Can Vraylar (cariprazine) be prescribed in a patient with mildly elevated alanine aminotransferase and aspartate aminotransferase?

Can Vraylar Be Used With These Liver Enzyme Levels?

Yes, Vraylar (cariprazine) can be prescribed in a patient with ALT 73 U/L and AST 45 U/L, as these values represent mild elevations that do not contraindicate initiation of this medication.

Rationale Based on FDA Labeling and Clinical Guidelines

Vraylar's Hepatic Safety Profile

• The FDA label for Vraylar reports that hepatic enzyme elevations (ALT, AST) occurred in clinical trials but were generally mild and did not require specific dosage adjustments or contraindications based on baseline liver enzyme levels 1
• In schizophrenia trials, hepatic enzyme increases occurred in 2-3% of Vraylar-treated patients versus 1% of placebo patients, indicating a low overall risk 1
• In bipolar mania trials, hepatic enzyme increases occurred in approximately 2% of patients across all dose ranges 1
• Vraylar does not carry specific warnings against use in patients with mildly elevated transaminases, and no dosage adjustment is recommended for mild hepatic impairment 1

Clinical Context of These Enzyme Levels

• Your patient's ALT of 73 U/L represents approximately 2× the upper limit of normal for males (ULN ~30-33 U/L) or 3× ULN for females (ULN ~19-25 U/L), which is classified as a mild elevation (<5× ULN) 2
• The AST of 45 U/L is only minimally elevated and less clinically significant than the ALT 2
• These values fall well below the threshold of ≥3× ULN that would trigger urgent evaluation or medication discontinuation in most clinical scenarios 3, 2

Recommended Management Algorithm

Before Starting Vraylar

1. Obtain baseline complete liver panel including ALT, AST, alkaline phosphatase, total and direct bilirubin, albumin, and INR to establish synthetic function 2
2. Document that bilirubin and INR are normal, as elevation of these markers would indicate synthetic dysfunction requiring further evaluation before starting any new medication 2
3. Review all current medications against the LiverTox® database to identify other potential hepatotoxic agents that might be contributing to the mild elevation 2
4. Assess for common causes of mild ALT elevation:
   • Metabolic syndrome components (obesity, diabetes, hypertension, dyslipidemia) suggesting NAFLD 2
   • Alcohol consumption history (≥14-21 drinks/week in men, ≥7-14 drinks/week in women) 2
   • Viral hepatitis serologies (HBsAg, anti-HCV) 2
   • Recent strenuous exercise or muscle injury that could transiently elevate transaminases 2

Monitoring Strategy After Initiating Vraylar

• Repeat liver enzymes at 2-4 weeks after starting Vraylar to establish trend and ensure values are stable or improving 2
• If ALT remains <3× ULN and patient is asymptomatic, continue Vraylar and monitor liver enzymes every 4-8 weeks until stabilized 2
• If ALT increases to ≥3× ULN (>90 U/L for men, >57 U/L for women), repeat testing within 2-5 days and intensify evaluation for alternative causes 2
• If ALT rises to ≥5× ULN or if ALT ≥3× ULN plus bilirubin ≥2× ULN, discontinue Vraylar immediately and evaluate urgently for drug-induced liver injury 3, 2

Critical Thresholds to Remember

Threshold	Action Required
ALT <3× ULN	Continue Vraylar with routine monitoring [2]
ALT 3-5× ULN	Repeat within 2-5 days; evaluate for other causes [2]
ALT ≥5× ULN	Consider discontinuation; urgent hepatology referral [2]
ALT ≥3× ULN + bilirubin ≥2× ULN	Discontinue immediately (Hy's Law pattern) [3,2]

Common Pitfalls to Avoid

• Do not assume the mild ALT elevation is due to Vraylar before starting it—the elevation is pre-existing and likely reflects an underlying condition such as NAFLD, which is extremely common 2, 4
• Do not withhold necessary psychiatric treatment for mild, asymptomatic transaminase elevations—the mental health benefits of treating schizophrenia or bipolar disorder far outweigh the minimal hepatic risk at these enzyme levels 1, 5
• Do not forget to calculate the FIB-4 score (using age, ALT, AST, platelet count) to assess for advanced fibrosis risk, especially if the patient has metabolic risk factors; a score >2.67 would warrant hepatology referral before or concurrent with starting Vraylar 2, 6
• Do not overlook non-hepatic causes of AST elevation, such as recent exercise, muscle injury, or cardiac conditions, which can elevate AST more than ALT 2

Additional Considerations

• If the patient has metabolic syndrome or NAFLD (the most common cause of mild ALT elevation), emphasize lifestyle modifications including 7-10% weight loss, low-carbohydrate diet, and 150-300 minutes/week of moderate exercise 2, 6
• Screen for hypothyroidism and celiac disease if no other cause is identified, as both can cause isolated ALT elevation 7
• Consider abdominal ultrasound if ALT remains elevated after 4-6 weeks to assess for hepatic steatosis, which has 84.8% sensitivity and 93.6% specificity for moderate-to-severe fatty liver 2