The Safety of Diabetes, Hyperlipidemia, Hypertension and Meds with Cirrhosis

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Pain Medications
Pain Medications Recommended dose Additional Information
NSAIDs Refer to Symptom Management→ Pain for dosing and additional information

    Pain – Cirrhosis Care

Acetaminophen Refer to Symptom Management→ Pain for dosing and additional information

    Pain – Cirrhosis Care

Opioids Refer to Symptom Management→ Pain for dosing and additional information

    Pain – Cirrhosis Care

Lipid Lowering Therapies
Lipid Lowering Therapies Recommended Dose
Statins Refer to Cirrhosis →Etiology management specific to cirrhosis for dosing and additional information
Etiology management specific to cirrhosis – Cirrhosis Care

Ezetimibe Child-Pugh Class A: No dosage adjustment necessary

Child-Pugh Class B/C: Contraindicated

Fenofibrate Contraindicated
Alirocumab (PCSK9 Inhibitor) Child-Pugh Class A/B: No dosage adjustment necessary

Child-Pugh Class C: Has not been studied

Evolocumab (PCSK9 Inhibitor) Child-Pugh Class A/B: No dosage adjustment necessary

Child-Pugh Class C:Has not been studied

Diabetes Medications
Diabetes Medications Recommended Dose Additional Information
Acarbose Contraindicated
Metformin Initial: 500 mg PO twice daily OR 850 mg PO once daily with meals; may adjust dose in 500 mg increments weekly OR 850 mg every 2 weeks.

Max: 2550 mg/day

Use cautiously in those with advanced liver disease, and in patients at risk of lactic acidosis (e.g. patients with renal impairment, alcohol use).
Contraindicated in hepatic failure.
Metformin may reduce the risk of hepatocellular carcinoma.
Rosiglitazone (Thiazolidinedione) Contraindicated
Pioglitazone (Thiazolidinedione) Contraindicated
Glyburide (Sulfonylurea) Initial: 2.5 – 5 mg PO once daily

Max: 20 mg/day

Contraindicated in Child-Pugh Class C. Least likely sulfonylurea to cause clinically apparent liver injury. Discontinue if the transaminase levels go above 2.5x the upper limit of normal.
Gliclazide (Sulfonylurea) Initial: 40 – 80 mg PO once daily with breakfast

Max: 320 mg/day

Contraindicated in Child-Pugh Class C. Discontinue if the transaminase levels go above 2.5x the upper limit of normal.
Glimepiride (Sulfonylurea) Initial: 1 – 2 mg PO once daily

Max: 8 mg/day

Contraindicated in Child-Pugh Class C. Discontinue if the transaminase levels go above 2.5x the upper limit of normal.
Repaglinide Initial: If HbA1c < 8%, 0.5 mg PO within 30 minutes before a meal, 2 to 4 times daily. If HbA1c > 8%, 1 – 2 mg PO within 30 minutes before a meal, 2 to 4 times daily.

Max: 4 mg/dose (16 mg/day).

Do not take dose if meal is skipped.

Use with caution. Consider longer intervals between dosage adjustments. Increased risk of hypoglycemia in patients with hepatic dysfunction.
Nateglinide Initial: 60 mg PO three times daily, within 30 minutes before a meal.

Max: 120 mg PO three times daily, within 30 minutes before a meal.

Use with caution. Consider longer intervals between dosage adjustments. Increased risk of hypoglycemia in patients with hepatic dysfunction. Theoretically safer than repaglinide based on pharmacokinetic observations from trials.
Sitagliptin (DPP-4 Inhibitor) Initial: 100 mg PO once daily with or without food DPP-4 inhibitors are minimally metabolized by the liver and are relatively safe in cirrhosis patients.
Alogliptin (DPP-4 Inhibitor) Initial: 25 mg PO once daily with or without food DPP-4 inhibitors are minimally metabolized by the liver and are relatively safe in cirrhosis patients. However, there have been post-marketing reports of hepatic failure with alogliptin.
Linagliptin (DPP-4 Inhibitor) Initial: 5 mg PO once daily with or without food DPP-4 inhibitors are minimally metabolized by the liver and are relatively safe in cirrhosis patients.
Saxagliptin (DPP-4 Inhibitor) Initial: 2.5 mg – 5 mg PO once daily with or without food DPP-4 inhibitors are minimally metabolized by the liver and are relatively safe in cirrhosis patients.
Liraglutide (GLP-1 Agonist) Initial: 0.6 mg subcutaneous once daily for 1 week; maintenance 1.2 mg once daily. May increase to 1.8 mg/day after at least 1 week of treatment with the 1.2 mg/day regimen.

Max: 1.8 mg/day

Use with caution due to limited experience. Few studies have demonstrated that liraglutide may decrease hepatic inflammation, liver fibrosis, and body weight.
Dapagliflozin (SGLT2 Inhibitor) Initial: 5 mg PO once daily in the morning.

Max: 10 mg/day

Studies have demonstrated higher systemic drug levels compared to healthy subjects. Long term efficacy has not been well studied. Use with caution in severe impairment.
Empagliflozin (SGLT2 Inhibitor) Initial: 10 mg PO once daily in the morning.

Max: 25 mg/day

Studies have demonstrated higher systemic drug levels compared to healthy subjects. Long term efficacy has not been well studied. Use with caution in severe impairment.
Canagliflozin (SGLT2 Inhibitor) Initial: 100 mg PO once daily taken before the first meal of the day

Max: 300 mg/day (if eGFR < 60 mL/min/1.73 m2, max 100 mg/day)

Studies have demonstrated higher systemic drug levels compared to healthy subjects. Long term efficacy has not been well studied. Use with caution in severe impairment.
Ertugliflozin (SGLT2 Inhibitor) Initial: 5 mg PO once daily

Max: 15 mg/day

Studies have demonstrated higher systemic drug levels compared to healthy subjects. Long term efficacy has not been well studied. Use with caution in severe hepatic impairment.
Insulin (many formulations) Patient specific Insulin requirements can change based on the severity of cirrhosis. Decompensated cirrhosis patients have decreased hepatic metabolism and reduced capacity for gluconeogenesis therefore lower doses are required. Compensated patients are predominantly insulin resistant which would potentially require higher doses of insulin.
Anti-hypertensives
Antihypertensives Recommended Dose Additional Information
Non-Selective Beta Blockers Refer to Treatment → Varices for dosing and additional information
Varices - Cirrhosis Care

ACE Inhibitors/ARBs Max: 20 mg PO once daily

Avoid in patients with ascites.
Nifedipine XL (CCB) Initial: 30 mg PO once daily

Max: 90 mg/day

Has not been studied in patients with hepatic dysfunction; use with caution. May cause small transient rises in liver enzymes which will resolve with continued drug use. However, clearance in cirrhotic patients is reduced, leading to increased systemic exposure. Monitor closely for adverse effects/toxicity and consider dose adjustments.
Amlodipine (CCB) Initial: 2.5 mg PO once daily

Max: 10 mg PO once daily

Titrate slowly in patients with cirrhosis/hepatic impairment.
Felodipine (CCB) Initial: 2.5 mg PO once daily

Max: 10 mg PO daily

Diltiazem (CCB) Initial:30 mg PO four times daily (immediate release), or 120 mg PO once daily (extended release)

Max: 360 mg PO daily

Increased half-life in patients with cirrhosis therefore use with caution. Mild and significant elevations in hepatic transaminases have been observed, reversible upon discontinuation.
Verapamil Immediate Release (CCB) Initial: 20 mg PO three times daily

Max: 480 mg/day in three divided doses

Max: 360 mg PO daily

Verapamil Extended Release (CCB) Initial: 100 mg PO at bedtime

Max: 480 mg/day in one or two divided doses

Thiazide Diuretics Avoid use in ascites due to risk of hyponatremia
Furosemide (Loop Diuretic) Refer to Treatment →Ascites for dosing and additional information
Ascites - Cirrhosis Care
Spironolactone (Potassium-Sparing Diuretic) Refer to Treatment →Ascites for dosing and additional information
Ascites - Cirrhosis Care
Antidepressants
Antidepressants Recommended Dose Additional Information
SSRIs Refer to Symptom Management →Depression for dosing and additional information
Depression – Cirrhosis Care

SNRIs Refer to Symptom Management →Depression for dosing and additional information
Depression – Cirrhosis Care

Amitriptyline (TCA) For depression:

Initial: 25 mg PO once daily or in divided doses

Max: 100 mg PO once daily

Nortriptyline (TCA) For depression:

Initial: 25 mg PO once daily or in divided doses

Max: 100 mg PO once daily

Bupropion (NDRI) Child-Pugh Class A: Manufacturer recommends dose and/or frequency reduction. No specific recommendations provided, however, some experts recommend decreasing initial dose to 50% of usual dose and reducing dosing frequency

Child-Pugh Class B/C: Max 150 mg every other day.

Half-life for active metabolites increased 2- to 5-fold in patients with severe hepatic impairment.
Mirtazapine Refer to Symptom Management →Depression for dosing and additional information
Depression – Cirrhosis Care
Sedatives
Sedatives Recommended Dose Additional Information
Zopiclone Refer to Symptom Management → Sleep Disturbance for dosing and additional information
Sleep Disturbance – Cirrhosis Care

Proton Pump Inhibitors
Proton Pump Inhibitors Recommended Dose Additional Information
Esomeprazole Max: 20 mg PO once daily Consider deprescribing. Algorithm can be found at: Proton Pump Inhibitor (PPI) Deprescribing
Pantoprazole Max: 20 mg PO once daily

Consider deprescribing. Algorithm can be found at: Proton Pump Inhibitor (PPI) Deprescribing
Lansoprazole 15 – 30 mg PO once daily

Consider deprescribing. Algorithm can be found at: Proton Pump Inhibitor (PPI) Deprescribing
Rabeprazole 20 mg PO once daily

Consider deprescribing. Algorithm can be found at: Proton Pump Inhibitor (PPI) Deprescribing
Dexlansoprazole Max: 30 mg PO once daily Consider deprescribing. Algorithm can be found at: Proton Pump Inhibitor (PPI) Deprescribing
Omeprazole Max: 20 mg PO once daily Consider deprescribing. Algorithm can be found at: Proton Pump Inhibitor (PPI) Deprescribing
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