Pomalidomide - Indications, Contraindications, Dosage, Warnings and Precautions and Side Effects

Overview:

Kaposi's sarcoma (KS) is a cancer linked to a virus called Kaposi's sarcoma associated herpesvirus (KSHV). It commonly affects the skin and sometimes other organs, notably in regions with high Human Immunodeficiency Virus (HIV) and KSHV rates. KS mainly afflicts people with weakened immune systems, like those with HIV, transplant patients, and the elderly. Lower CD4 immune cell counts correlate with higher KS risk. Treating HIV with antiretroviral therapy (ART) reduces this risk. While ART is a fundamental KS treatment, some patients do not respond fully. Pomalidomide, an immune-modulating drug, was studied as a potential KS treatment, irrespective of HIV status. Food and Drug Administration (FDA) Approval and Targeted Patient Groups on May 14, 2020. The FDA approved the drug Pomalidomide for treating Kaposi sarcoma in two specific patient groups: one is adults with Kaposi sarcoma who are HIV-positive and have not responded well to standard HIV treatment, and the other is adults with Kaposi sarcoma who are HIV-negative.

Drug Group:

Pomalidomide is a medication that is taken as a capsule and falls into the category of drugs that affect the immune system. Pomalidomide has a dual action, which includes supporting the bone marrow in making healthy blood cells and boosting the ability of the immune system to eliminate abnormal cells in the bone marrow.

Dosage:

For AIDS-Related (Acquired Immunodeficiency Syndrome) Kaposi Sarcoma:

• Pomalidomide is used when highly active antiretroviral therapy (HAART) has not worked.

• The recommended dose is five mg taken by mouth once a day from days one to 21 of a 28-day cycle.

• Keep taking it until the Kaposi sarcoma gets worse or it cannot be tolerated by the individual.

• Continue taking HAART for HIV alongside this treatment.

For Kaposi Sarcoma in HIV-Negative Adults:

• Pomalidomide is used to treat Kaposi sarcoma in adults without HIV.

• Take five mg by mouth once a day from days one to 21 of a 28-day cycle.

• Keep taking it until the Kaposi sarcoma gets worse or cannot be tolerated.

Recommended Dosage and Duration:

• The recommended Pomalidomide dosage for Kaposi sarcoma is 5 mg (milligrams) taken orally once daily.

• Typically taken on days one through 21 of a 28-day cycle.

• Continue standard HIV treatment alongside Pomalidomide for HIV-positive patients.

For Patients

What Is Kaposi Sarcoma?

Kaposi sarcoma is a cancer that begins in blood vessel linings, creating cell growths called lesions on the skin, typically on the face, arms, and legs. These lesions can have colors like pink, red, purple, or brown. They might also show up on the genitals, in the mouth, or even in the digestive tract and lungs in severe cases.

How Does Pomalidomide Work?

Pomalidomide is a specific cancer medication that operates in various ways:

• It prevents myeloma cells from growing.

• It hinders the development of blood vessels that support cancer cell growth, acting as an anti-angiogenic drug.

• It boosts the immune system to attack and eliminate myeloma cells.

What Is the Dosage of Pomalidomide?

Dose Forms:

Capsule:

• 1 mg (milligram)

• 2mg

• 3mg

• 4mg

Dose Strength:

This information is about a drug used to treat a type of cancer called Kaposi sarcoma. It's meant for two groups of people:

• Those with Kaposi sarcoma related to AIDS: Take 5 mg by mouth every day for 21 days in a 28-day cycle, and keep doing so until the cancer gets worse or the side effects are too severe. Continue the HIV treatment.

• Adults with Kaposi sarcoma who don't have HIV: Take 5 mg by mouth every day for 21 days in a 28-day cycle, and continue until the cancer worsens or side effects become too problematic.

How Effective Is Pomalidomide?

• Pomalidomide is a medication for treating certain cancers like multiple myeloma and AIDS-related Kaposi sarcoma.

• It's used when other treatments have not been effective.

• This drug works by slowing down the growth of cancer cells and helping the body eliminate them.

• Its effectiveness can vary from person to person.

• Its impact depends on factors like a patient's specific condition and overall health.

What Are the Things to Inform the Doctor Before Taking Pomalidomide?

• Before using Pomalidomide, let the doctor and pharmacist know if a person has any allergies to this drug, other medications, or any ingredients in Pomalidomide capsules.

• Inform the doctor and pharmacist about all the medications the person is currently taking, whether they are prescribed, over-the-counter, vitamins, supplements, or herbal products. Especially mention drugs like Carbamazepine, Ciprofloxacin, Fluvoxamine, and Ketoconazole, as they may require adjustments in the medication doses or closer monitoring for side effects. Keep in mind that numerous other medications can also interact with Pomalidomide, so it is essential to disclose everything the person is using.

• Let the doctor know if the person is undergoing dialysis or has a history of liver disease.

• Let the doctor know if the person is pregnant or breastfeeding.

How Is Pomalidomide Administered?

• Administered orally.

• Ingest the capsule whole with water. Do not manipulate it by breaking, chewing, or opening.

• Take it on an empty stomach, at least two hours before or after a meal.

• Adhere to proper handling and disposal procedures in accordance with anticancer drug guidelines.

What Are the Side Effects of Pomalidomide?

Here are the common side effects experienced by patients taking this medication:

The most common side effects, including abnormalities seen in blood tests (experienced by more than 30 percent of patients), are:

• Low levels of certain white blood cells or neutrophils.

• Elevated levels of creatinine or glucose in the blood.

• Skin rash.

• Constipation.

• Feeling tired.

• Low level of hemoglobin.

• Low platelet count.

• Low levels of phosphate, albumin, or calcium in the blood.

• Increased ALT (a liver enzyme).

• Nausea.

• Diarrhea.

Dietary Considerations:

• If the person smokes, they should be aware that smoking might reduce the effectiveness of Pomalidomide.

• Take Pomalidomide with a glass of water daily, on an empty stomach, either at least two hours before eating or two hours after a meal.

• It's crucial to inform the doctor about all the medications, vitamins, and herbs the person is using.

• Never stop taking any of the medications without consulting the doctor first.

Missed Dose:

• If a person forgets to take a dose of this medication, they should take it when they remember, unless the next dose is almost due. In that case, don't take the missed dose and stick to the usual schedule. Avoid taking double doses to make up for the missed one.

• If a person misses a dose and it's been less than 12 hours since the usual time, take it as soon as possible and then continue with the next dose at the usual time. However, if more than 12 hours have passed, skip the missed dose and take the next one as scheduled. Never use extra medicine to compensate for a missed dose.

Overdose:

• Taking too much Pomalidomide is dangerous and can cause severe, life-threatening effects.

• If a person suspects an overdose or experiences symptoms like extreme dizziness, fainting, or difficulty breathing while using Pomalidomide, seek immediate medical help or contact a poison control center.

• Follow the doctor's prescribed dosage carefully and do not exceed it.

• If a person has concerns about the medication or believes they have taken too much, consult the doctor or a healthcare professional for guidance.

Storage:

• Store within the temperature range of 68 to -77 degrees FahrenheitºF (20 to 2 degrees Celsius 5º C).

• Excursions to temperatures between 59 to -86 degrees FahrenheitºF (15 to 30 degrees Celsiusº C) are acceptable.

For Doctors

Indications:

• Pomalidomide serves as a therapeutic intervention in the management of Kaposi sarcoma.

• It is administered to individuals with Kaposi sarcoma who exhibit resistance or inadequate response to the conventional antiretroviral therapy designed for HIV (in cases where HIV infection is present) or to those individuals without HIV who have been diagnosed with Kaposi sarcoma.

• The regulatory approval for this application is contingent upon the evaluation of the tumor's response to the treatment. Additional research may be necessary to establish its therapeutic efficacy conclusively.

Dosage and Usage:

• For Kaposi Sarcoma (KS): Take 5 mg of Pomalidomide by mouth every day, again only on days one through 21 of a 28-day cycle. Continue taking it until cancer gets worse or if a person experiences serious side effects.

• If a patient has kidney or liver problems, the doctor may adjust the dosage accordingly.

Forms and Strengths:

• Pomalidomide is available in capsule form, and it comes in different strengths: 1 mg, 2 mg, 3 mg, and 4 mg.

Clinical Pharmacology

Pharmacodynamics:

Pomalidomide exhibits significantly greater potency compared to Thalidomide, with a 100-fold increase, and also surpasses Lenalidomide, demonstrating a 10-fold increase in potency. Exposure-response analyses of Pomalidomide indicated that there is no discernible relationship between the level of systemic Pomalidomide exposure and its effectiveness or safety, even when administered at a 4mg dose.

Mechanism of Action:

• Pomalidomide, an analog of thalidomide.

• Immunomodulatory, antiangiogenic, and antineoplastic properties.

• Mediated cellular actions via cereblon, a component of the E3 ubiquitin ligase complex.

In Vitro Effects:

• Ubiquitination and degradation of proteins.

• Cytotoxic effects and immune system adjustments.

• Inhibition of cell growth and induction of apoptosis in blood cancer cells.

Anti-Angiogenic Activity:

• Inhibition of new blood vessel formation.

• Nourishment blockade for tumors.

• Effects demonstrated in mouse models and in vitro human umbilical cord Cell Tests.

Pharmacokinetics:

• Absorption and peak plasma time (two to three hours).

• The peak plasma concentration for Kaposi sarcoma is 53.1 ng/mL (nanogram/milliliter).

• The area under the curve (AUC) value for Kaposi sarcoma is 462.3 ng⋅hr/mL (nanogram. hour/milliliter).

• Impact of smoking on AUC (CYP1A2 Induction).

• Protein binding (12 to 44 Percent) and steady-state volume of distribution (62 to 138 Liters).

• Semen concentration (67 Percent of Plasma Level at four Hours Post-Dose).

• Substrate of P-glycoprotein (P-gp).

Metabolism and Elimination:

• Liver metabolism via CYP1A2, CYP3A4 (Primary), CYP2C19, and CYP2D6 (Minor).

• Elimination half-life (7.5 hours in Multiple Myeloma/ Kaposi Sarcoma (MM/KS), 9.5 hours in Healthy Subjects).

• Total body clearance (7 to 10 Liter/hr).

• Excretion (73 Percent Urine, 15 Percent Feces; Unchanged Components).

Toxicity:

Patients taking Pomalidomide experienced common side effects and blood test abnormalities:

• Decrease in specific white blood cells.

• Increased levels of creatinine and glucose in the blood.

• Skin rashes.

• Constipation.

• Fatigue.

• Various abnormalities in blood components.

Clinical Studies:

• The study was conducted to evaluate the effectiveness of Pomalidomide.

• 28 patients participated (18 with HIV, 10 without).

• Treatment Regimen: Once-daily oral administration for 21 days within a 28-day cycle until disease progression or severe side effects occur.

Response Rates:

HIV-Positive Patients:

• Positive Response Rate: Approximately 67 percent.

• Median Response Duration: About 12.5 months.

HIV-Negative Patients:

• Positive Response Rate: Approximately 80 Percent.

• Median Response Duration: About 10.5 months.

What Are the Contraindications of Pomalidomide?

• Pregnancy: Pomalidomide should not be used by individuals who are currently pregnant or are planning to become pregnant. It poses risks to pregnancy and fetal development.

• Hypersensitivity: Individuals with a history of a severe allergic reaction to Pomalidomide or similar substances should avoid its use, as it may trigger another serious allergic reaction.

Warnings and Precautions:

Here are some important things to be aware of and careful about when using this medication:

1. There have been cases of more deaths observed in patients with a specific type of cancer (multiple myeloma) when they took Pembrolizumab along with Dexamethasone and a similar drug to this one.

2. Some patients experience significant problems with their blood, particularly a condition called neutropenia. Doctors should regularly check for blood-related issues, especially neutropenia.

3. In some cases, the liver stops working properly, and this could even be fatal. Doctors will monitor the liver function with blood tests every month to catch any issues early.

4. If a person has a severe skin reaction while taking this medication, it is important to stop using it.

5. Some patients with a lot of cancer cells in their body are at risk of Tumor Lysis Syndrome (TLS), a condition where cancer cells break down quickly, which can be harmful. Doctors will watch for this and take necessary precautions.

6. Some individuals may have a strong allergic reaction to this medication. Doctors will be on the lookout for signs of this and will discontinue if present medication.

Drug Interactions of Pomalidomide

• Be cautious when taking Pomalidomide with other medications that strongly inhibit an enzyme called CYP1A2.

• If avoiding the combination is not possible, the doctor may reduce the Pomalidomide dose to 2 mg to minimize potential issues.

• This precaution is to ensure that the medications work effectively together and do not pose a risk to health.

Dosage Modifications for Different Adverse Effects:

1. Hematologic Side Effects in Kaposi Sarcoma (KS): To start a new cycle of Pomalidomide in patients with Kaposi Sarcoma (KS), their blood counts should meet certain criteria:

• Neutrophil count (a type of white blood cell) should be at least 1000 per microliter (mcL).

• The platelet count should be at least 75,000 per mcL.

Depending on the severity of hematologic (blood-related) side effects, dosage modifications for Pomalidomide are as follows:

Neutropenia (Low Neutrophil Count):

If the absolute neutrophil count (ANC) is between 500 and less than 1000 per mcL at the start of the cycle:

• Stop Pomalidomide until ANC is at least 1000 per mcL.

• Then, resume Pomalidomide at the same dose.

• If ANC drops below 500 per mcL during the cycle, stop Pomalidomide until ANC is at least 1000 per mcL. Later, resume Pomalidomide at the same dose.

Febrile Neutropenia (Low Neutrophil Count with Fever):

If ANC is less than 1000 per mcL and the patient has a fever of 38.3 °C or higher or a sustained fever of 38 °C or higher for more than 1 hour:

• Pause Pomalidomide until ANC is at least 1000 per mcL.

• Resume Pomalidomide at a dose 1 mg lower than the previous dose.

Thrombocytopenia (Low Platelet Count):

If the platelet count is between 25,000 and less than 50,000 per mcL at the start of the cycle:

• Stop Pomalidomide until the platelet count is at least 50,000 per mcL.

• Resume Pomalidomide at the same dose.

2. Non-Hematologic Side Effects:

• For severe non-blood-related side effects like angioedema, anaphylaxis, Grade four rash, or other severe skin reactions, Pomalidomide should be permanently discontinued.

• For other Grade three or four toxicities (side effects) not related to blood, treatment may be temporarily stopped. It can be restarted at a dose one mg lower than the previous dose when the toxicity has improved to Grade two or lower, as determined by the physician.

3. Strong CYP1A2 Inhibitors:

• It is recommended to avoid using Pomalidomide with strong CYP1A2 inhibitors. If it is necessary to use both drugs together, the Pomalidomide dose should be reduced to two mg to minimize potential interactions.

4. Severe Renal Impairment (Kidney Problems) on Hemodialysis:

• For patients with multiple myeloma (MM) with severe renal impairment requiring dialysis, the recommended dosage should be reduced to three mg orally daily.

• For patients with Kaposi sarcoma (KS) with severe renal impairment requiring dialysis, the recommended dosage should be reduced to four mg orally daily. This adjustment helps ensure safe use of the medication when kidneys are not functioning well.

5. Hepatic Impairment (Liver Problems):

• For patients with KS with mild, moderate, or severe hepatic impairment (Child-Pugh A, B, or C), the recommended dosage should be reduced to 3 mg orally daily. This adjustment helps ensure safe use of the medication when there are liver problems.

Special Recommendations:

• Avoid using Pomalidomide during pregnancy because it can harm the developing fetus.

• If pregnancy occurs while taking this medication, stop it right away and consult a reproductive health specialist for guidance.

• For women who are breastfeeding, it is recommended to advise them not to breastfeed while using this medication.