Bisphonates include-

Alendronate, Etidronate, Pamidronate Refer Alendronate

Interacting drugs- summary

+ Alendronate

Ranitidine/ +

 IV ranitidine doubled alendronate bioavailability. The clinical significance unknown 

Calcium Supplement +

 product containing calcium and other multi-valent cations interfere with  alendronate and etidronate absorptin

Alendronate + Apirin

Risk of GI adverse effects associated with aspirin increased with alendroate doses > 10mg/day

Calcium supplements, iron and antacids may hinder absorption of alendronate. Avoid concomittant use with aspirin or NSAIDs for they may increase the incidence of adverse effects

Post menopausal osteoporosis

Cardiovascular

Atrial fibrillation, hypotension, syncope, tachycardia, atrial flutter, cardiac failure

GI-

Nausea, anorexia, constipation, GI hemorrhage, abdominal pain, stomatitis, diarrhea, dyspepsia, vomiting

CNS-

Somnolence, insomnia, pschosis, convulsion Hemic/lymphatic- anemia, leukopenia, thrombocytopenia

Lab abnormalities-

Hypophosphatemia, hypokalemia, hypomagnesiumia, hypocalcemia, abnormal hepatic function

Other-

Hypothyroidism, myalgia, uremia, taste perversion

Hypocalcaemia, abnormalites of oesophagus and other factors which delay emptying (stricture or achalasia), severe renal impairment, hypersensitivity, pregnancy and lactation, and inability to stand or sit upright for 30 min.

Special precautions:

In patients with upper gastro-intestinal disorders such as; esophageal symptoms, gastritis, duodenitis, or ulcers, extreme caution is warranted while administering alderonate.

Correct disturbances of calcium and mineral metabolism, if present ie., vitamin deficiency, hypocalcemia,between starting alendronate therapy.

Before treating postmenopausal osteoporosis with alendronate exclude other possible causes of osteoporosis.

Monitoring- carefully monitor standard hypercalcemia-related metabolic parameters, such as serum levels, of calcium, phosphate, magnesium, and potassium folowing pamidronate initiation.

Carefully monitor patients who have preexisting anemia, leukopenia, or thrombocytopenia in the first 2 weeks following treatment

Nutrition- patients should maintain adequate nutrition particularly an adequate intake of calcium and Vitamin D GI

Disorders- use caution while using bisphonates in patients with active upper GI problems (eg. dysphagia,symptomatic esophageal diseases, gastritis, duodenitis, ulcers)

Etidronate therapy has been withheld from patients with enterocolitis because diarrhea is seen in some patients, particularly at higher doses.

Osteoid- etodronate suppresses bone turnover and retard mineralization of osteiod laid down during the bone acceration process. These effects are dose -time dependent.

Fracture- In Pagets treatment regimens of etodronate exceeding the daily recommended daily maximum dose of 20mg/kg or continous administration for periods > 6 months may be associated with an increased risk of fracture.

Hormone replacement therapy- concurrent use with aldrenoate for osteoporosis in menopausal women is not recommended

Hypocalcemia- Hypocalcemia has occured with pamidronate therapy. If hypcalcemia occurs, consider short-term calcium therapy. Hypocalcemia must be corrected before therapy initiation with aldronate.Other disturbances of mineral metabolism eg vitaminn D deficiency, should also be effectively treated.

Warnings

Osteoporosis- (alendronate ) - consider causes other thannoestrogen deficiency and aging.

Pagets disease- response may be slow and may continue for months after treatment discontinuation. Do not increase dosage prematurely or resume treatment before there is evidence of reactivation of the disease process. Do not initiate retreatment until at least a 90 day drug-free interval.

Renal function impairment- Alendronate- no dosage adjustment is necessary in mild to moderate renal insufficiency(creatinine clearance Ccr 35 to 60ml/min ) Alendronate use is not recommended in more severe renal insufficiency ( Ccr < 35ml/min)

Etodrinate- in some patients with pre-esisting renal impairment or who had received potentially nephrotoxic drugs ,further renal depression was sometimes seen. Monitor renal function.

Pamidronate- patients with hypercalcemia who receive an IV infusion of pamidronate should have periodic lab and clinical evaluations of renal function.

Carcinogenesis- Alendronate- parafollicular cell (thyroid) adenomas were increased in high dose male rats at doses equivalent to 1 and 3 times the 10mg human dos.

Pregnancy- use alendronate during pregnancy only if the potential benefit justifies the risk to the mother and the fetus.

Lactation- excercise caution when administering etidronate or pamidronate to a nursing mother. Do not give alendronate to a nursing mother.

Children- safety and efficacy for use in children have not been established.

Approved by FDA on September 29,1995

Indication-

Post menopausal osteoporosis

Dosage:

Alendronate must be taken at least 30 minutes before the first food, beverages or medication of the with plain water only Pagets disease of the bone- 40mg once daily for 6 months

Overdosage- Symptoms Alendronate- Hypocalcemia, hypophosphatemia, and upper GI adverse eventseg. upset stomach, heartburn, esophagitis, gastritis, or ulcer may result from overdosage

Treatment

1. Consider the administration of milk or antacids to bind alendronate.

2. Dialysis may be beneficial.

Symptoms-

Etidronate- Clinical experience with etidronate overdosage is extremely limited. Decreases in serum calcium following substantial overdosage may be expected in some patients. Signs and symptoms of hypocalcemia may also occur. Some patients may develop vomiting and expel the drug.

Treatment

1. Gastric lavage may remove unabsorbed drug.

2. Standard procedures for treating hypocalcemia, including administration of calcium IV would be expected to restore physiologic amounts of ionized calcium and relieve signs and symptoms of hypocalcemia. Such treatment may be effective.

Symptoms

Pamidronate- There has been several cases of drug maladministration of IV pamidronate in hypercalcemia patients with total doses of 225 to 300mg given over 2.5 to 4 days. All survived but experienced hypocalcemia requiring IV and or or oral calcium .Obese woman treated with palmidronate 285mg/day for 3 days experienced high fever, hypotension, and transcient taste perversion, noted about 6 hours after the first infusion

Treatment

1. Fever and hypotension were rapidly corrected with steroids

Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is time for your next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

1. Patients are advised to stop medications if symptoms worsen and seek medical attention at the earliset.

2. Patients are appropiately counselled to strictly adhere to dosage instructions and mode of use.

3. Alendronate must be taken at least 30 minutes before the first food, beverages or medication of the day, with plain water only.

Other beverages(including mineral water) food and some medications are likely to reduce the absorption of alendronate..

4. Instruct patients that the expected benefits of alendronate may only be obtained when each tablet is taken with plain water first thing in the morning and at least 30 minutes before the first food, beverage or medication of the day.

5. Instruct them that waiting >than 30 minutes will improve alendronate absorption. Even dosing with orange juice or coffee markedly reduces the absorption of alendronate

6. Take with a full glass of plain water at least 1/2 hr before the 1st food/drink/medication of the day and remain in  sitting/upright position for at least 1/2 hr. Swallow whole do not chew/crush

Pharmacology

Alendronate is an aminobisphonate, appears to attentuate bone turnover by suppressing the activity of ostroclasts. Even though the exact mechanism of action is unclear, it is suggested that inhibition of bone resorption appears to be the result of the ostroclast membrane becoming leaky to small ions in the presence of local alendronate concentration attached to the expanded bone surfaces.

Pharmacokinetics

The bioavailability of alendronate after oral dosing is less than 1%. Food and divalent ions, such as calcium interfere with absorption of oral alendronate. Black coffee and orange juice reduce absorption of alendronate. Elimination of alendronate appears to be exclusively via the urine.

Beverages including mineral water, food and some medications are likely to reduce the absoption of alendronate

Take with a full glass of plain water at least 1/2 hr before the 1st food/drink/medication of the day and remain in  sitting/upright position for at least 1/2 hr. Swallow whole do not chew/crush

Pregnancy

Use alendronate during p[regnancy only if the potential benefit justifies the risk to the mother and the fetus.

Lactation

Excercise caution when administering etidronate or pamidronate to a nursing mother. Do not give alendronate to a nursing mother.

Children-

Safety and efficacy for use in children have not been established.