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Letrozole side effects and how to avoid them

Letrozole side effects include nausea, trouble sleeping, and cough
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By | Sep. 7, 2022 Medically reviewed by Marissa Walsh, Pharm.D., BCPS-AQ ID
Rx pill bottle: Letrozole side effects and how to avoid them

Key takeaways

  • Letrozole is a medication used to treat hormone receptor-positive breast cancer in postmenopausal women by blocking estrogen production, but it comes with side effects such as bone fractures, chest pain, and nausea.

  • Common side effects include elevated cholesterol levels, hot flashes, joint pain, weight changes, and fatigue, with serious side effects like new tumors, blood clots, and heart issues.

  • To avoid side effects, patients should provide a complete medical history, follow the prescription closely, reduce smoking and alcohol, take the medication with food, and increase calcium and vitamin D intake.

  • Management of side effects involves lifestyle adjustments and over-the-counter medications for symptoms like hot flashes and joint pain, and medical intervention for severe side effects such as bone loss and allergic reactions.

Common letrozole side effects | Serious side effects | Nausea | Difficulty sleeping | Cough | Side effects timeline | Contraindications | Warnings | Interactions | How to avoid side effects | How to treat side effects

Letrozole is a generic prescription drug used to treat postmenopausal women with hormone receptor-positive breast cancer. Hormone receptor-positive breast cancers encompass those cancers which express either estrogen or progestin receptors on cells, and when the hormones attach to such available receptors, this stimulates the cancer to grow and spread. Hormone-receptor breast cancers are further defined as estrogen receptor-positive or negative, and progestin receptor positive or negative. . As a breast cancer treatment, letrozole is intended to be taken for years to prevent cancer from returning. It is typically prescribed after surgery and with other drugs 

Letrozole, its brand-name version, Femara, and another drug, Arimidex (anastrozole), belong to a family of drugs called aromatase inhibitors. These drugs block the enzyme that synthesizes estrogen. Shutting down estrogen production stops the growth of hormone receptor-positive breast cancer tumors. As a hormone-blocking drug, letrozole’s side effects are commonly experienced. It is, however, a life-saving drug, so it’s important to learn about, prepare for, and manage side effects.

Common side effects of letrozole

Many of the most commonly-experienced side effects of letrozole are serious side effects such as bone fractures and chest pain. In order of incidence, the most common side effects of letrozole include:

  • Elevated cholesterol levels
  • Hot flashes
  • Joint pain
  • Bone fractures
  • Night sweats
  • Weight gain
  • Nausea
  • Fatigue
  • Muscle pain
  • Vaginal bleeding
  • Edema
  • Weight decrease
  • Osteoporosis
  • Dizziness
  • Hair loss
  • Vomiting
  • Constipation
  • Loss of appetite
  • Vaginal dryness or irritation

Serious side effects of letrozole

The most serious side effects of letrozole include:

  • Bone fractures
  • Chest pain
  • New tumors or malignancies including ovarian cancer
  • Blood clots including pulmonary embolism
  • Stroke
  • Heart attack
  • Heart failure
  • Chest pain
  • High blood pressure
  • High cholesterol
  • Osteoporosis
  • Severe allergic reactions

Nausea

Nausea is a common side effect of letrozole treatment, but it tends to be mild. In clinical trials, about 6% to 11% of participants complained of nausea, but severe nausea was rare. If nausea becomes severe or debilitating, get medical attention.

Difficulty sleeping

In clinical trials, trouble sleeping was reported in close to 8% of participants, but most of these problems were mild to moderate in severity. Since letrozole is intended for years of daily dosing, even mild sleeplessness can interfere with daily life. When trouble falling asleep or staying asleep becomes a problem, report the problem to the prescribing healthcare provider.

Cough

Coughing is a very common side effect of letrozole. About 6% to 13% of participants in clinical trials complained about coughing while taking the drug. Even mild coughing can be bothersome, but there are effective treatment options, so report any unwanted coughing to the prescribing healthcare provider.

How soon do letrozole side effects start?

Some of letrozole’s side effects appear early in treatment. These include weakness, drowsiness, and some other mild side effects. Most adverse effects of letrozole, however, are delayed side effects due to the accumulating effects of reduced estrogen production. They could take weeks or months before becoming a problem. However, letrozole therapy continues for several years, so delayed side effects are possible. 

How long do letrozole side effects last?

Some of letrozole’s mild side effects could resolve as the body adapts to the medicine. Delayed side effects, however, could persist as long as the drug is taken. These include coughing, hair thinning, swelling, and bone loss. Some of these longer-term side effects should resolve when treatment is discontinued. Some very serious side effects such as blood clots, stroke, or serious heart problems may have long-term or lifelong consequences.

What are the long-term side effects of letrozole?

Guidelines call for letrozole to be taken daily for five, seven, or 10 years to significantly reduce the risk of recurrence. Many of letrozole’s adverse effects occur because the drug is used for so long. Long-term side effects are primarily due to a prolonged drop in estrogen and mimic the symptoms of menopause. These long-term effects—hair thinning, bone loss, increased risk for bone fractures, and increased risk for cardiovascular disease—are possible consequences of long-term hormone suppression treatment.

Letrozole contraindications

Letrozole is never prescribed to:

  • Pregnant women
  • Women who have a known allergy to the drug

Pregnancy

Letrozole is contraindicated in pregnant women. Letrozole can harm or kill a fetus or cause spontaneous abortion. It is never used in pregnant women. However, women of reproductive age are often prescribed letrozole off-label as part of fertility treatment. The drug is only used for a short time and will not be reused if the woman becomes pregnant.

Breastfeeding

Although there is no research on whether letrozole is present in human breast milk or can harm a nursing infant, healthcare providers will advise women to stop breastfeeding while taking letrozole. They may also advise women not to begin breastfeeding until three weeks after the last dose of letrozole has been taken.

Children

The Food and Drug Administration (FDA) has not approved the use of letrozole in children or teens. However, letrozole is sometimes prescribed off-label to increase the height of boys with short stature or whose puberty is delayed or in young females experiencing precocious puberty. This treatment may affect fertility later in life.

Seniors

Healthcare professionals consider letrozole to be safe and effective in older women. Because letrozole is intended for postmenopausal women, clinical trials focused mainly on older women. A substantial percentage were older than 65 and many were older than 70. Women older than 70 had more side effects in comparison to younger women in clinical trials but overall responded well to this treatment. 

Letrozole warnings

All prescription drugs may cause problems either because of pre-existing conditions or other issues. Letrozole is no exception.

Cautions

Some pre-existing medical conditions can be worsened by the side effects of letrozole. These include: 

Abuse and dependence

Letrozole is not a drug that is used recreationally or abused. It is not associated with physical dependence or withdrawal.

Overdose

Call a poison control center or get medical attention if too much letrozole is taken. There are no known symptoms of a letrozole overdose. The maximum approved dosage is a single 2.5 mg tablet taken once per day, but fertility treatment doses can be as high as 20 mg per day. The best advice is to never take more than the prescribed dose.

Recalls

Letrozole has never been taken off the market entirely. However, individual batches from individual manufacturers have been recalled because of manufacturing irregularities. 

Letrozole interactions

Letrozole does not have many significant drug interactions. Because letrozole is used to suppress estrogen, estrogen-containing medicines are avoided. These include birth control pills and female hormone therapies containing estrogens or ethinyl estradiol. 

Tamoxifen, a drug used to block the effects of estrogen in women with certain types of breast cancer, is not used at the same time as letrozole. However, it is usually taken for several years before letrozole treatment.

How to avoid letrozole side effects

Letrozole is a long-term treatment, so managing possible side effects contributes a lot to the drug’s success.

1. Make sure the prescriber has a complete medical history

Realistically speaking, the cancer doctor, called an oncologist, will have a complete medical history and a great deal of information from medical tests before any drugs are prescribed. Anything you can do to fill out that history will help. The oncologist will be most concerned about a few particular medical conditions or drugs, including:

  • Problems with osteoporosis 
  • High cholesterol
  • Liver problems
  • Any female hormone replacement treatments
  • Tamoxifen treatment

2. Take letrozole as instructed

Follow all the instructions given by the prescriber or written on the prescription label when taking letrozole. Don’t miss doses, and don’t take extra medicine. If a dose is missed, take that dose when remembered. If it’s almost time for the next dose, though, skip the missed dose and take the next dose as scheduled. Do not take extra medicine to make up for a missed dose.

3. Cut back on smoking, alcohol, and hot drinks

Avoiding nicotine, alcohol, and hot drinks can help reduce the severity of hot flashes. Stopping smoking can help prevent bone loss and bone fractures.

4. Take letrozole with food

Letrozole can be taken with a meal or on an empty stomach. Taking it with or after eating can help prevent nausea and vomiting.

5. Get more calcium and vitamin D

To prevent bone loss, take daily calcium and vitamin D supplements. It also helps to add more calcium-rich and vitamin D-rich foods to the diet, foods like milk, cheese, eggs, and fatty fish.

6. Exercise

Another way to stave off bone loss is exercise and stretching. The best are exercises that involve staying on your feet, such as walking, jogging, dancing, or stair-climbing. Exercise can also help improve any tiredness or fatigue experienced during letrozole treatment.

How to treat side effects of letrozole

It is highly probable that you will experience at least some side effects when taking letrozole. Remember that letrozole is a life-saving cancer treatment. It reduces the probability that certain types of breast cancer will return in the same breast or other parts of the body. Managing side effects, then, can have a payoff that lasts a lifetime.

Some of letrozole’s most common side effects—especially early in the treatment—are menopausal symptoms. Women past menopause already have reduced estrogen because of changes to the ovaries. However, other tissues in the body still produce a little estrogen. Letrozole shuts that down, so estrogen levels fall even further, causing menopausal symptoms like hot flashes, vaginal dryness, and night sweats.

Hot flashes

To manage hot flashes, dress in layers—cotton clothing is best—and remove clothes when feeling too hot. Cooling pads, cold drinks, and spraying the face with cool water can also help. Report serious problems with hot flashes to the prescriber. Some drugs may help reduce the incidence and severity of hot flashes, particularly types of antidepressants called SSRIs and SNRIs.

Vaginal irritation

Vaginal dryness and irritation is another menopausal symptom associated with letrozole treatment. Over-the-counter lubricants and moisturizers can help.

Joint and muscle pain

Joint and muscle pain is a very common side effect of letrozole. It is also one of the most frequent reasons people stop taking letrozole. There are a few things that can help. Talk to the prescriber about over-the-counter pain relievers. Exercise and stretching can also help. If pain is severe, the prescriber could refer you to a joint specialist or a pain management specialist.

Headaches

Headaches are not that common a side effect, but when they do happen, try using over-the-counter pain relievers. If the pain is too debilitating, ask the prescribing healthcare provider for medical advice or treatment options.

Nausea and vomiting

An over-the-counter antiemetic (antinausea) medicine such as an antihistamine might help. If vomiting is severe or persistent, talk to a healthcare professional.

Vaginal bleeding

There may be some vaginal bleeding or spotting early in letrozole treatment. If, however, bleeding continues, contact the prescribing healthcare provider.

Bone loss

There are ways to help prevent bone loss, but healthcare professionals will regularly test patients for bone mineral density using a scanner or blood tests. There are no symptoms of bone loss, but fractures are more likely as bones get thinner. Healthcare providers will treat bone loss with medicines called bisphosphonates to help increase bone density.

Allergic reactions

Allergic reactions to letrozole require immediate medical attention and that the medicine be immediately discontinued. Symptoms include hives, trouble breathing, shortness of breath, and swelling of the face, mouth, or neck.

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