Dalteparin Sodium Injection 2500IU/0.2ml Taj Pharma

Dalteparin Sodium Injection 2500IU/0.2ml &  5000 IU/0.2ml Taj Pharma

1.Name of the medicinal product

Dalteparin Sodium Injection 2500 IU/0.2ml & 5000IU/0.2ml Taj Pharma

2. Qualitative and quantitative composition

Active ingredient

Dalteparin sodium

Quality according to Ph.Eur. and in-house specification.

Potency is described in International anti-Factor Xa units (IU) of the 1st International Standard for Low Molecular Weight Heparin.

Content of active ingredient

Dalteparin Sodium 2500 IU: single dose syringe containing dalteparin sodium 2500 IU (anti-Factor Xa) in 0.2 ml solution.

Dalteparin Sodium 5000 IU: single dose syringe containing dalteparin sodium 5000 IU (anti-Factor Xa) in 0.2 ml solution.

Dalteparin Sodium syringes do not contain preservatives.

3. Pharmaceutical form

Solution for injection for subcutaneous administration.

4. Clinical particulars

4.1 Therapeutic indications

Peri- and post-operative surgical thromboprophylaxis.

The prophylaxis of proximal deep venous thrombosis in patients bedridden due to a medical condition, including, but not limited to; congestive cardiac failure (NYHA class III or IV), acute respiratory failure or acute infection, who also have a predisposing risk factor for venous thromboembolism such as age over 75 years, obesity, cancer or previous history of VTE.

Patients with solid tumours: Extended treatment of symptomatic venous thromboembolism (VTE) and prevention of its recurrence.

4.2 Posology and method of administration

Peri- and post-operative surgical thromboprophylaxis:

Adults

Surgical thromboprophylaxis in patients at high risk of thrombosis: 2,500 IU is administered subcutaneously 1-2 hours before the surgical procedure and 2,500 IU subcutaneously 8-12 hours later. On the following days, 5,000 IU subcutaneously each morning.

As an alternative, 5,000 IU is administered subcutaneously the evening before the surgical procedure and 5,000 IU subcutaneously the following evenings.

Treatment is continued until the patient is mobilised, in general 5-7 days or longer.

Prolonged thromboprophylaxis in hip replacement surgery: 5,000IU is given subcutaneously the evening before the operation and 5,000IU subcutaneously the following evenings. Treatment is continued for five post-operative weeks.

If pre-operative administration of Dalteparin Sodium is not considered appropriate because the patient is at high risk of haemorrhage during the procedure, post-operative Dalteparin Sodium may be administered (see Section 5.1).

Prophylaxis of venous thromboembolism in medical patients: The recommended dose of dalteparin sodium is 5,000 IU once daily. Treatment with dalteparin sodium is prescribed for up to 14 days.

Patients with solid tumours: Extended treatment of symptomatic venous thromboembolism (VTE) and prevention of its recurrence.

Month 1

Administer Dalteparin Sodium 200 IU/kg total body weight subcutaneously (SC) once daily for the first 30 days of treatment. The total daily dose should not exceed 18,000 IU daily.

Body Weight (kg) Dose (IU)
<46 7 500
46-56 10 000
57-68 12 500
69-82 15 000
83 and over 18 000*

*Maximum dose of 18, 000 IU was used in patient weighing up to 132 kg in the CLOT study.

Abbreviations: IU = International Unit

In the case of chemotherapy-induced thrombocytopenia, Dalteparin Sodium dose should be adopted as follows:

– In patients receiving Dalteparin Sodium who experience platelet counts between 50,000 and 100,000/mm3, the daily dose of Dalteparin Sodium should be reduced by 2,500 IU until the platelet count recovers to ≥100,000/mm3.

– In patients receiving Dalteparin Sodium who experience platelet counts <50,000/mm3, Dalteparin Sodium should be discontinued until the platelet count recovers above 50,000/mm3.

Months 2-6

Dalteparin Sodium should be administered at a dose of approximately 150 IU/kg, subcutaneously, once daily using fixed dose syringes and the table shown below.

Body Weight (kg) Dose (IU)
≤56 7 500
57 to 68 10 000
69 to 82 12 500
83 to 98 15 000
≥99 18 000

Recommended duration of treatment is 6 months (first month of Dalteparin Sodium treatment is included). Relevance of continuing treatment beyond this period will be evaluated according to individual risk/benefit ratio, taking into account particularly the progression of cancer. No data is available with dalteparin beyond 6 months of treatment in the CLOT study.

In the case of chemotherapy-induced thrombocytopenia, Dalteparin Sodium dose should be adopted as follows:

– With platelet counts <50,000/mm3, Dalteparin Sodium dosing should be interrupted until the platelet count recovers above 50,000/mm3.

– For platelet counts between 50,000 and 100,000/mm3, Dalteparin Sodium should be reduced as illustrated in the table below depending on the patient’s weight. Once the platelet count has recovered to ≥100,000/mm3, Dalteparin Sodium should be re-instituted at full dose.

Body Weight (kg) Scheduled Dalteparin Sodium Dose (IU) Reduced Dalteparin Sodium Dose (IU)
≤56 7 500 5 000
57 to 68 10 000 7 500
69 to 82 12 500 10 000
83 to 98 15 000 12 500
≥99 18 000 15 000

Renal failure:

In the case of significant renal failure, defined as a creatinine clearance <30 ml/min, the dose of Dalteparin Sodium should be adjusted based on anti-Factor Xa activity. If the anti-Factor Xa level is below or above the desired range, the dose of Dalteparin Sodium should be increased or reduced respectively, and the anti-Factor Xa measurement should be repeated after 3-4 new doses. This dose adjustment should be repeated until the desired anti-Factor Xa level is achieved.

As an indication, on the basis of the data available in CLOT, the observed mean levels (min, max) between 4 and 6 hours after administration in patients without severe renal insufficiency were 1.11 IU anti-Factor Xa/ml (0.6; 1.88) and 1.03 IU anti-Factor Xa/ml (0.54; 1.70), respectively, on week 1 and 4 of dalteparin 200 IU/kg OD. Anti-Factor Xa activity determinations were conducted by the chromogenic method.

For patients with an increased risk of bleeding, it is recommended that Dalteparin Sodium be administered according to the twice daily regimen detailed for Dalteparin Sodium 10,000 IU/ml ampoules or Dalteparin Sodium Multidose Vial.

Paediatric population

The safety and efficacy of dalteparin sodium in children has not been established. Currently available data are described in sections 5.1 and 5.2 but no recommendation on a posology can be made.

Monitoring Anti-Xa levels in children

Measurement of peak anti-Xa levels at about 4 hours post-dose should be considered for certain special populations receiving Dalteparin Sodium, such as children. For therapeutic treatment with doses administered once daily, peak anti-Xa levels should generally be maintained between 0.5 and 1.0 IU/mL measured at 4 hours post-dose. In the case of low and changing physiologic renal function such as in neonates, close monitoring of anti-Xa levels is warranted. For prophylaxis treatment the anti- Xa levels should generally be maintained between 0.2-0.4 IU/mL.

As with all antithrombotic agents, there is a risk of systemic bleeding with Dalteparin Sodium administration. Care should be taken with Dalteparin Sodium use in high dose treatment of newly operated patients. After treatment is initiated patients should be carefully monitored for bleeding complications. This may be done by regular physical examination of the patients, close observation of the surgical drain and periodic measurements of hemoglobin, and anti-Xa determinations.

Elderly

Dalteparin Sodium has been used safely in elderly patients without the need for dosage adjustment.

Method of administration

By subcutaneous injection, preferably into the abdominal subcutaneous tissue anterolaterally or posterolaterally, or into the lateral part of the thigh. Patients should be supine and the total length of the needle should be introduced vertically, not at an angle, into the thick part of a skin fold, produced by squeezing the skin between the thumb and forefinger; the skin fold should be held throughout the injection.

4.3 Contraindications

Known hypersensitivity to Dalteparin Sodium or other low molecular weight heparins and/or heparins e.g. history of confirmed or suspected immunologically mediated heparin induced thrombocytopenia (type II); acute gastroduodenal ulcer; cerebral haemorrhage; known haemorrhagic diathesis or other active haemorrhage; serious coagulation disorders; acute or sub-acute septic endocarditis; haemorrhagic pericardial effusion and haemorrhagic pleural effusion; injuries to and operations on the central nervous system, eyes and ears.

In patients receiving Dalteparin Sodium for treatment rather than prophylaxis, local and/or regional anaesthesia in elective surgical procedures is contra-indicated with high doses of dalteparin (such as those needed to treat acute deep-vein thrombosis, pulmonary embolism, and unstable coronary artery disease).

In cancer patients with body weight < 40kg at time of venous thromboembolic event, Dalteparin Sodium should not be used for extended treatment of symptomatic VTE and prevention of its recurrences due to lack of data.

Dalteparin should not be used in patients who have suffered a recent (within 3 months) stroke unless due to systemic emboli.

4.4 Special warnings and precautions for use

Do not administer by the intramuscular route. Due to the risk of haematoma, intramuscular injection of other medical preparations should be avoided when the twenty-four-hour dose of dalteparin exceeds 5,000 IU.

Caution should be exercised in patients in whom there is an increased risk of bleeding complications, e.g. following surgery or trauma, haemorrhagic stroke, severe liver or renal failure, thrombocytopenia or defective platelet function, uncontrolled hypertension, hypertensive or diabetic retinopathy, patients receiving concurrent anticoagulant/antiplatelet agents (see Interactions Section). Caution shall also be observed at high-dose treatment with dalteparin (such as those needed to treat acute deep-vein thrombosis, pulmonary embolism, and unstable coronary artery disease).

Limited data are available regarding the safety and efficacy of antithrombotic therapy in patients with primary or metastatic tumours of the brain who develop concurrent thromboembolic events. There is a risk of fatal intracranial bleeding with use of anticoagulation in this category of patients. Therefore, if the treatment with Dalteparin Sodium was considered, it should be monitored closely with regular re-assessment of the status of tumour involvement of the brain and other individual risks.

Thrombocytopenia, should it occur, usually appears within three weeks following the beginning of therapy. Therefore, it is recommended that the platelet counts are measured before starting treatment with Dalteparin Sodium and monitored closely in first three weeks and regularly thereafter during treatment. Special caution is necessary in rapidly developing thrombocytopenia and severe thrombocytopenia (<100,000/µl) associated with positive or unknown results of in-vitro tests for anti-platelet antibody in the presence of Dalteparin Sodium or other low molecular weight (mass) heparins and/or heparin.

Dalteparin Sodium induces only a moderate prolongation of the APTT and thrombin time. Accordingly, dosage increments based upon prolongation of the APTT may cause overdosage and bleeding. Therefore, prolongation of the APTT should only be used as a test of overdosage.

Monitoring Anti-Xa Levels

Monitoring of Anti-Xa Levels in patients using Dalteparin Sodium is not usually required but should be considered for specific patient populations such as paediatrics, those with renal failure, those who are very thin or morbidly obese, pregnant or at increased risk for bleeding or rethrombosis

Where monitoring is necessary, laboratory assays using a chromogenic substrate are considered the method of choice for measuring anti-Xa levels. Activated partial thromboplastin time (APTT) or thrombin time should not be used because these tests are relatively insensitive to the activity of dalteparin. Increasing the dose of dalteparin in an attempt to prolong APTT may result in bleeding (see section 4.9).

Patients under chronic haemodialysis with dalteparin need as a rule fewer dosage adjustments and as a result fewer controls of anti-Xa levels. Patients undergoing acute haemodialysis may be more unstable and should have a more comprehensive monitoring of anti-Xa levels (see section 5.2).

Patients with severely disturbed hepatic function, significant renal failure or chemotherapy induced thrombocytopenia may need a reduction in dosage and should be monitored accordingly.

If a transmural myocardial infarction occurs in patients where thrombolytic treatment might be appropriate, this does not necessitate discontinuation of treatment with Dalteparin Sodium but might increase the risk of bleeding.

As individual low molecular weight (mass) heparins have differing characteristics, switching to an alternative low molecular weight heparin should be avoided. The directions for use relating to each specific product must be observed as different dosages may be required.

Interchangeability with other anticoagulants

Dalteparin cannot be used interchangeably (unit for unit) with unfractionated heparin, other low molecular weight heparins, or synthetic polysaccharides. Each of these medicines differ in their starting raw materials, manufacturing process, physico-chemical, biological, and clinical properties, leading to differences in biochemical identity, dosing and possibly clinical efficacy and safety. Each of these medicines is unique and has its own instructions for use.

Heparin can suppress adrenal secretion of aldosterone leading to hyperkalaemia, particularly in patients such as those with diabetes mellitus, chronic renal failure, pre-existing metabolic acidosis, a raised plasma potassium or taking potassium sparing drugs. The risk of hyperkalaemia appears to increase with duration of therapy but is usually reversible. Plasma potassium should be measured in patients at risk before starting heparin therapy and monitored regularly thereafter particularly if treatment is prolonged beyond about 7 days.

When neuraxial anaesthesia (epidural/spinal anaesthesia) or spinal puncture is employed, patients are at risk of developing an epidural or spinal hematoma, which can result in long-term or permanent paralysis. The risk of these events is increased by the use of indwelling epidural catheters or by the concomitant use of drugs affecting hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, or other anticoagulants. The risk also appears to be increased by traumatic or repeated epidural or spinal puncture. Patients should be monitored frequently for signs and symptoms of neurological impairment when anticoagulation is given in connection with epidural/spinal anaesthesia.

Insertion or removal of the epidural or spinal catheter should be postponed to 10-12 hours after dalteparin doses administered for thrombosis prophylaxis, while in those receiving higher therapeutic dalteparin doses (such as 100 IU/kg -120 IU/kg every 12 hours or 200 IU/kg once daily), the interval should be a minimum of 24 hours.

Should a physician, as a clinical judgement, decide to administer anticoagulation in the context of epidural or spinal anaesthesia, extreme vigilance and frequent monitoring must be exercised to detect any signs and symptoms of neurologic impairment such as back pain, sensory or motor deficits (numbness and weakness in lower limbs) and bowel or bladder dysfunction. Nurses should be trained to detect such signs and symptoms. Patients should be instructed to inform immediately a nurse or a clinician if they experience any of these.

If signs or symptoms of epidural or spinal haematoma are suspected, urgent diagnosis and treatment may include spinal cord decompression. There have been no adequate studies to assess the safe and effective use of Dalteparin Sodium in preventing valve thrombosis in patients with prosthetic heart valves. Prophylactic doses of Dalteparin Sodium are not sufficient to prevent valve thrombosis in patients with prosthetic heart valves. The use of Dalteparin Sodium cannot be recommended for this purpose.

At long-term treatment of unstable coronary artery disease, such as e.g., before revascularisation, dose reduction should be considered at reduced kidney function (S-creatinine > 150 μmol/l).

Paediatric population:

Clinical experience of treatment of children is limited. If dalteparin is used in children the anti-Xa levels should be monitored.

The administration of medications containing benzyl alcohol as a preservative to premature neonates has been associated with a fatal “Gasping Syndrome” (see section 4.6).

Elderly patients (especially patients aged eighty years and above) may be at an increased risk for bleeding complications within the therapeutic dosage ranges. Careful clinical monitoring is advised.

4.5 Interaction with other medicinal products and other forms of interaction

The possibility of the following interactions with Dalteparin Sodium should be considered:

  1. i) An enhancement of the anticoagulant effect by anticoagulant/antiplatelet agents e.g. aspirin/dipyridamole, GP IIb/IIIa receptor antagonists, Vitamin K antagonists, NSAIDs e.g. indometacin, cytostatics, dextran, thrombolytics, sulfinpyrazone, probenecid, and etacrynic acid.
  2. ii) A reduction of the anticoagulant effect may occur with concomitant administration of antihistamines, cardiac glycosides, tetracycline and ascorbic acid.

Because NSAIDs and ASA analgesic/anti-inflammatory doses reduce production of vasodilatatory prostaglandins, and thereby renal blood flow and the renal excretion, particular care should be taken when administering dalteparin concomitantly with NSAIDs or high dose ASA in patients with renal failure.

However, if there are no specific contraindications, patients with unstable coronary artery disease (unstable angina and non-Q-wave infarction) can be treated with low doses of acetylsalicylic acid.

As heparin has been shown to interact with intravenous nitroglycerine, high dose penicillin, quinine and tobacco smoking interaction cannot be ruled out for dalteparin.

Paediatric population

Interaction studies have only been studied in adults.

4.6 Fertility, pregnancy and lactation

Pregnancy

Dalteparin does not pass the placenta. A large amount of data on pregnant women (more than 1000 exposed outcomes) indicate no malformative nor feto/ neonatal toxicity. Dalteparin Sodium can be used during pregnancy if clinically needed.

If dalteparin is used during pregnancy, the possibility of foetal harm appears remote. However, because the possibility of harm cannot be completely ruled out, dalteparin should be used during pregnancy only if clearly needed.

There are more than 2,000 published cases (studies, case series and case reports) on administration of dalteparin in pregnancy. As compared with unfractionated heparin, a lower bleeding tendency and reduced risk of osteoporotic fracture was reported. The largest prospective study “Efficacy of Thromboprophylaxis as an Intervention during Gravidity“ (EThIG), involved 810 pregnant women and investigated a pregnancy-specific scheme for risk stratification (low, high, very high risk of venous thromboembolism) with daily doses of dalteparin between 50 – 150 IU/kg body weight (in single cases up to max. 200 IU/kg body weight). However, only limited randomised controlled studies are available on the use of low molecular weight heparins in pregnancy.

Animal experiments did not show any teratogenic or fetotoxic properties of dalteparin (see section 5.3).

Epidural anaesthesia during childbirth is absolutely contraindicated in women who are being treated with high-dose anticoagulants (see section 4.3). Caution is recommended when treating patients with an increased risk of haemorrhage, such as perinatal women (see section 4.4). In pregnant women during the last trimester, dalteparin anti-Xa half-lives of 4 to 5 hours were measured.

Dalteparin Sodium 100,000 IU/4ml multidose vial contains benzyl alcohol as a preservative. As benzyl alcohol may cross the placenta, Dalteparin Sodium without preservative should therefore be used during pregnancy.

Therapeutic failures have been reported in pregnant women with prosthetic heart valves on full anti-coagulant doses of low molecular weight heparin. In the absence of clear dosing, efficacy and safety information in this circumstance, Dalteparin Sodium is not recommended for use in pregnant women with prosthetic heart valves.

Breast-feeding

Limited data are available for excretion of dalteparin in human milk. One study in 15 women (between day 3 and 5 of lactation and 2 to 3 hours after receiving prophylactic doses of dalteparin detected small amounts of anti- factor Xa levels of 2 to 8% of plasma levels in breast milk, equivalent to a milk/plasma ratio of <0.025-0.224. An anticoagulant effect on the infant appears unlikely.

A risk to the suckling child cannot be excluded. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with Dalteparin Sodium should be made taking into account the benefit of breast-feeding to the child and the benefit of Dalteparin Sodium therapy to the woman.

Fertility

Based on current clinical data there is no evidence that dalteparin sodium effects fertility. No effects on fertility, copulation or peri- and postnatal development were noted when dalteparin sodium was tested in animals.

4.7 Effects on ability to drive and use machines

Dalteparin Sodium does not affect the ability to drive or operate machinery.

4.8 Undesirable effects

About 3% of the patients having had prophylactic treatment reported side-effects.

The reported adverse reactions, which may possibly be associated to dalteparin sodium, are listed in the following table by system organ class and frequency group: common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10 000).

System Organ Class Frequency Adverse reactions
Blood and lymphatic system disorders Common Mild thrombocytopenia (type I), which usually is reversible during the treatment
Not Known* Immunologically-mediated heparin-induced thrombocytopenia (type II, with or without associated thrombotic complications)
Immune system disorders Uncommon Hypersensitivity
Not Known* Anaphylactic reactions
Nervous system disorders Not Known* Intracranial bleeds have been reported and some have been fatal
Cardiac disorders Not Known* Prosthetic cardiac valve thrombosis
Vascular disorders Common Haemorrhage
Gastrointestinal disorders Not Known* Retroperitoneal bleeds have been reported and some have been fatal
Hepatic and biliary disorders Common Transient elevation of transaminases
Skin and subcutaneous tissue disorders Uncommon Urticaria, pruritus
Rare Skin necrosis, transient alopecia
Not Known* Rash
General disorders and administration site conditions Common Subcutaneous haematoma at the injection site

Pain at the injection site

Injury, Poisoning and Procedural Complications Not Known* Spinal or epidural hematoma

*(cannot be established from available data)

The risk of bleeding is depending on dose. Most bleedings are mild. Severe bleedings have been reported, some cases with fatal outcome.

Heparin products can cause hypoaldosteronism which may result in an increase in plasma potassium. Rarely, clinically significant hyperkalaemia may occur particularly in patients with chronic renal failure and diabetes mellitus (see section 4.4).

Long term treatment with heparin has been associated with a risk of osteoporosis. Although this has not been observed with dalteparin, the risk of osteoporosis cannot be excluded.

Paediatric population

Frequency, type and severity of adverse reactions in children are expected to be the same as in adults. The safety of long term dalteparin administration has not been established.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.

4.9 Overdose

The anticoagulant effect (i.e. prolongation of the APTT) induced by Dalteparin Sodium is inhibited by protamine. Since protamine itself has an inhibiting effect on primary haemostasis it should be used only in an emergency. The prolongation of the clotting time induced by Dalteparin Sodium may be fully neutralised by protamine, but the anti-Factor Xa activity is only neutralised to about 25-50%. 1 mg of protamine inhibits the effect of 100 IU (anti-Factor Xa) of Dalteparin Sodium.

5. Pharmacological properties

5.1 Pharmacodynamic properties

ATC Code BO1AB 04: Antithrombotics

Dalteparin sodium is a low molecular weight heparin fraction (weight average molecular weight of 6000 Daltons (range between 5,600 to 6,400 Daltons)) produced from porcine-derived heparin sodium.

Mechanism of action

Dalteparin sodium is an antithrombotic agent, which acts mainly through its ability to potentiate the inhibition of Factor Xa and thrombin by antithrombin. It has a relatively higher ability to potentiate Factor Xa inhibition than to prolong plasma clotting time (APTT).

Pharmacodynamic effects

Compared with standard, unfractionated heparin, dalteparin sodium has a reduced adverse effect on platelet function and platelet adhesion, and thus has only a minimal effect on primary haemostasis. Some of the antithrombotic properties of dalteparin sodium are thought to be mediated through the effects on vessel walls or the fibrinolytic system.

Clinical efficacy and safety

In a randomised, actively controlled, double-blind trial in 1500 patients undergoing hip replacement surgery (North American Dalteparin Sodium Trial), both pre-operative and post-operative Dalteparin Sodium were found to be superior to warfarin (see table below). There was a numerical superiority for pre-operative Dalteparin Sodium over post-operative Dalteparin Sodium. Thus in patients where the risk of bleeding is perceived to be too great for pre-operative Dalteparin Sodium administration other means of reducing thromboembolic risk such as post-operative Dalteparin Sodium administration may be considered.

Incidence of verified thromboembolic events in ITT efficacy population within 6 ± 2 post-operative days.

Phase 1 Pre-op. dalteparin Post-op dalteparin Warfarin
n/N % n/N % n/N %
DVT and or PE 37/338* 10.9 44/336* 13.1 81/338 24.0
Proximal DVT 3/354 0.8 3/358 0.8 11/363 3.0

*p < 0.001 vs. warfarin (Cochran-Mantel-Haenszel test, two-sided)

Abbreviations: n/N = number of patients affected/number of efficacy-evaluable patients; post-op. = treatment at earliest 4 hours after surgery; pre-op. = treatment within 2 hours before surgery.

In a randomised; placebo-controlled double-blind trial (PREVENT) in 3700 patients with acute medical conditions requiring a projected stay in hospital of >4 days and with recent (<3 days) immobilisation (defined as patients mainly confined to bed during waking hours), the incidence of clinically relevant thromboembolic events was reduced by 45% in patients randomised to receive Dalteparin Sodium compared with those who received placebo. The incidence of the events comprising the primary endpoint was 2.77% compared with 4.96% in placebo treated patients (difference: – 2.19; 95% CI: – 3.57 to – 0.81; p=0.0015. Therefore, a clinically meaningful reduction in the risk of venous thromboembolism was seen in this study.

The randomized, open-label, controlled, multicenter CLOT study (Randomized Comparison of Low-Molecular Weight Heparin Versus Oral Anticoagulant Therapy for Long Term Anticoagulation in Cancer patients with Venous Thomboembolism) compared dalteparin to standard oral anticoagulant (OAC) therapy in the long term treatment of venous thromboembolism (VTE) in 676 patients with active malignancy who had experienced an acute symptomatic VTE (deep venous thrombosis (DVT) and/or a pulmonary embolism (PE)).

Patients were randomized to one of two groups:

– dalteparin arm prescribed at 200 IU/kg/day administered by subcutaneous (SC) injections (maximum 18,000 IU/day) during 1 month, then approximately 150 IU/kg/day from 2nd – 6th month, or

– VKA arm prescribed during 6 months (target INR 2-3), preceded by SC dalteparin 200 IU/kg/day OD (maximum 18,000 IU/day) during 5 to 7 days.

The most frequent diagnoses were: tumors of the gastrointestinal tract and pancreas (23.7%), genitourinary tumors (prostate, testicle, cervix, uterus, ovary and bladder) (21.5%), breast (16.0%), lung (13.3%). 10.4% of patients had haematological malignancies ; 75.1% of patients had metastatic disease.

The index VTE event was DVT alone in nearly 70% and PE with or without DVT in 30% of patients.

The primary endpoint was the time to first recurrence of symptomatic VTE (DVT and/or PE) during 6 months.

A total of 27 patients of 338 (8.0%) in the dalteparin arm and 53 patients of 338 (15.7%) in the VKA arm experienced at least one of the events of the composite primary endpoint. A significant 52% risk reduction in VTE recurrence at 6 months was seen with dalteparin (RR= 0.48, 95% CI [0.30-0.77], p=0.0016).

In the dalteparin arm, 19 patients (5.6%) experienced at least one episode of major bleeding compared to 12 patients (3.6%) in the VKA arm. The cumulative probability of experiencing a major bleeding at 6 months was respectively 6.5% and 4.9%, respectively. Any bleeding occurred with a higher frequency in the VKA arm (18.5% VKA vs 13.6% dalteparin). The comparison of the cumulative probability of first bleeding episode for the 2 treatments was of statistical significance in favour of dalteparin treatment (p=0.0487).

There was no significant difference in mortality between the two groups in deaths at 6 and 12 months (131 vs. 137 and 190 vs. 194 in the dalteparin and VKA arms, respectively).

There was no significant difference in the assessment of Quality of Life between the two groups of treatment.

Paediatric population

There is limited safety and efficacy information on the use of dalteparin in paediatric patients. If dalteparin is used in these patients, anti-Xa levels should be monitored.

The largest prospective study investigated the efficacy, safety and relation of dose to plasma anti-Xa activity of dalteparin in prophylaxis and therapy of arterial and venous thrombosis in 48 paediatric patients (Nohe et al, 1999).

Nohe et al (1999) Study Demographics and Trial Design

Trial design Patients Diagnosis Indication, Dalteparin Sodium Dose, Target anti-Xa, Duration
Single-center, open label trial; Age:

31 week preterm to 18 years

Arterial or venous thrombosis; PVOD; PPH Prophylaxis: Primary Therapy: Secondary Therapy:
(n = 48) (n = 10) (n = 25) (n = 13)
Gender:

32 males, 16 females

95 ± 52 anti-Xa IU/kg sc qd; 129 ± 43 anti-Xa IU/kg sc qd; 129 ± 43 anti-Xa IU/kg sc qd;
0.2 to 0.4 IU/mL 0.4 to 1.0 IU/mL 0.4 to 1.0 IU/mL
3-6 months 3-6 months 3-6 months

In this study, no thromboembolic events occurred in the 10 patients receiving dalteparin for thromboprophylaxis. In the 23 patients given dalteparin for primary antithrombotic therapy of arterial or venous thrombosis, complete recanalization was seen in 7/23 (30%), partial recanalization in 7/23 (30%) and no recanalization in 9/23 (40%). In the 8 patients administered dalteparin for secondary antithrombotic therapy following successful thrombolysis, recanalisation was maintained or improved. In the 5 patients receiving dalteparin for secondary therapy following failed thrombolysis, no recanalization was seen. Minor bleeding, reported in 2/48 children (4%), resolved after dose reduction. Patient platelet counts ranged from 37,000/μl to 574,000/μl. The authors attributed platelet counts below normal (150,000/μl) to immunosuppressive therapy. A reduction in platelet count ≥ 50% of the initial value, a sign of heparin-induced thrombocytopenia type 2 (HIT 2), was not observed in any patient. For both prophylaxis and therapy groups, the dalteparin doses (anti-Xa IU/kg) required to achieve target anti-Xa activities (IU/ml) were inversely related to age (r2 = 0.64, P = 0.017; r2 = 0.13, P = 0.013). The predictability of the anticoagulant effect with weight-adjusted doses appears to be reduced in children compared to adults, presumably due to altered plasma binding (see section 5.2).

5.2 Pharmacokinetic properties

Elimination

The half-life following i.v. and s.c. administration is 2 hours and 3.5-4 hours respectively, twice that of unfractionated heparin.

Bioavailability

The bioavailability following s.c. injection is approximately 87 per cent and the pharmacokinetics are not dose dependent. The half life is prolonged in uraemic patients as dalteparin sodium is eliminated primarily through the kidneys.

Special Populations

Haemodialysis:

In patients with chronic renal insufficiency requiring haemodialysis, the mean terminal hal-life of anti-Factor Xa activity following a single intravenous dose of 5000 IU dalteparin was 5.7 ± 2.0 hours, i.e. considerably longer than values observed in healthy volunteers, therefore, greater accumulation can be expected in these patients.

Paediatric Population:

Infants less than approximately 2 to 3 months of age or < 5 kg have increased LMWH requirements per kg likely due to their larger volume of distribution. Alternative explanations for the increased requirement of LMWH per body weight in young children include altered heparin pharmacokinetics and/or a decreased expression of anticoagulant activity of heparin in children due to decreased plasma concentrations of antithrombin.

5.3 Preclinical safety data

The acute toxicity of dalteparin sodium is considerably lower than that of heparin. The only significant finding, which occurred consistently throughout the toxicity studies after subcutaneous administration of the higher dose levels was local haemorrhage at the injection sites, dose-related in incidence and severity. There was no cumulative effect on injection site haemorrhages.

The haemorrhagic reaction was reflected in dose related changes in the anticoagulant effects as measured by APTT and anti-Factor Xa activities.

It was concluded that dalteparin sodium may have an osteopenic effect at very high concentrations, and that this effect is less than that of unfractionated heparin at equivalent doses.

The results revealed no organ toxicity irrespective of the route of administration, doses or duration of treatment. No mutagenic effect was found. No embryotoxic or teratogenic effects and no effect on fertility, reproductive capacity or peri- and post natal development was shown.

6. Pharmaceutical particulars

6.1 List of excipients

Water for Injections (Ph. Eur.)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

Store below 25°C

6.5 Nature and contents of container

Dalteparin Sodium 5,000 IU/0.2ml solution for injection is supplied in 0.5ml glass Ph. Eur Type I single dose pre-filled syringes with a latex-free needle shield, chlorobutyl rubber, polypropylene rod and a needle-trap (safety) feature. Each pack contains 10 syringes.

6.6 Special precautions for disposal and other handling

The Needle-Trap consists of a plastic needle “catcher” which is firmly attached to the syringe label. Together, these two components comprise the Needle-Trap (safety) feature. The Needle-Trap is designed to specifically help prevent accidental needle sticks following the proper administration of injectable medications.

The Needle-Trap requires specific actions by the user to “activate” the Needle-Trap, which will render the needle harmless after the injection is administered:

  • The user grasps the tip of the plastic needle catcher and bends it away from needle shield.
  • The needle shield is removed from the syringe.
  • The injection is administered normally.
  • The needle is removed from the patient. The Needle-Trap is activated by placing the plastic catcher against a hard, stable surface and with one hand, pivoting the syringe barrel upward against the needle forcing the needle into the catcher where it locks in place (an audible ‘click” is heard when the needle is locked in the catcher). The needle is bent until the syringe exceeds a 45 degree angle with the flat surface to render it permanently unusable.
  • The syringe is properly disposed of normally.7. Manufactured in India by:
    TAJ PHARMACEUTICALS LTD.
    Mumbai, India
    Unit No. 214.Old Bake House,
    Maharashtra chambers of  Commerce Lane,
    Fort, Mumbai – 400001
    at:Gujarat, INDIA.
    Customer Service and Product Inquiries:
    1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
    Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
    E-mail: tajgroup@tajpharma.com

Dalteparin Sodium Prefilled Syringe 2,500 IU/0.2 ml & 5,000 IU/0.2 ml Solution for Injection Taj Pharma.
(dalteparin sodium)

Package leaflet: Information for the user

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor, pharmacist or nurse.

This medicine has been prescribed for you only. If your doctor has given you this medicine to use at home do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

If you get any side effects talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

  1. What Dalteparin Sodium Prefilled Syringe is and what it is used for
  2. What you need to know before you are given or use Dalteparin Sodium Prefilled Syringe
  3. How Dalteparin Sodium Prefilled Syringe is given to you
  4. Possible side effects
  5. How to store Dalteparin Sodium Prefilled Syringe
  6. Contents of the pack and other information

1. What Dalteparin Sodium Prefilled Syringe is and what it is used for

Dalteparin Sodium Prefilled Syringe is a solution for injection. Its active ingredient is dalteparin sodium.

Dalteparin Sodium Prefilled Syringe belongs to a group of medicines called low molecular weight heparins or anti-thrombotics, which help prevent the formation of blood clots by thinning the blood.

Venous thromboembolism is a condition where blood clots develop in the legs (deep vein thrombosis) or the lungs (pulmonary embolism), e.g. after surgery, prolonged bed rest or in patients with certain types of cancer.

Dalteparin Sodium Prefilled Syringe is used to prevent blood clots (venous thromboembolism) forming before and after an operation or if you are bedridden due to illness and to prevent their recurrence.

The 5000 IU product can also be used for:

Prevention of deep vein thrombosis in patients bedridden due to a medical condition but not limited to, for example heart failure and respiratory failure.

Treatment of patients with solid tumours who suffer from low platelet counts.

Ask your doctor if you are unsure why you have been given Dalteparin Sodium Prefilled Syringe.

2.What you need to know before you are given or use Dalteparin Sodium Prefilled Syringe

You should not be given Dalteparin Sodium Prefilled Syringe:

if you are allergic (hypersensitive) to the active ingredient dalteparin sodium or a similar product or any of the other ingredients of this medicine (listed in section 6).

if you have an active stomach ulcer or ulcer of the duodenum (small intestine).

if you have suffered from a brain haemorrhage (bleeding in your brain).

if you have fluid mixed with blood that appears around heart and lungs.

if you suffer from any condition which may cause you to bleed more easily (e.g. haemophilia, liver failure). Ask your doctor if you are unsure.

if you have a condition called septic endocarditis (an infection and inflammation of the lining of the heart and heart valves). Your doctor will have told you if you have this.

if you have had a condition called “heparin-induced thrombocytopenia” (a decrease in the

number of clotting cells (platelets) in your blood caused by heparin, which may cause you to bruise and bleed more easily). Your doctor will have told you if you have this.

if you have an injury to, or have had an operation involving your spine, head, eyes or ears.

If you are receiving Dalteparin Sodium Prefilled Syringe to treat blood clots, you should not have a local, spinal or epidural

anaesthetic.

If you are given this medicine as part of your cancer treatment your doctor will check that you weigh more than 40 kg, and that you have not had a stroke within the last 3 months

Warnings and precautions

Talk to your doctor, pharmacist or nurse before you are given or use Dalteparin Sodium Prefilled Syringe:

if you have conditions which make you more susceptible to bleeding e.g.:

  • after an operation or trauma
  • a stroke caused by a bleed
  • a brain tumour
  • severe liver or kidney failure
  • abnormal or low numbers of platelets (clotting cells)
  • eye disease caused by blood pressure or diabetes
  • taking other medicines that thin the blood (e.g. aspirin, warfarin, dipyridamole)
  • uncontrolled high blood pressure
  • if you have been told by your doctor that you have a lot of potassium in your blood or have a low blood pH. Your doctor will monitor your blood regularly before and during
  • if you have ever had an operation to insert an artificial heart
  • if you need to have any other

You may need to have blood tests to monitor the effects of Dalteparin Sodium Prefilled Syringe:

  • if you have kidney failure or liver problems
  • if you are very thin or morbidly obese
  • if you are pregnant
  • if you are at increased risk of bleeding or rethrombosis (more blood clots)
  • if you are a child
  • if you have blood problems due to cancer treatment

Children and adolescents

Dosing recommendations in children are based on clinical experience; there are limited data from clinical trials, which will help your doctor calculate the dose of Dalteparin Sodium Prefilled Syringe.

Other medicines and Dalteparin Sodium Prefilled Syringe

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or are planning to take or use any other medicines. This includes medicines that you have bought for yourself.

Some medicines can affect the way Dalteparin Sodium Prefilled Syringe works, or Dalteparin Sodium Prefilled Syringe itself can reduce the effectiveness of other medicines taken at the same time.

Medicines that increase the effect of Dalteparin Sodium Prefilled Syringe include:

  • Those used to thin your blood (e.g. aspirin, dipyridamole, glycoprotein receptor antagonists and warfarin).
  • Medicines called non-steroidal anti-inflammatory drugs (NSAIDs) used to reduce pain and inflammation (e.g. indometacin).
  • Some medicines for gout (e.g. sulfinpyrazone and probenecid).
  • Etacrynic acid (a water retention tablet (diuretic)).
  • Solutions given to increase the blood volume (e.g. dextrans).
  • Medicines known as cytostatics (used in cancer treatment).
  • Thrombolytic medications for treating transmural heart attack (e.g. TPA-tissue plasminogen activator).
  • Medicines that can reduce the effect of Dalteparin Sodium Prefilled Syringe include:
  • Those for allergy and hay fever (e.g. antihistamines).
  • Those used for heart or circulation problems (e.g. digoxin or digitoxin).
  • Antibiotics known as tetracyclines which are used to treat bacterial
  • Vitamin C (e.g. some vitamin supplements).Other medicines that may interfere with Dalteparin Sodium Prefilled Syringe include:
  • Those used to treat angina (intravenous nitroglycerine).
  • Antibiotics such as high dose penicillin which are used to treat bacterial
  • Anti-malarials (e.g. quinine).
  • Tobacco

Please note that if you are being treated with Dalteparin Sodium Prefilled Syringe for unstable coronary artery disease your doctor may adjust your dose of aspirin accordingly.

Please tell your doctor or pharmacist if you are taking or have recently taken any other low molecular weight heparins or anti-thrombotics.

Pregnancy and breast-feeding

Dalteparin Sodium Prefilled Syringe has not been found to cause harmful effects during pregnancy. The possibility of harm to the baby appears remote. Tell your doctor if you are pregnant and they will advise you.

Dalteparin Sodium Prefilled Syringe is not recommended for the prevention of blood clots on artificial heart valves during pregnancy.

If you are receiving Dalteparin Sodium Prefilled Syringe to treat blood clots, you should not have a local, spinal or epidural

anaesthetic.

Ask your doctor or pharmacist for advice before being given or using this medicine whilst breast- feeding.

Driving and using machines

Dalteparin Sodium Prefilled Syringe does not affect the ability to drive and operate machinery.

How Dalteparin Sodium Prefilled Syringe is given to you

Your medicine will usually be administered by a doctor or nurse or you may be shown how to give the injection yourself at home (see section on How to Inject Dalteparin Sodium Prefilled Syringe). The amount of Dalteparin Sodium Prefilled Syringe you receive will depend on your body weight.

Dalteparin Sodium Prefilled Syringe is given as a single, once daily, subcutaneous injection, which means it is injected beneath the skin. It is usually injected into a skin fold in your abdomen (stomach), or the outer aspects of your thigh. It should not be injected into your muscles.

Use in adults and the elderly

To prevent blood clots (venous thromboprophylaxis)

Patients with a moderate risk of developing a clot:

The recommended dose is 2,500 IU one to two hours before the operation, then 2,500 IU each morning. This is continued for five to seven days, or until you are fully able to move about.

Patients with a greater risk of developing a clot e.g. those who have had clots in the past:

For this type of patient, the recommended dose is 2,500 IU one to two hours before the operation, the same dose 8 to 12 hours later, then 5,000 IU each morning. As an alternative, 5,000 IU may be given the evening before the operation, then 5,000 IU on following evenings. The first dose (2,500 IU) may also be given as soon as possible after your operation and is to be continued for five to seven days, or until you are able to move about.

Hip Replacement Surgery

After a hip operation, your doctor may decide to continue treating you with Dalteparin Sodium Prefilled Syringe for five weeks using a dose of 5,000 IU every evening. If you have an artificial heart valve, the normal dose for prevention of blood clots is not sufficient. Your doctor will discuss this with you.

The maximum dose you will be given in a 12 hour period is 10,000 IU.

If you are bedridden due to illness, the dose of Dalteparin Sodium Prefilled Syringe given will be 5,000 IU daily. The length of treatment will be up to 14 days, depending on your illness.

These are typical doses for adults, including elderly patients. Your doctor will work out the right dose for you. Some of the liquid in the syringe may have to be expelled before the injection is given.

To treat blood clots (venous thromboembolism) in certain types of cancer and prevent recurrence

The usual dose used to treat venous thromboembolism in cancer is 200 IU (units) for every kilogram you weigh (see table below) once daily during the first month after a thromboembolic event (blood clot), followed by 150 IU for every kilogram you weigh (during months 2-6).

Dose of Dalteparin Sodium Prefilled Syringe during month 1

 

Body weight (kg) Dose (IU)
< 46 7,500
46-56 10,000
57-68 12,500
69-82 15,000
³ 83 18,000

 

Dose of Dalteparin Sodium Prefilled Syringe during months 2-6

Body Weight (kg) Dose (IU)
£ 56 7,500
57 to 68 10,000
69 to 82 12,500
83 to 98 15,000
³ 99 18,000

 

This treatment course is not recommended for patients weighing less than 40 kg.

The maximum daily dose is 18,000 IU. The recommended duration of treatment is 6 months. If you are suffering from severe kidney disease or a decreased platelet count (clotting cells) caused by chemotherapy or another condition with an elevated bleeding risk, your doctor will adjust this dose accordingly.

In some cases of decreased platelet count (clotting cells), your doctor may interrupt your treatment

with Dalteparin Sodium Prefilled Syringe for a short period.

Medical staff may take blood samples during your treatment to monitor the effects of Dalteparin Sodium Prefilled Syringe.

3. How to Inject Dalteparin Sodium Prefilled Syringe

This section of the leaflet explains how you should go about injecting Dalteparin Sodium Prefilled Syringe yourself, but you should only do so if you have been given permission by your doctor. It is a simple process and one that you can do at home.

Dalteparin Sodium Prefilled Syringe is given by a small injection under the skin. You should inject (or give) the dose of Dalteparin Sodium Prefilled Syringe

at the time recommended by your doctor. Please follow the steps explained below.

Gather the single dose Dalteparin Sodium Prefilled Syringe and the yellow sharps bin.

Wash and dry your hands. The injection site should be cleaned.

Please note that if a carer is doing the injecting, it is recommended that they wear gloves to perform the injection.

Step 1:

Get yourself in a comfortable sitting down position where you can see your stomach.

Step 2:

Choose an injection site either on your stomach or outer aspects of your left or right thigh (see shaded areas). Your stomach is usually best as the injection site and it is important that you change the site each time.

Step 3:

Pick up the syringe, grasp the tip of the plastic needle catcher and bend it away from the shield. Remove the grey rubber cover by pulling it straight off. You will notice an air bubble in the syringe. It is supposed to be there and you can just ignore it. It is important not to press the plunger just yet as some of the medicine may be lost.

Step 5:

Hold the syringe above the folded skin keeping it at a right angle (i.e. vertically as in the diagram and

not at an angle). Insert the needle into the skin until the needle is fully inserted.

Step 6:

Now press the plunger and inject the Dalteparin Sodium Prefilled Syringe slowly until all of the medicine has been injected. Keep pinching the fold of skin while you are injecting and then release the fold of skin and pull the needle out.

If there is any oozing of blood at the injection site, apply gentle pressure. Do not rub the injection site as this may encourage bruising.

Step 7:

Place the plastic catcher against a hard, stable surface and with one hand pivot the syringe barrel upwards against the needle forcing the needle into the catcher where it locks in place.

Continue bending the needle until the syringe exceeds a 45 degree angle with the flat surface to render

it permanently unusable.

Dispose of the syringe in the yellow sharps bin provided. Keep your sharps bin out of reach of other people. When the sharps bin is almost full please speak to your doctor or nurse.

Children and adolescents

The dose will be based on both the child’s age and weight. Younger children may need slightly more Dalteparin Sodium Prefilled Syringe per kg than adults. Your doctor will work out the right dose for you. Medical staff may take blood samples during your treatment to monitor the effects of Dalteparin Sodium Prefilled Syringe.

If you are given more Dalteparin Sodium Prefilled Syringe than you should

If you feel that you have been given more Dalteparin Sodium Prefilled Syringe than you should, inform your doctor or nursing staff immediately. Your doctor may initiate measures to decrease the risk of bleeding.

If you forget to use Dalteparin Sodium Prefilled Syringe

Tell your doctor or pharmacist if you think that a dose has been forgotten. A double dose should not be given to make up for a forgotten dose.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop using Dalteparin Sodium Prefilled Syringe and talk to a doctor or nurse at once if you get any signs of a severe allergic reaction (such as difficulty breathing, swelling of the lips, mouth, throat or eyes).

Common side effects (may affect up to 1 in 10 people):

A reversible decrease in the number of clotting cells (platelets) in your blood (Type I thrombocytopenia). This may make you bruise more easily.

Bleeding at any site

Certain substances produced by your liver may increase

Pain and reactions at the injection site

Haematoma – you may notice blood collecting under the skin

Uncommon side effects (may affect up to 1 in 100 people):

Increased levels of potassium in your blood (symptoms may include temporary

muscle weakness, loss of feeling and changes in your heartbeat)

Red skin rash and itchiness

Itching

Allergic reactions

Rare side effects (may affect up to 1 in 1,000 people):

An immune system problem resulting in a severe decrease in the number of clotting cells (platelets) in your blood (Type II thrombocytopenia)

Alopecia (hair loss)

Painful skin lesions

Not known (frequency cannot be estimated from the available data):

Bleeding inside or around your brain, symptoms may include sudden severe headache

Bleeding behind your abdomen (stomach), symptoms may include a feeling of tenderness and swelling around your stomach

Bruising of the spine which may lead to back pain, tingling, numbness or weakness in your legs, bowel or bladder problems

If you have an artificial heart valve, treatment with Dalteparin Sodium Prefilled Syringe might not be sufficient to prevent a blood clot, and you might develop a clot in the heart valve.

The adverse reactions in children are expected to be the same as in adults, however there is only a little information about the possible side effects of long-term use in children.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly.

By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Dalteparin Sodium Prefilled Syringe

Keep this medicine out of the sight and reach of children.

Dalteparin Sodium Prefilled Syringe should not be used after the expiry date which is printed on the label and carton. The expiry

the date refers to the last day of that month.

Store below 25°C.

Your doctor or nurse will store Dalteparin Sodium Prefilled Syringe in a safe place under the above conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to

throw away medicines that you no longer use. These measures will help to protect the environment.

6.Contents of the pack and other information
What Dalteparin Sodium Prefilled Syringe contains

The active ingredient in Dalteparin Sodium Prefilled Syringe is dalteparin sodium. Two strengths of Dalteparin Sodium Prefilled Syringe syringes are available, containing either 2,500 IU (International Units) or 5,000 IU of dalteparin sodium in 0.2 ml of solution.

The other ingredients are water for injections and in the 2,500 IU product, sodium chloride.

What Dalteparin Sodium Prefilled Syringe looks like and contents of the pack

Dalteparin Sodium Prefilled Syringe is available as a clear, colourless or straw-coloured solution in pre-filled single dose

syringes, each containing 0.2 ml of dalteparin sodium solution. 10 syringes are packed in each box.

7. Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com