Monthly Archives: Maret 2020

Side effects

report in September 2009 from Health and Human Services’ Agency for Healthcare Research and Quality suggests that tamoxifen, raloxifene, and tibolone used to treat breast cancer significantly reduce invasive breast cancer in midlife and older women, but also increase the risk of adverse side effects.[35]

Some cases of lower-limb lymphedema have been associated with the use of tamoxifen, due to the blood clots and deep vein thrombosis (DVT) that can be caused by this medication. Resolution of the blood clots or DVT is needed before lymphedema treatment can be initiated.

Bone[edit]

A beneficial side effect of tamoxifen is that it prevents bone loss by acting as an ER agonist (i.e., mimicking the effects of estrogen) in this cell type. Therefore, by inhibiting osteoclasts, it prevents osteoporosis.[36][37] When tamoxifen was launched as a drug, it was thought that tamoxifen would act as an ER antagonist in all tissue, including bone, and therefore it was feared that it would contribute to osteoporosis. It was therefore very surprising that the opposite effect was observed clinically. Hence tamoxifen’s tissue selective action directly led to the formulation of the concept of SERMs.[38] In contrast tamoxifen appears to be associated with bone loss in premenopausal women who continue to menstruate after adjuvant chemotherapy.[39]

Endometrial cancer[edit]

Tamoxifen is a SERM.[40] Even though it is an antagonist in breast tissue it acts as partial agonist on the endometrium and has been linked to endometrial cancer in some women. Therefore, endometrial changes, including cancer, are among tamoxifen’s side effects.[41] With time, risk of endometrial cancer may be doubled to quadrupled, which is a reason tamoxifen is typically only used for five years.[42]

The American Cancer Society lists tamoxifen as a known carcinogen, stating that it increases the risk of some types of uterine cancer while lowering the risk of breast cancer recurrence.[43] The ACS states that its use should not be avoided in cases where the risk of breast cancer recurrence without the drug is higher than the risk of developing uterine cancer with the drug.

Cardiovascular and metabolic[edit]

Tamoxifen treatment of postmenopausal women is associated with beneficial effects on serum lipid profiles. However, long-term data from clinical trials have failed to demonstrate a cardioprotective effect.[44] For some women, tamoxifen can cause a rapid increase in triglyceride concentration in the blood. In addition, there is an increased risk of thromboembolism especially during and immediately after major surgery or periods of immobility.[45] Use of tamoxifen has been shown to slightly increase risk of deep vein thrombosispulmonary embolism, and stroke.[46] Tamoxifen is also a cause of fatty liver, otherwise known as steatorrhoeic hepatosis or steatosis hepatis.[47]

Central nervous system[edit]

Tamoxifen-treated breast cancer patients show evidence of reduced cognition,[48] and semantic memory scores.[49] However, memory impairment in patients treated with tamoxifen was less severe compared with those treated with anastrozole (an aromatase inhibitor).[50]

A significant number of tamoxifen-treated breast cancer patients experience a reduction of libido.[51][52]

Liver toxicity[edit]

Tamoxifen has been associated with a number of cases of hepatotoxicity.[53] Several different varieties of hepatotoxicity have been reported.[53]

Weight gain[edit]

Weight gain is a commonly reported side effect,[54] but studies have not been able to find significant evidence of a correlation.[55]

Overdose[edit]

Acute overdose of tamoxifen has not been reported in humans.[4] In dose-ranging studies, tamoxifen was administered at very high doses in women (e.g., 300 mg/m2) and was found to produce acute neurotoxicity including tremorhyperreflexiaunsteady gait, and dizziness.[4] These symptoms occurred within three to five days of therapy and disappeared within two to five days of discontinuation of therapy.[4] No indications of permanent neurotoxicity were observed.[4] QT prolongation was also observed with very high doses of tamoxifen.[4] There is no specific antidote for overdose of tamoxifen.[4] Instead, treatment should be based on symptoms.[4]

Interactions[edit]

Patients with variant forms of the gene CYP2D6 (also called simply 2D6) may not receive full benefit from tamoxifen because of too slow metabolism of the tamoxifen prodrug into its active metabolites.[56][57] On 18 October 2006, the Subcommittee for Clinical Pharmacology recommended relabeling tamoxifen to include information about this gene in the package insert.[58]

Certain CYP2D6 variations in breast cancer patients lead to a worse clinical outcome for tamoxifen treatment.[59] Genotyping therefore has the potential for identification of women who have these CYP2D6 phenotypes and for whom the use of tamoxifen is associated with poor outcomes.

Recent studies suggest that taking the selective serotonin reuptake inhibitors (SSRIs) antidepressants paroxetine (Paxil), fluoxetine (Prozac), and sertraline (Zoloft) can decrease the effectiveness of tamoxifen, as these drugs compete for the CYP2D6 enzyme which is needed to metabolize tamoxifen into its active forms.[60] A U.S. study presented at the American Society of Clinical Oncology’s annual meeting in 2009 found that after two years, 7.5% of women who took only tamoxifen had a recurrence, compared with 16% who took either paroxetine, fluoxetine or sertraline, drugs considered to be the most potent CYP2D6 inhibitors. That difference translates to a 120% increase in the risk of breast cancer recurrence. Patients taking the SSRIs; Celexa (citalopram), Lexapro (escitalopram), and Luvox (fluvoxamine), did not have an increased risk of recurrence, due to their lack of competitive metabolism for the CYP2D6 enzyme.[61] A newer study demonstrated a clearer and stronger effect from paroxetine in causing the worst outcomes. Patients treated with both paroxetine and tamoxifen have a 67% increased risk of death from breast cancer, from 24% to 91%, depending on the duration of coadministration.[62]

Recent research has shown that 7–10% of women with breast cancer may not receive the full medical benefit from taking tamoxifen due to their genetic make-up. DNA Drug Safety Testing can examine DNA variations in the CYP2D6 and other important drug processing pathways. More than 20% of all clinically used medications are metabolized by CYP2D6 and knowing the CYP2D6 status of a person can help the doctor with the future selection of medications.[63] Other molecular biomarkers may also be used to select appropriate patients likely to benefit from tamoxifen.[64]

Tamoxifen interacts with certain other antiestrogens.[3] The aromatase inhibitor aminoglutethimide induces the metabolism of tamoxifen.[3] Conversely, the aromatase inhibitor letrozole does not affect the metabolism of tamoxifen.[3] However, tamoxifen induces the metabolism of letrozole and significantly reduces its concentrations.[3]

Infertility

Tamoxifen is used for ovulation induction to treat infertility in women with anovulatory disorders. It is given at days three to seven of a woman’s cycle.[24]

Tamoxifen improves fertility in males with infertility by disinhibiting the hypothalamic–pituitary–gonadal axis (HPG axis) via ER antagonism and thereby increasing the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and increasing testicular testosterone production.[25]

Gynecomastia[edit]

Tamoxifen is used to prevent and treat gynecomastia.[26][27] It is taken as a preventative measure in small doses, or used at the onset of any symptoms such as nipple soreness or sensitivity. Other medications are taken for similar purposes such as clomifene and the anti-aromatase drugs which are used in order to try to avoid the hormone-related adverse effects.

Tamoxifen doses and rates of bicalutamide-induced breast symptoms in men 

Early puberty[edit]

Tamoxifen is useful in the treatment of peripheral precocious puberty, for instance due to McCune–Albright syndrome, in both girls and boys.[30][31][32] It has been found to decrease growth velocity and the rate of bone maturation in girls with precocious puberty, and hence to improve final height in these individuals.[30][31]

Available forms[edit]

Nolvadex (tamoxifen) 20 mg tablets.

Tamoxifen is available as a tablet or oral solution.[33][34]

Contraindications[edit]

Tamoxifen has a number of contraindications, including known hypersensitivity to tamoxifen or other ingredients, individuals taking concomitant coumarin-type anticoagulant therapy, and women with a history of venous thromboembolism (deep vein thrombosis or pulmonary embolism).[4]

Tamoxifen

Tamoxifen, sold under the brand name Nolvadex among others, is a medication that is used to prevent breast cancer in women and treat breast cancer in women and men.[8] It is also being studied for other types of cancer.[8] It has been used for Albright syndrome.[9] Tamoxifen is typically taken daily by mouth for five years for breast cancer.[9]

Serious side effects include a small increased risk of uterine cancerstroke, vision problems, and pulmonary embolism.[9] Common side effects include irregular periods, weight loss, and hot flashes.[9] It may cause harm to the baby if taken during pregnancy or breastfeeding.[9] It is a selective estrogen-receptor modulator (SERM) and works by decreasing the growth of breast cancer cells.[9][10] It is a member of the triphenylethylene group of compounds.[11]

Tamoxifen was initially made in 1962, by chemist Dora Richardson.[12][13] It is on the World Health Organization’s List of Essential Medicines, the safest and most effective medicines needed in a health system.[14] Tamoxifen is available as a generic medication.[9] The wholesale price in the developing world is about US$0.07–0.23 per day.[15] In the United States, it costs about $1 per day.[9] In 2016, it was the 238th most prescribed medication in the United States, with more than two million prescriptions.[16]

Medical uses[edit]

Breast cancer[edit]

Tamoxifen is used for the treatment of both early and advanced estrogen receptor-positive (ER-positive or ER+) breast cancer in pre- and post-menopausal women.[17] Additionally, it is the most common hormone treatment for male breast cancer.[18] It is also approved by the FDA for the prevention of breast cancer in women at high risk of developing the disease.[19] It has been further approved for the reduction of contralateral (in the opposite breast) cancer. The use of tamoxifen is recommended for 10 years.[20]

In 2006, the large STAR clinical study concluded that raloxifene is also effective in reducing the incidence of breast cancer. Updated results after an average of 6.75 years of follow up found that raloxifene retains 76% of tamoxifen’s effectiveness in preventing invasive breast cancer, with 45% fewer uterine cancers and 25% fewer blood clots in women taking raloxifene than in women taking

Self-Care Tips:

  • Do not stop taking this medication unless your healthcare provider tells you. You may be on it for as long as 5 years.
  • If you are experiencing hot flashes, wearing light clothing, staying in a cool environment, and putting cool cloths on your head may reduce symptoms. Consult you health care provider if these worsen, or become intolerable
  • This medication causes little nausea.  But if you should experience nausea, take anti-nausea medications as prescribed by your doctor, and eat small frequent meals.  Sucking on lozenges and chewing gum may also help.
  • Avoid sun exposure.  Wear SPF 15 (or higher) sunblock and protective clothing.
  • In general, drinking alcoholic beverages should be kept to a minimum or avoided completely.  You should discuss this with your doctor.
  • Get plenty of rest.
  • Maintain good nutrition.
  • If you experience symptoms or side effects, be sure to discuss them with your health care team.  They can prescribe medications and/or offer other suggestions that are effective in managing such problems.

Monitoring and Testing:

You will be checked regularly by your health care professional while you are taking tamoxifen, to monitor side effects and check your response to therapy.  Periodic blood work to monitor your complete blood count (CBC) as well as the function of other organs (such as your kidneys and liver) may also be ordered by your doctor.

Women will need a gynecologic (GYN) examination before therapy, and during therapy, at regular intervals.  Discuss the appropriate schedule with your health care provider.

How This Drug Works:

Hormones are chemical substances that are produced by glands in the body, which enter the bloodstream and cause effects in other tissues.  For example, the hormone testosterone, made in the testicles and is responsible for male characteristics such as deepening voice and increased body hair.  The use of hormone therapy to treat cancer is based on the observation that receptors for specific hormones that are needed for cell growth are on the surface of some tumor cells.  Hormone therapy can work by stopping the production of a certain hormone, blocking hormone receptors, or substituting chemically similar agents for the active hormone, which cannot be used by the tumor cell.  The different types of hormone therapies are categorized by their function and/or the type of hormone that is affected.

Tamoxifen is an antiestrogen.  Antiestrogens bind to estrogen receptor site on cancer cells thus blocking estrogen from going into the cancer cell.  This interferes with cell growth and eventually leads to cell death. The following are antiestrogen medications.

  • tamoxifen, toremifene

Note:  We strongly encourage you to talk with your health care professional about your specific medical condition and treatments. The information contained in this website is meant to be helpful and educational, but is not a substitute for medical advice.

Nolvadex

Generic name:  Tamoxifen

Chemocare.com uses generic names in all descriptions of drugs. Nolvadex is the trade name for Tamoxifen. In some cases, health care professionals may use the trade name Nolvadex when referring to the generic drug name Tamoxifen.

Drug type:  Nolvadex is a hormone therapy.  This medication is classified as an “anti-estrogen.”  (For more detail, see “How this drug works” section below).

What This Drug Is Used For:

  • Tamoxifen may be given as adjuvant therapy (treatment after successful surgery) in women or men with lymph node negative or lymph node positive breast cancer.  Cancers with positive estrogen and progesterone receptors are more likely to benefit from tamoxifen.  Tamoxifen reduces the risk of getting breast cancer in the opposite breast.
  • Tamoxifen may be prescribed in metastatic (cancer that has spread) breast cancer in both women and men.
  • Tamoxifen may be prescribed in women with ductal carcinoma in situ (DCIS) who have completed surgery and radiation therapy.  Tamoxifen may reduce the risk of invasive breast cancer.  Risks and benefits of tamoxifen therapy should be discussed in this setting.
  • Tamoxifen may be prescribed for women at high risk of breast cancer to reduce the incidence of developing breast cancer.  Risks and benefits of tamoxifen therapy should be discussed in this setting.
  • Tamoxifen may also be prescribed for treatment of ovarian cancer.
    Note:  If a drug has been approved for one use, physicians may elect to use this same drug for other problems if they believe it may be helpful.

How This Drug Is Given:

  • Tamoxifen is a pill, given by mouth.  The pill should be swallowed whole.
  • Tamoxifen should be taken at about the same time each day with a full glass of water.  If you miss a dose, do not take a double dose the next day.
  • The amount of tamoxifen that you will receive depends on many factors, including your general health or other health problems, and the type of cancer or condition being treated.  Your doctor will determine your dose, schedule and duration of treatment.

Side Effects:

Important things to remember about the side effects of tamoxifen:

  • Most people do not experience all of the side effects listed.
  • Side effects are often predictable in terms of their onset and duration.
  • Side effects are almost always reversible and will go away after treatment is complete.
  • There are many options to help minimize or prevent side effects.
  • There is no relationship between the presence or severity of side effects and the effectiveness of the medication.

The following side effects are common (occurring in greater than 30%) for patients taking tamoxifen:

  • Hot flashes (see sexuality)
  • Vaginal discharge (see sexuality)
  • Swelling (fluid retention in feet, ankles, or hands)
  • Loss of libido (particularly in men) (see sexuality)

These side effects are less common side effects (occurring in about 10-29%) of patients receiving tamoxifen:

  • Nausea
  • Menstrual irregularities
  • Vaginal bleeding
  • Weight loss
  • Mood changes (see anxiety and/or depression)

rare, but serious side effect of tamoxifen is blood clots, including deep vein thrombosis (DVT) and pulmonary embolus.  You should seek emergency help and notify your health care provider immediately if you develop sudden chest pain and shortness of breath.  Notify your health care provider within 24 hours if you notice that one leg is swollen, red, painful and/or warm to touch and the other is not.

rare, but serious side effect of tamoxifen can be the development of uterine cancer.  Women who have not had a hysterectomy should have regular pap smears and gyn examinations.  Abnormal vaginal bleeding should be reported to your health care provider.

Your fertility, meaning your ability to conceive or father a child, may be affected by tamoxifen.  Please discuss this issue with your health care provider.

Not all side effects are listed above. Some that are rare (occurring in less than 10% of patients) are not listed here.  However, you should always inform your health care provider if you experience any unusual symptoms.

When to contact your doctor or health care provider:

Seek emergency help immediately and notify your health care provider, it you experience the following symptoms:

  • Sudden shortness of breath and/or chest pain

The following symptoms require medical attention, but are not an emergency.  Contact your health care provider within 24 hours of noticing any of the following:

  • Swelling, redness and/or pain in one leg or arm and not the other
  • New breast lumps
  • Excessive vaginal discharge or bleeding, menstrual (period) pain or irregularities
  • Nausea (interferes with ability to eat and unrelieved with prescribed medication)
  • Depression (interfering with your ability to carry on your regular activities)
  • Changes in vision

Always inform your health care provider if you experience any unusual symptoms.

Precautions:

  • Before starting tamoxifen treatment, make sure you tell your doctor about any other medications you are taking (including prescription, over-the-counter, vitamins, herbal remedies, etc.). Do not take aspirin, products containing aspirin unless your doctor specifically permits this.
  • Let your health care professional know if you have ever had a blood clot that required medical treatment.
  • Inform your health care professional if you are pregnant or may be pregnant prior to starting this treatment. Pregnancy category D (tamoxifen may be hazardous to the fetus.  Women who are pregnant or become pregnant must be advised of the potential hazard to the fetus).
  • For both men and women: Do not conceive a child (get pregnant) while taking tamoxifen. Barrier methods of contraception, such as condoms, are recommended. Discuss with your doctor when you may safely become pregnant or conceive a child after therapy.
  • Do not breast feed while taking this medication.