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
Lopid Side Effects, and Drug Interactions - Gemfibrozil
Lopid Side Effects, and Drug Interactions - Gemfibrozil
SIDE EFFECTS
In the double-blind controlled phase
of the primary prevention
component of the Helsinki Heart Study, 2046 patients received gemfibrozil
for up to 5 years. In that
study, the following adverse reactions were statistically more frequent
in subjects in the gemfibrozil
group (TABLE 4):
| TABLE 4 |
| |
Gemfibrozil |
Placebo |
| |
(N = 2046) |
(N = 2035) |
| |
Frequency in percent
of subjects |
| Gastrointestinal reactions |
34.2 |
23.8 |
| Dyspepsia |
19.6 |
11.9 |
| Abdominal pain |
9.8 |
5.6 |
Acute appendicitis
(histologically confirmed in most cases
where data were available) |
1.2 |
0.6 |
| Atrial fibrillation |
0.7 |
0.1 |
| Adverse events reported by more
than 1% subjects, but without a significant
difference between groups: |
| Diarrhea |
7.2 |
6.5 |
| Fatigue |
3.8 |
3.5 |
| Nausea/Vomiting |
2.5 |
2.1 |
| Eczema |
1.9 |
1.2 |
| Rash |
1.7 |
1.3 |
| Vertigo |
1.5 |
1.3 |
| Constipation |
1.4 |
1.3 |
| Headache |
1.2 |
1.1 |
Gallbladder surgery was performed in 0.9% of gemfibrozil
and 0.5% of placebo
subjects in the primary prevention
component, a 64% excess, which is not statistically different from
the excess of gallbladder surgery observed in the clofibrate
compared to the placebo
group of the WHO study.
Gallbladder surgery was also performed more frequently in the gemfibrozil
group compared to placebo
(1.9% vs 0.3%, p=0.07) in the secondary prevention component. A
statistically significant
increase in appendectomy in the gemfibrozil
group was seen also in
the secondary prevention
component (6 on gemfibrozil
vs 0 on placebo, p=0.014).
Nervous system and special
senses adverse reactions were more common in the gemfibrozil
group. These included hypesthesia, paresthesias, and taste perversion.
Other adverse reactions that were more common among gemfibrozil
treatment group subjects
but where a causal relationship was not established include cataracts,
peripheral vascular
disease, and intracerebral
hemorrhage.
From other studies it seems probable that gemfibrozil
is causally related to the occurrence of MUSCULOSKELETAL SYMPTOMS
(see WARNINGS), and to ABNORMAL
LIVER FUNCTION TESTS and HEMATOLOGIC CHANGES (see PRECAUTIONS).
Reports of viral and
bacterial infections (common cold, cough, urinary tract infections)
were more common in gemfibrozil
treated patients in other controlled clinical
trials of 805 patients. Additional adverse reactions that have been
reported for gemfibrozil
are listed below by system
(TABLE 5). These are categorized according to whether a causal relationship
to treatment with gemfibrozil
is probable or not established:
| TABLE 5 |
| |
|
CAUSAL RELATIONSHIP
|
| |
PROBABLE
|
NOT ESTABLISHED
|
| General |
|
|
| Cardiac |
|
|
| Gastrointestinal |
|
|
| |
|
|
| |
|
|
| Central Nervous System |
| |
|
|
| |
|
|
| |
|
|
| |
|
|
| |
|
|
| |
|
|
| |
|
|
| Eye |
|
|
| Genitourinary |
|
|
| |
|
|
| |
|
|
| Musculoskeletal |
|
|
| |
|
|
| |
|
|
| |
|
|
| |
|
|
| |
|
|
| |
|
|
| Clinical Laboratory |
| |
|
|
| |
|
|
| |
|
|
| |
|
|
| |
|
|
| |
|
|
| |
|
|
| |
|
|
| Hematopoietic |
|
|
| |
|
|
| |
|
|
| |
|
|
| Immunologic |
|
|
| |
|
|
| |
|
|
| Integumentary |
|
|
| |
|
|
| |
|
|
| |
|
|
DRUG INTERACTIONS
HMG-CoA reductase inhibitors: The risk of myopathy and
rhabdomyolysis is increased with combined gemfibrozil and HMG-CoA reductase
inhibitor therapy (see CONTRAINDICATIONS). Myopathy or rhabdomyolysis with or
without acute renal failure have been reported as early as three weeks after initiation of
combined therapy or after several months (refs. 8, 9, 10, 11). (See WARNINGS.) There
is no assurance that periodic monitoring of creatine kinase will prevent the occurrence of
severe myopathy and kidney damage.
Anticoagulants: CAUTION SHOULD BE EXERCISED WHEN ANTICOAGULANTS
ARE GIVEN IN CONJUNCTION WITH LOPID. THE DOSAGE OF
THE ANTICOAGULANT SHOULD BE REDUCED TO MAINTAIN THE
PROTHROMBIN TIME AT THE DESIRED LEVEL TO PREVENT BLEEDING
COMPLICATIONS. FREQUENT PROTHROMBIN DETERMINATIONS ARE
ADVISABLE UNTIL IT HAS BEEN DEFINITELY DETERMINED THAT THE
PROTHROMBIN LEVEL HAS STABILIZED.
Repaglinide: In vivo data from a study that evaluated the co-administration of
gemfibrozil with repaglinide in healthy subjects resulted in a significant increase in
repaglinide blood levels. Patients taking repaglinide should not start taking gemfibrozil;
patients taking gemfibrozil should not start taking repaglinide. Concomitant use may
result in enhanced and prolonged blood glucose-lowering effects of repaglinide. Caution
should be used in patients already on repaglinide and gemfibrozil – blood glucose levels
should be monitored and repaglinide dose adjustment may be needed. Rare post
marketing events of serious hypoglycemia have been reported in patients taking
repaglinide and gemfibrozil together. In this same study, gemfibrozil and itraconazole
had a synergistic metabolic inhibitory effect on repaglinide. Therefore, patients taking
repaglinide and gemfibrozil should not take itraconazole.
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