Fragmin
- Generic Name: dalteparin
- Brand Name: Fragmin
Fragmin (Dalteparin) side effects drug center
Fragmin Side Effects Center
What Is Fragmin?
Fragmin (dalteparin) is an anticoagulant (blood thinner), a type of heparin indicated to prevent ischemic complications in unstable angina and non-Q-wave myocardial infarction, when concurrently administered with aspirin therapy. Fragmin is also used for the prevention of deep vein thrombosis in certain patients.
What Are Side Effects of Fragmin?
Side effects of Fragmin include:
- easy bruising or bleeding, or
- pain, redness, irritation, bruising, or swelling where the medicine was injected.
- Fragmin can cause bleeding if its effect on your blood clotting proteins is too strong.
Tell your doctor if you have serious side effects of Fragmin including:
- serious signs of bleeding, including unusual pain/swelling/discomfort,
- unusual or prolonged bleeding,
- unusual or easy bruising,
- purple or red pinpoints under your skin,
- dark urine,
- black or bloody stools,
- severe headache,
- confusion,
- trouble concentrating,
- vision changes,
- unusual dizziness,
- pale skin,
- shortness of breath,
- trouble breating,
- rapid heart rate,
- lightheartedness,
- fainting,
- coughing up blood or vomit that looks like coffee grounds,
- numbness, tingling, or muscle weakness (especially in your legs and feet),
- loss of movement in any part of your body,
- problems with speech, vision, or balance,
- seizures, or
- sudden weakness.
Dosage for Fragmin
Fragmin is available in single-dose, prefilled syringes preassembled with a needle guard device, and multiple-dose vials. Fragmin is administered by subcutaneous injection.
What Drugs, Substances, or Supplements Interact with Fragmin?
Fragmin may interact with dextran, abciximab, eptifibatide, ticagrelor, tirofiban, alteplase, reteplase, tenecteplase, urokinase, anagrelide, cilostazol, clopidogrel, dipyridamole, eltrombopag, oprelvekin, prasugrel, romiplostim, ticagrelor, ticlopidine, argatroban, bivalirudin, dabigatran, lepirudin, enoxaparin, fondaparinux, heparin, rivaroxaban, tinzaparin, warfarin, NSAIDs (nonsteroidal anti-inflammatory drugs) or salicylates such as aspirin and others. Tell your doctor all medications and supplements you use.
Fragmin During Pregnancy and Breastfeeding
This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether dalteparin passes into breast milk or if it could harm a nursing baby. Consult your doctor before breastfeeding.
Additional Information
Our Fragmin Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
Fragmin Consumer Information
Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Also seek emergency medical attention if you have symptoms of a spinal blood clot: back pain, numbness or muscle weakness in your lower body, or loss of bladder or bowel control.
Stop using dalteparin and call your doctor at once if you have:
- unusual bleeding (nose, mouth, vagina, or rectum), bleeding from wounds or needle injections, any bleeding that will not stop;
- easy bruising, purple or red pinpoint spots under your skin;
- black or bloody stools, coughing up blood or vomit that looks like coffee grounds;
- sudden weakness, severe headache, confusion, or problems with speech, vision, or balance; or
- trouble breathing.
Common side effects may include:
- low platelet levels (bruising, bleeding); or
- pain, bruising, or swelling where the medicine was injected.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Read the entire detailed patient monograph for Fragmin (Dalteparin)
Fragmin Professional Information
SIDE EFFECTS
The following clinically significant adverse reactions are described in more detail in other sections of the prescribing information.
- Risk of Hemorrhage including Spinal/Epidural Hematomas [see WARNINGS AND PRECAUTION]
- Thrombocytopenia [see WARNINGS AND PRECAUTION]
- Benzyl Alcohol Preservative Risk to Premature Infants [see WARNINGS AND PRECAUTION]
Clinical Trials Experience
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.
Hemorrhage
The most commonly reported adverse reactions are hematoma at the injection site and hemorrhagic complications. The risk for bleeding varies with the indication and may increase with higher doses.
Unstable Angina And Non-Q-Wave Myocardial Infarction
Table 7 summarizes major bleeding reactions that occurred with FRAGMIN, heparin, and placebo in clinical trials of unstable angina and non-Q-wave myocardial infarction.
Table 7 : Major Bleeding Reactions in Unstable Angina and Non-Q-Wave Myocardial Infarction
| Indication | Dosing Regimen | ||
| Unstable Angina and Non-Q-Wave MI | FRAGMIN 120 IU/kg/12 hr subcutaneous* n (%) | Heparin intravenous and subcutaneous† n (%) | Placebo every 12 hr subcutaneous n (%) |
| Major Bleeding Reactions‡,§ | 15/1497 (1.0) | 7/731 (1.0) | 4/760 (0.5) |
| *Treatment was administered for 5 to 8 days. †Heparin intravenous infusion for at least 48 hours, APTT 1.5 to 2 times control, then 12,500 U subcutaneously every 12 hours for 5 to 8 days. ‡Aspirin (75 to 165 mg per day) and beta blocker therapies were administered concurrently. §Bleeding reactions were considered major if: 1) accompanied by a decrease in hemoglobin of ≥2 g/dL in connection with clinical symptoms; 2) a transfusion was required; 3) bleeding led to interruption of treatment or death; or 4) intracranial bleeding. | |||
Hip Replacement Surgery
Table 8 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.
Table 8 : Bleeding Reactions Following Hip Replacement Surgery
| Indication | FRAGMIN vs Warfarin Sodium | FRAGMIN vs Heparin | ||
| Dosing Regimen | Dosing Regimen | |||
| Hip Replacement Surgery | FRAGMIN* 5,000 IU once daily subcutaneous n (%) | Warfarin Sodium† oral n (%) | FRAGMIN‡ 5,000 IU once daily subcutaneous n (%) | Heparin 5,000 U three times a day subcutaneous n (%) |
| Major Bleeding Reactions§ | 7/274 (2.6) | 1/279 (0.4) | 0 | 3/69 (4.3) |
| Other Bleeding Reactions¶ Hematuria | 8/274 (2.9) | 5/279 (1.8) | 0 | 0 |
| Wound Hematoma | 6/274 (2.2) | 0 | 0 | 0 |
| Injection Site Hematoma | 3/274 (1.1) | NA | 2/69 (2.9) | 7/69(10.1) |
| *Includes three treated patients who did not undergo a surgical procedure. †Warfarin sodium dosage was adjusted to maintain a prothrombin time index of 1.4 to 1.5, corresponding to an International Normalized Ratio (INR) of approximately 2.5. ‡Includes two treated patients who did not undergo a surgical procedure. §A bleeding event was considered major if: 1) hemorrhage caused a significant clinical event, 2) it was associated with a hemoglobin decrease of ≥2 g/dL or transfusion of 2 or more units of blood products, 3) it resulted in reoperation due to bleeding, or 4) it involved retroperitoneal or intracranial hemorrhage. ¶ Occurred at a rate of at least 2% in the group treated with FRAGMIN 5,000 IU once daily. | ||||
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.
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.
Abdominal Surgery
Table 9 summarizes bleeding reactions that occurred in clinical trials which studied FRAGMIN 2,500 and 5,000 IU administered once daily to abdominal surgery patients.
Table 9 : Bleeding Reactions Following Abdominal Surgery
| Indication | FRAGMIN vs Placebo | FRAGMIN vs FRAGMIN | ||
| Dosing Regimen | Dosing Regimen | |||
| Abdominal Surgery | FRAGMIN 2,500 IU once daily subcutaneous n (%) | Placebo once daily subcutaneous n (%) | FRAGMIN 2,500 IU once daily subcutaneous n (%) | FRAGMIN 5,000 IU once daily subcutaneous n (%) |
| Postoperative Transfusions | 14/182 | 13/182 | 89/1.025 | 125/1.033 |
| (7.7) | (7.1) | (8.7) | (12.1) | |
| Wound Hematoma | 2/79 | 2/77 | 1/1.030 | 4/1.039 |
| (2.5) | (2.6) | (0.1) | (0.4) | |
| Reoperation Due to | 1/79 | 1/78 | 2/1.030 | 13/1.038 |
| Bleeding | (1.3) | (1.3) | (0.2) | (1.3) |
| Injection Site Hematoma | 8/172 | 2/174 | 36/1.026 | 57/1.035 |
| (4.7) | (1.1) | (3.5) | (5.5) | |
| Postoperative Transfusions | 26/459 | 36/454 | 81/508 | 63/498 |
| (5.7) | (7.9) | (15.9) | (12.7) | |
| Wound Hematoma | 16/467 | 18/467 | 12/508 | 6/498 |
| (3.4) | (3.9) | (2.4) | (1.2) | |
| Reoperation Due to | 2/392 | 3/392 | 4/508 | 2/498 |
| Bleeding | (0.5) | (0.8) | (0.8) | (0.4) |
| Injection Site Hematoma | 1/466 | 5/464 | 36/506 | 47/493 |
| (0.2) | (1.1) | (7.1) | (9.5) | |
In a trial comparing FRAGMIN 5,000 IU once daily to FRAGMIN 2,500 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 5,000 IU once daily to heparin 5,000 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.).
Medical Patients With Severely Restricted Mobility During Acute Illness
Table 10 summarizes major bleeding reactions that occurred in a clinical trial of medical patients with severely restricted mobility during acute illness.
Table 10 : Bleeding Reactions in Medical Patients with Severely Restricted Mobility During Acute Illness
| Indication | Dosing Regimen | |
| Medical Patients with Severely Restricted Mobility | FRAGMIN 5,000 IU once daily subcutaneous n (%) | Placebo once daily subcutaneous n (%) |
| Major Bleeding Reactions* at Day 14 | 8/1.848 (0.4) | 0/1.833 (0) |
| Major Bleeding Reactions* at Day 21 | 9/1.848 (0.5) | 3/1.833 (0.2) |
| *A bleeding event was considered major if: 1) it was accompanied by a decrease in hemoglobin of ≥2 g/dL in connection with clinical symptoms; 2) intraocular, spinal/epidural, intracranial, or retroperitoneal bleeding; 3) required transfusion of ≥2 units of blood products; 4) required significant medical or surgical intervention; or 5) led to death. | ||
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).
Adult Patients With Cancer And Acute Symptomatic VTE
Table 11 summarizes the number of patients with bleeding reactions that occurred in the clinical trial of adult patients with cancer and acute symptomatic VTE. 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.
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.
Table 11 : Bleeding Reactions (Major and Any) (As treated population)*
| Study period | FRAGMIN 200 IU/kg (max. 18,000 IU) subcutaneous once daily x 1 month, then 150 IU/kg (max. 18,000 IU) subcutaneous once daily x 5 months | OAC FRAGMIN 200 IU/kg (max 18,000 IU) subcutaneous once daily x 5-7 days and OAC for 6 months (target INR 2-3) | ||||
| Number at risk | Patients with Major Bleeding n (%) | Patients with Any Bleeding n (%) | Number at risk | Patients with Major Bleeding n (%) | Patients with Any Bleeding n (%) | |
| Total during study | 338 | 19 (5.6) | 46 (13.6) | 335 | 12 (3.6) | 62 (18.5) |
| Week 1 | 338 | 4 (1.2) | 15 (4.4) | 335 | 4 (1.2) | 12 (3.6) |
| Weeks 2-A | 332 | 9 (2.7) | 17 (5.1) | 321 | 1 (0.3) | 12 (3.7) |
| Weeks 5-28 | 297 | 9 (3.0) | 26 (8.8) | 267 | 8 (3.0) | 40 (15.0) |
| *Patients with multiple bleeding episodes within any time interval were counted only once in that interval. However, patients with multiple bleeding episodes that occurred at different time intervals were counted once in each interval in which the event occurred. | ||||||
Elevations Of Serum Transaminases
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.
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.
Other
Allergic Reactions
Allergic reactions (i.e., pruritus, rash, fever, injection site reaction, bullous eruption) have occurred. Cases of anaphylactoid reactions have been reported.
Local Reactions
Pain at the injection site was reported in 4.5% of patients treated with FRAGMIN 5,000 IU once daily vs 11.8% of patients treated with heparin 5,000 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 5,000 IU once daily vs 13% of patients treated with heparin 5,000 U three times a day.
Pediatric Patients With Symptomatic VTE
The data below reflect exposure to FRAGMIN from two studies in pediatric patients from newborn to less than 18 years of age with or without cancer and symptomatic VTE (n = 50). Patients were started on FRAGMIN using age and weight-based dosing via subcutaneous injection twice daily. Anti-Xa levels were measured prior to the 4th dose and then periodically to determine whether dose adjustments were required, using 25 IU/kg increments, to achieve a target anti-Xa level of 0.5 - 1.0 IU/ml. The median time on treatment with FRAGMIN was 86 days (range 2 to 170 days).
In pediatric patients with symptomatic VTE, the most common (greater than 10%) adverse reactions were injection site bruising (30%), contusion (12%), and epistaxis (10%).
Major bleeding was defined as any fatal bleeding, clinically overt bleeding with a decrease in hemoglobin of ≥2gm/dl in 24 hours, overt bleeding deemed by the attending physician to be unrelated to the subject's underlying condition and accompanied by blood product administration, overt bleeding that was retroperitoneal, intracranial, intraspinal, intraocular, or intraarticular, or overt bleeding deemed by the attending physician to necessitate permanent discontinuation of trial medication. Major bleeding (intestinal hematoma) occurred in one patient (2%). Discontinuation due to adverse reactions occurred in 12% of patients, most often due to thrombocytopenia (4%).
Postmarketing Experience
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.
Since first international market introduction in 1985, there have been more than 15 reports of epidural or spinal hematoma formation with concurrent use of FRAGMIN 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].
Musculoskeletal System: Osteoporosis
Skin or subcutaneous tissues disorders: Skin necrosis, cases of alopecia reported that improved on drug discontinuation
Read the entire FDA prescribing information for Fragmin (Dalteparin)
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