Approved Drug Label (PDF)
5
Warnings and Precautions
5.2 Immune-Mediated Necrotizing Myopathy
(New subsection added)
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.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Skeletal Muscle Effects
(Additions and/or revisions underlined)
Cases of myopathy and rhabdomyolysis with acute renal
failure secondary to myoglobinuria have been reported with HMG-CoA reductase inhibitors,
including CRESTOR. These risks can occur at any dose level, but are increased at
the highest dose (40 mg).
CRESTOR
should be prescribed with caution in patients with predisposing factors for myopathy
(e.g., age ?65 years, inadequately treated hypothyroidism, renal impairment).
The
risk of myopathy during treatment with CRESTOR may be increased with concurrent
administration of gemfibrozil, some other lipid-lowering therapies (other
fibrates or niacin), cyclosporine, darolutamide, regorafenib, atazanavir/ritonavir,
lopinavir/ritonavir, simeprevir or combination of
sofosbuvir/velpatasvir/voxilaprevir, dasabuvir/ombitasvir/paritaprevir/ritonavir,
elbasvir/grazoprevir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, all
combinations with ledipasvir (including ledipasvir/sofosbuvir). Cases of myopathy,
including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors,
including rosuvastatin, coadministered with colchicine, and caution should be exercised
when prescribing CRESTOR with colchicine.
…
7
Drug Interactions
7.3 Anti-viral Medications
(Subsection title
revised)
(Additions and/or
revisions underlined)
Coadministration
of rosuvastatin with certain anti-viral drugs has differing effects on rosuvastatin
exposure and may increase risk of myopathy.
The
combination of sofosbuvir/velpatasvir/voxilaprevir which are anti-Hepatitis C
virus (anti- HCV) drugs, increases rosuvastatin exposure. Similarly, the
combination of ledipasvir/sofosbuvir may significantly increase rosuvastatin
exposure. For these combinations of anti-HCV drugs, concomitant use with CRESTOR
is not recommended.
Simeprevir
and combinations of dasabuvir/ombitasvir/paritaprevir/ritonavir, elbasvir/grazoprevir,
sofosbuvir/velpatasvir and glecaprevir/pibrentasvir which are anti-HCV drugs, increase
rosuvastatin exposure. Combinations of atazanavir/ritonavir and lopinavir/ritonavir,
which are anti-HIV-1 drugs, increase rosuvastatin exposure. For these anti-viral
drugs, the dose of CRESTOR should not exceed 10 mg once daily.
The
combinations of fosamprenavir/ritonavir or tipranavir/ritonavir, which are anti-HIV-1
drugs, produce little or no change in rosuvastatin exposure. No dose
adjustment is needed for concomitant use with these combinations.
7.5 Regorafenib
(Newly added
subsection)
Regorafenib
increased rosuvastatin exposure and may increase the risk of myopathy. If used together,
the dose of CRESTOR should not exceed 10 mg once daily.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATION
(Additions and/or
revisions underlined)
…
Tell your doctor about
all the medicines you take, including prescription and over-the-counter
medicines, vitamins, and herbal supplements.
Talk
to your doctor before you start taking any new medicines.
Taking
CRESTOR with certain other medicines may affect each other causing side effects.
CRESTOR may affect the way other medicines work, and other medicines may affect
how CRESTOR works.
Especially
tell your doctor if you take:
cyclosporine
(a medicine for your immune system)
gemfibrozil
(a fibric acid medicine for lowering cholesterol)
darolutamide (a medicine for the treatment of prostate
cancer)
regorafenib (a medicine used to treat cancer of the colon
and rectum)
anti-viral
medicines including certain HIV or hepatitis C virus drugs such as:
lopinavir,
ritonavir, fosamprenavir, tipranavir, atazanavir, simeprevir
combination of
sofosbuvir/velpatasvir/voxilaprevir
dasabuvir/ombitasvir/paritaprevir/ritonavir
elbasvir/grazoprevir
sofosbuvir/velpatasvir
glecaprevir/pibrentasvir
and
certain
anti-fungal medicines (such as itraconazole, ketoconazole and fluconazole)
coumarin
anticoagulants (medicines that prevent blood clots, such as warfarin)
niacin
or nicotinic acid
fibric
acid derivatives (such as fenofibrate)
- colchicine
(a medicine used to treat gout)
Ask
your doctor or pharmacist for a list of these medicines if you are not sure. Know
all of the medicines you take. Keep a list of them to show your doctor and pharmacist
when you get new medicine.
…
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Skeletal Muscle Effects
(Additions and/or revisions underlined)
Cases of myopathy and rhabdomyolysis with acute renal
failure secondary to myoglobinuria have been reported with HMG-CoA reductase inhibitors,
including CRESTOR. These risks can occur at any dose level, but are increased at
the highest dose (40 mg).
CRESTOR
should be prescribed with caution in patients with predisposing factors for myopathy
(e.g., age ?65 years, inadequately treated hypothyroidism, renal impairment).
The
risk of myopathy during treatment with CRESTOR may be increased with concurrent
administration of gemfibrozil, some other lipid-lowering therapies (other
fibrates or niacin), cyclosporine, darolutamide, regorafenib, atazanavir/ritonavir,
lopinavir/ritonavir, simeprevir or combination of
sofosbuvir/velpatasvir/voxilaprevir, dasabuvir/ombitasvir/paritaprevir/ritonavir,
elbasvir/grazoprevir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, all
combinations with ledipasvir (including ledipasvir/sofosbuvir). Cases of myopathy,
including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors,
including rosuvastatin, coadministered with colchicine, and caution should be exercised
when prescribing CRESTOR with colchicine.
…
7
Drug Interactions
7.4 Darolutamide
(Newly added
subsection)
Darolutamide
increased rosuvastatin exposure more than 5 fold. Therefore, in patients taking
darolutamide, the dose of CRESTOR should not exceed 5 mg once daily.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATION
(Additions and/or
revisions underlined)
…
Tell your doctor about
all the medicines you take, including prescription and over-the-counter
medicines, vitamins, and herbal supplements.
Talk
to your doctor before you start taking any new medicines.
Taking
CRESTOR with certain other medicines may affect each other causing side effects.
CRESTOR may affect the way other medicines work, and other medicines may affect
how CRESTOR works.
Especially
tell your doctor if you take:
cyclosporine
(a medicine for your immune system)
gemfibrozil
(a fibric acid medicine for lowering cholesterol)
darolutamide (a medicine for the treatment of prostate
cancer)
regorafenib (a medicine used to treat cancer of the colon
and rectum)
anti-viral
medicines including certain HIV or hepatitis C virus drugs such as:
lopinavir,
ritonavir, fosamprenavir, tipranavir, atazanavir, simeprevir
combination of
sofosbuvir/velpatasvir/voxilaprevir
dasabuvir/ombitasvir/paritaprevir/ritonavir
elbasvir/grazoprevir
sofosbuvir/velpatasvir
glecaprevir/pibrentasvir
and
certain
anti-fungal medicines (such as itraconazole, ketoconazole and fluconazole)
coumarin
anticoagulants (medicines that prevent blood clots, such as warfarin)
niacin
or nicotinic acid
fibric
acid derivatives (such as fenofibrate)
- colchicine
(a medicine used to treat gout)
Ask
your doctor or pharmacist for a list of these medicines if you are not sure. Know
all of the medicines you take. Keep a list of them to show your doctor and pharmacist
when you get new medicine.
…
Approved Drug Label (PDF)
7
Drug Interactions
7.1 Cyclosporine
(additions
underlined)
Cyclosporine
increased rosuvastatin exposure and may result in increased risk of myopathy.
Therefore, in patients taking cyclosporine, the dose of CRESTOR should not
exceed 5 mg once daily.
7.3 Protease Inhibitors
(additions
underlined)
Coadministration
of rosuvastatin with certain protease inhibitors has differing effects on rosuvastatin
exposure and may increase risk of myopathy. Simeprevir, which is a
hepatitis C virus (HCV) protease inhibitor,
or combinations of
atazanavir/ritonavir or
lopinavir/ritonavir, which are HIV-1 protease inhibitors, increase rosuvastatin exposure.
…
Approved Drug Label (PDF)
4
Contraindications
Replace bullets 3 and 4 with the following:
- Lactation.
Limited data indicate that CRESTOR is present in human milk. Because
statins have the potential for serious adverse reactions in nursing
infants, women who require CRESTOR treatment should not breastfeed their
infants.
6
Adverse Reactions
Clinical Studies Experience
- In the CRESTOR controlled clinical trials database (placebo or
active-controlled) of 5394 patients with a mean treatment duration of 15
weeks, 1.4% of patients discontinued due to adverse reactions. The most
common adverse reactions that led to treatment discontinuation were:
- myalgia
- abdominal pain
- nausea
- The
most commonly reported adverse reactions (incidence greater than or equal to 2%) in the CRESTOR
controlled clinical trial database of 5394 patients were:
- headache
- myalgia
- abdominal pain
- asthenia
- nausea
- Adverse
reactions reported in (greater than or equal to 2%) of patients in placebo-controlled clinical
studies and at a rate greater than placebo are shown in Table 1. These
studies had a treatment duration of up to 12 weeks.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MG - What is CRESTOR?
CRESTOR is used to treat:
- adults who cannot control their cholesterol levels by diet and exercise alone
- children
8 to 17 years of age with heterozygous familial hypercholesterolemia
(an inherited condition that causes high levels of LDL)
- children
7 to 17 years of age with homozygous familial hypercholesterolemia (an
inherited condition that causes high levels of LDL).
CRESTOR
is not approved for use in children with heterozygous familial
hypercholesterolemia younger than 8 years of age or for use in children
with homozygous familial hypercholesterolemia younger than 7 years of
age.
PCI - Embryofetal Toxicity (add new section)
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.
PCI - Lactation (add new section)
Advise women not to breastfeed during treatment with CRESTOR.