Emily Tesar; Jane M. Armer. Rehabilitation Oncology 2018; 36:7-12

Main findings

• Little is known about the effect that certain medications have on a known diagnosis of lymphedema.
• There are more than 900 medications that can cause fluid retention and oedema as a side effect, there is a significant lack of literature outlining the effects of medications on secondary lymphedema, specifically lymphedema following breast cancer treatment.
• Certain types of drug therapy can result in an increase in peripheral oedema. Typically, when a person develops oedema secondary to a medication, swelling develops gradually with a generalized presentation throughout the body or it develops in limbs bilaterally.
• Knowing that oedema is caused by a disruption in the balance of capillary filtration and drainage, individuals with lymphatic damage to a particular limb will often develop this otherwise generalized oedema unilaterally (in the affected limb). Both limbs might increase in size, but a limb with lymphatic or venous damage will often present larger in size.
• Anticancer agents docetaxel has fluid retention as a common cumulative toxicity for this drug and this side effect can often limit both the dose and duration of treatment. Statistics show that 44% to 65% of patients treated with docetaxel experience significant fluid retention despite premedication. The pathophysiological mechanism for fluid retention in docetaxel, as with many taxoids, is thought to pertain directly to the capillary filtration/lymphatic drainage system.
• Calcium channel blockers have been known to cause peripheral oedema and, depending on the dose and specific drug, peripheral oedema can have an incidence rate of anywhere from 5% to 70%. Calcium channel blocker–associated oedema results from a disruption in capillary filtration flow. Essentially, there is precapillary dilation without compensatory dilation in the post– capillary circulation. In order for subsequent oedema to develop, this movement of fluid in the capillary circulation must exceed the overall capacity of the lymphatic or venous draining system. It makes sense, then, that limbs with impaired lymphatic flow would succumb to oedema more rapidly than unaffected limbs. Research shows that the phenomenon of oedema with this medication tends to be higher in women and presents gradually, thereby making it difficult to attribute swelling to the calcium channel blocker. The most clinically effective way to manage this side effect is to either change the type of calcium channel blocker or cease this classification of drug altogether. More research in this area is required.
• Nonsteroidal Anti-Inflammatories can influence sodium/water retention due to the drugs renal effect. NSAIDs could potentially increase tubular reabsorption of sodium, and individuals who are already at risk for oedema (e.g. underlying lymphedema) experience these symptoms more frequently than those without an underlying disease process or injury. It is estimated that fluid retention is seen in up to 25% of patients who are taking NSAIDs.
• Anticonvulsants/Antineuralgics. Under this heading are the drugs that treat neuropathic pain. Two common medications seen are pregabalin (Lyrica) and gabapentin (Neurontin). The risk of fluid retention with this type of medication is high. With pregabalin, the prevalence of peripheral oedema is reported up to 15% of the time.
• Antidepressants. There has been some reports of fluid retention after taking trazadone. The mechanism for this is unclear.
• Antidiabetics. Many medications used to treat diabetes cause peripheral oedema, in particular rosiglitazone (Avandia) and pioglitazone (Actos).These medications are a type of thiazolidinediones, medications used in the treatment of type II diabetes. In patients who are taking a thiazolidinedione as singular therapy, oedema is reported at an incidence rate of 5% to 10%. However, thiazolidinediones paired with daily insulin have an oedema incidence rate of 15% to 20%. The mechanism is unclear but recent research suggests that fluid retention results from increases in tubular sodium and water retention.