Eligard Side Effects

Generic Name: leuprolide,leuprolide acetate

Please note - some side effects for Eligard may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of Eligard - for the Consumer

Eligard Kit

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Eligard Kit:

Dizziness; hot flashes; increased sweating; mild burning, bruising, itching, pain, redness, stinging, or swelling at the injection site; muscle pain; tiredness.

Seek medical attention right away if any of these SEVERE side effects occur when using Eligard Kit:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blood in the urine; bone pain; burning, numbness, or tingling; fainting; mental or mood changes (eg, depression); seizures; severe dizziness or lightheadedness; symptoms of heart attack (eg, chest, jaw, or left arm pain; numbness of an arm or leg; sudden, severe headache or vomiting); symptoms of high blood sugar (eg, drowsiness; fast breathing; flushing; fruit-like breath odor; increased thirst, hunger, or urination); symptoms of stroke (eg, confusion, one-sided weakness, slurred speech); unusual tiredness or weakness; urination problems (eg, inability to urinate, loss of bladder control, painful urination); vision changes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

Eligard Suspension

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Eligard Suspension:

Dizziness; hot flashes; increased sweating; mild burning, bruising, itching, pain, redness, stinging, or swelling at the injection site; muscle pain; tiredness.

Seek medical attention right away if any of these SEVERE side effects occur when using Eligard Suspension:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blood in the urine; bone pain; burning, numbness, or tingling; fainting; mental or mood changes (eg, depression); seizures; severe dizziness or lightheadedness; symptoms of heart attack (eg, chest, jaw, or left arm pain; numbness of an arm or leg; sudden, severe headache or vomiting; vision changes); symptoms of high blood sugar (eg, drowsiness; fast breathing; flushing; fruit-like breath odor; increased thirst, hunger, or urination); symptoms of stroke (eg, confusion, one-sided weakness, slurred speech, vision changes); unusual tiredness or weakness; urination problems (eg, inability to urinate, loss of bladder control, painful urination); vision changes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

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Eligard Side Effects - for the Professional

Eligard

The safety of all Eligard® formulations was evaluated in clinical trials involving patients with advanced prostate cancer. In addition, the safety of Eligard® 7.5 mg was evaluated in 8 surgically castrated males (Table 7). Eligard®, like other LH-RH analogs, caused a transient increase in serum testosterone concentrations during the first one to two weeks of treatment. Therefore, potential exacerbations of signs and symptoms of the disease during the first weeks of treatment are of concern in patients with vertebral metastases and/or urinary obstruction or hematuria. If these conditions are aggravated, it may lead to neurological problems such as weakness and/or paresthesia of the lower limbs or worsening of urinary symptoms.

During the clinical trials, injection sites were closely monitored. Refer to Table 6 for a summary of reported injection site events.

Table 6 Reported Injection Site Adverse Events
7.5 mg 22.5 mg 30 mg 45 mg
*
Following injection of Eligard® 30 mg, three of the 35 burning/stinging events were reported as moderate.
A single event reported as moderate pain resolved within two minutes and all 3 mild pain events resolved within several days following injection of Eligard® 30 mg.
Transient pain was reported as mild in intensity in nine of ten (90%) events and moderate in intensity in one of ten (10%) events following injection of Eligard® 45 mg.
§
Erythema was reported following 2 injections of Eligard® 22.5 mg. One report characterized the erythema as mild and it resolved within 7 days. The other report characterized the erythema as moderate and it resolved within 15 days. Neither patient experienced erythema at multiple injections.
Mild bruising was reported following 5 (2.3%) study injections and moderate bruising was reported following 2 (<1%) study injections of Eligard® 45 mg.
Study Number AGL9904 AGL9909 AGL0001 AGL0205
Number of patients 120 117 90 111
Treatment 1 injection every month up to 6 months 1 injection every 3 months up to 6 months 1 injection every 4 months up to 8 months 1 injection every 6 months up to 12 months
Number of injections 716 230 175 217
 
Transient burning/stinging 248 (34.6%) injections;84% reported as mild 50 (21.7%) injections; 86% reported as mild 35 (20%) injections; 100% reported as mild 35 (16%) injections; 91.4% reported as mild*
Pain (generally brief and mild) 4.3% of injections (18.3% of patients) 3.5% of injections (6.0% of patients) 2.3% of injections (3.3% of patients) 4.6% of injections
Erythema (generally brief and mild) 2.6% of injections (12.5% of patients) 0.9% of injections§ (1.7% of patients) 1.1% of injections (2.2% of patients)
Bruising (Mild) 2.5% of injections (11.7% of patients) 1.7% of injections (3.4% of patients) 2.3% of injections
Pruritis 1.4% of injections (9.2% of patients) 0.4% of injections (0.9% of patients)
Induration 0.4% of injections (2.5% of patients)
Ulceration 0.1% of injections (> 0.8% of patients)

These localized adverse events were non-recurrent over time. No patient discontinued therapy due to an injection site adverse event.

The following possibly or probably related systemic adverse events occurred during clinical trials with Eligard®, and were reported in > 2% of patients (Table 7). Often, causality is difficult to assess in patients with metastatic prostate cancer. Reactions considered not drug-related are excluded.

Table 7 Summary of Possible or Probably Related Systemic Adverse Events Reported by > 2% of Patients treated with Eligard®
7.5 mg 7.5 mg 22.5 mg 30 mg 45 mg
In the patient populations studied with Eligard® 7.5 mg, a total of 86 hot flashes/sweats adverse events were reported in 70 patients. Of these, 71 events (83%) were mild; 14 (16%) were moderate; 1 (1%) was severe.
In the patient population studied with Eligard® 22.5 mg, a total of 84 hot flashes/sweats adverse events were reported in 66 patients. Of these, 73 events (87%) were mild; 11 (13%) were moderate; none were severe.
In the patient population studied with Eligard® 30 mg, a total of 75 hot flash adverse events were reported in 66 patients. Of these, 57 events (76%) were mild; 16 (21%) were moderate; 2 (3%) were severe.
In the patient population studied with Eligard® 45 mg, a total of 89 hot flash adverse events were reported in 64 patients. Of these, 62 events (70%) were mild; 27 (30%) were moderate; none were severe.
*
Expected pharmacological consequences of testosterone suppression.
Study Number AGL9904 AGL9802 AGL9909 AGL0001 AGL0205
Number of patients 120 8 117 90 111
Treatment 1 injection every month up to 6 months 1 injection (surgically castrated patients) 1 injection every 3 months up to 6 months 1 injection every 4 months up to 8 months 1 injection every 6 months up to 12 months
Body System Adverse Event Number (Percent)
Body as a Whole Malaise and Fatigue 21 (17.5 %) 7 (6.0%) 12 (13.3%) 13 (11.7%)
Weakness 4 (3.6%)
Nervous System Dizziness 4 (3.3%) 4 (4.4%)
Vascular Hot flashes/sweats 68 (56.7%)* 2 (25.0%)* 66 (56.4%)* 66 (73.3%)* 64 (57.7%)*
Renal/Urinary Urinary frequency 3 (2.6%) 2 (2.2%)
Nocturia 2 (2.2%)
Gastrointestinal Nausea 4 (3.4%) 2 (2.2%)
Gastroenteritis/colitis 3 (2.5%)
Skin Pruritis 3 (2.6%)
Clamminess 4 (4.4%)*
Night sweats 3 (3.3%)* 3 (2.7%)*
Alopecia 2 (2.2%)
Musculoskeletal Arthralgia 4 (3.4%)
Myalgia 2 (2.2%) 5 (4.5%)
Pain in limb 3 (2.7%)
Reproductive Testicular atrophy 6 (5.0%) 4 (4.4%)* 8 (7.2%)*
Gynecomastia 2 (2.2%)* 4 (3.6%)*
Testicular pain 2 (2.2%)
Psychiatric Decreased libido 3 (3.3%)*

In addition, the following possibly or probably related systemic adverse events were reported by < 2% of the patients treated with Eligard® in these clinical studies.

Body System Adverse Event
*
Expected pharmacological consequences of testosterone suppression.
General Sweating, insomnia, syncope, rigors, weakness, lethargy
Gastrointestinal Flatulence, constipation, dyspepsia
Hematologic Decreased red blood cell count, hematocrit and hemoglobin
Metabolic Weight gain
Musculoskeletal Tremor, backache, joint pain, muscle atrophy, limb pain
Nervous Disturbance of smell and taste, depression, vertigo
Psychiatric Insomnia, depression, loss of libido*
Renal/Urinary Difficulties with urination, pain on urination, scanty urination, bladder spasm, blood in urine, urinary retention, urinary urgency, incontinence, nocturia, nocturia aggravated
Reproductive/
Urogenital:
Testicular soreness/pain, impotence*, decreased libido*, gynecomastia*, breast soreness/tenderness*, testicular atrophy*, erectile dysfunction, penile disorder*, reduced penis size
Skin Alopecia, clamminess, night sweats*, sweating increased*
Vascular Hypertension, hypotension

Changes in Bone Density

Decreased bone density has been reported in the medical literature in men who have had orchiectomy or who have been treated with an LH-RH agonist analog.3 It can be anticipated that long periods of medical castration in men will have effects on bone density.


3
Hatano T et al. Incidence of bone fracture in patients receiving luteinizing hormone-releasing hormone agonists for prostate cancer. BJU International 2000 86: 449–452.

Post-Marketing

Pituitary apoplexy

During post-marketing surveillance, rare cases of pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) have been reported after the administration of gonadotropin-releasing hormone agonists. In a majority of these cases, a pituitary adenoma was diagnosed with a majority of pituitary apoplexy cases occurring within 2 weeks of the first dose, and some within the first hour. In these cases, pituitary apoplexy has presented as sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. Immediate medical attention has been required.

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Side Effects by Body System - for Healthcare Professionals

Endocrine

Endocrine side effects of leuprolide have included hot flashes (56% to 91%), gynecomastia (7%), breast changes (7%), breast enlargement (7%), breast tenderness (7% to 14%), decrease in testicular size, diabetes, and impotence. In addition, rare cases of pituitary apoplexy have been reported after the use of gonadotropin-releasing hormone agents.

Endocrine side effects occur in the majority of patients treated with leuprolide and are due to drug-induced hypoestrogenism and hypoandrogenism.

Pituitary apoplexy is a clinical syndrome secondary to infarction of the pituitary gland. In a majority of the cases reported, a pituitary adenoma was diagnosed. A majority of pituitary apoplexy cases occurred within two weeks of the first dose, and some occurred within the first hour. In those cases, pituitary apoplexy presented as sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. Immediate medical attention has been required.

Psychiatric

Psychiatric side effects have included depression and emotional lability (up to 45%), insomnia (2% to 7%), anxiety, nervousness, decreased libido (both males and females), increased libido (females), and short-term memory loss.

Nervous system

Nervous system side effects have included headache (7% to 39%), dizziness (5%), blurred vision, lethargy, paresthesias, numbness, peripheral neuropathy, spinal fracture, convulsions, transient ischemic attack, and paralysis. A case of atypical absence seizures induced by leuprolide acetate has also been reported.

Genitourinary

A number of cases of vaginal hemorrhage are reported in the literature. The presence of submucous leiomyomatas may be responsible for these events. These patients typically required emergency surgery and blood transfusions.

Massive ascites developed in one patient 3 weeks after receiving a 3.75 mg leuprolide depot injection for the treatment of leiomyomata uteri. Upon surgical resection, the uterine myomas were noted to be seeping large amounts of serous fluid.

Genitourinary side effects have included vaginal dryness (37%), urinary frequency, hematuria, ovarian hyperstimulation, testicular soreness/pain, breast soreness/tenderness,testicular atrophy, erectile dysfunction, penile disorder, reduced penis size and vaginal hemorrhage.

Cardiovascular

Cardiovascular side effects have included ECG changes (19%), ischemia (19%), peripheral edema (12%), hypertension, hypotension, murmur, phlebitis, venous and arterial thromboembolism, deep vein thrombosis, stroke, sudden cardiac death, arrhythmias, angina, pulmonary edema, pulmonary embolism, and myocardial infarction.

Gastrointestinal

Gastrointestinal side effects have included constipation (7%), anorexia (3% to 6%), nausea and vomiting (5%), weight loss, flatulence, dyspepsia, and weight gain.

Dermatologic

Dermatologic side effects have included skin rash (7%), acne, dry skin, ecchymosis, hair loss (up to 18% of females), pruritus, photosensitivity, clamminess, night sweats, increased sweating, and skin pigmentation.

Musculoskeletal

An initial increase in testosterone levels may occur during the first 2 weeks of therapy with leuprolide. An increase in bone pain, as well as worsening of other signs and symptoms of advanced prostate cancer, may be noted during this time period.

Hypoestrogenism induced by leuprolide may result in small losses in bone density. Prolonged use of leuprolide in females may increase the risk of osteoporosis.

Musculoskeletal side effects have included increased bone pain in patients with advanced prostate cancer, myalgias, arthralgias, muscle atrophy, limb pain, lower bone density scores, and tenosynovitis-like symptoms. A case of polymyositis and a case of noninflammatory myopathy have also been reported.

Hypersensitivity

A case of anaphylaxis after a single intramuscular injection of leuprolide depot is reported in the literature. On two occasions, 24 hours and 6 weeks after injection, the patient required emergency airway management. The patient continued to require regular doses of antihistamines and intermittent epinephrine injections up to 14 weeks after leuprolide administration.

Hypersensitivity reactions have included a rare report of urticaria, shortness of breath, and anaphylaxis with the depot form. Other reports of anaphylactic reactions to synthetic GnRH or GnRH agonist analogs have also been reported in the medical literature.

Hematologic

Hematologic side effects have included anemia, leukopenia, and hemoptysis.

Respiratory

Respiratory side effects have included dyspnea, sinus congestion, cough, pleural rub, and pulmonary fibrosis.

Local

Local side effects have included erythema, ecchymosis, induration, abscess, and irritation at the site of injection.

Oncologic

Oncologic side effects have been reported including case reports of granulomas. Animal studies including an increase in benign pituitary hyperplasia and benign pituitary adenomas, an increase of pancreatic islet cell adenomas in females, and an increase of testicular cell adenomas in males have also been reported.

Other

Other side effects including symptoms consistent with fibromyalgia (e.g., joint and muscle pain, headaches, sleep disorders, gastrointestinal distress, and shortness of breath) have been reported. Hearing disorder, hard nodule in throat, weight gain, and increased uric acid have also been reported.

Hepatic

Hepatic side effects including hepatic dysfunction have been reported.

General

General side effects including sweating, syncope, rigors, weakness, and lethargy have been reported.

Renal

Renal side effects have included difficulties with urination, pain on urination, scanty urination, bladder spasm, blood in urine, urinary retention, urinary urgency, incontinence, nocturia, and aggravated nocturia.

Metabolic

Metabolic side effects have included hyperglycemia.

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