Can Otezla (apremilast) cause renal impairment or flank pain?

Otezla Does Not Directly Cause Kidney Damage, But Requires Dose Adjustment in Severe Renal Impairment

Otezla (apremilast) does not cause kidney damage or impair renal function, but it does require dose reduction in patients with severe pre-existing renal impairment due to increased drug exposure. The medication is metabolized primarily by the liver, not the kidneys, and is safe to use across a wide range of renal function 1, 2.

Key Points About Otezla and Kidney Function

No Direct Renal Toxicity

• Apremilast is not nephrotoxic and does not cause kidney impairment 1
• The drug is metabolized by the liver via CYP450 enzymes (primarily CYP3A4), not eliminated unchanged by the kidneys 2
• Only 3% of the drug is recovered unchanged in urine 2
• Severe renal impairment is not a contraindication to use 1

Dosing Adjustments Required for Severe Renal Impairment

For patients with severe renal impairment (creatinine clearance <30 mL/min or eGFR <30 mL/min):

• Reduce dose to 30 mg once daily (instead of twice daily) 1, 2
• This is because drug exposure (AUC) increases by approximately 88% and peak levels (Cmax) increase by 42% in severe renal impairment 2, 3

No dose adjustment needed for:

• Mild renal impairment (eGFR 60-89 mL/min) 2, 3
• Moderate renal impairment (eGFR 30-59 mL/min) 2, 3

Regarding Flank Pain or "Kidney Area" Pain

Flank pain is not a recognized adverse effect of Otezla based on FDA labeling and major clinical guidelines 1, 2. The most common adverse effects are:

• Diarrhea and nausea (gastrointestinal, not renal)
• Upper respiratory tract infections
• Headache
• Depression (in ~1% of patients) 1

Important Caveat: One Case Report

There is one published case report of Fanconi syndrome (proximal renal tubular acidosis) potentially associated with apremilast 4. This patient developed:

• Hypokalemia
• Hyperchloremic metabolic acidosis
• Low uric acid
• Proteinuria

However, this is an extremely rare, isolated case and has not been replicated in any clinical trials or post-marketing surveillance involving thousands of patients 5. This should not change prescribing practices but warrants awareness.

Clinical Approach

If a patient on Otezla reports flank pain:

1. Do not automatically attribute it to the medication - flank pain is not a known side effect
2. Evaluate for common causes: kidney stones, urinary tract infection, musculoskeletal pain, or other unrelated conditions
3. Check basic metabolic panel and urinalysis if clinically indicated
4. Consider that gastrointestinal side effects (common with Otezla) can sometimes be mislocalized by patients

Otezla can be safely used in patients with complex medical conditions, including those with renal disease, making it an excellent option when other systemic agents are contraindicated 1, 5.