In a 38-year-old woman with severe hypertriglyceridemia, high LDL cholesterol, and low HDL cholesterol, which of the following medications—adalimumab, clozapine, combined estrogen‑progestin oral contraceptive, fluoxetine, or mirabegron—should be discontinued or replaced?

Discontinue the Estrogen-Progesterone Oral Contraceptive Immediately

The combined estrogen-progestin oral contraceptive must be replaced in this 38-year-old woman with severe hypertriglyceridemia (442 mg/dL), elevated LDL (177 mg/dL), and critically low HDL (24 mg/dL). This medication is directly worsening her lipid profile and substantially increasing her cardiovascular risk.

Why the Oral Contraceptive Must Be Stopped

Direct Triglyceride Elevation

• Combined oral contraceptives increase triglycerides by 13-75% above baseline, with the estrogen component being the primary driver of hypertriglyceridemia 1, 2.
• The estrogen in oral contraceptives causes insulin resistance and hypertriglyceridemia, which are features of the metabolic syndrome that increase cardiovascular disease risk 3.
• At triglyceride levels >500 mg/dL, bile acid sequestrants (like colesevelam) are contraindicated due to risk of hypertriglyceridemia-induced pancreatitis 1. While this patient is at 442 mg/dL, continuing oral contraceptives will likely push her above this dangerous threshold.

HDL Cholesterol Suppression

• Depending on the progestin type and dose, oral contraceptives can decrease HDL cholesterol by up to 16%, particularly formulations containing levonorgestrel 2.
• This patient's HDL of 24 mg/dL is already critically low (normal >50 mg/dL for women), and oral contraceptives are likely contributing to this dangerous level 1.

Guideline-Based Contraindications

• The ACC/AHA guidelines explicitly recommend avoiding oral contraceptives in women with severe or uncontrolled hypertension and using them for the shortest duration possible 1.
• When oral contraceptives must be used in women with dyslipidemia, only low-dose formulations (20-30 mcg ethinyl estradiol) or progestin-only contraception should be considered 1.
• Alternative contraceptive measures should be considered for patients with severe uncontrolled hypercholesterolemia or lipid disorders carrying high risk of coronary heart disease 4.

Why the Other Medications Can Continue

Adalimumab (TNF-alpha inhibitor)

• No evidence links adalimumab to dyslipidemia in the provided guidelines or research [1-5].

Clozapine

• While atypical antipsychotics including clozapine are listed as potentially elevating blood pressure, the primary concern is hypertension, not dyslipidemia 1.
• The guideline recommends discontinuing or limiting use when possible, but this is in the context of blood pressure management, not lipid disorders 1.

Fluoxetine (SSRI)

• SSRIs are actually recommended as alternative agents to other antidepressants that may affect blood pressure 1.
• No evidence in the provided materials suggests fluoxetine worsens lipid profiles [1-5].

Mirabegron (Beta-3 agonist)

• No evidence links mirabegron to dyslipidemia in the provided guidelines or research [1-5].

Recommended Replacement Strategy

Immediate Action

• Discontinue the combined oral contraceptive immediately given the severe dyslipidemia and cardiovascular risk 1, 4.

Alternative Contraceptive Options

• Switch to progestin-only contraception (progestin-only pills, implant, or IUD), which have only minor metabolic effects and do not significantly affect lipid profiles 2, 1.
• Consider barrier methods or copper IUD as metabolically neutral alternatives 1.
• Avoid any estrogen-containing contraceptives given this patient's severe hypertriglyceridemia 4, 5.

Critical Monitoring After Discontinuation

• Recheck lipid panel 4-8 weeks after discontinuing oral contraceptives to assess improvement in triglycerides and HDL 6.
• Expect triglyceride levels to decrease by 13-75% from current levels once the estrogen effect is removed 2.
• If triglycerides remain >500 mg/dL after oral contraceptive discontinuation, bile acid sequestrants remain contraindicated and fibrate therapy should be considered 1.

Common Pitfall to Avoid

Do not attempt to manage this dyslipidemia with lipid-lowering therapy while continuing the oral contraceptive. The estrogen component will continue to drive triglyceride elevation and HDL suppression, making lipid management significantly more difficult and potentially ineffective 6, 3. The offending medication must be removed first before initiating or optimizing lipid-lowering therapy.