Leuprolide Side Effects

Brand Names: Eligard, Lupron Depot, Lupron Depot-PED, Viadur

Please note - some side effects for Leuprolide 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 Leuprolide - for the Consumer

Leuprolide

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 Leuprolide:

Breast tenderness; constipation; decreased sexual desire or ability; difficulty sleeping; hot flashes or sweating; infection (fever, chills, sore throat); nausea or vomiting; pain, redness, or swelling at the injection site.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blood in the urine; burning, numbness, tingling, or weakness; fainting; fast, slow, or irregular heartbeat; mental or mood changes (eg, anxiety, delusions, depression, nervousness); new or worsening bone pain; paralysis; seizures; severe dizziness or light-headedness; severe drowsiness; severe headache; shortness of breath; swelling of the hands, ankles, or feet; 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); trouble urinating or inability to urinate; 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.

Leuprolide Depot 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 Leuprolide Depot Suspension:

Constipation; dizziness; hot flashes; injection-site irritation (eg, mild burning, itching, pain, stinging, swelling); mild joint or back pain; tiredness; trouble sleeping.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); black, tarry stools; blood in the urine; burning, numbness, tingling, or weakness; decreased hearing; fainting; mood or mental changes (eg, anxiety, delusions, depression, nervousness); new or worsening bone pain; paralysis; seizures; severe dizziness or light-headedness; severe drowsiness; severe headache; shortness of breath; slow, fast, or irregular heartbeat; swelling of the hands, ankles, or feet; 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 infection (eg, chills, fever); symptoms of stroke (eg, confusion, one-sided weakness, slurred speech, vision changes); unusual bruising or bleeding; urination problems (eg, trouble urinating, inability to urinate, painful urination); vision changes or blurred vision; vomit that looks like coffee grounds.

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.

Leuprolide Implant

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 Leuprolide Implant:

Breast tenderness; burning, redness, itching, pain, or swelling around the implant; constipation; decreased sex drive; difficulty sleeping; headache; hot flashes/sweating; impotence; infection (fever, chills, sore throat); nausea or vomiting.

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

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blood in urine; dizziness or lightheadedness; increase in bone pain; muscle weakness; paralysis; severe drowsiness; severe headache; shortness of breath; trouble urinating or inability to urinate; unusual or one-sided numbness or weakness; 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.

Leuprolide 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 Leuprolide Kit:

Acne; hot flushes; mild headache; mild pain at the injection site; oily skin; sweating.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); fainting; injection-site irritation (eg, burning, itching, oozing, pain, stinging, swelling); mood or mental changes (eg, anxiety, depression, nervousness); numbness or tingling of the arms or legs; seizures; severe drowsiness; severe or persistent dizziness, lightheadedness, or headache; shortness of breath; signs of infection (eg, fever, chills, sore throat); slow, fast, or irregular heartbeat; trouble urinating (eg, loss of bladder control); unusual swelling of the hands, ankles, or feet; unusual weight gain; vaginal itching, irritation, odor, bleeding, or discharge; vision changes or blurred vision.

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.

Leuprolide 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 Leuprolide Suspension:

Dizziness; general body pain; injection-site irritation (eg, mild burning, itching, pain, stinging, swelling); tiredness; trouble sleeping; weakness.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); black, tarry stools; blood in the urine; burning, numbness, tingling, or weakness; decreased hearing; fainting; mood or mental changes (eg, anxiety, delusions, depression, nervousness); new or worsening bone pain; paralysis; seizures; severe dizziness or light-headedness; severe drowsiness; severe headache; shortness of breath; slow, fast, or irregular heartbeat; swelling of the hands, ankles, or feet; 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 infection (eg, chills, fever); symptoms of stroke (eg, confusion, one-sided weakness, slurred speech, vision changes); unusual bruising or bleeding; urination problems (eg, trouble urinating, inability to urinate, painful urination); vision changes or blurred vision; vomit that looks like coffee grounds.

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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Leuprolide Side Effects - for the Professional

Leuprolide

Clinical Trials

In the majority of patients testosterone levels increased above baseline during the first week, declining thereafter to baseline levels or below by the end of the second week of treatment. This transient increase was occasionally associated with a temporary worsening of signs and symptoms, usually manifested by an increase in bone pain. In a few cases a temporary worsening of existing hematuria and urinary tract obstruction occurred during the first week. Temporary weakness and paresthesia of the lower limbs have been reported in a few cases.

Potential exacerbations of signs and symptoms during the first few weeks of treatment is a concern in patients with vertebral metastases and/or urinary obstruction which, if aggravated, may lead to neurological problems or increase the obstruction.

In a comparative trial of Leuprolide acetate versus DES, in 5% or more of the patients receiving either drug, the following adverse reactions were reported to have a possible or probable relationship to drug as ascribed by the treating physician. Often, causality is difficult to assess in patients with metastatic prostate cancer. Reactions considered not drug related are excluded.

	Leuprolide Acetate (N=98)	DES (N=101)
	Number of Reports
* Physiologic effect of decreased testosterone.
Cardiovascular System
Congestive heart failure	1	5
ECG changes/ischemia	19	22
High blood pressure	8	5
Murmur	3	8
Peripheral edema	12	30
Phlebitis/thrombosis	2	10
Gastrointestinal System
Anorexia	6	5
Constipation	7	9
Nausea/vomiting	5	17
Endocrine System
*Decreased testicular size	7	11
*Gynecomastia/breast tenderness or pain	7	63
*Hot flashes	55	12
*Impotence	4	12
Hemic and Lymphatic System
Anemia	5	5
Musculoskeletal System
Bone pain	5	2
Myalgia	3	9
Central/Peripheral Nervous System
Dizziness/lightheadedness	5	7
General pain	13	13
Headache	7	4
Insomnia/sleep disorders	7	5
Respiratory System
Dyspnea	2	8
Sinus congestion	5	6
Integumentary System
Dermatitis	5	8
Urogenital System
Frequency/urgency	6	8
Hematuria	6	4
Urinary tract infection	3	7
Miscellaneous
Asthenia	10	10

In this same study, the following adverse reactions were reported in less than 5% of the patients on Leuprolide acetate injection.

Cardiovascular System—Angina, Cardiac arrhythmias, Myocardial infarction, Pulmonary emboli; Gastrointestinal System—Diarrhea, Dysphagia, Gastrointestinal bleeding, Gastrointestinal disturbance, Peptic ulcer, Rectal polyps; Endocrine System—Libido decrease, Thyroid enlargement; Musculoskeletal System—Joint pain; Central/Peripheral Nervous System—Anxiety, Blurred vision, Lethargy, Memory disorder, Mood swings, Nervousness, Numbness, Paresthesia, Peripheral neuropathy, Syncope/blackouts, Taste disorders; Respiratory System—Cough, Pleural rub, Pneumonia, Pulmonary fibrosis; Integumentary System—Carcinoma of skin/ear, Dry skin, Ecchymosis, Hair loss, Itching, Local skin reactions, Pigmentation, Skin lesions; Urogenital System—Bladder spasms, Dysuria, Incontinence, Testicular pain, Urinary obstruction; Miscellaneous—Depression, Diabetes, Fatigue, Fever/chills, Hypoglycemia, Increased BUN, Increased calcium, Increased creatinine, Infection/inflammation, Ophthalmologic disorders, Swelling (temporal bone).

In an additional clinical trial and from long-term observation of both studies, the following additional adverse events (excluding those considered not drug related) were reported for patients receiving Leuprolide acetate injection.

Cardiovascular System—Bradycardia, Carotid bruit, Extrasystole, Palpitations, Perivascular cuffing (eyes), Ruptured aortic aneurysm, Stroke, Tachycardia, Transient ischemic attack; Gastrointestinal System—Flatus, Dryness of mouth and throat, Hepatitis, Hepatomegaly, Occult blood (rectal exam), Rectal fistula/erythema; Endocrine System—Libido increase, Thyroid nodule; Musculoskeletal System—Ankylosing spondylosis, Arthritis, Blurred disc margins, Bone fracture, Muscle stiffness, Muscle tenderness, Pelvic fibrosis, Spasms/cramps; Central/Peripheral Nervous System—Auditory hallucinations/tinnitus, Decreased hearing, Decreased reflexes, Euphoria, Hyperreflexia, Loss of smell, Motor deficiency; Respiratory System—Chest tightness, Decreased breathing sounds, Hemoptysis, Pleuritic chest pain, Pulmonary infiltrate, Rales/rhonchi, Rhinitis, Strep throat, Wheezing/bronchitis; Integumentary System—Boil (pubic), Bruises, Hives, Keratosis, Mole, Shingles, Spiders; Urogenital System— Blisters on penis, Inguinal hernia, Penile swelling, Post void residual, Prostatic pain, Pyuria; Miscellaneous—Abdominal distention, Facial swelling/edema, Feet burning, Flu, Eyelid growth, Hypoproteinemia, Accidental injury, Knee effusion, Mass, Pallid, Sallow, Weakness.

Postmarketing

During postmarketing surveillance which includes other dosage forms and other patient populations, the following adverse events were reported.

Symptoms consistent with an anaphylactoid or asthmatic process have been rarely (incidence rate of about 0.002%) reported. Rash, urticaria, and photosensitivity reactions have also been reported.

Localized reactions including induration and abscess have been reported at the site of injection.

Symptoms consistent with fibromyalgia (e.g., joint and muscle pain, headaches, sleep disorders, gastrointestinal distress, and shortness of breath) have been reported individually and collectively.

Cardiovascular System – Hypotension, Myocardial infarction; Endocrine System - Diabetes; Gastrointestinal System – Hepatic dysfunction; Hemic and Lymphatic System – Decreased WBC; Integumentary System – Hair growth; Central/Peripheral Nervous System – Convulsion, Spinal fracture/paralysis, Hearing disorder; Miscellaneous – Hard nodule in throat, Weight gain, Increased uric acid; Musculoskeletal System – Tenosynovitis-like symptoms; Respiratory System – Respiratory disorders.

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. In a clinical trial, 25 men with prostate cancer, 12 of whom had been treated previously with Leuprolide acetate for at least six months, underwent bone density studies as a result of pain. The Leuprolide-treated group had lower bone density scores than the nontreated control group. It can be anticipated that long periods of medical castration in men will have effects on bone density.

Pituitary apoplexy: During postmarketing 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.

See other LUPRON DEPOT* and Leuprolide acetate injection package inserts for other events reported in the same and different patient populations.

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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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