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Safety of intravenous and oral bisphosphonates and compliance with dosing regimens.
Oncologist. 2004; 9 Suppl 4:28-37.O

Abstract

Patients with advanced cancers--particularly breast and prostate cancers--are at high risk for bone metastasis, leading to accelerated bone resorption and clinically significant skeletal morbidity. Bisphosphonates are effective inhibitors of bone resorption and reduce the risk of skeletal complications in patients with bone metastases. The standard routes of administration for bisphosphonates used in clinical practice are either oral or i.v. infusion. Oral administration of bisphosphonates is complicated by poor bioavailability (generally <5%) and poor gastrointestinal tolerability. First-generation bisphosphonates, such as clodronate (Bonefos; Anthra Pharmaceuticals; Princeton, NJ), must be administered at high oral doses (1,600-3,200 mg/day) to achieve therapeutic effects, which leads to poor tolerability and compliance with oral dosing regimens. Infusion of bisphosphonates is associated with dose- and infusion-rate-dependent effects on renal function. In particular, high bisphosphonate doses (e.g., 1,500 mg clodronate) can cause severe renal toxicity unless infused slowly over many hours. In contrast, the newer, more potent bisphosphonates effectively inhibit bone resorption at micromolar concentrations, and the small doses required can be administered via relatively short i.v. infusions without adversely affecting renal function. Zoledronic acid (Zometa; Novartis Pharmaceuticals Corp.; East Hanover, NJ) is a new generation bisphosphonate, and the recommended dose of 4 mg can be safely infused over 15 minutes. The 90-mg dose of pamidronate (Aredia; Novartis Pharmaceuticals Corp.) and the 6-mg dose of ibandronate (Bondronat; Hoffmann-La Roche Inc.; Nutley, NJ) require 1- to 4-hour infusions. Intravenous bisphosphonates require less frequent dosing (once a month) and are generally well tolerated with long-term use in patients with bone metastases. Zoledronic acid has demonstrated the broadest clinical activity in patients with bone metastases.

Authors+Show Affiliations

Department of Oncology and Hematology, University Hospital, via del Pozzo 71, 41100 Modena, Italy. conte.pierfranco@unimore.itNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

15459427

Citation

Conte, PierFranco, and Valentina Guarneri. "Safety of Intravenous and Oral Bisphosphonates and Compliance With Dosing Regimens." The Oncologist, vol. 9 Suppl 4, 2004, pp. 28-37.
Conte P, Guarneri V. Safety of intravenous and oral bisphosphonates and compliance with dosing regimens. Oncologist. 2004;9 Suppl 4:28-37.
Conte, P., & Guarneri, V. (2004). Safety of intravenous and oral bisphosphonates and compliance with dosing regimens. The Oncologist, 9 Suppl 4, 28-37.
Conte P, Guarneri V. Safety of Intravenous and Oral Bisphosphonates and Compliance With Dosing Regimens. Oncologist. 2004;9 Suppl 4:28-37. PubMed PMID: 15459427.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety of intravenous and oral bisphosphonates and compliance with dosing regimens. AU - Conte,PierFranco, AU - Guarneri,Valentina, PY - 2004/10/2/pubmed PY - 2004/12/23/medline PY - 2004/10/2/entrez SP - 28 EP - 37 JF - The oncologist JO - Oncologist VL - 9 Suppl 4 N2 - Patients with advanced cancers--particularly breast and prostate cancers--are at high risk for bone metastasis, leading to accelerated bone resorption and clinically significant skeletal morbidity. Bisphosphonates are effective inhibitors of bone resorption and reduce the risk of skeletal complications in patients with bone metastases. The standard routes of administration for bisphosphonates used in clinical practice are either oral or i.v. infusion. Oral administration of bisphosphonates is complicated by poor bioavailability (generally <5%) and poor gastrointestinal tolerability. First-generation bisphosphonates, such as clodronate (Bonefos; Anthra Pharmaceuticals; Princeton, NJ), must be administered at high oral doses (1,600-3,200 mg/day) to achieve therapeutic effects, which leads to poor tolerability and compliance with oral dosing regimens. Infusion of bisphosphonates is associated with dose- and infusion-rate-dependent effects on renal function. In particular, high bisphosphonate doses (e.g., 1,500 mg clodronate) can cause severe renal toxicity unless infused slowly over many hours. In contrast, the newer, more potent bisphosphonates effectively inhibit bone resorption at micromolar concentrations, and the small doses required can be administered via relatively short i.v. infusions without adversely affecting renal function. Zoledronic acid (Zometa; Novartis Pharmaceuticals Corp.; East Hanover, NJ) is a new generation bisphosphonate, and the recommended dose of 4 mg can be safely infused over 15 minutes. The 90-mg dose of pamidronate (Aredia; Novartis Pharmaceuticals Corp.) and the 6-mg dose of ibandronate (Bondronat; Hoffmann-La Roche Inc.; Nutley, NJ) require 1- to 4-hour infusions. Intravenous bisphosphonates require less frequent dosing (once a month) and are generally well tolerated with long-term use in patients with bone metastases. Zoledronic acid has demonstrated the broadest clinical activity in patients with bone metastases. SN - 1083-7159 UR - https://www.unboundmedicine.com/medline/citation/15459427/Safety_of_intravenous_and_oral_bisphosphonates_and_compliance_with_dosing_regimens_ L2 - https://doi.org/10.1634/theoncologist.9-90004-28 DB - PRIME DP - Unbound Medicine ER -