Literature Scan |
|
|
|
Continued from page 57 |
|
|
|
|
information on coexisting illnesses , reasons for transfusions , co-interventions , nonfatal cardiovascular outcomes , and causes of death . In addition , the study outcomes may not be directly applicable to patients with type B or AB blood due to the study ’ s design and inclusion criteria .
“ The study results support the practice [ of using ] the oldest red cell products in the hospital inventory to reduce the number of blood units being wasted ,”
|
Prof . Heddle told ASH Clinical News . “ Being able to store red blood cells for a longer period also helps blood suppliers to maintain an adequate supply of blood and ensure availability of product when patients need it .”
In an editorial accompanying the IN- FORM results , Aaron A . R . Tobian , MD , PhD , and Paul M . Ness , MD , commented on the study ’ s design and applicability to real-world practice . 2
|
“ Even though the results of the IN- FORM trial should end the debate regarding whether short-term or long-term storage of blood is advantageous , the question is still open as to whether the transfusion of red cells during the last week of storage ( 35 to 42 days ) poses more risk than the transfusion of blood stored for the shorter intervals ,” Drs . Tobian and Ness wrote . “ The transfusion-medicine community needs to know whether the storage period |
should be reduced ( e . g ., < 35 days ) or new preservative solutions should be sought .”
REFERENCES
1 . Heddle NM , Cook RJ , Arnold DM , et al . Effect of short-term vs . longterm blood storage on mortality after transfusion . N Engl J Med . 2016 October 24 . [ Epub ahead of print ]
2 . Tobian AAR and Ness PM . Red cells — aging gracefully in the blood bank . N Engl J Med . 2016 October 24 . [ Epub ahead of print ]
|
REVLIMID [ lenalidomide ] capsules , for oral use
The following is a Brief Summary ; refer to full Prescribing Information for complete product information .
WARNING : EMBRYO-FETAL TOXICITY , HEMATOLOGIC TOXICITY , and VENOUS and ARTERIAL THROMBOEMBOLISM
Embryo-Fetal Toxicity Do not use REVLIMID during pregnancy . Lenalidomide , a thalidomide analogue , caused limb abnormalities in a developmental monkey study . Thalidomide is a known human teratogen that causes severe lifethreatening human birth defects . If lenalidomide is used during pregnancy , it may cause birth defects or embryo-fetal death . In females of reproductive potential , obtain 2 negative pregnancy tests before starting REVLIMID ® treatment . Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after REVLIMID treatment [ see Warnings and Precautions ( 5.1 ), and Medication Guide ( 17 )]. To avoid embryo-fetal exposure to lenalidomide , REVLIMID is only available through a restricted distribution program , the REVLIMID REMS™ program ( formerly known as the “ RevAssist ® ” program ) ( 5.2 ).
Information about the REVLIMID REMS™ program is available at www . celgeneriskmanagement . com or by calling the manufacturer ’ s toll-free number 1-888-423-5436 .
Hematologic Toxicity ( Neutropenia and Thrombocytopenia ) REVLIMID can cause significant neutropenia and thrombocytopenia . Eighty percent of patients with del 5q myelodysplastic syndromes had to have a dose delay / reduction during the major study . Thirty-four percent of patients had to have a second dose delay / reduction . Grade 3 or 4 hematologic toxicity was seen in 80 % of patients enrolled in the study . Patients on therapy for del 5q myelodysplastic syndromes should have their complete blood counts monitored weekly for the first 8 weeks of therapy and at least monthly thereafter . Patients may require dose interruption and / or reduction . Patients may require use of blood product support and / or growth factors [ see Dosage and Administration ( 2.2 )].
Venous and Arterial Thromboembolism REVLIMID has demonstrated a significantly increased risk of deep vein thrombosis ( DVT ) and pulmonary embolism ( PE ), as well as risk of myocardial infarction and stroke in patients with multiple myeloma who were treated with REVLIMID and dexamethasone therapy . Monitor for and advise patients about signs and symptoms of thromboembolism . Advise patients to seek immediate medical care if they develop symptoms such as shortness of breath , chest pain , or arm or leg swelling . Thromboprophylaxis is recommended and the choice of regimen should be based on an assessment of the patient ’ s underlying risks [ see Warnings and Precautions ( 5.4 )].
1 INDICATIONS AND USAGE 1.1 Multiple Myeloma REVLIMID in combination with dexamethasone is indicated for the treatment of patients with multiple myeloma ( MM ).
1.4 Limitations of Use : REVLIMID is not indicated and is not recommended for the treatment of patients with CLL outside of controlled clinical trials [ see Warnings and Precautions ( 5.5 )].
2 DOSAGE AND ADMINISTRATION REVLIMID should be taken orally at about the same time each day , either with or without food . REVLIMID capsules should be swallowed whole with water . The capsules should not be opened , broken , or chewed .
2.1 Multiple Myeloma Multiple Myeloma The recommended starting dose of REVLIMID is 25 mg orally once daily on Days 1-21 of repeated 28-day cycles in combination with dexamethasone . Refer to Section 14.1 for specific dexamethasone dosing . For patients > 75 years old , the starting dose of dexamethasone may be reduced . Treatment should be continued until disease progression or unacceptable toxicity .
In patients who are not eligible for autologous stem cell transplantation ( ASCT ), treatment should continue until disease progression or unacceptable toxicity . For patients who are ASCT-eligible , hematopoietic stem cell mobilization should occur within 4 cycles of a REVLIMID-containing therapy [ see Warnings and Precautions ( 5.11 )].
Dose Adjustments for Hematologic Toxicities During Multiple Myeloma Treatment Dose modification guidelines , as summarized in Table 1 below , are recommended to manage Grade 3 or 4 neutropenia or thrombocytopenia or other Grade 3 or 4 toxicity judged to be related to REVLIMID .
Table 1 : Dose Adjustments for Hematologic Toxicities for MM Platelet counts Thrombocytopenia in MM When Platelets
Recommended Course
Fall to < 30,000 / mcL
Interrupt REVLIMID treatment , follow CBC weekly
Return to ≥30,000 / mcL Resume REVLIMID at next lower dose . Do not dose below 2.5 mg daily
For each subsequent drop Interrupt REVLIMID treatment < 30,000 / mcL Return to ≥30,000 / mcL Resume REVLIMID at next lower dose .
Do not dose below 2.5 mg daily
Absolute Neutrophil counts ( ANC ) Neutropenia in MM When Neutrophils
Recommended Course
Fall to < 1000 / mcL
Interrupt REVLIMID treatment , follow
CBC weekly Return to ≥1,000 / mcL and Resume REVLIMID at 25 mg daily or neutropenia is the only toxicity initial starting dose
Return to ≥1,000 / mcL and if Resume REVLIMID at next lower dose . other toxicity
Do not dose below 2.5 mg daily
For each subsequent drop Interrupt REVLIMID treatment < 1,000 / mcL Return to ≥1,000 / mcL Resume REVLIMID at next lower dose .
Do not dose below 2.5 mg daily
Other Toxicities in MM |
For other Grade 3 / 4 toxicities judged to be related to REVLIMID , hold |
treatment and restart at the physician ’ s discretion at next lower dose level |
when toxicity has resolved to ≤ Grade 2 . |
Starting Dose Adjustment for Renal Impairment in MM : |
[ See Dosage and Administration ( 2.4 )]. |
2.4 Starting Dose for Renal Impairment in MM |
Since REVLIMID is primarily excreted unchanged by the kidney , adjustments |
to the starting dose of REVLIMID are recommended to provide appropriate |
drug exposure in patients with moderate or severe renal impairment and |
in patients on dialysis . Based on a pharmacokinetic study in patients with |
renal impairment due to non-malignant conditions , REVLIMID starting |
dose adjustment is recommended for patients with CLcr < 60 mL / min . |
The recommendations for initial starting doses for patients with MM are |
as follows : |
Table 3 : Starting Dose Adjustments for Patients with |
Renal Impairment in MM |
Category |
Renal Function |
Dose in MM |
|
( Cockcroft-Gault ) |
|
Moderate Renal |
CLcr 30-50 mL / min |
10 mg |
Impairment |
|
Every 24 hours |
Severe Renal |
CLcr < 30 mL / min |
15 mg |
Impairment |
( not requiring dialysis ) |
Every 48 hours |
End Stage |
CLcr < 30 mL / min |
5 mg |
Renal Disease |
( requiring dialysis ) |
Once daily . On dialysis days , administer the dose following dialysis . |
Moderate renal impairment for MM : Consider escalating the dose to 15 mg after 2 cycles if the patient tolerates the 10 mg dose of lenalidomide without dose-limiting toxicity .
After initiation of REVLIMID therapy , subsequent REVLIMID dose increase or decrease is based on individual patient treatment tolerance , as described elsewhere [ See Dosage and Administration ( 2.1-2.3 )].
4 CONTRAINDICATIONS 4.1 Pregnancy REVLIMID can cause fetal harm when administered to a pregnant female . Limb abnormalities were seen in the offspring of monkeys that were dosed with lenalidomide during organogenesis . This effect was seen at all doses tested . Due to the results of this developmental monkey study , and lenalidomide ’ s structural similarities to thalidomide , a known human teratogen , lenalidomide is contraindicated in females who are pregnant [ see Boxed Warning ]. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug , the patient should be apprised of the potential hazard to the fetus [ see Warnings and Precautions ( 5.1 , 5.2 ), Use in Special Populations ( 8.1 ), ( 8.6 )].