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
Flumadine Side Effects, and Drug Interactions - Rimantadine
Flumadine Side Effects, and Drug Interactions - Rimantadine
SIDE EFFECTS
In 1,027 patients treated with rimantadine HCl in controlled clinical
trials at the recommended dose
of 200 mg daily, the most
frequently reported adverse events involved the gastrointestinal
and nervous systems.
Incidence > 1%: Adverse events reported most frequently
(1-3%) at the recommended dose
in controlled clinical
trials are shown in the table below (TABLE 1).
TABLE 1
|
|
Rimantadine |
Control |
| (n=1027) |
(n=986) |
|
Nervous System
|
|
Insomnia
|
2.1% |
0.9% |
|
Dizziness
|
1.9% |
1.1% |
|
Headache
|
1.4% |
1.3% |
|
Nervousness
|
1.3% |
0.6% |
|
Fatigue
|
1.0% |
0.9% |
|
Gastrointestinal System
|
|
Nausea
|
2.8% |
1.6% |
|
Vomiting
|
1.7% |
0.6% |
|
Anorexia
|
1.6% |
0.8% |
|
Dry Mouth
|
1.5% |
0.6% |
|
Abdominal Pain
|
1.4% |
0.8% |
|
Body as a Whole
|
|
Asthenia
|
1.4% |
0.5% |
Less frequent adverse events (0.3 to 1%) at the recommended
dose in controlled clinical
trials were:
Gastrointestinal System: diarrhea,
dyspepsia
Nervous System: impairment
of concentration,
ataxia, somnolence, agitation,
depression
Skin and Appendages: rash
Hearing and Vestibular: tinnitus
Respiratory: dyspepsia
Additional adverse events (less than 0.3%) reported at recommended
doses in controlled clinical
trials were:
Nervous System: gait
abnormality, euphoria,
hyperkinesia, tremor,
hallucination, confusion,
convulsions
Respiratory: bronchospasm,
cough
Cardiovascular: pallor,
palpitation, hypertension,
cerebrovascular disorder, cardiac
failure, pedal edema,
heart block, tachycardia,
syncope
Reproduction: non-pleural lactation
Special Senses: taste
loss/chance, parosmia
Rates of adverse events, particularly those involving the gastrointestinal
and nervous systems,
increased significantly in controlled studies using higher than
recommended dose of rimantadine
HCl. In most cases, symptoms
resolved rapidly with discontinuation of treatment. In
addition to the adverse
events reported above, the following were also reported at higher
than recommended doses: increased lacrimation,
increased micturition
frequency, fever, rigors, agitation,
constipation, diaphoresis,
dysphagia, stomatitis,
hypesthesia and eye pain.
Adverse Reactions in Trials of Rimantadine and Amantadine:
In a six-week prophylaxis
study of 436 healthy
adults comparing rimantadine with amantadine and placebo,
the following adverse reactions were reported with an incidence
> 1% (TABLE 2).
TABLE 2
|
|
Rimantadine |
Placebo |
Amantadine |
| 200 mg/day |
200 mg/day |
200 mg/day |
| (n=145) |
(n=143) |
(n=148) |
|
Nervous System
|
|
Insomnia
|
3.4% |
0.7% |
7.0% |
|
Nervousness
|
2.1% |
0.7% |
2.8% |
|
Impaired Concentration
|
2.1% |
1.4% |
2.1% |
|
Dizziness
|
0.7% |
0.0% |
2.1% |
|
Depression
|
0.7% |
0.7% |
3.5% |
|
Total % of subjects with adverse reactions
|
6.9% |
4.1% |
14.7% |
|
Total % of subjects withdrawn due to adverse
reactions
|
6.9% |
3.4% |
14.0% |
Usage In The Elderly
In general, the incidence
of adverse events in controlled clinical
trials in the elderly was higher in both the rimantadine HCl and
placebo-treated groups compared to younger adults and children.
Most of these patients had other chronic
illnesses. In a placebo-controlled
study of 83 nursing home patients with influenza,
10.6% of those treated with rimantadine HCl compared with 8.3% in
the placebo group
experienced events related to the central nervous
system. The profile
of these events was similar to that for the most frequent adverse
events reported in other controlled trials (see TABLE 2).
Pooled data from controlled studies of prophylaxis
and treatment of influenza
with rimantadine HCl in persons over 65 years of age
showed an increase in adverse clinical
events associated with the recommended dose of rimantadine HCl (100
mg twice a day) compared
to controls as follows: central and peripheral
nervous systems, 12.5%
for rimantadine HCl versus 8.7% for control
patients; gastrointestinal
systems, 17.0% for rimantadine HCl versus 11.3% for controls.
DRUG INTERACTIONS
Cimetidine: The effects of chronic
cimetidine use on
the metabolism of rimantadine are not known. When a single 100 mg
dose of rimantadine HCl
was administered one hour after the initiation of Cimetidine (300
mg four times a day), the apparent
total rimantadine clearance
of this single dose in normal
healthy adults was reduced
by 18% (compared to the apparent total rimantadine clearance
in the same subjects in the absence
of cimetidine).
Acetaminophen: Rimantadine HCl, 100 mg, was given twice
daily for 13 days to 12 healthy
volunteers. On day 11, acetaminophen
(650 mg four times daily) was started and continued for 8 days.
The pharmacokinetics of rimantadine were assessed on days 11 and
13. Coadministration with acetaminophen reduced the peak concentration
and AUC values for rimantadine
by approximately 11%.
Aspirin: Rimantadine HCl, 100 mg, was given twice daily
fro 13 days to 12 healthy
volunteers. On day 11, aspirin
(650 mg, four times daily) was started and continued for 8 days.
The pharmacokinetics
of rimantadine were assessed on days 11 and 13. Peak plasma
concentrations and AUC of
rimantadine were reduced approximately 10% in the presence of aspirin.
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