Alendronate - Uses, Dosage, Side-Effects and Precautions

Overview

Alendronate is used to treat and prevent osteoporosis. It is a disorder marked by thin, brittle bones prone to breaking. It is mostly used for osteoporosis in postmenopausal women and men. It is also used in patients on corticosteroids as corticosteroids could worsen osteoporosis. In addition, Alendronate is used to treat Paget's disease of the bone, which is a disorder that results in weak and soft bones that can break easily, be broken or deformed, and are painful. It was approved by the US FDA (United States Food and Drug Administration) in 1995.

Drug Group

Alendronate belongs to the drug group bisphosphonates. It is used to treat and prevent osteoporosis by preventing osteoclastic bone resorption.

Dosage

Take the five mg (milligram) and 10 mg capsules once daily on an empty stomach in the morning. Take the 70 mg bottle of oral solution once a week in the morning. Also, 35 mg and 70 mg Alendronate tablets are taken once a week on an empty stomach. Paget’s disease is treated with an Alendronate dose of 40 mg every day in the morning on an empty stomach.

For Patients

What Is Osteoporosis?

Osteoporosis is a disease that weakens an individual's bones. Individuals with osteoporosis will have weaker, less dense, and thinner bones than they should have. The chance of developing fractures is increased in people with osteoporosis. Bones undergo regular breakdown and reconstruction. When the rate at which new bone grows is slower than the rate at which old bone is lost, osteoporosis results in thinner, weaker bones that are more likely to break.

Most people do not even realize they have osteoporosis until it causes a bone fracture. Osteoporosis causes bones to become more brittle. The most common places for fractures are the hips, wrists, and spine (fractured vertebrae).

How Does Alendronate Work?

Alendronate belongs to the group of drugs known as bisphosphonates. It functions by improving bone density (thickness) while preventing the breakdown of bones.

What Is the Dosage of Alendronate?

• Oral Tablets - Available as 5 mg (milligrams), 10 mg, 35 mg, 40 mg, and 70 mg.

• Oral Suspension - Available as 70 mg.

What Are the Things to Inform the Doctor Before Taking the Drug?

• If there is an allergy to Alendronate or any other medicine, let the doctor and pharmacist know.

• Alendronate may result in osteonecrosis of the jaw (ONJ). This condition is more likely to occur if a person has dental surgery or therapy while using the drug. Before starting Alendronate, the patient should get a dental checkup, including all the necessary treatments, such as cleaning or mending dentures that are not fitting properly. When using Alendronate, one must wash one’s teeth and maintain a clean mouth. Consult a physician before beginning any dental procedures while using this medication.

How Is Alendronate Administered?

1. Alendronate comes in several oral dosage forms, such as pills, effervescent tablets, and liquid solutions. The dosage guidelines differ depending on the product.

• The 5 mg (milligram) and 10 mg pills are typically taken every day in the morning on an empty stomach.

• The oral solution available in a 70 mg bottle is typically taken once a week in the morning.

• 35 mg and 70 mg tablets are taken once a week on an empty stomach.

• 40 mg pills are used daily in the morning for six months as a treatment for Paget's disease of the bone.

• The patient must stick to the directions on the prescription label and see the physician or pharmacist if they have any questions.

2. Alendronate is taken as soon as one wakes up on an empty stomach. Wait at least half an hour before eating any food or drinks. The patient must stay upright after taking the medicine. When taking the tablets, drink a full glass of pure water and avoid other drinks. Avoid chewing or breaking the tablets. After consuming the oral solution, drink at least two ounces of water.

3. Alendronate does not treat Paget's disease or osteoporosis. However, it manages both conditions. Improvements in bone density may only be seen for a few months. It must only be stopped if instructed by the doctor. The patient must visit their doctor from time to time to determine whether they still need the therapy or not. Only consult the physician before changing the dosage or frequency.

What Are the Side Effects of Alendronate?

• Constipation, diarrhea, nausea, gastritis, and stomach discomfort are among the adverse effects of Alendronate that may occur. Patients should immediately notify their doctor or pharmacist if these symptoms worsen or continue.

• Serious adverse effects, such as discomfort in the jaw or ears, severe bone, joint, or muscle pain, unusual hip, thigh, or groin pain, swelling in the hands, ankles, or feet, black or tarry stools, or vomit that looks like coffee grounds should be reported to the doctor immediately.

• Patients should know that this drug rarely causes serious esophageal irritation or ulcers. It is important to stop taking Alendronate and see a doctor or pharmacist right away if they encounter unusual but serious side symptoms like chest pain, increasing heartburn, or trouble swallowing.

• Even though a serious allergic reaction to this drug is rare, people should get help immediately if they experience any symptoms like rash, swelling (especially in the face, tongue, or throat), itching, and trouble breathing.

• Risks for thigh bone fractures may rise when Alendronate is used to treat osteoporosis. Even in cases when there is no trauma or falling, people may have pain in their thighs, groin, or hips for weeks or months before a fracture. Even though thigh bone fractures are rare in healthy people, osteoporosis patients are susceptible to them even if they do not take Alendronate. Talking to a doctor about the hazards associated with Alendronate is important.

Dietary Considerations:

Alendronate users should consume a diet high in calcium and vitamin D. Healthcare professionals will suggest appropriate food and drink sources and guidelines for daily portion sizes. Patients should notify their doctors if their dietary intake is inadequate so that the doctors can recommend or prescribe necessary supplements.

Missed Dose

• Once-Daily Dose - Taking Alendronate later in the day is only advisable if receiving a once-daily dose. The missing dose should be skipped, and the next dose should be started as usual the next morning. Refrain from taking two doses to make up for the missed one.

• Once-Weekly Dose - Patients who miss the once-weekly Alendronate dosing should take the missed dose in the morning after remembering. They should also resume their regular weekly schedule. Take only one dose daily, and never take two doses to make up for a missed one.

Overdose

There is currently no particular information available about the management of Alendronate overdose. An oral overdose of Alendronate might result in upper gastrointestinal side effects such as upset stomach, heartburn, esophagitis (esophagus inflammation), gastritis (stomach lining gets inflamed), or ulcers, as well as hypophosphatemia (phosphate level decreases) and hypocalcemia (reduction in calcium level). Milk or antacids may be administered to assist in binding Alendronate in cases of suspected overdose. Keep the patient upright to prevent chances of vomiting, which can lead to esophageal irritation. Dialysis is not beneficial in case of overdosing.

Storage

Keep Alendronate in an airtight container at room temperature, 15 to 30 degrees Celsius (59 to 86 degrees Fahrenheit). It should be stored away from the children and pets.

For Doctors

Indications:

• Osteoporosis Treatment for Postmenopausal Women - Alendronate is administered in postmenopausal women to treat osteoporosis. Osteoporosis increases the risk of fractures, especially in the hip and spine (vertebral compression fractures) areas, and decreases bone density. Alendronate increases bone mass and thus lowers the risk of fractures.

• Osteoporosis Prevention in Postmenopausal Women - Alendronate is recommended to prevent osteoporosis. This drug is recommended to help lower a woman's postmenopausal osteoporosis risk. It encourages bone density and health, which can help stop bones from deteriorating.

• Treatment for Osteoporosis in Men to Increase Bone Mass - For males with osteoporosis, Alendronate is recommended as a treatment to improve bone mass.

• Management of Osteoporosis Induced by Glucocorticoids - Alendronate is given to treat osteoporosis caused by glucocorticoids in patients who take 7.5 milligrams (mg) of Prednisone equivalent dosage or more of glucocorticoids daily. Men and women with low bone mineral density can benefit from this treatment.

• Treatment for Paget’s Disease of the Bone - Alendronate treats Paget’s disease in both men and women. For patients with Paget's disease of the bone, treatment is recommended if their alkaline phosphatase level is at least two times the maximum value of normal, if they exhibit symptoms, or if they are at risk of developing difficulties in the future.

Dose:

• Osteoporosis Treatment for Postmenopausal Women - The dosage advised to an individual is one bottle of 70 mg oral solution once a week, one tablet of 70 mg weekly, or one 10 mg tablet daily once.

• Osteoporosis Prevention in Postmenopausal Women - One 35 mg pill once a week or one 5 mg tablet once a day is the suggested dosage.

• Treatment for Osteoporosis in Men to Increase Bone Mass - The suggested dosage is one 70 mg tablet once a week, one 70 mg oral solution bottle once a week, or one 10 mg tablet once a day.

• Glucocorticoid-Induced Osteoporosis Treatment - One 5 mg tablet once a day is the suggested dosage, except for postmenopausal women who are not receiving estrogen. Then, the recommended dosage is one 10 mg tablet once daily.

• Treatment for Paget’s Disease of the Bone - It is advised to use 40 mg of Alendronate once a day for six months as the first line of treatment for Paget's disease of the bone. After a six-month review period following initial treatment, re-treatment with Alendronate may be considered in situations of relapse or failure to normalize serum alkaline phosphatase levels. Evaluation of serum alkaline phosphatase should be done periodically to know the success of the treatment plan.

Dosing Considerations:

While taking Alendronate, adhering to prescribed dosing administration guidelines is critical to improve its efficacy and lower the possibility of esophageal problems.

• Use only plain water when taking Alendronate, as other substances may interfere with absorption.

• After taking Alendronate, wait at least half an hour before consuming any other food, drink, or medication.

• It is recommended to take this medication as soon as one wakes up.

• Swallow the tablet with a full glass of water (nearly six to eight ounces). The oral solution of Alendronate should be taken with at least two ounces of water.

• It is advisable to wait at least 30 minutes before the patient lies down after the day's first meal. Meanwhile, the patient is advised to sit upright.

• Alendronate should not be taken right before bed or in the morning.

• Esophageal problems are more likely to occur when dosing guidelines are not followed.

Dosage for Severe Kidney Disease - Alendronate is not advised if a patient's creatinine clearance is less than 35 milliliters per minute.

Guidelines for Vitamin D and Calcium Supplementation - Patients should take calcium supplements if dietary consumption is insufficient. Supplementing with vitamin D may be necessary for patients more susceptible to vitamin D insufficiency, such as those over 70 years old, homebound, or chronically unwell. 25-hydroxyvitamin D measurements should be considered, as patients with gastrointestinal malabsorption syndromes may need greater vitamin D treatment. Adequate calcium and vitamin D intake is recommended for patients undergoing glucocorticoid treatment.

What Are the Pharmacological Aspects of Alendronate?

Properties of the Drug

• Drug Group - Bisphosphonate.

• Empirical Formula - C4H12NNaO7P2•3H2O.

• Molecular Formula - (4-amino-1-hydroxybutylidene) bisphosphonic acid monosodium salt trihydrate.

• Molecular Weight - 325.12.

Mechanism of Action:

Alendronate exhibits a unique cellular preference for sites of bone resorption, especially those located beneath osteoclasts. Even though they are still attached to the surface of the bone, osteoclasts do not have the characteristic ruffled border that denotes active resorption when alendronate is present. Crucially, Alendronate efficiently suppresses osteoclast activity while maintaining osteoclast recruitment and attachment. When radioactive [3H]Alendronate was used in mouse research, the absorption on osteoclast surfaces was remarkably ten times higher than on osteoblast surfaces. Subsequent studies in rats and mice, looking at the bones six and forty-nine days after [3H]Alendronate was given, showed that Alendronate was incorporated into the bone matrix, where it turned pharmacologically inert. As such, ongoing Alendronate treatment is required to inhibit osteoclasts on recently established resorption sites. Alendronate medication decreases bone turnover, which leads to an excess of bone formation over resorption at remodeling sites, resulting in progressive increases in bone mass, as shown by histomorphometry studies in rats and baboons.

Pharmacodynamics:

Alendronate belongs to the bisphosphonate drug group. It attaches itself to bone hydroxyapatite and selectively stops osteoclasts from bone resorption. Although Alendronate does not directly affect bone production, it decreases bone resorption, which slows down bone creation because the two processes are intertwined throughout bone turnover. Alendronate has extremely little oral bioavailability. Following ingestion, it either dissipates into the bone and soft tissue or is eliminated by the urine. There is no metabolism of Alendronate.

Pharmacokinetics

• Availability - Alendronate had a mean oral bioavailability of 0.59 percent in males and 0.64 percent in women. If Alendronate is consumed within one hour after a meal, its bioavailability can drop by as much as 40 percent. Hence, it is always advisable to consume Alendronate on an empty stomach.

• Metabolism - Alendronate's metabolism in humans or animals has not been demonstrated.

• Excretion - When radiolabeled Alendronate is administered, urine recovers 50 percent of the same within 72 hours. The presence of Alendronate was not noted in feces. Although race and advanced age do not affect elimination, it was noted that men excrete less Alendronate than women.

Clinical Studies:

Fracture Intervention Trial (FIT) is the first megatrial with over 6,400 participants suffering from osteoporosis. It was conducted to study osteoporosis and the effectiveness of Alendronate on osteoporosis. As per the study, Alendronate effectively increases bone density and significantly lowers the risk of hip and vertebral fractures by about half within the first 12 to 18 months of treatment. It also lessens the serious health consequences associated with fractures. Alendronate has also shown promise in preventing bone loss in early postmenopausal women, making it an essential treatment and prevention strategy in such groups of people.

What Are the Contraindications of Alendronate?

• People with esophageal anomalies (such as stricture or achalasia) that prevent normal esophageal emptying should not take Alendronate oral solution.

• Patients who are unable to remain upright for at least thirty minutes after taking Alendronate should not be prescribed this medication.

• Patients with a high risk of aspiration should not take Alendronate oral solution.

• Alendronate oral solution should not be used by anyone who shows signs of hypersensitivity or allergic responses to any ingredient in the medication, including urticaria and angioedema.

• Hypocalcemia.

Warnings and Precautions:

• Adverse Reactions in the Upper Gastrointestinal System - Alendronate can potentially irritate the upper gastrointestinal system like other oral bisphosphonates. Doctors should use the drug with caution while prescribing it for patients with active upper gastrointestinal problems (for example, dysphagia, gastritis, ulcers, and Barrett's esophagus). These patients should pay extra attention to all the instructions their doctors provide. Oral bisphosphonates, including Alendronate, have been linked to esophageal issues, which might sometimes require hospitalization. These issues include esophagitis, ulcers, erosions, bleeding, and uncommon strictures or perforations. Patients who have symptoms such as worsening heartburn, dysphagia, retrosternal pain, or odynophagia should discontinue taking Alendronate and get medical attention. Physicians should be on the lookout for these signals. Patients who lie down after taking Alendronate, do not drink enough water, or keep taking Alendronate even after symptoms start appearing are more likely to experience side effects. Patients should carefully follow the directions on dosage, including water that needs to be consumed with the medicine. In patients with mental disability, Alendronate should always be used under proper guidance.

• Mineral Metabolism - Before starting Alendronate medication, hypocalcemia needs to be treated. Efficient treatment of other problems impacting mineral metabolism, such as vitamin D deficiency, is also required. Individuals with these disorders should have their serum calcium levels and hypocalcemia symptoms closely evaluated when on Alendronate. Alendronate may slightly decrease serum calcium and phosphate levels. This particularly happens in patients with Paget's disease, where bone turnover rates are often high, and in those on glucocorticoids, where Calcium absorption is decreased. Hence, patients receiving Alendronate for Paget’s disease and glucocorticoids should receive additional calcium and vitamin D supplementation.

• Musculoskeletal Pain - According to post-marketing data, patients taking bisphosphonates, including Alendronate, for the treatment and prevention of osteoporosis have occasionally had severe bone, joint, and muscle pain. The majority of the patients who complained about such symptoms included postmenopausal women. After beginning the medication, symptoms could appear one day or several months later. If a person gets severe effects, they should stop using it. Most patients experienced relief in the symptoms after quitting the medication.

• Osteonecrosis of the Jaw - Osteonecrosis of the jaw (ONJ) can develop independently or may be associated with tooth removal, localized infections, and delayed healing. It has been reported in patients who use bisphosphonates like Alendronate. Invasive dental operations, a cancer diagnosis, concurrent treatments such as corticosteroids and chemotherapy, inadequate oral hygiene, and co-morbid disorders are risk factors. The risk of ONJ may be reduced by stopping bisphosphonates before invasive dental operations. Clinical judgment should be used to customize the therapy regimen. Patients using bisphosphonates should see an oral surgeon if ONJ develops. Depending on the individual's assessment, stopping bisphosphonates should be considered, as extensive dental surgery may exacerbate the problem.

• Osteoporosis Induced by Glucocorticoids - There is no demonstrated risk vs benefit when using Alendronate to treat glucocorticoids at daily dosages less than 7.5 mg of Prednisone or equivalent. Before starting treatment, it is important to determine each person's gonadal hormonal state and take suitable replacement into account. After six to twelve months of treatment using a drug combination of Alendronate and glucocorticoid treatment, a bone mineral density measurement should be conducted for the patient.

• Renal Impairment - Alendronate is not advised if a patient's creatinine clearance is less than 35 milliliters per minute.

• Atypical Diaphyseal and Subtrochanteric Femoral Fractures - Alendronate-treated osteoporotic patients are susceptible to atypical femur fractures. Minimal or no trauma, bilateral involvement, and early pain in the affected thigh are common symptoms. Several people who experienced such fractures were also on glucocorticoids at the time of fracture. If a person with a history of bisphosphonates consumption reports groin or thigh pain, they should be considered for an atypical fracture, and incomplete femur fracture should be ruled out. Examine the leg on the opposite side as well for such patients. A personalized risk/benefit analysis should be used to determine whether to stop taking bisphosphonates.

What Are the Drug Interactions of Alendronate?

• Antacids and Calcium Supplements - The absorption of Alendronate will be hampered if it is taken along with calcium, antacids, or oral drugs that contain multivalent cations. As a result, patients cannot take any other oral drugs for at least 30 minutes after taking Alendronate.

• Aspirin - In clinical studies, patients receiving simultaneous treatment with daily dosages of Alendronate and Aspirin of more than 10 mg saw an increased risk of upper gastrointestinal side effects.

• Nonsteroidal Anti-inflammatory Drugs (NSAIDs) - Alendronate can be used by people who are on NSAIDs. As per a three-year study, the stomach and intestinal issues were the same for those using Alendronate at five or ten mg daily as for those taking a placebo. The majority of the people who participated in the study were also using NSAIDs. However, it is still good to use caution while using NSAIDs with Alendronate because they can occasionally irritate the stomach and intestines.

Specific Considerations:

• Pregnant Population - There is no research on expectant mothers. When a woman and fetus are at risk, Alendronate should only be administered if the possible benefits outweigh the risks.

• Breast Feeding Population - The excretion of Alendronate in human milk is unknown. It is important to use caution when giving Alendronate to breastfeeding mothers because a lot of medications are secreted in human milk.

• Pediatric Population - Alendronate is not recommended in the pediatric population. Although children's oral bioavailability is comparable to adult patients, there has been a noted rise in the proportion of vomiting patients in the pediatric group.

• Geriatric Population - Alendronate safety and effectiveness in elderly populations are not significantly different. However, patients older than those in the study may be even more sensitive.

• Renal Impairment - Alendronate is not advised if a patient's creatinine clearance is less than 35 milliliters per minute. There is no need to change the dosage for individuals whose creatinine clearance is between 35 and 60 mL/min.

• Hepatic Impairment - No research was done on patients with hepatic impairment because there is evidence that Alendronate is not metabolized or eliminated in the bile. There is no need to change the dosage.