Approved Drug Label (PDF)
4
Contraindications
Additions and/or
revisions underlined:
·
Acute liver failure or
decompensated cirrhosis [see Warnings and
Precautions (5.3)].
·
Hypersensitivity to
amlodipine, atorvastatin or any excipients in CADUET. Hypersensitivity
reactions, including anaphylaxis, angioneurotic edema, erythema multiforme,
Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported [see Adverse Reactions (6.2)].
5
Warnings and Precautions
5.3 Hepatic Dysfunction
Additions
and/or revisions underlined:
Increases
in serum transaminases have been reported with use of atorvastatin [see Adverse Reactions (6.1)]. In most
cases, these changes appeared soon after initiation, were transient, were not
accompanied by symptoms, and resolved or improved on continued therapy or
after a brief interruption in therapy. Persistent increases to more than
three times the ULN in serum transaminases have occurred in approximately
0.7% of patients receiving atorvastatin in clinical trials.
There
have been rare postmarketing reports of fatal and non-fatal hepatic failure in
patients taking statins, including atorvastatin.
Patients
who consume substantial quantities of alcohol and/or have a history of liver
disease may be at increased risk for hepatic injury [see Use in Specific Populations (8.7)].
Consider
liver enzyme testing before atorvastatin initiation and when clinically
indicated thereafter. Atorvastatin is contraindicated in patients with acute
liver failure or decompensated cirrhosis [see
Contraindications (4)]. If serious hepatic injury with clinical
symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue
atorvastatin.
5.6 Increases in HbA1c and Fasting Serum Glucose Levels
Additions
and/or revisions underlined:
Increases
in HbA1c and fasting serum glucose levels have been reported with statins,
including atorvastatin.Optimize lifestyle measures, including regular
exercise, maintaining a healthy body weight, and making healthy food choices.
5.7 Increased Risk of Hemorrhagic Stroke in Patients on Atorvastatin 80 mg with Recent Hemorrhagic Stroke
Additions
and/or revisions underlined:
In
a post-hoc analysis of the Stroke Prevention by Aggressive Reduction in
Cholesterol Levels (SPARCL) trial where 2365 adult patients, without CHD
who had a stroke or Transient Ischemic aAttack (TIA) within the
preceding 6 months, were treated with atorvastatin 80 mg, a higher
incidence of hemorrhagic stroke was seen in the atorvastatin 80 mg group
compared to placebo (55, 2.3% atorvastatin vs. 33, 1.4% placebo; HR: 1.68, 95%
CI: 1.09, 2.59; p=0.0168). The incidence of fatal hemorrhagic stroke was
similar across treatment groups (17 vs. 18 for the atorvastatin and placebo
groups, respectively). The incidence of non-fatal hemorrhagic stroke was
significantly higher in the atorvastatin group (38, 1.6%) as compared to the
placebo group (16, 0.7%).
Some
baseline characteristics, including hemorrhagic and lacunar stroke on study
entry, were associated with a higher incidence of hemorrhagic stroke in the
atorvastatin group [see Adverse Reactions
(6.1)]. Consider the risk/benefit of use of atorvastatin 80 mg in patients
with recent hemorrhagic stroke.
6
Adverse Reactions
Additions and/or
revisions underlined:
The following important adverse reactions are
described below and elsewhere in the labeling:
Myopathy and Rhabdomyolysis [see Warnings and Precautions
(5.1)]
Immune-Mediated Necrotizing
Myopathy [see Warnings and Precautions (5.2)]
Hepatic Dysfunction [see Warnings and Precautions (5.3)]
Increases in HbA1c and
Fasting Serum Glucose Levels [see Warnings and Precautions (5.6)]
6.1 Clinical Trials
Experience
Extensive additions
and/or revisions; please refer to label.
6.2 Postmarketing
Experience
Additions
and/or revisions underlined:
…
Atorvastatin
Gastrointestinal
disorders: pancreatitis
General disorders: fatigue
Hepatobiliary Disorders: fatal and non-fatal hepatic failure
Immune system
disorders: anaphylaxis
Injury: tendon rupture
Musculoskeletal
and connective tissue disorders: rhabdomyolysis,
myositis.
There
have been rare reports of immune-mediated necrotizing myopathy associated with
statin use.
Nervous system
disorders: dizziness,
peripheral neuropathy.
There
have been rare reports of cognitive impairment (e.g., memory loss,
forgetfulness, amnesia, memory impairment, confusion) associated with the use
of all statins.
Cognitive impairment was generally nonserious, and reversible upon statin discontinuation, with
variable times to symptom onset (1 day to years) and symptom resolution (median
of 3 weeks).
Psychiatric disorders: depression
Respiratory disorders: interstitial lung disease
Skin and subcutaneous tissue disorders: angioneurotic
edema, bullous rashes (including erythema multiforme, Stevens-Johnson syndrome,
and toxic epidermal necrolysis)
8
Use in Specific Populations
8.4 Pediatric Use
Additions
and/or revisions underlined:
…
Atorvastatin
…based on a
double-blind,
placebo-controlled clinical trial in 187 pediatric patients 10 years of age and
older with HeFH. In this limited controlled trial, there was no significant
effect on growth or sexual maturation in the boys or girls, or on
menstrual cycle length in girls.
The
safety and effectiveness of atorvastatin as an adjunct to other LDL-C-lowering
therapies to reduce LDL-C have been established in pediatric patients
10 years of age and older with HoFH. Use of CADUET for this indication is based
on a trial without a concurrent control group in 8 pediatric patients 10 years
of age and older with HoFH [see Clinical
Studies (14)].
The
safety and effectiveness of atorvastatin have not been established in pediatric
patients younger than 10 years of age with HeFH or HoFH, or in pediatric
patients with other types of hyperlipidemia (other than HeFH or HoFH).
8.5 Geriatric Use
Additions
and/or revisions underlined:
…
Atorvastatin
Of
the total number of atorvastatin-treated patients in clinical
trials, 15813 (40%) were greater than or equal to 65 years old and 2800 (7%)
were greater than or equal to 75 years old. No overall differences in safety or
effectiveness were observed between these patients and younger patients.
Advanced
age (greater than or equal to 65 years) is a risk factor for atorvastatin
-associated myopathy and rhabdomyolysis.
Dose
selection for an elderly patient should be cautious, recognizing the greater
frequency of decreased hepatic, renal, or cardiac function, and of concomitant
disease or
other drug therapy and the higher risk of myopathy. Monitor geriatric
patients receiving CADUET for the increased risk of myopathy [see Warnings and Precautions (5.1) and
Clinical Pharmacology (12.3)].
8.6 Renal Impairment
New
subsection added:
Renal
impairment is a risk factor for myopathy and rhabdomyolysis. Monitor all
patients with renal impairment for development of myopathy. Renal impairment
does not affect the plasma concentrations of atorvastatin, therefore there is
no dosage adjustment in patients with renal impairment [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)].
8.7 Hepatic Impairment
Additions
and/or revisions underlined:
In
patients with chronic alcoholic liver disease, plasma concentrations of
atorvastatin are markedly increased. Cmax and AUC are each 4-fold greater in
patients with Childs-Pugh A disease. Cmax and AUC are approximately 16-fold
and 11-fold increased, respectively, in patients with Childs-Pugh B disease.
CADUET is contraindicated in patients with acute liver failure or
decompensated cirrhosis [see
Contraindications (4)].
8.1 Pregnancy
Additions and/or revisions underlined:
Atorvastatin
Discontinue atorvastatin when pregnancy is
recognized. Alternatively, consider the ongoing therapeutic needs of the
individual patient. Atorvastatin decreases synthesis of cholesterol
and possibly other biologically active substances derived from cholesterol; therefore,
atorvastatin may cause fetal harm when administered to pregnant patients
based on the mechanism of action [see
Clinical Pharmacology (12.1)]. In addition, treatment of hyperlipidemia is
not generally necessary during pregnancy.
Atherosclerosis is a chronic process and the
discontinuation of lipid-lowering drugs during pregnancy should have little
impact on the outcome of long-term therapy of primary hyperlipidemia for most
patients.
Available data from case series and prospective and
retrospective observational cohort studies over decades of use with statins in
pregnant women have not identified a
drug-associated risk of major congenital malformations. Published data from
prospective and retrospective observational cohort studies with atorvastatin
use in pregnant women are insufficient to determine if there is a
drug-associated risk of miscarriage (see
Data). In animal reproduction studies, no adverse
developmental effects were observed in pregnant rats or rabbits orally
administered atorvastatin at doses that resulted in up to 30 and 20
times, respectively, the human exposure at the maximum recommended human
dose (MRHD) of 80 mg, based on body surface area (mg/m2). In
rats administered atorvastatin during gestation and lactation, decreased
postnatal growth and development delay were observed at doses greater
than or equal to 6 times the MRHD (see
Data).
…
Data
Human Data
Atorvastatin
A Medicaid cohort linkage study of 1152
statin-exposed pregnant women compared to 886,996 controls did not find a
significant teratogenic effect from maternal
use of statins in the first trimester of pregnancy, after adjusting for
potential confounders– including maternal age, diabetes mellitus, hypertension,
obesity, and alcohol and tobacco use – using propensity score-based
methods. The relative risk of congenital malformations between the group
with statin use and the group with no statin use in the first trimester was 1.07
(95% confidence interval 0.85 to 1.37) after controlling for confounders,
particularly pre-existing diabetes mellitus. There were also no statistically
significant increases in any of the organ-specific malformations assessed after
accounting for confounders. In the majority of pregnancies, statin
treatment was initiated prior to pregnancy and was discontinued at some point
in the first trimester when pregnancy was identified. Study limitations
include reliance on physician coding to define the presence of a malformation,
lack of control for certain confounders such as body mass index, use of
prescription dispensing as verification for the use of a statin, and lack of
information on non-live births.
Animal Data
Atorvastatin
…
Atorvastatin crosses the rat placenta and reaches a
level in fetal liver equivalent to that of maternal plasma.
…
8.2 Lactation
Additions and/or revisions underlined:
Atorvastatin
There is no information about the presence of
atorvastatin in human milk, the effects of the drug on the breastfed infant
or the effects of the drug on milk production. However, it has been
shown that another drug in this class passes into human milk. Studies in
rats have shown that atorvastatin and/or its metabolites are present in
the breast milk of lactating rats. When a drug is present in animal
milk, it is likely that the drug will be present in human milk (see Data). Statins, including
atorvastatin, decrease cholesterol synthesis and possibly the synthesis of
other biologically active substances derived from cholesterol and may cause
harm to the breastfed infant.
Because of the potential for serious adverse
reactions in a breastfed infant, based on the mechanism of action, advise
patients that breastfeeding is not recommended during treatment with CADUET [see Use in Specific Populations (8.1)
and Clinical Pharmacology (12.1)].
Data
Following a single oral administration of 10 mg/kg
of radioactive atorvastatin to lactating rats, the concentration of total radioactivity
was determined. Atorvastatin and/or its metabolites were measured in the breast
milk and pup plasma at a 2:1 ratio (milk:plasma).
…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
Additions
and/or revisions underlined:
Advise
the patient to read the FDA-approved patient labeling (Patient Information).
Myopathy and
Rhabdomyolysis
Advise
patients that CADUET may cause myopathy and rhabdomyolysis. Inform patients
that the risk is also increased when taking certain types of medication or
consuming large quantities of grapefruit juice and they should discuss all
medication, both prescription and over the counter, with their healthcare
provider. Instruct patients to promptly report any unexplained muscle pain,
tenderness or weakness particularly if accompanied by malaise or fever [see Warnings and Precautions (5.1), Drug
Interactions (7.1)].
Hepatic
Dysfunction
Inform
patients that CADUET may cause liver enzyme elevations and possibly liver
failure.
Advise patients to promptly report fatigue, anorexia, right upper abdominal
discomfort, dark urine, or jaundice [see
Warnings and Precautions (5.3)].
Increases in HbA1c
and Fasting Serum Glucose Levels
Inform
patients that increases in HbA1c and fasting serum glucose levels may occur
with CADUET. Encourage patients to optimize lifestyle measures, including
regular exercise, maintaining a healthy body weight, and making healthy food
choices [see Warnings and Precautions
(5.6)].
Pregnancy
Advise
pregnant patients and patients who can become pregnant of the
potential risk to a fetus. Advise patients to inform their healthcare provider
of a known or suspected pregnancy to discuss if CADUET should be
discontinued [see Use in Specific
Populations (8.1)].
Lactation
Advise
patients that breastfeeding is not recommended during treatment
with CADUET [see Use in Specific
Populations (8.2)]. This product’s labeling may have been updated. For the
most recent prescribing information, please visit www.pfizer.com.
PATIENT
INFORMATION
Extensive additions and/or revisions, please refer
to label.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Myopathy
and Rhabdomyolysis
(Additions and/or revisions underlined)
CADUET may cause myopathy
(muscle pain, tenderness, or weakness with creatine kinase (CK) above
ten times the upper limit of normal) and rhabdomyolysis (with or
without acute renal failure secondary to myoglobinuria). Rare fatalities have
occurred as a result of rhabdomyolysis with statin use, including CADUET.
Risk
Factors for Myopathy
Risk
factors for myopathy include age 65 years or greater, uncontrolled
hypothyroidism, renal impairment, concomitant use with certain other
drugs, and higher CADUET dosage [see
Drug Interactions (7.3)].
Steps to Prevent or Reduce the Risk
of Myopathy and Rhabdomyolysis
CADUET exposure may be increased by drug interactions due to inhibition
of cytochrome P450 enzyme 3A4 (CYP3A4) and/or transporters (e.g., breast cancer
resistant protein [BCRP], organic anion-transporting polypeptide
[OATP1B1/OATP1B3] and P-glycoprotein [P-gp]), resulting in an increased risk of
myopathy and rhabdomyolysis. Concomitant use of cyclosporine, gemfibrozil,
tipranavir plus ritonavir or glecaprevir plus pibrentasvir with CADUET is not
recommended. CADUET dosage modifications are recommended for patients taking
certain anti-viral, azole antifungals, or macrolide antibiotic medications [see Dosage and Administration (2)].
Cases of myopathy/rhabdomyolysis.
have been reported with atorvastatin co-administered with lipid modifying
doses (>1 gram/day) of niacin, fibrates, colchicine, and ledipasvir plus
sofosbuvir. Consider if the benefit of use of these products outweighs the
increased risk of myopathy and rhabdomyolysis [see Drug Interactions (7.3)].
Concomitant
intake of large quantities, more than 1.2 liters daily, of grapefruit juice is
not recommended in patients taking CADUET [see
Drug Interactions (7.3)].
Discontinue
CADUET if markedly elevated CK levels occur or myopathy is diagnosed or
suspected. Muscle symptoms and CK increases may resolve if CADUET is
discontinued. Temporarily discontinue CADUET in patients experiencing an acute
or serious condition at high risk of developing renal failure secondary to
rhabdomyolysis (e.g., sepsis; shock; severe hypovolemia; major surgery; trauma;
severe metabolic, endocrine, or electrolyte disorders; or uncontrolled
epilepsy).
Inform patients of the
risk of myopathy and rhabdomyolysis when starting or increasing the CADUET
dosage. Instruct patients to promptly report any unexplained muscle pain,
tenderness or weakness, particularly if accompanied by malaise or fever
5.2
Immune-Mediated Necrotizing Myopathy
(Additions and/or revisions underlined)
There have
been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune
myopathy, associated with statin use. IMNM is characterized by: proximal muscle
weakness and elevated serum creatine kinase, which persist despite
discontinuation of statin
treatment; positive anti-HMG
CoA reductase antibody; muscle biopsy showing
necrotizing myopathy; and improvement with immunosuppressive
agents. Additional neuromuscular and serologic testing may be necessary.
Treatment with immunosuppressive agents may be required. Consider risk of IMNM
carefully prior to initiation of a different statin. If therapy is initiated
with a different statin, monitor for signs and symptoms of IMNM.
7
Drug Interactions
7.3 Drug
Interactions that may Increase the Risk of Myopathy and Rhabdomyolysis with Atorvastatin
(Additions and/or revisions underlined; Newly added Table 3)
Atorvastatin
is a substrate of CYP3A4 and transporters (e.g., OATP1B1/1B3, P-gp, or BCRP).
Atorvastatin plasma levels can be significantly increased with concomitant
administration of inhibitors of CYP3A4 and transporters. Table 3 includes a
list of drugs that may increase exposure to atorvastatin and may increase the risk of myopathy and rhabdomyolysis when used
concomitantly and instructions for preventing or managing them [see Warnings and Precautions (5.1) and
Clinical Pharmacology (12.3)].
Table 3. Drug Interactions that may Increase the Risk
of Myopathy and Rhabdomyolysis with Atorvastatin
7.4 Drug
Interactions that may Decrease Exposure to Atorvastatin
(Additions and/or revisions underlined; Newly added Table 4)
Table 4 presents drug
interactions that may decrease exposure to atorvastatin and instructions for
preventing or managing them.
Table 4. Drug Interactions that may Decrease Exposure
to Atorvastatin
7.5
Atorvastatin Effects on Other Drugs
(Additions and/or revisions underlined; Newly added Table 5)
Table 5 presents
atorvastatin’s effect on other drugs and instructions for preventing or
managing them.
Table 5. Atorvastatin Effects on Other Drugs
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Myopathy and Rhabdomyolysis
(Additions and/or revisions are underlined)
Atorvastatin, like other statins,
occasionally causes myopathy, defined as muscle aches or muscle weakness in
conjunction with increases in creatine phosphokinase (CPK) values > 10 times
upper limit of normal [ULN]. The concomitant use of higher doses of
atorvastatin with certain drugs such as cyclosporine and strong cytochrome
P450 3A4 (CYP3A4) inhibitors (e.g., clarithromycin, itraconazole,
and HIV and HCV protease inhibitors) increases the risk of myopathy/rhabdomyolysis.
The risk of myopathy during
treatment with statins is increased with concurrent administration of the
drugs listed in Table 2. Physicians considering combined therapy of
CADUET with any of these drugs should carefully weigh the potential
benefits and risks and should carefully monitor patients for any signs or
symptoms of muscle pain, tenderness, or weakness, particularly during the
initial months of therapy and during any periods of upward dosage titration of
either drug. Lower starting and maintenance doses of atorvastatin should be
considered when taken concomitantly with the aforementioned drugs. Periodic
creatine phosphokinase (CPK) determinations may be considered in such
situations, but there is no assurance that such monitoring will prevent the
occurrence of severe myopathy.
7
Drug Interactions
7.2 Impact of Amlodipine on Other Drugs
(Additions and/or revisions are underlined)
Atorvastatin
The risk of myopathy during treatment with statins
is increased with concurrent administration of fibric acid derivatives,
lipid-modifying doses of niacin, cyclosporine, or strong CYP3A4 inhibitors
(e.g., clarithromycin, HIV and HCV protease inhibitors,
and itraconazole).
7.3 Strong Inhibitors of CYP3A4
(Additions and/or revisions
are underlined)
Combination
of Protease Inhibitors: Atorvastatin AUC was significantly increased with
concomitant administration of atorvastatin with several combinations of
protease inhibitors. In patients taking tipranavir plus ritonavir or glecaprevir
plus pibrentasvir, concomitant use of atorvastatin should be avoided. In
patients taking lopinavir plus ritonavir or simeprevir, use the lowest
necessary atorvastatin dose. In patients taking saquinavir plus
ritonavir, darunavir plus ritonavir, fosamprenavir, fosamprenavir plus
ritonavir, or elbasvir plus grazoprevir, the dose of atorvastatin should
not exceed 20 mg. In patients taking nelfinavir, the dose of atorvastatin
should not exceed 40 mg and close clinical monitoring is recommended.
7.5 Transporter Inhibitors
(Additions and/or revisions
are underlined)
Atorvastatin is a substrate of the hepatic
transporters. Atorvastatin-metabolites
are substrates of the OATP1B1 transporter.
Cyclosporine: Inhibitors of the OATP1B1 (e.g., cyclosporine) can
increase the bioavailability of atorvastatin. Atorvastatin AUC was
significantly increased with concomitant administration of atorvastatin 10 mg
and cyclosporine 5.2 mg/kg/day compared to that of atorvastatin alone. The co-administration of atorvastatin with
cyclosporine should be avoided.
Concomitant administration of glecaprevir and
pibrentasvir or elbasvir and grazoprevir may lead to increased plasma
concentrations of atorvastatin and an increased risk of myopathy.
Coadministration of glecaprevir and pibrentasvir
with atorvastatin increase plasma concentrations of atorvastatin by 8.3-fold
due in part to BCRP, OATP1B1/1B3, and CYP3A inhibition; therefore,
coadministration of atorvastatin in patients receiving concomitant medications
with products containing glecaprevir and pibrentasvir is not recommended.
Coadministration of elbasvir and grazoprevir with
atorvastatin increase plasma concentrations of atorvastatin by 1.9-fold due in
part to BCRP, OATP1B1/1B3, and CYP3A inhibition; therefore, the dose of
atorvastatin should not exceed 20 mg daily in patients receiving concomitant
medications with products containing elbasvir and grazoprevir.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATION
(Additions and/or revisions
are underlined)
Tell your doctor about all the medicines you take
including prescription and nonprescription medicines, vitamins, and herbal
supplements. CADUET and some other medicines can interact, causing serious side
effects. Especially tell your doctor if you take medicines for:
Approved Drug Label (PDF)
6
Adverse Reactions
6.1 Clinical Trials Experience
(additions
underlined)
…
Adverse
Reactions from Clinical Studies of Atorvastatin in Pediatric Patients
In a 26-week controlled study in boys and postmenarchal
girls with HeFH (ages 10 years to 17 years) (n=140, 31% female; 92%
Caucasians, 1.6% Blacks, 1.6% Asians, 4.8% Other), the safety and tolerability
profile of atorvastatin 10 to 20 mg daily, as an adjunct to diet to reduce
TC, LDL-C, and apo B levels, was generally similar to that of placebo.
8
Use in Specific Populations
8.4 Pediatric Use
(additions underlined)
…
Atorvastatin
Heterozygous
Familial Hypercholesterolemia (HeFH)
Safety and effectiveness of atorvastatin have been
established in patients 10 years to 17 years of age with HeFH as an
adjunct to diet to reduce total cholesterol, LDL-C, and apo B levels when,
after an adequate trial of diet therapy, the following are present:
a positive family history of FH, or
premature CVD in a first, or second-degree relative, or
two or more other CVD risk factors are
present.
Use of atorvastatin for this indication is
supported by evidence from:
A placebo-controlled clinical trial of
6 months duration in 187 boys and postmenarchal girls, 10 years to 17
years of age. Patients treated with 10 mg or 20 mg daily
atorvastatin had an adverse reaction profile generally similar to that of
patients treated with placebo. In this limited controlled study, there was no
significant effect on growth or sexual maturation in boys or on menstrual cycle
length in girls
A three year open-label uncontrolled
trial that included 163 pediatric patients 10 to 15 years of age with HeFH who
were titrated to achieve a target LDL-C <130 mg/dL. The safety and efficacy
of atorvastatin in lowering LDL-C appeared generally consistent with that
observed for adult patients, despite limitations of the uncontrolled study
design
Advise postmenarchal girls of contraception
recommendations, if appropriate for the patient.
The long-term efficacy of atorvastatin
therapy initiated in childhood to reduce morbidity and mortality in adulthood has
not been established.
The safety and efficacy of atorvastatin have not been
established in pediatric patients younger than 10 years of age with
HeFH.
Homozygous
Familial Hypercholesterolemia (HoFH)
Clinical efficacy of atorvastatin with dosages up to 80
mg/day for 1 year was evaluated in an uncontrolled study of patients with HoFH
including 8 pediatric patients.
Approved Drug Label (PDF)
4
Contraindications
(Additions and/or revisions are underlined)
Pregnancy
8
Use in Specific Populations
8.1 Pregnancy
(Pregnancy and
Lactation Labeling Rule (PLLR) Conversion; Extensive changes – please refer to
labeling)
8.2 Lactation
(Pregnancy and
Lactation Labeling Rule (PLLR) Conversion; Additions and/or revisions are underlined)
Risk Summary
CADUET is contraindicated during breastfeeding.
Atorvastatin use is contraindicated during breastfeeding
[see Contraindications (4)]. There is
no available information on the effects of the drug on the breastfed infant or the
effects of the drug on milk production. It is not known whether atorvastatin
is present in human milk, but it has been shown that another drug
in this class passes into human milk and atorvastatin is present in rat milk. Because of the potential for serious adverse
reactions in a breastfed infant, advise women that breastfeeding is not recommended
during treatment with CADUET.
Amlodipine
Limited available data from a published clinical lactation
study reports that amlodipine is present in human milk at an estimated median relative
infant dose of 4.2%. No adverse effects of amlodipine on the breastfed infant have
been observed. There is no available information on the effects of amlodipine on
milk production.
8.3 Females and Males of Reproductive Potential
(Newly added section; additions and/or
revisions are underlined)
Contraception
Atorvastatin may cause fetal harm when administered to
a pregnant woman. Advise females of reproductive potential to use effective contraception
during treatment with CADUET.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(Additions and/or revisions are underlined)
Embryofetal Toxicity:
Advise females of reproductive potential of the risk to a fetus,
to use effective contraception during treatment and to inform their healthcare
provider of a known or suspected pregnancy while using CADUET.
Lactation: Advise
women not to breastfeed during treatment with CADUET.
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