-
Expert Opinion on Pharmacotherapy Aug 2001Dalteparin sodium (Fragmin, Pharmacia Corporation) is a low molecular weight heparin (LMWH) with a mean molecular weight of approximately 5000 Da. As with the other... (Review)
Review
Dalteparin sodium (Fragmin, Pharmacia Corporation) is a low molecular weight heparin (LMWH) with a mean molecular weight of approximately 5000 Da. As with the other LMWHs, dalteparin sodium has certain advantages over unfractionated heparin (UFH), most important of which are improved bio-availability by sc. injection, a prolonged antithrombotic activity which is highly correlated with body weight permitting the o.d. administration of the drug. Dalteparin sodium has been subjected to a large number of well-designed randomised clinical trials for the prevention and treatment of thrombotic disorders. Based on data from the randomised clinical trials, dalteparin sodium has been approved internationally for a wide spectrum of clinical indications (e.g., prevention of thromboembolic events after surgery). Dalteparin sodium has also been studied in randomised controlled trials in the maintenance of graft patentcy following peripheral vascular surgery, in place of warfarin for the long-term treatment of patients presenting with deep vein thrombosis (DVT), in the prevention of upper extremity thrombosis in patients with indwelling portacath devices and in pregnant patients with a history of previous venous thromboembolism with or without thrombophilia. Dalteparin sodium has been compared with heparin for the prevention of thrombotic complications during haemodyalisis and haemofiltration. These studies have shown promising results but further work is required before dalteparin sodium can be recommended for these indications.
Topics: Animals; Anticoagulants; Clinical Trials as Topic; Dalteparin; Humans; Myocardial Infarction; Venous Thrombosis
PubMed: 11585001
DOI: 10.1517/14656566.2.8.1325 -
Drugs Aug 1996The low molecular weight heparin (LMWH) dalteparin sodium is notable for its improved pharmacokinetic characteristics (chiefly increased bioavailability and plasma... (Comparative Study)
Comparative Study Review
The low molecular weight heparin (LMWH) dalteparin sodium is notable for its improved pharmacokinetic characteristics (chiefly increased bioavailability and plasma elimination half-life) compared with unfractionated heparin (UFH). These properties enable the drug to be given subcutaneously as a single daily dose, compared with the 8- to 12-hourly regimens necessary with UFH. Dalteparin sodium also appears to exert a greater inhibitory effect than UFH on plasma activity of coagulation factor Xa relative to its effects on clotting times [usually expressed as activated partial thromboplastin time (APTT)] and activity of factor IIa. It is not associated with any clinically significant effects on the fibrinolytic system and may have less lipolytic activity than UFH. Extensive clinical studies have been conducted to compare the antithrombotic efficacy of dalteparin sodium with that of UFH in surgical thromboprophylaxis, treatment of established deep vein thrombosis (DVT) and the anticoagulation of patients undergoing haemodialysis and haemofiltration. The majority of trails of patients receiving thromboprophylactic heparin perioperatively have shown similar efficacy of dalteparin sodium and UFH in the prevention of DVT and pulmonary embolism (PE), although 2 groups of investigators reported superior antithrombotic potency for dalteparin sodium. The two types of heparin appear similarly effective in the management of established DVT and the maintenance of the extracorporeal circulation in haemodialysis circuits. Dalteparin sodium has also shown clinical benefit in the management of patients with unstable angina or non-Q-wave myocardial infarction. The overall incidence of haemorrhagic complications observed with daltparin sodium therapy is no greater than that associated with UFH, and data suggest that perioperative transfusion requirements and frequency of bleeding are lower after dalteparin sodium. The antithrombotic efficacy of dalteparin sodium is at least equivalent to that of UFH, although further clinical comparisons with other LMWHs are required. Further studies are also needed to clearly define any advantages of dalteparin sodium over UFH (and other antithrombotics) with regard to the incidence of haemorrhagic complications. The drug has also shown clinical efficacy in the prevention of myocardial infarction and death in patients with unstable coronary artery disease. In addition, there may be cost advantages attached to the once-daily subcutaneous regimen of dalteparin sodium, but this requires further examination. Thus, dalteparin sodium is an effective antithrombotic agent for perioperative thromboprophylaxis, the management of established DVT, and the anticoagulation of patients undergoing haemodialysis.
Topics: Anticoagulants; Blood Coagulation; Dalteparin; Fibrinolytic Agents; Humans; Thromboembolism
PubMed: 8841743
DOI: 10.2165/00003495-199652020-00011 -
Journal of Thrombosis and Haemostasis :... Feb 2020Low-molecular-weight heparin is the guideline-endorsed treatment for cancer-associated venous thromboembolism (VTE). While apixaban is approved for the treatment of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Low-molecular-weight heparin is the guideline-endorsed treatment for cancer-associated venous thromboembolism (VTE). While apixaban is approved for the treatment of acute VTE, limited data support its use in cancer patients.
OBJECTIVES
The primary outcome was major bleeding. Secondary outcomes included VTE recurrence and a composite of major plus clinically relevant non-major bleeding (CRNMB).
PATIENTS/METHODS
Patients with cancer-associated VTE were randomly assigned to receive either apixaban 10 mg twice daily for seven days followed by 5 mg twice daily for six months or subcutaneous dalteparin (200 IU/kg for one month followed by 150 IU/kg once daily).
RESULTS
Of 300 patients randomized, 287 were included in the primary analysis. Metastatic disease was present in 66% of subjects; 74% were receiving concurrent chemotherapy. Major bleeding occurred in 0% of 145 patients receiving apixaban, compared with 1.4% of 142 patients receiving dalteparin [P = .138; hazard ratio (HR) not estimable because of 0 bleeding event in apixaban group]. Recurrent VTE occurred in 0.7% of apixaban, compared to 6.3% of dalteparin patients [HR 0.099, 95% confidence interval [CI], 0.013-0.780, P = .0281). Major bleeding or CRNMB rates were 6% for both groups.
CONCLUSIONS
Oral apixaban was associated with low major bleeding and VTE recurrence rates for the treatment of VTE in cancer patients.
Topics: Anticoagulants; Dalteparin; Humans; Neoplasm Recurrence, Local; Pyrazoles; Pyridones; Treatment Outcome; Venous Thromboembolism
PubMed: 31630479
DOI: 10.1111/jth.14662 -
The New England Journal of Medicine Feb 2018Low-molecular-weight heparin is the standard treatment for cancer-associated venous thromboembolism. The role of treatment with direct oral anticoagulant agents is... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Low-molecular-weight heparin is the standard treatment for cancer-associated venous thromboembolism. The role of treatment with direct oral anticoagulant agents is unclear.
METHODS
In this open-label, noninferiority trial, we randomly assigned patients with cancer who had acute symptomatic or incidental venous thromboembolism to receive either low-molecular-weight heparin for at least 5 days followed by oral edoxaban at a dose of 60 mg once daily (edoxaban group) or subcutaneous dalteparin at a dose of 200 IU per kilogram of body weight once daily for 1 month followed by dalteparin at a dose of 150 IU per kilogram once daily (dalteparin group). Treatment was given for at least 6 months and up to 12 months. The primary outcome was a composite of recurrent venous thromboembolism or major bleeding during the 12 months after randomization, regardless of treatment duration.
RESULTS
Of the 1050 patients who underwent randomization, 1046 were included in the modified intention-to-treat analysis. A primary-outcome event occurred in 67 of the 522 patients (12.8%) in the edoxaban group as compared with 71 of the 524 patients (13.5%) in the dalteparin group (hazard ratio, 0.97; 95% confidence interval [CI], 0.70 to 1.36; P=0.006 for noninferiority; P=0.87 for superiority). Recurrent venous thromboembolism occurred in 41 patients (7.9%) in the edoxaban group and in 59 patients (11.3%) in the dalteparin group (difference in risk, -3.4 percentage points; 95% CI, -7.0 to 0.2). Major bleeding occurred in 36 patients (6.9%) in the edoxaban group and in 21 patients (4.0%) in the dalteparin group (difference in risk, 2.9 percentage points; 95% CI, 0.1 to 5.6).
CONCLUSIONS
Oral edoxaban was noninferior to subcutaneous dalteparin with respect to the composite outcome of recurrent venous thromboembolism or major bleeding. The rate of recurrent venous thromboembolism was lower but the rate of major bleeding was higher with edoxaban than with dalteparin. (Funded by Daiichi Sankyo; Hokusai VTE Cancer ClinicalTrials.gov number, NCT02073682 .).
Topics: Adult; Aged; Anticoagulants; Dalteparin; Follow-Up Studies; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasms; Pyridines; Recurrence; Thiazoles; Venous Thromboembolism
PubMed: 29231094
DOI: 10.1056/NEJMoa1711948 -
Thrombosis and Haemostasis May 2022Efficacy and safety of anticoagulant treatment for venous thromboembolism (VTE) may vary in patients with different cancer sites. We evaluated the rates of VTE... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of anticoagulant treatment for venous thromboembolism (VTE) may vary in patients with different cancer sites. We evaluated the rates of VTE recurrence and major bleeding and the relative efficacy and safety of 6-month treatment with oral apixaban or subcutaneous dalteparin in patients with different cancer sites randomized in the Caravaggio study. Primary cancer was located at gastrointestinal sites in 375 patients (32.5%), lung in 200 (17.3%), breast in 155 (13.4%), genitourinary sites in 139 (12%), gynecological sites in 119 (10.3%), and was hematological in 85 patients (7.4%). Rates of VTE recurrence were 10.9% in patients with gynecological, 8.8% with gastrointestinal, 6.5% with genitourinary, and 5.5% with lung cancer with lower rates in the other sites of cancer. Rates of major bleeding were 7.2% in patients with genitourinary and 4.8% with gastrointestinal cancer, with lower rates in patients with other sites of cancer. The observed absolute risk difference in VTE recurrence in favor of apixaban was 11.9% in patients with gynecological, 5.5% with lung, 3.7% with genitourinary cancer, and 0.6% with gastrointestinal cancer. None of the risk differences was statistically significant. The rates of major bleeding in patients treated with apixaban or dalteparin was similar across patients with different cancer sites. In conclusion, recurrences appear to be more common in patients with gastrointestinal and gynecological cancer and major bleedings in patients with genitourinary and gastrointestinal cancer. Oral apixaban is a valid oral alternative to subcutaneous dalteparin for the treatment of a large spectrum of patients with cancer-associated VTE.
Topics: Anticoagulants; Dalteparin; Hemorrhage; Humans; Neoplasms; Pyrazoles; Pyridones; Venous Thromboembolism
PubMed: 34530482
DOI: 10.1055/s-0041-1735194 -
The American Journal of Nursing Oct 2019
Topics: Anticoagulants; Child; Child, Preschool; Dalteparin; Humans; Infant; Venous Thromboembolism
PubMed: 31567246
DOI: 10.1097/01.NAJ.0000586148.11015.7e -
The Annals of Pharmacotherapy Feb 1997To discuss the chemistry, pharmacology, and pharmacokinetics of dalteparin, a low-molecular-weight heparin (LMWH), and to review the comparative clinical trial data... (Review)
Review
OBJECTIVE
To discuss the chemistry, pharmacology, and pharmacokinetics of dalteparin, a low-molecular-weight heparin (LMWH), and to review the comparative clinical trial data evaluating the efficacy and safety of dalteparin and unfractionated heparin (UH) for the prophylaxis and treatment of venous thromboembolism.
DATA SOURCES
A MEDLINE search identified pertinent English-language publications on dalteparin and venous thromboembolism. Key search terms were dalteparin, Fragmin, LMWH, and venous thromboembolism. The search was supplemented by review articles, articles obtained from the bibliographies of the review articles, and the dalteparin approval database.
STUDY SELECTION
The most pertinent studies describing the pharmacology and pharmacokinetics of dalteparin in humans were selected; all abstracts and clinical evaluating the use of dalteparin for antithrombotic therapy were reviewed. Review articles by authors of international reputation were selected.
DATA EXTRACTION
Pertinent information from the review articles on the pharmacology of LMWHs and UH was summarized. Clinical trial data were extracted for study design, patient demographics, therapeutic regimens, methods of evaluation, and outcomes.
DATA SYNTHESIS
Dalteparin is an LMWH indicated for patients undergoing abdominal surgery who are considered to be at risk for deep-vein thrombosis (DVT), which may lead to pulmonary embolism (PE). In this population, numerous clinical trials have demonstrated comparable efficacy between dalteparin and fixed-dose UH for DVT prophylaxis. Dalteparin has a predictable dose response and can be administered as a standard single daily subcutaneous dose for all patients. In therapeutic doses, dalteparin does not alter coagulation tests and therefore does not require routine laboratory monitoring, in contrast with adjusted-dose UH. Bleeding risks with dalteparin are comparable with and possibly less than those associated with UH. Preliminary studies suggest that dalteparin may be effective for other indications, including DVT prophylaxis for hip replacement surgery and the treatment of DVT and PE. Comparative cost-effectiveness data are not yet available.
CONCLUSIONS
Dalteparin is the second LMWH to receive approval by the Food and Drug Administration. Dalteparin is indicated for prophylaxis against DVT in patients undergoing abdominal surgery. Clinical studies have shown that single daily doses of dalteparin provide a safe and effective alternative to fixed-dose UH therapy. Additional studies are needed to determine the cost-effectiveness of dalteparin compared with UH and other LMWHs.
Topics: Abdomen; Adult; Aged; Anticoagulants; Biological Availability; Dalteparin; Drug Costs; Female; Heparin, Low-Molecular-Weight; Hip Prosthesis; Humans; Male; Middle Aged; Postoperative Complications; Pulmonary Embolism; Thrombophlebitis
PubMed: 9034422
DOI: 10.1177/106002809703100212 -
BMJ Case Reports Oct 2016Drug fever caused by dalteparin-sodium (DS), a low-molecular-weight derivative of heparin, is neither listed in the official drug information and nor published as a case...
Drug fever caused by dalteparin-sodium (DS), a low-molecular-weight derivative of heparin, is neither listed in the official drug information and nor published as a case report until today. A preterm infant, born at 26 weeks of gestation, developed fever 2 days after starting a treatment with DS for an intracardial thrombus. The fever reverses soon after changing the treatment to unfractionated heparin and reappeared after reintroduction of DS. Once again, after discontinuing DS, the infant regained normothermia. Bacterial and viral infections, tissue damage, impaired liver or kidney function, preservative agents and comedications could be ruled out as fever origin. By using the Naranjo adverse drug reaction (ADR) probability scale and the Liverpool ADR causality assessment tool, this case can be classified as 'probable ADR' and 'definite ADR'. This is the first case report of a drug fever caused by the low-molecular-weight heparin DS in a preterm infant.
Topics: Anticoagulants; Dalteparin; Fever; Heart Diseases; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Thrombosis
PubMed: 27737872
DOI: 10.1136/bcr-2016-217621 -
International Journal of Pharmaceutical... 2017The stability of dalteparin 1,000 units/mL in 0.9% sodium chloride for injection stored in polypropylene syringes under refrigeration was examined. Dalteparin...
The stability of dalteparin 1,000 units/mL in 0.9% sodium chloride for injection stored in polypropylene syringes under refrigeration was examined. Dalteparin 1,000-units/mL syringes were prepared by adding 9 mL of 0.9% sodium chloride for injection to 1 mL of dalteparin sodium 10,000 unit/mL from commercial single-use syringes. Compounded solutions in 0.5-mL aliquots were transferred to 1-mL polypropylene syringes and sealed with a Luer lock tip cap and stored at refrigerated temperatures (2°C to 8°C) with ambient fluorescent light exposure. Syringes from three batches of dalteparin 1,000 units/mL were potency tested in duplicate by a stability-indicating high-performance liquid chromatography assay using a 0.5-mL sample at specified intervals. Visual and pH testing were performed on each batch. Samples were visually inspected for container integrity, color, and clarity. Samples for pH testing were prepared using a 1:1 dilution of dalteparin 1,000 units/mL in sterile water for injection and underwent duplicate analysis at each time point. High-performance liquid chromatography analyses showed a remaining percent of the initial dalteparin content at day 30 of 94.88% ± 2.11%. Samples remained colorless and clear with no signs of container compromise and no visual particulate matter at each time point. Throughout the 30-day study period, pH values remained within 0.3-pH units from the initial value of 5.84. Dalteparin 1,000 unit/mL in 0.9% sodium chloride for injection, packaged in 1-mL polypropylene syringes was stable for at least 30 days while stored at refrigerated conditions with ambient fluorescent light exposure.
Topics: Chromatography, High Pressure Liquid; Dalteparin; Drug Stability; Factor Xa Inhibitors; Hydrogen-Ion Concentration; Injections; Polypropylenes; Sodium Chloride; Syringes
PubMed: 29216619
DOI: No ID Found -
Journal of Cancer Research and... Dec 2018To investigate the effects of dalteparin sodium on the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), and hypoxia-inducible factor 1α...
PURPOSE
To investigate the effects of dalteparin sodium on the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), and hypoxia-inducible factor 1α (HIF-1α) in A549 human lung cancer (LC) cell line and a human A549-grafted nude mouse model.
MATERIALS AND METHODS
A549 human lung adenocarcinoma cell line was divided into control group, treated using normal saline (NS); and dalteparin sodium groups, receiving 5, 15, 50, and 150 IU/ml of dalteparin sodium, respectively. Human A549-grafted nude mouse was induced through subcutaneous (SC) injection of A549 (5 × 10/0.2 ml) into the right armpit, and randomly assigned into control group (n = 6) receiving intraperitoneal (i.p.) injection of NS, cisplatin (DDP) group (n = 6, 3 mg/kg DDP alone, i.p., for 3 days), low molecular weight heparin (LMWH) group (n = 6) receiving SC injection of 1500 IU/kg dalteparin sodium for 35 days, and DDP plus LMWH group (n = 6, 3 mg/kg DDP, i.p., for 3 days, followed by SC injection of 1500 IU/kg dalteparin sodium for 35 days).
RESULTS
Significant difference was noted in the messenger RNA expression of VEGF, VEGFR, and HIF-1α after treating with heparin with a concentration of 15, 50, or 150 IU/ml in the A549 cell line at 24 and 48 h, respectively. In the human A549-grafted nude mouse model, a significant reduction was noted in the expression of VEGF, VEGFR, and HIF-1α in the tumor mass harvested from the mice receiving administration of dalteparin sodium plus DDP.
CONCLUSION
Dalteparin sodium had the inhibitory effects on the growth of human LC A549 cells in vitro and A549 LC xenograft model, which could be enhanced when administrated together with DDP.
Topics: A549 Cells; Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Proliferation; Cisplatin; Dalteparin; Drug Synergism; Female; Humans; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Neovascularization, Pathologic; Receptors, Vascular Endothelial Growth Factor; Treatment Outcome; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assays
PubMed: 30539834
DOI: 10.4103/0973-1482.192765