ZETIA + a statin: Overall safety profile compared to a statin alone, median duration of 8 weeks

  • • The effect of ZETIA on cardiovascular morbidity and mortality has not been determined.
  • • ZETIA, administered alone or in combination with an HMG-CoA reductase inhibitor (statin), is indicated as adjunctive therapy to diet for the reduction of elevated TOTAL-C, LDL-C, Apo B, and non–HDL-C in patients with primary (heterozygous familial and nonfamilial) hyperlipidemia when diet alone is not enough.
  • • Contraindications: hypersensitivity to any component of this medication.
  • • Statin contraindications apply when used with a statin: active liver disease; unexplained persistent elevations in hepatic transaminase levels. Statins are contraindicated in pregnant and nursing women. Refer to the statin label for details.

Clinical adverse reactionsa

Body System/Organ Class
Adverse Reaction		 All Statins,b %
(n=9,361)		 ZETIA + All Statins,b %
(n=11,308)
Gastrointestinal Disorders
Diarrhea
2.2
2.5
General Disorders and
Administration Site Conditions
Fatigue

1.6

2.0
Infection and Infestations
Influenza
Nasopharyngitis
Upper respiratory tract infection
2.1
3.3
2.8
2.2
3.7
2.9
Musculoskeletal and Connective Tissue Disorders
Arthralgia
Back pain
Myalgia
Pain in extremity

2.4
2.3
2.7
1.9

2.6
2.4
3.2
2.1
aClinical adverse reactions occurring in >2% of patients treated with ZETIA coadministered with a statin and at an incidence greater than statin, regardless of causality.
bAll statins = all doses of all statins.

  • SELECTED CAUTIONARY INFORMATION
  • • When using ZETIA with a statin, also follow the label recommendations for that specific statin.
  • • When ZETIA was coadministered with a statin, consecutive elevations in hepatic transaminase levels (>3 × ULN) were slightly higher (1.3%) than those of statins alone (0.4%). Liver function tests should be performed when ZETIA is added to statin therapy and according to statin recommendations. Should an increase in ALT or AST >3 × ULN persist, consider withdrawal of ZETIA and/or the statin.
  • • Patients should be advised to promptly report muscle pain, tenderness, or weakness. Risk for skeletal muscle toxicity increases with higher statin doses, advanced age (>65), hypothyroidism, renal impairment, and depending on the statin used, concomitant use of other drugs. Discontinue drug if myopathy is diagnosed or suspected.
  • • Because renal impairment is a risk factor for statin-associated myopathy, doses of simvastatin exceeding 20 mg should be used with caution and close monitoring when administered concomitantly with ZETIA in patients with moderate to severe renal impairment (eGFR <60 mL/min/1.73 m2).

ZETIA + a statin: Tolerability profile in patients aged <65 and >65 years

  • IMPORTANT INFORMATION ABOUT GERIATRIC PATIENTS
  • • Of the patients who received ZETIA in clinical studies, 4,256 were 65 and older (this included 1,035 who were 75 and older). No overall differences in safety and effectiveness were observed between these patients and younger patients. Greater sensitivity of some older individuals cannot be ruled out.
  • • No dosage adjustment is needed in geriatric patients.
  • SELECTED CAUTIONARY INFORMATION (continued)
  • • ZETIA is not recommended in patients with moderate to severe hepatic impairment.
  • • The coadministration of ZETIA with fibrates other than fenofibrate is not recommended until use in patients is adequately studied.
  • • Exercise caution when using ZETIA and cyclosporine concomitantly because exposure to both drugs is increased. Cyclosporine concentrations should be monitored in these patients.
  • • ZETIA should be used in pregnant or nursing women only if the benefit outweighs the risk.

Clinical adverse events occurring in >2% of patients and at an incidence greater than placebo, regardless of causality1

  <65 Years >65 Years
Placebo
 (n=183)		 ZETIA
 (n=198)		 All statins
 (n=676)		 ZETIA + all statins
 (n=656)		 Placebo
 (n=76)		 ZETIA
(n=64)		 All statins
 (n=260)		 ZETIA + all statins (n=269)
Body as a whole—General disorders                
Asthenia 0.0 0.5 0.7 0.0 1.3 3.1 0.4 0.0
Chest pain 1.1 3.5 1.9 2.0 1.3 3.1 2.3 1.5
Dizziness 0.5 3.0 1.5 1.7 2.6 1.6 1.2 2.2
Fatigue 1.6 1.5 1.0 2.9 2.6 3.1 2.3 2.6
Headache 7.1 7.1 7.8 6.6 1.3 10.9 5.8 5.6
Influenza-like symptoms 0.0 2.0 0.7 1.1 0.0 0.0 0.0 0.0
Gastrointestinal system disorders                
Abdominal pain 2.2 2.0 3.0 2.6 2.6 4.7 3.5 5.6
Constipation 2.2 3.5 2.2 0.8 2.6 1.6 1.2 1.9
Diarrhea 1.6 3.0 2.8 3.2 1.3 4.7 3.1 1.9
Dyspepsia 2.7 2.5 2.5 1.7 1.3 4.7 2.7 1.9
Nausea 4.4 2.0 5.0 3.5 5.3 6.3 5.0 3.7
Vomiting 0.0 1.0 2.2 1.5 1.3 1.6 0.4 1.9
Infections and infestations                
Pharyngitis 2.2 3.0 2.7 2.3 1.3 3.1 1.9 2.2
Sinusitis 2.7 6.1 4.1 3.7 0.0 0.0 2.3 3.0
Upper respiratory tract infection 13.1 15.7 15.4 13.3 5.3 4.7 8.8 8.2
Musculoskeletal system disorders                
Arthralgia 2.7 4.0 3.8 3.7 1.3 3.1 5.4 2.6
Arthritis aggravated 0.0 0.0 0.0 0.0 0.0 3.1 0.4 0.4
Back pain 2.7 3.0 4.4 5.0 5.3 4.7 1.9 2.6
Musculoskeletal pain 4.9 5.6 3.8 3.7 5.3 3.1 5.0 3.3
Myalgia 5.5 6.1 3.8 3.4 2.6 1.6 4.6 7.4

+ View data origin

Additional Important Safety Information

Before prescribing ZETIA, please read the Prescribing Information. The Patient Information also is available.

Reference: 1. Data available on request from Merck, Professional Services-DAP, WP1-27, PO Box 4, West Point, PA 19486-0004. Please specify information package CARD-1014663-0000.


This site is intended for health care professionals of the United States, its territories, and Puerto Rico.

For non-US health care professionals, click here.

CARD-1000584-0005 04/12