Didrocal (Etidronate Sodium & Calcium Carbonate) postmenopausal osteoporosis medication ) therapy is a nonhormonal treatment consisting of etidronate disodium administered for 14 days followed by calcium carbonate administered for the next 76 days.
Didrocal (Etidronate Sodium & Calcium Carbonate): Didrocal (Etidronate Sodium & Calcium Carbonate) is a bisphosphonate (diphosphonate) that inhibits bone resorption, primarily through the drug's effect on osteoclasts. Didrocal (Etidronate Sodium & Calcium Carbonate) owes its highly selective bone effects to its ability to adsorb to hydroxyapatite on the bone surface.
For the treatment of established postmenopausal osteoporosis diagnosed by means of objective measuring techniques such as bone densitometry (a bone mineral density of more than 2.67 standard deviations below the young adult mean) or by radiographic evaluation of the spine (³2 vertebral fractures) in women at least 8 years postmenopause. The assessment of vertebral fractures is based upon a minimum 25% reduction in the height of vertebral bodies (anterior, posterior, or central) on lateral radiographs of the spine.
In a minority of patients bone mineral density measurements of the lumbar spine are falsely elevated by the presence of vascular calcification, osteophytes, scoliosis, or facet joint sclerosis. Such abnormalities may affect only certain vertebrae, in which case appropriate densitometric assessment of the nonaffected vertebrae can be performed, or radiographic criteria (minimum 25% reduction in the height of vertebral bodies) for treatment may be relied upon.
Dosage And Administration:
The Didrocal (postmenopausal osteoporosis medication (Etidronate/Calcium) therapy is a cyclical regimen administered in 90-day cycles. Each cycle provides 14 white 400 mg etidronate disodium tablets to be taken once daily for 14 days, followed by 76 blue calcium carbonate tablets to be taken once daily for the next 76 days. Patients should maintain an adequate nutritional intake, including calcium and vitamin D. Data from placebo-controlled clinical studies show a significant increase in bone mass of 4 to 5% (p <0.05%) occurred for up to 12 cycles (3 years) in patients who received DIDROCAL (Etidronate/Calcium) therapy compared with patients receiving calcium supplementation alone. Safety and tolerance, with maintenance of gains in vertebral bone mass, have been established for 20 cycles (5 years) of therapy. Limited data through 7 years of therapy provide support for maintenance of bone mass benefit with biopsy-proven normal bone quality (no evidence of generalized osteomalacia).
The etidronate disodium tablet portion of the DIDROCAL (Etidronate/Calcium) therapy should be administered on an empty stomach, 1 tablet/day with a full glass of water. To aid compliance, it is recommended that patients take the therapy at bedtime, at least 2 hours before or after eating. To maximize absorption of etidronate disodium, patients should not take the following within 2 hours of dosing: food, especially food high in calcium, such as milk or milk products; antacids; vitamins with mineral supplements such as iron; calcium supplements; laxatives containing magnesium.
The calcium carbonate tablet portion of the DIDROCAL (Etidronate/Calcium) therapy may be administered with food and this is recommended for patients with a diagnosis of achlorhydria.
In the clinical studies of Didrocal therapy, serum alkaline phosphatase was shown to decrease 15 to 20% during the first 2 cycles and to maintain the new level with continuing therapy.
The effect of treatment should be assessed by monitoring changes in bone mass. If this is done, then discontinuation of the therapy should be considered if the bone mass does not stabilize or increase after 4 cycles (1 year) of therapy. Patients who attain adequate response to treatment but discontinue treatment for other reasons should be monitored periodically.
The overall safety of the Didrocal postmenopausal osteoporosis medication (Etidronate/Calcium) therapy was evaluated in postmenopausal osteoporotic women enrolled in clinical trials. The 3 pivotal trials were randomized, parallel, double blind, and placebo controlled; 2 of these were multicentre trials conducted in the United States. The most common Didrocal side effects during the first 2 years of the two U.S. trials are listed in Table I. In general, Didrocal side effects in patients were comparable to those in patients who received placebo.
In osteoporosis clinical trials, the most common side effects were diarrhea and nausea.
Didrocal side effects less frequently include flatulence, dyspepsia, abdominal pain, constipation and vomiting. The incidence of these Didrocal side effects was comparable to that with placebo. In addition, 4 Didrocal side effects, headache, gastritis, leg cramps and arthralgia, occurred with a significantly greater incidence in patients who received Didrocal cyclical therapy compared with those who received placebo. All episodes of Didrocal side effects like leg cramps were transient in nature, most occurred at night, and most required no treatment. All patients with arthralgia reported Didrocal side effects likejoint discomfort or pain that was generally mild and related to underlying osteoarthritis.
The numbers of both deaths and withdrawals due to adverse events were similar in the DIDROCAL(Etidronate/Calcium) and placebo groups.
Postmarketing Experience: Other Didrocal side effects that have been reported in postmarketing studies of a number of indications, and were thought to be possibly related to etidronate disodium include the following: alopecia; arthropathies, including arthralgia and arthritis; bone fracture; esophagitis; glossitis; hypersensitivity reactions, including angioedema, skin rashes (such as follicular eruption, macular rash, maculopapular rash), pruritus, Stevens-Johnson syndrome, and urticaria; osteomalacia; neuropsychiatric events, including amnesia, confusion, depression, and hallucination; paresthesias; burning tongue; erythema multiforme; and exacerbation of asthma.
In patients there have been rare reports of Didrocal side effects like leukopenia, agranulocytosis, and pancytopenia. Also, there have been very rare cases of Didrocal side effects like leukemia reported with etidronate use (1/100 000) in ongoing safety surveillance since 1978 encompassing approximately 1.5 million patient-years of treatment. Any causal relationship to either the treatment or to the patients' underlying disease has not been established.
Exacerbation of existing peptic ulcer disease with resulting complications has been a few of the Didrocal side effects reported in a few patients.