Pravastatin Sodium (Page 3 of 9)

6.1 Adverse Clinical Events

Short-Term Controlled Trials

In the pravastatin sodium placebo-controlled clinical trials database of 1313 patients (age range 20 to 76 years, 32.4% women, 93.5% Caucasians, 5% Blacks, 0.9% Hispanics, 0.4% Asians, 0.2% Others) with a median treatment duration of 14 weeks, 3.3% of patients on pravastatin sodium and 1.2% patients on placebo discontinued due to adverse events regardless of causality. The most common adverse reactions that led to treatment discontinuation and occurred at an incidence greater than placebo were: liver function test increased, nausea, anxiety/depression, and dizziness.

All adverse clinical events (regardless of causality) reported in ≥ 2% of pravastatin-treated patients in placebo-controlled trials of up to 8 months duration are identified in Table 1:

Table 1: Adverse Events in ≥ 2% of Patients Treated with Pravastatin 5 to 40 mg and at an Incidence Greater Than Placebo in Short-Term Placebo-Controlled Trials (% of Patients)

	5 mg	10 mg	20 mg	40 mg	Any Dose	Placebo
Body System/Event	N = 100	N = 153	N = 478	N = 171	N = 902	N = 411
Cardiovascular
Angina Pectoris	5.0	4.6	4.8	3.5	4.5	3.4
Dermatologic Rash	3.0	2.6	6.7	1.2	4.5	1.4
Gastrointestinal
Nausea/Vomiting	4.0	5.9	10.5	2.3	7.4	7.1
Diarrhea	8.0	8.5	6.5	4.7	6.7	5.6
Flatulence	2.0	3.3	4.6	0.0	3.2	4.4
Dyspepsia/Heartburn	0.0	3.3	3.6	0.6	2.5	2.7
Abdominal Distension	2.0	3.3	2.1	0.6	2.0	2.4
General
Fatigue	4.0	1.3	5.2	0.0	3.4	3.9
Chest Pain	4.0	1.3	3.3	1.2	2.7	1.9
Influenza	4.0	2.6	1.9	0.6	2.0	0.7
Musculoskeletal
Musculoskeletal Pain	13.0	3.9	13.2	5.3	10.1	10.2
Myalgia	1.0	2.6	2.9	1.2	2.3	1.2
Nervous System
Headache	5.0	6.5	7.5	3.5	6.3	4.6
Dizziness	4.0	1.3	5.2	0.6	3.5	3.4
Respiratory
Pharyngitis	2.0	4.6	1.5	1.2	2.0	2.7
Upper Respiratory Infection	6.0	9.8	5.2	4.1	5.9	5.8
Rhinitis	7.0	5.2	3.8	1.2	3.9	4.9
Cough	4.0	1.3	3.1	1.2	2.5	1.7
Investigation
ALT Increased	2.0	2.0	4.0	1.2	2.9	1.2
g-GT Increased	3.0	2.6	2.1	0.6	2.0	1.2
CPK Increased	5.0	1.3	5.2	2.9	4.1	3.6

The safety and tolerability of pravastatin sodium at a dose of 80 mg in 2 controlled trials with a mean exposure of 8.6 months was similar to that of pravastatin sodium at lower doses except that 4 out of 464 patients taking 80 mg of pravastatin had a single elevation of CK > 10 times ULN compared to 0 out of 115 patients taking 40 mg of pravastatin.

Long-Term Controlled Morbidity and Mortality Trials

In the pravastatin sodium placebo-controlled clinical trials database of 21,483 patients (age range 24 to 75 years, 10.3% women, 52.3% Caucasians, 0.8% Blacks, 0.5% Hispanics, 0.1% Asians, 0.1% Others, 46.1% Not Recorded) with a median treatment duration of 261 weeks, 8.1% of patients on pravastatin sodium and 9.3% patients on placebo discontinued due to adverse events regardless of causality.

Adverse event data were pooled from 7 double-blind, placebo-controlled trials (West of Scotland Coronary Prevention Study [WOS]; Cholesterol and Recurrent Events study [CARE]; Long-term Intervention with Pravastatin in Ischemic Disease study [LIPID]; Pravastatin Limitation of Atherosclerosis in the Coronary Arteries study [PLAC I]; Pravastatin, Lipids and Atherosclerosis in the Carotids study [PLAC II]; Regression Growth Evaluation Statin Study [REGRESS]; and Kuopio Atherosclerosis Prevention Study [KAPS]) involving a total of 10,764 patients treated with pravastatin 40 mg and 10,719 patients treated with placebo. The safety and tolerability profile in the pravastatin group was comparable to that of the placebo group. Patients were exposed to pravastatin for a mean of 4.0 to 5.1 years in WOS, CARE, and LIPID and 1.9 to 2.9 years in PLAC I, PLAC II, KAPS, and REGRESS. In these long-term trials, the most common reasons for discontinuation were mild, non-specific gastrointestinal complaints. Collectively, these 7 trials represent 47,613 patient-years of exposure to pravastatin. All clinical adverse events (regardless of causality) occurring in ≥ 2% of patients treated with pravastatin in these studies are identified in Table 2.

Table 2: Adverse Events in ≥ 2% of Patients Treated with Pravastatin 40 mg and at an Incidence Greater Than Placebo in Long-Term Placebo-Controlled Trials

	Pravastatin	Placebo
	(N = 10,764)	(N = 10,719)
Body System/Event	% of patients	% of patients
Dermatologic
Rash (including dermatitis)	7.2	7.1
General
Edema	3.0	2.7
Fatigue	8.4	7.8
Chest Pain	10.0	9.8
Fever	2.1	1.9
Weight Gain	3.8	3.3
Weight Loss	3.3	2.8
Musculoskeletal
Musculoskeletal Pain	24.9	24.4
Muscle Cramp	5.1	4.6
Musculoskeletal Traumatism	10.2	9.6
Nervous System
Dizziness	7.3	6.6
Sleep Disturbance	3.0	2.4
Anxiety/Nervousness	4.8	4.7
Paresthesia	3.2	3.0
Renal/Genitourinary
Urinary Tract Infection	2.7	2.6
Respiratory
Upper Respiratory Tract Infection	21.2	20.2
Cough	8.2	7.4
Influenza	9.2	9.0
Pulmonary Infection	3.8	3.5
Sinus Abnormality	7.0	6.7
Tracheobronchitis	3.4	3.1
Special Senses
Vision Disturbance (includes blurred vision, diplopia)	3.4	3.3
Infections
Viral Infection	3.2	2.9

In addition to the events listed above in the long-term trials table, events of probable, possible, or uncertain relationship to study drug that occurred in < 2.0% of pravastatin-treated patients in the long-term trials included the following:

Dermatologic: scalp hair abnormality (including alopecia), urticaria.

Endocrine/Metabolic: sexual dysfunction, libido change.

General: flushing.

Immunologic: allergy, edema head/neck.

Musculoskeletal: muscle weakness.

Nervous System: vertigo, insomnia, memory impairment, neuropathy (including peripheral neuropathy).

Special Senses: taste disturbance.