| Well-Established Safety Profile |
General safety
According to product labeling:
The table above shows frequency of myalgia rates occurring in ≥2% and at a rate greater than placebo in
patients treated with LIPITOR (n=8755) from 17 placebo-controlled trials.
No dose adjustment required in patients with renal dysfunction:
- Supported by the NKF KDOQI guidelines for diabetes and CKD management1
No clinically significant INR increase with warfarin:
- Warfarin is one of the most common drugs involved with concomitant interactions2
Safety in higher-risk patients
LIPITOR has a well-established safety profile in many higher-risk patients.
Patients with CHD
In TNT, a 5-year study of >10,000 patients with CHD3:
Patients with CHD and type 2 diabetes
In patients with CHD and type 2 diabetes as seen in a post hoc subgroup analysis of TNT (n=1501)4
Patients with CHD who also have CKD
In patients with CHD who also have CKD as seen in a post hoc subgroup analysis of TNT (n=3107)5:
No persistent elevations in creatine phosphokinase (CPK) levels‡ were observed among patients in either the LIPITOR 10 mg or 80 mg arms.5
Rare cases of rhabdomyolysis have been reported with LIPITOR and other statins. Renal impairment may be a predisposing factor for the development of rhabdomyolysis. Therefore, such patients merit closer monitoring.
Patients aged ≥65 years
According to product labeling, >15,000 patients aged ≥ 65 years:
In multiple clinical trials, no overall differences in safety have been observed in patients aged ≥ 65 years (n=15,813) vs younger patients (n=24,015). Greater sensitivity of some older adults cannot be ruled out.
In an analysis of pooled data from 50 clinical trials including nearly 6000 patients7:
Rare cases of rhabdomyolysis have been reported with LIPITOR and other statins. Predisposing factors include advanced age (≥65). Therefore, LIPITOR should be prescribed with caution in patients aged >65 years. In cases of myopathy or rhabdomyolysis, therapy should be temporarily withheld or discontinued.
Renal safety data in patients with CKD
NKF/KDOQI guidelines provide comprehensive direction when evaluating patients with CKD, including8:
- Review of medications at all visits to detect potentially adverse effects on kidney function or complications of CKD
- Periodic assessment of eGFR, proteinuria, and hematuria
Based on an analysis of renal safety of long-term (≥1 year) LIPITOR use in 4 placebo-controlled clinical trials, the incidence of albuminuria|| and hematuria with LIPITOR was low and comparable to placebo.6,9
In a post hoc subgroup analysis of CARDS in patients with type 2 diabetes with and without albuminuria, LIPITOR 10 mg showed no adverse effects on eGFR.10
In post hoc subgroup analyses from multiple landmark trials, LIPITOR showed no adverse effect on eGFR in patients with CKD across the approved dose range5,10-11
Rare cases of rhabdomyolysis have been reported with LIPITOR and other statins. Renal impairment may be a predisposing factor for the development of rhabdomyolysis. Therefore, such patients merit closer monitoring.
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*LIPITOR 80 mg is not a starting dose.
†Persistent ALT/AST elevations were >3 x ULN twice within 4 to 10 days.
‡CPK levels were defined as 2 measurements ≥10 times the upper limit of normal, obtained 4 to 10 days apart.
§Persistent ALT/AST elevations were >3 x ULN twice within a 14-day period.
||Albuminuria was defined as albumin-creatinine ratio ≥22 mg/g.9
LIPITOR Important Safety Information and Indications
Please scroll to see the Indications below.
Important Safety Information
LIPITOR is contraindicated in patients with active liver disease or unexplained persistent elevations of hepatic transaminases; in women who are or may become pregnant or who are nursing; in patients with hypersensitivity to any component of this medication.
Rare cases of rhabdomyolysis have been reported with LIPITOR and other statins. Tell patients to promptly report muscle pain, tenderness, or weakness. Predisposing factors include advanced age (≥65), uncontrolled hypothyroidism, and renal impairment. Patients with a history of renal impairment merit closer monitoring. In cases of myopathy or rhabdomyolysis, therapy should be temporarily withheld or discontinued.
The concomitant use of higher doses of LIPITOR with certain drugs such as cyclosporine and strong CYP3A4 inhibitors (eg, clarithromycin, itraconazole, and HIV protease inhibitors) increases the risk of myopathy/rhabdomyolysis. Lower doses of LIPITOR should be considered. Physicians should carefully monitor patients for signs or symptoms of myopathy early during therapy and when titrating the dose of either drug.
It is recommended that liver function tests be performed prior to and 12 weeks following both the initiation of therapy and any elevation of dose, and periodically thereafter. If ALT or AST values >3 x ULN persist, dose reduction or withdrawal is recommended.
In a post hoc analysis of the SPARCL study in patients without CHD who had a stroke or TIA within the preceding 6 months, a higher incidence of hemorrhagic stroke was seen in the LIPITOR 80-mg group compared with placebo (2.3% vs 1.4%). Some baseline characteristics, including hemorrhagic and lacunar stroke on study entry, were associated with a higher incidence of hemorrhagic stroke in the LIPITOR group.
The most commonly reported adverse reactions with LIPITOR in placebo-controlled trials were: nasopharyngitis, arthralgia, diarrhea, pain in extremity, and urinary tract infection.
Indications
LIPITOR is indicated as an adjunct to diet to reduce the risk of myocardial infarction (MI), stroke, revascularization procedures, and angina in adult patients with multiple risk factors but without clinically evident coronary heart disease (CHD); to reduce the risk of MI and stroke in patients with type 2 diabetes and without clinically evident CHD, but with multiple risk factors; to reduce the risk of nonfatal MI, fatal and nonfatal stroke, revascularization procedures, hospitalization for congestive heart failure, and angina in adult patients with clinically evident CHD.
LIPITOR, as an adjunct to diet, is also indicated to reduce elevated total-C, LDL-C, apo B, and TG levels; and to increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia.
¶ LIPITOR $4 Co-Pay Card Terms & Conditions
By using the LIPITOR $4 Co-Pay Card (the "Card"), you acknowledge that you currently meet the eligibility criteria and will comply with the terms and conditions described below:
This Card is not valid for prescriptions that are eligible to be reimbursed, in whole or in part, by Medicaid, Medicare, or other federal or state healthcare programs (including any state prescription drug assistance programs and the Government Health Insurance Plan available in Puerto Rico [formerly known as "La Reforma de Salud"]). The Card is not valid for prescriptions that are eligible to be reimbursed by private insurance plans or other health or pharmacy benefit programs which reimburse you for the entire cost of your prescription drugs. To qualify for this offer, your out-of-pocket expense must be greater than $4 per prescription. If your out-of-pocket expenses for a 1-month supply (30 tablets) are $54 or less, you will pay $4 for a 1-month supply. If your out-of-pocket expenses for a 1-month supply (30 tablets) exceed $54, you qualify for up to $50 in savings for a 1-month supply. In either case, you can only qualify for up to $600 of savings per calendar year. After a maximum of $600, you will pay usual monthly out-of-pocket costs. You must deduct the value received under this program from any reimbursement request submitted to your insurance plan, either directly by you or on your behalf. The Card is not valid for Massachusetts residents whose prescriptions are covered in whole or in part by third-party insurance, or where otherwise prohibited by law. This Card cannot be combined with any other rebate/coupon, free trial, or similar offer for the specified prescription. The Card will be accepted only at participating pharmacies. This Card is not health insurance. Offer good only in the US and Puerto Rico. The Card is limited to 1 per person during this offering period and is not transferable. Offer limited to 1 use per month. Pfizer reserves the right to rescind, revoke or amend the program without notice at any time. Card and Program expire 12/31/2012. No membership fees.
For reimbursement when using a non-participating pharmacy/mail order: Pay for LIPITOR prescription and mail copy of original pharmacy receipt (cash register receipt NOT valid) with product name, date, and amount circled to: LIPITOR Co-Pay Card, 6501 Weston Parkway, Suite 370, Cary, NC 27513. Be sure to include a copy of the front of your Co-Pay Card, your name, and mailing address.
For healthcare professional customer service, call 1-800-505-4426 Monday through Friday, 8:30 AM to 5:30 PM EST or visit www.LipitorHCP.com. Pfizer Inc., 235 East 42nd Street, New York, NY 10017.
Please see full prescribing and patient information
Study Descriptions
TNT (N=10,001) assessed the efficacy and safety of lowering LDL-C <100 mg/dL in CHD patients who achieved a mean LDL-C target level of <130 mg/dL after an 8-week, open-label, run-in period with LIPITOR 10 mg and were then randomized to receive either LIPITOR 80 mg or LIPITOR 10 mg. Eligible patients with CHD were defined as having 1 or more of the following: previous MI, previous or current angina with objective evidence of atherosclerotic CHD, and a history of coronary revascularization. The primary end point was time to first occurrence of a major CV event, defined as fatal CHD, nonfatal non-procedure-related MI, resuscitated cardiac arrest, or fatal or nonfatal stroke.3
A post hoc subgroup analysis of TNT assessed the effect of LIPITOR 80 mg vs 10 mg in patients with CHD and type 2 diabetes (n=1501). Patients were included in the current analysis if they had prior history of diabetes noted in their prescreening form (fasting glucose levels at screening were not used). The primary end point evaluated was the same as in the overall study: the first occurrence of a major CV event.4
A post hoc subgroup analysis of TNT assessed the effect of LIPITOR 80 mg vs 10 mg in patients with CHD and CKD (n=3107). The primary end point evaluated was the same as in the overall study: the first occurrence of a major CV event. Patients with CKD were identified at baseline on the basis of an eGFR <60 mL/min/1.73 m2 using the MDRD equation. At baseline, of the 3107 patients that had CKD, 3078 had stage 3 CKD (eGFR >30 to <59 mL/min/1.73 m2 ) and 29 had stage 4 CKD (eGFR >15 to <29 mL/min/1.73 m2 ).5
The Long Term Renal Safety Analysis was a retrospective, pooled analysis investigating the long-term renal safety of LIPITOR using data from 4 long-term (at least 1 year in duration) placebo-controlled clinical trials. Trials included were ASPEN, BONES, CARDS, and SPARCL. This database includes a broad spectrum of patients (N=10,533) at varying risk of cardiovascular events (including patients with diabetes with and without CHD, post-stroke patients, and postmenopausal women) with baseline serum creatinine measurement. The incidence of albuminuria and hematuria presented in the table was analyzed in both treated and untreated (placebo) patients with CKD (n=4380). CKD was defined as eGFR <60 mL/min/1.73 m2 at baseline using the MDRD equation.6,9
In a post hoc subgroup analysis of CARDS, the effect of LIPITOR 10 mg on annual change in eGFR patients with type 2 diabetes, with or without albuminuria at baseline, was evaluated. A patient was defined as albuminuric if all available pretreatment ACR values were 22 mg/g or greater, and normoalbuminuric if all available values were less than 22 mg/g. At baseline, 521 participitants had albuminuria and 1951 were normoalbuminuric. Median duration of follow-up was 3.9 years.10
References: 1. KDOQI. KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease. Am J Kidney Dis. 2007;49(2 suppl 2):S1-S179. 2. Hanlon JT, Pieper CF, Hajjar ER, et al. Incidence and predictors of all and preventable adverse drug reactions in frail elderly persons after hospital stay. J Gerontol A Biol Sci Med Sci. 2006;61(5):511-515. 3. LaRosa JC, Grundy SM, Waters DD, et al, for the Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352(14):1425-1435. 4. Shepherd J, Barter P, Carmena R, et al; for the Treating to New Targets Investigators. Effect of lowering LDL cholesterol substantially below currently recommended levels in patients with coronary heart disease and diabetes: the Treating to New Targets (TNT) study. Diabetes Care. 2006;29(6):1220-1226. 5. Shepherd J, Kastelein JJP, Bittner V, et al; for the TNT (Treating to New Targets) Investigators. Intensive lipid lowering with atorvastatin in patients with coronary heart disease and chronic kidney disease: the TNT (Treating to New Targets) study. J Am Coll Cardiol. 2008;51(15):1448-1454. 6. Data on file. Pfizer Inc, New York, NY. 7. Hey-Hadavi JH, Kuntze E, Luo D, Silverman P, Pittman D, LePetri B. Tolerability of atorvastatin in a population aged ≥65 years: a restrospective pooled analysis of results from fifty randomized clinical trials. Am J Geriatr Pharmacother. 2006;4(2):112-122. 8. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification. Am J Kidney Dis. 2002;39(2 suppl 1):S1-S266. 9. Jeffers BW, Laskey R, Schou M, Wilson DJ. Analysis of the renal safety of long-term atorvastatin use in a broad range of patients. Poster presented at: World Congress of Nephrology; April 21-25, 2007; Rio de Janeiro, Brazil. 10. Colhoun HM, Betteridge DJ, Durrington PN, et al; for CARDS Investigators. Effects of atorvastatin on kidney outcomes and cardiovascular disease in patients with diabetes: an analysis from the Collaborative Atorvastatin Diabetes Study (CARDS). Am J Kidney Dis. 2009;54(5):810-819. doi:10.1053/j.ajkd.2009.03.022. 11. Koren MJ, Davidson MH, Wilson DJ, Fayyad RS, Zuckerman A, Reed DP; for ALLIANCE Investigators. Focused atorvastatin therapy in managed-care patients with coronary heart disease and CKD. Am J Kidney Dis. 2009;53(5):741-750.
