Orgaran

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Studies on this medicine have been done only in adult patients, and there is no specific information comparing use of danaparoid in children with use in other age groups.

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Bleeding problems or
• Heart infection or
• High blood pressure (hypertension) or
• Kidney disease or
• Stomach or intestinal ulcer (active) or
• Stroke—The risk of bleeding may be increased.

Also, tell your doctor if you have received danaparoid before and had a reaction to it called thrombocytopenia (a low platelet count in the blood), or if new blood clots formed while you were receiving the medicine.

In addition, tell your doctor if you have recently had medical surgery. This may increase the risk of serious bleeding when you are taking danaparoid.

Danaparoid is used to prevent deep venous thrombosis, a condition in which harmful blood clots form in the blood vessels of the legs. These blood clots can travel to the lungs and can become lodged in the blood vessels of the lungs, causing a condition called pulmonary embolism. Danaparoid is used for several days after hip replacement surgery, while you are unable to walk. It is during this time that blood clots are most likely to form. Danaparoid also may be used for other conditions as determined by your doctor.

Danaparoid was available only with your doctor's prescription.

Organon, Inc. discontinued manufacturing Orgaran® (danaparoid) on August 14, 2002 .

If you are using danaparoid at home, your health care professional will teach you how to inject yourself with the medicine. Be sure to follow the directions carefully. Check with your health care professional if you have any problems using the medicine.

Put used syringes in a puncture-resistant, disposable container, or dispose of them as directed by your health care professional.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For injection dosage form:
  • For prevention of deep venous thrombosis (leg clots) and pulmonary embolism (lung clots):
    • Adults—750 anti-factor Xa units, injected under the skin, two times a day for up to fourteen days after surgery.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Stop taking this medicine and get emergency help immediately if any of the following effects occur:

• Bleeding gums
• coughing up blood
• difficulty in breathing or swallowing
• dizziness
• headache
• increased menstrual flow or vaginal bleeding
• nosebleeds
• paralysis
• prolonged bleeding from cuts
• red or black, tarry stools
• red or dark brown urine
• shortness of breath
• unexplained pain, swelling, or discomfort, especially in the chest, abdomen, joints, or muscles
• unusual bruising
• vomiting of blood or coffee ground–like material; weakness

• Back pain
• burning, pricking, tickling, or tingling sensation
• leg weakness
• numbness
• problems with bowel or bladder function

Check with your doctor as soon as possible if any of the following side effects occur:

• Fever

• Skin rash

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Pain at injection site

• Constipation
• nausea

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Applies to danaparoid: subcutaneous solution

Hematologic

A fatal bleeding episode has been reported in a patient with renal insufficiency. Overall, probable or possible danaparoid-associated mortality due to bleeding, thrombosis, or septic shock occurred in 7 of 230 patients (3.0%).

Danaparoid has shown a much lower in vitro cross-reactivity with heparin-induced antibody than some low molecular weight heparins (6.3% versus 95%, respectively). In fresh patient plasma, 14 of 143 (9.8%) of danaparoid (the active ingredient contained in Orgaran) tests showed positive cross-reactivity with heparin-induced antibody.

Patients previously exposed to unfractionated heparin or a low-molecular-weight heparin appear to be more susceptible to developing heparin-induced thrombocytopenia (HIT) and HIT-related thromboembolic complications (e.g., transient ischemic attack, stroke) than those who were never exposed.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated, prothrombotic reaction that occurs in 0.5% to 5% of patients treated with unfractionated heparin and in less than 1% of patients treated with a low molecular weight heparin (LMWH). The decrease in platelet count associated with HIT usually begins 5 to 14 days after starting heparin. However, patients with a previous exposure to heparin may have an abrupt decrease in platelets upon restarting heparin. Patients with LMWH-induced HIT exhibit a longer delay in the onset of symptoms compared with those who develop it from unfractionated heparin. Following discontinuation, platelet counts begin to recover within 4 days, but may take more than 2 weeks in patients with high-titer HIT antibodies. Thrombocytopenia is caused by heparin-dependent IgG antibodies that bind to a specific platelet protein, platelet factor 4 (PF4). The heparin-PF4-IgG immune complex binds to platelets causing platelet activation. The activated platelets cause release of platelet-derived procoagulant microparticles, which accelerate coagulation reactions and generates thrombin. LMWHs have a high cross-reactivity with circulating heparin-PF4-IgG immune complex. Factors associated with a higher risk for developing HIT-associated thrombosis include women, nonwhites, severity of thrombocytopenia, and lower body weight. Complications associated with HIT include exacerbation of venous thromboembolism, arterial or venous thrombosis, limb gangrene, stroke, and skin necrosis. The antibodies that cause HIT will usually disappear after approximately 3 months; therefore, use of unfractionated heparin or LMWH may be considered in a patient with a history of HIT if the antibody test is negative.[Ref]

Patients undergoing spinal/epidural anesthesia or puncture and anticoagulated or scheduled to be anticoagulated with low molecular weight heparins or heparinoids are at risk for long-term or permanent paralysis due to epidural or spinal hematoma. The risk of these events is increased by the use of indwelling epidural catheters or by concomitant use of platelet inhibitors, other anticoagulants, or drugs that affect hemostasis.

Hematologic adverse effects that have been reported include hemorrhage (intraoperative and postoperative blood loss), bruising and wound hematoma. Incidence of bleeding complications appear to be similar to heparin (approximately 10%). Thrombocytopenia has been reported to occur significantly less than with heparin or low molecular weight heparins. Danaparoid is considered a useful substitute for heparin or low molecular weight heparins in thrombocytopenia for the majority of patients who require immediate anticoagulation, although thrombocytopenia has been reported in patients receiving danaparoid.[Ref]

Local

Local effects may include injection site discomfort and bruising. The incidence of bruising appears to be less with heparin.[Ref]

Hypersensitivity

Hypersensitivity reactions have included a Type IV (IgE) delayed hypersensitivity cutaneous reaction due to subcutaneous injection danaparoid (the active ingredient contained in Orgaran) The reaction was described as a red, itchy, indurated and erythematous.[Ref]

Some side effects of Orgaran may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.