Bisphosphonates injectable

There is considerable interest in using injectable bisphosphonates, such as pamidronate and zoledronic acid, in patients unable to tolerate or absorb oral bisphosphonates. Zoledronic acid in particular has a potential advantage of once-yearly dosing. Currently, neither drug has received FDA approval for this indication. Ibandronate has recently been approved for this indication. 

The most common bisphosphonate adverse effects are nausea, abdominal pain, and dyspepsia. Esophageal, gastric, or duodenal irritation, perforation, ulceration, or bleeding may occur when administration directions are not followed or when bisphosphonates are prescribed for patients with contraindications. The most common adverse effects of IV bisphosphonates include fever, flu-like symptoms, and local injection-site reactions. Osteonecrosis of the jaw occurs rarely if it develops, oral chlorhexidine washes, systemic antibiotics, and systemic analgesics are used based on severity. 

Metastatic bone disease (MBD) is characterized by very high levels of bone turnover in regions proximal to the tumour [33]. Bone resorption inhibitors such as bisphosphonates represent the current standard of care for the treatment of bone metastases primarily due to breast or prostate cancer and multiple myeloma. It has been proposed that other strong anti-resorptives such as a Cat K inhibitor could be useful in the treatment of bone metastases. Evidence for this has been presented in the form of a preclinical MBD model in which human breast cancer cells are implanted into nude mice. Treatment with a Cat K inhibitor gave a significantly lower area of breast cancer-mediated osteolytic lesions in the tibia [34]. In a separate study, the efficacy of a Cat K inhibitor in the reduction in tumour-induced osteolysis was found to be enhanced in the presence of the bisphosphonate zolendronic acid [35,36]. When prostate cancer cells were injected into the tibia of SCID mice, treatment with a Cat K inhibitor both prevented and diminished the progression of cancer growth in bone [37]. 

Bonviva consists of ibandronic acid, a bisphosphonate and is available as 150 mg tablets and 1 mg/mL injection. Patients receiving the oral formulation for the treatment of postmenopausal osteoporosis are advised to take one tablet once a month. Absorption of bisphosphonates from the gastrointestinal tract may be effected by food or other administered drugs. Therefore patients are advised to take the Bonviva 150 mg tablet at least 1 hour before breakfast or another oral medicine and to continue standing or sitting upright for at least 1 hour after administration. 

With the exception of the possible development of a hypervitaminosis associated with high-dose administration of vitamin D2 or D3, the compounds discussed in this chapter are relatively safe. Allergic reactions to the injection of calcitonin and PTH have occurred and chronic use of some bisphosphonates has been associated with the development of osteomalacia. The principal side effects of intravenous bisphosphonates are mild and include low-grade fever and transient increases in serum creatinine and phosphate levels. Oral bisphosphonates are poorly absorbed and can cause esophageal and gastric ulceration. They should be taken on an empty stomach the individual must remain upright for 30 minutes after ingestion. 

Calcitonin is also another option that may be used if a patient cannot take bisphosphonates. It is administered intranasally or via subcutaneous or intramuscular injection. It is usually only prescribed in specialist clinics. 

First, Mrs TY should be advised that teriparatide is only available as an injection and, therefore, Mrs TY may not find this an acceptable route of administration. Second, the NICE guidelines state that teriparatide should only be used in postmenopausal women who are unable to take bisphosphonates or strontium or who have had an unsatisfactory response bisphosphonates. They must also have experienced more than two fractures and have a T-score which fits into the range specified in the NICE guidance (NICE 2008). 

Daily calcitonin or PTH administration is an effective alternative to bisphosphonates for treating osteoporosis, but much less convenient. Calcitonin and PTH are destroyed by proteases in the intestine and also by proteases in the bloodstream and must be given by daily injection. By contrast, bisphosphonates are not only stable after ingestion, but they also bind to the surface of calcified tissues and are not easily removed. Bisphosphonates can be administered orally, weekly or even monthly. (See Sect. 10.2.3). 

Metal metabolism Currently there are no recommendations for monitoring serum calcium in patients taking teriparatide. Symptomatic hypercalcemia is rare but has been reported. Patients should be warned of the potential for hypercalcemia and testing should be guided by symptoms. In studies of the use of teriparatide 20 micrograms/ day in patients with osteoporosis with and without prior bisphosphonates [63 ] and in patients with severe periodontal disease [64 ] injection site reactions and small increases in serum calcium were attributed to teriparatide. The serum calcium rose above the reference range in about 5% of patients on at least one occasion but was not associated with symptoms and did not lead to drug withdrawal. 

Figure 8.121 Separation of selected bisphosphonates, excipients, and anionic rate 20pL/min detection suppressed conductivity injection volume lOpL ...

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