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
Baycol Side Effects, and Drug Interactions - Cerivastatin
Baycol Side Effects, and Drug Interactions - Cerivastatin
SIDE EFFECTS
In the U. S. placebo-controlled clinical
studies, discontinuations due to adverse events occurred in 3% of
cerivastatin sodium treated
patients and in 3% of patients treated with placebo. Adverse reactions
have usually been mild and transient. Cerivastatin sodium
has been evaluated for adverse events in more than 3,000 patients
and is generally well-tolerated.
Clinical Adverse Experiences: Adverse experiences occurring
with a frequency 22%
for marketed doses of cerivastatin sodium,
regardless of causality assessment, in U. S. placebo-controlled
clinical studies, are
shown in the Table 3 below:
Table 3
Adverse Experiences Occurring In
22% of Patients in U. S. Placebo-Controlled Clinical Studies
Adverse Event Body as a Whole
|
Adverse Event
|
BAY COL
(n= 552)
|
Placebo
(n = 247)
|
| Body as a Whole
|
| Headache |
11.8%
|
12.6%
|
| Accidental Injury
|
7.1 %
|
6.9%
|
| Flu Syndrome |
6.3%
|
8.1%
|
| Back Pain |
4.0%
|
6.1%
|
| Abdominal Pain |
3.4%
|
3.6%
|
| Asthenia |
3.4%
|
2.8%
|
| Chest Pain |
2.9%
|
2.8%
|
| Leg Pain |
2.0%
|
1.2%
|
| Cardiovascular |
| Peripheral Edema
|
2.0%
|
1.2%
|
| Digestive |
| Dyspepsia |
5.6%
|
4 .9 %
|
| Diarrhea |
4.0%
|
3 .6 %
|
| Flatulence |
3.4%
|
3 .6 %
|
| Nausea |
2.7%
|
3 .2 %
|
| Constipation |
1.8%
|
2 .0 %
|
| Surgery |
1 .4 %
|
3 .6 %
|
| Musculoskeletal
|
| Arthralgia |
6 .7 %
|
4 .5 %
|
| Myalgia |
2 .7 %
|
1.20%
|
| Nervous |
| Dizziness |
2 .5 %
|
3.6%
|
| Insomnia |
2 .2 %
|
1.2%
|
| Respiratory |
| Rhinitis |
13.2%
|
12.1%
|
| Pharyngitis |
12.0%
|
17.0%
|
| Sinusitis |
6.9%
|
5.7%
|
| Cough Increased |
2.7%
|
2.0%
|
| Skin and Appendages
|
| Rash |
3.4%
|
5.3%
|
| Urogenital |
| Urinary Tract Infection
|
1.60%
|
2.4%
|
The following effects have been reported with drugs in this class.
Skeletal: myopathy,
muscle cramps, rhabdomyolysis,
arthralgias, myalgia.
Neurological: dysfunction
of certain cranial nerves
(including alteration of taste, impairment
of extra- ocular movement,
facial paresis), tremor,
dizziness, memory
loss, vertigo, paresthesia,
peripheral neuropathy,
peripheral nerve palsy,
anxiety, insomnia,
depression, psychic
disturbances.
Hypersensitivity Reactions: An
apparent hypersensitivity
syndrome has been reported rarely that included one or more of the
following features: anaphylaxis,
angioedema, lupus
erythematosus-like syndrome,
,polymyalgia rheumatica, dermatomyositis, vasculitis,
purpura, thrombocytopenia,
leukopenia, hemolytic anemia,
positive A.A.
ESR increase, eosinophilia,
arthritis, arthralgia, urticaria,
asthenia, photosensitivity,
fever, chills, flushing,
malaise, dyspnea, toxic
epidermal necrolysis,
erythema multiforme,
including Stevens-Johnson syndrome.
Gastrointestinal: pancreatitis,
hepatitis, including
chronic active hepatitis,
cholestatic jaundice,
fatty change in liver,
and rarely, cirrhosis,
fulminant hepatic
necrosis, and hepatoma:
anorexia, vomiting.
Skin: alopecia,
pruritus. A variety
of skin changes, e.g.,
nodules, discoloration, dryness of skin/mucous membranes, changes
to hair/ nails, have been reported.
Reproductive: gynecomastia,
loss of libido,
erectile dysfunction
Eye: progression
of cataracts (lens opacities), ophthalmoplegia. Laboratory Abnormalities:
elevated transaminases, alkaline
phosphatase, y- glutamyl transpeptidase, and bilirubin; thyroid
function abnormalities.
Concomitant Therapy: In
studies where cerivastatin sodium
has been administered concomitantly with cholestyramine, no
adverse reactions unique to this combination or in addition
to those previously reported for this class
of drugs were reported. Myopathy and rhabdomyolysis
(with or without acute
renal failure) have been
reported when another HMG-CoA reductase inhibitor
was used in combination with immunosuppressive drugs, fibric acid
derivatives, erythromycin, azole antifungals or lipid-lowering doses
of nicotinic acid.
Concomitant therapy
with HMG-CoA reductase
inhibitors and these agents is generally not recommended (See WARNINGS:
Skeletal Muscle).
DRUG INTERACTIONS
Immunosuppressive Drugs, Fibric Acid Derivatives, Niacin (Nicotinic
Acid, Erythromycin, Azole Antifungals: (See WARNINGS)
Skeletal Muscle.
ANTACID (Magnesium-Aluminum Hydroxide): Cerivastatin
plasma concentrations were not affected by co-administration of
antacid.
CIMETlDINE: Cerivastatin plasma
concentrations were not affected by co-administration of cimetidine.
CHOLESTYRAMINE: The influence of the bile-acidsequestering
agent cholestyramine on the pharmacokinetits of cerivastatin sodium
was evaluated in 12 healthy
males in 2 separate randomized crossover
studies. In the first study, concomitant
administration
of 0.2 mg cerivastatin sodium
and 12 g cholestyramine resulted in decreases of more than 22% for
AUC and 40% for Cmax when compared to dosing cerivastatin
sodium alone. However, in the second study, administration
of 12 g cholestyramine 1 hour before the evening meal
and 0.3 mg cerivastatin sodium
approximately 4 hours after the same evening meal
resulted in a decrease in the cerivastatin AUC of less than 8%,
and a decrease in Cmax of about 30% when compared to
dosing cerivastatin sodium
alone. Therefore, it would be expected that a dosing schedule
of cerivastatin sodium
given at bedtime and cholestyramine given before the evening meal
would not result in a significant
decrease in the clinical
effect of cerivastatin
sodium.
DIGOXIN: Plasma digoxin
levels and digoxin clearance
at steady-state were not affected by co-administration of 0.2 mg
cerivastatin sodium. Cerivastatin plasma
concentrations were also not affected by co-administration of digoxin.
WARFARIN: Co- administration
of warfarin and cerivastatin to healthy
volunteers did not result in any changes in prothrombin
time or clotting factor
VII when compared to co-administration of warfarin and placebo.
The AUC and Cmax
of both the (R) and (S) isomers of warfarin were unaffected by concurrent
dosing of 0.3 mg cerivastatin
sodium. Co-administration of warfarin and cerivastatin did not alter
the pharmacokinetics of cerivastatin sodium.
ERYTHROMYCIN: In
hypercholesterolemic patients, steady-state cerivastatin AUC
and Cmax increased approximately 50% and 24% respectively after
10 days with co-administration of erythromycin, a known inhibitor
of cytochrome P450
3A4.
OTHER CONCOMITANT THERAPY: Although specific
interaction studies were not performed, in clinical
studies, cerivastatin sodium
was used concomitantly with angiotensin- converting enzyme
(ACE) inhibitors, betablockers, calcium-channel blockers, diuretics,
and nonsteroidal anti-inflammatory drugs (NSAIDs) without evidence
of clinically significant
adverse interactions.
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