PRAVIGARD PAC (COPACKAGED)
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PRAVIGARD PAC (COPACKAGED) (PRAVIGARD PAC (COPACKAGED)).
Pravigard PAC (copackaged) contains pravastatin, an HMG-CoA reductase inhibitor that competitively inhibits the conversion of HMG-CoA to mevalonate, reducing cholesterol synthesis, and buffered aspirin, which irreversibly acetylates cyclooxygenase (COX-1 and COX-2), inhibiting thromboxane A2 synthesis and platelet aggregation.
| Metabolism | Pravastatin undergoes minimal hepatic metabolism via CYP3A4 (minor pathway) and is primarily excreted unchanged in urine and feces. Aspirin is rapidly hydrolyzed to salicylic acid, which is conjugated with glycine (salicyluric acid) and glucuronic acid in the liver. |
| Excretion | Pravastatin: ~20% renal, ~70% fecal (biliary); Aspirin: renal (dose-dependent, ~50-80% as salicylates, ~10-20% as salicyluric acid) |
| Half-life | Pravastatin: 1.5-2 hours (terminal, clinical significance minimal due to prolonged HMG-CoA reductase inhibition); Aspirin: 15-20 minutes (acetylated form), salicylate: 2-3 hours (low dose) to 15-30 hours (high dose, due to saturable metabolism) |
| Protein binding | Pravastatin: ~50% bound (albumin); Aspirin: dose-dependent, 50-90% bound (albumin) for salicylate |
| Volume of Distribution | Pravastatin: 0.46 L/kg; Aspirin: 0.15-0.2 L/kg (salicylate: 0.1-0.35 L/kg, increased in acidosis) |
| Bioavailability | Pravastatin: oral, 34% (tablet); Aspirin: oral, 100% (immediate-release), but systemic bioavailability of active aspirin is limited due to presystemic hydrolysis (40-50% for enteric-coated) |
| Onset of Action | Pravastatin: oral, 1-2 weeks for lipid-lowering effect; Aspirin: oral immediate-release, 30-60 minutes for antiplatelet effect; enteric-coated, 3-4 hours |
| Duration of Action | Pravastatin: 24 hours (clinical lipid-lowering, taken once daily); Aspirin: platelet inhibition for lifespan of platelet (7-10 days), analgesic/antipyretic 4-6 hours |
| Molecular Weight | 424.53 |
PRAVIGARD PAC (copackaged) is not a single drug but a copackaged product containing pravastatin and aspirin. The typical adult dose of pravastatin is 40 mg orally once daily; aspirin is 81 mg orally once daily. Both are taken together as a single daily dose.
| Dosage form | TABLET |
| Renal impairment | For pravastatin: No dose adjustment is recommended for mild to moderate renal impairment. In severe renal impairment (CrCl <30 mL/min), start with 10 mg orally once daily and titrate cautiously. Aspirin: Avoid in severe renal impairment (GFR <30 mL/min/1.73m²) due to increased risk of bleeding and renal toxicity. For CrCl 30-60 mL/min, no adjustment specified. |
| Liver impairment | Pravastatin is contraindicated in active liver disease or unexplained persistent transaminase elevations. For Child-Pugh Class A or B: No specific dose adjustment provided; use with caution. For Child-Pugh Class C: Not studied; avoid. Aspirin: Use with caution in hepatic impairment; avoid in severe hepatic insufficiency due to risk of bleeding and fluid retention. |
| Pediatric use | Pravastatin: Not recommended for pediatric patients <8 years. For ages 8-18 with heterozygous familial hypercholesterolemia: 20 mg orally once daily for ages 8-13; 40 mg orally once daily for ages 14-18. Aspirin: Use not advisable in children due to risk of Reye's syndrome; avoid use except in specific pediatric conditions (e.g., Kawasaki disease) under specialist guidance. |
| 1st trimester | Contraindicated in first trimester due to risk of fetal malformations associated with HMG-CoA reductase inhibitors; pravastatin is a statin. |
| 2nd trimester | Contraindicated in second trimester; no safety data; potential for fetal harm. |
| 3rd trimester | Contraindicated in third trimester; may cause adverse effects on fetal development (e.g., reduced birth weight). |
Clinical note
Comprehensive clinical and safety monograph for PRAVIGARD PAC (COPACKAGED) (PRAVIGARD PAC (COPACKAGED)).
| Placental transfer | Pravastatin crosses the placenta based on animal studies; human data limited but transfer is likely given molecular weight and lipophilicity. |
| Breastfeeding | Pravastatin is excreted into human milk at low levels; however, due to potential for serious adverse effects in nursing infants (e.g., interference with lipid metabolism), breastfeeding is not recommended during therapy. Consider alternatives or discontinue drug. |
■ FDA Black Box Warning
Reye's syndrome: Aspirin should not be used in children and teenagers with viral infections due to risk of Reye's syndrome.
| Serious Effects |
Active liver disease or unexplained persistent elevations of serum transaminasesHypersensitivity to pravastatin or any component of the formulationPregnancyLactation
| Precautions | Risk of bleeding (e.g., gastrointestinal, intracranial) due to aspirin, Hepatic impairment: monitor liver function tests with pravastatin, Renal impairment: pravastatin dose adjustment may be required, Hypersensitivity reactions to aspirin or pravastatin, Peptic ulcer disease or gastrointestinal bleeding history with aspirin |
| Food/Dietary | Take with food to reduce gastrointestinal irritation from aspirin. Avoid grapefruit juice as it may modestly increase pravastatin levels, though the effect is less than with other statins. Limit alcohol intake to ≤1 drink/day for women and ≤2 drinks/day for men to reduce risk of liver toxicity and GI bleeding. Avoid high-fat meals specifically at the time of dosing as they may interfere with pravastatin absorption; however, a low-fat diet is recommended overall for cholesterol management. |
Loading safety data…
| Geriatric use |
| Pravastatin: No specific dose adjustment required for elderly; consider lower starting doses (e.g., 10 mg) due to increased risk of myopathy and age-related renal decline. Aspirin: Use lowest effective dose (e.g., 81 mg daily) due to increased risk of gastrointestinal bleeding. Monitor renal function and bleeding risk. |
| Lactation Rating | L4 (Hazardous) |
| Teratogenic Risk | Pravigard PAC contains pravastatin (Pregnancy Category X) and aspirin. First trimester: aspirin use associated with increased risk of gastroschisis; statins contraindicated due to risk of fetal malformations. Second trimester: aspirin may increase risk of intracranial hemorrhage in fetus. Third trimester: aspirin increases risk of premature closure of ductus arteriosus and oligohydramnios; statins may impair fetal development. |
| Fetal Monitoring | Monitor liver function tests at baseline and periodically; monitor creatine kinase if symptoms of myopathy; monitor coagulation parameters if high-dose aspirin; fetal ultrasound for ductus arteriosus and amniotic fluid index in third trimester if aspirin continued. |
| Fertility Effects | Pravastatin may reduce cholesterol, a precursor for steroid hormone synthesis, potentially impairing fertility. Aspirin at high doses may inhibit prostaglandin synthesis, affecting ovulation and implantation. Reversible upon discontinuation. |
| Clinical Pearls | PRAVIGARD PAC is a copackaged combination of pravastatin and aspirin. Pravastatin is a hydrophilic statin with minimal CYP metabolism, reducing drug interaction risk. Aspirin irreversibly inhibits COX-1; monitor for bleeding, especially in elderly or on anticoagulants. Note that the aspirin component is not enteric-coated; administer with food to reduce GI upset. Evaluate renal function before starting: pravastatin is excreted renally, aspirin may worsen renal impairment. Do not use in children <18 years (safety not established). |
| Patient Advice | Take this medication exactly as prescribed, usually once daily with a full glass of water and with food to reduce stomach upset. · Do not crush or chew the tablets; swallow them whole. · You may notice reddish or pinkish urine; this is harmless from the aspirin component. · Avoid alcohol while taking this medicine to lower the risk of stomach bleeding. · Tell your doctor if you experience unusual bruising, bleeding, black/tarry stools, or coughing up blood. · Notify your physician promptly about muscle pain, tenderness, or weakness, especially with fever or malaise. · Keep all appointments for blood tests to monitor liver function, kidney function, and cholesterol levels. · Do not take other NSAIDs or aspirin-containing products without consulting your doctor. |