Accutane (Isotretinoin) Cardiovascular Impact: What the Long-Term Evidence Shows

At a glance

• Drug / oral isotretinoin (Accutane, Absorica, generics)
• Main lipid effect / higher triglycerides, lower HDL, higher cholesterol during treatment [2][1]
• Label triglyceride data / above 800 mg/dL reported; marked elevations in about 25% of trial patients [1]
• Reversibility / lipid changes reversible after stopping in clinical trials [1]
• Monitoring / fasting lipid profile and liver tests before treatment; repeat until response established, usually within 4 weeks [2][1]
• Animal finding / myocardial and arterial calcification in rats at 1.3 to 5.3 times the clinical dose after body-surface-area normalization [1]

What the label says about the heart

The Accutane label's lipid warning gives the numbers. Marked triglyceride elevations occurred in approximately 25% of patients in clinical trials, HDL decreased in about 15%, and cholesterol increased in about 7%; triglycerides above 800 mg/dL have been reported [1]. The label says these effects on triglycerides, HDL and cholesterol were reversible when Accutane was stopped [1]. It then states: 'The cardiovascular consequences of hypertriglyceridemia associated with Accutane are unknown' [1].

Does isotretinoin cause heart attack or stroke?

The Accutane label's adverse reaction list includes palpitation, tachycardia, vascular thrombotic disease and stroke, and says the relationship of some listed events to Accutane therapy is unknown [1]. The Absorica label lists the same four under Cardiovascular and notes that some reactions were reported voluntarily from a population of uncertain size, so frequency and causal relationship cannot always be reliably established [2]. A listed report is not proof of cause.

What about the heart muscle and arteries?

The Accutane label describes animal findings. In rats given 8 or 32 mg/kg/day for 18 months or longer, it lists focal calcification, fibrosis and inflammation of the myocardium, and calcification of coronary, pulmonary and mesenteric arteries [1]. Those doses were 1.3 to 5.3 times the recommended clinical dose of 1 mg/kg/day after normalization for total body surface area [1].

Who needs closer lipid monitoring?

The Accutane label calls for especially careful risk/benefit consideration in patients with diabetes, obesity, increased alcohol intake, lipid metabolism disorder or a family history of lipid metabolism disorder, and says more frequent checks of serum lipids and/or blood sugar are recommended if treatment is started [1]. The Absorica label says to complete a fasting lipid profile and liver function tests in all patients before use [2]. The Accutane label says blood lipids should be determined before treatment and then at intervals until the lipid response is established, which usually occurs within 4 weeks [1].

The Accutane label says acute pancreatitis has been reported in patients with either elevated or normal serum triglycerides, and that Accutane should be stopped if hypertriglyceridemia cannot be controlled at an acceptable level or if pancreatitis symptoms occur [1].

Frequently asked questions

›Does isotretinoin cause permanent heart damage?

The label says the lipid effects were reversible after stopping in clinical trials [1]. It also reports myocardial calcification, fibrosis, inflammation, and arterial calcification in rats given 1.3 to 5.3 times the recommended clinical dose after body-surface-area normalization [1].

›How much does isotretinoin raise triglycerides?

The Accutane label reports marked triglyceride elevations in about 25% of patients and says levels above 800 mg/dL have been reported; the lipid effects were reversible when the drug was stopped [1].

›Does isotretinoin cause heart attack or stroke?

The Accutane label lists vascular thrombotic disease and stroke as adverse reactions but says the relationship of some listed events to the drug is unknown [1]. The Absorica label lists the same reactions [2].

›What lipid monitoring does the label recommend?

The Absorica label says to complete a fasting lipid profile and liver function tests before use [2]. The Accutane label says to repeat blood lipid determinations until the lipid response is established, usually within 4 weeks, and to check more often in patients with diabetes, obesity, increased alcohol intake or lipid disorders [1].

References

1. U.S. National Library of Medicine, DailyMed. Accutane-format isotretinoin label (older non-PLR format) prescribing information. Accutane-format isotretinoin label (older non-PLR format) label
2. U.S. National Library of Medicine, DailyMed. Absorica and Absorica LD isotretinoin capsules (Sun Pharma) prescribing information. Absorica and Absorica LD isotretinoin capsules (Sun Pharma) label