Leuprolide / Norethindrone Side Effects

Medically reviewed by Drugs.com. Last updated on Apr 20, 2024.

Applies to leuprolide / norethindrone: powder for suspension 1 month, powder for suspension 3 month, tablet.

Serious side effects

Along with its needed effects, leuprolide/norethindrone 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 leuprolide / norethindrone:

More common side effects

• crying
• depersonalization
• dysphoria
• euphoria
• feeling of warmth
• mental depression
• paranoia
• quick to react or overreact emotionally
• rapidly changing moods
• redness of the face, neck, arms, and occasionally, upper chest
• sudden sweating
• swelling

Incidence not known

• anxiety
• bladder pain
• bloody or cloudy urine
• blurred vision
• chest pain or tightness
• confusion
• cough
• dark urine
• difficult, burning, or painful urination
• difficulty speaking
• difficulty swallowing
• dizziness or lightheadedness
• double vision
• fainting
• fast heartbeat
• flu-like symptoms
• frequent urge to urinate
• headache
• hives or welts
• inability to move the arms, legs, or facial muscles
• increased sensitivity of the skin to sunlight
• itching
• joint or muscle pain or stiffness
• lower back or side pain
• nausea and vomiting
• numbness or tingling in the face, arms, or legs
• pain in the groin or genitals
• pain, redness, or swelling in the arm or leg
• pounding in the ears
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• redness of the skin
• seizures
• severe sunburn
• sharp back pain just below the ribs
• skin rash
• slow or fast heartbeat
• slow speech
• stomach tenderness
• sudden shortness of breath or trouble breathing
• sweating
• thoughts or attempts at killing oneself
• trouble breathing
• trouble sleeping
• trouble thinking or walking
• unusual tiredness or weakness
• yellow eyes or skin

Other side effects

Some side effects of leuprolide / norethindrone 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 side effects

• acid or sour stomach
• being forgetful
• belching
• bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
• blemishes on the skin
• bloated or full feeling
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• changes in appetite
• decreased interest in sexual intercourse
• diarrhea
• difficulty having a bowel movement (stool)
• excess air or gas in the stomach or intestines
• feeling of constant movement of self or surroundings
• hair loss or thinning of the hair
• headache, severe and throbbing
• heartburn
• inability to have or keep an erection
• indigestion
• lack or loss of strength
• loss in sexual ability, desire, drive, or performance
• pain or tenderness from the breasts
• passing gas
• pimples
• sensation of spinning
• stomach discomfort, upset, or pain
• weight gain

Less common side effects

• absent missed or irregular menstrual periods
• itching of the vagina or genital area
• pain during sexual intercourse
• stopping of menstrual bleeding
• thick, white vaginal discharge with no odor or with a mild odor

For healthcare professionals

Applies to leuprolide / norethindrone: oral and injectable kit.

General adverse events

The most common adverse reactions leading to discontinuation of therapy included hot flashes (4%), emotional lability (4%), depression (4%) and acne (2%).

The most common adverse reaction observed were hot flashes and headaches.^[Ref]

Cardiovascular

Leuprolide-Norethindrone:

• Very common (10% or more): Hot flashes/sweats (up to 87%)

Leuprolide:

• Very common (10% or more): Hot flashes/sweats (98%)
• Postmarketing reports: Hypotension, hypertension, serious venous and arterial thrombotic and thromboembolic events (deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, transient ischemic attack^[Ref]

Dermatologic

Leuprolide-Norethindrone:

• Very common (10% or more): Androgen-like effects (acne, alopecia) (up to 18%), skin/mucous membrane reaction (up to 11%)

Leuprolide:

• Common (1% to 10%): Androgen-like effects (acne, alopecia) (4%), skin/mucous membrane reaction (4%)^[Ref]

Gastrointestinal

Leuprolide-Norethindrone:

• Very common (10% or more): Altered bowel function (constipation, diarrhea) (up to 15%), nausea/vomiting (up to 29%)
• Common (1% to 10%): GI disturbances (dyspepsia, flatulence) (up to 7%), changes in appetite (6%)

Leuprolide:

• Very common (10% or more): Nausea/vomiting (25%), altered bowel function (constipation, diarrhea) (14%)
• Common (1% to 10%): Changes in appetite (4%)%), GI disturbances (dyspepsia, flatulence) (4%)^[Ref]

Genitourinary

Leuprolide-Norethindrone:

• Very common (10% or more): Vaginitis (up to 15%%), breast changes/pain/tenderness (up to 13%)
• Common (1% to 10%): Menstrual disorders (5%)
• Frequency not reported: Urinary tract infection

Leuprolide:

• Very common (10% or more): Vaginitis (20%)
• Common (1% to 10%): Breast changes/pain/tenderness (6%), menstrual disorders (2%)^[Ref]

Hematologic

Leuprolide:

• Postmarketing reports: Decreased white blood count^[Ref]

Hepatic

Leuprolide:

• Postmarketing reports: Serious liver injury

Leuprolide-Norethindrone:

• Common (1% to 10%): Elevated SGPT (at least twice the upper limit) (2%), elevated GGT (1.5%)^[Ref]

Hypersensitivity

Leuprolide-Norethindrone:

• Postmarketing reports: Allergic reactions (anaphylactic, rash, urticaria, photosensitivity)^[Ref]

Local

Leuprolide-Norethindrone:

• Common (1% to 10%): Injection site reaction (up to 9%)

Leuprolide:

• Common (1% to 10%): Injection site reaction (2%)
• Postmarketing reports: Localized reactions including induration and abscess at the site of injection^[Ref]

Metabolic

Leuprolide-Norethindrone:

• Very common (10% or more): Weight gain (up to 13%)
• Common (1% to 10%): Edema (up to 9%), elevated SGPT (at least twice the upper limit) (2%), elevated GGT (1.5%)
• Frequency not reported: Increased total cholesterol (greater than 240 mg/dL), decreased HDL cholesterol (less than 40 mg/dL), increased LDL cholesterol (greater than 160 mg/dL), increased LDL/HDL ratio (greater than 4), increased triglycerides (greater than 200 mg/dL)

Leuprolide:

• Common (1% to 10%): Weight gain (12%)^[Ref]

Musculoskeletal

Leuprolide:

• Postmarketing reports: Spinal fracture, tenosynovitis-like symptoms, symptoms consistent with fibromyalgia^[Ref]

Nervous system

Leuprolide-Norethindrone:

• Very common (10% or more): Headache/migraine (up to 51%), insomnia/sleep disorders (up to 15%), dizziness/vertigo (up to 11%)
• Common (1% to 10%): Neuromuscular disorder (leg cramps, paraesthesia) (up to 9%), decreased libido (up to 7%), memory disorder (up to 4%)

Leuprolide:

• Very common (10% or more): Headache/migraine (65%), insomnia/sleep disorders (31%), dizziness/vertigo (16%), decreased libido (10%)
• Common (1% to 10%): Memory disorder (6%), neuromuscular disorder (leg cramps, paraesthesia) (2%)
• Postmarketing reports: Pituitary apoplexy, convulsion, peripheral neuropathy, paralysis^[Ref]

Other

Leuprolide-Norethindrone:

• Very common (10% or more): Pain (up to 29%), asthenia (up to 18%)

Leuprolide:

• Very common (10% or more): Pain (24%), asthenia (18%)

Psychiatric

Leuprolide-Norethindrone:

• Very common (10% or more): Depression/emotional lability (up to 34%), nervousness/anxiety (up to 11%)

Leuprolide:

• Very common (10% or more): Depression/emotional lability (31%)
• Common (1% to 10%): Nervousness/anxiety (8%)
• Postmarketing reports: Mood swings, suicidal ideation and attempt^[Ref]

Renal

Leuprolide-Norethindrone:

• Frequency not reported: Renal calculus^[Ref]

Respiratory

Leuprolide:

• Postmarketing reports: Symptoms consistent with an asthmatic process^[Ref]

Further information

Leuprolide/norethindrone side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.

Medical Disclaimer