DRUG PRESENTATION:

ZOLEDRONIC ACID (ACLASTA)

Presented by: CZARINA MAE F. CID

Zoledronic Acid (ACLASTA)

CLASS Biphosphonates

First and only once-yearly medicine for osteoporosis

MECHANISM OF ACTION Aclasta slows down bone resorption,

allowing the bone-forming cells time to rebuild normal bone.

DOSING

In ready to use plastic bottles 5 mg doses in 100 mL aqueous solution Single dose should not exceed 5 mg Given once a year.

BONE

STRUCTURE Compact (cortical) bone

The hard outer layer of bones is composed of compact bone tissue, so-called due to its minimal gaps and spaces. This tissue gives bones their smooth, white, and solid appearance, and accounts for 80% of the total bone mass of an adult skeleton.

Trabecular (cancellous) bone Filling the interior of the bone is the trabecular

bone tissue (an open cell porous network also called cancellous or spongy bone), which is composed of a network of rod- and plate-like elements that make the overall organ lighter and allow room for blood vessels and marrow.

BONE

CELLULAR STRUCTURE Osteoblasts are mononucleate bone-forming

cells which mineralizes to become bone. Osteocytes originate from osteoblasts that

have migrated into and become trapped and surrounded by bone matrix that they themselves produce. They are mature bone cells.

Osteoclasts are the cells responsible for bone resorption, thus they break down bone.

INDICATIONS & DOSING

INDICATION DOSING

Prevention of postmenopausal osteoporosis in women

5 mg IV infusion every 2 years

Treatment of osteoporosis in men 5 mg IV per year

Treatment of Paget’s disease of bone

5 mg given as one-time IV infusion; rarely needs re-treatment within 5 years

Treatment of glucocorticoid-induced osteoporosis

5 mg IV per year

Prevention of clinical fractures in patients after hip fracture

5 mg IV per year

Prevention of glucocorticoid-induced osteoporosis

5 mg IV per year

Treatment of postmenopausal osteoporosis in women

5 mg IV per year

OSTEOPOROSIS

A disease where the bone mineral density (BMD) is reduced, bone microarchitecture deteriorates, and the amount and variety of proteins in bone is altered which leads to an increased risk of fracture

Osteoporotic fractures are those that occur in situations where healthy people would not normally break a bone; aka. fragility fractures - vertebral column, rib, hip and wrist

OSTEOPOROSIS

POST MENOPAUSAL OSTEOPOROSIS Results from a lack of estrogen (e.g. as a

result of menopause) which increases bone resorption as well as decreases the deposition of new bone that normally takes place in weight-bearing bones.

OSTEOPOROSIS

Glucocortocoid-induced osteoporosis (GIOP)

PAGET’S DISEASE

Aka osteitis deformans or osteodystrophia deformans

Chronic disorder that can result in enlarged and misshapen bones. The excessive breakdown and formation of bone tissue causes affected bone to weaken, resulting in pain, misshapen bones, fractures, and arthritis in the joints near the affected bones.

Typically is localized Of viral or genetic etiology No cure

CONTRAINDICATION

Aspirin-sensitive asthma Dental disease Kidney disease Hypocalcemia Allergic sensitivity to similar medicine Pregnant or trying to get pregnant Breast feeding Patients already receiving Zometa Malabsorption syndrome Bone cancer

DRUG INTERACTIONS

Medicines that can harm your kidneys Diuretics – bumetanide and furosemide Certain antibiotics given by injection NSAIDs, medicines for pain and inflammation

– ibuprofen, naproxen Cancer medicine* Tell health care provider all medicines, herbs,

non-prescription drugs and dietary supplements,

* Smoking, drinking or illegal drugs

SIDE EFFECTS

Needs immediate intervention (Emergency): Allergic reactions: skin rash, itching or hives,

swelling of the face, lips or tongue, breathing problems

Serious side-effects: Urinating less than usual or not at all Muscle spasms, numb or tingly feeling (especially

around your mouth) Severe joint, bone, or muscle pain Jaw burning, cramping or pain – OSTEONECROSIS Fainting

HYPOCALCEMIA

Less than 2.1 mmol/L or 9 mg/dl or an ionized calcium level of less than 1.1 mmol/L or 4.5 mg/Dl Normal serum calcium: 2.2-2.6 mmol/L (9-

10.5 mg/dL)  Normal ionized calcium:1.1-1.4 mmol/L

(4.5-5.6 mg/dL)

HYPOCALCEMIA

"CATS go numb” Petechiae  Oral, perioral and acral paresthesias, tingling or 'pins and needles'

sensation in and around the mouth and lips, and in the extremities of the hands and feet

Carpopedal and generalized tetany Latent tetany

Trousseau sign of latent tetany Chvostek's sign 

Tendon reflexes are hyperactive Life threatening complications

Laryngospasm Cardiac arrhythmias

ECG changes include: Intermittent QT prolongation; puts the patient at high risk of torsades de

pointes

OSTEONECROSIS OF THE JAW (ONJ)

severe bone disease that affects the maxilla and the mandible.

Signs / symptoms: The definitive symptom of ONJ is the exposure of mandibular or maxillary bone through lesions in the gingiva that do not heal. Pain inflammation of the surrounding soft tissue secondary infection or drainage may or

may not be present.

SIDE EFFECTS

Do not usually require medical attention (report if it continues): Bone, joint or muscle pain Fever Irritation at IV site Loss of appetite Nausea and vomiting Stomach upset Feeling of fatigue

OVERDOSE

Signs and Symptoms Numbness or tingling in your hands and

feet Muscle stiffness Spasms in the muscles of your face Uneven heartbeats Wheezing or trouble breathing.

PRE-INFUSION CONSIDERATIONS Dental exam for preventive tooth and gum care Correct disturbances of mineral metabolism - Calcium and

vitamin D Ensure calcium is in normal range: 2.0-2.6mmol/L Vitamin D supplementation:

If patient is not on Vitamin D, administer 2 x 1.25mg calciferol during the week before infusion

Instruct patients to continue taking Vitamin D supplements (calciferol 1.25mg per month)

Confirm creatinine clearance is ≥35 mL/min. Do not infuse Aclasta in patients with creatinine clearance of <35 mL/min

On the day of the infusion, it is important to drink at least 500 mL (2 cups) of fluids before and after the treatment.

DURING THE INFUSION

Infuse over no less than 15 minutes over a constant infusion rate

Infuse at a slower rate in elderly patients Flushing is recommended Must be given in a separate, vented IV

line. Do not mix with other medication and must not come in contact with any calcium- or divalent cation-containing solution

POST INFUSION

In patients at risk for renal failure, consider interim monitoring of renal function

All patients should be instructed on the importance of calcium and vitamin D supplementation. Paget's disease: patient should also receive 1500 mg of elemental calcium and

800 IU vitamin D daily, especially during the 2 weeks after the injection of zoledronic acid.

It is strongly advised that patients with Paget’s disease receive adequate supplemental calcium corresponding to at least 500 mg elemental calcium twice a day and vitamin D, this should be ensured during the initial 10 days following Aclasta administrationn

Transient postdose symptoms (fever, myalgia, flu-like symptoms, headache and arthralgia) occur within 3 days of infusion and most resolved within 3 days of onset - Paracetamol or ibuprofen given up to 3 days after Aclasta

Adequate calcium and vitamin D intake prior to Aclasta therapy in patients with preexisting hypocalcaemia, and for 10 days following Aclasta in patients with Paget's disease of the bone

STORAGE AND STABILITY

Keep unopened vial below 30˚C. Opened vials should be used

immediately. Unused, opened vials can be stored up

to 24hrs at 2-8 ˚ C Discard any unused contents of the vial

after infusion. Alcasta must reach room temperature

prior to infusion if refrigerated.

THANK YOU!