Risedronate Sodium - Uses, Dosage, Overdose, and Side Effects

Overview:

Risedronate sodium is a prescription medicine for patients at risk of osteoporosis. The bones get weaker, brittle, and more prone to fracture with osteoporosis. The medicine Risedronate Sodium is classified as bisphosphonate and helps to keep the bones stronger. Hence, they may also be prescribed to patients with Paget's disease, where the normal recycling of bone is disrupted, and the bones become fragile and bent.

Risedronate Sodium is available in tablet form. The tablets are taken daily or weekly according to the prescription. The instructions suggested are to have the tablet first in the morning, with a minimum of 30 minutes before consuming food, drink, or other medicines.

Risedronate Sodium comes under Actonel and Actonel - Once a Week.

It's important to look after your teeth and have regular dental check-ups while taking Risedronate.

How Does Risedronate Sodium Work?

The osteoclast is a bone cell that breaks down the old bone tissues, and that new bone is formed by the osteoblast (bone-forming cell). Osteoblast and osteoclast functions are critical in bone remodeling and repair. In a few conditions, the actions of osteoclast over-perform lead to more bone degradation and weakness.

Risedronate Sodium is known to inhibit the action of osteoclasts by preserving the bony tissues. The tablet thus reduces resorption and remodeling. Risedronate Sodium also possesses a high affinity for hydroxyapatite crystals (an essential mineral) in the bone.

Uses:

Osteoporosis in Women After Menopause:

After menopause, women are more prone to develop primary osteoporosis because of the reduced estrogen (sex hormone) level. During the transition period of menopause, there is more breakdown of bony tissues than formation.

Risedronate sodium is used to treat and prevent osteoporosis in women post-menopause. Studies have shown a reduced rate of fracture (especially the vertebra) associated with osteoporosis in post-menopausal women.

Osteoporosis in Men:

Men are generally less susceptible to osteoporosis than older women. However, Risedronate Sodium is indicated for men diagnosed with osteoporosis.

Glucocorticoid-Induced Osteoporosis:

Prolonged use of steroids is associated with rapid bone loss. Steroids act in an unusual way causing more bone depletion than formation. However, patients with chronic inflammatory diseases strongly depend on steroids (glucocorticoids) to reduce the symptoms to perform daily activities.

Risedronate Sodium is indicated in patients (both men and women) with osteoporosis induced by long-term steroid usage.

Paget's Disease:

Patients with Paget's disease will highly benefit from Risedronate Sodium, which significantly reduces the disease activity and progression.

Dosage:

• Risedronate Sodium is taken much earlier in the day, with a minimum of 30 minutes before the first food, drink, or other medicines.

• The tablet is swallowed in an upright position. A glass full of water is taken along with it. It is strictly advised not to lie down for at least 30 minutes after consuming the tablet.

• Calcium and vitamin D supplements are provided along with the specified prescription.

• Few calcium supplement pills inhibit the absorption of Risedronate Sodium. Hence recommended taking these tablets at different times of the day.

• Patients with severe renal impairment (creatinine clearance value lesser than 30 mL per minute) should not take this medication. However, patients having creatinine greater than the specified value do not need any dose adjustment.

Warning:

Upper Gastrointestinal Adverse Reactions:

Risedronate Sodium is a bisphosphonate, which may generally create gastrointestinal issues like dysphagia (swallowing difficulty), esophagitis (inflammation of the esophagus), and esophageal or gastric ulcers. For patients who are already suffering from gastrointestinal disorders or develop one of the symptoms mentioned above, there should be some dose modifications according to their specific risk factors. However, it is suggested to discontinue the tablet if the symptoms prolong or worsen over time.

Mineral Metabolism:

Calcium deficiency and other bone metabolic disorders must be addressed before starting treatment with Risedronate Sodium. Calcium and vitamin D supplements are essential in patients with osteoporosis and Paget's disease.

Jaw Osteonecrosis:

Osteonecrosis or avascular necrosis refers to the death of bone tissue due to the lack of blood and oxygen supply. Osteonecrosis of the jaw can happen following a local infection after tooth extraction, dental implant placement, or jaw-related surgeries. This event has also been noted in patients taking Risedronate Sodium.

Patients receiving Risedronate Sodium may discontinue the drug before invasive dental procedures to diminish the possibility of acquiring jaw osteonecrosis. Each patient has to be assessed and guided according to their risk factors.

If the patient under Risedronate Sodium develops osteonecrosis of the jaw, proper treatment of the condition has to be undertaken, and the decision to continue the drug will be based on the patient's benefit and risk factors of the drug.

Musculoskeletal Pain:

Intake of Risedronate Sodium may occasionally cause pain in the bones, joints, and muscles. Some patients may develop such pains immediately after taking the drug, and others may experience it after a few days or months. Most of the time, the pain reduces after stopping the drug intake. Recurrence of pain may happen, and discontinuing the medication is considered if the symptoms become severe.

Renal Impairment:

Patients with severe kidney disease (creatinine clearance of less than 30 mL per minute) are restricted from using Risedronate Sodium.

Glucocorticoid-Induced Osteoporosis:

When Risedronate Sodium is used for the prevention and treatment of glucocorticoid-induced osteoporosis, the level of sex hormones has to be assessed, and the appropriate replacement therapy should be done.

Laboratory Test Interactions:

Risedronate Sodium, bisphosphonate, may impede the results of bone-imaging agents, but there is no demonstration of this specific to the drug.

For Patients:

What Is Osteoporosis?

Osteoporosis means brittle bone disease; the bone goes fragile and can frequently break under unusual circumstances. The bones will have less bone mineral density. Fractures are very common in osteoporotic patients, and nearly half of the women after menopause will encounter osteoporosis-related fractures. Senior women will find it very difficult to resume regular activities even after recovering from fractures. The quality of life is compromised.

What Are the Causes of Osteoporosis?

Based on the etiology, osteoporosis can be-

Primary Osteoporosis:

Estrogen is one of the female sex hormones involved in developing and maintaining the female reproductive system. They also help preserve bone mineral density by enhancing the action of osteoblasts (bone-forming cells).

Aging in women is associated with a decrease in the sex hormone - estrogen- negatively affecting bone metabolism. The loss of mineral density and microstructure in bone increases the fracture risk. The condition is primary osteoporosis.

Secondary Osteoporosis:

When osteoporosis develops as an adverse event to medications, it is termed secondary osteoporosis. The most common drugs are glucocorticoids and anti-epileptics. Less commonly, proton pump inhibitors and chemotherapy drugs can also be attributed to bone loss.

What Are the Risk Factors for Osteoporosis?

The following are the risk factors that increase the chance of osteoporosis,

• Aging.

• Women have more risk than men.

• Familial history of osteoporosis.

• Prior fracture incidence.

• Prolonged usage of steroids.

• Less BMI (body mass index).

• Smoking and alcoholism.

• Secondary to certain drugs.

• Thyroid disorders.

• Chronic kidney disease.

• Malnutrition, malabsorption, and low body weight.

How Does Osteoporosis Develop?

Osteoporosis develops when there is a disparity between bone depletion and bone formation. As age advances, usually, the bones start to deplete more than the generation of new bone. But when this process of bone depletion intensifies than usual, it can lead to osteoporosis.

About Risedronate Sodium:

What Is Risedronate Sodium?

Risedronate Sodium is a bisphosphonate used to treat and prevent osteoporosis. The medicine is only available with a doctor's prescription. Risedronate Sodium helps to keep the bones stronger and makes them less vulnerable to fracture. They are also used in treating Paget's disease, where the bones are weak and flexible. Risedronate is available as tablets and comes under Actonel and Actonel - Once a Week.

What Are the Precautions to Be Taken Before Taking Risedronate Sodium?

Risedronate Sodium is prescribed to adults over the age of 18 years. It is safer to inform the healthcare provider about the following medical conditions before taking Risedronate Sodium.

• Prior history of allergy to Risedronate Sodium or any other medicines.

• Gastrointestinal problems like issues with digestion, swallowing, heartburn, or acid reflux.

• Kidney disease.

• Reduced level of calcium in the blood.

• Cancer with the treatment of chemotherapy or radiotherapy.

• Dental problems.

• Habits like smoking and alcohol consumption.

• Pregnancy or while trying to get pregnant.

• Breastfeeding mothers.

How to Take Risedronate Sodium?

• Risedronate Sodium is to be taken daily or weekly once a day.

• The time of taking the tablet should be on an empty stomach as early as 30 minutes before the first food or drink. It is better to maintain the same timing every day.

• If the tablet is supposed to be taken once a week, then a specific day is fixed and followed routinely. Hence the time and the day is very particular for the drug intake.

• Take the tablet upright (sitting or standing straight), and do not lie down for at least 30 minutes after the drug intake.

• It is advisable to swallow the tablet without breaking, crushing, chewing, sucking, or dissolving it.

• The tablet can be taken with a full glass of plain water.

• One tablet a day would be sufficient.

What Is the Dosage of Risedronate Sodium?

For the Treatment of Osteoporosis: The regular adult dosage is 35 mg per week or 5 mg daily.

For the Treatment of Paget's Disease: The regular adult dosage is 30 mg per day.

What to Do if a Dose of Risedronate Sodium Is Missed?

Daily, if one forgets to take the tablet in the morning at a specific time, the instruction is to have them later but on an empty stomach (no eating or drinking for 2 hours before and after the drug intake). Water can be consumed. If that is not possible, it is better to switch to the schedule the next day.

Every week, take the tablet at the same time with the same instructions on the following day and later next week and stick to the usual day of the weekly dosage.

What to Do for Overdosage of Risedronate Sodium?

Do not take the extra dosage of risedronate Sodium until it is compulsory or necessary. If in case, the dosage is exceeded, it is advisable to have a full glass of milk immediately in an upright position and hold on to it for at least 30 minutes. This instruction applies to patients taking Risedronate Sodium for osteoporosis or Paget's disease.

If an overdose occurs in children, the same instruction of drinking milk and upright position is followed immediately. But then seek the help of a healthcare professional as early as possible.

What Are the Side Effects of Risedronate Sodium?

The common side effects of Risedronate Sodium are:

• Digestion issues - bloating, gas formation, and pain in the stomach.

• Diarrhea or constipation.

• Nausea and lightheadedness.

• Headache.

• Mild pain in the bone, joint, or muscle.

Some unusual serious side effects that are to be addressed appropriately are:

• Heartburn.

• Swallowing difficulty.

• Chest pain.

• Dental problems like loose teeth, gum sores, and swelling.

• Severe pain in the bone, joint, or muscle.

• Changes in the stool color.

• Eye and ear problems.

• Serious allergic reaction or anaphylaxis (seek immediate help).

For Doctors:

Indication:

Risedronate Sodium is indicated as the following,

• To treat and prevent osteoporosis in post-menopausal women.

• To treat osteoporosis in men by increasing bone mass.

• To treat and prevent glucocorticoid-induced osteoporosis.

• To treat Paget's disease.

Pharmacology:

Mechanism of Action:

Risedronate Sodium possesses a great affinity to hydroxyapatite crystals in the bone. They prevent the resorption of the bone. As in the usual bone modeling process, the osteoblasts attach to the bony surface, but using Risedronate Sodium limits their resorption action.

Animal studies have shown less resorption and remodeling.

Pharmacodynamics:

In general, the rate of bone turnover increases as age advances, especially in women, due to the diminishing levels of estrogen in the body. Risedronate Sodium hampers the raised bone turnover rate in post-menopausal women. This is clear with reduced biomarkers like urinary deoxypyridinoline, urinary collagen cross-linked N-telopeptide, and serum bone-specific alkaline phosphatase. The evidence of decreased bone turnover can be observed as early as 14 days after the onset of medication.

Chemical Taxonomy:

Ingredients:

Risedronate Sodium tablet is a pyridinyl bisphosphonate in the form of hemi-pentahydrate with small amounts of monohydrate.

Inactive Ingredients:

The inactive ingredients present in all dosage forms of Risedronate Sodium tablets are:

• Crospovidone.

• Hydroxypropyl cellulose.

• Hypromellose.

• Magnesium stearate.

• Microcrystalline cellulose.

• Polyethylene glycol.

• Silicon dioxide.

• Titanium dioxide.

Some of the ingredients that are present specific to the dosage are

• 5 mg - ferric oxide yellow and lactose monohydrate.

• 30 mg - lactose monohydrate.

• 35 mg - ferric oxide red, ferric oxide yellow, and lactose monohydrate.

• 75 mg - ferric oxide red.

• 150 mg - FD&C blue No.2 aluminum lake (Food, Drugs, and Cosmetics dyes).

Absorption:

• The absorption takes place entirely in the upper gastrointestinal tract.

• The average peak concentration of Risedronate sodium in the blood is reached at less than 1 hour.

• The average oral bioavailability documented is 0.63 % for a 30 mg tablet.

Distribution:

• The average distribution volume for Risedronate Sodium is 13.8 liter per kilogram.

Metabolism:

There is no active metabolism of Risedronate Sodium before elimination.

Elimination:

Most of the absorbed form of Risedronate Sodium is excreted through urine, and the unabsorbed volume is eliminated in the feces. The terminal half-life noted was 561 hours.

Toxicity:

The overdosage of Risedronate Sodium will eventually decrease the level of calcium and phosphorus in the blood. Milk can be used as an antidote, binding to the drug and decreasing its absorption. Gastric lavage may be required based on the severity. However, children seek immediate help from doctors when suspecting overdosage of Risedronate Sodium.

Dosage and Forms:

Risedronate Sodium comes in tablet form and is a prescription medicine.

They are available in the following dosage forms:

• 5 mg - yellow tablet in an oval shape, with a film coating and debossed letters of RSN on one face and 5 mg on the other.

• 30 mg - white tablet in an oval shape, with a film coating and debossed letters of RSN on one face and 30 mg on the other.

• 35 mg - orange tablet in an oval shape, with a film coating and debossed letters of RSN on one face and 35 mg on the other.

• 75 mg - pink tablet in an oval shape, with a film coating and debossed letters of RSN on one face and 75 mg on the other.

• 150 mg - blue tablet in an oval shape, with a film coating and debossed letters of RSN on one face and 150 mg on the other.

Administration of the Drug:

For Postmenopausal Women:

The suggested dosage for preventing and treating osteoporosis is the same as follows,

• One 5 mg tablet is taken orally once a day.

• One 35 mg tablet is taken orally once a week.

• One 75 mg tablet is taken twice a month orally.

• One 150 mg tablet is taken orally once a month.

For Men With Osteoporosis to Increase Bone Mass:

The suggested dosage is one 35 mg tablet taken orally once a week.

For the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis:

The suggested dosage is one 5 mg tablet taken orally once a day.

For the Treatment of Paget's Disease:

The suggested dosage is a 30 mg tablet taken orally once a day for two months.

Contraindications:

Risedronate Sodium is contraindicated in patients who cannot maintain an upright position for at least 30 minutes. People with hypocalcemia and a known history of hypersensitivity to product ingredients are also refrained from having Risedronate Sodium.

Clinical Studies for Risedronate Sodium:

1. For the Treatment of Osteoporosis in Postmenopausal Women:

• Randomized, double-blinded, placebo-controlled trials involving 4000 postmenopausal women were enrolled.

• All patients were given 5 mg of Risedronate Sodium daily.

Results:

Vertebral Fracture - the tablet significantly reduced the occurrence of new vertebral fractures and the worsening of their symptoms.

Osteoporosis -Related Nonvertebral Fractures - the incidence of nonvertebral osteoporosis-related fractures over three years significantly reduced with a corresponding reference of 36 % over three years.

Bone mineral density of the spine, hip, and wrist increased in trials than in the placebo.

2. For the Prevention of Osteoporosis in Postmenopausal Women:

A two-year double-blinded, placebo-controlled study was done on 383 patients receiving Risedronate Sodium of 5 mg.

Results:

The mean bone mineral density significantly increased as early as three months after the initiation of treatment. The bone mineral density at the lumbar spine, femoral neck, and trochanter increased compared to the placebo group.

3. For the Treatment of Osteoporosis in Men:

A two-year, double-blinded, placebo-controlled, multinational study of 285 men with osteoporosis was conducted with Risedronate Sodium of 35 mg. The patient's mean age was 60.6 years.

Results:

There was a significant increase in the mean bone mineral density at the lumbar spine, femoral neck, trochanter, and hip compared to the placebo after two years of treatment.

4. For the Treatment of Glucocorticoid-Induced Osteoporosis:

One year, double-blinded, placebo-controlled trials were undertaken in patients receiving glucocorticoids with Risedronate Sodium of 5 mg daily in 228 patients.

Results:

After one year, the incidence of vertebral fractures had reduced to about 10 %.

5. For the Treatment of Paget's Disease:

Two clinical studies were conducted in patients with Paget's disease involving 120 men and 65 women. It was a double-blinded, active-controlled study. All patients received 30 mg of Risedronate Sodium for two months or etidronate disodium for 400 mg daily for six months.

Results:

The patient who received Risedronate Sodium showed a 36 % reduction in serum alkaline

phosphatase excess while only a 6 % reduction in patients who received etidronate disodium simultaneously.