Note: This document contains side effect information about zoledronic acid. Some dosage forms listed on this page may not apply to the brand name Aclasta.

Applies to zoledronic acid: intravenous powder for solution, intravenous solution.

Serious side effects of Aclasta

Along with its needed effects, zoledronic acid (the active ingredient contained in Aclasta) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking zoledronic acid:

More common

• Agitation
• black, tarry stools
• blurred vision
• chest pain
• chills
• coma
• confusion
• convulsions
• cough
• depression
• difficult or labored breathing
• dizziness
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fever
• irregular heartbeat
• irritability
• lack or loss of strength
• lethargy
• lower back or side pain
• muscle pain or cramps
• muscle trembling or twitching
• nausea or vomiting
• numbness and tingling around the mouth, fingertips, or feet
• painful or difficult urination
• pale skin
• rapid weight gain
• seizures
• shaking of the hands, arms, feet, legs, or face
• skin rash, cracks in the skin at the corners of the mouth, or soreness or redness around the fingernails and toenails
• sore throat
• sores, ulcers, or white spots on the lips or mouth
• stupor
• sudden sweating
• swollen glands
• tightness in the chest
• trouble breathing with exercise
• unusual bleeding or bruising
• unusual tiredness or weakness

Less common

• Feeling of constant movement of self or surroundings
• muscle cramps in the hands, arms, feet, legs, or face
• muscle spasms
• neck pain
• pounding in the ears
• rapid breathing
• sensation of spinning
• slow or fast heartbeat
• sunken eyes
• tingling of the hands or feet
• tremor

Incidence not known

• Blurred vision or other change in vision
• decreased frequency or amount of urine
• decreased vision
• eye pain
• eye tenderness
• heavy jaw feeling
• increased blood pressure
• increased tearing
• increased thirst
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• loosening of a tooth
• pain, swelling, or numbness in the mouth or jaw
• redness of the eye
• sensitivity of the eye to light
• severe eye pain
• swelling of the face, hands, fingers, lower legs, or ankles
• weight gain

Other side effects of Aclasta

Some side effects of zoledronic acid may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Abdominal or stomach pain
• back pain
• bad, unusual, or unpleasant (after) taste
• bladder pain
• blistering, crusting, irritation, itching, or reddening of the skin
• bloody or cloudy urine
• bone pain
• burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings
• change in taste
• constipation
• cracked lips
• cracked, dry, or scaly skin
• diarrhea
• difficulty with swallowing
• discouragement
• dry mouth
• ear congestion
• feeling sad or empty
• frequent urge to urinate
• hair loss or thinning hair
• headache
• hyperventilation
• joint pain or swollen joints
• loss of appetite
• loss of interest or pleasure
• loss of voice
• muscle stiffness or difficulty with moving
• nasal congestion or runny nose
• pain, swelling, or redness in the joints
• partial loss of feeling
• seeing, hearing, or feeling things that are not there
• sleepiness or unusual drowsiness
• swelling or inflammation of the mouth
• thirst
• trouble concentrating
• trouble sleeping
• unusually cold, shivering
• vomiting
• weight loss

Less common

• Acid or sour stomach
• belching
• heartburn
• indigestion
• red streaks on the skin
• stomach discomfort or upset
• swelling, tenderness, or pain at the injection site
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
• wrinkled skin

Rare

• Burning, dry, or itching eyes
• discharge or excessive tearing
• redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid
• throbbing pain

For Healthcare Professionals

Applies to zoledronic acid: intravenous powder for injection, intravenous solution.

General

In general, side effects have been mild and transient and similar to other bisphosphonates.

Acute phase reactions have occurred within three days after administration of this drug with symptoms of pyrexia, fatigue, bone pain and/or arthralgias, myalgias, chills, and influenza-like illness. Symptoms usually resolve within three days of onset, but resolution can take up to 7 to 14 days, and some symptoms have persisted for a longer duration.^[Ref]

Cardiovascular

Very common (10% or more): Hypotension (10.5%)

Common (1% to 10%): Atrial fibrillation

Uncommon (0.1% to 1%): Palpitations, flushing, hypotension, hypotension leading to syncope or circulatory collapse

Rare (less than 0.1%): Bradycardia

Very rare (less than 0.01%): Cardiac arrhythmia (secondary to hypocalcemia)

Postmarketing reports: Atrial fibrillation, hypertension, bradycardia, and hypotension^[Ref]

In the postmenopausal osteoporosis trial, adjudicated serious adverse events of atrial fibrillation in the zoledronic acid treatment group occurred in 1.3% of patients (50 out of 3862) compared to 0.4% (17 out of 3852) in the placebo group. The overall incidence of all atrial fibrillation adverse events in the zoledronic acid treatment group was, reported in 2.5% of patients (96 out of 3862) in the Reclast group vs. 1.9% of patients (75 out of 3852) in the placebo group.^[Ref]

Dermatologic

Very common (10% or more): Alopecia (12%) and dermatitis (11%)

Uncommon (0.1% to 1%): Pruritus, hyperhidrosis, rash (including erythematous and macular rash), increased sweating

Frequency not reported: Stevens-Johnson syndrome, epidermal necrolysis

Postmarketing reports: Increased sweating and urticaria^[Ref]

Gastrointestinal

Very common (10% or more): Nausea (29.1% to 46%), vomiting (14% to 32%), constipation (26.7% to 31%), diarrhea (17.4% to 24%), abdominal pain (14% to 16.3%), dyspepsia (10%)

Common (1% to 10%): Stomatitis, sore throat, dysphagia

Uncommon (0.1% to 1%): Gastroesophageal reflux disease, esophagitis, toothache, gastritis

Postmarketing reports: Dry mouth^[Ref]

Genitourinary

Very common (10% or more): Urinary tract infection (14%)^[Ref]

Hematologic

Very common (10% or more): Anemia (22.1% to 33%) and neutropenia (12%)

Common (1% to 10%): Granulocytopenia, thrombocytopenia and pancytopenia

Uncommon (0.1% to 1%): Leukopenia^[Ref]

Metabolic

Grade 3 and 4 laboratory abnormalities have included hypophosphatemia (51.4%, grade 3; 1.4%, grade 4) and hypocalcemia (1.2%, grade 3).^[Ref]

Very common (10% or more): Hypophosphatemia (12.8%), hypokalemia (11.6%), hypomagnesemia (10.5%),

Common (1% to 10%): Dehydration, hypocalcemia

Uncommon (0.1% to 1%): Anorexia, decrease appetite

Rare (less than 0.1%): Hyperkalemia, hypernatremia^[Ref]

Musculoskeletal

Very common (10% or more): Bone pain (55%), myalgia (23%), arthralgia (21%), back pain (15%), and limb pain (14%)

Common (1% to 10%): Myalgia, arthralgia, generalized pain, pain in extremity

Uncommon (0.1% to 1%): Muscle cramps, osteonecrosis of the jaw (ONJ), neck pain, musculoskeletal stiffness, joint swelling, muscle spasms, shoulder pain, musculoskeletal chest pain, musculoskeletal pain, joint stiffness, arthritis, muscular weakness

Rare (less than 0.1%): Atypical subtrochanteric and diaphyseal femoral fractures (bisphosphonate class adverse reaction)

Postmarketing reports: Muscle cramps; osteonecrosis of the jaw, hip, and femur have been reported predominantly in cancer patients treated with intravenous bisphosphonates (many of these patients were also receiving chemotherapy and corticosteroids which may be a risk factor for ONJ).^[Ref]

Cases of osteonecrosis (primarily of the jaws) have been reported, predominantly in cancer patients taking this drug. Many of these patients had signs of local infection including osteomyelitis, and the majority of the reports refer to cancer patients following tooth extractions or other dental surgeries. Osteonecrosis of the jaws has multiple documented risk factors including a diagnosis of cancer, concomitant therapies (e.g. chemotherapy, radiotherapy, corticosteroids) and co-morbid conditions (e.g. anemia, coagulopathies, infection, pre-existing oral disease).^[Ref]

Nervous system

Very common (10% or more): Headache (19%), dizziness (18%), paresthesia (15%), hypoesthesia (12%)

Common (1% to 10%): Somnolence

Uncommon (0.1% to 1%): Paraesthesia, taste disturbance, hyperesthesia, tremor, somnolence, syncope, dysgeusia, lethargy

Very rare (less than 0.01%): Seizures, numbness and tetany (secondary to hypocalcemia)

Frequency not reported: Neurological events due to hypokalemia (e.g., seizures, numbness, tetany)

Postmarketing reports: Taste disturbance, hyperesthesia, tremor^[Ref]

Other

Fever is the most common adverse effect associated with zoledronic acid (the active ingredient contained in Aclasta) infusion.

Flu-like syndromes including fever, chills, bone pain, and/or arthralgias and myalgias have also occasionally been reported. These symptoms generally did not require treatment and resolved within 24 to 48 hours.^[Ref]

Very common (10% or more): Fever (44.2%), moniliasis (11.6%)

Common (1% to 10%): Nonspecific infections, asthenia, mucositis, chest pain, leg edema

Uncommon (0.1% to 1%): Vertigo

Postmarketing reports: Flu-like syndrome, pyrexia, fatigue, malaise; osteonecrosis of the external auditory canal have been reported predominantly in cancer patients treated with intravenous bisphosphonates (many of these patients were also receiving chemotherapy and corticosteroids which may be a risk factor for ONJ).^[Ref]

Psychiatric

Very common (10% or more): Insomnia (15.1%), anxiety (14%), depression (14%), agitation (12.8%)

Common (1% to 10%): Confusion^[Ref]

Renal

The following factors have been associated with an increased risk: Pre-existing renal dysfunction, dehydration, multiple cycles of zoledronic acid (the active ingredient contained in Aclasta) or other bisphosphonates, concomitant use of nephrotoxic medicines and use of a shorter infusion time than what is recommended.

The frequency of renal impairment adverse events suspected to be related to this drug was as follows: Multiple myeloma (3.2%), prostate cancer (3.1%), breast cancer (4.3%), lung and other solid tumors (3.2%). Renal deterioration, progression to renal failure and dialysis have been reported in patients after the initial dose or a single dose of 4 mg zoledronic acid.^[Ref]

Very common (10% or more): Renal toxicity (deterioration of renal function or renal failure),

Common (1% to 10%): Grade 3 increases (more than 3 times upper limit of normal) in serum creatinine in 2.3% of patients, blood urea increased

Uncommon (0.1% to 1%): Acute renal failure, hematuria, proteinuria, pollakiuria

Postmarketing reports: Hematuria, proteinuria, hyperkalemia, hypernatremia^[Ref]

Respiratory

Very common (10% or more): Dyspnea (22.1% to 27%), coughing (11.6% to 22%), upper respiratory infection (10%)

Uncommon (0.1% to 1%): Pleural effusion

Rare (less than 0.1%): Interstitial lung disease

Postmarketing reports: Bronchoconstriction and asthma exacerbations^[Ref]

Ocular

Common (1% to 10%): Conjunctivitis, ocular hyperemia

Uncommon (0.1% to 1%): Blurred vision, scleritis, orbital inflammation, eye pain

Very rare (less than 0.01%): Uveitis, episcleritis, iritis

Frequency not reported: Scleritis

Postmarketing reports: Uveitis, scleritis, episcleritis, conjunctivitis, iritis, and orbital inflammation including orbital edema^[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Hypersensitivity reaction including bronchoconstriction, urticaria, angioedema, anaphylactic reaction/shock^[Ref]

Local

Uncommon (0.1% to 1%): Injection site reactions (including pain, irritation, swelling, induration)

Postmarketing reports: Itching and pain at the injection site^[Ref]

Immunologic

Rare (less than 0.1%): Angioneurotic edema^[Ref]

Oncologic

Frequency not reported: Aggravation of malignant neoplasm and progression of cancer^[Ref]