Acido Alendronico Semanal Gervasi may be available in the countries listed below.
Alendronic Acid sodium trihydrate (a derivative of Alendronic Acid) is reported as an ingredient of Acido Alendronico Semanal Gervasi in the following countries:
International Drug Name Search
Fluoro-Uracile ICN may be available in the countries listed below.
Fluorouracil is reported as an ingredient of Fluoro-Uracile ICN in the following countries:
International Drug Name Search
Lorinol may be available in the countries listed below.
Loratadine is reported as an ingredient of Lorinol in the following countries:
International Drug Name Search
Antidepressants may increase the risk of suicidal thoughts or actions in children, teenagers, and young adults. However, depression and certain other mental problems may also increase the risk of suicide. Talk with the patient's doctor to be sure that the benefits of using Doxepin Concentrate outweigh the risks.
Family and caregivers must closely watch patients who take Doxepin Concentrate. It is important to keep in close contact with the patient's doctor. Tell the doctor right away if the patient has symptoms like worsened depression, suicidal thoughts, or changes in behavior. Discuss any questions with the patient's doctor.
Treating depression or anxiety in certain patients. It may also be used for other conditions as determined by your doctor.
Doxepin Concentrate is a tricyclic antidepressant. It is not known exactly how it works. It may increase the activity of certain chemicals in the brain, which help elevate mood.
Contact your doctor or health care provider right away if any of these apply to you.
Treatments for depression are getting better everyday and there are things you can start doing right away.
Some medical conditions may interact with Doxepin Concentrate. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
Some MEDICINES MAY INTERACT with Doxepin Concentrate. Tell your health care provider if you are taking any other medicines, especially any of the following:
This may not be a complete list of all interactions that may occur. Ask your health care provider if Doxepin Concentrate may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
Use Doxepin Concentrate as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Ask your health care provider any questions you may have about how to use Doxepin Concentrate.
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:
Appetite loss; constipation; diarrhea; dizziness; drowsiness; dry mouth; excess sweating; headache; heartburn; increased appetite; indigestion; nausea; unpleasant taste; urinary retention; vomiting; weakness; weight gain.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); abnormal movements; aggressive or bizarre behavior; agitation; anxiety; blurred vision or other vision changes; chest pain; difficulty speaking and swallowing; disorientation; eye pain; fainting; fast, slow, or irregular heartbeat; hair loss; hallucinations; hostility; irritability; loss of balance; mood swings; nervousness or restlessness; panic attacks; ringing in the ears; seizures; shakiness; sore throat or fever; trouble sleeping; twitching of the face or tongue; unusual bleeding or bruising; yellowing of the skin or eyes.
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.
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include agitation; confusion; drowsiness; dry mouth; enlarged pupils; fast or irregular heartbeat; flushing; loss of consciousness; seizures.
Store Doxepin Concentrate at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Doxepin Concentrate out of the reach of children and away from pets.
This information is a summary only. It does not contain all information about Doxepin Concentrate. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Diclostar PF may be available in the countries listed below.
Diclofenac sodium salt (a derivative of Diclofenac) is reported as an ingredient of Diclostar PF in the following countries:
International Drug Name Search
Valpakine may be available in the countries listed below.
Valproic Acid sodium (a derivative of Valproic Acid) is reported as an ingredient of Valpakine in the following countries:
International Drug Name Search
Generic Name: l-methylfolate (L-METH il FOE late)
Brand Names: Deplin, Zervalx
Folate is a form of B vitamin that occurs naturally in many foods. Folic acid is the man-made form of folate that is added to processed foods or vitamin and mineral supplements. Folate is needed in the human body for production of red blood cells.
A lack (deficiency) of folate in the human body can be caused by certain diseases, by taking certain medications, or by not getting enough folate in your diet. Folate deficiency can lead to decreased red blood cells, or anemia.
L-methylfolate is a medical food for use in people who have conditions related to folate deficiency.
The Zervalx brand of l-methylfolate is used in the following situations:
in people who have high levels of a certain amino acid in their blood, a condition called hyperhomocysteinemia (HYE-per-HOE-moe-sis-tin-EE-mee-a). This condition can be related to folate deficiency or may be caused by receiving methotrexate (Rheumatrex, Trexall);
in women with high-risk pregnancies who need additional folate in their diets to prevent hyperhomocysteinemia; or
in people with certain types of anemia (a lack of red blood cells) that may be complicated by a folate deficiency.
The Deplin brand of l-methylfolate is used in the following situations:
in people with major depressive disorder who have folate deficiency. Deplin is used together with anti-depressant medications in people with major depressive disorder and low folate levels.
in people with schizophrenia who have hyperhomocysteinemia related to folate deficiency.
L-methylfolate may also be used for other purposes not listed in this medication guide.
Before you take this medication, tell your doctor if you have a vitamin B12 deficiency, pernicious anemia, a history of bipolar disorder (manic depression), or if you are pregnant or breast-feeding.
Treatments for depression are getting better everyday and there are things you can start doing right away.
Tell your doctor about all other medications you use, especially seizure medications. Do not start a new medication without telling your doctor.
If you have certain conditions, you may need a dose adjustment or special tests to safely use this medication. Before using l-methylfolate, tell your doctor if you have:
a history of bipolar disorder (manic depression);
vitamin B12 deficiency; or
pernicious anemia.
Use this product exactly as prescribed by your doctor. Do not use it in larger amounts or for longer than recommended. Follow the directions on your prescription label.
You may take l-methylfolate with or without food. Follow your doctor's instructions.
L-methylfolate is only part of a complete program of treatment that may also include other medications, and psychological counseling when used in people with depression or schizophrenia. Follow your medication and counseling routines very closely.
Take the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to take the medicine and skip the missed dose. Do not take extra medicine to make up the missed dose.
An overdose of l-methylfolate is not likely to cause life-threatening symptoms.
Less serious side effects may include:
nausea;
loss of appetite;
bloating;
gas; or
bitter taste in your mouth.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Tell your doctor about all other medications you use, especially seizure medication such as:
carbamazepine (Carbatrol, Tegretol);
ethosuximide (Zarontin);
fosphenytoin (Cerebyx);
lamotrigine (Lamictal);
phenobarbital (Solfoton);
phenytoin (Dilantin);
primidone (Mysoline); or
valproic acid valproate.
Other drugs that can interact with l-methylfolate include:
birth control pills;
cholestyramine (Prevalite, Questran), colestipol (Colestid);
colchicine;
isotretinoin (Accutane);
methylprednisolone (Medrol);
methotrexate (Rheumatrex, Trexall);
pancreatin (Hi-Vegi-Lip), pancrelipase (Cotazym, Pancrease, Ultrase);
pentamidine (Nebupent);
pyrimethamine (Daraprim);
sulfasalazine (Azulfidine);
triamterene (Dyrenium);
trimethoprim (Proloprim, Bactrim, Septra); or
a non-steroidal anti-inflammatory drug (NSAID) such as ibuprofen (Advil, Motrin), indomethacin (Indocin), naproxen (Aleve, Naprosyn), or sulindac (Clinoril).
This list is not complete and there may be other drugs that can interact with l-methylfolate. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.
See also: Deplin side effects (in more detail)
Nerfeco may be available in the countries listed below.
Mecobalamin is reported as an ingredient of Nerfeco in the following countries:
International Drug Name Search
Omebloc may be available in the countries listed below.
Omeprazole is reported as an ingredient of Omebloc in the following countries:
International Drug Name Search
The incidence of treatment-related mortality associated with Docetaxel therapy is increased in patients with abnormal liver function, in patients receiving higher doses, and in patients with non-small cell lung carcinoma and a history of prior treatment with platinum-based chemotherapy who receive Docetaxel as a single agent at a dose of 100 mg/m2 [see Warnings and Precautions (5.1)].
Docetaxel Injection should not be given to patients with bilirubin > upper limit of normal (ULN), or to patients with AST and/or ALT >1.5 × ULN concomitant with alkaline phosphatase >2.5 × ULN. Patients with elevations of bilirubin or abnormalities of transaminase concurrent with alkaline phosphatase are at increased risk for the development of grade 4 neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death. Patients with isolated elevations of transaminase >1.5 × ULN also had a higher rate of febrile neutropenia grade 4 but did not have an increased incidence of toxic death. Bilirubin, AST or ALT, and alkaline phosphatase values should be obtained prior to each cycle of Docetaxel Injection therapy [see Warnings and Precautions (5.2)].
Docetaxel Injection therapy should not be given to patients with neutrophil counts of <1500 cells/mm3. In order to monitor the occurrence of neutropenia, which may be severe and result in infection, frequent blood cell counts should be performed on all patients receiving Docetaxel Injection [see Warnings and Precautions (5.3)].
Severe hypersensitivity reactions characterized by generalized rash/erythema, hypotension and/or bronchospasm, or very rarely fatal anaphylaxis, have been reported in patients who received a 3-day dexamethasone premedication. Hypersensitivity reactions require immediate discontinuation of the Docetaxel Injection infusion and administration of appropriate therapy [see Warnings and Precautions (5.4)]. Docetaxel Injection must not be given to patients who have a history of severe hypersensitivity reactions to Docetaxel or to other drugs formulated with polysorbate 80 [see Contraindications (4)].
Severe fluid retention occurred in 6.5% (6/92) of patients despite use of a 3-day dexamethasone premedication regimen. It was characterized by one or more of the following events: poorly tolerated peripheral edema, generalized edema, pleural effusion requiring urgent drainage, dyspnea at rest, cardiac tamponade, or pronounced abdominal distention (due to ascites) [see Warnings and Precautions (5.5)].
Docetaxel Injection is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy.
Docetaxel Injection in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer.
Docetaxel Injection as a single agent is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy.
Docetaxel Injection in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer who have not previously received chemotherapy for this condition.
Docetaxel Injection in combination with prednisone is indicated for the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer.
For all indications, toxicities may warrant dosage adjustments [see Dosage and Administration (2.7)].
Administer in a facility equipped to manage possible complications (e.g. anaphylaxis).
All patients should be premedicated with oral corticosteroids (see below for prostate cancer) such as dexamethasone 16 mg per day (e.g., 8 mg twice daily) for 3 days starting 1 day prior to Docetaxel Injection administration in order to reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions [see Boxed Warning, Warnings and Precautions (5.4)].
For hormone-refractory metastatic prostate cancer, given the concurrent use of prednisone, the recommended premedication regimen is oral dexamethasone 8 mg, at 12 hours, 3 hours and 1 hour before the Docetaxel Injection infusion [see Warnings and Precautions (5.4)].
Breast Cancer
Patients who are dosed initially at 100 mg/m2 and who experience either febrile neutropenia, neutrophils <500 cells/mm3 for more than 1 week, or severe or cumulative cutaneous reactions during Docetaxel Injection therapy should have the dosage adjusted from 100 mg/m2 to 75 mg/m2. If the patient continues to experience these reactions, the dosage should either be decreased from 75 mg/m2 to 55 mg/m2 or the treatment should be discontinued. Conversely, patients who are dosed initially at 60 mg/m2 and who do not experience febrile neutropenia, neutrophils <500 cells/mm3 for more than 1 week, severe or cumulative cutaneous reactions, or severe peripheral neuropathy during Docetaxel Injection therapy may tolerate higher doses. Patients who develop ≥grade 3 peripheral neuropathy should have Docetaxel Injection treatment discontinued entirely.
Combination Therapy with Docetaxel Injection in the Adjuvant Treatment of Breast Cancer
Docetaxel Injection in combination with doxorubicin and cyclophosphamide should be administered when the neutrophil count is ≥1,500 cells/mm3. Patients who experience febrile neutropenia should receive G-CSF in all subsequent cycles. Patients who continue to experience this reaction should remain on G-CSF and have their Docetaxel Injection dose reduced to 60 mg/m2. Patients who experience grade 3 or 4 stomatitis should have their Docetaxel Injection dose decreased to 60 mg/m2. Patients who experience severe or cumulative cutaneous reactions or moderate neurosensory signs and/or symptoms during Docetaxel Injection therapy should have their dosage of Docetaxel Injection reduced from 75 to 60 mg/m2. If the patient continues to experience these reactions at 60 mg/m2, treatment should be discontinued.
Non-Small Cell Lung Cancer
Monotherapy with Docetaxel Injection for NSCLC treatment after failure of prior platinum-based chemotherapy
Patients who are dosed initially at 75 mg/m2 and who experience either febrile neutropenia, neutrophils <500 cells/mm3 for more than one week, severe or cumulative cutaneous reactions, or other grade 3/4 non-hematological toxicities during Docetaxel Injection treatment should have treatment withheld until resolution of the toxicity and then resumed at 55 mg/m2. Patients who develop ≥grade 3 peripheral neuropathy should have Docetaxel Injection treatment discontinued entirely.
Combination therapy with Docetaxel Injection for chemotherapy-naïve NSCLC
For patients who are dosed initially at Docetaxel Injection 75 mg/m2 in combination with cisplatin, and whose nadir of platelet count during the previous course of therapy is <25,000 cells/mm3, in patients who experience febrile neutropenia, and in patients with serious non-hematologic toxicities, the Docetaxel Injection dosage in subsequent cycles should be reduced to 65 mg/m2. In patients who require a further dose reduction, a dose of 50 mg/m2 is recommended. For cisplatin dosage adjustments, see manufacturers' prescribing information.
Prostate Cancer
Combination therapy with Docetaxel Injection for hormone-refractory metastatic prostate cancer
Docetaxel Injection should be administered when the neutrophil count is ≥1,500 cells/mm3. Patients who experience either febrile neutropenia, neutrophils <500 cells/mm3 for more than one week, severe or cumulative cutaneous reactions or moderate neurosensory signs and/or symptoms during Docetaxel Injection therapy should have the dosage of Docetaxel Injection reduced from 75 mg to 60 mg/m2. If the patient continues to experience these reactions at 60 mg/m2, the treatment should be discontinued.
Combination Therapy with Strong CYP3A4 Inhibitors
Avoid using concomitant strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole). There are no clinical data with a dose adjustment in patients receiving strong CYP3A4 inhibitors. Based on extrapolation from a pharmacokinetic study with ketoconazole in 7 patients, consider a 50% Docetaxel dose reduction if patients require co-administration of a strong CYP3A4 inhibitor [see Drug Interactions (7), Clinical Pharmacology (12.3)].
Docetaxel Injection is a cytotoxic anticancer drug and, as with other potentially toxic compounds, caution should be exercised when handling and preparing Docetaxel Injection solutions. The use of gloves is recommended. Please refer to [see How Supplied/Storage and Handling (16.3)].
If Docetaxel Injection or diluted solution for intravenous infusion should come into contact with the skin, immediately and thoroughly wash with soap and water. If Docetaxel Injection or diluted solution for intravenous infusion should come into contact with mucosa, immediately and thoroughly wash with water.
Contact of the Docetaxel Injection with plasticized PVC equipment or devices used to prepare solutions for infusion is not recommended. In order to minimize patient exposure to the plasticizer DEHP (di-2-ethylhexyl phthalate), which may be leached from PVC infusion bags or sets, the Docetaxel Injection diluted solution for infusion should be stored in bottles (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administered through polyethylene-lined administration sets.
Docetaxel Injection requires dilution prior to administration.
Please follow the preparation instructions provided below.
Docetaxel Injection (10 mg/mL) requires NO prior dilution with a diluent and is ready to add to the infusion solution.
Dilution for Infusion
1. Aseptically withdraw the required amount of Docetaxel Injection (10 mg Docetaxel/mL) with a calibrated syringe and inject into a 250 mL infusion bag or bottle of either 0.9% Sodium Chloride solution or 5% Dextrose solution to produce a final concentration of 0.3 mg/mL to 0.74 mg/mL.
If a dose greater than 200 mg of Docetaxel is required, use a larger volume of the infusion vehicle so that a concentration of 0.74 mg/mL Docetaxel is not exceeded.
2. Thoroughly mix the infusion by gentle manual rotation.
3. As with all parenteral products, Docetaxel Injection should be inspected visually for particulate matter or discoloration prior to administration whenever the solution and container permit. If the Docetaxel Injection or diluted solution is not clear or appears to have precipitation, it should be discarded.
Docetaxel Injection infusion solution, if stored between 2°C and 25°C (36°F and 77°F) is stable for 4 hours in either 0.9% Sodium Chloride solution or 5% Dextrose solution. Use within 4 hours including the 1 hour intravenous administration.
• Docetaxel Injection is contraindicated in patients who have a history of severe hypersensitivity reactions to Docetaxel or to other drugs formulated with polysorbate 80. Severe reactions, including anaphylaxis, have occurred [see Warnings and Precautions (5.4)].
• Docetaxel Injection should not be used in patients with neutrophil counts of <1500 cells/mm3.
Breast Cancer
Docetaxel administered at 100 mg/m2 was associated with deaths considered possibly or probably related to treatment in 2.0% (19/965) of metastatic breast cancer patients, both previously treated and untreated, with normal baseline liver function and in 11.5% (7/61) of patients with various tumor types who had abnormal baseline liver function (AST and/or ALT >1.5 times ULN together with AP >2.5 times ULN). Among patients dosed at 60 mg/m2, mortality related to treatment occurred in 0.6% (3/481) of patients with normal liver function, and in 3 of 7 patients with abnormal liver function. Approximately half of these deaths occurred during the first cycle. Sepsis accounted for the majority of the deaths.
Non-Small Cell Lung Cancer
Docetaxel administered at a dose of 100 mg/m2 in patients with locally advanced or metastatic non-small cell lung cancer who had a history of prior platinum-based chemotherapy was associated with increased treatment-related mortality (14% and 5% in two randomized, controlled studies). There were 2.8% treatment-related deaths among the 176 patients treated at the 75 mg/m2 dose in the randomized trials. Among patients who experienced treatment-related mortality at the 75 mg/m2 dose level, 3 of 5 patients had an ECOG PS of 2 at study entry [see Dosage and Administration (2.2), Clinical Studies (14)].
Perform frequent peripheral blood cell counts on all patients receiving Docetaxel Injection. Patients should not be retreated with subsequent cycles of Docetaxel Injection until neutrophils recover to a level >1500 cells/mm3 and platelets recover to a level >100,000 cells/mm3.
A 25% reduction in the dose of Docetaxel Injection is recommended during subsequent cycles following severe neutropenia (<500 cells/mm3) lasting 7 days or more, febrile neutropenia, or a grade 4 infection in a Docetaxel Injection cycle [see Dosage and Administration (2.7)].
Neutropenia (<2000 neutrophils/mm3) occurs in virtually all patients given 60 mg/m2 to 100 mg/m2 of Docetaxel and grade 4 neutropenia (<500 cells/mm3) occurs in 85% of patients given 100 mg/m2 and 75% of patients given 60 mg/m2. Frequent monitoring of blood counts is, therefore, essential so that dose can be adjusted. Docetaxel Injection should not be administered to patients with neutrophils <1500 cells/mm3.
Febrile neutropenia occurred in about 12% of patients given 100 mg/m2 but was very uncommon in patients given 60 mg/m2.
Hematologic responses, febrile reactions and infections, and rates of septic death for different regimens are dose related [see Adverse Reactions (6.1), Clinical Studies (14)].
Three breast cancer patients with severe liver impairment (bilirubin >1.7 times ULN) developed fatal gastrointestinal bleeding associated with severe drug-induced thrombocytopenia [see Dosage and Administration (2.7), Adverse Reactions (6)].
Patients should be observed closely for hypersensitivity reactions, especially during the first and second infusions. Severe hypersensitivity reactions characterized by generalized rash/erythema, hypotension and/or bronchospasm, or very rarely fatal anaphylaxis, have been reported in patients premedicated with 3 days of corticosteroids. Severe hypersensitivity reactions require immediate discontinuation of the Docetaxel Injection infusion and aggressive therapy. Patients with a history of severe hypersensitivity reactions should not be rechallenged with Docetaxel Injection.
Hypersensitivity reactions may occur within a few minutes following initiation of a Docetaxel Injection infusion. If minor reactions such as flushing or localized skin reactions occur, interruption of therapy is not required. All patients should be premedicated with an oral corticosteroid prior to the initiation of the infusion of Docetaxel Injection [see Dosage and Administration (2.6)].
Severe fluid retention has been reported following Docetaxel therapy. Patients should be premedicated with oral corticosteroids prior to each Docetaxel Injection administration to reduce the incidence and severity of fluid retention [see Dosage and Administration (2.6)].Patients with pre-existing effusions should be closely monitored from the first dose for the possible exacerbation of the effusions.
When fluid retention occurs, peripheral edema usually starts in the lower extremities and may become generalized with a median weight gain of 2 kg.
Among 92 breast cancer patients premedicated with 3-day corticosteroids, moderate fluid retention occurred in 27.2% and severe fluid retention in 6.5%. The median cumulative dose to onset of moderate or severe fluid retention was 819 mg/m2. Nine of 92 patients (9.8%) of patients discontinued treatment due to fluid retention: 4 patients discontinued with severe fluid retention; the remaining 5 had mild or moderate fluid retention. The median cumulative dose to treatment discontinuation due to fluid retention was 1021 mg/m2.
Fluid retention was completely, but sometimes slowly, reversible with a median of 16 weeks from the last infusion of Docetaxel to resolution (range: 0 to 42+ weeks). Patients developing peripheral edema may be treated with standard measures, e.g., salt restriction, oral diuretic(s).
Treatment-related acute myeloid leukemia (AML) or myelodysplasia has occurred in patients given anthracyclines and/or cyclophosphamide, including use in adjuvant therapy for breast cancer. In the adjuvant breast cancer trial (TAX316) AML occurred in 3 of 744 patients who received Docetaxel, doxorubicin and cyclophosphamide (TAC) and in 1 of 736 patients who received fluorouracil, doxorubicin and cyclophosphamide [see Clinical Studies (14.2)]. In TAC-treated patients, the risk of delayed myelodysplasia or myeloid leukemia requires hematological follow-up.
Localized erythema of the extremities with edema followed by desquamation has been observed. In case of severe skin toxicity, an adjustment in dosage is recommended [see Dosage and Administration (2.7)]. The discontinuation rate due to skin toxicity was 1.6% (15/965) for metastatic breast cancer patients. Among 92 breast cancer patients premedicated with 3-day corticosteroids, there were no cases of severe skin toxicity reported and no patient discontinued Docetaxel due to skin toxicity.
Severe neurosensory symptoms (e.g. paresthesia, dysesthesia, pain) were observed in 5.5% (53/965) of metastatic breast cancer patients, and resulted in treatment discontinuation in 6.1%. When these symptoms occur, dosage must be adjusted. If symptoms persist, treatment should be discontinued [see Dosage and Administration (2.7)]. Patients who experienced neurotoxicity in clinical trials and for whom follow-up information on the complete resolution of the event was available had spontaneous reversal of symptoms with a median of 9 weeks from onset (range: 0 to 106 weeks). Severe peripheral motor neuropathy mainly manifested as distal extremity weakness occurred in 4.4% (42/965).
Severe asthenia has been reported in 14.9% (144/965) of metastatic breast cancer patients but has led to treatment discontinuation in only 1.8%. Symptoms of fatigue and weakness may last a few days up to several weeks and may be associated with deterioration of performance status in patients with progressive disease.
Docetaxel Injection can cause fetal harm when administered to a pregnant woman. Docetaxel caused embryofetal toxicities including intrauterine mortality when administered to pregnant rats and rabbits during the period of organogenesis. Embryofetal effects in animals occurred at doses as low as 1/50 and 1/300 the recommended human dose on a body surface area basis. There are no adequate and well-controlled studies in pregnant women using Docetaxel Injection. If Docetaxel Injection is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with Docetaxel Injection [see Use in Specific Populations (8.1)].
The most serious adverse reactions from Docetaxel are:
The most common adverse reactions across all Docetaxel indications are infections, neutropenia, anemia, febrile neutropenia, hypersensitivity, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, skin reactions, and myalgia. Incidence varies depending on the indication. Adverse reactions are described according to indication. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Responding patients may not experience an improvement in performance status on therapy and may experience worsening. The relationship between changes in performance status, response to therapy, and treatment-related side effects has not been established.
Breast Cancer
Monotherapy with Docetaxel for locally advanced or metastatic breast cancer after failure of prior chemotherapy
Docetaxel 100 mg/m2: Adverse drug reactions occurring in at least 5% of patients are compared for three populations who received Docetaxel administered at 100 mg/m2 as a 1-hour infusion every 3 weeks: 2045 patients with various tumor types and normal baseline liver function tests; the subset of 965 patients with locally advanced or metastatic breast cancer, both previously treated and untreated with chemotherapy, who had normal baseline liver function tests; and an additional 61 patients with various tumor types who had abnormal liver function tests at baseline. These reactions were described using COSTART terms and were considered possibly or probably related to Docetaxel. At least 95% of these patients did not receive hematopoietic support. The safety profile is generally similar in patients receiving Docetaxel for the treatment of breast cancer and in patients with other tumor types (See Table 1).
| Adverse Reaction | All Tumor Types Normal LFTs* n=2045 % | All Tumor Types Elevated LFTs** n=61 % | Breast Cancer Normal LFTs* n=965 % |
|---|---|---|---|
Hematologic Neutropenia <2000 cells/mm3 <500 cells/mm3 Leukopenia <4000 cells/mm3 <1000 cells/mm3 Thrombocytopenia <100,000 cells/mm3 Anemia <11 g/dL <8 g/dL Febrile Neutropenia*** |
96 75
96 32
8
90 9 11 |
96 88
98 47
25
92 31 26 |
99 86
99 44
9
94 8 12 |
Septic Death Non-Septic Death | 2 1 | 5 7 | 1 1 |
Infections Any Severe |
22 6 |
33 16 |
22 6 |
Fever in Absence of Infection Any Severe |
31 2 |
41 8 |
35 2 |
Hypersensitivity Reactions Regardless of Premedication Any Severe With 3-day Premedication Any Severe |
21 4 n=92 15 2 |
20 10 n=3 33 0 |
18 3 n=92 15 2 |
Fluid Retention Regardless of Premedication Any Severe With 3-day Premedication Any Severe |
47 7 n=92 64 7 |
39 8 n=3 67 33 |
60 9 n=92 64 7 |
Neurosensory Any Severe |
49 4 |
34 0 |
58 6 |
Cutaneous Any Severe |
48 5 |
54 10 |
47 5 |
Nail Changes Any Severe |
31 3 |
23 5 |
41 4 |
Gastrointestinal Nausea Vomiting Diarrhea Severe |
39 22 39 5 |
38 23 33 5 |
42 23 43 6 |
Stomatitis Any Severe |
42 6 |
49 13 |
52 7 |
Alopecia | 76 | 62 | 74 |
Asthenia Any Severe |
62 13 |
53 25 |
66 15 |
Myalgia Any Severe |
19 2 |
16 2 |
21 2 |
Arthralgia | 9 | 7 | 8 |
Infusion Site Reactions | 4 | 3 | 4 |
*Normal Baseline LFTs: Transaminases ≤1.5 times ULN or alkaline phosphatase ≤2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN **Elevated Baseline LFTs: AST and/or ALT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN ***Febrile Neutropenia: ANC grade 4 with fever >38°C with intravenous antibiotics and/or hospitalization | |||
Hematologic Reactions
Reversible marrow suppression was the major dose-limiting toxicity of Docetaxel [see Warnings and Precautions (5.3)]. The median time to nadir was 7 days, while the median duration of severe neutropenia (<500 cells/mm3) was 7 days. Among 2045 patients with solid tumors and normal baseline LFTs, severe neutropenia occurred in 75.4% and lasted for more than 7 days in 2.9% of cycles.
Febrile neutropenia (<500 cells/mm3 with fever >38°C with intravenous antibiotics and/or hospitalization) occurred in 11% of patients with solid tumors, in 12.3% of patients with metastatic breast cancer, and in 9.8% of 92 breast cancer patients premedicated with 3-day corticosteroids.
Severe infectious episodes occurred in 6.1% of patients with solid tumors, in 6.4% of patients with metastatic breast cancer, and in 5.4% of 92 breast cancer patients premedicated with 3-day corticosteroids.
Thrombocytopenia (<100,000 cells/mm3) associated with fatal gastrointestinal hemorrhage has been reported.
Hypersensitivity Reactions
Severe hypersensitivity reactions have been reported [see Boxed Warning, Warnings and Precautions (5.4)]. Minor events, including flushing, rash with or without pruritus, chest tightness, back pain, dyspnea, drug fever, or chills, have been reported and resolved after discontinuing the infusion and instituting appropriate therapy.
Fluid Retention
Fluid retention can occur with the use of Docetaxel [see Boxed Warning, Dosage and Administration (2.6), Warnings and Precautions (5.5)].
Cutaneous Reactions
Severe skin toxicity is discussed elsewhere in the label [see Warnings and Precautions (5.7)]. Reversible cutaneous reactions characterized by a rash including localized eruptions, mainly on the feet and/or hands, but also on the arms, face, or thorax, usually associated with pruritus, have been observed. Eruptions generally occurred within 1 week after Docetaxel infusion, recovered before the next infusion, and were not disabling.
Severe nail disorders were characterized by hypo- or hyperpigmentation, and occasionally by onycholysis (in 0.8% of patients with solid tumors) and pain.
Neurologic Reactions
Neurologic reactions are discussed elsewhere in the label [see Warnings and Precautions (5.8)].
Gastrointestinal Reactions
Nausea, vomiting, and diarrhea were generally mild to moderate. Severe reactions occurred in 3–5% of patients with solid tumors and to a similar extent among metastatic breast cancer patients. The incidence of severe reactions was 1% or less for the 92 breast cancer patients premedicated with 3-day corticosteroids.
Severe stomatitis occurred in 5.5% of patients with solid tumors, in 7.4% of patients with metastatic breast cancer, and in 1.1% of the 92 breast cancer patients premedicated with 3-day corticosteroids.
Cardiovascular Reactions
Hypotension occurred in 2.8% of patients with solid tumors; 1.2% required treatment. Clinically meaningful events such as heart failure, sinus tachycardia, atrial flutter, dysrhythmia, unstable angina, pulmonary edema, and hypertension occurred rarely. Seven of 86 (8.1%) of metastatic breast cancer patients receiving Docetaxel 100 mg/m2 in a randomized trial and who had serial left ventricular ejection fractions assessed developed deterioration of LVEF by ≥10% associated with a drop below the institutional lower limit of normal.
Infusion Site Reactions
Infusion site reactions were generally mild and consisted of hyperpigmentation, inflammation, redness or dryness of the skin, phlebitis, extravasation, or swelling of the vein.
Hepatic Reactions
In patients with normal LFTs at baseline, bilirubin values greater than the ULN occurred in 8.9% of patients. Increases in AST or ALT >1.5 times the ULN, or alkaline phosphatase >2.5 times ULN, were observed in 18.9% and 7.3% of patients, respectively. While on Docetaxel, increases in AST and/or ALT >1.5 times ULN concomitant with alkaline phosphatase >2.5 times ULN occurred in 4.3% of patients with normal LFTs at baseline. Whether these changes were related to the drug or underlying disease has not been established.
Hematologic and Other Toxicity: Relation to dose and baseline liver chemistry abnormalities
Hematologic and other toxicity is increased at higher doses and in patients with elevated baseline liver function tests (LFTs). In the following tables, adverse drug reactions are compared for three populations: 730 patients with normal LFTs given Docetaxel at 100 mg/m2 in the randomized and single arm studies of metastatic breast cancer after failure of previous chemotherapy; 18 patients in these studies who had abnormal baseline LFTs (defined as AST and/or ALT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN); and 174 patients in Japanese studies given Docetaxel at 60 mg/m2 who had normal LFTs (see Tables 2 and 3).
| Docetaxel 100 mg/m2 | Docetaxel 60 mg/m2 | |
| Normal LFTs* n=730 % | Elevated LFTs** n=18 % | Normal LFTs* |
Adverse Reaction | n=174 | ||
| % | |||
Neutropenia Any <2000 cells/mm3 Grade 4 <500 cells/mm3 |
98 84 |
100 94 |
95 75 |
Thrombocytopenia Any <100,000 cells/mm3 Grade 4 <20,000 cells/mm3 |
11 1 |
44 17 |
14 1 |
Anemia <11 g/dL | 95 | 94 | 65 |
Infection*** Any Grade 3 and 4 |
23 7 |
39 33 |
1 0 |
Febrile Neutropenia**** By Patient By Course |
12 2 |
33 9 |
0 0 |
Septic Death | 2 | 6 | 1 |
Non-Septic Death | 1 | 11 | 0 |
*Normal Baseline LFTs: Transaminases ≤1.5 times ULN or alkaline phosphatase ≤2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN **Elevated Baseline LFTs: AST and/or ALT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN ***Incidence of infection requiring hospitalization and/or intravenous antibiotics was 8.5% (n=62) among the 730 patients with normal LFTs at baseline; 7 patients had concurrent grade 3 neutropenia, and 46 patients had grade 4 neutropenia. ****Febrile Neutropenia: For 100 mg/m2, ANC grade 4 and fever >38°C with intravenous antibiotics and/or hospitalization; for 60 mg/m2, ANC grade 3/4 and fever >38.1°C | |||
| Docetaxel 100 mg/m2 | Docetaxel 60 mg/m2 | |
| Normal LFTs* n=730 % | Elevated LFTs** n=18 % | Normal LFTs* |
Adverse Reaction | n=174 | ||
| % | |||
Acute Hypersensitivity Reaction Regardless of Premedication Any Severe |
13 1 |
6 0 |
1 0 |
Fluid Retention*** Regardless of Premedication Any Severe |
56 8 |
61 17 |
13 0 |
Neurosensory Any Severe |
57 6 |
50 0 |
20 0 |
Myalgia | 23 | 33 | 3 |
Cutaneous Any Severe |
45 | ||
