10 — Medication Reference
Table of Contents
1.0 Medication Summary
| Class | Agent(s) | Expected LDL-C Effect | Route | Key Consideration |
|---|---|---|---|---|
| HMG-CoA Reductase Inhibitor (Statin) | Atorvastatin, Rosuvastatin, others | ↓ 30–55% | PO daily | First-line therapy |
| Cholesterol Absorption Inhibitor | Ezetimibe | ↓ 15–20% | PO daily | First add-on to statin |
| PCSK9 Monoclonal Antibody | Evolocumab, Alirocumab | ↓ 50–60% | SC q2w or monthly | Prior auth required |
| siRNA PCSK9 Inhibitor | Inclisiran | ↓ ~50% | SC q6 months | In-office injection; prior auth required |
| ACL Inhibitor | Bempedoic acid | ↓ 15–25% | PO daily | No muscle effects |
| ACL Inhibitor + Absorption Inhibitor | Bempedoic acid/ezetimibe | ↓ 35–40% | PO daily | Fixed-dose combination |
| Purified EPA | Icosapent ethyl | ↓ TG; ASCVD reduction | PO BID | Not a substitute for LDL-C lowering |
| Fibrate | Fenofibrate, Gemfibrozil | ↓ TG 30–50% | PO daily/BID | Pancreatitis prevention |
| Niacin | Extended-release niacin | ↓ 15–25%; ↓ Lp(a) 20–30% | PO QHS | Limited role; last-line |
2.0 Statins
2.1 High-Intensity Statins (≥ 50% LDL-C Reduction)
| Agent | Dose | Notes |
|---|---|---|
| Atorvastatin | 40–80 mg daily | No renal dose adjustment; take any time of day |
| Rosuvastatin | 20–40 mg daily | Most potent per mg; take any time of day; caution at 40 mg with Asian patients |
2.2 Moderate-Intensity Statins (30–49% LDL-C Reduction)
| Agent | Dose | Notes |
|---|---|---|
| Atorvastatin | 10–20 mg daily | — |
| Rosuvastatin | 5–10 mg daily | — |
| Simvastatin | 20–40 mg daily | Max 20 mg with amlodipine, diltiazem, amiodarone |
| Pravastatin | 40–80 mg daily | Not CYP3A4 metabolized; fewer drug interactions |
| Lovastatin | 40–80 mg daily | Take with evening meal |
| Fluvastatin XL | 80 mg daily | CYP2C9 metabolized |
| Pitavastatin | 1–4 mg daily | Minimal CYP metabolism; favorable diabetes risk profile [1] |
2.3 Common Statin Drug Interactions
| Interacting Drug | Statins Affected | Mechanism | Action |
|---|---|---|---|
| Strong CYP3A4 inhibitors (itraconazole, ketoconazole, HIV protease inhibitors, clarithromycin) | Atorvastatin, lovastatin, simvastatin | ↑ Statin levels | Avoid combination or switch to rosuvastatin/pravastatin/pitavastatin |
| Cyclosporine | All statins | Multiple mechanisms; ↑↑ statin levels | Use lowest dose; prefer pravastatin or fluvastatin; monitor closely |
| Gemfibrozil | All statins | Inhibits glucuronidation; ↑ myopathy risk | Contraindicated with statins — use fenofibrate instead [2] |
| Amlodipine | Simvastatin | CYP3A4 inhibition | Max simvastatin 20 mg; or switch to atorvastatin/rosuvastatin |
| Diltiazem, verapamil | Simvastatin, lovastatin | CYP3A4 inhibition | Max simvastatin 20 mg; consider alternative statin |
| Amiodarone | Simvastatin, lovastatin | CYP3A4 inhibition | Max simvastatin 20 mg; consider alternative statin |
| Warfarin | All statins (variable) | CYP competition | Monitor INR when starting/changing statin |
| Grapefruit juice (large quantities) | Atorvastatin, lovastatin, simvastatin | CYP3A4 inhibition | Avoid large quantities; no interaction with rosuvastatin/pravastatin |
2.4 Statin Monitoring
| Parameter | When |
|---|---|
| Lipid panel | 4–8 weeks after start/change; then per follow-up cadence |
| ALT | Baseline; only repeat if symptoms suggest hepatotoxicity |
| CK | Not routine; check if myalgia symptoms |
| HbA1c / fasting glucose | Periodically in patients with diabetes risk factors |
2.5 Statin Safety
- Hepatotoxicity: Rare clinically significant liver injury; mild ALT elevations (< 3× ULN) are common and do not require discontinuation [3]
- New-onset diabetes: ~9% relative increase in diabetes incidence with high-intensity statins; absolute risk is small and outweighed by ASCVD benefit in indicated populations [4]
- Myopathy: 1–5% incidence of myalgia; rhabdomyolysis is very rare (< 0.01%)
- Cognitive effects: No causal link established in randomized trials [3]
3.0 Ezetimibe
| Parameter | Details |
|---|---|
| Brand name | Zetia |
| Dose | 10 mg daily (only available dose) |
| Administration | With or without food; any time of day |
| Mechanism | Inhibits NPC1L1-mediated cholesterol absorption at intestinal brush border |
| LDL-C reduction | 15–20% as monotherapy; additive with statin |
| Key trial | IMPROVE-IT: reduced CV events when added to simvastatin post-ACS [5] |
| Side effects | Generally well-tolerated; rare GI symptoms, myalgia |
| Drug interactions | Minimal; avoid with cholestyramine (reduces ezetimibe absorption) |
| Renal/hepatic | No renal adjustment; avoid in active hepatic disease |
4.0 PCSK9 Inhibitors
4.1 Evolocumab (Repatha)
| Parameter | Details |
|---|---|
| Dose | 140 mg SC every 2 weeks or 420 mg SC monthly |
| Administration | Prefilled syringe or SureClick autoinjector; patient self-administration after training |
| Storage | Refrigerated (2–8°C); may store at room temperature (≤ 25°C) for up to 30 days |
| LDL-C reduction | 55–60% when added to statin |
| Key trial | FOURIER: 15% relative reduction in MACE over 2.2 years in stable ASCVD [6] |
| Side effects | Injection site reactions (3–5%), nasopharyngitis, back pain |
| Monitoring | Lipid panel 4–8 weeks after initiation |
| Prior auth | Required — see 11 — Prior Authorization |
4.2 Alirocumab (Praluent)
| Parameter | Details |
|---|---|
| Dose | 75 mg SC every 2 weeks (may increase to 150 mg if LDL-C not at target) |
| Administration | Prefilled pen; patient self-administration after training |
| Storage | Refrigerated; may store at room temperature (≤ 25°C) for up to 30 days |
| LDL-C reduction | 45–60% depending on dose |
| Key trial | ODYSSEY Outcomes: 15% relative reduction in MACE post-ACS [7] |
| Side effects | Similar to evolocumab |
| Monitoring | Lipid panel 4–8 weeks; consider down-titration if LDL-C < 25 mg/dL |
| Prior auth | Required — see 11 — Prior Authorization |
5.0 Inclisiran (Leqvio)
| Parameter | Details |
|---|---|
| Dose | 284 mg SC |
| Schedule | Day 0 → Day 90 → every 6 months thereafter |
| Administration | Healthcare provider administered (in-office injection, not self-administered) |
| Mechanism | Small interfering RNA (siRNA) targeting hepatic PCSK9 mRNA |
| LDL-C reduction | ~50% when added to statin |
| Key trials | ORION-10, ORION-11: sustained LDL-C reduction through 18 months [8] |
| Side effects | Injection site reactions (mild, transient) |
| Storage | Refrigerated or room temperature (≤ 25°C); single-use prefilled syringe |
| Prior auth | Required — see 11 — Prior Authorization |
| Advantage | Eliminates adherence concerns with biannual in-office dosing |
6.0 Bempedoic Acid
6.1 Bempedoic Acid (Nexletol)
| Parameter | Details |
|---|---|
| Dose | 180 mg daily |
| Administration | Oral; with or without food |
| Mechanism | ATP-citrate lyase (ACL) inhibitor; prodrug activated in liver (not in skeletal muscle) |
| LDL-C reduction | 15–25% as monotherapy; additive with statin and ezetimibe |
| Key trial | CLEAR Outcomes: 13% MACE reduction in statin-intolerant patients [9] |
| Side effects | Hyperuricemia/gout, tendon rupture (rare), ↑ creatinine |
| Monitoring | Uric acid at baseline and periodically; creatinine |
| Drug interactions | Simvastatin and pravastatin levels may increase (bempedoic acid inhibits OATP1B1) — limit simvastatin to 20 mg, pravastatin to 40 mg |
6.2 Bempedoic Acid / Ezetimibe (Nexlizet)
| Parameter | Details |
|---|---|
| Dose | 180 mg bempedoic acid / 10 mg ezetimibe daily |
| LDL-C reduction | 35–40% combined |
| Advantage | Single pill combining two non-statin agents; convenient for statin-intolerant patients |
| Same monitoring | As bempedoic acid above |
7.0 Icosapent Ethyl (Vascepa)
| Parameter | Details |
|---|---|
| Dose | 2 g twice daily with food (total 4 g/day) |
| Mechanism | Purified EPA ethyl ester; reduces TG, inflammation, platelet aggregation; membrane stabilization |
| Indication | Established ASCVD or DM with ≥ 2 risk factors AND fasting TG 135–499 mg/dL on stable statin |
| Key trial | REDUCE-IT: 25% relative reduction in MACE [10] |
| Side effects | Atrial fibrillation/flutter (5.3% vs. 3.9%); bleeding risk; musculoskeletal pain |
| Drug interactions | Monitor with anticoagulants (bleeding risk); no significant CYP interactions |
| Distinction | Not interchangeable with OTC fish oil/omega-3 supplements |
8.0 Fibrates
8.1 Fenofibrate (Tricor / Trilipix)
| Parameter | Details |
|---|---|
| Dose | Fenofibrate 145 mg daily or fenofibric acid (Trilipix) 135 mg daily |
| Indication | Severe hypertriglyceridemia (TG ≥ 500 mg/dL) for pancreatitis prevention |
| TG reduction | 30–50% |
| Safety with statins | Acceptable combination (does not inhibit statin glucuronidation) [2] |
| Renal dosing | Contraindicated if eGFR < 30; dose reduce if eGFR 30–59 |
| Monitoring | Renal function (may ↑ creatinine); hepatic panel; CBC |
| Other effects | ↑ HDL-C 10–20%; modest ↓ LDL-C 5–15%; ↑ cholelithiasis risk |
8.2 Gemfibrozil (Lopid)
| Parameter | Details |
|---|---|
| Dose | 600 mg twice daily, 30 min before meals |
| Statin interaction | Contraindicated with all statins due to myopathy/rhabdomyolysis risk [2] |
| Use | Only when fibrate is needed and patient is NOT on a statin |
| Monitoring | CK if combined with other medications; hepatic/renal function |
9.0 Niacin (Extended-Release)
| Parameter | Details |
|---|---|
| Dose | Start 500 mg QHS; titrate by 500 mg q4 weeks; max 2000 mg |
| Formulation | Extended-release only (Niaspan); immediate-release has higher hepatotoxicity risk |
| LDL-C effect | ↓ 15–25% |
| TG effect | ↓ 20–50% |
| HDL-C effect | ↑ 15–35% |
| Lp(a) effect | ↓ 20–30% (one of few agents that lowers Lp(a)) |
| Side effects | Flushing (60–70%; mitigate with aspirin 325 mg 30 min prior), hepatotoxicity, hyperglycemia, hyperuricemia, GI symptoms |
| Monitoring | Hepatic panel q6–12 weeks during titration; fasting glucose/HbA1c; uric acid |
| Limited role | AIM-HIGH [11] and HPS2-THRIVE [12] showed no ASCVD benefit when added to statin; use as last-line only |
| Potential niche | Markedly elevated Lp(a) when all other options exhausted |
10.0 Excluded Agents
10.1 Bile Acid Sequestrants
Cholestyramine, colestipol, and colesevelam are not used at this clinic due to:
- Poor gastrointestinal tolerability (bloating, constipation, nausea)
- Multiple drug interactions (bind other medications in the GI tract)
- Triglyceride elevation
- Availability of better-tolerated alternatives with superior outcomes data
10.2 Nutraceuticals
Nutraceuticals such as plant sterols/stanols, red yeast rice, bergamot, berberine, and omega-3 supplements are not included in this clinic’s therapeutic plan. These agents lack sufficient randomized controlled trial evidence for ASCVD event reduction.
10.3 Investigational Agents
Obicetrapib (CETP inhibitor) and Lp(a)-targeted therapies (muvalaplin, lepodisiran, olpasiran) are not currently included. These may be incorporated in future versions as trial data and regulatory approvals emerge.
11.0 Drug Interaction Quick Reference
| Drug A | Drug B | Interaction | Action |
|---|---|---|---|
| Any statin | Gemfibrozil | ↑↑ Myopathy/rhabdo risk | Contraindicated |
| Simvastatin/lovastatin | Strong CYP3A4 inhibitors | ↑↑ Statin levels | Switch to rosuvastatin or pravastatin |
| Simvastatin | Amlodipine | ↑ Simvastatin levels | Max simvastatin 20 mg |
| Bempedoic acid | Simvastatin | OATP1B1 inhibition | Max simvastatin 20 mg |
| Bempedoic acid | Pravastatin | OATP1B1 inhibition | Max pravastatin 40 mg |
| Icosapent ethyl | Anticoagulants | ↑ Bleeding risk | Monitor for bleeding |
| Cyclosporine | All statins | ↑↑ Statin levels | Use lowest statin dose; close monitoring |
| Fibrate + statin | Fenofibrate preferred | Gemfibrozil contraindicated | Never use gemfibrozil with statin |
| Ezetimibe | Cholestyramine | ↓ Ezetimibe absorption | Avoid combination |
12.0 Version History
| Version | Date | Description |
|---|---|---|
| 1.0.0 | 2026-03-30 | Initial release |
References
- Yokote K, Shimano H, Urashima M, et al. Efficacy and safety of pitavastatin in Japanese patients with hypercholesterolemia (LIVES study). Circ J. 2009;73(8):1466–1472.
- Jacobson TA. Myopathy with statin–fibrate combination therapy: clinical considerations. Nat Rev Endocrinol. 2009;5(9):507–518.
- Newman CB, Preiss D, Tobert JA, et al. Statin safety and associated adverse events: a scientific statement from the American Heart Association. Arterioscler Thromb Vasc Biol. 2019;39(2):e52–e81.
- Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735–742.
- Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes (IMPROVE-IT). N Engl J Med. 2015;372(25):2387–2397.
- Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease (FOURIER). N Engl J Med. 2017;376(18):1713–1722.
- Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome (ODYSSEY Outcomes). N Engl J Med. 2018;379(22):2097–2107.
- Ray KK, Wright RS, Kallend D, et al. Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol (ORION-10 and ORION-11). N Engl J Med. 2020;382(16):1507–1519.
- Nissen SE, Lincoff AM, Brennan D, et al. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients (CLEAR Outcomes). N Engl J Med. 2023;388(15):1353–1364.
- Bhatt DL, Steg PG, Miller M, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia (REDUCE-IT). N Engl J Med. 2019;380(1):11–22.
- AIM-HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255–2267.
- HPS2-THRIVE Collaborative Group. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203–212.