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| __NOTOC__
| | #REDIRECT [[Dalteparin#Adverse Reactions]] |
| {{Dalteparin}}
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| {{CMG}}; {{AE}} {{SS}}
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| ==Adverse Reactions==
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| ===Clinical Trials Experience===
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| Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not accurately reflect the rates observed in practice.
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| ===Hemorrhage===
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| The incidence of hemorrhagic complications during treatment with FRAGMIN Injection has been low. The most commonly reported side effect is [[hematoma]]at the injection site. The risk for bleeding varies with the indication and may increase with higher doses.
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| ===[[unstable angina]] and Non-Q-Wave [[myocardial infarction]]===
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| Table 5 summarizes major bleeding reactions that occurred with FRAGMIN, [[heparin]], and placebo in clinical trials of [[unstable angina]] and non-Q-wave[[myocardial infarction]].
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| ===Hip Replacement Surgery===
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| Table 6 summarizes: 1) all major bleeding reactions and, 2) other bleeding reactions possibly or probably related to treatment with FRAGMIN (preoperative dosing regimen), [[warfarin]] sodium, or [[heparin]] in two hip replacement surgery clinical trials.
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| Six of the patients treated with FRAGMIN experienced seven major bleeding reactions. Two of the reactions were wound [[hematoma]] (one requiring reoperation), three were bleeding from the operative site, one was intraoperative bleeding due to vessel damage, and one was gastrointestinal bleeding. None of the patients experienced retroperitoneal or intracranial hemorrhage or died of bleeding complications.
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| In the third hip replacement surgery clinical trial, the incidence of major bleeding reactions was similar in all three treatment groups: 3.6% (18/496) for patients who started FRAGMIN before surgery; 2.5% (12/487) for patients who started FRAGMIN after surgery; and 3.1% (15/489) for patients treated with [[warfarin]] sodium.
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| ===Abdominal Surgery===
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| Table 7 summarizes bleeding reactions that occurred in clinical trials which studied FRAGMIN 2500 and 5000 IU administered once daily to abdominal surgery patients.
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| In a trial comparing FRAGMIN 5000 IU once daily to FRAGMIN 2500 IU once daily in patients undergoing surgery for malignancy, the incidence of bleeding reactions was 4.6% and 3.6%, respectively (n.s.). In a trial comparing FRAGMIN 5000 IU once daily to [[heparin]] 5000 U twice daily, in the malignancy subgroup the incidence of bleeding reactions was 3.2% and 2.7%, respectively for FRAGMIN and [[heparin]] (n.s.).
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| ===Medical Patients with Severely Restricted Mobility During Acute Illness===
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| Table 8 summarizes major bleeding reactions that occurred in a clinical trial of medical patients with severely restricted mobility during acute illness.
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| Three of the major bleeding reactions that occurred by Day 21 were fatal, all due to [[gastrointestinal hemorrhage]] (two patients in the group treated with FRAGMIN and one in the group receiving placebo).
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| ===Patients with Cancer and Acute Symptomatic [[venous thromboembolism]]===
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| Table 9 summarizes the number of patients with bleeding reactions that occurred in the clinical trial of patients with cancer and acute symptomatic [[venous thromboembolism]]. A bleeding event was considered major if it: 1) was accompanied by a decrease in hemoglobin of ≥ 2 g/dL in connection with clinical symptoms; 2) occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or [[pericardial bleeding]]); 3) required transfusion of ≥ 2 units of blood products; or 4) led to death. Minor bleeding was classified as clinically overt bleeding that did not meet criteria for major bleeding.
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| At the end of the six-month study, a total of 46 (13.6%) patients in the FRAGMIN arm and 62 (18.5%) patients in the OAC arm experienced any bleeding event. One bleeding event (hemoptysis in a patient in the FRAGMIN arm at Day 71) was fatal.
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| ===Thrombocytopenia===
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| [See Warnings and Precautions (5.2)]
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| ===Elevations of Serum Transaminases===
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| In FRAGMIN clinical trials supporting non-cancer indications, where hepatic transaminases were measured, asymptomatic increases in transaminase levels (SGOT/AST and SGPT/ALT) greater than three times the upper limit of normal of the laboratory reference range were seen in 4.7% and 4.2%, respectively, of patients during treatment with FRAGMIN.
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| In the FRAGMIN clinical trial of patients with cancer and acute symptomatic [[venous thromboembolism]] treated with FRAGMIN for up to 6 months, asymptomatic increases in transaminase levels, AST and ALT, greater than three times the upper limit of normal of the laboratory reference range were reported in 8.9% and 9.5% of patients, respectively. The frequencies of Grades 3 and 4 increases in AST and ALT, as classified by the National Cancer Institute, Common Toxicity Criteria (NCI-CTC) Scoring System, were 3% and 3.8%, respectively. Grades 2, 3 & 4 combined have been reported in 12% and 14% of patients, respectively.
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| ===Other===
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| ‘’‘Allergic Reactions’‘’: Allergic reactions (i.e., pruritus, rash, fever, injection site reaction, bullous eruption) have occurred. Cases of anaphylactoid reactions have been reported.
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| ‘’‘Local Reactions’‘’: Pain at the injection site, the only non-bleeding event determined to be possibly or probably related to treatment with FRAGMIN and reported at a rate of at least 2% in the group treated with FRAGMIN, was reported in 4.5% of patients treated with FRAGMIN 5000 IU once daily vs 11.8% of patients treated with [[heparin]] 5000 U twice daily in the abdominal surgery trials. In the hip replacement trials, pain at injection site was reported in 12% of patients treated with FRAGMIN 5000 IU once daily vs 13% of patients treated with [[heparin]] 5000 U three times a day.
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| ===Post-Marketing Experience===
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| The following adverse reactions have been identified during postapproval use of FRAGMIN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
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| Since first international market introduction in 1985, there have been more than 15 reports of epidural or spinal [[hematoma]] formation with concurrent use of dalteparin sodium and spinal/epidural anesthesia or spinal puncture. The majority of patients had postoperative indwelling epidural catheters placed for analgesia or received additional drugs affecting hemostasis. In some cases the [[hematoma]] resulted in long-term or permanent paralysis (partial or complete). [see Boxed Warning]
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| Skin necrosis has occurred. There have been cases of alopecia reported that improved on drug discontinuation.<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = FRAGMIN (DALTEPARIN SODIUM) INJECTION [EISAI INC.] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=c5cd4a8e-14c0-440b-b453-9f3d3250c951 | publisher = | date = | accessdate = 2 February 2014 }}</ref>
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| ==References==
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| {{Reflist|2}}
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| [[Category:[[heparin]] group]]
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| [[Category:Anticoagulants]]
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| [[Category:Cardiovascular Drugs]]
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