Pravachol Side Effects Center

SIDE EFFECTS

Pravastatin is generally well tolerated; adverse reactions have usually been mild and transient. In 4-month-long placebo-controlled trials, 1.7% of pravastatin-treated patients and 1.2% of placebo-treated patients were discontinued from treatment because of adverse experiences attributed to study drug therapy; this difference was not statistically significant.

Adverse Clinical Events

Short-Term Controlled Trials

In the PRAVACHOL placebo-controlled clinical trials database of 1313 patients (age range 20-76 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 PRAVACHOL 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)

Body System/Event	5 mg N=100	10 mg N=153	20 mg N=478	40 mg N=171	Any Dose N=902	Placebo 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 PRAVACHOL at a dose of 80 mg in 2 controlled trials with a mean exposure of 8.6 months was similar to that of PRAVACHOL 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 PRAVACHOL placebo-controlled clinical trials database of 21,483 patients (age range 24-75 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 PRAVACHOL 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

Body System/Event	Pravastatin (N=10,764) % of patients	Placebo (N=10,719) % 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.

Postmarketing Experience

In addition to the events reported above, as with other drugs in this class, the following events have been reported during postmarketing experience with PRAVACHOL, regardless of causality assessment:

Musculoskeletal: myopathy, rhabdomyolysis, tendon disorder, polymyositis.

There have been rare reports of immune-mediated necrotizing myopathy associated with statin use [see WARNINGS AND PRECAUTIONS].

Nervous System: dysfunction of certain cranial nerves (including alteration of taste, impairment of extraocular movement, facial paresis), peripheral nerve palsy.

There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).

Hypersensitivity: anaphylaxis, angioedema, lupus erythematosus-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, purpura, hemolytic anemia, positive ANA, ESR increase, arthritis, arthralgia, asthenia, photosensitivity, chills, malaise, toxic epidermal necrolysis, erythema multiforme (including Stevens-Johnson syndrome).

Gastrointestinal: abdominal pain, constipation, pancreatitis, hepatitis (including chronic active hepatitis), cholestatic jaundice, fatty change in liver, cirrhosis, fulminant hepatic necrosis, hepatoma, fatal and non-fatal hepatic failure.

Dermatologic: a variety of skin changes (e.g., nodules, discoloration, dryness of mucous membranes, changes to hair/nails).

Renal: urinary abnormality (including dysuria, frequency, nocturia).

Respiratory: dyspnea, interstitial lung disease.

Psychiatric: nightmare.

Reproductive: gynecomastia.

Laboratory Abnormalities: liver function test abnormalities, thyroid function abnormalities.

Laboratory Test Abnormalities

Increases in ALT, AST values and CPK have been observed [see WARNINGS AND PRECAUTIONS].

Transient, asymptomatic eosinophilia has been reported. Eosinophil counts usually returned to normal despite continued therapy. Anemia, thrombocytopenia, and leukopenia have been reported with statins.

Pediatric Patients

In a 2-year, double-blind, placebo-controlled study involving 100 boys and 114 girls with HeFH (n=214; age range 8-18.5 years, 53% female, 95% Caucasians, <1% Blacks, 3% Asians, 1% Other), the safety and tolerability profile of pravastatin was generally similar to that of placebo. [see WARNINGS AND PRECAUTIONS, Use In Specific Populations, and CLINICAL PHARMACOLOGY]

DRUG INTERACTIONS

For the concurrent therapy of either cyclosporine, fibrates, niacin (nicotinic acid), or erythromycin, the risk of myopathy increases [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].

Cyclosporine

The risk of myopathy/rhabdomyolysis is increased with concomitant administration of cyclosporine. Limit pravastatin to 20 mg once daily for concomitant use with cyclosporine [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS, and CLINICAL PHARMACOLOGY].

Clarithromycin And Other Macrolide Antibiotics

The risk of myopathy/rhabdomyolysis is increased with concomitant administration of clarithromycin. Limit pravastatin to 40 mg once daily for concomitant use with clarithromycin [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS , and CLINICAL PHARMACOLOGY].

Other macrolides (e.g., erythromycin and azithromycin) have the potential to increase statin exposures while used in combination. Pravastatin should be used cautiously with macrolide antibiotics due to a potential increased risk of myopathies.

Colchicine

The risk of myopathy/rhabdomyolysis is increased with concomitant administration of colchicine [see WARNINGS AND PRECAUTIONS].

Gemfibrozil

Due to an increased risk of myopathy/rhabdomyolysis when HMG-CoA reductase inhibitors are coadministered with gemfibrozil, concomitant administration of PRAVACHOL with gemfibrozil should be avoided [see WARNINGS AND PRECAUTIONS].

Other Fibrates

Because it is known that the risk of myopathy during treatment with HMG-CoA reductase inhibitors is increased with concurrent administration of other fibrates, PRAVACHOL should be administered with caution when used concomitantly with other fibrates [see WARNINGS AND PRECAUTIONS].

Niacin

The risk of skeletal muscle effects may be enhanced when pravastatin is used in combination with niacin; a reduction in PRAVACHOL dosage should be considered in this setting [see WARNINGS AND PRECAUTIONS].

Read the entire FDA prescribing information for Pravachol (Pravastatin Sodium)