McKenna's Pharmacology for Nursing, 2e

266

P A R T 3  Drugs acting on the immune system

Clinically important drug–drug interactions There is an increased risk of toxicity if these drugs are combined with other drugs that are hepatotoxic or nephrotoxic. Extreme care should be used if such combinations are necessary. Other reported drug–drug interactions are drug specific; consult a drug guide or drug handbook. I nterleukin - receptor antagonist An interleukin-receptor antagonist works to block the activity of the interleukins that are released in an inflammatory or immune response. The only available interleukin receptor antagonist is anakinra ( Kineret ). See Table 17.2 for additional information about this drug. Therapeutic actions and indications Anakinra specifically antagonises human interleukin-1 receptors, blocking the activity of interleukin-1. Inter- leukin-1 levels are elevated in response to inflammation or immune reactions and are thought to be responsible for the degradation of cartilage that occurs in rheum­ atoid arthritis. Anakinra is used to reduce the signs and symptoms of moderately to severely active rheumatoid arthritis in people 18 years of age and older who have not responded to the traditional anti-rheumatic drugs. As one of the most common chronic conditions in Australia, arthritis is one of the Australian government’s nine National Health Priority Areas. Data from the 2007–08 National Health Survey suggest that 428,000 Australians are affected by rheumatoid arthritis. For more information on arthritis, see www.aihw.gov.au/ arthritis-and-musculoskeletal-conditions. Pharmacokinetics The recommended dosage is 100 mg/day by subcutane- ous injection. Anakinra is administered by subcutaneous injection and is absorbed slowly, reaching peak effects in 3 to 7 hours. It is metabolised in the tissues with a 4- to 6-hour half-life and is excreted in the urine. Contraindications and cautions Anakinra is contraindicated with any known allergy to E. coli –produced products or to anakinra itself. It should be used with caution during pregnancy and breastfeed- ing because the drug may cross the placenta and enter breast milk . It is also used cautiously in people with renal impairment, immunosuppression or any active infection because these could be exacerbated by the effects of the drug . There is an increased risk of infection whenever this drug is used, and the person needs to be protected

from exposure to infections and monitored closely after any invasive procedures. Immunisations cannot be given while the person is on this drug. Adverse effects Headache, sinusitis, nausea, diarrhoea, upper respira- tory and other infections and injection-site reactions are among the most common adverse effects. Clinically important drug–drug interactions People who are also receiving etanercept ( Enbrel ) must be monitored very closely because severe and even life-threatening infections have occurred. Anakinra should not be combined with abatacept because of the potential for serious infections. M onoclonal antibodies Antibodies that attach to specific receptor sites are being developed to respond to very specific situations. Every year, several new monoclonal antibodies are marketed, showing the rapid pace with which these agents are being developed and approved for clinical use. Monoclonal antibodies include adalimumab ( Humira ), alemtuzumab ( MabCampath ), basiliximab ( Simulect ), bevacizumab ( Avastin ), certolizumab pegol ( Cimzia ), cetuximab ( Erbitux ), erlotinib ( Tarceva ), goli- mumab ( Simponi ), infliximab ( Remicade ), natalizumab ( Tysabri ), omalizumab ( Xolair ), palivizumab ( Synagis ), panitumumab ( Vectibix ), rituximab ( Mabthera ), tocili- zumab ( Actemra ), trastuzumab ( Herceptin, Kadcyla ) and ustekinumab ( Stelara ). Therapeutic actions and indications Adalimumab, certolizumab pegol, golimumab and infliximab are antibodies specific for human tumour necrosis factor. They keep the inflammatory reaction in check by reacting with and deactivating the free-floating tumour necrosis factor released by active leucocytes. Alemtuzumab is an antibody specific for lympho- cytereceptor sites. Basiliximab is specific to interleukin-2 receptor sites on activated T lymphocytes; it reacts with those sites and blocks cellular response to allograft transplants. Cetuximab is an antibody specific to epidermal growth factor receptor sites. Trastuzumab also reacts with human epidermal growth factor receptor 2 (HER2), a genetic defect that is seen in certain metastatic breast cancers. It is used in the treatment of metastatic breast cancer in tumours that over-express HER2. Erlotinib, bevacizumab and panitumumab are effec- tive against specific malignant receptor sites.