Koselugo (Selumetinib)

Koselugo (selumetinib) is indicated for conditions involving dysregulated MAPK/ERK signaling, particularly neurofibromatosis type 1.

• Neurofibromatosis type 1 (NF1) with symptomatic, inoperable plexiform neurofibromas: reduces tumor volume and related symptoms.
• NF1‑associated plexiform neurofibromas: slows disease progression and may improve quality of life.
• NF1 patients with measurable plexiform neurofibromas: provides a targeted oral therapy option when surgery is not feasible.

• Selumetinib selectively inhibits the serine/threonine kinases MEK1 and MEK2, which are key components of the MAPK/ERK signaling cascade. By blocking MEK activity, the drug prevents downstream phosphorylation of ERK proteins, thereby reducing cellular proliferation and survival signals that drive the growth of neurofibromas in patients with NF1.

Common Side Effects

• Diarrhea: mild to moderate watery stools.
• Nausea and vomiting: gastrointestinal upset.
• Rash or skin irritation: often mild erythema.
• Fatigue: reduced energy levels.
• Edema: swelling of extremities.
• Headache: occasional throbbing pain.

Serious or Rare Side Effects

• Retinal vein occlusion: visual disturbances requiring urgent ophthalmic evaluation.
• Interstitial lung disease: respiratory symptoms such as cough or shortness of breath.
• Cardiac dysfunction: decreased left‑ventricular ejection fraction.
• Severe hypertension: markedly elevated blood pressure.
• Hepatic toxicity: elevated liver enzymes or jaundice.
• Stevens‑Johnson syndrome or toxic epidermal necrolysis: severe skin reactions.

Patients receiving Koselugo should be monitored closely for organ‑specific toxicities and other safety concerns.

• Monitor cardiac function: obtain baseline and periodic ECG/ECHO due to risk of reduced ejection fraction.
• Assess ocular health: perform baseline eye examination and watch for visual changes.
• Check liver enzymes: monitor hepatic function as hepatotoxicity may occur.
• Evaluate blood pressure: manage hypertension that can develop during therapy.
• Avoid use in pregnancy: teratogenic potential is unknown; contraindicated.
• Store at ambient temperature below 25 °C: keep in original packaging, protect from moisture and light.

Selumetinib may interact with other medicines that affect its metabolism or increase toxicity.

Major Interactions (Avoid)

• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole): may increase selumetinib exposure.
• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine): may reduce therapeutic effect.
• Concomitant use with other MEK inhibitors: additive toxicity risk.

Moderate Interactions (Monitor Closely)

• Anticoagulants (e.g., warfarin): monitor INR for potential increased bleeding.
• QT‑prolonging agents: observe ECG for arrhythmia risk.
• Immunosuppressants: watch for heightened infection susceptibility.