{"boxed_warning":["SPINAL/EPIDURAL HEMATOMAS When neuraxial anesthesia (epidural/spinal anesthesia) or spinal puncture is employed, patients anticoagulated or scheduled to be anticoagulated with low molecular weight heparins or heparinoids for prevention of thromboembolic complications 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 for administration of analgesia 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. Patient should be frequently monitored for signs and symptoms of neurological impairment. If neurologic compromise is noted, urgent treatment is necessary. The physician should consider the potential benefit versus risk before intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis (see also WARNINGS, Hemorrhage and PRECAUTIONS, Drug Interactions )."],"carcinogenesis_and_mutagenesis_and_impairment_of_fertility":["Carcinogenesis, Mutagenesis, Impairment of Fertility No long term studies in animals have been performed to evaluate the carcinogenic potential of ORGARAN ® (danaparoid sodium) Injection. ORGARAN ® was not genotoxic in the Ames test, the in vitro CHL/HGPRT forward gene mutation assay, the in vitro CHO cell chromosome aberration test, the in vitro HeLa cell unscheduled DNA synthesis (UDS) test or the in vivo mouse micronucleus test. ORGARAN ® at intravenous doses of up to 1090 anti-Xa units/kg/day was found to have no effect on fertility or reproductive performance of male and female rats. This dose is 5.9 times the recommended human subcutaneous dose based on body surface area (50 kg body weight and 1.46 m 2 body surface area assumed)."],"clinical_pharmacology":["CLINICAL PHARMACOLOGY Pharmacodynamics Effect on Coagulation Factors ORGARAN ® (danaparoid sodium) Injection is an antithrombotic agent. ORGARAN ® prevents fibrin formation in the coagulation pathway via thrombin generation inhibition by anti-Xa and anti-IIa (thrombin) effects. The anti-Xa: anti-IIa activity ratio is greater than 22. Inactivation of factor Xa is mediated by antithrombin-llI (AT-III) while factor IIa inactivation is mediated by both AT-III and heparin cofactor II (HC II). ORGARAN ® has only minor effect on platelet function and platelet aggregability. Measurements of Hemostasis Because of its predominant anti-Xa activity, ORGARAN ® has little effect on clotting assays ( e.g. , prothrombin time [PT], partial thromboplastin time [PTT]). ORGARAN ® has minimal effect on fibrinolytic activity and bleeding time. Pharmacokinetics The pharmacokinetics of ORGARAN ® (danaparoid sodium) Injection have been described by monitoring its biological activity (plasma anti-Xa activity) since no specific chemical assay methods are currently available for the components of ORGARAN ® . By subcutaneous route of administration, ORGARAN ® was approximately 100% bioavailable, compared with the same dose administered intravenously. The maximum anti-Xa activity (T max ) occurred at approximately two to five hours. For single subcutaneous doses of 750,1500, 2250, and 3250 anti-Xa units of ORGARAN ® the mean peak plasma anti-Xa activities were 102.4, 206.1, 283.9, and 403.4 mU/mL, respectively. The mean terminal half-life (T 1/2 ) was about 24 hours and the clearance was 0.36 L/hour. Clearance was affected by body surface area in that the higher the body surface, the faster the clearance. ORGARAN ® is mainly eliminated via the kidneys. In patients with severely impaired renal function, the half-life of elimination of plasma anti-Xa activity may be prolonged, therefore, monitoring such patients carefully is recommended. Special Populations Geriatrics There are insufficient pharmacokinetic data to determine if the absorption, distribution, and elimination of ORGARAN ® (danaparoid sodium) Injection are different in elderly (≥65 years) subjects when compared with younger subjects. Pediatrics The safety and efficacy of ORGARAN ® in pediatric patients have not been established. Race There is no information to determine the effect of race on the pharmacokinetics of ORGARAN ® . Hepatic Insufficiency No formal studies were conducted to evaluate the effect of hepatic disease on the disposition of ORGARAN ® . Renal Insufficiency No formal studies were conducted to evaluate the effect of renal disease on the disposition of ORGARAN ® although ORGARAN ® is mainly eliminated by the kidneys. In patients with severely impaired renal function, the half-life of elimination of plasma anti-Xa activity may be prolonged, therefore, careful monitoring of such patients is recommended (see PRECAUTIONS ). Drug-Drug Interactions In clinical studies for the prophylaxis of DVT, no significant drug interactions have been noted with the following drugs: digoxin, cloxacillin, ticarcillin, chlorthalidone, and pentobarbital (see PRECAUTIONS ). ORGARAN ® should be used with caution in patients receiving oral anticoagulants and/or platelet inhibitors. Monitoring of anticoagulants by Prothrombin Time and Thrombotest is unreliable within 5 hours after ORGARAN ® administration (see PRECAUTIONS ). Clinical Studies In a European multicenter double-blind trial, ORGARAN ® (danaparoid sodium) Injection was compared with placebo in 196 patients undergoing elective hip replacement surgery. The administration of ORGARAN ® tor 7 to 14 days post-operatively significantly reduced the overall incidence of DVT to 15% (15/98 patients) compared to the incidence of 57% (56/98 patients) observed with placebo. Number (%) of Patients with DVT* Intent-to-Treat *A patient may be counted more than once (proximal and/or distal) a Using the Cochran Mantel-Haenszel test ORGARAN ® N=98 Placebo N=98 p-value a Proximal; N (%) 8 (8) 26 (27) 0.001 Distal; N (%) 14 (14) 51 (52) <0.001 Overall; N (%) 15 (15) 56 (57) <0.001 In a United States multicenter trial, ORGARAN ® was compared with warfarin in 396 patients undergoing elective hip replacement. A significant reduction in the overall incidence of DVT was observed with ORGARAN ® (14.6%; 29/199 patients) compared with warfarin (26.9%; 53/197 patients), p=0.003. Number (%) of Patients with DVT a Intent-to-Treat a By positive venogram only b Using the Cochran Mantel-Haenszel test c Popiteal, iliac, and femoral d Calf e A patient may be counted more than once (proximal and distal) ORGARAN ® N=199 Warfarin N=197 p-value b Proximal c ; N (%) 3 (1.5) 8 (4.1) 0.13 Distal d ; N (%) 28 (14.1) 49 (24.9) 0.007 Overall e ; N (%) 29 (14.6) 53 (26.9) 0.003"],"clinical_pharmacology_table":["
Number (%) of Patients with DVT* Intent-to-Treat
*A patient may be counted more than once (proximal and/or distal)
a Using the Cochran Mantel-Haenszel test
ORGARAN® N=98Placebo N=98p-valuea
Proximal; N (%) 8 (8) 26 (27) 0.001
Distal; N (%) 14 (14) 51 (52) <0.001
Overall; N (%) 15 (15) 56 (57) <0.001
","
Number (%) of Patients with DVTa Intent-to-Treat
a By positive venogram only
b Using the Cochran Mantel-Haenszel test
c Popiteal, iliac, and femoral
d Calf
e A patient may be counted more than once (proximal and distal)
ORGARAN® N=199Warfarin N=197p-valueb
Proximalc; N (%) 3 (1.5) 8 (4.1) 0.13
Distald; N (%) 28 (14.1) 49 (24.9) 0.007
Overalle; N (%) 29 (14.6) 53 (26.9) 0.003
"],"clinical_studies":["Clinical Studies In a European multicenter double-blind trial, ORGARAN ® (danaparoid sodium) Injection was compared with placebo in 196 patients undergoing elective hip replacement surgery. The administration of ORGARAN ® tor 7 to 14 days post-operatively significantly reduced the overall incidence of DVT to 15% (15/98 patients) compared to the incidence of 57% (56/98 patients) observed with placebo. Number (%) of Patients with DVT* Intent-to-Treat *A patient may be counted more than once (proximal and/or distal) a Using the Cochran Mantel-Haenszel test ORGARAN ® N=98 Placebo N=98 p-value a Proximal; N (%) 8 (8) 26 (27) 0.001 Distal; N (%) 14 (14) 51 (52) <0.001 Overall; N (%) 15 (15) 56 (57) <0.001 In a United States multicenter trial, ORGARAN ® was compared with warfarin in 396 patients undergoing elective hip replacement. A significant reduction in the overall incidence of DVT was observed with ORGARAN ® (14.6%; 29/199 patients) compared with warfarin (26.9%; 53/197 patients), p=0.003. Number (%) of Patients with DVT a Intent-to-Treat a By positive venogram only b Using the Cochran Mantel-Haenszel test c Popiteal, iliac, and femoral d Calf e A patient may be counted more than once (proximal and distal) ORGARAN ® N=199 Warfarin N=197 p-value b Proximal c ; N (%) 3 (1.5) 8 (4.1) 0.13 Distal d ; N (%) 28 (14.1) 49 (24.9) 0.007 Overall e ; N (%) 29 (14.6) 53 (26.9) 0.003"],"clinical_studies_table":["
Number (%) of Patients with DVT* Intent-to-Treat
*A patient may be counted more than once (proximal and/or distal)
a Using the Cochran Mantel-Haenszel test
ORGARAN® N=98Placebo N=98p-valuea
Proximal; N (%) 8 (8) 26 (27) 0.001
Distal; N (%) 14 (14) 51 (52) <0.001
Overall; N (%) 15 (15) 56 (57) <0.001
","
Number (%) of Patients with DVTa Intent-to-Treat
a By positive venogram only
b Using the Cochran Mantel-Haenszel test
c Popiteal, iliac, and femoral
d Calf
e A patient may be counted more than once (proximal and distal)
ORGARAN® N=199Warfarin N=197p-valueb
Proximalc; N (%) 3 (1.5) 8 (4.1) 0.13
Distald; N (%) 28 (14.1) 49 (24.9) 0.007
Overalle; N (%) 29 (14.6) 53 (26.9) 0.003
"],"contraindications":["CONTRAINDICATIONS ORGARAN ® (danaparoid sodium) Injection is contraindicated in the following conditions: severe hemorrhagic diathesis, e.g., hemophilia and idiopathic thrombocytopenic purpura; active major bleeding state, including hemorrhagic stroke in the acute phase; hypersensitivity to ORGARAN ® ; Type II thrombocytopenia associated with a positive in vitro test for antiplatelet antibody in the presence of ORGARAN ® Injection. ORGARAN ® is contraindicated in patients with known hypersensitivity to pork products."],"description":["DESCRIPTION ORGARAN ® (danaparoid sodium) Injection is a sterile, glycosaminoglycuronan antithrombotic agent. The active components of ORGARAN®, isolated from porcine intestinal mucosa, are heparan sulfate (~84%), dermatan sulfate ( approximately 13% with a range between 9-17.5%) and chondroitin sulfate (less than 8.5%). The average molecular weight is approximately 5500 Daltons. The molecular weight distribution is: <2000 daltons ≤13% <4000 daltons ≤39% 4000 to 8000 daltons ≥50% >8000 daltons ≤19% >10000 daltons ≤11% ORGARAN ® is intended for subcutaneous injection. Each ampule contains 750 anti-Xa units of danaparoid sodium in 0.6 mL solution. ORGARAN ® Injection is made isotonic with sodium chloride, adjusted to pH 5.0-7.5 with hydrochloric acid, or sodium hydroxide. ORGARAN ® Injection contains 0.15% (w/v) sodium sulfite as an antioxidant to prevent discoloration of the solution. The structural formula of the main repeating disaccharide units is as follows: Structural Formula: Main Repeating Disaccharide Units Heparan Sulfate: R 1 = H or SO 3 – , R 2 = COCH 3 or SO 3 – Dermatan Sulfate R = H or SO 3 – Chondroitin Sulfate R = H or SO 3 – Structural Formula Structural Formula Structural Formula"],"description_table":["
<2000 daltons≤13%
<4000 daltons≤39%
4000 to 8000 daltons≥50%
>8000 daltons≤19%
>10000 daltons≤11%
","
Dermatan SulfateR = H or SO3–Chondroitin SulfateR = H or SO3–
"],"dosage_and_administration":["DOSAGE AND ADMINISTRATION Usual Adult Dosage In patients undergoing hip replacement surgery, the recommended dose of ORGARAN ® (danaparoid sodium) Injection is 750 anti-Xa units twice daily administered by subcutaneous injection beginning 1 to 4 hours pre-operatively, and then not sooner than two hours after surgery. Treatment should be continued throughout the period of post-operative care until the risk of deep vein thrombosis has diminished. The average duration of administration in clinical trials was 7 to 10 days, up to 14 days. Patients with serum creatinine ≥2.0 mg/dL should be carefully monitored. Use in Geriatrics No overall differences in safety and effectiveness of ORGARAN ® (danaparoid sodium) Injection were observed in patients ≥65 years when compared with patients <65 years undergoing elective hip replacement surgery. No dosage adjustments are recommended in elderly patients. Administration Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. ORGARAN ® (danaparoid sodium) Injection is intended for subcutaneous administration only. Subcutaneous injection technique: Patients should be lying down and ORGARAN ® Injection administered by deep subcutaneous injection using a fine needle (25 to 26 gauge) to minimize tissue trauma. Administration should be alternated between the left and right anterolateral and left and right posterolateral abdominal wall. The whole length of the 5/8 inch (16mm) needle should be introduced into a skin fold held gently between the thumb and forefinger; the skin fold should be held throughout the injection and should neither be pinched nor rubbed afterwards."],"drug_interactions":["Drug Interactions ORGARAN ® (danaparoid sodium) Injection should be used with caution in patients receiving oral anticoagulants and/or platelet inhibitors. Monitoring of anticoagulant activity of oral anticoagulants by Prothrombin Time and Thrombotest is unreliable within 5 hours after ORGARAN ® Injection administration."],"effective_time":"20230509","general_precautions":["General The risks and benefits of ORGARAN ® (danaparoid sodium) Injection should be carefully considered before use in patients with severely impaired renal function or hemorrhagic disorders (see DOSAGE AND ADMINISTRATION )."],"geriatric_use":["Geriatric Use Of the total number of patients undergoing elective hip replacement surgery who received ORGARAN ® (danaparoid sodium) Injection in clinical studies, 62% (397/645 patients) were ≥65 years and 22% (141/645 patients) were ≥75 years old. No overall differences in safety and effectiveness of ORGARAN ® were observed between elderly (≥65 years) subjects and younger subjects. Other reported clinical experience with ORGARAN ® has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals to ORGARAN ® cannot be ruled out. ORGARAN ® is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. ADVERSE REACTIONS The following table summarizes adverse bleeding events that occurred in clinical trials which studied ORGARAN ® (danaparoid sodium) Injection compared to placebo, warfarin, and others (heparin, heparin/DHE, acetylsalicylic acid, dextran, and low molecular weight heparins). Blood Loss and Transfusions DVT and PE Prophylaxis for Orthopedic Hip Surgery All Patients Treated Blood Loss and Transfusions Total N ORGARAN ® Placebo Warfarin Other a a “Other” includes the following active reference agents; heparin, heparin/DHE, acetylsalicylic acid, dextran, and low molecular weight heparins. Total N = Total number of patients with available data across all treatment groups. n = The number of patients with available data in each respective treatment group and by gender. Total (728 Males: 1675 Females) (n) Mean±SD (n) Mean±SD (n) Mean±SD (n) Mean±SD Intraoperative Blood Loss (mL) Males 596 (330) 694±555 (27) 586±737 (141) 689±499 (98) 754±661 Females 1259 (686) 486±430 (66) 416±252 (219) 471±306 (288) 530±456 Postoperative Blood Loss (mL) Males 580 (318) 954±879 (45) 908±812 (88) 817±585 (129) 1056±1055 Females 1256 (639) 700±778 (122) 715±520 (80) 619±352 (415) 798±779 Transfusions (units PRBCs) Males 462 (258) 2.6±1.8 (35) 2.7±1.4 (87) 2.5±1.4 (82) 2.9±2.1 Females 1152 (604) 2.6±1.7 (92) 2.8±1.4 (177) 2.1 ±1.1 (279) 2.8±2.0"],"geriatric_use_table":["
Blood Loss and Transfusions DVT and PE Prophylaxis for Orthopedic Hip Surgery All Patients Treated
Blood Loss and TransfusionsTotal NORGARAN®PlaceboWarfarinOthera
a “Other” includes the following active reference agents; heparin, heparin/DHE, acetylsalicylic acid, dextran, and low molecular weight heparins.
Total N = Total number of patients with available data across all treatment groups.
n = The number of patients with available data in each respective treatment group and by gender.
Total (728 Males: 1675 Females) (n) Mean±SD (n) Mean±SD (n) Mean±SD (n) Mean±SD
Intraoperative Blood Loss (mL)
Males 596 (330) 694±555 (27) 586±737 (141) 689±499 (98) 754±661
Females 1259 (686) 486±430 (66) 416±252 (219) 471±306 (288) 530±456
Postoperative Blood Loss (mL)
Males 580 (318) 954±879 (45) 908±812 (88) 817±585 (129) 1056±1055
Females 1256 (639) 700±778 (122) 715±520 (80) 619±352 (415) 798±779
Transfusions (units PRBCs)
Males 462 (258) 2.6±1.8 (35) 2.7±1.4 (87) 2.5±1.4 (82) 2.9±2.1
Females 1152 (604) 2.6±1.7 (92) 2.8±1.4 (177) 2.1 ±1.1 (279) 2.8±2.0
"],"how_supplied":["HOW SUPPLIED ORGARAN ® (danaparoid sodium) Injection is a clear and colorless to slightly yellow solution supplied in: - Single-dose Ampules containing 0.6 mL (750 anti-Xa units) of danaparoid sodium: boxes of 10, NDC 76388-830-16. Storage - Ampules should be stored at temperatures of 2° to 30°C (36° to 86°F). - Do not freeze. - Protect from light. Rx only Manufactured for: Aspen Global Incorporated GBS Plaza, Cnr La Salette & Royal Roads, Grand Bay, Mauritius Manufactured by: Aspen SVP (Pty) Ltd 8B Gibaud Rd, Korsten Port Elizabeth 6020 South Africa Revised: 05/2019"],"id":"4ff36428-ddcc-41a1-89a1-370b84990b1b","indications_and_usage":["INDICATIONS AND USAGE ORGARAN ® (danaparoid sodium) Injection is indicated for the prophylaxis of post-operative deep venous thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients undergoing elective hip replacement surgery."],"laboratory_tests":["Laboratory Tests ORGARAN ® (danaparoid sodium) Injection has only a small effect on factor lla (thrombin) activity, therefore, when administered at recommended prophylaxis doses, routine coagulation tests (e.g., Prothrombin Time [PT], Activated Partial Thromboplastin Time [APTT], Kaolin Cephalin Clotting Time [KCCT], Whole Blood Clotting Time [WBCT], and Thrombin Time [TT] are relatively insensitive measures of ORGARAN ® activity and, therefore, unsuitable for monitoring. Periodic complete blood counts, including platelet count, and stool occult blood tests are recommended during the course of treatment with ORGARAN ® ."],"nursing_mothers":["Nursing Mothers It is not known whether ORGARAN ® (danaparoid sodium) Injection is excreted in breast milk. Because many drugs are excreted in human milk, caution should be exercised when ORGARAN ® is administered to a nursing woman."],"openfda":{},"overdosage":["OVERDOSAGE Symptoms/Treatment Accidental overdosage following administration of ORGARAN ® (danaparoid sodium) Injection may lead to bleeding complications. The effects of ORGARAN ® on anti-Xa activity cannot be antagonized with any known agent at this time. Although protamine sulfate partially neutralizes the anti-Xa activity of ORGARAN ® and can be safely co-administered, there is no evidence that protamine sulfate is capable of reducing severe non-surgical bleeding during treatment with ORGARAN ® . In the event of serious bleeding, ORGARAN ® should be stopped and blood or blood product transfusions should be administered as needed. Withdrawal of ORGARAN ® may be expected to restore the coagulation balance without rebound phenomenon. Single subcutaneous doses of ORGARAN ® at 3800 anti-Xa units/kg (20.5 times the recommended human dose based on body surface area) and 15200 anti-Xa units/kg (82 times the recommended human dose based on body surface area) were lethal to female and male rats, respectively. Symptoms of acute toxicity after intravenous dosing were respiratory depression, prostration and twitching."],"package_label_principal_display_panel":["Principal Display Panel - Orgaran Carton Label 10 x 0.6 mL single-dose ampules NDC 76388-830-16 ORGARAN ® (danaparoid sodium) Injection 750 anti-Xa units / 0.6 mL For Subcutaneous Use Only Each 0.6 mL contains: 750 Anti-Xa units of danaparoid sodium in a sterile, aqueous solution; made isotonic with sodium chloride; pH adjusted with hydrochloric acid or sodium hydroxide; contains 0.15% (W/V) sodium sulfite to prevent discoloration. Usual dosage: See prescribing information Storage: 2° - 30°C (36°-86°F). Do not freeze. Protect from light. Rx only Mfg for: Aspen Global Inc. Grand Bay, Mauritius Mfg by: Aspen SVP (Pty) Ltd Korsten, Port Elizabeth 6020 South Africa Figure","Principal Display Panel - Orgaran Ampule Label ORGARAN ® (danaparoid sodium) Injection 750 anti-Xa units / 0.6 mL For Subcutaneous Use Only Storage: 2°-30°C [36°-86°F] Do not freeze Protect from light aspen NDC 76388-830-06 Rx only Figure"],"pediatric_use":["Pediatric Use Safety and effectiveness of ORGARAN ® (danaparoid sodium) Injection in pediatric patients have not been established."],"pharmacodynamics":["Pharmacodynamics Effect on Coagulation Factors ORGARAN ® (danaparoid sodium) Injection is an antithrombotic agent. ORGARAN ® prevents fibrin formation in the coagulation pathway via thrombin generation inhibition by anti-Xa and anti-IIa (thrombin) effects. The anti-Xa: anti-IIa activity ratio is greater than 22. Inactivation of factor Xa is mediated by antithrombin-llI (AT-III) while factor IIa inactivation is mediated by both AT-III and heparin cofactor II (HC II). ORGARAN ® has only minor effect on platelet function and platelet aggregability. Measurements of Hemostasis Because of its predominant anti-Xa activity, ORGARAN ® has little effect on clotting assays ( e.g. , prothrombin time [PT], partial thromboplastin time [PTT]). ORGARAN ® has minimal effect on fibrinolytic activity and bleeding time."],"pharmacokinetics":["Pharmacokinetics The pharmacokinetics of ORGARAN ® (danaparoid sodium) Injection have been described by monitoring its biological activity (plasma anti-Xa activity) since no specific chemical assay methods are currently available for the components of ORGARAN ® . By subcutaneous route of administration, ORGARAN ® was approximately 100% bioavailable, compared with the same dose administered intravenously. The maximum anti-Xa activity (T max ) occurred at approximately two to five hours. For single subcutaneous doses of 750,1500, 2250, and 3250 anti-Xa units of ORGARAN ® the mean peak plasma anti-Xa activities were 102.4, 206.1, 283.9, and 403.4 mU/mL, respectively. The mean terminal half-life (T 1/2 ) was about 24 hours and the clearance was 0.36 L/hour. Clearance was affected by body surface area in that the higher the body surface, the faster the clearance. ORGARAN ® is mainly eliminated via the kidneys. In patients with severely impaired renal function, the half-life of elimination of plasma anti-Xa activity may be prolonged, therefore, monitoring such patients carefully is recommended."],"precautions":["PRECAUTIONS General The risks and benefits of ORGARAN ® (danaparoid sodium) Injection should be carefully considered before use in patients with severely impaired renal function or hemorrhagic disorders (see DOSAGE AND ADMINISTRATION ). Laboratory Tests ORGARAN ® (danaparoid sodium) Injection has only a small effect on factor lla (thrombin) activity, therefore, when administered at recommended prophylaxis doses, routine coagulation tests (e.g., Prothrombin Time [PT], Activated Partial Thromboplastin Time [APTT], Kaolin Cephalin Clotting Time [KCCT], Whole Blood Clotting Time [WBCT], and Thrombin Time [TT] are relatively insensitive measures of ORGARAN ® activity and, therefore, unsuitable for monitoring. Periodic complete blood counts, including platelet count, and stool occult blood tests are recommended during the course of treatment with ORGARAN ® . Thrombocytopenia ORGARAN ® (danaparoid sodium) Injection shows a low cross-reactivity with antiplatelet antibodies in individuals with Type II heparin-induced thrombocytopenia. No cases of white clot syndrome or cases of Type II thrombocytopenia have been reported in clinical studies for the prophylaxis of DVT in patients receiving multiple doses of ORGARAN ® up to 14 days. Drug Interactions ORGARAN ® (danaparoid sodium) Injection should be used with caution in patients receiving oral anticoagulants and/or platelet inhibitors. Monitoring of anticoagulant activity of oral anticoagulants by Prothrombin Time and Thrombotest is unreliable within 5 hours after ORGARAN ® Injection administration. Carcinogenesis, Mutagenesis, Impairment of Fertility No long term studies in animals have been performed to evaluate the carcinogenic potential of ORGARAN ® (danaparoid sodium) Injection. ORGARAN ® was not genotoxic in the Ames test, the in vitro CHL/HGPRT forward gene mutation assay, the in vitro CHO cell chromosome aberration test, the in vitro HeLa cell unscheduled DNA synthesis (UDS) test or the in vivo mouse micronucleus test. ORGARAN ® at intravenous doses of up to 1090 anti-Xa units/kg/day was found to have no effect on fertility or reproductive performance of male and female rats. This dose is 5.9 times the recommended human subcutaneous dose based on body surface area (50 kg body weight and 1.46 m 2 body surface area assumed). Pregnancy Teratogenic Effects-Pregnancy Category B Teratology studies have been performed in pregnant rats at intravenous doses up to 1600 anti-Xa units/kg/day (8.7 times the recommended human dose based on body surface area) and pregnant rabbits at intravenous doses up to 780 anti-Xa units/kg/day (6 times the recommended human dose based on body surface area) and have not revealed evidence of impaired fertility or harm to the fetus due to ORGARAN ® (danaparoid sodium) Injection. 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. Nursing Mothers It is not known whether ORGARAN ® (danaparoid sodium) Injection is excreted in breast milk. Because many drugs are excreted in human milk, caution should be exercised when ORGARAN ® is administered to a nursing woman. Pediatric Use Safety and effectiveness of ORGARAN ® (danaparoid sodium) Injection in pediatric patients have not been established. Geriatric Use Of the total number of patients undergoing elective hip replacement surgery who received ORGARAN ® (danaparoid sodium) Injection in clinical studies, 62% (397/645 patients) were ≥65 years and 22% (141/645 patients) were ≥75 years old. No overall differences in safety and effectiveness of ORGARAN ® were observed between elderly (≥65 years) subjects and younger subjects. Other reported clinical experience with ORGARAN ® has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals to ORGARAN ® cannot be ruled out. ORGARAN ® is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. ADVERSE REACTIONS The following table summarizes adverse bleeding events that occurred in clinical trials which studied ORGARAN ® (danaparoid sodium) Injection compared to placebo, warfarin, and others (heparin, heparin/DHE, acetylsalicylic acid, dextran, and low molecular weight heparins). Blood Loss and Transfusions DVT and PE Prophylaxis for Orthopedic Hip Surgery All Patients Treated Blood Loss and Transfusions Total N ORGARAN ® Placebo Warfarin Other a a “Other” includes the following active reference agents; heparin, heparin/DHE, acetylsalicylic acid, dextran, and low molecular weight heparins. Total N = Total number of patients with available data across all treatment groups. n = The number of patients with available data in each respective treatment group and by gender. Total (728 Males: 1675 Females) (n) Mean±SD (n) Mean±SD (n) Mean±SD (n) Mean±SD Intraoperative Blood Loss (mL) Males 596 (330) 694±555 (27) 586±737 (141) 689±499 (98) 754±661 Females 1259 (686) 486±430 (66) 416±252 (219) 471±306 (288) 530±456 Postoperative Blood Loss (mL) Males 580 (318) 954±879 (45) 908±812 (88) 817±585 (129) 1056±1055 Females 1256 (639) 700±778 (122) 715±520 (80) 619±352 (415) 798±779 Transfusions (units PRBCs) Males 462 (258) 2.6±1.8 (35) 2.7±1.4 (87) 2.5±1.4 (82) 2.9±2.1 Females 1152 (604) 2.6±1.7 (92) 2.8±1.4 (177) 2.1 ±1.1 (279) 2.8±2.0 Other The following table summarizes adverse events that occurred at a frequency greater than, or equal to, 2% of patients in clinical trials for the prophylaxis of DVT and PE following elective hip surgery which studied ORGARAN ® (danaparoid sodium) Injection compared to placebo, warfarin, and others (dextran, heparin/DHE, aspirin). Incidence of Adverse Experiences (≥2%) DVT and PE Prophylaxis for Elective Hip Surgery All Patients Treated Adverse Experience ORGARAN® N=645 N(%) Placebo N=135 N(%) Warfarin N=243 N(%) Other N=168 N(%) Fever 143(22.2) 1(0.7) 138(56.8) 3(1.8) Nausea 92(14.3) 3(2.2) 78(32.1) 8(4.8) Constipation 73(11.3) 0(0.0) 70(28.8) 2(1.2) Injection Site Pain 49(7.6) 4(3.0) 0(0.0) 34(20.2) Rash 31(4.8) 0(0.0) 18(7.4) 2(1.2) Pruritus 25(3.9) 1(0.7) 14(5.8) 0(0.0) Peripheral Edema 21(3.3) 0(0.0) 19(7.8) 4(2.4) Insomnia 20(3.1) 0(0.0) 32(13.2) 0(0.0) Vomiting 19(2.9) 3(2.2) 20(8.2) 3(1.8) Joint Disorder 17(2.6) 0(0.0) 15(6.2) 0(0.0) Headache 17(2.6) 1(0.7) 13(5.3) 0(0.0) Urinary Tract Infection 17(2.6) 1(0.7) 5(2.1) 5(3.0) Edema 17(2.6) 0(0.0) 14(5.8) 2(1.2) Asthenia 15(2.3) 0(0.0) 10(4.1) 1(0.6) Dizziness 15(2.3) 0(0.0) 14(5.8) 0(0.0) Anemia 14(2.2) 3(2.2) 5(2.1) 5(3.0) Urinary Retention 13(2.0) 0(0.0) 14(5.8) 1(0.6) In addition, the following table summarizes adverse events that occurred at a frequency greater than, or equal to, 2% of patients in clinical trials for the prophylaxis of DVT and PE which studied ORGARAN ® compared to placebo, warfarin, and others (heparin, heparin sodium, heparin calcium, enoxaparin, dalteparin, dextran, heparin/DHE, aspirin). Incidence of Adverse Experiences (≥2%) DVT and PE Prophylaxis Indication All Patients Treated Adverse Experience ORGARAN® N=2383 N(%) Placebo N=276 N(%) Warfarin N=421 N(%) Other N=1163 N(%) Injection Site Pain 327(13.7) 53(19.2) 0(0.0) 153(13.2) Pain 207(8.7) 0(0 .0) 202(48.0) 20(1.7) Fever 173(7.3) 1(0.4) 150(35.6) 21(1.8) Nausea 98(4.1) 3(1.1) 79(18.8) 13(1.1) Urinary Tract Infection 96(4.0) 3(1.1) 27(6.4) 65(5.6) Constipation 83(3.5) 0(0.0) 73(17.3) 3(0.3) Rash 51(2.1) 0(0.0) 25(5.9) 5(0.4) Infection 51(2.1) 3(1.1) 0(0.0) 47(4.0)"],"precautions_table":["
Blood Loss and Transfusions DVT and PE Prophylaxis for Orthopedic Hip Surgery All Patients Treated
Blood Loss and TransfusionsTotal NORGARAN®PlaceboWarfarinOthera
a “Other” includes the following active reference agents; heparin, heparin/DHE, acetylsalicylic acid, dextran, and low molecular weight heparins.
Total N = Total number of patients with available data across all treatment groups.
n = The number of patients with available data in each respective treatment group and by gender.
Total (728 Males: 1675 Females) (n) Mean±SD (n) Mean±SD (n) Mean±SD (n) Mean±SD
Intraoperative Blood Loss (mL)
Males 596 (330) 694±555 (27) 586±737 (141) 689±499 (98) 754±661
Females 1259 (686) 486±430 (66) 416±252 (219) 471±306 (288) 530±456
Postoperative Blood Loss (mL)
Males 580 (318) 954±879 (45) 908±812 (88) 817±585 (129) 1056±1055
Females 1256 (639) 700±778 (122) 715±520 (80) 619±352 (415) 798±779
Transfusions (units PRBCs)
Males 462 (258) 2.6±1.8 (35) 2.7±1.4 (87) 2.5±1.4 (82) 2.9±2.1
Females 1152 (604) 2.6±1.7 (92) 2.8±1.4 (177) 2.1 ±1.1 (279) 2.8±2.0
","
DVT and PE Prophylaxis for Elective Hip Surgery All Patients Treated
Adverse ExperienceORGARAN® N=645 N(%)Placebo N=135 N(%)Warfarin N=243 N(%)Other N=168 N(%)
Fever 143(22.2) 1(0.7) 138(56.8) 3(1.8)
Nausea 92(14.3) 3(2.2) 78(32.1) 8(4.8)
Constipation 73(11.3) 0(0.0) 70(28.8) 2(1.2)
Injection Site Pain 49(7.6) 4(3.0) 0(0.0) 34(20.2)
Rash 31(4.8) 0(0.0) 18(7.4) 2(1.2)
Pruritus 25(3.9) 1(0.7) 14(5.8) 0(0.0)
Peripheral Edema 21(3.3) 0(0.0) 19(7.8) 4(2.4)
Insomnia 20(3.1) 0(0.0) 32(13.2) 0(0.0)
Vomiting 19(2.9) 3(2.2) 20(8.2) 3(1.8)
Joint Disorder 17(2.6) 0(0.0) 15(6.2) 0(0.0)
Headache 17(2.6) 1(0.7) 13(5.3) 0(0.0)
Urinary Tract Infection 17(2.6) 1(0.7) 5(2.1) 5(3.0)
Edema 17(2.6) 0(0.0) 14(5.8) 2(1.2)
Asthenia 15(2.3) 0(0.0) 10(4.1) 1(0.6)
Dizziness 15(2.3) 0(0.0) 14(5.8) 0(0.0)
Anemia 14(2.2) 3(2.2) 5(2.1) 5(3.0)
Urinary Retention 13(2.0) 0(0.0) 14(5.8) 1(0.6)
","
Incidence of Adverse Experiences (≥2%) DVT and PE Prophylaxis Indication All Patients Treated
Adverse ExperienceORGARAN® N=2383 N(%)Placebo N=276 N(%)Warfarin N=421 N(%)Other N=1163 N(%)
Injection Site Pain 327(13.7) 53(19.2) 0(0.0) 153(13.2)
Pain 207(8.7) 0(0 .0) 202(48.0) 20(1.7)
Fever 173(7.3) 1(0.4) 150(35.6) 21(1.8)
Nausea 98(4.1) 3(1.1) 79(18.8) 13(1.1)
Urinary Tract Infection 96(4.0) 3(1.1) 27(6.4) 65(5.6)
Constipation 83(3.5) 0(0.0) 73(17.3) 3(0.3)
Rash 51(2.1) 0(0.0) 25(5.9) 5(0.4)
Infection 51(2.1) 3(1.1) 0(0.0) 47(4.0)
"],"pregnancy":["Pregnancy Teratogenic Effects-Pregnancy Category B Teratology studies have been performed in pregnant rats at intravenous doses up to 1600 anti-Xa units/kg/day (8.7 times the recommended human dose based on body surface area) and pregnant rabbits at intravenous doses up to 780 anti-Xa units/kg/day (6 times the recommended human dose based on body surface area) and have not revealed evidence of impaired fertility or harm to the fetus due to ORGARAN ® (danaparoid sodium) Injection. 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."],"set_id":"3256da8e-2c0b-4396-9c41-d5d8f1c1e4f1","spl_product_data_elements":["ORGARAN Danaparoid Sodium danaparoid sodium danaparoid sodium sulfite sodium chloride sodium hydroxide hydrochloric acid water"],"storage_and_handling":["Storage - Ampules should be stored at temperatures of 2° to 30°C (36° to 86°F). - Do not freeze. - Protect from light. Rx only Manufactured for: Aspen Global Incorporated GBS Plaza, Cnr La Salette & Royal Roads, Grand Bay, Mauritius Manufactured by: Aspen SVP (Pty) Ltd 8B Gibaud Rd, Korsten Port Elizabeth 6020 South Africa Revised: 05/2019"],"teratogenic_effects":["Teratogenic Effects-Pregnancy Category B Teratology studies have been performed in pregnant rats at intravenous doses up to 1600 anti-Xa units/kg/day (8.7 times the recommended human dose based on body surface area) and pregnant rabbits at intravenous doses up to 780 anti-Xa units/kg/day (6 times the recommended human dose based on body surface area) and have not revealed evidence of impaired fertility or harm to the fetus due to ORGARAN ® (danaparoid sodium) Injection. 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."],"version":"9","warnings":["WARNINGS General ORGARAN ® (danaparoid sodium) Injection is not intended for intramuscular administration. Since a specific standard for the anti-Xa activity of ORGARAN ® is used, the anti-Xa unit activity of ORGARAN ® is not equivalent to that described for heparin or low molecular weight heparin. Therefore, ORGARAN ® cannot be dosed interchangeably (unit for unit) with either heparin or any low molecular weight heparin. Miscellaneous ORGARAN ® (danaparoid sodium) Injection contains sodium sulfite which may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic patients. Hemorrhage Hemorrhage can occur at virtually any site in patients receiving ORGARAN ® (danaparoid sodium) Injection. An unexplained fall in hematocrit and/or fall in blood pressure should lead to serious consideration of a hemorrhagic event. ORGARAN ® , like anticoagulants, should be used with extreme caution in disease states in which there is increased risk of hemorrhage, such as severe uncontrolled hypertension, acute bacterial endocarditis, congenital or acquired bleeding disorders, active ulcerative and angiodysplastic gastrointestinal disease, non-hemorrhagic stroke, shortly after brain, spinal or ophthalmological surgery and post-operative indwelling epidural catheter use. 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 post-operative indwelling epidural catheters or concomitant use of additional drugs affecting hemostasis such as NSAIDs (see boxed WARNING )."]}