Alendronate (Fosamax) - Uses, Dose, MOA, Brands, Side effects

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 for the treatment and prevention of osteoporosis who are receiving a daily dose of 7.5 mg of prednisolone or more. It is also used in patients with the Paget's disease who are symptomatic, are at risk of complications and those with an alkaline phosphatase level of greater than twice the upper limits of normal.

Contraindications to alendronate:

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

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.

The patient may experience severe debilitating pain after the initiation of bisphosphonate therapy. Therapy may need to be interrupted.

The patient may develop dysphagia, erosive esophagitis, and esophageal strictures. Patients who can not sit upright or have anatomical esophageal defects like achalasia of cardia should avoid using oral alendronate.

Severe hypocalcemia may occur with the use of alendronate. Calcium supplements should be added to the therapy.

The patient may notice eye redness and swelling, conjunctivitis and uveitis. Ophthalmology consultation may be required.

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 who have been 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 once weekly.
For the treatment of osteoporosis:
- 10 mg once daily or 70 mg once weekly.

Alendronate for osteoporosis in men:

10 mg once daily or 70 mg once weekly

Osteoporosis due to prolonged glucocorticoid use:

5 mg once daily or 10 mg once daily in women who are not receiving estrogen. It is not recommended for pregnant women and those who plan to become pregnant.

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 advised to take the dose the next morning and then resume on the scheduled day. Two doses on the same day should be avoided.

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 fracture 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 Childrens

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

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

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

<25 kgs:
- 5 mg once daily
>25 Kgs:
- 10 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):

Less than 20 Kgs:
- 5 mg once daily
20 to 30 kgs:
- 5 or 10 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 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
- flatulence
- Gastroesophageal reflux disease
- Constipation/ diarrhea
- dyspepsia
- nausea
- esophageal ulcer
- dysphagia
- melena
- gastritis, and
- Gastric ulcer
Muscle cramps and musculoskeletal pain

Rare side effects:

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

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 months intervals.
For those with liver or biliary tract disease, alkaline phosphatase levels may be deceptive.
In such cases, other specific markers of bone turn over 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%

Bioavailability: 40 to 60 %

Half-life elimination exceeds 10 years

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:

Solution (Alendronate Sodium Oral):

70 mg/75 mL (per mL): $0.76

Tablet, effervescent (Binosto Oral):

70 mg (per each): $60.48

Tablets (Alendronate Sodium Oral):

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

Tablets (Fosamax Oral):

70 mg (per each): $38.35

Alendronate Brands in Pakistan:

Alendronate (Na) Injection 70 Mg]
Lendra	Lowitt Pharmaceuticals (Pvt) Ltd

Alendronate (Na) Tablets 5 Mg
Alendroflex	Novins International

Alendronate (Na) [Tabs 10 Mg]
Adonat	Medizan Labs (Pvt) Ltd
Adronate	Jinnah Pharmaceuticals
Aland	Heal Pharmaceuticals Pvt Ltd
Alandat	Swan Pharmaceuticals(Pvt) Ltd
Alemax	Medera Pharmaceuticals (Pvt) Ltd.
Alena	Cherwel Pharmaceuticals (Pvt) Ltd
Alendrate	Global Pharmaceuticals
Alendroflex	Novins International
Alendroscot	Scotmann Pharmaceuticals
Alenso	Goodman Laboratories
Bismax	Delux Chemical Industries
Bonate	Wilshire Laboratories (Pvt) Ltd.
Bonemed	Medicraft Pharmaceuticals (Pvt) Ltd.
Bonfit	Searle Pakistan (Pvt.) Ltd.
Bongard	Pharmevo (Pvt) Ltd.
Bonpart	Barrett Hodgson Pakistan (Pvt) Ltd.
Bostrong	P.D.H. Pharmaceuticals (Pvt) Ltd.
Drate	S.J. & G. Fazul Ellahie (Pvt) Ltd.
Firmofos	Zafa Pharmaceutical Laboratories (Pvt) Ltd.
Geonic	Everest Pharmaceuticals
Maxbon	Shrooq Pharmaceuticals
Osfre	Nexus Pharma (Pvt) Ltd
Osmaxx	Candid Pharmaceuticals
Ossomax	Hansel Pharmacueutical Pvt (Ltd)
Ostalend	Envoy Pharma
Ostamed	Rakaposhi Pharmaceutical (Pvt) Ltd.
Osteopor	Werrick Pharmaceuticals
Osto	Nabiqasim Industries (Pvt) Ltd.
Ostoimp	English Pharmaceuticals Industries
Oxopor	Medicaids Pakistan (Pvt) Ltd.
Ronate	Elko Organization (Pvt) Ltd.
Vitalit	Genera Pharmaceuticals

Alendronate (Na) [Tabs 40 Mg]
Bonate	Wilshire Laboratories (Pvt) Ltd.

Alendronate (Na) [Tabs 70 Mg]
Alen-Dro	Semos Pharmaceuticals (Pvt) Ltd.
Alendra	Miracle Pharmaceuticals(Pvt) Ltd
Alendrate	Global Pharmaceuticals
Alendroflex	Novins International
Alenkeu	High - Q International
Bonafide	Medisure Laboratories Pakistan (Pvt.) Ltd.
Bonate Ow	Wilshire Laboratories (Pvt) Ltd.
Bonemed	Medicraft Pharmaceuticals (Pvt) Ltd.
Bonfit	Searle Pakistan (Pvt.) Ltd.
Bongard	Pharmevo (Pvt) Ltd.
Bonpart	Barrett Hodgson Pakistan (Pvt) Ltd.
Calnate	Macter International (Pvt) Ltd.
Deonate	Cirin Pharmaceuticals (Pvt) Ltd.
Drate	S.J. & G. Fazul Ellahie (Pvt) Ltd.
Firmofos Weekly	Zafa Pharmaceutical Laboratories (Pvt) Ltd.
Fosamax	Obs
Fronate	Pearl Pharmaceuticals
Geonic	Everest Pharmaceuticals
Maxbon	Shrooq Pharmaceuticals
Opadronate	Opal Laboratories (Pvt) Ltd.
Orthonate	Schazoo Zaka
Ossel	Nova Med Pharmaceuticals
Ossomax	Hansel Pharmacueutical Pvt (Ltd)
Ostim	Genome Pharmaceuticals (Pvt) Ltd
Ostim	Genome Pharmaceuticals (Pvt) Ltd
Osto	Nabiqasim Industries (Pvt) Ltd.
Ostoimp	English Pharmaceuticals Industries
Reventa	Getz Pharma Pakistan (Pvt) Ltd.
Ronate Ow	Elko Organization (Pvt) Ltd.
Vitalit	Genera Pharmaceuticals