Pomalidomide is a medication that belongs to a class of drugs known as immunomodulatory agents. It is primarily used in the treatment of certain types of cancer, specifically multiple myeloma. Pomalidomide works by affecting the immune system and inhibiting the growth of cancer cells. It is taken orally in the form of capsules, usually once daily, and is often used in combination with other medications.

Pomalidomide (Pomalyst) is a derivative of thalidomide. It has got cytotoxic, immune-modulator, and anti-angiogenic properties. It is used in combination with dexamethasone to treat patients with multiple myeloma.

Pomalidomide (Pomalyst) Uses:

• Relapsed/ refractory Multiple Myeloma:
  • It is used in treatment of multiple myeloma along with dexamethasone in patients who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor, and have demonstrated disease progression after or within 60 days of completion of the prior therapy.

Pomalidomide (Pomalyst) Dose in Adults

Note: Before starting new cycles of therapy with pomalidomide, it is important to make sure that certain blood cell counts are within a specific range. The ANC (absolute neutrophil count) should be equal to or greater than 500 cells per millimeter (mm), and the platelet count should be equal to or greater than 50,000 cells per mm. These counts help ensure that the body has enough healthy white blood cells and platelets to fight infections and prevent bleeding.

Pomalidomide (Pomalyst) Dose in the treatment of relapsed/ refractory multiple myeloma:

• The recommended dose of pomalidomide for the treatment of relapsed/refractory multiple myeloma is 4 mg taken orally once daily.
• This dosage is typically followed for 21 days out of a 28-day cycle.
• It is commonly used in combination with dexamethasone, a steroid medication.
• This treatment regimen should be continued until there is disease progression or the patient experiences unacceptable side effects.

Off-label combinations:

• Pomalidomide may be used off-label in combination with other medications.
• For example, when combined with elotuzumab and dexamethasone or daratumumab and dexamethasone, the recommended dose and schedule remain the same.

Dosage adjustment for concomitant therapy with strong CYP1A2 inhibitors:

• If a patient is also taking strong CYP1A2 inhibitors, it is generally advised to avoid using them concurrently with pomalidomide.
• However, if avoiding concomitant use is not possible, the pomalidomide dose should be reduced by 50% to mitigate potential interactions or adverse effects.

Use in Children:

Not indicated.   

Pomalidomide (Pomalyst) Pregnancy Category: X

• Pomalidomide should never be used during pregnancy as it can cause severe birth defects or death to the developing baby.
• It is similar to a medication called thalidomide, which is known to be harmful to human babies.
• Some of the birth defects caused by thalidomide include missing limbs, bone problems, eye and ear abnormalities, facial paralysis, heart defects, and problems with the urinary and genital organs.
• If a pregnancy occurs while taking pomalidomide, the treatment should be stopped immediately.
• Women who can become pregnant should have two negative pregnancy tests before starting pomalidomide and use two forms of birth control or completely avoid sexual activity for at least four weeks after stopping the medication.
• Regular pregnancy tests should be done during treatment and for four weeks after stopping pomalidomide.
• Men taking pomalidomide should also use condoms during sexual contact with women who can become pregnant, and they should not donate sperm.
• If there is any suspicion of pregnancy or exposure to the drug, it should be reported to the FDA and the prescribing company.

Use of pomalidomide while breastfeeding

• The presence of pomalidomide in breast milk is unknown, and it is advised not to use it while breastfeeding.
• The medication can potentially cause significant side effects, so its use during breastfeeding should be avoided.
• If there is a need to continue therapy with pomalidomide, the healthcare provider should carefully evaluate whether the benefits of treatment outweigh any potential risks to the nursing infant.

Pomalidomide (Pomalyst) Dose in Kidney Disease:

• For patients with a creatinine clearance (CrCl) level of 15 to less than 60 mL/minute, there is no specific dosage adjustment mentioned in the manufacturer's labeling for pomalidomide. Studies have shown that the pharmacokinetics of pomalidomide were not significantly affected in patients with CrCl between 15 and 60 mL/minute compared to those with normal kidney function.

 

• In the case of patients undergoing hemodialysis, an initial dose of 3 mg of pomalidomide is recommended once daily. It should be administered after the hemodialysis procedure on dialysis days since hemodialysis can remove pomalidomide from the bloodstream.

 

• In some off-label cases where the CrCl is less than 45 mL/minute, including patients requiring hemodialysis, a phase II study suggested that a dose of 4 mg of pomalidomide once daily for 21 days out of a 28-day treatment cycle was safe and effective when used in combination with low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma.

 

• To assess renal function in multiple myeloma patients with a stable serum creatinine, the International Myeloma Working Group (IMWG) recommends using either the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (preferred) or the Modification of Diet in Renal Disease (MDRD) formula.

 

• For patients with a CrCl of 45 mL/minute or higher, no dosage adjustment is required for pomalidomide.

Pomalidomide (Pomalyst) Dose in Liver disease:

Before starting treatment with pomalidomide, the dosage may need to be adjusted based on the severity of hepatic impairment.

• For patients with mild or moderate impairment (Child-Pugh class A or B), the initial dose is typically 3 mg once daily.
• For patients with severe impairment (Child-Pugh class C), the initial dose is usually reduced to 2 mg once daily.

 

• During the course of treatment, if liver enzymes become elevated, it is recommended to discontinue pomalidomide and evaluate the liver function.
• Once the liver enzymes return to baseline levels, the healthcare provider may consider restarting the medication at a lower dose to minimize the risk of liver-related side effects.
• It's important to closely monitor liver function throughout treatment with pomalidomide and promptly report any signs of liver problems, such as jaundice (yellowing of the skin or eyes), dark urine, or abdominal pain.
• Individualized dosage adjustments and careful monitoring are necessary for patients with hepatic impairment to ensure the medication is safely and effectively administered.

Common Side Effects of Pomalidomide (Pomalyst):

• Cardiovascular:
  • Peripheral Edema
• Central Nervous System:
  • Fatigue
  • Dizziness
  • Peripheral Neuropathy
  • Neuropathy
  • Headache
  • Anxiety
  • Confusion
• Dermatologic:
  • Skin Rash
  • Pruritus
• Endocrine & Metabolic:
  • Hypercalcemia
  • Weight Loss
  • Hypokalemia
  • Hyperglycemia
  • Hyponatremia
• Gastrointestinal:
  • Constipation
  • Nausea
  • Diarrhea
  • Decreased Appetite
  • Vomiting
• Hematologic & Oncologic:
  • Neutropenia
  • Anemia
  • Thrombocytopenia
  • Leukopenia
• Neuromuscular & Skeletal:
  • Weakness
  • Back Pain
  • Musculoskeletal Chest Pain
  • Muscle Spasm
  • Arthralgia
  • Myasthenia
  • Musculoskeletal Pain
  • Ostealgia
• Renal:
  • Increased Serum Creatinine
  • Renal Failure
• Respiratory:
  • Upper Respiratory Tract Infection
  • Dyspnea
  • Pneumonia
  • Cough
  • Epistaxis
• Miscellaneous:
  • Fever

Less Common Side Effects Of Pomalidomide (Pomalyst):

• Central Nervous System:
  • Chills
  • Insomnia
• Dermatologic:
  • Xeroderma
  • Hyperhidrosis
• Endocrine & Metabolic:
  • Dehydration
  • Hypocalcemia
• Genitourinary:
  • Urinary Tract Infection
• Hematologic & Oncologic:
  • Febrile Neutropenia
  • Lymphocytopenia
• Infection:
  • Sepsis
• Neuromuscular & Skeletal:
  • Tremor
  • Limb Pain
• Respiratory:
  • Productive Cough
  • Oropharyngeal Pain
• Miscellaneous:
  • Night Sweats

Frequency of Side effects Not Defined:

• Cardiovascular:
  • Angina Pectoris
  • Atrial Fibrillation
  • Congestive Cardiac Failure
  • Hypotension
  • Myocardial Infarction
  • Septic Shock
  • Syncope
• Central Nervous System:
  • Altered Mental Status
  • Falling
  • Impaired Consciousness
  • Noncardiac Chest Pain
  • Vertigo
• Dermatologic:
  • Cellulitis
• Endocrine & Metabolic:
  • Hyperkalemia
• Gastrointestinal:
  • Abdominal Pain
  • Clostridioides Difficile
• Genitourinary:
  • Pelvic Pain
  • Urinary Retention
  • Urosepsis
• Hepatic:
  • Hyperbilirubinemia
  • Increased Serum ALT
• Infection:
  • Bacteremia
  • Neutropenic Sepsis
  • Viral Infection
• Neuromuscular & Skeletal:
  • Bone Fracture
  • Vertebral Compression Fracture
• Respiratory:
  • Bronchospasm
  • Interstitial Pulmonary Disease
  • Lobar Pneumonia
  • Pneumonia Due To Pneumocystis Carinii
  • Respiratory Syncytial Virus Infection
• Miscellaneous:
  • Failure To Thrive
  • Multiorgan Failure
  • Physical Health Deterioration

Contraindications to Pomalidomide (Pomalyst):

• In addition to the contraindications mentioned in the US labeling, the Canadian labeling for pomalidomide includes some additional contraindications.
• These contraindications state that pomalidomide should not be used in individuals who have hypersensitivity or allergic reactions to pomalidomide, thalidomide, lenalidomide, or any of the components of the medication's formulation.
• Pomalidomide is also contraindicated in breastfeeding individuals.
• Furthermore, women of childbearing potential who are not using two effective methods of contraception and male patients who are unable to comply with the required contraceptive measures should not use pomalidomide.
• These contraindications aim to prevent potential harm to the patient and the developing baby during pregnancy and breastfeeding and to ensure proper contraceptive practices are followed to avoid unintended pregnancies.

Warnings and precautions

Suppression of bone marrow

• During clinical trials, it was often observed that pomalidomide can cause bone marrow suppression, which includes low levels of neutrophils (a type of white blood cell), red blood cells (anemia), and platelets (thrombocytopenia).
• Among these, neutropenia was the most commonly reported severe adverse event, followed by anemia and thrombocytopenia.
• Neutropenic fever has also been reported.
• To monitor for these effects, complete blood counts should be checked weekly for the first 8 weeks of treatment and then monthly or as advised by the healthcare professional.
• Depending on the severity, it may be necessary to interrupt, reduce the dose, or discontinue pomalidomide therapy.

CNS effects

• Pomalidomide may have effects on the central nervous system (CNS) such as dizziness and confusion.
• Patients should be cautious and avoid engaging in activities that require mental alertness, like operating machinery or driving, while taking this medication.
• It is important to also avoid taking other medications that may worsen dizziness and confusion as a result of their interactions with pomalidomide.

Hepatotoxicity

• Pomalidomide has been associated with hepatotoxicity, including cases of liver failure that have resulted in fatalities.
• Elevated levels of bilirubin (a marker of liver function) and ALT (a liver enzyme) have also been observed.
• It is important to monitor liver function tests regularly while taking this medication.
• If liver enzymes become elevated, treatment with pomalidomide should be temporarily interrupted.
• Once the liver enzymes return to baseline levels, the healthcare provider may consider reducing the dose of the medication.
• Prompt monitoring and appropriate management of liver function are crucial to minimize the risk of hepatotoxicity and ensure the safety of the patient.

Hypersensitivity reactions

• Hypersensitivity reactions have been reported with the use of pomalidomide.
• These reactions can include angioedema (swelling), as well as severe cutaneous reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS).
• DRESS can present with symptoms such as rash, exfoliative dermatitis (skin peeling), eosinophilia (elevated levels of a type of white blood cell), fever, and/or swollen lymph nodes.
• It may also involve systemic complications affecting the liver, kidneys, lungs, heart, or lining around the heart.
• If angioedema, severe skin reactions, or other serious cutaneous reactions occur, treatment with pomalidomide should be immediately stopped, and reinitiating the therapy should be avoided.
• Prompt medical attention and appropriate management are necessary to ensure the patient's safety and well-being.

Interstitial lung disease (ILD).

• Cases of interstitial lung disease (ILD) and related events, such as pneumonitis, have been reported in individuals taking pomalidomide.
• ILD is a condition that involves inflammation and scarring of the lung tissue, which can lead to breathing difficulties and other respiratory symptoms.
• It is important for patients taking pomalidomide to be aware of the potential risk of ILD and to promptly report any new or worsening respiratory symptoms to their healthcare provider.
• Early detection and appropriate management are crucial in order to minimize the impact of ILD and related complications.

Neuropathy

• During clinical trials, peripheral and sensory neuropathy, including some cases of grade 3 severity, were reported in patients receiving pomalidomide.
• However, no cases of grade 4 neuropathy were observed.
• It is important to closely monitor for any signs or symptoms of neuropathy while taking pomalidomide.
• This may include numbness, tingling, pain, or weakness in the hands or feet.
• If neuropathy develops or worsens, the healthcare provider may consider interrupting the therapy, modifying the dosage, or discontinuing pomalidomide as necessary.

Secondary malignancy

• In some cases, the development of acute myelogenous leukemia (AML) as a secondary malignancy has been reported in patients who received pomalidomide as part of investigational treatment for conditions other than multiple myeloma.
• AML is a type of cancer that affects the bone marrow and blood cells.
• While the occurrence of AML as a secondary malignancy is rare, it is important to be aware of this potential risk.
• Patients should discuss any concerns or symptoms with their healthcare provider, who can provide guidance on monitoring and managing the risks associated with pomalidomide treatment.

[US Boxed Warning]: Thromboembolic Events

• It is important to be aware of the risk of thromboembolic events, as indicated by a boxed warning in the United States.
• Patients with multiple myeloma who receive pomalidomide therapy may experience venous and arterial thromboembolic events, such as deep vein thrombosis (DVT), pulmonary embolism (PE), heart attack (MI), and stroke.
• Clinical trials have used preventive measures against blood clots.
• It is recommended to assess the patient's individual risk factors and provide appropriate thromboprophylaxis.
• Arterial thrombotic events can also include conditions like cerebrovascular ischemia (reduced blood flow to the brain) and ischemic heart disease (reduced blood flow to the heart).
• It is important to monitor for signs and symptoms of blood clots, such as shortness of breath, chest pain, or swelling in the arms or legs, and advise patients to seek immediate medical attention if these symptoms occur.

Tumor lysis syndrome

• Patients with a high tumor burden who are receiving pomalidomide treatment may be at risk for a condition called tumor lysis syndrome.
• Tumor lysis syndrome can occur when cancer cells are rapidly destroyed, releasing their contents into the bloodstream.
• This can lead to electrolyte imbalances and an increase in uric acid levels, resulting in potential complications.
• It is important to closely monitor patients at risk and take appropriate measures to manage hyperuricemia (high levels of uric acid in the blood).
• This may involve medications or other interventions to prevent or treat elevated uric acid levels.

Hepatic impairment

• Caution should be exercised when using pomalidomide in patients with hepatic impairment.
• Pomalidomide is processed by the liver, and individuals with liver dysfunction may experience increased levels of the drug in their system.
• Therefore, it is recommended to make an initial dosage adjustment for patients with hepatic impairment.

Multiple myeloma

• In clinical studies, the use of pembrolizumab (a PD-1 or PD-L1 blocking antibody) in combination with a thalidomide analogue and dexamethasone in patients with multiple myeloma was associated with an increased risk of death.
• The causes of death observed in the group receiving the experimental treatment included various serious conditions such as myocarditis, Stevens-Johnson syndrome, heart attack, pericardial hemorrhage, cardiac failure, respiratory tract infection, and others.
• It is important to note that using pembrolizumab to treat multiple myeloma in combination with a thalidomide analogue and dexamethasone is not an approved treatment and should only be considered as part of a clinical trial.
• The findings highlight the need for caution and careful evaluation of treatment options in multiple myeloma patients.

Renal impairment

• Patients with renal impairment, particularly those undergoing hemodialysis, may require an initial dosage adjustment when using pomalidomide.
• The manufacturer recommends considering a modified dosage regimen for these individuals.
• Since hemodialysis can remove pomalidomide from the circulation, it is important to administer the medication after the dialysis procedure on dialysis days.

Pomalidomide: Drug Interaction

Risk Factor C (Monitor therapy)
Abiraterone Acetate	May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors).
Alcohol (Ethyl)	CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl).
Alizapride	May enhance the CNS depressant effect of CNS Depressants.
Bisphosphonate Derivatives	Angiogenesis Inhibitors (Systemic) may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Specifically, the risk for osteonecrosis of the jaw may be increased.
Brexanolone	CNS Depressants may enhance the CNS depressant effect of Brexanolone.
Brimonidine (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Bromopride	May enhance the CNS depressant effect of CNS Depressants.
Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Cannabis	May enhance the CNS depressant effect of CNS Depressants.
Chloramphenicol (Ophthalmic)	May enhance the adverse/toxic effect of Myelosuppressive Agents.
Chlorphenesin Carbamate	May enhance the adverse/toxic effect of CNS Depressants.
CloZAPine	Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased.
CNS Depressants	May enhance the adverse/toxic effect of other CNS Depressants.
Coccidioides immitis Skin Test	Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test.
CYP1A2 Inhibitors (Moderate)	May decrease the metabolism of CYP1A2 Substrates (High risk with Inhibitors).
Deferasirox	May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors).
Denosumab	May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
Dimethindene (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Doxylamine	May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended.
Dronabinol	May enhance the CNS depressant effect of CNS Depressants.
Erythropoiesis-Stimulating Agents	May enhance the thrombogenic effect of Pomalidomide.
Esketamine	May enhance the CNS depressant effect of CNS Depressants.
HydrOXYzine	May enhance the CNS depressant effect of CNS Depressants.
Kava Kava	May enhance the adverse/toxic effect of CNS Depressants.
Lofexidine	May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Magnesium Sulfate	May enhance the CNS depressant effect of CNS Depressants.
Mesalamine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
MetyroSINE	CNS Depressants may enhance the sedative effect of MetyroSINE.
Minocycline	May enhance the CNS depressant effect of CNS Depressants.
Mirtazapine	CNS Depressants may enhance the CNS depressant effect of Mirtazapine.
Nabilone	May enhance the CNS depressant effect of CNS Depressants.
Obeticholic Acid	May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors).
Ocrelizumab	May enhance the immunosuppressive effect of Immunosuppressants.
Peginterferon Alfa-2b	May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors).
Pidotimod	Immunosuppressants may diminish the therapeutic effect of Pidotimod.
Piribedil	CNS Depressants may enhance the CNS depressant effect of Piribedil.
Pramipexole	CNS Depressants may enhance the sedative effect of Pramipexole.
Promazine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
ROPINIRole	CNS Depressants may enhance the sedative effect of ROPINIRole.
Rotigotine	CNS Depressants may enhance the sedative effect of Rotigotine.
Rufinamide	May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced.
Selective Serotonin Reuptake Inhibitors	CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced.
Siponimod	Immunosuppressants may enhance the immunosuppressive effect of Siponimod.
Tertomotide	Immunosuppressants may diminish the therapeutic effect of Tertomotide.
Tetrahydrocannabinol	May enhance the CNS depressant effect of CNS Depressants.
Tetrahydrocannabinol and Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Tobacco (Smoked)	May enhance the adverse/toxic effect of Pomalidomide. Specifically, the risk for thrombosis may be increased. Tobacco (Smoked) may decrease the serum concentration of Pomalidomide.
Trastuzumab	May enhance the neutropenic effect of Immunosuppressants.
Trimeprazine	May enhance the CNS depressant effect of CNS Depressants.
Risk Factor D (Consider therapy modification)
Baricitinib	Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted.
Blonanserin	CNS Depressants may enhance the CNS depressant effect of Blonanserin.
Buprenorphine	CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants.
Chlormethiazole	May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used.
Ciprofloxacin (Systemic)	May increase the serum concentration of Pomalidomide. Management: Avoid concomitant use of pomalidomide and ciprofloxacin when possible. If coadministration is considered necessary, consider reducing the pomalidomide dose 50% and monitoring patients for increased pomalidomide effects/toxicities.
CYP1A2 Inhibitors (Strong)	May increase the serum concentration of Pomalidomide. Management: Avoid when possible. If coadministration is necessary, reduce the pomalidomide dose 50% and monitor for increased pomalidomide effects/toxicities.
Deferiprone	Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely.
Droperidol	May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Echinacea	May diminish the therapeutic effect of Immunosuppressants.
Estrogen Derivatives	Pomalidomide may enhance the thrombogenic effect of Estrogen Derivatives. Management: Canadian pomalidomide labeling recommends caution with use of hormone replacement therapy and states that hormonal contraceptives are not recommended. US pomalidomide labeling does not contain these specific recommendations.
Fingolimod	Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections).
Flunitrazepam	CNS Depressants may enhance the CNS depressant effect of Flunitrazepam.
HYDROcodone	CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Leflunomide	Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly.
Methotrimeprazine	CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established.
Nivolumab	Immunosuppressants may diminish the therapeutic effect of Nivolumab.
Opioid Agonists	CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
OxyCODONE	CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Perampanel	May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination.
Progestins	May enhance the thrombogenic effect of Pomalidomide. Management: Canadian pomalidomide labeling recommends caution with use of hormone replacement therapy and states that hormonal contraceptives are not recommended. US pomalidomide labeling does not contain these specific recommendations.
Roflumilast	May enhance the immunosuppressive effect of Immunosuppressants.
Sipuleucel-T	Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy.
Sodium Oxybate	May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated.
Suvorexant	CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended.
Tapentadol	May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Tofacitinib	Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants.
Vaccines (Inactivated)	Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation.
Vemurafenib	May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Management: Consider alternatives to such combinations whenever possible, particularly if the CYP1A2 substrate has a relatively narrow therapeutic index. Drugs listed as exceptions to this monograph are discussed in separate drug interaction monographs.
Zolpidem	CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol.
Risk Factor X (Avoid combination)
Abatacept	Anti-TNF Agents may enhance the adverse/toxic effect of Abatacept. An increased risk of serious infection during concomitant use has been reported.
Anakinra	Anti-TNF Agents may enhance the adverse/toxic effect of Anakinra. An increased risk of serious infection during concomitant use has been reported.
Azelastine (Nasal)	CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal).
BCG (Intravesical)	Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical).
BCG (Intravesical)	Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical).
Bromperidol	May enhance the CNS depressant effect of CNS Depressants.
Canakinumab	Anti-TNF Agents may enhance the adverse/toxic effect of Canakinumab. Specifically, the risk for serious infections and/or neutropenia may be increased.
Certolizumab Pegol	Anti-TNF Agents may enhance the immunosuppressive effect of Certolizumab Pegol.
Cladribine	May enhance the immunosuppressive effect of Immunosuppressants.
Cladribine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Dipyrone	May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased
Natalizumab	Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
Orphenadrine	CNS Depressants may enhance the CNS depressant effect of Orphenadrine.
Oxomemazine	May enhance the CNS depressant effect of CNS Depressants.
Paraldehyde	CNS Depressants may enhance the CNS depressant effect of Paraldehyde.
Pembrolizumab	May enhance the adverse/toxic effect of Thalidomide Analogues. Specifically, mortality may be increased when this combination is used for treatment of refractory multiple myeloma.
Pimecrolimus	May enhance the adverse/toxic effect of Immunosuppressants.
Rilonacept	Anti-TNF Agents may enhance the adverse/toxic effect of Rilonacept.
Tacrolimus (Topical)	May enhance the adverse/toxic effect of Immunosuppressants.
Thalidomide	CNS Depressants may enhance the CNS depressant effect of Thalidomide.
Tocilizumab	May enhance the immunosuppressive effect of Anti-TNF Agents.
Vaccines (Live)	Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants.
Vedolizumab	Anti-TNF Agents may enhance the adverse/toxic effect of Vedolizumab.

Monitoring parameters:

• CBC with differential and platelets:
  • Weekly for the first 8 weeks
  • Monthly or as clinically necessary thereafter
• Renal function:
  • Measure serum creatinine and creatinine clearance
• Liver function tests:
  • Monthly monitoring
• Signs/symptoms to monitor:
  • Thromboembolism (shortness of breath, chest pain, arm or leg swelling)
  • Neuropathy (peripheral and sensory symptoms)
  • Tumor lysis syndrome (in patients at risk)
  • Hypersensitivity/dermatologic reactions
  • Interstitial lung disease
• Consider thyroid function tests:
  • TSH recommended at baseline
  • Repeat every 2 to 3 months during treatment (based on similar medications)
• Adherence monitoring:
  • Regularly assess patient adherence to the treatment regimen

For Women of Childbearing Potential:

• Pregnancy testing:
  • 10 to 14 days and 24 hours before starting therapy
  • Weekly during the first month
  • Monthly thereafter for women with regular menstrual cycles
  • Every 2 weeks for women with irregular menstrual cycles
• Continue pregnancy testing for at least 4 weeks after discontinuation of pomalidomide treatment.

How to administer Pomalidomide (Pomalyst)?

• Administer the medication without regard to meals.
• Take the capsules whole with water. Do not break, chew, or open the capsules.

Missed Doses:

• If you miss a dose but it is within 12 hours of your usual dosing time, you may still take the missed dose.
• If it has been more than 12 hours since your usual dosing time, skip the missed dose for that day. Resume your regular dosing schedule the following day.
• Do not take two doses to make up for a missed dose.

Mechanism of action of Pomalidomide (Pomalyst):

• Cell cycle arrest and apoptosis: Pomalidomide directly induces cell cycle arrest and promotes apoptosis in multiple myeloma cells.
• Enhanced cytotoxicity: It enhances the cytotoxicity mediated by T cells and natural killer (NK) cells, leading to the destruction of cancer cells.
• Inhibition of proinflammatory cytokines: Pomalidomide inhibits the production of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-12 (IL-12), which are involved in the inflammatory response.
• Angiogenesis inhibition: It also inhibits angiogenesis, the formation of new blood vessels, which is crucial for tumor growth and spread.

These mechanisms contribute to the therapeutic effects of pomalidomide in the treatment of multiple myeloma.

Absorption:

• Pomalidomide is rapidly absorbed, but its absorption is slowed down by food.

Distribution:

• It has a large volume of distribution (V) ranging from 62 to 138 liters.
• The drug is also distributed in semen, with levels approximately 67% of plasma levels.

Protein binding:

• Pomalidomide is moderately bound to proteins in the blood, with binding ranging from 12% to 44%.

Metabolism:

• The drug is primarily metabolized in the liver by enzymes CYP1A2 and CYP3A4, with minor contributions from CYP2C19 and CYP2D6.

Elimination half-life:

• In healthy subjects, the elimination half-life of pomalidomide is approximately 9.5 hours, while in patients with multiple myeloma, it is around 7.5 hours.

Time to peak:

• Pomalidomide reaches its peak concentration in the blood around 2 to 3 hours after administration.

Excretion:

• The drug is mainly eliminated through the urine, with approximately 73% of the dose excreted in this way (including 2% as unchanged drug).
• About 15% of the dose is excreted in the feces (including 8% as unchanged drug).

International Brand Names of Pomalidomide:

• Pomalyst
• Imnovid

Pomalidomide Brand Names in Pakistan:

No Brands Available in Pakistan.