Dosage adjustment recommendations for patients with hepatic and renal insufficiency when using apremilast (Otelac)

Patients with hepatic and renal insufficiency need to pay special attention to dose adjustment when using apremilast, because the drug is mainly excreted through the kidneys, and its metabolism and clearance rate will be significantly affected by renal function status. For patients with mild and moderate hepatic impairment, current studies show that apremilast does not significantly increase blood concentration, so there is usually no need to adjust the dose and can still be taken orally at the regular dose. However, clinically it is still recommended to closely observe the patient's tolerance, including gastrointestinal reactions, weight changes, and mental status in the early stages of use, so that treatment strategies can be adjusted in a timely manner.

Relative to hepatic insufficiency, renal insufficiency has a greater impact on the pharmacokinetics of apremilast. For patients with moderate renal insufficiency (such as eGFR 30–59 ml/min), the conventional dose can still be maintained in most cases, but care should be taken not to gradually increase the dose too fast, and the medication adjustment period should be extended if necessary. For patients with severe renal insufficiency (such as eGFR<30 ml/min), due to reduced drug clearance, blood drug concentrations may increase significantly, increasing the risk of adverse reactions, especially nausea, diarrhea, decreased appetite, or weight loss. Therefore, guidelines often recommend halving the dose or reducing the frequency of daily administration to reduce the incidence of adverse effects.

In addition, patients with hepatic and renal insufficiency should pay more attention to monitoring during the use of apremilast. It is recommended to regularly check glomerular filtration rate (eGFR), liver function indicators (ALT, AST, TBil), electrolytes and weight changes, and record the time and frequency of adverse drug reactions. The first 1–2 weeks after dose adjustment are the focus of observation, because gastrointestinal reactions or psychiatric adverse reactions, such as depression or sleep changes, are most likely to occur during this period. Once symptoms worsen, the drug should be discontinued in time or the dose should be further adjusted.

Overall, dose adjustment of apremilast is generally not required in patients with hepatic impairment, but in patients with renal insufficiency, especially those with severe renal impairment, individualized dose reduction is required based on renal function class. When formulating a medication plan, doctors will evaluate the final dose based on the patient's age, weight, previous underlying diseases, and tolerance. Patients should not increase or decrease the dose on their own, but should take it according to the adjusted plan under the guidance of a doctor. At the same time, liver and kidney function and adverse reactions should be strictly monitored to ensure medication safety and maximum efficacy.

Reference materials:https://www.nlm.nih.gov/