Drug information of Romidepsin

Mechanism of effect

Romidepsin is a prodrug, where it becomes active once taken up into the cell. The active metabolite has a free thiol group, which interacts with zinc ions in the active site of class 1 and 2 HDAC enzymes, resulting in inhibition of its enzymatic activity.

Pharmacodynamic

not available

Pharmacokinetics

Absorption

Romidepsin exhibited linear pharmacokinetics at standard doses.

Volume of distribution

44.5L

Protein binding

Highly protein bound in plasma (92%-94%)

Metabolism

Romidepsin undergoes extensive hepatic metabolism in vitro primarily by CYP3A4 with minor contribution from CYP3A5, CYP1A1, CYP2B6 and CYP2C19.

Half life

Approximately 3 hours

Clearance

8.4L/h

Drug indications

Cutaneous T-cell lymphoma: Treatment of cutaneous T-cell lymphoma (CTCL) in adult patients who have received at least one prior systemic therapy.

Peripheral T-cell lymphoma: Treatment of peripheral T-cell lymphoma (PTCL) in adult patients who have received at least one prior therapy.

Dosage

Cutaneous T-cell lymphoma: IV: 14 mg/m² days 1, 8, and 15 of a 28-day treatment cycle; repeat cycle as long as benefit continues and treatment is tolerated.

Peripheral T-cell lymphoma: IV: 14 mg/m² days 1, 8, and 15 of a 28-day treatment cycle; repeat cycle as long as benefit continues and treatment is tolerated.

Drug contraindications

Hypersensitivity

Side effects

• bleeding gums
• blood in the urine or stools
• blurred vision
• bone pain
• chest pain
• chills
• confusion
• cough
• decreased urine output
• difficulty with breathing
• dry mouth
• fast or irregular heartbeat
• fever
• flushed, dry skin
• headache
• increased hunger
• increased urination
• joint pain, stiffness, or swelling
• loss of appetite
• lower back or side pain
• muscle cramps in the hands, arms, feet, legs, or face
• nausea
• painful or difficult urination
• seizures
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• stomach cramps or pain
• sweating
• swelling of the face, ankles, feet, lower legs, or hands
• tremor
• unexplained weight loss
• unusual bleeding or bruising
• unusual tiredness or weakness
• vomiting

Interactions

Carbamazepine , nelfinavir , Dolasetron , vandetanib , Droperidol , Procainamide , Dofetilide , Arsenic trioxide , Etravirine , Halofantrine , Grepafloxacin , Paliperidone , Butabarbital , Entrectinib , Amiodarone , Infliximab , Deferiprone , Disopyramide , Citalopram , Cisapride , Anagrelide , Efavirenz , Amisulpride , Baricitinib , Ceritinib , bedaquiline , escitalopram , Influenza vaccine , BCG vaccine , Adalimumab , Certolizumab , Mifepristone , Fingolimod , Methadone , Haloperidol , Hydroxychloroquine , cladribine , Clozapine , Bepridil , Gemtuzumab , Sarecycline , vemurafenib , Meningococcal conjugate vaccine

• adalimumab, amiodarone, amisulpride, anagrelide, arsenic trioxide, baricitinib, bcg, bcg vaccine, bedaquiline, bepridil, ceritinib, certolizumab, chloroquine, cisapride, citalopram, cladribine, clozapine, deferiprone, disopyramide, efavirenz, escitalopram, etanercept, fingolimod, haloperidol, hydroxychloroquine, infliximab, influenza virus vaccine, h1n1, live, leflunomide, methadone, mifepristone
• Coadministration with other drugs that prolong QT interval (eg, sotalol, dofetilide, erythromycin) may increase risk for serious arrhythmias
• Binds to estrogen and may reduce effectiveness of oral contraceptives

Alerts

QT prolongation; potassium and magnesium should be within normal limits before administration

Monitor hematologic parameters; interrupt/discontinue treatment if thrombocytopenia, leukopenia, or anemia becomes severe

Serious and sometimes fatal infections reported with 30 days after treatment including pneumonia, sepsis, and viral reactivation (eg, Epstein Barr, hepatitis B viruses); risk may be greater in patients with a history of monoclonal antibodies treatment directed against lymphocyte antigens and in patients with disease involvement of the bone marrow

Avoid during pregnancy, no adequate trials exist; based on MOA, likely to cause fetal harm

Points of recommendation

Tell your doctor if you have ever had:

• heart problems, heart rhythm disorder;
• long QT syndrome(in you or a family member);
• kidney disease;
• liver disease(especially hepatitis B);
• an electrolyte imbalance (such as high or low levels of potassium or magnesium in your blood); or

if you are sick with nausea, vomiting, or diarrhea

Pregnancy level

Based on its mechanism of action and findings from animal studies, may cause embryo-fetal harm when administered to a pregnant woman

Related drugs

Infliximab , belinostat