DRUGS & SUPPLEMENTS
INDICATIONS AND USAGE
Daltehep Injection is indicated for the prophylaxis of ischemic complications in unstable angina and non-Q-wave myocardial infarction, when concurrently administered with aspirin therapy (as described in CLINICAL TRIALS, Prophylaxis of Ischemic Complications in Unstable Angina and Non-Q-Wave Myocardial Infarction).
Daltehep is also indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE):
Daltehep Injection is contraindicated in patients with known hypersensitivity to the drug, active major bleeding, or thrombocytopenia associated with positive in vitro tests for antiplatelet antibody in the presence of Daltehep.
Patients undergoing regional anesthesia should not receive Daltehep for unstable angina or non-Q-wave myocardial infarction, and patients with cancer undergoing regional anesthesia should not receive Daltehep for extended treatment of symptomatic VTE, due to an increased risk of bleeding associated with the dosage of Daltehep recommended for these indications. Patients with known hypersensitivity to heparin or pork products should not be treated with Daltehep.
Daltehep Injection is not intended for intramuscular administration.
Daltehep cannot be used interchangeably with unfractionated heparin or other low molecular weight heparins.Daltehep should be used with extreme caution in patients with history of heparin-induced thrombocytopenia.
Daltehep, like other anticoagulants, should be used with extreme caution in patients who have an increased risk of hemorrhage, such as those with severe uncontrolled hypertension, bacterial endocarditis, congenital or acquired bleeding disorders, active ulceration and angiodysplastic gastrointestinal disease, hemorrhagic stroke, or shortly after brain, spinal or ophthalmological surgery.
Spinal or epidural hematomas can occur with the associated use of low molecular weight heparins or heparinoids and neuraxial (spinal/epidural) anesthesia or spinal puncture, which can result in long-term or permanent paralysis. The risk of these events is higher with the use of indwelling epidural catheters or concomitant use of additional drugs affecting hemostasis such as NSAIDs.As with other anticoagulants, bleeding can occur at any site during therapy with Daltehep. An unexpected drop in hematocrit or blood pressure should lead to a search for a bleeding site.
In Daltehep clinical trials supporting non-cancer indications, platelet counts of < 100,000/mm3 and < 50,000/mm3 occurred in < 1% and < 1% of patients, respectively.
In the clinical trial of patients with cancer and acute symptomatic venous thromboembolism treated for up to 6 months in the Daltehep treatment arm, platelet counts of < 100,000/mm3 occurred in 13.6% of patients, including 6.5% who also had platelet counts less than 50,000/mm3. In the same clinical trial, thrombocytopenia was reported as an adverse event in 10.9% of patients in the Daltehep arm and 8.1% of patients in the OAC arm. Daltehep dose was decreased or interrupted in patients whose platelet counts fell below 100,000/mm3.Thrombocytopenia of any degree should be monitored closely. Heparin-induced thrombocytopenia can occur with the administration of Daltehep. The incidence of this complication is unknown at present. In clinical practice, rare cases of thrombocytopenia with thrombosis have also been observed.
Each multiple-dose vial of Daltehep contains benzyl alcohol as a preservative. Benzyl alcohol has been reported to be associated with a fatal "Gasping Syndrome" in premature infants. Because benzyl alcohol may cross the placenta, Daltehep preserved with benzyl alcohol should be used with caution in pregnant women and only if clearly needed. If anticoagulation with Daltehep is needed during pregnancy, preservative-free formulations should be used, where possible. (see PRECAUTIONS, Pregnancy Category B, Nonteratogenic Effects).
Daltehep Injection should not be mixed with other injections or infusions unless specific compatibility data are available that support such mixing.
Daltehep should be used with caution in patients with bleeding diathesis, thrombocytopenia or platelet defects; severe liver or kidney insufficiency, hypertensive or diabetic retinopathy, and recent gastrointestinal bleeding. If a thromboembolic event should occur despite dalteparin prophylaxis, Daltehep should be discontinued and appropriate therapy initiated.
Daltehep should be used with care in patients receiving oral anticoagulants, platelet inhibitors, and thrombolytic agents because of increased risk of bleeding. Aspirin, unless contraindicated, is recommended in patients treated for unstable angina or non-Q-wave myocardial infarction (see DOSAGE AND ADMINISTRATION).
Periodic routine complete blood counts, including platelet count, blood chemistry, and stool occult blood tests are recommended during the course of treatment with Daltehep. No special monitoring of blood clotting times (i.e., APTT) is needed.
When administered at recommended prophylaxis doses, routine coagulation tests such as Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) are relatively insensitive measures of Daltehep activity and, therefore, unsuitable for monitoring the anticoagulant effect of Daltehep. Anti-Factor Xa may be used to monitor the anticoagulant effect of Daltehep, such as in patients with severe renal impairment or if abnormal coagulation parameters or bleeding should occur during Daltehep therapy.
Drug/Laboratory Test Interactions
Elevations of Serum Transaminases
In Daltehep clinical trials supporting non-cancer indications where hepatic transaminases were measured, asymptomatic increases in transaminase levels 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 Daltehep.
In the Daltehep clinical trial of patients with cancer and acute symptomatic venous thromboembolism treated with Daltehep 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.
Carcinogenicity, Mutagenesis, Impairment of Fertility
Daltehep has not been tested for its carcinogenic potential in long-term animal studies. It was not mutagenic in the in vitro Ames Test, mouse lymphoma cell forward mutation test and human lymphocyte chromosomal aberration test and in the in vivo mouse micronucleus test. Daltehep at subcutaneous doses up to 1200 IU/kg (7080 IU/m2) did not affect the fertility or reproductive performance of male and female rats.
Pregnancy Category B
Reproduction studies with Daltehep at intravenous doses up to 2400 IU/kg in pregnant rats and 4800 IU/kg (40,800 IU/m2) in pregnant rabbits did not produce any evidence of impaired fertility or harm to the fetuses. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Cases of "Gasping Syndrome" have occurred when large amounts of benzyl alcohol have been administered (99–404 mg/kg/day). The 9.5 mL and the 3.8 mL multiple-dose vials of Daltehep contain 14 mg/mL of benzyl alcohol.
Limited data are available for excretion of dalteparin in human milk. One study in 15 lactating women receiving prophylactic doses of dalteparin detected small amounts of anti-Xa activity in breast milk, equivalent to a milk/plasma ratio of <0.025–0.224. As oral absorption of LMWH is extremely low, the clinical implications, if any, of this small amount of anticoagulant activity on the nursing infant are unknown. Caution should be exercised when Daltehep is administered to nursing women.
Safety and effectiveness in pediatric patients have not been established.
Of the total number of patients in clinical studies of Daltehep, 5516 patients were 65 years of age or older and 2237 were 75 or older. No overall differences in effectiveness were observed between these subjects and younger subjects. Some studies suggest that the risk of bleeding increases with age. Postmarketing surveillance and literature reports have not revealed additional differences in the safety of Daltehep between elderly and younger patients. Careful attention to dosing intervals and concomitant medications (especially antiplatelet medications) is advised, particularly in geriatric patients with low body weight (< 45 kg) and those predisposed to decreased renal function (see also CLINICAL PHARMACOLOGY and General and Drug Interactions subsections of PRECAUTIONS).
The incidence of hemorrhagic complications during treatment with Daltehep Injection has been low. The most commonly reported side effect is hematoma at the injection site. The incidence of bleeding may increase with higher doses; however, in abdominal surgery patients with malignancy, no significant increase in bleeding was observed when comparing Daltehep 5000 IU to either Daltehep 2500 IU or low dose heparin.
In a trial comparing Daltehep 5000 IU once daily to Daltehep 2500 IU once daily in patients undergoing surgery for malignancy, the incidence of bleeding events was 4.6% and 3.6%, respectively. In a trial comparing Daltehep 5000 IU once daily to heparin 5000 U twice daily, the incidence of bleeding events was 3.2% and 2.7%, respectively (n.s.) in the malignancy subgroup.
Unstable Angina and Non-Q-Wave Myocardial Infarction
Table 8 summarizes major bleeding events that occurred with Daltehep, heparin, and placebo in clinical trials of unstable angina and non-Q-wave myocardial infarction.
Hip Replacement Surgery
Table 9 summarizes: 1) all major bleeding events and, 2) other bleeding events possibly or probably related to treatment with Daltehep, warfarin sodium, or heparin in two hip replacement surgery clinical trials.
Six of the patients treated with Daltehep experienced seven major bleeding events. Two of the events 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 nor died of bleeding complications.
In the third hip replacement surgery clinical trial, the incidence of major bleeding events was similar in all three treatment groups: 3.6% (18/496) for patients who started Daltehep before surgery; 2.5% (12/487) for patients who started Daltehep after surgery; and 3.1% (15/489) for patients treated with warfarin sodium.
Table 10 summarizes bleeding events that occurred in clinical trials which studied Daltehep 2500 and 5000 IU administered once daily to abdominal surgery patients.
Medical Patients with Severely Restricted Mobility During Acute Illness
Table 11 summarizes major bleeding events that occurred in a clinical trial of medical patients with severely restricted mobility during acute illness.
Three of the major bleeding events that occurred by Day 21 were fatal, all due to gastrointestinal hemorrhage (two patients in the group treated with Daltehep and one in the group receiving placebo). Two deaths occurred after Day 21: one patient in the placebo group died from a subarachnoid hemorrhage that started on Day 55, and one patient died on day 71 (two months after receiving the last dose of Daltehep) from a subdural hematoma.
Patients with Cancer and Acute Symptomatic Venous Thromboembolism
Table 12 summarizes the number of patients with bleeding events 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.
At the end of the six-month study, a total of 46 (13.6%) patients in the Daltehep arm and 62 (18.5%) patients in the OAC arm experienced any bleeding event. One bleeding event (hemoptysis in a patient in the Daltehep arm at Day 71) was fatal.
Allergic reactions have occurred rarely. A few cases of anaphylactoid reactions have been reported.
Pain at the injection site, the only non-bleeding event determined to be possibly or probably related to treatment with Daltehep and reported at a rate of at least 2% in the group treated with Daltehep, was reported in 4.5% of patients treated with Daltehep 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 Daltehep 5000 IU once daily vs 13% of patients treated with heparin 5000 U three times a day.
Ongoing Safety Surveillance
Since first international market introduction in 1985, there have been more than 15 reports of epidural or spinal hematoma formation with concurrent use of Daltehep 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. Because these events were reported voluntarily from a population of unknown size, estimates of frequency cannot be made.
Skin necrosis has occurred rarely. There have been isolated cases of alopecia reported that improved on drug discontinuation.
An excessive dosage of Daltehep Injection may lead to hemorrhagic complications. These may generally be stopped by the slow intravenous injection of protamine sulfate (1% solution), at a dose of 1 mg protamine for every 100 anti-Xa IU of Daltehep given. A second infusion of 0.5 mg protamine sulfate per 100 anti-Xa IU of Daltehep may be administered if the APTT measured 2 to 4 hours after the first infusion remains prolonged. Even with these additional doses of protamine, the APTT may remain more prolonged than would usually be found following administration of conventional heparin. In all cases, the anti-Factor Xa activity is never completely neutralized (maximum about 60 to 75%).
Particular care should be taken to avoid overdosage with protamine sulfate. Administration of protamine sulfate can cause severe hypotensive and anaphylactoid reactions. Because fatal reactions, often resembling anaphylaxis, have been reported with protamine sulfate, it should be given only when resuscitation techniques and treatment of anaphylactic shock are readily available. For additional information, consult the labeling of Protamine Sulfate Injection, USP, products. A single subcutaneous dose of 100,000 IU/kg of Daltehep to mice caused a mortality of 8% (1/12) whereas 50,000 IU/kg was a non-lethal dose. The observed sign was hematoma at the site of injection.
DOSAGE AND ADMINISTRATION
Prophylaxis of Ischemic Complications in Unstable Angina and Non-Q-Wave Myocardial Infarction
In patients with unstable angina or non-Q-wave myocardial infarction, the recommended dose of Daltehep Injection is 120 IU/kg of body weight, but not more than 10,000 IU, subcutaneously every 12 hours with concurrent oral aspirin (75 to 165 mg once daily) therapy. Treatment should be continued until the patient is clinically stabilized. The usual duration of administration is 5 to 8 days. Concurrent aspirin therapy is recommended except when contraindicated.
Table 13 lists the volume of Daltehep, based on the 9.5 mL multiple-dose vial (10,000 IU/mL), to be administered for a range of patient weights.
Prophylaxis of Venous Thromboembolism Following Hip Replacement Surgery
Table 14 presents the dosing options for patients undergoing hip replacement surgery. The usual duration of administration is 5 to 10 days after surgery; up to 14 days of treatment with Daltehep have been well tolerated in clinical trials.
Prophylaxis of Venous Thromboembolism Following Abdominal Surgery
In patients undergoing abdominal surgery with a risk of thromboembolic complications, the recommended dose of Daltehep is 2500 IU administered by s.c. injection once daily, starting 1 to 2 hours prior to surgery and repeated once daily postoperatively. The usual duration of administration is 5 to 10 days.
In patients undergoing abdominal surgery associated with a high risk of thromboembolic complications, such as malignant disorder, the recommended dose of Daltehep is 5000 IU s.c. the evening before surgery, then once daily postoperatively. The usual duration of administration is 5 to 10 days. Alternatively, in patients with malignancy, 2500 IU of Daltehep can be administered s.c. 1 to 2 hours before surgery followed by 2500 IU s.c. 12 hours later, and then 5000 IU once daily postoperatively. The usual duration of administration is 5 to 10 days. Dosage adjustment and routine monitoring of coagulation parameters are not required if the dosage and administration recommendations specified above are followed.
Medical Patients with Severely Restricted Mobility During Acute Illness
In medical patients with severely restricted mobility during acute illness, the recommended dose of Daltehep is 5000 IU administered by s.c. injection once daily. In clinical trials, the usual duration of administration was 12 to 14 days.
Extended Treatment of Symptomatic Venous Thromboembolism in Patients with Cancer
In patients with cancer and symptomatic venous thromboembolism, the recommended dosing of Daltehep is as follows: for the first 30 days of treatment administer Daltehep 200 IU/kg total body weight subcutaneously once daily. The total daily dose should not exceed 18,000 IU. Table 15 lists the dose of Daltehep to be administered once daily during the first month for a range of patient weights.
Months 2 to 6
Administer Daltehep at a dose of approximately 150 IU/kg, s.c. once daily during Months 2 through 6. The total daily dose should not exceed 18,000 IU. Table 16 lists the dose of Daltehep to be administered once daily for a range of patient weights during months 2–6.
Safety and efficacy beyond six months have not been evaluated in patients with cancer and acute symptomatic VTE (see WARNINGS, Thrombocytopenia and ADVERSE REACTIONS, Patients with Cancer and Acute Symptomatic VTE).
Dose reductions for thrombocytopenia in patients with cancer and acute symptomatic VTE
In patients receiving Daltehep who experience platelet counts between 50,000 and 100,000/mm3, reduce the daily dose of Daltehep by 2,500 IU until the platelet count recovers to ≥100,000/mm3. In patients receiving Daltehep who experience platelet counts < 50,000/mm3, Daltehep should be discontinued until the platelet count recovers above 50,000/mm3.
Dose reductions for renal insufficiency in extended treatment of acute symptomatic venous thromboembolism in patients with cancer
In patients with severely impaired renal function, monitoring for anti-Xa levels is recommended to determine the appropriate Daltehep dose. Target anti-Xa range is 0.5–1.5 IU/mL. When monitoring anti-Xa in these patients, sampling should be performed 4–6 hrs after Daltehep dosing and only after the patient has received 3–4 doses.
Daltehep is administered by subcutaneous injection. It must not be administered by intramuscular injection.
Subcutaneous injection technique: Patients should be sitting or lying down and Daltehep administered by deep s.c. injection. Daltehep may be injected in a U-shape area around the navel, the upper outer side of the thigh or the upper outer quadrangle of the buttock. The injection site should be varied daily. When the area around the navel or the thigh is used, using the thumb and forefinger, you must lift up a fold of skin while giving the injection. The entire length of the needle should be inserted at a 45 to 90 degree angle. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. After first penetration of the rubber stopper, store the multiple-dose vials at room temperature for up to 2 weeks. Discard any unused solution after 2 weeks.
Instructions for using the prefilled single-dose syringes preassembled with needle guard devices
Fixed dose syringes
To ensure delivery of the full dose, do not expel the air bubble from the prefilled syringe before injection. Hold the syringe assembly by the open sides of the device. Remove the needle shield. Insert the needle into the injection area as instructed above. Depress the plunger of the syringe while holding the finger flange until the entire dose has been given. The needle guard will not be activated unless the entire dose has been given. Remove needle from the patient. Let go of the plunger and allow syringe to move up inside the device until the entire needle is guarded. Discard the syringe assembly in approved containers.
Hold the syringe assembly by the open sides of the device. Remove the needle shield. With the needle pointing up, prepare the syringe by expelling the air bubble and then continuing to push the plunger to the desired dose or volume, discarding the extra solution in an appropriate manner. Insert the needle into the injection area as instructed above. Depress the plunger of the syringe while holding the finger flange until the entire dose remaining in the syringe has been given. The needle guard will not be activated unless the entire dose has been given. Remove needle from the patient. Let go of the plunger and allow syringe to move up inside the device until the entire needle is guarded. Discard the syringe assembly in approved containers.
Daltehep Injection is available in the following strengths and package sizes:
Store at controlled room temperature 20° to 25°C (68° to 77°F).
Daltehep is a registered trademark of Pfizer Health AB and is licensed to Eisai Inc.
* UltraSafe Passive™ Needle Guard is a trademark of Safety Syringes, Inc.
Woodcliff Lake, NJ 07677
New York, NY 10017
Made in Belgium
Jointly manufactured by
Pfizer Inc, New York, NY 10017
and Vetter Pharma-Fertigung, GmbH & Co. KG
Daltehep pharmaceutical active ingredients containing related brand and generic drugs:
Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.
Daltehep available forms, composition, doses:
Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.
Daltehep destination | category:
Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.
Daltehep Anatomical Therapeutic Chemical codes:
A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.
Daltehep pharmaceutical companies:
Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.
Frequently asked QuestionsCan i drive or operate heavy machine after consuming Daltehep?
Depending on the reaction of the Daltehep after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Daltehep not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.Is Daltehep addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
ReviewsDrugs.com conducted a study on Daltehep, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Daltehep consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.
The information was verified by Dr. Arunabha Ray, MD Pharmacology