Dalteparin Sodium and Probuphine

• Generic Name: dalteparin
• Dosage Forms: n.a.
• Other Brand Names: Fragmin

Used to reduce the risk of acute cardiac ischemic events (death, MI) in patients with unstable angina or NSTEMI (i.e., non-ST-segment-elevation acute coronary syndromes [NSTE ACS]). Used concurrently with aspirin and/or other standard therapy (e.g., nitrates, β-adrenergic blockers, clopidogrel, platelet glycoprotein [GP] IIb/IIIa-receptor inhibitors).

If an LMWH is selected for initial parenteral anticoagulation in patients with NSTE ACS, the American Heart Association (AHA) and American College of Cardiology Foundation (ACCF) recommend the use of enoxaparin; other parenteral anticoagulants with established efficacy include heparin, bivalirudin (only in patients being managed with an early invasive strategy), and fondaparinux.

Thromboprophylaxis in Hip-Replacement, Knee-Replacement, or Hip-Fracture Surgery

Prevention of postoperative DVT, which may lead to PE, in patients undergoing hip-replacement surgery.

LMWHs also have been used for prophylaxis of DVT and/or PE in patients undergoing total knee-replacement and hip-fracture surgery.

ACCP recommends routine thromboprophylaxis with a pharmacologic (e.g., LMWH) and/or mechanical method in all patients undergoing major orthopedic surgery because of high risk of postoperative venous thromboembolism; continue thromboprophylaxis for at least 10–14 days, and possibly for up to 35 days after surgery.

Several antithrombotic agents (e.g., LMWHs, fondaparinux, low-dose heparin, warfarin, aspirin) are recommended by ACCP for pharmacologic prophylaxis during major orthopedic surgery. When selecting an appropriate thromboprophylaxis regimen, consider factors such as relative efficacy, safety, logistics, and compliance.

Thromboprophylaxis in General/Abdominal Surgery

Prevention of postoperative DVT, which may lead to PE, in patients undergoing general/abdominal surgery who are at risk for thromboembolic complications.

ACCP recommends pharmacologic (e.g., LMWHs) and/or nonpharmacologic/mechanical (e.g., intermittent pneumatic compression) methods of thromboprophylaxis in patients undergoing general surgery, including abdominal, GI, gynecologic, and urologic surgery, according to the patient’s risk of thromboembolism and bleeding. In general, pharmacologic prophylaxis is recommended in patients with high (and possibly moderate) risk of venous thromboembolism who do not have a high risk of bleeding, while mechanical methods are suggested in patients who require thromboprophylaxis but have a high risk of bleeding.

If pharmacologic prophylaxis is used in patients undergoing general surgery, ACCP states that an LMWH or low-dose heparin is preferred.

Because risk of venous thromboembolism is particularly high in patients undergoing abdominal or pelvic surgery for cancer, extended (4 weeks) prophylaxis with an LMWH is recommended in such patients.

ACCP states that the recommendations for use of antithrombotic agents in general surgery patients can be applied to patients undergoing bariatric, vascular, and plastic/reconstructive surgery.

Medical Conditions Predisposing to Thromboembolism

Prevention of DVT, which may lead to PE, in patients with severely restricted mobility during acute illness.

In general, pharmacologic thromboprophylaxis recommended only in patients considered to be at high risk of venous thromboembolism.

ACCP recommends anticoagulant prophylaxis (e.g., LMWH) in acutely ill, hospitalized medical patients at increased risk of thrombosis who are not actively bleeding and do not have an increased risk of bleeding. Continued thromboprophylaxis suggested for 6–21 days until full mobility is restored or until hospital discharge, whichever comes first.

Use of LMWHs also suggested by ACCP for pharmacologic thromboprophylaxis in critically ill patients (e.g., those in an intensive care unit [ICU]) who are not actively bleeding and do not have risk factors for bleeding.

Risk of venous thromboembolism particularly high in patients with cancer. Use of LMWH prophylaxis suggested by ACCP in cancer outpatients with solid tumors who have additional risk factors for thromboembolism provided risk of bleeding is low.

Thromboprophylaxis in Cardiac Surgery

Mechanical methods of prophylaxis generally recommended in patients undergoing cardiac surgery; however, ACCP states that an LMWH may be considered for thromboprophylaxis in cardiac surgery patients with a complicated postoperative course.

Thromboprophylaxis in Thoracic Surgery

Pharmacologic thromboprophylaxis (e.g., LMWH) recommended by ACCP in patients undergoing thoracic surgery who are at high risk of venous thromboembolism, provided risk of bleeding is low.

Thromboprophylaxis in Neurosurgery

LMWHs have been used for prevention of venous thromboembolism in patients undergoing craniotomy; however, benefits of such prophylaxis may be outweighed by possible increased risk of intracranial hemorrhage. ACCP states that LMWH prophylaxis may be considered in patients at very high risk of thromboembolism (e.g., those undergoing craniotomy for malignant disease) once adequate hemostasis established and risk of bleeding decreases.

Thromboprophylaxis with LMWHs also may be considered in high-risk patients undergoing spinal surgery (e.g., those with malignancy or those undergoing surgery with a combined anterior-posterior approach) once adequate hemostasis established and risk of bleeding decreases.

Thromboprophylaxis in Trauma

LMWHs may be used for thromboprophylaxis in patients with major trauma. For major trauma patients at high risk of venous thromboembolism, including those with acute spinal cord injury, traumatic brain injury, or spinal surgery for trauma, ACCP suggests use of both a pharmacologic and mechanical method of prophylaxis unless contraindications exist.

Extended Treatment of Acute Venous Thromboembolism in Cancer Patients

Used for extended (6 months' duration) treatment of symptomatic DVT and/or PE in patients with cancer to reduce recurrence (secondary prevention) of venous thromboembolism. Manufacturer states that safety and efficacy of treatment durations >6 months not established.

Acute Venous Thromboembolism

Manufacturer states that dalteparin not indicated for the acute treatment of venous thromboembolism; however, has been recommended by ACCP as an appropriate option for initial treatment of acute proximal DVT and/or PE.

LMWHs or fondaparinux generally preferred over heparin for initial treatment of acute venous thromboembolism; however, heparin may be preferred in patients with renal impairment. IV heparin also may be preferred over LMWHs in patients with PE in whom thrombolytic therapy is being considered or if there is concern about adequate sub-Q absorption.

For long-term anticoagulant therapy, warfarin generally preferred in patients without cancer; however, ACCP suggests use of an LMWH in patients with cancer because of a possible reduced response to warfarin.

Continue anticoagulant therapy for ≥3 months and possibly longer depending on individual clinical situation.

Venous Thromboembolism in Pediatric Patients

An LMWH has been used for treatment and secondary prevention of venous thromboembolism in pediatric patients; venous thromboembolism usually occurs secondary to an identifiable risk factor (e.g., presence of central venous access device in such patients).

Recommendations regarding use of antithrombotic therapy in children generally based on extrapolation from adult guidelines.

ACCP recommends an LMWH or heparin for both initial and ongoing treatment of venous thromboembolism in children. Potential advantages of an LMWH over heparin include reduced need for monitoring, lack of drug or dietary interactions, reduced risk of heparin-induced thrombocytopenia (HIT), and possible reduced risk of osteoporosis.

In children with central venous catheter-related thromboembolism, ACCP recommends removal of catheter if no longer functioning or required; at least 3–5 days of therapeutic anticoagulation is suggested prior to removal. If such catheters must remain in place, ACCP suggests anticoagulant therapy until catheter is removed.

Treatment of Superficial Vein Thrombosis

LMWHs also have been used for spontaneous superficial vein thrombosis (superficial thrombophlebitis); ACCP suggests use of prophylactic dosages for 45 days in patients with superficial vein thrombosis of ≥5 cm in length.

Treatment of Renal Vein Thrombosis

Although use of anticoagulant therapy for renal vein thrombosis (the most common cause of spontaneous venous thromboembolism in neonates) is controversial, LMWHs are suggested by ACCP as a possible treatment option.

Thromboprophylaxis in Acute Ischemic Stroke

Heparin anticoagulants (i.e., LMWHs or heparin) have been used for thromboprophylaxis in selected patients with acute ischemic stroke; those with additional risk factors for venous thromboembolism are more likely to benefit from such prophylaxis.

ACCP suggests thromboprophylaxis with an LMWH, sub-Q heparin, or intermittent pneumatic compression in patients with acute ischemic stroke and restricted mobility; LMWH is preferred over heparin.

Prophylactic-dose heparin (heparin or an LMWH) usually initiated within 48 hours of onset of stroke and is continued throughout hospital stay until patient regains mobility; do not administer within the first 24 hours after thrombolytic therapy.

LMWHs also recommended by ACCP as an option for initial management of acute arterial ischemic stroke in children until dissection and embolic causes have been excluded. If arterial ischemic stroke is associated with dissection or a cardioembolic origin, continued anticoagulant therapy suggested.

In children with acute arterial ischemic stroke secondary to non-Moyamoya vasculopathy, ACCP recommends ongoing antithrombotic therapy (e.g., with an LMWH) for 3 months.

LMWHs may be considered in neonates with a first episode of arterial ischemic stroke associated with a documented cardioembolic source.

Thromboembolism During Pregnancy

Used during pregnancy for prevention and treatment of venous thromboembolism and for prevention and treatment of systemic embolism associated with mechanical heart valves. (See Prevention and Treatment of Thromboembolism During Pregnancy under Dosage and Administration.)

Also has been used in combination with low-dose aspirin for prevention of recurrent pregnancy loss in women with antiphospholipid antibody (APLA) syndrome.

LMWHs (rather than heparin or warfarin) are recommended by ACCP for prevention and treatment of thromboembolism during pregnancy.

In pregnant women with an acute venous thromboembolic event, ACCP recommends an LMWH for initial treatment and secondary prevention throughout the remainder of the pregnancy. To prevent recurrence, postpartum anticoagulation (for ≥6 weeks and for a total duration of ≥3 months) is suggested.

In general, thromboprophylaxis (e.g., with an LMWH) is suggested during the antepartum period only in pregnant women who have a history of thromboembolism and are considered to be at moderate to high risk of recurrent events (e.g., those with a single episode of unprovoked venous thromboembolism, pregnancy- or estrogen-related venous thromboembolism, history of multiple unprovoked events).

Postpartum thromboprophylaxis for 6 weeks suggested in all pregnant women with a prior venous thromboembolic event; an LMWH (in prophylactic or intermediate dosages) or warfarin (INR 2–3) may be used for such prophylaxis.

ACCP suggests antepartum and postpartum prophylaxis with an LMWH in some pregnant women with high-risk hereditary thrombophilias (e.g., homozygous genetic mutations for factor V Leiden or prothrombin G20210A) who have not experienced a prior venous thromboembolic event, but have a family history of thromboembolism.

Discontinue LMWH therapy ≥24 hours prior to induction of labor or cesarean section (or expected time of neuraxial anesthesia) to avoid an unwanted anticoagulant effect on fetus.

Cardioversion of Atrial Fibrillation/Flutter

LMWHs have been used for prevention of stroke and systemic embolism in patients with atrial fibrillation or atrial/flutter undergoing electrical or pharmacologic cardioversion.

As an alternative to prolonged anticoagulation (e.g., usually with warfarin) prior to cardioversion in patients with atrial fibrillation lasting >48 hours or of unknown duration, an LMWH (in therapeutic dosages) may be used at the time of transesophageal echocardiography (TEE), followed by cardioversion within 24 hours if no thrombus is detected.

In patients with atrial fibrillation of short duration (e.g., ≤48 hours), an LMWH (in therapeutic dosages) may be used at presentation, followed by immediate cardioversion.

In patients with hemodynamic instability who require urgent cardioversion, ACCP suggests administration of a parenteral anticoagulant (in therapeutic dosages) prior to cardioversion if possible; however, such anticoagulant therapy must not delay any emergency intervention.

After successful cardioversion to sinus rhythm, all patients should receive therapeutic anticoagulation for ≥4 weeks.

Thromboprophylaxis in Patients with Prosthetic Heart Valves

Used during conversion to maintenance therapy with warfarin to reduce the incidence of thromboembolism in patients with prosthetic mechanical heart valves.

ACCP suggests bridging anticoagulation (an LMWH in either prophylactic or therapeutic dosages or IV heparin in prophylactic dosages) during the early postoperative period after insertion of a mechanical heart valve in patients without bleeding risk, until an adequate response to warfarin is obtained.

Also may be used for bridging anticoagulation in patients with a mechanical heart valve in whom therapy with warfarin must be temporarily discontinued (e.g., those undergoing major surgery).

Has been used for thromboprophylaxis in pregnant women with prosthetic mechanical heart valves. (See Thromboembolism During Pregnancy under Uses.)

Treatment of Cerebral Venous Sinus Thrombosis

May be used for the treatment of acute cerebral venous sinus (sinovenous) thrombosis in adults. Once patient stabilized, may convert to coumarin anticoagulant therapy.

Reasonable to use full-dose LMWH rather than heparin for treatment of acute cerebral venous sinus thrombosis during pregnancy. Prophylaxis with an LMWH during pregnancy and the postpartum period is reasonable in women with history of cerebral venous sinus thrombosis.

Recommended by ACCP as an option for initial and follow-up anticoagulation in children with cerebral venous sinus thrombosis without substantial intracranial hemorrhage. Also has been suggested for use in children with substantial intracranial hemorrhage.

LMWHs also suggested by ACCP as a treatment option for neonates with cerebral sinovenous thrombosis.

Perioperative Antithrombotic Prophylaxis

ACCP suggests use of an LMWH or IV heparin during temporary interruption of warfarin therapy (bridging anticoagulation) in selected patients with venous thromboembolism, atrial fibrillation, or mechanical prosthetic heart valves undergoing surgery or other invasive procedures; use and type of bridging anticoagulation depend on patients' risk of developing thromboembolism without warfarin therapy.

In general, bridging anticoagulation is suggested in such patients who are considered to be at particularly high risk of venous thromboembolism without oral anticoagulant therapy.

• Generic Name: buprenorphine
• Dosage Forms: implant
• Other Brand Names: Probuphine, Belbuca, Buprenex, Butrans, Sublocade, Subutex

Probuphine (buprenorphine) is an opioid medication. An opioid is sometimes called a narcotic.

Probuphine implants are used to treat narcotic addiction in certain people whose addiction has already been treated and controlled with other forms of buprenorphine (such as Subutex or Suboxone). Probuphine implants are for adults and teenagers who are at least 16 years old.

Probuphine implants are available only from a certified pharmacy under a special program. You must be registered in the program and understand the risks and benefits of using this medicine. The implants are not for use as a pain medication.