Brands, Medical Use, Clinical Data
- Antihypocalcemic Agents
Brands / Synonyms
Actonel; Pyridine N-oxide; Pyridostigmine bromide; Pyridostigmine bromine; Risedronate sodium; Risedronic acid
For the treatment of Paget's disease of the bone (osteitis deformans), postmenopausal and glucocorticoid-induced osteoporosis
Risedronate is a pyridinyl bisphosphonate that inhibits osteoclast-mediated bone resorption and modulates bone metabolism and is indicated for the treatment and prevention of osteoporosis in postmenopausal women.
Mechanism of Action
The action of risedronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Risedronate also targets farnesyl pyrophosphate (FPP) synthase. Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass.
Rapid absorption (~1 hr) after an oral dose, occurs throughout the upper gastrointestinal tract
Side effects include abdominal pain, anxiety, back pain, belching, bladder irritation, bone disorders and pain, bronchitis, bursitis, cataracts, chest pain, colitis, constipation, depression, diarrhea, difficulty breathing, dizziness, dry eyes, eye infection, flu-like symptoms, gas, headache, high blood pressure, infection, insomnia, itching, joint disorders and pain, leg cramps, muscle pain, muscle weakness, nausea, neck pain, nerve pain, pain, pneumonia, rash, ringing in ears, sinus problems, sore throat, stomach bleeding, stuffy or runny nose, swelling, tendon problems, tumor, ulcers, urinary tract infection, vertigo, vision problems, and weakness.
Biotrnasformation / Drug Metabolism
No evidence found for metabolization of risedronate in humans or mammals
· Known hypersensitivity to any component of this product
· Inability to stand or sit upright for at least 30 minutes
No specific drug-drug interaction studies were performed. Risedronate is not metabolized and does not
induce or inhibit hepatic microsomal drug-metabolizing enzymes (Cytochrome P450).
Co-administration of ACTONEL and calcium, antacids, or oral medications containing divalent cations
will interfere with the absorption of ACTONEL.
Hormone Replacement Therapy
One study of about 500 early postmenopausal women has been conducted to date in which treatment with
ACTONEL (5 mg/day) plus estrogen replacement therapy was compared to estrogen replacement therapy alone. Exposure to
study drugs was approximately 12 to 18 months and the primary endpoint was change in BMD. If considered appropriate,
ACTONEL may be used concomitantly with hormone replacement therapy.
Aspirin/Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Of over 5700 patients enrolled in the ACTONEL Phase 3 osteoporosis studies, aspirin use was reported
by 31% of patients, 24% of whom were regular users (3 or more days per week). Forty-eight percent of patients
reported NSAID use, 21% of whom were regular users. Among regular aspirin or NSAID users, the incidence of upper
gastrointestinal adverse experiences in ACTONEL-treated patients (24.5%) was similar to that in placebo-treated
H2 Blockers and Proton Pump Inhibitors (PPIs)
Of over 5700 patients enrolled in the ACTONEL Phase 3 osteoporosis studies, 21% used H2
blockers and/or PPIs. Among these patients, the incidence of upper gastrointestinal adverse experiences in the
ACTONEL-treated patients was similar to that in placebo-treated patients.
Drug/Laboratory Test Interactions
Bisphosphonates are known to interfere with the use of bone-imaging agents. Specific studies with
ACTONEL have not been performed.