Carfilzomib – Uses, Dosage, Side Effects, Interaction

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Article Summary

Carfilzomib is an irreversible proteasome inhibitor and antineoplastic agent that is used in the treatment of refractory multiple myeloma. Carfilzomib is associated with a low rate of serum enzyme elevations during treatment and has been implicated in rare instances of clinically apparent, acute liver injury some of which have been fatal. Carfilzomib is an injectable antineoplastic agent (IV only). Chemically, it is a modified tetrapeptide...

Key Takeaways

  • This article explains Mechanism of Action in simple medical language.
  • This article explains Indications in simple medical language.
  • This article explains Contraindications in simple medical language.
  • This article explains Dosage in simple medical language.
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Mechanism of Action

Carfilzomib is made up of four modified peptides and acts as a proteasome inhibitor. Carfilzomib irreversibly and selectively binds to N-terminal threonine-containing active sites of the 20S proteasome, the proteolytic core particle within the 26S proteasome. This 20S core has 3 catalytic active sites: the chymotrypsin, trypsin, and caspase-like sites. Inhibition of the chymotrypsin-like site by carfilzomib (β5 and β5i subunits) is the most effective target in decreasing cellular proliferation, ultimately resulting in cell cycle arrest and apoptosis of cancerous cells. At higher doses, carfilzomib will inhibit the trypsin-and capase-like sites.

Intravenous carfilzomib administration resulted in suppression of proteasome chymotrypsin-like activity when measured in blood 1 hour after the first dose. On Day 1 of Cycle 1, proteasome inhibition in peripheral blood mononuclear cells (PBMCs) ranged from 79% to 89% at 15 mg/m2, and from 82% to 83% at 20 mg/m2. In addition, carfilzomib administration resulted in inhibition of the LMP2 and MECL1 subunits of the immunoproteasome ranging from 26% to 32% and 41% to 49%, respectively, at 20 mg/m2. Proteasome inhibition was maintained for ≥ 48 hours following the first dose of carfilzomib for each week of dosing. Resistance against carfilzomib has been observed and although the mechanism has not been confirmed, it is thought that up-regulation of P-glycoprotein may be a contributing factor. Furthermore, studies suggest that carfilzomib is more potent than bortezomib.

Indications

  • Carfilzomib is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy in combination with lenalidomide and dexamethasone, or dexamethasone, or daratumumab and dexamethasone; or daratumumab and hyaluronidase-fihj and dexamethasone. It is also indicated as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.
  • Kyprolis in combination with daratumumab and dexamethasone, with lenalidomide and dexamethasone, or with dexamethasone alone is indicated for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.
  • Carfilzomib is an irreversible proteasome inhibitor and antineoplastic agent that is used in the treatment of refractory multiple myeloma.
  • Carfilzomib is a proteasome inhibitor used either alone or in conjunction with a regimen to treat patients with relapsed or refractory multiple myeloma.
  • Treatment of Multiple Myeloma
  • Treatment of acute lymphoblastic

Use in Cancer

Carfilzomib is approved to be used alone or with other drugs to treat:

  • Multiple myeloma that has relapsed (come back) or is refractory (does not respond to treatment). It is used:
    • Alone in adults who have received one or more other therapies.
    • With other drugs in adults who have received one to three other therapies. It is used with dexamethasone with or without one of the following drugs:
      • Lenalidomide
      • Daratumumab
      • Daratumumab and hyaluronidase-fihj

Carfilzomib is also being studied in the treatment of other types of cancer.

Contraindications

  • is allergic to levonorgestrel or to any of the ingredients or components of the device
  • is or may be pregnant
  • has a of the heart valves
  • has a genital
  • has a poorly functioning immune system
  • has abnormal cells in the
  • has abnormalities of the (e.g., fibroids) that distort the shape of the uterus
  • has acute liver disease or a liver tumor
  • has cancer of the uterus or cervix
  • has current or pelvic inflammatory disease
  • has had an abortion complicated by an infection within the past 3 months
  • has of the cervix
  • has inflammation of the endometrium (lining of the uterus) after pregnancy
  • has leukemia or other cancers affecting the blood
  • has recently had an abnormal growth of cells inside the uterus
  • has unexplained bleeding of the uterus
  • has progestin-dependent cancer, including breast cancer
  • hemolytic uremic , a condition that affects the and the blood
  • decreased blood platelets
  • low levels of a type of white blood cell called neutrophils
  • high blood pressure
  • a
  • a low supply of oxygen rich blood to the heart
  • complete stoppage of the heart
  • obstruction of a blood vessel by a blood clot
  • , a type of lung disorder
  • acute
  • trouble breathing
  • abnormal liver function tests
  • pregnancy
  • a patient who is producing milk and breastfeeding
  • progressive multifocal leukoencephalopathy, a type of brain infection
  • a type of brain disorder called posterior reversible encephalopathy syndrome

Strengths: 60 mg; 30 mg; 10 mg

Multiple Myeloma

BEFORE INITIATING THIS DRUG:

  • Hydrate patients with both oral fluids (30 mL/kg at least 48 hours before Cycle 1, Day 1) and IV fluids (250 to 500 mL prior to each dose in Cycle 1). If needed, give an additional 250 to 500 mL of IV fluids following drug administration.
  • Continue oral and/or IV hydration, as needed, in subsequent cycles.
  • Monitor for volume overload and adjust hydration to individual needs (especially in patients with or at risk for cardiac failure).
  • Monitor serum potassium levels regularly.
  • Premedicate with dexamethasone at the recommended dose for either monotherapy or combination therapy.
  • Administer dexamethasone orally or IV at least 30 minutes but no more than 4 hours prior to all doses during Cycle 1 to reduce infusion reactions.
  • Reinstate dexamethasone if symptoms occur during subsequent cycles.
  • Provide thromboprophylaxis for patients being treated with this drug in combination with other therapies.
  • Consider antiviral prophylaxis to decrease the risk of herpes zoster reactivation.

DOSE CALCULATION:

  • Calculate the dose based on the actual BSA of the patient at .
  • Patients with a BSA greater than 2.2 m2 should receive a dose based upon a BSA of 2.2 m2.
  • Dose adjustments do not need to be made for weight changes of 20% or less.

CARFILZOMIB IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE:
CARFILZOMIB:

  • Cycle 1: 20 mg/m2 IV over 10 minutes on Days 1 and 2; if tolerated, increase to 27 mg/m2 IV over 10 minutes on Days 8, 9, 15, and 16 of the 28-day cycle
  • Cycles 2 through 12: 27 mg/m2 IV over 10 minutes on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle
  • Cycle 13 and later: 27 mg/m2 IV over 10 minutes on Days 1, 2, 15, and 16 of each 28-day cycle (omit the Day 8 and 9 doses)
  • Discontinue carfilzomib after Cycle 18.

LENALIDOMIDE/DEXAMETHASONE:

  • All cycles: Lenalidomide 25 mg orally on Days 1 through 21 and dexamethasone 40 mg orally or IV on Days 1, 8, 15, and 22 of the 28-day cycles
  • Administer dexamethasone 30 minutes to 4 hours before carfilzomib.
  • Continue lenalidomide and dexamethasone until or unacceptable toxicity.
  • Refer to the lenalidomide and dexamethasone prescribing information.

CARFILZOMIB IN COMBINATION WITH DEXAMETHASONE:
TWICE WEEKLY 20/56 MG/M2 REGIMEN BY 30-MINUTE INFUSION:
CARFILZOMIB:

  • Cycle 1: 20 mg/m2 IV over 30 minutes on Days 1 and 2; if tolerated, increase to 56 mg/m2 IV over 30 minutes on Days 8, 9, 15, and 16 of the 28-day cycle
  • Cycles 2 and later: 56 mg/m2 IV over 30 minutes on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle

DEXAMETHASONE:

  • Cycle 1: 20 mg orally or IV Days 1, 2, 8, 9, 15, 16, 22, and 23 of the 28-day cycle
  • Cycle 2 and later: 20 mg orally or IV Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle
  • Administer dexamethasone 30 minutes to 4 hours before carfilzomib.
  • Continue until disease or unacceptable toxicity.
  • Refer to the dexamethasone prescribing information.

CARFILZOMIB IN COMBINATION WITH DEXAMETHASONE:
ONCE WEEKLY 20/70 MG/M2 REGIMEN BY 30-MINUTE INFUSION:
CARFILZOMIB:

  • Cycle 1: 20 mg/m2 IV over 30 minutes on Day 1; if tolerated, increase to 70 mg/m2 IV over 30 minutes on Days 8 and 15 of the 28-day cycle
  • Cycles 2 through 9: 70 mg/m2 IV over 30 minutes on Days 1, 8, and 15 of each 28-day cycle

DEXAMETHASONE:

  • Cycles 1 through 9: 40 mg orally or IV Days 1, 8, 15, and 22 of each 28-day cycle
  • Cycles 10 and later: 40 mg orally or IV Days 1, 8, and 15 of each 28-day cycle
  • Administer dexamethasone 30 minutes to 4 hours before carfilzomib.
  • Continue until disease progression or unacceptable toxicity.
  • Refer to the dexamethasone prescribing information.

CARFILZOMIB IN COMBINATION WITH DARATUMUMAB AND DEXAMETHASONE:
TWICE WEEKLY 20/56 MG/M2 REGIMEN BY 30-MINUTE INFUSION:
CARFILZOMIB:

  • Cycle 1: 20 mg/m2 IV over 30 minutes on Days 1 and 2; if tolerated, increase to 56 mg/m2 IV over 30 minutes on Days 8, 9, 15, and 16 of the 28-day cycle
  • Cycles 2 and later: 56 mg/m2 IV over 30 minutes on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle

DEXAMETHASONE (NOTE: For patients 75 years or older, administer 20 mg of dexamethasone orally or IV weekly after the first week):

  • All Cycles: 20 mg orally or IV on Days 1, 2, 8, 9, 15, and 16 and 40 mg orally or IV on Day 22 of each 28-day cycle

DARATUMUMAB:

  • Cycle 1: 8 mg/kg on Days 1 and 2 and 16 mg/kg on Days 8, 15, and 22 of the 28-day cycle
  • Cycle 2: 16 mg/kg IV on Days 1, 8, 15, and 22 of the 28-day cycle
  • Cycles 3 through 6: 16 mg/kg IV on Days 1 and 15 of each 28-day cycle
  • Cycles 7 and later: 16 mg/kg on Day 1 of each 28-day cycle
  • Administer dexamethasone 30 minutes to 4 hours before carfilzomib.
  • Continue until disease progression or unacceptable toxicity.
  • Refer to the dexamethasone and daratumumab prescribing information.

CARFILZOMIB IN COMBINATION WITH DARATUMUMAB AND DEXAMETHASONE:
ONCE WEEKLY 20/70 MG/M2 REGIMEN BY 30-MINUTE INFUSION:
CARFILZOMIB:

  • Cycle 1: 20 mg/m2 IV over 30 minutes on Day 1 and 70 mg/m2 IV over 30 minutes on Days 8 and 15 of the 28-day cycle
  • Cycle 2 and later: 70 mg/m2 IV over 30 minutes on Days 1, 8, and 15 of each 28-day cycle

DEXAMETHASONE (NOTE: For patients 75 years or older, administer 20 mg of dexamethasone orally or IV weekly after the first week):

  • Cycles 1 and 2: 20 mg orally or IV on Days 1, 2, 8, 9, 15, 16, 22, and 23 of the 28-day cycle
  • Cycles 3 through 6: 20 mg orally or IV on Days 1,2, 15, and 16 and 40 mg orally or IV on Days 8 and 22 of each 28-day cycle
  • Cycle 7 and later: 20 mg orally or IV on Days 1 and 2 and 40 mg orally or IV on Days 8, 15, and 22 of each 28-day cycle

DARATUMUMAB:

  • Cycle 1: 8 mg/kg on Days 1 and 2 and 16 mg/kg on Days 8, 15, and 22 of the 28-day cycle
  • Cycle 2: 16 mg/kg IV on Days 1, 8, 15, and 22 of the 28-day cycle
  • Cycles 3 through 6: 16 mg/kg IV on Days 1 and 15 of the 28-day cycle
  • Cycles 7 and later: 16 mg/kg on Day 1 of each 28-day cycle
  • Administer dexamethasone 30 minutes to 4 hours before carfilzomib.
  • Continue until disease progression or unacceptable toxicity.
  • Refer to the dexamethasone and daratumumab prescribing information.

MONOTHERAPY BY THE 10-MINUTE INFUSION:
20/27 MG/M2 TWICE WEEKLY REGIMEN BY 10-MINUTE INFUSION:

  • Cycle 1: 20 mg/m2 IV over 10 minutes on Days 1 and 2; if tolerated, increase to 27 mg/m2 IV over 10 minutes on Days 8, 9, 15, and 16 of the 28-day cycle
  • Cycles 2 through 12: 27 mg/m2 IV over 10 minutes on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle
  • Cycles 13 and later: 27 mg/m2 IV over 10 minutes on Days 1, 2, 15, and 16 of each 28-day cycle
  • Premedicate with dexamethasone 4 mg orally or IV 30 minutes to 4 hours before each dose of this drug in Cycle 1, then as needed to prevent infusion reactions.
  • Continue therapy until the disease progresses or has unacceptable toxicity.

MONOTHERAPY BY THE 30-MINUTE INFUSION:
20/56 MG/M2 TWICE WEEKLY REGIMEN BY 30-MINUTE INFUSION:

  • Cycle 1: 20 mg/m2 IV over 30 minutes on Days 1 and 2; if tolerated, increase to 56 mg/m2 IV over 30 minutes on Days 8, 9, 15, and 16 of the 28-day cycle
  • Cycles 2 through 12: 56 mg/m2 IV over 30 minutes on Days 1, 2, 8, 9, 15, and 16 of each 28-day treatment cycle
  • Cycles 13 and later: 56 mg/m2 IV over 30 minutes on Days 1, 2, 15, and 16 of each 28-day treatment cycle
  • Premedicate with dexamethasone 8 mg orally or IV 30 minutes to 4 hours before each dose of this drug in Cycle 1, then as needed to prevent infusion reactions.
  • Continue therapy until the disease progresses or has unacceptable toxicity.
  • For patients with relapsed or refractory multiple myeloma who have received 1 to 3 lines of therapy in combination with lenalidomide and dexamethasone, or dexamethasone, or daratumumab and dexamethasone
  • As a single agent for the treatment of relapsed or refractory multiple myeloma who have received 1 or more lines of therapy

Dose Adjustments

  • Serum creatinine 2 x baseline or greater, OR CrCl less than 15 mL/min, OR CrCl decreased to 50% or less of baseline, OR need for hemodialysis: Withhold dose and monitor renal function (serum creatinine or CrCl).
  • If attributable to this drug, resume when renal function has recovered to within 25% of baseline; start at 1 dose level reduction.
  • If not attributable to this drug, dosing may be resumed at the discretion of the physician.
  • The dose is to be administered after the hemodialysis procedure for patients on hemodialysis.

Liver Dose Adjustments

  • Mild (total bilirubin 1 to 1.5 x upper limit of normal [ULN] and any AST or total bilirubin less than or equal to ULN and AST greater than ULN) or moderate (total bilirubin greater than 1.5 to 3 x ULN and any AST) hepatic impairment: Reduce the dose of by 25%
    Severe hepatic impairment: Data not available

Dose Adjustments

HEMATOLOGIC TOXICITY:

  • Absolute neutrophil count (ANC) less than 0.5 X 10(9)/L: Withhold dose; if recovered to 0.5 x 10(9)/L or greater, continue at the same dose level. For subsequent drops to less than 0.5 x 10(9) /L, follow the same recommendations as above and consider 1 dose level reduction when restarting therapy.
  • Febrile neutropenia (ANC less than 0.5 x 10(9)/L and an oral temperature of more than 38.5C or 2 consecutive readings of more than 38C for 2 hours): Withhold dose; if ANC returns to baseline grade and fever resolve, resume at the same dose level.
  • Platelets less than 10 X 10(9)/L or evidence of bleeding with thrombocytopenia: Withhold dose; if recovered to greater than or equal to 10 x 10(9)/L and/or bleeding is controlled, continue at the same dose level. For subsequent drops to less than 10 x 10(9)/L, follow the same recommendations as above and consider 1 dose level reduction when restarting therapy.

OTHER NONHEMATOLOGIC TOXICITY:

  • All other severe or life-threatening nonhematologic toxicities (Grades 3 and 4): Withhold therapy until resolved or returned to baseline; consider restarting the next scheduled dose at 1 dose level reduction.

DOSE LEVEL REDUCTION GUIDELINES:
CARFILZOMIB AND DEXAMETHASONE OR CARFILZOMIB, DARATUMUMAB, AND DEXAMETHASONE (ONCE WEEKLY):

  • Initial dose: 70 mg/m2
  • First dose reduction: 56 mg/m2
  • Second dose reduction: 45 mg/m2
  • Third dose reduction: 36 mg/m2; if toxicity persists, discontinue therapy

CARFILZOMIB AND DEXAMETHASONE OR KYPROLIS, DARATUMUMAB, AND DEXAMETHASONE OR KYPROLIS MONOTHERAPY (TWICE WEEKLY):

  • Initial dose: 56 mg/m2
  • First dose reduction: 45 mg/m2
  • Second dose reduction: 36 mg/m2
  • Third dose reduction: 27 mg/m2; if toxicity persists, discontinue therapy

CARFILZOMIB, LENALIDOMIDE, AND DEXAMETHASONE OR CARFILZOMIB MONOTHERAPY (TWICE WEEKLY):

  • Initial dose: 27 mg/m2
  • First dose reduction: 20 mg/m2
  • Second dose reduction: 15 mg/m2; if toxicity persists, discontinue therapy

Administration advice:

  • The IV administration line should be flushed with normal saline or 5% dextrose injection immediately before and after drug administration.
  • This drug is available for IV use only.
  • Do not administer this drug as a bolus.
  • Do not mix this drug with or administer it as an infusion with other medicinal products.
  • Infuse over 10 or 30 minutes depending on the dosing regimen.

Monitoring:

  • Cardiovascular: Fluid overload, cardiac complications
  • Hematologic: Blood chemistries, platelet counts, Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome
  • Hepatic: Liver function (transaminases, bilirubin)
  • Nervous: Posterior Reversible Encephalopathy Syndrome
  • Oncologic: Tumor Lysis Syndrome
  • Other: Infusion reactions (immediately following or up to 24 hours after treatment administration)
  • Renal: Renal function (serum creatinine)
  • Respiratory: Dyspnea, pulmonary arterial hypertension

Side Effects

The Most Common

  • headache
  • diarrhea
  • constipation
  • muscle spasm
  • pain in the arms or legs; back pain
  • difficulty falling asleep or staying asleep
  • cough
  • dry mouth, dark urine, decreased sweating, dry skin, and other signs of dehydration
  • swelling of the feet of legs
  • pain, tenderness, or redness in one leg
  • shortness of breath or difficulty breathing
  • chest pain
  • pain, burning, numbness, or tingling in the hands or feet
  • nausea
  • unusual tiredness or weakness
  • unusual bleeding or bruising
  • lack of energy
  • loss of appetite
  • pain in the upper right part of the stomach
  • yellowing of the skin or eyes
  • flu-like symptoms
  • bloody or black, tarry stools
  • rash of pinpoint-sized reddish-purple spots, usually on the lower legs
  • blood in the urine
  • decreased urination
  • seizures
  • vision changes or loss of vision
  • confusion, memory loss, dizziness or loss of balance, difficulty talking or walking, changes in vision, decreased strength or weakness on one side of the body

More Common

  • abdominal pain
  • acne (usually less common after 3 months of treatment, and may improve if acne already exists)
  • breast pain, tenderness, or swelling
  • changes in the menstrual pattern, such as:
    • breakthrough bleeding or spotting between periods
    • complete lack of menstrual flow for several months in a row
    • decreased bleeding during periods
    • occasional stopping of menstrual bleeding
    • prolonged bleeding during periods
  • decreased sex drive
  • feeling of fullness or tightness in the abdomen
  • headache
  • nausea
  • weight gain

Rare

  • back pain
  • dizziness
  • expulsion of the device
  • mood changes
  • nervousness
  • persistent or severe lower abdominal pain along with fever or unusual vaginal discharge
  • severe headaches or migraines (headaches may lessen in many users, or they may increase in number or become worse for other users)
  • signs of depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities, thoughts of suicide)
  • signs of a liver problem (e.g., yellow skin or eyes, dark urine, pale stools, abdominal pain, or itchy skin)
  • skin rash, hives, or itchy skin
  • symptoms of pregnancy (e.g., abdominal pain, nausea, breast tenderness)
  • vaginal discharge
  • vaginal infection with vaginal itching or irritation, or thick, white, or curd-like discharge
  • abdominal or stomach pain (sudden, severe, or continuing)
  • signs of a serious allergic reaction (e.g., abdominal cramps, difficulty breathing, nausea and vomiting, or swelling of the face and throat)
  • signs of a blood clot in the leg (e.g., sudden unexplained pain in the leg, especially in the calf)
  • signs of a blood clot in the lungs (e.g., sudden or unexplained shortness of breath, chest pain, coughing up of blood)
  • signs of a heart attack (e.g., pain or discomfort in the chest or upper body, shortness of breath, nausea, cold sweats, or lightheadedness)
  • signs of a stroke (e.g., sudden slurring of speech; sudden unexplained weakness, numbness, or pain in the arm or leg; sudden loss of coordination; sudden, severe headache)

Drug Interaction

Pregnancy and Lactation

Pregnancy Category D

Pregnancy

This device should not be used during pregnancy. You should have this device removed if you become pregnant. Any device in the uterus during pregnancy can result in an increased risk of miscarriage or early labour. There is no evidence of birth defects when the device remains in the uterus for the full term. However, there is no conclusive evidence of this because of limited experience.

Lactation

No information is available on the clinical use of carfilzomib during breastfeeding. Because carfilzomib is 97% bound to plasma proteins, the amount in milk is likely to be low. The manufacturer recommends that breastfeeding be discontinued during carfilzomib therapy and for 2 weeks after the last dose.

How should this medicine be used?

Carfilzomib comes as a powder to be mixed with liquid to be injected intravenously (into a vein). Carfilzomib is given by a doctor or nurse in a medical office or clinic usually over a period of 10 or 30 minutes. It may be given 2 days in a row each week for 3 weeks followed by a 12-day rest period or it may be given once a week for 3 weeks followed by a 13-day rest period. The length of treatment will depend on how well your body responds to the medication.

Carfilzomib injection may cause severe or life-threatening reactions for up to 24 hours after you receive a dose of the medication. You will receive certain medications to help prevent a reaction before you receive each dose of carfilzomib. Tell your doctor immediately if you experience any of these symptoms after your treatment: fever, chills, joint or muscle pain, flushing or swelling of the face, swelling or tightening of the throat, vomiting, weakness, shortness of breath, dizziness or fainting, or chest tightness or pain.

Be sure to tell your doctor how you are feeling during your treatment. Your doctor may stop your treatment for a while or decrease your dose of carfilzomib if you experience side effects of the medication.

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Blood pressure: Levonorgestrel can cause an increase in blood pressure. If you have high blood pressure, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

If you experience an increase in your blood pressure after having this device inserted, contact your doctor.

Breast cancer: Cases of breast cancer have been reported by women using levonorgestrel-releasing IUDs. However, some studies have shown that progestin-only forms of birth control do not appear to increase the risk of breast cancer. Discuss any concerns you have with your doctor.

Depression: Hormones, such as progestins, are known to contribute to mood swings and symptoms of depression. If you have depression or a history of depression, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

If you experience symptoms of depression such as poor concentration, changes in weight, changes in sleep, decreased interest in activities, or notice them in a family member who is taking this medication, contact your doctor as soon as possible.

Diabetes: Low-dose contraceptives such as this device have very little effect on blood sugar control. However, people with diabetes or those with a family history of diabetes should monitor their blood sugar closely to detect any worsening of blood sugar control.

Ectopic pregnancy: If you have a history of ectopic pregnancy (when a fertilized egg implants itself outside of the uterus), have had surgery on the fallopian tubes, or have had a pelvic infection, you should speak to your doctor or pharmacist before using this device. If you experience lower abdominal pain along with a missed period or unexpected bleeding while using this medication, contact your doctor.

Expulsion of device: Bleeding or pain may indicate that the device has either moved out of position or has been expelled from the uterine cavity. A device that is out of position is less effective and should be removed and replaced by a new device.

Eye problems: Some women may experience a change in vision or contact lens tolerance. If this occurs, contact your eye doctor.

Headache: Levonorgestrel, like other hormones, may cause severe headache or migraine. If you have a history of migraines, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

If you notice increasing numbers or severity of headaches after the device has been inserted, contact your doctor as soon as possible.

Heart disease: Levonorgestrel may increase the risk of developing blood clots, causing reduced blood flow to organs or the extremities. If you have a history of clotting you may be at increased risk of experiencing blood clot-related problems such as heart attack, stroke, or clots in the deep veins of your leg. Cigarette smoking increases the risk of serious adverse effects on the heart and blood vessels. Discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

If you experience symptoms such as sharp pain and swelling in the leg, difficulty breathing, chest pain, blurred vision, or difficulty speaking, contact your doctor immediately.

Heart valve disorders: This medication can increase your risk of getting an infection in your heart valves if you were born with or have acquired a heart valve defect. You may need to take antibiotics before the insertion and removal of this medication to prevent the infection.

Insertion and removal of the device: Some women may experience some pain and bleeding when the device is inserted or removed. The procedure may also cause fainting or a seizure for someone with a seizure disorder.

Liver disease: If you develop signs of a liver problem (yellow skin or eyes, dark urine, pale stools, abdominal pain, or itchy skin), talk to your doctor about whether you should have the device removed.

Menstrual bleeding: Some women may experience some pain and bleeding when the device is inserted or removed. Irregular menstrual bleeding is common for the first few months after the device is inserted. Over time, menstrual bleeding decreases and may stop completely while the device is inserted.

Ovarian cysts: This medication can cause the development of ovarian cysts. Most of these don’t have any symptoms and disappear on their own within 2 to 3 months. However, if you experience pain in the pelvic area, contact your doctor.

Perforation: The chance of the device puncturing the cervix or uterus is very rare (between 1 in 1,000 and 1 in 10,000). If it were to occur, it would most likely be when the device is being inserted. If this happens, the device should be removed as soon as possible.

Removal of the device: If you experience any of the following, check with your doctor to see if you should have your device removed:

  • confirmed or suspected breast or endometrial cancer
  • migraines or severe headaches
  • recurrent inflammation of the lining of the uterus
  • recurrent pelvic infections
  • significantly elevated blood pressure
  • stroke or heart attack

Return to fertility: Your usual level of fertility should return soon after the device is removed. Nearly 90% of women wishing to become pregnant conceive within 24 months after the removal of the device.

Sexually transmitted infections (STIs): This device does not protect against STIs, including HIV/AIDS. For protection against STIs, use latex condoms.

What special precautions should I follow?

Before receiving carfilzomib injection,

  • tell your doctor and pharmacist if you are allergic to carfilzomib, any other medications, or any of the ingredients in carfilzomib injection. Ask your pharmacist for a list of the ingredients.
  • tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor if you have or have ever had heart failure, a heart attack, irregular heartbeat, or other heart problems; high blood pressure; a herpes infection (cold sores, shingles, or genital sores); or seizures or any other neurologic disorder. Also, tell your doctor if you have liver or kidney disease or are on dialysis.
  • tell your doctor if you are pregnant or plan to become pregnant, or if you plan to father a child. You or your partner should not become pregnant while you are receiving carfilzomib. If you are female, you must take a pregnancy test before starting treatment and should use birth control to prevent pregnancy during your treatment with carfilzomib and for 6 months after your final dose. If you are a male, you and your partner should use birth control methods to prevent pregnancy during your treatment with carfilzomib and for 3 months after your final dose. If you or your partner become pregnant while receiving this medication, call your doctor. Carfilzomib may harm the fetus.
  • tell your doctor if you are breastfeeding. Do not breastfeed while you are receiving carfilzomib injection and for 2 weeks after your final dose.
  • you should know that carfilzomib may make you drowsy, dizzy, or lightheaded, or cause fainting. Do not drive or operate machinery until you know how this medication affects you.

References

  1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202714lbl.pdf
  2. https://pubchem.ncbi.nlm.nih.gov/compound/Carfilzomib
  3. https://pubchem.ncbi.nlm.nih.gov/compound/Carfilzomib
  4. https://www.drugs.com/carfilzomib.html
  5. https://go.drugbank.com/drugs/DB08889
  6. https://en.wikipedia.org/wiki/Carfilzomib
  7. https://medlineplus.gov/druginfo/meds/a612031.html
  8. https://www.medbroadcast.com/drug/getdrug/mirena
  9. Guide to Pharmacology Target Classification
  10. NCI Thesaurus Tree
  11. ChemIDplus Chemical Information Classification
  12. CompTox Chemicals Dashboard Chemical Lists
  13. LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    NORMAN Suspect List Exchange Classification
  14. PubChem
  15. LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    Therapeutic category of drugs in Japan
    Anatomical Therapeutic Chemical (ATC) classification
    Target-based classification of drugs
  16. NCBI

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  2. Recognize symptoms Learn common symptoms, signs, and patterns of presentation.
  3. Know when to seek help Review urgent warning signs and when professional assessment may be needed.
  4. Understand causes and risks Explore causes, risk factors, mechanisms, and contributing conditions.
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Doctor visit helper

Prepare before seeing a doctor

A simple rural-patient checklist to help you explain symptoms clearly, ask better questions, and avoid unsafe self-treatment.

Safety note: This is not a prescription or diagnosis. For severe symptoms, pregnancy danger signs, children with serious illness, chest pain, breathing difficulty, stroke-like weakness, or major injury, seek urgent care.

Which doctor may help?

Start with a registered doctor or the nearest qualified health center.

What to tell the doctor

  • Write when the problem started and how it changed.
  • Bring old prescriptions, investigation reports, and current medicines.
  • Write allergies, pregnancy status, diabetes, kidney/liver disease, and major past illnesses.
  • Bring one family member if the patient is weak, elderly, confused, or a child.

Questions to ask

  • What is the most likely cause of my symptoms?
  • Which danger signs mean I should go to hospital quickly?
  • Which tests are necessary now, and which can wait?
  • How should I take medicines safely and what side effects should I watch for?
  • When should I come for follow-up?

Tests to discuss

  • Vital signs: temperature, pulse, blood pressure, oxygen saturation
  • Basic physical examination by a clinician
  • CBC, urine test, blood sugar, or imaging only when clinically needed

Avoid these mistakes

  • Do not use antibiotics, steroid tablets/injections, or strong painkillers without proper medical advice.
  • Do not hide pregnancy, kidney disease, ulcer, allergy, or blood thinner use.
  • Do not delay emergency care when danger signs are present.

Medicine safety and first-aid guide

This section is for patient education only. It does not replace a doctor, pharmacist, or emergency care.

Safe first steps

  • Avoid heavy lifting, sudden bending, and prolonged bed rest.
  • Use comfortable posture and gentle movement as tolerated.
  • Discuss physiotherapy, X-ray, or MRI only when clinically needed.

OTC medicine safety

  • For mild back pain, pain-relief medicine may be discussed with a doctor or pharmacist.
  • Avoid repeated painkiller use if you have kidney disease, stomach ulcer, uncontrolled blood pressure, or are taking blood thinners.

Avoid these mistakes

  • Do not start antibiotics without a proper medical decision.
  • Do not use steroid tablets or injections casually for quick relief.
  • Do not delay emergency care because of home remedies.

Get urgent help if

  • Back pain with leg weakness, numbness around private area, loss of urine/stool control, fever, cancer history, or major injury needs urgent care.
Medicine names, dose, and timing must be decided by a qualified clinician or pharmacist after checking age, pregnancy, allergy, other diseases, and current medicines.

For rural patients and family caregivers

Patient health record and symptom diary

Write your symptoms, medicines already taken, test results, and questions before visiting a doctor. This note stays on your device unless you print or copy it.

Doctor to discuss: Orthopedic / spine specialist, physical medicine doctor, or qualified clinician
Tests to discuss with doctor
  • Neurological examination for leg power, sensation, reflexes, and straight leg raise
  • X-ray only if injury, deformity, long-lasting pain, or doctor suspects bone problem
  • MRI discussion if severe nerve symptoms, weakness, bladder/bowel problem, or persistent symptoms
Questions to ask
  • What is the most likely cause of my symptoms?
  • Which warning signs mean I should go to emergency care?
  • Which tests are really needed now?
  • Which medicines are safe for my age, pregnancy status, allergy, kidney/liver/stomach condition, and current medicines?
  • Is physiotherapy, posture correction, or activity modification needed?

Emergency warning signs such as chest pain, severe breathing difficulty, sudden weakness, confusion, severe dehydration, major injury, or loss of bladder/bowel control need urgent medical care. Do not wait for online information.

Safe pathway to proper treatment

Care roadmap for: Carfilzomib – Uses, Dosage, Side Effects, Interaction

Use this simple roadmap to understand the next safe steps. It is educational and does not replace examination by a doctor.

Go to emergency care if you notice:
  • Severe or rapidly worsening symptoms
  • Breathing difficulty, chest pain, fainting, confusion, severe weakness, major injury, or severe dehydration
Doctor / service to discuss: Qualified healthcare provider; specialist depends on symptoms and examination.
  1. Step 1

    Check danger signs first

    If danger signs are present, seek emergency care and do not wait for online information.

  2. Step 2

    Record the symptom story

    Write when symptoms started, severity, medicines already taken, allergies, pregnancy status, and test results.

  3. Step 3

    Visit a qualified clinician

    A doctor, nurse, or qualified healthcare provider can examine you and decide which tests or treatment are needed.

  4. Step 4

    Do only useful tests

    Do tests after clinical assessment. Avoid unnecessary tests, random antibiotics, or repeated medicines without diagnosis.

  5. Step 5

    Follow up and return early if worse

    If symptoms worsen, new warning signs appear, or treatment is not helping, return for review quickly.

Rural patient practical tips
  • Take a written symptom diary and all previous prescriptions/test reports.
  • Do not hide medicines already taken, even herbal or over-the-counter medicines.
  • Ask which warning signs mean urgent referral to hospital.

This roadmap is for education. A real diagnosis and treatment plan requires history, examination, and clinical judgment.

Internal learning pathway

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