in any one of the ZOMIG 1 mg, ZOMIG 2.5 mg
or ZOMIG 5 mg dose
groups of the controlled clinical
trials. Only events that were more frequent in a ZOMIG group
compared to the placebo
groups are included. 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.
Several of the adverse events appear dose
related, notably paresthesia, sensation of heaviness or tightness
in chest, neck, jaw, and
throat, dizziness, somnolence,
and possibly asthenia
and nausea.
-
- Table 2: Adverse Experience Incidence
in Five Placebo-controlled
- Migraine Clinical Trials: Events
Reported By ³2%
Patients Treated
- With ZOMIG
|
|
Adverse Event Type
|
|
|
|
|
| ATYPICAL
SENSATIONS |
6%
|
1%
|
1%
|
18%
|
| Hypesthesia
|
1%
|
1%
|
1%
|
2%
|
| Paresthesia
(all types) |
2%
|
5%
|
7%
|
9%
|
| Sensation
warm/cold |
4%
|
6%
|
5%
|
7%
|
| PAIN
AND PRESSURE SENSATIONS |
7%
|
13%
|
14%
|
22%
|
- Chest-pain/ tightness/ pressure
and or heaviness
|
- 1%
|
- 2%
|
- 3%
|
- 4%
|
- Neck/throat/jaw-pain/ tightness/ pressure
|
- 3%
|
- 4%
|
- 7%
|
- 10%
|
| Heaviness
other than chest
or neck |
1%
|
1%
|
2%
|
5%
|
| Pain-
location specified |
1%
|
2%
|
2%
|
3%
|
| Other-
Pressure/ tightness / heaviness |
0%
|
2%
|
2%
|
2%
|
| DIGESTIVE
|
8%
|
11%
|
16%
|
14%
|
| Dry
mouth |
2%
|
5%
|
3%
|
3%
|
| Dyspepsia
|
1%
|
3%
|
2%
|
1%
|
| Dysphagia
|
0%
|
0%
|
0%
|
2%
|
| Nausea
|
4%
|
4%
|
9%
|
6%
|
| NEUROLOGICAL
|
10%
|
11%
|
17%
|
21%
|
| Dizziness
|
4%
|
6%
|
8%
|
10%
|
| Somnolence
|
3%
|
5%
|
6%
|
8%
|
| Vertigo
|
0%
|
0%
|
0%
|
2%
|
| OTHER
|
| Asthenia
|
3%
|
5%
|
3%
|
9%
|
| Palpitations
|
1%
|
0%
|
<1%
|
2%
|
| Myalgia
|
<1%
|
1%
|
1%
|
2%
|
| Myasthenia
|
<1%
|
0%
|
1%
|
2%
|
| Sweating
|
1%
|
0%
|
2%
|
3%
|
ZOMIG is generally well tolerated. Across all doses, most adverse
reactions were mild and transient
and did not lead to long-lasting
effects. The incidence of adverse events in controlled clinical
trials was not affected by gender, weight, or age
of the patients; use of prophylactic
medications; or presence of aura. There were insufficient data to
assess the impact of race
on the incidence of adverse events.
Other Events
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 ZOMIG
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 who used ZOMIG (n=4,027) and reported an event divided
by the total number of
patients exposed to ZOMIG. 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: infrequent
adverse events are those occurring in 1/100 to 1/1,000 patients
and rare adverse events are those occurring in fewer than 1/1,000
patients.
Atypical sensation: Infrequent was hyperesthesia
General: Infrequent were allergy
reaction, chills, facial
edema, fever, malaise
and photosensitivity.
Cardiovascular: Infrequent were arrhythmias, hypertension
and syncope. Rare were bradycardia,
extrasystoles, postural
hypotension, QT prolongation, tachycardia
and thrombophlebitis.
Digestive: Infrequent were increased appetite, tongue
edema, esophagitis,
gastroenteritis,
liver function
abnormality and
thirst. Rare were anorexia,
constipation, gastritis,
hematemesis, pancreatitis,
melena and ulcer.
Hemic: Infrequent was ecchymosis. Rare were cyanosis,
thrombocytopenia, eosinophilia
and leukopenia.
Metabolic: Infrequent was edema. Rare were hyperglycemia
and alkaline phosphatase
increased.
Musculoskeletal: Infrequent were back
pain, leg
cramps and tenosynovitis. Rare were arthritis,
tetany and twitching.
Neurological: Infrequent were agitation,
anxiety, depression,
emotional lability
and insomnia; Rare were akathesia, amnesia,
apathy, ataxia, dystonia,
euphoria, hallucinations,
cerebral ischemia,
hyperkinesia, hypotonia, hypertonia
and irritability.
Respiratory: Infrequent were bronchitis,
bronchospasm, epistaxis, hiccup,
laryngitis and yawn.
Rare were apnea and voice
alteration.
Skin: Infrequent were pruritus,
rash and urticaria.
Special Senses: Infrequent were dry eye,
eye pain,
hyperacusis, ear pain,
parosmia, and tinnitus.
Rare were diplopia
and lacrimation.
Urogenital: Infrequent were hematuria,
cystitis, polyuria,
urinary frequency, urinary
urgency. Rare were miscarriage
and dysmenorrhea.
DRUG ABUSE AND DEPENDENCE
The abuse potential
of ZOMIG has not been assessed in clinical
trials.
DRUG INTERACTIONS
All drug interaction studies
were performed in healthy
volunteers using a single 10 mg
dose of zolmitriptan and
a single dose of the other
drug except where otherwise noted.
Fluoxetine: The pharmacokinetics
of zolmitriptan as well as its effect
on blood pressure
were unaffected by 4 weeks of pretreatment with oral
fluoxetine (20 mg/day).
MAO Inhibitors: Following one week of administration
of 150 mg bid moclobemide,
a specific MAO-A inhibitor,
there was an increase of about 25% in both Cmax and AUC
for zolmitriptan and a 3-fold increase in the Cmax and
AUC of the active N-desmethyl
metabolite of zolmitriptan (see CONTRAINDICATIONS
and PRECAUTIONS).
Selegiline, a selective MAO-B inhibitor,
at a dose of 10 mg/day
for 1 week, had no effect
on the pharmacokinetics
of zolmitriptan and its metabolite.
Propranolol: Cmax and AUC
of zolmitriptan increased 1.5-fold after one week of dosing with
propranolol (160 mg/day). Cmax and AUC
of the N-desmethyl metabolite
were reduced by 30% and 15%, respectively. There were no
interactive effects on blood
pressure or pulse
rate following administration
of propranolol with zolmitriptan.
Acetaminophen: A single 1 g dose
of acetaminophen
does not alter the pharmacokinetics
of zolmitriptan and its N-desmethyl metabolite. However, zolmitriptan
delayed the Tmax of acetaminophen
by one hour.
Metoclopramide: A single 10 mg
dose of metoclopramide
had no effect
on the pharmacokinetics
of zolmitriptan or its metabolites.
Oral Contraceptives: Retrospective analysis
of pharmacokinetic data across studies indicated that mean
plasma concentrations
of zolmitriptan were generally higher in females taking oral
contraceptives compared to those not taking oral
contraceptives. Mean Cmax and AUC
of zolmitriptan were found to be higher by 30% and 50%, respectively,
and Tmax was delayed by one-half hour in females taking
oral contraceptives. The
effect of zolmitriptan on the pharmacokinetics
of oral contraceptives
has not been studied.
Cimetidine: Following the administration
of cimetidine, the half life
and AUC of a 5 mg
dose of zolmitriptan and
its active metabolite were approximately doubled (see PRECAUTIONS).
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 zolmitriptan within
24 hours of each other should be avoided (see CONTRAINDICATIONS).
MAO-A inhibitors increase the systemic
exposure of zolmitriptan.
Therefore, the use of zolmitriptan in patients receiving MAO-A inhibitors
is contraindicated (see CLINICAL PHARMACOLOGY
and CONTRAINDICATIONS).
Concomitant use of other 5-HT1B/1D agonists within 24
hours of ZOMIG treatment
is not recommended. (see CONTRAINDICATIONS).
Following administration
of cimetidine, the half life
and AUC of zolmitriptan
and its active metabolites were approximately doubled (see CLINICAL
PHARMACOLOGY).
Selective serotonin
reuptake inhibitors (SSRIs) (e.g., fluoxetine, fluvoxamine, paroxetine,
sertraline) have been reported, rarely, to cause
weakness, hyperreflexia, and incoordination
when coadministered with 5HT1 agonists. If concomitant
treatment with zolmitriptan
and an SSRI is clinically warranted, appropriate
observation of the patient
is advised.
Drug/Laboratory Test Interactions
Zolmitriptan is not known to interfere with commonly employed clinical
laboratory tests.
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