1. FOSAMAX HISTORY
(How was Fosamax discovered?)

Fosamax is a product of Merck & Co.

Fosamax received U.S. Food and Drug Administration (FDA) approval in September 1995.

Note: World-drugs.net sells generic version of Fosamax

2. FOSAMAX FACTS

Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first.

Established in 1891, Merck discovers, develops, manufactures and markets vaccines and medicines in over 20 therapeutic categories.

Merck & Co. aims at helping to improve the health and well-being of people everywhere by discovering, developing and bringing to market breakthrough medicines. Their priorities are focused on turning cutting-edge science into breakthrough medicines that address significant unmet needs, and thus have the potential to become important medical advances. 

3.ABOUT FOSAMAX MEDICATION

What is Osteporosis?

Osteoporosis, or porous bone, is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fractures, especially of the hip, spine, and wrist, although any bone can be affected.

 

Osteoporosis may result from disease, dietary or hormonal deficiency or advanced age. 

Prevalence of Osteoporosis

Osteoporosis is a major public health threat for an estimated 44 million Americans, or 55 percent of the people 50 years of age or older. In the U.S. today, 10 million individuals are estimated to already have the disease and almost 34 million more are estimated to have low bone mass, placing them at increased risk for Osteoporosis.

• Of the 10 million Americans estimated to have Osteoporosis, eight million are women and 2 million are men.
• One in two women and one in four men over age 50 will have an Osteoporosis-related fracture in her/his remaining lifetime.
• Significant risk has been reported in people of all ethnic backgrounds.
• While Osteoporosis is often thought of as an older person's disease, it can strike at any age.

Women

• Eighty percent of those affected by Osteoporosis are women.
• Five percent of non-Hispanic black women over age 50 are estimated to have Osteoporosis; an estimated additional 35 percent have low bone mass that puts them at risk of developing Osteoporosis.
• Ten percent of Hispanic women aged 50 and older are estimated to have Osteoporosis, and 49 percent are estimated to have low bone mass.
• Twenty percent of non-Hispanic white and Asian women aged 50 and older are estimated to have Osteoporosis, and 52 percent are estimated to have low bone mass.

Men

• Twenty percent of those affected by Osteoporosis are men.
• Seven percent of non-Hispanic white and Asian men aged 50 and older are estimated to have Osteoporosis, and 35 percent are estimated to have low bone mass.
• Four percent of non-Hispanic black men aged 50 and older are estimated to have Osteoporosis, and 19 percent are estimated to have low bone mass.
• Three percent of Hispanic men aged 50 and older are estimated to have Osteoporosis, and 23 percent are estimated to have low bone mass.

Symptoms of Osteoporosis

Osteoporosis is often called the "silent disease" because bone loss occurs without symptoms. People may not know that they have Osteoporosis until their bones become so weak that a sudden strain, bump, or fall causes a fracture or a vertebra to collapse. Collapsed vertebrae may initially be felt or seen in the form of severe back pain, loss of height, or spinal deformities such as kyphosis or stooped posture.

Risk Factors for Osteoporosis

Certain people are more likely to develop Osteoporosis than others. Factors that increase the likelihood of developing Osteoporosis are called "risk factors." These risk factors include:

• Personal history of fracture after age 50
• Current low bone mass
• History of fracture in a 1st degree relative
• Being female
• Being thin and/or having a small frame
• Advanced age
• A family history of Osteoporosis
• Estrogen deficiency as a result of menopause, especially early or surgically induced
• Abnormal absence of menstrual periods (amenorrhea)
• Anorexia nervosa
• Low lifetime calcium intake
• Vitamin D deficiency
• Use of certain medications, such as corticosteroids and anticonvulsants
• Presence of certain chronic medical conditions
• Low testosterone levels in men
• An inactive lifestyle
• Current cigarette smoking
• Excessive use of alcohol
• Being Caucasian or Asian, although African Americans and Hispanic Americans are at significant risk as well
• Women can lose up to 20 percent of their bone mass in the five to seven years following menopause, making them more susceptible to Osteoporosis.

Detection of Osteoporosis

Specialized tests called bone density tests can measure bone density in various sites of the body.

A bone density scan measures the density of bone in a person. The lower the density of a bone the higher the risk of fractures. A bone scan, along with a patient's medical history, is a useful aid in evaluating the probability of a fracture and whether any preventative treatment is needed. A bone density scan has the advantage of being painless and exposing the patient to only a small amount of radiation.

Prevention of Osteoporosis

By about age 20, the average woman has acquired 98 percent of her skeletal mass. Building strong bones during childhood and adolescence can be the best defense against developing Osteoporosis later. There are four steps, which together, can optimize bone health and help prevent Osteoporosis. They are:

• A balanced diet rich in calcium and vitamin D;
• Weight-bearing exercise;
• A healthy lifestyle with no smoking or excessive alcohol intake; and
• Bone density testing and medication, when appropriate.  

Uses of Fosamax

Fosamax is used for the treatment and prevention of Osteoporosis in postmenopausal women.

For the treatment of Osteoporosis, Fosamax increases bone mass and reduces the incidence of fractures, including those of the hip and spine (vertebral compression fractures).

Fosamax is also used to increase bone mass in men with Osteoporosis

Fosamax is used for the treatment of glucocorticoid-induced Osteoporosis in men and women receiving glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and who have low bone mineral density. Patients treated with glucocorticoids should receive adequate amounts of calcium and vitamin D.

Fosamax treatment is indicated in patients with Paget's disease of bone having alkaline phosphatase at least two times the upper limit of normal, or those who are symptomatic, or those at risk for future complications from their disease. 

How does Fosamax work?

In Osteoporosis, Fosamax works by slowing down the process of old bone being removed, which allows the bone-forming cells time to rebuild normal bone. Fosamax not only helps prevent the loss of bone but actually helps to rebuild bone and makes bone less likely to fracture.

Thus, Fosamax prevents or reverses the progression of Osteoporosis. Fosamax starts working on the bone cells immediately, but measurable effects on bone mass may not be seen for several months or more.

In Paget's disease, Fosamax slows down bone resorption, which allows the bone-forming cells time to rebuild normal bone.

Fosamax belongs to a group of non-hormonal medicines called bisphosphonates.

4.FOSAMAX EFFECTIVENESS
When is Fosamax best taken?

Absorption

The mean oral bioavailability of Fosamax in women was 0.64% for doses of Fosamax ranging from 5 to 70 mg when administered after an overnight fast and two hours before a standardized breakfast. Oral bioavailability of the 10 mg tablet in men (0.59%) was similar to that in women when administered after an overnight fast and 2 hours before breakfast.

A study examining the effect of timing of a meal on the bioavailability of alendronate was performed in 49 postmenopausal women. Bioavailability was decreased (by approximately 40%) when 10 mg Fosamax was administered either 0.5 or 1 hour before a standardized breakfast, when compared to dosing 2 hours before eating. In studies of treatment and prevention of Osteoporosis, alendronate was effective when administered at least 30 minutes before breakfast.

Bioavailability was negligible whether alendronate was administered with or up to two hours after a standardized breakfast. Concomitant administration of Fosamax with coffee or orange juice reduced bioavailability by approximately 60%.

Distribution

Preclinical studies (in male rats) show that Fosamax transiently distributes to soft tissues following 1 mg/kg IV administration but is then rapidly redistributed to bone or excreted in the urine. The mean steady-state volume of distribution, exclusive of bone, is at least 28 L in humans. Concentrations of drug in plasma following therapeutic oral doses are too low (less than 5 ng/mL) for analytical detection. Protein binding in human plasma is approximately 78%. 

Metabolism

There is no evidence that alendronate is metabolized in animals or humans.

Excretion

Following a single dose of Fosamax, approximately 50% of the radioactivity was excreted in the urine within 72 hours and little or no radioactivity was recovered in the feces. It is estimated that after 10 years of oral treatment with Fosamax the amount of Fosamax released daily from the skeleton is approximately 25% of that absorbed from the gastrointestinal tract. 

5.FOSAMAX EFFECTS ON SPECIAL POPULATION
How do different people react to Fosamax?

Pregnant ladies
There are no studies in pregnant women. Fosamax should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus.

Nursing Mothers
It is not known whether Fosamax is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Fosamax is administered to nursing women.

Race
Pharmacokinetic differences due to race have not been studied.

Pediatric Use
Fosamax pharmacokinetics have not been investigated in patients <18 years of age.

Geriatric Use
Bioavailability and disposition (urinary excretion) of Fosamax were similar in elderly and younger patients. No dosage adjustment is necessary.

6.FOSAMAX EFFECTS ON MEDICAL CONDITIONS
How does Fosamax affect your existing condition/ailment?

Renal Insufficiency:

Preclinical studies show that, in rats with kidney failure, increasing amounts of drug are present in plasma, kidney, spleen, and tibia. In healthy controls, drug that is not deposited in bone is rapidly excreted in the urine. No evidence of saturation of bone uptake was found after 3 weeks dosing with cumulative IV doses of 35 mg/kg in young male rats. Although no clinical information is available, it is likely that, as in animals, elimination of Fosamax via the kidney will be reduced in patients with impaired renal function. Therefore, somewhat greater accumulation of alendronate in bone might be expected in patients with impaired renal function.

No dosage adjustment is necessary for patients with mild-to-moderate renal insufficiency (creatinine clearance 35 to 60 mL/min). Fosamax is not recommended for patients with more severe renal insufficiency (creatinine clearance <35 mL/min) due to lack of experience with alendronate in renal failure.

Hepatic Insufficiency:

As there is evidence that alendronate is not metabolized or excreted in the bile, no studies were conducted in patients with hepatic insufficiency. No dosage adjustment is necessary. 

7.OTHER/ALTERNATE USES OF FOSAMAX
What else does Fosamax treat?

Fosamax is used for the treatment of Osteoporosis and Paget's disease. 

8.ADVERSE/SIDE EFFECTS of FOSAMAX
What are the side effects of Fosamax?

Paget's disease of bone

In clinical studies (Osteoporosis and Paget's disease), adverse experiences reported in 175 patients taking Fosamax 40 mg/day for 3-12 months were similar to those in postmenopausal women treated with Fosamax 10 mg/day. However, there was an apparent increased incidence of upper gastrointestinal adverse experiences in patients taking Fosamax 40 mg/day. One case of esophagitis and two cases of gastritis resulted in discontinuation of treatment.

Additionally, musculoskeletal (bone, muscle or joint) pain, which has been described in patients with Paget's disease treated with other bisphosphonates, was considered by the investigators as possibly, probably, or definitely drug related in approximately 6% of patients treated with Fosamax 40 mg/day versus approximately 1% of patients treated with placebo, but rarely resulted in discontinuation of therapy. Discontinuation of therapy due to any clinical adverse experience occurred in 6.4% of patients with Paget's disease treated with Fosamax 40 mg/day and 2.4% of patients treated with placebo.

Laboratory Test Findings
In double-blind, multicenter, controlled studies, asymptomatic, mild, and transient decreases in serum calcium and phosphate were observed in approximately 18% and 10%, respectively, of patients taking Fosamax versus approximately 12% and 3% of those taking placebo. However, the incidences of decreases in serum calcium to <8.0 mg/dL (2.0 mM) and serum phosphate to </=2.0 mg/dL (0.65 mM) were similar in both treatment groups.

Post-Marketing Experience
The following adverse reactions have been reported in post-marketing use:

Body as a Whole: hypersensitivity reactions including urticaria and rarely angioedema.

As with other bisphosphonates, transient symptoms as in an acute-phase response (myalgia, malaise and rarely, fever) have been reported with Fosamax, typically in association with initiation of treatment. Rarely, symptomatic hypocalcemia has occurred, generally in association with predisposing conditions.

Gastrointestinal : esophagitis, esophageal erosions, esophageal ulcers, rarely esophageal stricture or perforation, and oropharyngeal ulceration. Gastric or duodenal ulcers, some severe and with complications have also been reported.

Skin : rash (occasionally with photosensitivity), pruritus, rarely severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis.

Special Senses : rarely uveitis, rarely scleritis.