FDA label 8dfe69f6-715c-4b8e-bb55-ccfc8fced45a

WARNING: SPINAL/EPIDURAL HEMATOMAS Epidural or spinal hematomas may occur in patients who are anticoagulated with low molecular weight heparins (LMWH) or heparinoids and are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include: Use of indwelling epidural catheters Concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants. A history of traumatic or repeated epidural or spinal punctures A history of spinal deformity or spinal surgery Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis (see WARNINGS, Hemorrhage, and PRECAUTIONS, Drug Interactions ).

WARNINGS INNOHEP® is not intended for intramuscular or intravenous administration. INNOHEP® cannot be used interchangeably (unit for unit) with heparin or other low molecular weight heparins as they differ in manufacturing process, molecular weight distribution, anti-Xa and anti-IIa activities, units, and dosage. Each of these medications has its own instructions for use. INNOHEP® should not be used in patients with a history of heparin-induced thrombocytopenia (see CONTRAINDICATIONS ). Increased Risk for Death in Elderly Patients with Renal Insufficiency: INNOHEP® may increase the risk for death, compared to UFH, when administered to elderly patients with renal insufficiency. A clinical study compared INNOHEP® (175 IU/kg once daily; N = 269) and UFH (N = 268) in the initial treatment of deep vein thrombosis (DVT) and/or pulmonary embolism (PE) in elderly patients with renal insufficiency (i.e., patients aged 70 years or older with estimated creatinine clearance of ≤ 30 mL/min or patients aged 75 years or older with estimated creatinine clearance of ≤ 60 mL/min). Oral anticoagulants were co-administered beginning on Days 1-3 and study treatment was continued for at least five days until the international normalized ratio (INR) was between 2-3 on two successive days; oral anticoagulants were then continued alone and patients were followed until 90 days after the start of treatment. Overall mortality rates were 6.3% in patients treated with UFH and 11.5% in patients treated with INNOHEP®. Consider the use of alternatives to INNOHEP® in elderly patients with renal insufficiency. Hemorrhage: INNOHEP®, like other anticoagulants, should be used with extreme caution in conditions with increased risk of hemorrhage, such as bacterial endocarditis; severe uncontrolled hypertension; congenital or acquired bleeding disorders including hepatic failure and amyloidosis; active ulcerative and angiodysplastic gastrointestinal disease; hemorrhagic stroke; shortly after brain, spinal or ophthalmological surgery, or in patients treated concomitantly with platelet inhibitors. Bleeding can occur in any tissue or organ of the body during therapy with INNOHEP®. Hemorrhage in some cases has been reported to result in death or permanent disability. A hemorrhagic event should be seriously considered in the presence of an unexplained fall in hematocrit, hemoglobin, or blood pressure. If severe hemorrhage occurs, INNOHEP® should be discontinued. Spinal or epidural hematomas can occur with the associated use of low molecular weight heparins or heparinoids and 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 with the concomitant use of additional drugs affecting hemostasis such as NSAIDs (see boxed WARNING and PRECAUTIONS, Drug Interactions ). Thrombocytopenia: Thrombocytopenia can occur with the administration of INNOHEP®. In clinical studies, thrombocytopenia (platelet count <100,000/mm 3 if baseline value ≥150,000/mm 3 , ≥50% decline if baseline <150,000/mm 3 ) was identified in 1% of patients given INNOHEP®; severe thrombocytopenia (platelet count less than 50,000/mm 3 ) occurred in 0.13%. Thrombocytopenia of any degree should be monitored closely. If the platelet count falls below 100,000/mm 3 , INNOHEP® should be discontinued. Cases of thrombocytopenia with disseminated thrombosis also have been observed in clinical practice with heparins, and low molecular weight heparins, including tinzaparin sodium. Some of these cases were complicated by organ infarction with secondary organ dysfunction or limb ischemia, and have resulted in death. Hypersensitivity: INNOHEP® contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown, but is probably low. Sulfite sensitivity is more frequent in asthmatic people than in non-asthmatic people. Priapism: Priapism has been reported from post-marketing surveillance as a rare occurrence. In some cases surgical intervention was required. Miscellaneous: INNOHEP® multiple dose vial contains benzyl alcohol as a preservative. The administration of medications containing benzyl alcohol as a preservative to premature neonates has been associated with a fatal “Gasping Syndrome." Because benzyl alcohol may cross the placenta, INNOHEP® preserved with benzyl alcohol should be used with caution in pregnant women only if clearly needed (see PRECAUTIONS, Pregnancy ).

ADVERSE REACTIONS Bleeding : Bleeding is the most common adverse event associated with INNOHEP® (tinzaparin sodium injection); however, the incidence of major bleeding is low. In clinical trials, the definition of major bleeding included bleeding accompanied by ≥2 gram/dL decrease in hemoglobin, requiring transfusion of 2 or more units of blood products, or bleeding which was intracranial, retroperitoneal, or into a major prosthetic joint. The data are provided in Table 4. Table 4 Major Bleeding Events 1 in Treatment of Acute Deep Vein Thrombosis With or Without Pulmonary Embolism Indication Treatment Group 1 Treatment of Acute DVT With or Without PE INNOHEP® N=519 % Heparin N=524 % 1 INNOHEP® 175 IU/kg once daily SC. Unfractionated heparin initial IV bolus of 5,000 IU followed by continuous IV infusion adjusted to an aPTT of 1.5 to 2.5 or initial IV bolus of 50 IU/kg followed by continuous IV infusion adjusted to an aPTT of 2.0 to 3.0. In all groups treatment continued for approximately 6 to 8 days, and all patients received oral anticoagulant treatment commencing in the first 2 to 3 days. 2 Bleeding accompanied by ≥2 gram/dL decline in hemoglobin, requiring transfusion of 2 or more units of blood products, or bleeding which was intracranial, retroperitoneal, or into a major prosthetic joint. 3 The 95% CI on the difference in major bleeding event rates (1.9%) was 0.33%, 3.47%. Major Bleeding Events 2 0.8 3 2.7 3 Fatal or nonfatal hemorrhage from any tissue or organ can occur. The signs, symptoms, and severity will vary according to the location and degree or extent of the bleeding. Hemorrhagic complications may present as, but are not limited to, paralysis; paresthesia; headache, chest, abdomen, joint, muscle or other pain; dizziness; shortness of breath, difficult breathing or swallowing; swelling; weakness; hypotension, shock, or coma. Therefore, the possibility of hemorrhage should be considered in evaluating the condition of any anticoagulated patient with complaints which do not indicate an obvious diagnosis (see WARNINGS, Hemorrhage ). Thrombocytopenia : In clinical studies thrombocytopenia was identified in 1% of patients treated with INNOHEP®. Severe thrombocytopenia (platelet count <50,000/mm 3 ) occurred in 0.13% (see WARNINGS, Thrombocytopenia ). Elevations of Serum Aminotransferases : Asymptomatic increases in aspartate (AST [SGOT]) and/or alanine (ALT [SGPT]) aminotransferase levels greater than 3 times the upper limit of normal of the laboratory reference range have been reported in up to 8.8% and 13% for AST and ALT, respectively, of patients receiving tinzaparin sodium for the treatment of DVT. Similar increases in aminotransferase levels have also been observed in patients and healthy volunteers treated with heparin and other low molecular weight heparins. Such elevations are reversible and are rarely associated with increases in bilirubin (see PRECAUTIONS, Laboratory Tests ). Local Reactions : Mild local irritation, pain, hematoma, and ecchymosis may follow SC injection of INNOHEP®. Injection site hematoma has been reported in approximately 16% of patients treated with INNOHEP®. Hypersensitivity : Anaphylactic/anaphylactoid reactions may occur in association with INNOHEP® use (see CONTRAINDICATIONS and WARNINGS ). Adverse Events : Adverse events with INNOHEP® or heparin reported at a frequency of ≥1% in clinical trials with patients undergoing treatment for proximal DVT with or without PE, are provided in Table 5. Table 5 Adverse Events Occurring in ≥ 1% in Treatment of Acute Deep Vein Thrombosis With or Without Pulmonary Embolism Studies Treatment Group 1 Adverse Events INNOHEP® N=519 n (%) Heparin N=524 n (%) NOS = not otherwise specified 1 INNOHEP® 175 IU/kg once daily SC. Unfractionated heparin initial IV bolus of 5,000 IU followed by continuous IV infusion adjusted to an aPTT of 1.5 to 2.5 or initial IV bolus of 50 IU/kg followed by continuous IV infusion adjusted to an aPTT of 2.0 to 3.0. In all groups treatment continued for approximately 6 to 8 days, and all patients received oral anticoagulant treatment commencing in the first 2 to 3 days. Urinary Tract Infection 19 (3.7%) 18 (3.4%) Pulmonary Embolism 12 (2.3%) 12 (2.3%) Chest Pain 12 (2.3%) 8 (1.5%) Epistaxis 10 (1.9%) 7 (1.3%) Headache 9 (1.7%) 9 (1.7%) Nausea 9 (1.7%) 10 (1.9%) Hemorrhage NOS 8 (1.5%) 23 (4.4%) Back Pain 8 (1.5%) 2 (0.4%) Fever 8 (1.5%) 11 (2.1%) Pain 8 (1.5%) 7 (1.3%) Constipation 7 (1.3%) 9 (1.7%) Rash 6 (1.2%) 8 (1.5%) Dyspnea 6 (1.2%) 9 (1.7%) Vomiting 5 (1.0%) 8 (1.5%) Hematuria 5 (1.0%) 6 (1.1%) Abdominal Pain 4 (0.8%) 6 (1.1%) Diarrhea 3 (0.6%) 7 (1.3%) Anemia 0 7 (1.3%) Other Adverse Events in Completed or Ongoing Trials : Other adverse events reported at a frequency of ≥1% in 4,000 patients who received INNOHEP® in completed or ongoing clinical trials are listed by body system: Body as a Whole: injection site hematoma, reaction unclassified. Cardiovascular Disorders, General: hypotension, hypertension. Central and Peripheral Nervous System Disorders: dizziness. Gastrointestinal System Disorders: flatulence, gastrointestinal disorder (not otherwise specified), dyspepsia. Heart Rate and Rhythm Disorders: tachycardia. Myo-, Endo-, Pericardial and Valve Disorders: angina pectoris. Platelet, Bleeding and Clotting Disorders: hematoma, thrombocytopenia. Psychiatric Disorders: insomnia, confusion. Red Blood Cell Disorders: anemia. Resistance Mechanism Disorders: healing impaired, infection. Respiratory System Disorders: pneumonia, respiratory disorder. Skin and Appendages Disorders: rash erythematous, pruritus, bullous eruption, skin disorder. Urinary System Disorders: urinary retention, dysuria. Vascular (Extracardiac) Disorders: thrombophlebitis deep, thrombophlebitis leg deep. Serious adverse events reported in clinical trials or from post-marketing experience are included in Tables 6 and 7 , respectively: Table 6 Serious Adverse Events Associated With INNOHEP® in Clinical Trials Category Serious Adverse Event Bleeding-related Anorectal bleeding Cerebral/intracranial bleeding Epistaxis Gastrointestinal hemorrhage Hemarthrosis Hematemesis Hematuria Hemopericardium Hemorrhage NOS Injection site bleeding Melena Purpura Retroperitoneal/intra-abdominal bleeding Vaginal hemorrhage Wound hematoma Organ dysfunction Angina pectoris Cardiac arrhythmia Dependent edema Myocardial infarction/coronary thrombosis Thromboembolism Fetal/neonatal Congenital anomaly Fetal death Fetal distress Cutaneous Bullous eruption Erythematous rash Maculopapular rash Skin necrosis Hematologic Granulocytopenia Thrombocytopenia Allergic reactions Allergic reaction Injection site reaction Cellulitis Neoplastic Neoplasm Table 7 Other Serious Adverse Events Associated With INNOHEP® from Post-Marketing Surveillance Category Serious Adverse Event Organ dysfunction Cholestatic hepatitis Increase in hepatic enzymes Peripheral ischemia Priapism Bleeding-related Hematoma Hemoptysis Ocular hemorrhage Rectal bleeding Cutaneous reactions Epidermal necrolysis Ischemic necrosis Stevens-Johnson syndrome Urticaria Hematologic Agranulocytosis Pancytopenia Thrombocythemia Injection site reactions Abscess Necrosis Allergic reactions Allergic purpura Angioedema Fetal/neonatal Cutis aplasia of the scalp Neonatal hypotonia General Acute febrile reaction Ongoing Safety Surveillance : 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 (see boxed WARNING ). Spinal epidural hematoma in association with neuraxial anesthesia or spinal puncture with INNOHEP® has been reported. Spinal epidural hematoma with INNOHEP® administered at a therapeutic dose has been reported in at least one patient who had not received neuraxial anesthesia or spinal puncture.

<table ID="t4" width="100%"> <caption>Table 4 Major Bleeding Events¹ in Treatment of Acute Deep Vein Thrombosis With or Without Pulmonary Embolism </caption> <col width="42.619%" align="left"/> <col width="25.958%" align="left"/> <col width="31.423%" align="left"/> <thead> <tr> <th align="center" valign="middle" styleCode="Toprule Lrule Rrule"> <content styleCode="bold">Indication</content> </th> <th colspan="2" align="center" valign="middle" styleCode="Toprule Rrule"> <content styleCode="bold">Treatment Group</content> ¹ </th> </tr> <tr> <th align="center" valign="top" styleCode="Lrule Toprule Rrule"> <content styleCode="bold">Treatment of Acute DVT</content> <content styleCode="bold">With or Without PE</content> </th> <th align="center" valign="top" styleCode="Toprule Rrule"> <content styleCode="bold">INNOHEP&#xAE;</content> <content styleCode="bold">N=519</content> <content styleCode="bold">%</content> </th> <th align="center" valign="top" styleCode="Toprule Rrule"> <content styleCode="bold">Heparin</content> <content styleCode="bold">N=524</content> <content styleCode="bold">%</content> </th> </tr> </thead> <tfoot> <tr> <td colspan="3" align="left" valign="top"> <paragraph styleCode="footnote"> ¹ INNOHEP&#xAE; 175 IU/kg once daily SC. Unfractionated heparin initial IV bolus of 5,000 IU followed by continuous IV infusion adjusted to an aPTT of 1.5 to 2.5 or initial IV bolus of 50 IU/kg followed by continuous IV infusion adjusted to an aPTT of 2.0 to 3.0. In all groups treatment continued for approximately 6 to 8 days, and all patients received oral anticoagulant treatment commencing in the first 2 to 3 days. </paragraph> </td> </tr> <tr> <td colspan="3" align="left" valign="top"> <paragraph styleCode="footnote"> ² Bleeding accompanied by &#x2265;2 gram/dL decline in hemoglobin, requiring transfusion of 2 or more units of blood products, or bleeding which was intracranial, retroperitoneal, or into a major prosthetic joint. </paragraph> </td> </tr> <tr> <td colspan="3" align="left" valign="top"> <paragraph styleCode="footnote"> ³ The 95% CI on the difference in major bleeding event rates (1.9%) was 0.33%, 3.47%. </paragraph> </td> </tr> </tfoot> <tbody> <tr> <td align="left" valign="middle" styleCode="Toprule Lrule Rrule">Major Bleeding Events² </td> <td align="center" valign="middle" styleCode="Toprule Rrule">0.8³ </td> <td align="center" valign="middle" styleCode="Toprule Rrule">2.7³ </td> </tr> </tbody> </table>

<table ID="t5" width="100%"> <caption>Table 5 Adverse Events Occurring in &#x2265; 1% in Treatment of Acute Deep Vein Thrombosis With or Without Pulmonary Embolism Studies </caption> <col width="42.314%" align="left"/> <col width="28.843%" align="left"/> <col width="28.843%" align="left"/> <thead> <tr> <th align="center" valign="top" styleCode="Toprule Lrule Rrule"/> <th colspan="2" align="center" valign="middle" styleCode="Toprule Rrule"> <content styleCode="bold">Treatment Group</content> ¹ </th> </tr> <tr> <th align="center" valign="top" styleCode="Toprule Lrule Rrule"> <content styleCode="bold">Adverse Events</content> </th> <th align="center" valign="top" styleCode="Toprule Rrule"> <content styleCode="bold">INNOHEP&#xAE;</content> <content styleCode="bold">N=519</content> <content styleCode="bold">n (%)</content> </th> <th align="center" valign="top" styleCode="Toprule Rrule"> <content styleCode="bold">Heparin</content> <content styleCode="bold">N=524</content> <content styleCode="bold">n (%)</content> </th> </tr> </thead> <tfoot> <tr> <td colspan="3" align="left" valign="top"> <paragraph styleCode="footnote">NOS = not otherwise specified </paragraph> </td> </tr> <tr> <td colspan="3" align="left" valign="top"> <paragraph styleCode="footnote"> ¹ INNOHEP&#xAE; 175 IU/kg once daily SC. Unfractionated heparin initial IV bolus of 5,000 IU followed by continuous IV infusion adjusted to an aPTT of 1.5 to 2.5 or initial IV bolus of 50 IU/kg followed by continuous IV infusion adjusted to an aPTT of 2.0 to 3.0. In all groups treatment continued for approximately 6 to 8 days, and all patients received oral anticoagulant treatment commencing in the first 2 to 3 days. </paragraph> </td> </tr> </tfoot> <tbody> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Urinary Tract Infection </td> <td align="center" valign="top" styleCode="Toprule Rrule">19 (3.7%) </td> <td align="center" valign="top" styleCode="Toprule Rrule">18 (3.4%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Pulmonary Embolism </td> <td align="center" valign="top" styleCode="Toprule Rrule">12 (2.3%) </td> <td align="center" valign="top" styleCode="Toprule Rrule">12 (2.3%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Chest Pain </td> <td align="center" valign="top" styleCode="Toprule Rrule">12 (2.3%) </td> <td align="center" valign="top" styleCode="Toprule Rrule">8 (1.5%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Epistaxis </td> <td align="center" valign="top" styleCode="Toprule Rrule">10 (1.9%) </td> <td align="center" valign="top" styleCode="Toprule Rrule">7 (1.3%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Headache </td> <td align="center" valign="top" styleCode="Toprule Rrule">9 (1.7%) </td> <td align="center" valign="top" styleCode="Toprule Rrule">9 (1.7%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Nausea </td> <td align="center" valign="top" styleCode="Toprule Rrule">9 (1.7%) </td> <td align="center" valign="top" styleCode="Toprule Rrule">10 (1.9%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Hemorrhage NOS </td> <td align="center" valign="top" styleCode="Toprule Rrule">8 (1.5%) </td> <td align="center" valign="top" styleCode="Toprule Rrule">23 (4.4%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Back Pain </td> <td align="center" valign="top" styleCode="Toprule Rrule">8 (1.5%) </td> <td align="center" valign="top" styleCode="Toprule Rrule">2 (0.4%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Fever </td> <td align="center" valign="top" styleCode="Toprule Rrule">8 (1.5%) </td> <td align="center" valign="top" styleCode="Toprule Rrule">11 (2.1%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Pain </td> <td align="center" valign="top" styleCode="Toprule Rrule">8 (1.5%) </td> <td align="center" valign="top" styleCode="Toprule Rrule">7 (1.3%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Constipation </td> <td align="center" valign="top" styleCode="Toprule Rrule">7 (1.3%) </td> <td align="center" valign="top" styleCode="Toprule Rrule">9 (1.7%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Rash </td> <td align="center" valign="top" styleCode="Toprule Rrule">6 (1.2%) </td> <td align="center" valign="top" styleCode="Toprule Rrule">8 (1.5%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Dyspnea </td> <td align="center" valign="top" styleCode="Toprule Rrule">6 (1.2%) </td> <td align="center" valign="top" styleCode="Toprule Rrule">9 (1.7%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Vomiting </td> <td align="center" valign="top" styleCode="Toprule Rrule">5 (1.0%) </td> <td align="center" valign="top" styleCode="Toprule Rrule">8 (1.5%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Hematuria </td> <td align="center" valign="top" styleCode="Toprule Rrule">5 (1.0%) </td> <td align="center" valign="top" styleCode="Toprule Rrule">6 (1.1%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Abdominal Pain </td> <td align="center" valign="top" styleCode="Toprule Rrule">4 (0.8%) </td> <td align="center" valign="top" styleCode="Toprule Rrule">6 (1.1%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Diarrhea </td> <td align="center" valign="top" styleCode="Toprule Rrule">3 (0.6%) </td> <td align="center" valign="top" styleCode="Toprule Rrule">7 (1.3%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Anemia </td> <td align="center" valign="top" styleCode="Toprule Rrule">0 </td> <td align="center" valign="top" styleCode="Toprule Rrule">7 (1.3%) </td> </tr> </tbody> </table>

<table ID="t6" width="100%"> <caption>Table 6 Serious Adverse Events Associated With INNOHEP&#xAE; in Clinical Trials </caption> <col width="40.000%" align="left"/> <col width="60.000%" align="left"/> <thead> <tr> <th align="left" valign="top" styleCode="Toprule Lrule Rrule"> <content styleCode="bold">Category</content> </th> <th align="left" valign="top" styleCode="Toprule Rrule"> <content styleCode="bold">Serious Adverse Event</content> </th> </tr> </thead> <tbody> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Bleeding-related </td> <td align="left" valign="top" styleCode="Toprule Rrule">Anorectal bleeding Cerebral/intracranial bleeding Epistaxis Gastrointestinal hemorrhage Hemarthrosis Hematemesis Hematuria Hemopericardium Hemorrhage NOS Injection site bleeding Melena Purpura Retroperitoneal/intra-abdominal bleeding Vaginal hemorrhage Wound hematoma </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Organ dysfunction </td> <td align="left" valign="top" styleCode="Toprule Rrule">Angina pectoris Cardiac arrhythmia Dependent edema Myocardial infarction/coronary thrombosis Thromboembolism </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Fetal/neonatal </td> <td align="left" valign="top" styleCode="Toprule Rrule">Congenital anomaly Fetal death Fetal distress </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Cutaneous </td> <td align="left" valign="top" styleCode="Toprule Rrule">Bullous eruption Erythematous rash Maculopapular rash Skin necrosis </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Hematologic </td> <td align="left" valign="top" styleCode="Toprule Rrule">Granulocytopenia Thrombocytopenia </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Allergic reactions </td> <td align="left" valign="top" styleCode="Toprule Rrule">Allergic reaction </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Injection site reaction </td> <td align="left" valign="top" styleCode="Toprule Rrule">Cellulitis </td> </tr> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule">Neoplastic </td> <td align="left" valign="top" styleCode="Toprule Rrule">Neoplasm </td> </tr> </tbody> </table>