Pravachol (Pravastatin Sodium) - Side Effects and Adverse Reactions

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. (See also PRECAUTIONS: Geriatric Use.)

Adverse Clinical Events

Short-Term Controlled Trials

All adverse clinical events (regardless of attribution) reported in more than 2% of pravastatin-treated patients in placebo-controlled trials of up to four months duration are identified in Table 8; also shown are the percentages of patients in whom these medical events were believed to be related or possibly related to the drug:

Table 8: Adverse Events in >2 Percent of Patients Treated with Pravastatin 10-40 mg in Short-Term Placebo-Controlled Trials

	All Events		Events Attributed to Study Drug
Body System/Event	Pravastatin (N=900) % of patients	Placebo (N=411) % of patients	Pravastatin (N=900) % of patients	Placebo (N=411) % of patients
*Statistically significantly different from placebo.
Cardiovascular     Cardiac Chest Pain	4.0	3.4	0.1	0.0
Dermatologic     Rash	4.0*	1.1	1.3	0.9
Gastrointestinal     Nausea/Vomiting     Diarrhea     Abdominal Pain     Constipation     Flatulence     Heartburn	7.3 6.2 5.4 4.0 3.3 2.9	7.1 5.6 6.9 7.1 3.6 1.9	2.9 2.0 2.0 2.4 2.7 2.0	3.4 1.9 3.9 5.1 3.4 0.7
General     Fatigue     Chest Pain     Influenza	3.8 3.7 2.4*	3.4 1.9 0.7	1.9 0.3 0.0	1.0 0.2 0.0
Musculoskeletal     Localized Pain     Myalgia	10.0 2.7	9.0 1.0	1.4 0.6	1.5 0.0
Nervous System         Headache     Dizziness	6.2 3.3	3.9 3.2	1.7* 1.0	0.2 0.5
Renal/Genitourinary     Urinary Abnormality	2.4	2.9	0.7	1.2
Respiratory     Common Cold     Rhinitis     Cough	7.0 4.0 2.6	6.3 4.1 1.7	0.0 0.1 0.1	0.0 0.0 0.0

The safety and tolerability of PRAVACHOL at a dose of 80 mg in two 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 >10X ULN compared to 0 out of 115 patients taking 40 mg of pravastatin.

Long-Term Controlled Morbidity and Mortality Trials

Adverse event data were pooled from seven 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 seven trials represent 47,613 patient-years of exposure to pravastatin. Events believed to be of probable, possible, or uncertain relationship to study drug, occurring in at least 1% of patients treated with pravastatin in these studies are identified in Table 9.

Table 9: Adverse Events in ≥1 Percent of Patients Treated with Pravastatin 40 mg in Long-Term Placebo-Controlled Trials

Body System/Event	Pravastatin (N=10,764) % of patients	Placebo (N=10,719) % of patients
Cardiovascular     Angina Pectoris	3.1	3.4
Dermatologic     Rash	2.1	2.2
Gastrointestinal     Dyspepsia/Heartburn     Abdominal Pain     Nausea/Vomiting     Flatulence     Constipation	3.5 2.4 1.6 1.2 1.2	3.7 2.5 1.6 1.1 1.3
General     Fatigue     Chest Pain	3.4 2.6	3.3 2.6
Musculoskeletal     Musculoskeletal Pain (includes arthralgia)     Muscle Cramp     Myalgia	6.0 2.0 1.4	5.8 1.8 1.4
Nervous System     Dizziness     Headache     Sleep Disturbance     Depression     Anxiety/Nervousness	2.2 1.9 1.0 1.0 1.0	2.1 1.8 0.9 1.0 1.2
Renal/Genitourinary     Urinary Abnormality (includes dysuria, frequency, nocturia)	1.0	0.8
Respiratory     Dyspnea     Upper Respiratory Infection     Cough	1.6 1.3 1.0	1.6 1.3 1.0
Special Senses     Vision Disturbance (includes blurred vision, diplopia)	1.6	1.3

Events of probable, possible, or uncertain relationship to study drug that occurred in <1.0% of pravastatin-treated patients in the long-term trials included the following; frequencies were similar in placebo-treated patients:

Dermatologic: pruritus, dermatitis, dryness skin, scalp hair abnormality (including alopecia), urticaria.

Endocrine/Metabolic: sexual dysfunction, libido change.

Gastrointestinal: decreased appetite.

General: fever, flushing.

Immunologic: allergy, edema head/neck.

Musculoskeletal: muscle weakness.

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

Special Senses: lens opacity, 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.

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

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: pancreatitis, hepatitis, including chronic active hepatitis, cholestatic jaundice, fatty change in liver, cirrhosis, fulminant hepatic necrosis, hepatoma.

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

Reproductive: gynecomastia.

Laboratory Abnormalities: Liver Function Test abnormalities, thyroid function abnormalities.

Laboratory Test Abnormalities

Increases in serum transaminase (ALT, AST) values and CPK have been observed (see WARNINGS).

Transient, asymptomatic eosinophilia has been reported. Eosinophil counts usually returned to normal despite continued therapy. Anemia, thrombocytopenia, and leukopenia have been reported with HMG-CoA reductase inhibitors.

Concomitant Therapy

Pravastatin has been administered concurrently with cholestyramine, colestipol, nicotinic acid, probucol and gemfibrozil. Preliminary data suggest that the addition of either probucol or gemfibrozil to therapy with lovastatin or pravastatin is not associated with greater reduction in LDL-cholesterol than that achieved with lovastatin or pravastatin alone. No adverse reactions unique to the combination or in addition to those previously reported for each drug alone have been reported. Myopathy and rhabdomyolysis (with or without acute renal failure) have been reported when another HMG-CoA reductase inhibitor was used in combination with immunosuppressive drugs, gemfibrozil, erythromycin, or lipid-lowering doses of nicotinic acid. Concomitant therapy with HMG-CoA reductase inhibitors and these agents is generally not recommended. (See WARNINGS: Skeletal Muscle and PRECAUTIONS: Drug Interactions.)

Pediatric Patients

In a two-year, double-blind, placebo-controlled study involving 100 boys and 114 girls with HeFH, the safety and tolerability profile of pravastatin was generally similar to that of placebo. (See CLINICAL PHARMACOLOGY: Pediatric Clinical Study and PRECAUTIONS: Pediatric Use.)

REPORTS OF SIDE EFFECTS / ADVERSE REACTIONS RELATED TO PRAVACHOL

Possible Pravachol side effects / adverse reactions in 68 year old male

Reported by a consumer/non-health professional from United States on 2007-01-16

Patient: 68 year old male

Reactions: Cerebrovascular Accident, Gastric Haemorrhage, Myocardial Infarction

Adverse event resulted in: hospitalization

Suspect drug(s):
Aspirin

Coumadin
    Administration route: Oral
    Start date: 2006-01-01

Plavix
    Start date: 2006-01-01
    End date: 2006-02-01

Pravachol
    Indication: Blood Cholesterol Increased

Possible Pravachol side effects / adverse reactions in 77 year old male

Reported by a health professional (non-physician/pharmacist) from Norway on 2007-01-16

Patient: 77 year old male

Reactions: Weight Decreased, Fatigue, Diarrhoea, Hepatotoxicity, General Physical Health Deterioration, Constipation

Adverse event resulted in: hospitalization

Suspect drug(s):
Cimetidine HCL

Pravachol

Other drugs received by patient: Tenormin; Albyl-E

Possible Pravachol side effects / adverse reactions in 81 year old male

Reported by a pharmacist from United States on 2007-01-24

Patient: 81 year old male weighing 65.3 kg (143.7 pounds)

Reactions: Abdominal Discomfort

Suspect drug(s):
Pravachol

Other drugs received by patient: Felodipine; Metoprolol Tartrate; Lactase; Lisinopril; Ranitidine HCL; Flunisolide Nasal INH Spray