Drugs in focus

Dabigatran (Pradaxa) for preventing venous thromboembolism after hip or knee replacement surgery

• Dabigatran is a direct thrombin inhibitor oral anticoagulant.
• Dabigatran is approved for short-term use after hip or knee replacement surgery.
• The recommended duration of therapy is 10 days after knee replacement and 28–35 days after hip replacement.
• Dabigatran appears to have similar efficacy to that of enoxaparin 40 mg once daily after knee or hip replacement, although a clinically important difference between the two drugs cannot be completely ruled out.
• Dabigatran, rivaroxaban and fondaparinux all appear to have broadly similar efficacy although this has not been tested in head-to-head trials.
• Bleeding rates with dabigatran are similar to those with enoxaparin.
• Advise patients about the risk of bleeding.
• Dabigatran is contraindicated in hepatic impairment that is expected to have an impact on survival or in severe renal impairment (creatinine clearance < 30 mL/min).

Rivaroxaban (Xarelto) for preventing venous thromboembolism after hip or knee replacement surgery:

• Rivaroxaban is an oral anticoagulant and the first direct factor Xa inhibitor.
• Rivaroxaban has only been evaluated for use in preventing deep vein thrombosis and pulmonary embolism after elective total hip or total knee replacement surgery.
• Duration of therapy is 14 days after knee replacement or 35 days after hip replacement, and no longer.
• Dose adjustment, dose titration and monitoring of prothrombin time are not required.
• There are only small differences in efficacy and safety between rivaroxaban, low molecular weight heparins, fondaparinux (Arixtra) and dabigatran (Pradaxa).
• Advise patients about the risk of bleeding.
• Rivaroxaban is contraindicated in renal impairment (creatinine clearance < 15 mL/min), moderate and severe hepatic impairment with elevated INR, or with azole antifungals or HIV-protease inhibitors. These increase blood levels of rivaroxaban and therefore bleeding risk.

Methylnaltrexone injection (Relistor) for opioid-induced constipation in palliative care

• Methylnaltrexone is an option for treating opioid-induced constipation in people receiving palliative care who have not responded to adequately titrated laxatives.
• Methylnaltrexone increases bowel movements without reversing analgesia.
• Methylnaltrexone is not a treatment for constipation caused by factors other than opioids.
• Exclude bowel obstruction before using methylnaltrexone.
• Around 50–60% of people with opioid-induced constipation experience a bowel movement within 4 hours of a single dose of methylnaltrexone. However, around 30% of people may not respond within 24 hours of a single dose.
• The recommended dose varies with weight.
• Only use methylnaltrexone in addition to other therapies that prevent or treat opioid-induced constipation.
• Ensure that toileting facilities are accessible, as bowel movements may occur within 30 minutes of an injection.
• Do not use methylnaltrexone more than once every 24 hours.
• Mild to moderate gastrointestinal adverse effects are common.

Rizatriptan (Maxalt) 10 mg wafers for migraine, and revised listings for other 5HT₁ agonists (‘triptans’)