Alendronate is a bisphosphonate available in an oral formulation. It inhibits bone resorption and increases bone density. It is used in the treatment and prevention of osteoporosis in men and postmenopausal women. It is also used in patients who receive a daily dose of 7.5 mg of prednisolone or more for the treatment and prevention of osteoporosis. It is also used in patients with Paget's disease who are symptomatic, is at risk of complications, and those with an alkaline phosphatase level greater than twice the upper limits of normal.

Contraindications to alendronate:

• Allergy/ hypersensitivity reactions
• Hypocalcemia
• CrCl of less than 35 ml/min.
• Disorders of the esophagus (stricture or achalasia)
• Patients who can not sit upright for 30 minutes

Warnings and Precautions:

• Atypical femur fractures have been reported with the use of bisphosphonates. Patients usually develop pain in the thigh or groin weeks or months prior to the development of fractures. Patients should also be evaluated for fracture of the opposite limb as well.

• After starting bisphosphonate medication, the patient could suffer from excruciating, incapacitating discomfort. There might need to be a break in therapy.
• Dysphagia, erosive esophagitis, and esophageal strictures might all occur in the patient. Oral alendronate should not be used by patients who are unable to sit up straight or who have anatomical esophageal anomalies such as achalasia of the cardia.
• Alendronate usage carries the risk of severe hypocalcemia. The treatment should include calcium supplements.
• The patient may have uveitis, conjunctivitis, ocular redness and edema. Consultations with ophthalmologists may be necessary.

• Osteonecrosis of the jaw (ONJ) or medication-related osteonecrosis of the jaw (MRONJ) is a rare complication of bisphosphonate therapy.
• The AAOMS (American Association of maxillofacial surgeons) recommends withholding bisphosphonate therapy two months prior to a dental procedure in patients who have been taking it for more than 4 years. Furthermore, patients taking it for less than 4 years but on concomitant steroids should also withhold alendronate therapy.

Alendronate Dose in Adults

Alendronate for osteoporosis in postmenopausal women:

• For Prophylaxis:
  • 5 mg once daily OR 35 mg one time per week.
• For the treatment of osteoporosis:
  • 10 mg once daily/70 mg one time per week.

Alendronate for osteoporosis in men:

• 10 mg once daily or 70 mg one time per week

Osteoporosis due to prolonged glucocorticoid use:

• Among women who are not getting estrogen, 5 mg or 10 mg once a day. For people who are or want to become pregnant, it is not advised.

Alendronate in Paget's disease:

• 40 mg once daily for 6 months (retreatment may be required in patients who fail to respond as evidenced by a raised alkaline phosphatase twice the upper limits of normal)

For the prevention of bone loss in patients on anti-androgens:

• 70 mg once weekly

Osteogenesis imperfecta:

• 10 mg once daily or 70 mg once weekly

What should be done if the weekly dose is missed?

The patient should be instructed to take the medication the next morning before continuing on the planned day. Avoid taking two doses on the same day.

For how long should alendronate be used?

Alendronate should be advised to postmenopausal women for at least five years who are at low risk of fractures and for at least ten years who are at high risk of fractures. The optimal treatment duration in men is not known, however, the above recommendations may be followed in older men as well. Patients whose diet is deficient in calcium and vitamin D should also be advised supplements containing adequate calcium and vitamin D. The once-weekly formulation should be preferred as it is easily tolerated with better compliance.

Alendronate Dose in Children

Alendronate dose in children with Osteogenesis imperfecta (children 2 years of age or older):

• Children weighing 30 - 40 kgs: 
  • 5 or 10 mg once daily
• Children weighing less than 30 Kgs:
  • 5 mg once daily
• Children weighing more than 40 kg:
  • 10 mg once daily

Osteopenia associated with cystic fibrosis (children 5 years of age or older):

• >25 Kgs:
  • 10 mg once daily
• <25 kgs:
  • 5 mg once daily

Osteopenia in bed-bound/ non-ambulatory patients:

• Children 6 years of age or older:
  • 35 mg once weekly

Osteopenia and osteoporosis in Patients with autoimmune rheumatic diseases (children 4 years of age or older):

• 20 to 30 kgs:
  • 5 or 10 mg once daily
• Less than 20 Kgs:
  • 5 mg once daily
• More than 30 kgs:
  • 10 mg once daily

Dose in Kidney disease:

• CrCl of more than 35 ml/min:
  • dose adjustment is not necessary
• CrCl of less than 35 ml/min:
  • avoid its use

Dose in Liver disease:

Dose adjustment is not necessary.

How to administer alendronate?

• Alendronate should be taken in the morning, at least 30 minutes before breakfast, preferably with two glasses of water.
• The patient should be advised to sit upright for 30 minutes or preferably walk around for 30 minutes. The tablets should not be chewed or sucked.

Pregnancy Risk factor C

• Bisphosphonates are not recommended for use during pregnancy. 
• Most authorities recommend that bisphosphonate therapy be stopped before conception.
• Also, monitor the neonate for hypocalcemia symptoms. Alendronate should be used with caution in breastfeeding women.

Side effects of alendronate:

Common side effects:

• Hypocalcemia (18% of patients)

Less common side effects:

• Headache
• Hypophosphatemia (low phosphate levels in the blood)
• Gastrointestinal side effects:
  • Abdominal pain
  • dyspepsia
  • nausea
  • flatulence
  • Gastroesophageal reflux disease
  • Constipation/ diarrhea
  • gastritis, and
  • Gastric ulcer
  • esophageal ulcer
  • dysphagia
  • melena
• Muscle cramps and musculoskeletal pain

Rare side effects:

• Abnormal taste,
• Alopecia,
• dizziness,
• episcleritis,
• erosive esophagitis,
• asthma exacerbation,
• cholesteatoma,
• conjunctivitis,
• esophageal stenosis,
• esophageal perforation,
• fever,
• skin rash,
• stevens-johnson syndrome,
• toxic epidermal necrolysis,
• hypersensitivity reactions,
• osteonecrosis of the jaw,
• pruritis,
• uveitis, and
• vertigo.

Monitoring Parameters:

Osteoporosis:

• Bone mineral density should be evaluated every 1 to 2 years.
• In patients on glucocorticoid therapy, bone mineral density should be evaluated at 6 and 12 months and then every 2 to 3 years after that.

Paget's disease:

• Patients with Paget's disease should be monitored every 6 to 12 weeks till normalization of the alkaline phosphatase and then at 6 monthly intervals.
• For those with liver or biliary tract disease, alkaline phosphatase levels may be deceptive.
• In such cases, other specific markers of bone turnover like P1NP (procollagen type 1 propeptide), NTX (n terminal telopeptide), and beta-CTx (c-terminal of telopeptide of type 1 collagen or c telopeptide)should be measured.

Serum calcium and 25 OH vitamin D levels should also be monitored.

Mechanism of action of alendronate:

• It inhibits bone resorption by inhibiting osteoclasts' activity and thus indirectly increases the bony matrix.

The volume of distribution: 28 Litres exclusive of bones

Proteins binding: 78%

Half-life elimination exceeds 10 years

Bioavailability: 40 to 60 %

Excretion is via urine and feces.

International Brand Names of Alendronate:

• Adronat
• Adronik
• Aldren 70
• Aldron
• Aldrox
• Alenato
• Alend
• Alendomax
• Alendra
• Alendrate
• Alendrex
• Alendro
• Alendro Once Weekly
• Alendrobell
• Alendronate
• Alendros
• Alendroxl
• Alenfos Alenfosa
• Allentop
• Alnate
• Alovell
• Arendal
• Armol
• Bifosa
• Binosto
• Bisbon
• Bonafide
• Bonaid
• Bonalene
• Bonalon
• Bonapex
• Bonmax
• BonMax
• Calidron
• Densate
• Drate
• Endronax
• Fonat
• Forosa
• Fosalan
• Fosamax
• Fosamax Once Weekly
• Fosmin
• Fostepor
• Fostolin
• Fosval Gendarin
• Gubang
• Kalosten
• Lendomax
• Malend
• Marvil
• MaxiBone
• MaxiBone 70
• Maxlen
• Nichospor
• Oseomax
• Oseotenk
• Osficar
• Osteo-Plus
• Osteocor
• Osteodron Osteofar
• Osteofos
• Osteol
• Osteomax
• Osteomel
• Osteopor
• Osteosan
• Osteovan
• Osteve
• Ostex
• Osto
• Porosal
• Prevost
• Reventa
• Romax
• Tevanate
• Valora
• Zeroclast

Pricing in US:

Tablet, effervescent (Binosto Oral):

• 70 mg (per each): $60.48

Solution (Alendronate Sodium Oral):

• 70 mg/75 mL (per mL): $0.76

Tablets (Alendronate Sodium Oral):

• 35 mg (per each): $20.48 - $20.63
• 40 mg (per each): $6.60
• 5 mg (per each): $2.92 - $2.93
• 10 mg (per each): $2.93
• 70 mg (per each): $20.41 - $20.49

Tablets (Fosamax Oral):

• 70 mg (per each): $38.35

Alendronate Brands in Pakistan: