ADVERSE REACTIONS
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 Diarrhea Flatulence Dyspepsia/Heartburn Abdominal Distension |
4.0 8.0 2.0 0.0 2.0 |
5.9 8.5 3.3 3.3 3.3 |
10.5 6.5 4.6 3.6 2.1 |
2.3 4.7 0.0 0.6 0.6 |
7.4 6.7 3.2 2.5 2.0 |
7.1 5.6 4.4 2.7 2.4 |
General Fatigue Chest Pain Influenza |
4.0 4.0 4.0 |
1.3 1.3 2.6 |
5.2 3.3 1.9 |
0.0 1.2 0.6 |
3.4 2.7 2.0 |
3.9 1.9 0.7 |
Musculoskeletal Musculoskeletal
Pain Myalgia |
13.0 1.0 |
3.9 2.6 |
13.2 2.9 |
5.3 1.2 |
10.1 2.3 |
10.2 1.2 |
Nervous System Headache Dizziness |
5.0 4.0 |
6.5 1.3 |
7.5 5.2 |
3.5 0.6 |
6.3 3.5 |
4.6 3.4 |
Respiratory Pharyngitis Upper Respiratory Infection Rhinitis Cough |
2.0 6.0 7.0 4.0 |
4.6 9.8 5.2 1.3 |
1.5 5.2 3.8 3.1 |
1.2 4.1 1.2 1.2 |
2.0 5.9 3.9 2.5 |
2.7 5.8 4.9 1.7 |
Investigation ALT Increased g-GT Increased CPK Increased |
2.0 3.0 5.0 |
2.0 2.6 1.3 |
4.0 2.1 5.2 |
1.2 0.6 2.9 |
2.9 2.0 4.1 |
1.2 1.2 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 Fatigue Chest Pain Fever Weight Gain Weight Loss |
3.0 8.4 10.0 2.1 3.8 3.3 |
2.7 7.8 9.8 1.9 3.3 2.8 |
Musculoskeletal Musculoskeletal
Pain Muscle Cramp Musculoskeletal Traumatism |
24.9 5.1 10.2 |
24.4 4.6 9.6 |
Nervous System Dizziness Sleep Disturbance Anxiety/Nervousness Paresthesia |
7.3 3.0 4.8 3.2 |
6.6 2.4 4.7 3.0 |
Renal/Genitourinary Urinary Tract Infection |
2.7 |
2.6 |
Respiratory Upper Respiratory Tract Infection Cough Influenza Pulmonary Infection Sinus Abnormality Tracheobronchitis |
21.2 8.2 9.2 3.8 7.0 3.4 |
20.2 7.4 9.0 3.5 6.7 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 rarely during postmarketing experience with PRAVACHOL, regardless of causality assessment:
Musculoskeletal: myopathy,
rhabdomyolysis.
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.
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 (5.1,
5.2)
].
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
.]
|
REPORTS OF SUSPECTED PRAVACHOL SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Pravachol. The information is not vetted and should not be considered as verified clinical evidence.
Possible Pravachol side effects / adverse reactions in 65 year old male
Reported by a consumer/non-health professional from United States on 2011-10-07
Patient: 65 year old male weighing 79.4 kg (174.6 pounds)
Reactions: Vomiting, Nausea
Suspect drug(s):
Pravachol
Possible Pravachol side effects / adverse reactions in 75 year old male
Reported by a consumer/non-health professional from United States on 2011-10-17
Patient: 75 year old male
Reactions: Neuropathy Peripheral, Prostatic Specific Antigen Increased, Rhinorrhoea, Headache, Blood Pressure Decreased, Muscle Spasms
Suspect drug(s):
Pravachol
Administration route: Oral
Indication: Blood Cholesterol
End date: 2011-09-01
Zytiga
Administration route: Oral
Indication: Prostate Cancer
Start date: 2011-08-01
Other drugs received by patient: Lupron
Possible Pravachol side effects / adverse reactions in 60 year old female
Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-17
Patient: 60 year old female
Reactions: Drug Dose Omission, Wrong Technique in Drug Usage Process, Palpitations, Headache, Influenza Like Illness
Adverse event resulted in: life threatening event, hospitalization
Suspect drug(s):
Mevacor
Administration route: Oral
End date: 2011-10-11
Pravachol
Mevacor
Administration route: Oral
Start date: 2002-09-01
End date: 2008-12-01
|