Docetaxel is a chemotherapy drug used in the treatment of various types of cancers, including breast, lung, prostate, gastric, head and neck, and ovarian cancer. It is a member of the taxane family and works by disrupting the microtubular network in cells that is essential for mitotic and interphase cellular functions.

Docetaxel (Taxotere) is a chemotherapeutic drug that is used to treat a variety of cancers including breast, lung, ovarian, prostate, and cancers of the head & neck.

Indications of Docetaxel (Taxotere):

• Breast cancer:
  • It is indicated for the treatment of breast cancer (locally advanced/metastatic) as second-line therapy.
• Non-small cell lung cancer:
  • Treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after the failure of platinum-based chemotherapy.
  • The treatment of newly diagnosed unresectable locally advanced or metastatic non-small cell lung cancer (concurrently with cisplatin)
• Prostate cancer:
  • Docetaxel is effective for treating a hormone-refractory metastatic prostate tumor in addition to  prednisone
• Taxotere (and various generic brands):
  • Breast cancer:
    • Treatment of breast cancer (locally advanced/metastatic) as a second-line drug.
    • It is also indicated for adjuvant treatment including with doxorubicin and cyclophosphamide of operable node-positive breast cancer
  • Gastric cancer:
    • Treatment of advanced gastric adenocarcinoma, including gastroesophageal junction adenocarcinoma concurrently with cisplatin and fluorouracil as first-line therapy for advanced disease
  • Head and neck cancer:
    • It is recommended as induction treatment of locally advanced squamous cell head and neck carcinoma concurrently with cisplatin and fluorouracil.
  • Non-small cell lung carcinoma:
    • Treatment of locally advanced or metastatic non-small cell lung carcinoma after failure of 1st line platinum-based chemotherapy.
    • The treatment of Newly diagnosed unresectable locally advanced or metastatic NSCLC concurrently with cisplatin.
  • Prostate cancer:
    • Treatment of metastatic castration-resistant prostate tumor (in addition to prednisone).
• Off Label Use of Docetaxel (Taxotere) in Adults:
  • Metastatic Bladder tumor, as single-agent
  • Esophageal cancer - for locally-advanced or metastatic disease
  • Ovarian malignancy
  • Metastatic hormone-sensitive Prostate cancer
  • Relapsed Small cell lung cancer
  • Soft tissue sarcoma
  • Adenocarcinoma of Unknown-primary

Docetaxel dosage in adults:

Note:

• Docetaxel is a medicine used to treat certain cancers.
• "Docefrez," a name for this medicine, is no longer available in the US.
• Before getting docetaxel, you need to take another medicine called a corticosteroid. This is to prevent severe allergic reactions and swelling.
• If you're getting docetaxel for prostate cancer and you're also on a drug called prednisone, you should take a specific corticosteroid called dexamethasone three times before getting docetaxel.
• The times to take it are 12 hours before, 3 hours before, and 1 hour before the docetaxel is given.

Docetaxel treatment dosage of Breast cancer:

For Advanced or Spread-Out Breast Cancer:

• Take 60 to 100 mg for each square meter of your body area (mg/m²). This is given through an IV every 3 weeks.

For Early Breast Cancer (after surgery to remove the tumor):

• TAC Regimen: 75 mg/m² every 3 weeks. This is given 6 times along with two other drugs (doxorubicin and cyclophosphamide).
• Other Methods (Not Always Used):
  • 75 mg/m² every 3 weeks, given 4 times with another drug (cyclophosphamide).
  • Or 75 mg/m² every 3 weeks, given 6 times with two other drugs (carboplatin and trastuzumab).

Before Surgery (to shrink the tumor):

• Start with 75 mg/m². If okay, you can get up to 100 mg/m² in the next times. Given every 3 weeks for 4 times with two drugs (trastuzumab and pertuzumab).

For Spread-Out Breast Cancer (Different Methods):

• Every 3 Weeks Method:
  • Start with 75 mg/m², can increase later. Given every 3 weeks for at least 6 times with two drugs (trastuzumab and pertuzumab).
  • Or 100 mg/m² every 3 weeks for 6 times with one drug (trastuzumab).
  • Or 75 mg/m² every 3 weeks until the cancer gets worse or side effects are too bad with one drug (capecitabine).
  • Or 60 mg/m², 75 mg/m², or 100 mg/m² every 3 weeks for at least 6 times until cancer gets worse or side effects are too bad.
• Every Week Method:
  • 40 mg/m² once a week for 6 weeks, then a 2-week break. Repeat until the cancer gets worse or side effects are too bad.
  • Or 35 mg/m² once a week for 3 weeks, then a 1-week break. If all's good, can increase to 40 mg/m² in the next round.
  • Or 35 mg/m² once a week for 3 weeks with a 1-week break, along with the drug trastuzumab. Repeat this until the cancer gets worse or side effects are too bad.

Docetaxel treatment dose of Gastric adenocarcinoma:

Standard Treatment:

• Use 75 mg for each square meter of your body area (mg/m²). This is given through IV every 3 weeks, alongside two other drugs (cisplatin and fluorouracil).

Treatment Before Radiotherapy (Not Always Used):

• First Part: Use 75 mg/m² on the first day and again on the 22nd day. This is given with another drug (cisplatin) and is repeated for 2 times (cycles).
• Second Part: During radiotherapy, use 20 mg/m² every week for 5 weeks. This is given with the drug cisplatin and alongside radiation treatment.

For Advanced or Spread-Out Gastric Cancer (Different Method & Not Always Used):

• Use 50 mg/m² on the first day and then repeat every 2 weeks. This is given alongside three other drugs (fluorouracil, leucovorin, and oxaliplatin).
• Continue this until the cancer gets worse or the side effects are too strong, but no more than 8 times (cycles).

Docetaxel treatment dose of Head and neck cancer:

• Take 75 mg for each square meter of your body area (mg/m²) through an IV.
• This dose is given every 3 weeks.
• You'll also get two other drugs with it: cisplatin and fluorouracil.
• You'll get this treatment for 3 or 4 times (cycles).
• After these treatments, you'll go through radiation therapy.

Docetaxel treatment dose of non-small cell lung cancer:

• Take 75 mg for every square meter of your body area (mg/m²) through an IV drip.
• This dose is given every 3 weeks.
• It can be given on its own or with another drug called cisplatin.

Docetaxel treatment dose of castration-resistant metastatic Prostate cancer:

• Take 75 mg for each square meter of your body area (mg/m²) through an IV drip.
• This dose is given every 3 weeks.
• It's combined with another drug called prednisone.

Docetaxel treatment dose of metastatic Bladder cancer:

Option 1:

• Take 100 mg for every square meter of your body area (mg/m²) through an IV drip.
• This dose is given every 3 weeks.
• It's used on its own, without any other drugs.

Option 2:

• Take 35 mg for every square meter of your body area (mg/m²) on the first day and then again on the 8th day. This is done in a 3-week (21-day) cycle.
• This is given with two other drugs: gemcitabine and cisplatin.
• Continue this for at least 6 times (cycles) or until the cancer gets worse or if side effects are too strong.

Docetaxel treatment dose of Esophageal cancer:

Treatment Before Radiotherapy:

• First Part: Take 75 mg for every square meter of your body area (mg/m²) on the first day and again on the 22nd day. This is given alongside another drug called cisplatin. Repeat this for 2 times (cycles).
• Second Part: During radiotherapy, use 20 mg/m² once every week for 5 weeks. This is given with cisplatin and along with radiation treatment.

Definitive Chemoradiation:

• Use 60 mg/m² on the first day and again on the 22nd day. This is given alongside cisplatin and with radiation. You'll do this just once (1 cycle).

For Advanced or Spread-Out Esophageal Cancer:

• Use 75 mg/m² on the first day, then every 3 weeks. This is given with cisplatin and another drug called fluorouracil.
• Or, use 50 mg/m² on the first day, then every 2 weeks with three other drugs (fluorouracil, leucovorin, and oxaliplatin). Do this up to 8 times (cycles) or until the cancer gets worse or side effects are too bad.
• Alternatively, use 35 mg/m² on several specific days (days 1, 8, 15, 29, 36, 43, 50, and 57). This is combined with three treatments: cisplatin, fluorouracil, and radiation.

Docetaxel treatment dose of recurrent or progressive Ewing sarcoma or osteosarcoma:

• Take 100 mg for each square meter of your body area (mg/m²) through an IV drip.
• This is given on the 8th day of a 3-week (21-day) cycle.
• It's combined with another drug called gemcitabine.

Docetaxel treatment dose of Ovarian cancer:

Option 1:

• Take 60 mg for every square meter of your body area (mg/m²) through an IV drip.
• This is given every 3 weeks.
• Combine it with another drug called carboplatin.
• Do this up to 6 times (cycles).

Option 2:

• Take 75 mg/m² through an IV drip every 3 weeks.
• Also, use it with carboplatin.
• Do this for 6 times (cycles).

Option 3:

• Take 35 mg/m² through an IV drip once a week. The maximum dose shouldn't go above 70 mg.
• This is given weekly for 3 weeks and then you take a 1-week break.
• Use it alongside carboplatin.

Docetaxel treatment dose of hormone-sensitive metastatic Prostate cancer:

Option 1:

• Take 75 mg for every square meter of your body area (mg/m²) through an IV drip.
• This dose is given on the first day, and then every 3 weeks.
• It's used with hormone-reducing therapy (androgen deprivation therapy) and another drug called prednisolone.
• Continue this for 6 times (cycles).

Option 2:

• Take 75 mg/m² through an IV drip on the first day, then every 3 weeks.
• This is combined with hormone-reducing therapy (androgen deprivation therapy).
• Unlike the first option, you don't need daily prednisone with this.
• Do this for 6 times (cycles).

Docetaxel treatment dose of relapsed small cell lung cancer:

• Take 100 mg for each square meter of your body area (mg/m²) through an IV drip.
• This dose is given every 3 weeks.

Docetaxel treatment dose of soft tissue sarcoma:

• Take 100 mg for each square meter of your body area (mg/m²) through an IV drip.
• This is given on the 8th day of a 3-week (21-day) treatment cycle.
• It's used with two other medicines: gemcitabine and either filgrastim or pegfilgrastim.

Docetaxel treatment dose of Unknown-primary adenocarcinoma:

Option 1:

• Take 65 mg for every square meter of your body area (mg/m²) through an IV drip.
• This is given every 3 weeks.
• Combine it with another drug called carboplatin.

Option 2:

• Take 75 mg/m² through an IV drip on the 8th day of a 3-week treatment cycle.
• Use it with another drug, gemcitabine.
• Do this treatment up to 6 times (cycles).

Option 3:

• Take 60 mg/m² through an IV drip on the first day of a 3-week treatment cycle.
• Combine it with another drug called cisplatin.

Dosing adjustment for concomitant CYP3A4 inhibitors:

• It's best to avoid using strong CYP3A4 inhibitors with docetaxel.
• If you must use them together, think about cutting the docetaxel dose in half (50% less). This suggestion is based on some limited drug interaction data.

Docetaxel dose in children

Note:

• Docefrez" (a version of docetaxel) isn't available in the US anymore. It's been gone for over a year.
• The amount of docetaxel, how often you take it, how many times you take it, and when you start might change depending on the specific plan your doctor gives you.
• Before getting docetaxel, you'll need to take another medicine called a corticosteroid. This starts a day before your docetaxel treatment. It helps prevent severe allergic reactions and swelling in the lungs or limbs. You'll take the corticosteroid for 1 to 3 days.
• Docetaxel doesn't usually make people throw up a lot, but you should still take anti-nausea medicines to be sure you feel okay.

Docetaxel treatment dose of Sarcomas, Ewing Sarcoma, and recurrent or progressive osteosarcoma:

G + D Regimen (Based on Mora 2009):

• For Kids and Teenagers:
  • Take 100 mg of docetaxel for every square meter of their body area (mg/m²).
  • This is given through an IV drip over 2 to 4 hours.
  • This is done on the 8th day of a 3-week (21-day) cycle.
  • It's combined with another medicine called gemcitabine.

GEMDOX Regimen (Based on Rapkin 2012):

• For Babies:
  • Take 2.5 mg of docetaxel for each kilogram they weigh.
  • This is given through an IV drip over 1 hour.
  • This is done on the 8th day of a 3-week (21-day) cycle.
  • It's combined with gemcitabine.
• For Kids and Teenagers:
  • Take 75 mg of docetaxel for every square meter of their body area (mg/m²).
  • This is given through an IV drip over 1 hour.
  • This is done on the 8th day of a 3-week (21-day) cycle.
  • It's combined with gemcitabine.

Docetaxel treatment dose in refractory or relapsed Hepatoblastoma:

For Babies and Kids:

• If they weigh less than 10 kg:
  • Give 3.3 mg of docetaxel for each kilogram they weigh.
  • This is given through an IV drip over 1 hour.
  • Repeat this every 3 weeks (21 days).
• If they weigh more than 10 kg:
  • Give 100 mg of docetaxel for every square meter of their body area (mg/m²).
  • This is given through an IV drip over 1 hour.
  • Repeat this every 3 weeks (21 days).

Important Note on Other Drugs:

• There aren't specific rules for kids about using docetaxel with drugs called strong CYP3A4 inhibitors. But in adults, it's recommended to avoid this combination.
• If you must use both, think about giving less docetaxel.

Dosing adjustment for toxicity:

General Info: The following changes are based on adult patients' experiences. For kids, specific guidance is limited. Always refer to the protocol if available.

Toxicities may include: Fever with low white blood cell count, low white blood cell count for more than a week, severe skin reactions, low platelet count, and other severe non-blood related side effects.

Breast Cancer:

• As a single drug:
  • If starting at 100 mg/m² and there are bad side effects, lower the dose to 75 mg/m². If problems continue, reduce to 55 mg/m² or stop the treatment.
  • If starting at 60 mg/m² without problems, higher doses might be okay.
• With other drugs (TAC regimen):
  • Only give when the white blood cell count is okay.
  • If fever with low white blood cell count happens, use G-CSF for future treatments.
  • For continued fever or other bad side effects, reduce docetaxel to 60 mg/m². Stop if problems persist after the reduction.

Non-Small Cell Lung Cancer:

• Alone: If started at 75 mg/m² and problems arise, pause treatment until problems resolve, then reduce dose to 55 mg/m².
• With cisplatin: If started at 75 mg/m² and problems arise, reduce to 65 mg/m². If more adjustments are needed, go down to 50 mg/m².

Prostate Cancer:

• Reduce to 60 mg/m². Stop the treatment if problems continue even with the reduced dose.

Gastric and Head and Neck Cancer:

• If certain problems happen, use G-CSF for future treatments.
• For persistent issues, reduce the dosage or stop the treatment.

Stomach Issues with combination treatment for Gastric or Head and Neck Cancer:

• Depending on the severity and type of stomach issue, adjust doses or stop specific drugs.

Pregnancy Risk Factor D

• Studies on animals have shown that docetaxel can cause problems during pregnancy.
• In tests with human placenta, docetaxel was found to cross the placenta but not in large amounts. The amount that crosses depends on the presence of albumin in the blood. More albumin means less docetaxel crossing the placenta.
• Docetaxel might behave differently in pregnant women because some of its properties could change.
• If you're a woman who could become pregnant, it's crucial to avoid getting pregnant while taking docetaxel.

Docetaxel should be used during breastfeeding

• We don't know if docetaxel gets into breast milk.
• Because there's a chance it could harm a baby who is breastfed, the company that makes the drug suggests either stopping breastfeeding or not taking the drug.
• This decision should consider how important the treatment is for the mother.

Docetaxel (Taxotere) dose adjustment in renal disease:

• Only a tiny amount (around 6%) of docetaxel is removed from the body through the kidneys.
• This means people with kidney problems probably don't need a different dose (Janus 2010; Li 2007).
• Hemodialysis (a treatment to clean the blood when kidneys don't work properly) doesn't remove docetaxel. So, it's okay to give docetaxel before or after a hemodialysis session (Janus 2010).

Docetaxel dose adjustment in liver disease:

• If total bilirubin (a liver enzyme) is higher than normal, or if AST and/or ALT (other liver enzymes) are more than 1.5 times the normal limit along with alkaline phosphatase (another liver enzyme) being more than 2.5 times the normal limit:
  • It's advised not to use docetaxel.
• For gastric or head and neck cancer:
  • If AST/ALT is slightly high but alkaline phosphatase is normal or just a bit high: Give 80% of the usual dose.
  • If AST/ALT is high and alkaline phosphatase is also elevated but not super high: Give 80% of the usual dose.
  • If AST/ALT or alkaline phosphatase is very high: Stop using docetaxel.
• Other recommendations (from Floyd 2006):
  • If transaminases (another name for liver enzymes like AST/ALT) are slightly to moderately elevated: Give 75% of the usual dose.
  • If transaminases are very high: Decide based on the specific situation and patient condition.

Common Side Effects of Docetaxel (Taxotere):

• Central Nervous System:
  • Neurotoxicity
• Dermatologic:
  • Alopecia
  • Dermatological Reaction
  • Nail Disease
• Endocrine & Metabolic:
  • Fluid Retention
• Gastrointestinal:
  • Stomatitis
  • Diarrhea
  • Nausea
  • Vomiting
• Hematologic & Oncologic:
  • Neutropenia
  • Leukopenia
  • Anemia
  • Thrombocytopenia
  • Febrile Neutropenia
• Hepatic:
  • Increased Serum Transaminases
• Hypersensitivity:
  • Hypersensitivity Reaction
• Infection:
  • Infection
• Neuromuscular & Skeletal:
  • Asthenia
  • Myalgia
  • Neuromuscular Reaction
• Respiratory:
  • Pulmonary Disorder
• Miscellaneous:
  • Fever

Less Common Side Effects Of Docetaxel (Taxotere):

• Cardiovascular:
  • Hypotension
• Central Nervous System:
  • Peripheral Motor Neuropathy
• Gastrointestinal:
  • Dysgeusia
• Hepatic:
  • Increased Serum Bilirubin
  • Increased Serum Alkaline Phosphatase
• Infection:
  • Severe Infection
• Local:
  • Infusion Site Reaction
• Neuromuscular And Skeletal:
  • Arthralgia

Uncommon Side effects of Docetaxel (Taxotere):

• Cardiovascular:
  • Cardiac Tamponade
  • Decreased Left Ventricular Ejection Fraction
  • Localized Phlebitis
  • Peripheral Edema
• Central Nervous System:
  • Fatigue
• Dermatologic:
  • Exfoliation Of Skin
  • Local Dryness
  • Localized Erythema Of The Extremities
  • Nail Depigmentation
  • Nail Hyperpigmentation
  • Skin Discoloration At Injection Site
• Hepatic:
  • Ascites
• Local:
  • Erythema At Injection Site
  • Inflammation At Injection Site
• Respiratory:
  • Pleural Effusion

Contraindications to Docetaxel (Taxotere):

You shouldn't use docetaxel if:

• You have a strong allergic reaction to docetaxel or any ingredient in it.
• You have a strong allergic reaction to other drugs that contain polysorbate 80.
• Your neutrophil count (a type of white blood cell) is less than 1,500 per cubic millimeter.

In Canada, there are a few more reasons not to use docetaxel (these aren't mentioned in US guidelines):

• If you have serious liver problems.
• If you're pregnant.
• If you're breastfeeding.

Warnings and precautions

Suppression of bone marrow: [US Boxed Warning]

• Important Warning: Don't give docetaxel to patients if their neutrophil (a type of white blood cell) count is below 1,500 per tiny bit of blood.
• This medicine can strongly decrease these cells, increasing the risk of infections.
• The most serious side effect is this decrease in neutrophils.
• Before giving the drug, make sure the patient's platelet (cells that help blood clot) count is above 100,000.
• Patients with liver problems face a higher risk of this decrease in neutrophils and more severe infections.
• It's important to regularly check blood counts and liver health.
• If blood cell counts drop too much, the medicine dose might need to be lowered or stopped.

Cutaneous reactions

• Some people taking docetaxel can experience skin reactions like redness, swelling, and skin peeling.
• If these happen, the dose of the medicine might need to be lowered.

Extravasation

• Docetaxel can irritate and damage the skin if it leaks out of the vein. Make sure the needle or tube is correctly placed before and during the drip to avoid any leakage.

Fluid retention: [US Boxed Warning]

• Some people taking docetaxel can experience serious fluid build-up in the body.
• This can show up as fluid in the lungs, belly swelling due to fluid, swelling in the legs, shortness of breath, and rapid weight gain.
• Even if patients take preventive medicine like dexamethasone for 3 days, this can still happen.
• This fluid issue often starts as leg swelling and can spread, with an average weight gain of about 2 kg.
• For breast cancer patients, this usually happens after a certain dose amount and takes about 16 weeks to go away after stopping the drug.
• To help reduce this problem, patients should take a steroid medicine starting a day before docetaxel.
• It's important to watch closely those who already have fluid build-up issues.

Toxicity to the GI:

• Docetaxel can cause serious problems in the gut, like inflammation or infections, especially when the white blood cell count is low.
• This can happen even if other drugs, like filgrastim, are given.
• The problems can start suddenly and be very dangerous, even on the first day symptoms appear.
• Patients with low white blood cell counts or at risk for gut problems should be extra careful.
• Patients should be told to let their doctor know right away if they have new or worsening stomach or gut symptoms, and doctors should watch them closely if they show any signs of these problems.

Hypersensitivity [US Boxed Warning]

• Some people taking docetaxel can have serious allergic reactions.
• Symptoms might include widespread skin redness, low blood pressure, difficulty breathing, or even life-threatening reactions.
• These can happen even if patients have taken preventive steroids for 3 days.
• If someone has a reaction, the docetaxel drip should be stopped immediately and they should get emergency treatment.
• People who are known to be allergic to docetaxel or its ingredients, especially polysorbate 80, should not take it.
• Also, if someone had an allergic reaction to a similar drug, paclitaxel, they might also react to docetaxel and it can be very serious.
• Doctors should closely watch anyone getting docetaxel, especially during their first two treatments.
• If someone has a serious reaction, they shouldn't take docetaxel again.
• Taking a steroid medicine starting a day before the docetaxel treatment can help lower the risk of allergic reactions.

Neurosensory symptoms

• Some people taking docetaxel can experience nerve-related symptoms like tingling, unusual sensations, or pain.
• If these symptoms are severe, the dose of docetaxel should be adjusted or might need to be stopped.
• Even after stopping the drug, it might take some time for these symptoms to go away.

Ocular adverse reactions:

• Docetaxel can cause issues with the eyes, like Cystoid macular edema (CME), which can affect vision.
• If someone notices vision problems while taking docetaxel, they should get a detailed eye check-up quickly.
• If CME is found, treatment for it should start, and docetaxel should be stopped.
• In a study with breast cancer patients, many experienced increased tearing while on docetaxel.
• This issue generally started after the first treatment and usually got better about 4 months after finishing the medicine.

Secondary malignancies

• Some people who took docetaxel with certain other cancer drugs (like anthracyclines or cyclophosphamide) developed new blood cancers, like acute myeloid leukemia or myelodysplasia.

Treatment-related Mortality: [US Boxed Warning]

• Some patients might have a higher risk of death from the treatment with docetaxel.
• This includes those with liver problems, those getting higher doses, and patients with non-small cell lung cancer who had previously been treated with platinum-based drugs.
• The risk is especially high when they get docetaxel at a dose of 100 mg/m.

Weakness

• People taking docetaxel might feel very tired or weak.
• This feeling can last from a few days to several weeks.
• For those with worsening disease, this weakness might be linked to a decline in their overall health and activity level.

Heart Failure:

• According to the American Heart Association, docetaxel might directly harm the heart or make existing heart problems worse.
• The level of concern is considered moderate.

Hepatic impairment: [US-Boxed Warning]

• Don't use docetaxel in patients with high levels of bilirubin or certain liver enzymes.
• These patients have a higher risk of severe side effects like very low white blood cell counts, fever, infections, low platelet counts, mouth sores, skin issues, and even death.
• Patients with only slightly raised liver enzymes also face higher risks, especially of fever due to low white blood cell counts.
• Before each round of docetaxel, check bilirubin and liver enzyme levels.
• Also, remember that docetaxel contains alcohol, which can affect those with liver problems.

Docetaxel: Drug Interaction

Risk Factor C (Monitor therapy)
Bosentan	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Chloramphenicol (Ophthalmic)	May enhance the adverse/toxic effect of Myelosuppressive Agents.
Clofazimine	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
CloZAPine	Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased.
Coccidioides immitis Skin Test	Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test.
CYP3A4 Inducers (Moderate)	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
CYP3A4 Inhibitors (Moderate)	May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors).
Deferasirox	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Denosumab	May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
Duvelisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Erdafitinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Erdafitinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Erdafitinib	May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Fosnetupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Ivosidenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Larotrectinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Netupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Ocrelizumab	May enhance the immunosuppressive effect of Immunosuppressants.
Palbociclib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
P-glycoprotein/ABCB1 Inhibitors	May increase the serum concentration of Pglycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of pglycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.).
Pidotimod	Immunosuppressants may diminish the therapeutic effect of Pidotimod.
Promazine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Ranolazine	May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Sarilumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Siltuximab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Simeprevir	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Siponimod	Immunosuppressants may enhance the immunosuppressive effect of Siponimod.
Sipuleucel-T	Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T.
SORAfenib	May increase the serum concentration of DOCEtaxel.
Tocilizumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Trastuzumab	May enhance the neutropenic effect of Immunosuppressants.
Risk Factor D (Consider therapy modification)
Anthracyclines	Taxane Derivatives may enhance the adverse/toxic effect of Anthracyclines. Taxane Derivatives may increase the serum concentration of Anthracyclines. Taxane Derivatives may also increase the formation of toxic anthracycline metabolites in heart tissue.
Baricitinib	Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted.
CYP3A4 Inducers (Strong)	May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.
CYP3A4 Inhibitors (Strong)	May increase the serum concentration of DOCEtaxel. Management: Avoid the concomitant use of docetaxel and strong CYP3A4 inhibitors when possible. If combined use is unavoidable, consider a 50% docetaxel dose reduction and monitor for increased docetaxel toxicities.
Dabrafenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects).
Dronedarone	May increase the serum concentration of DOCEtaxel. Management: Avoid this combination whenever possible. If this combination must be used, consider using a reduced docetaxel dose, and/or increase monitoring for evidence of serious docetaxel toxicity (e.g., neutropenia, mucositis, etc.).
Echinacea	May diminish the therapeutic effect of Immunosuppressants.
Enzalutamide	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring.
Fingolimod	Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections).
Leflunomide	Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly.
Lenograstim	Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy.
Lipegfilgrastim	Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy.
Lorlatinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences.
MiFEPRIStone	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus.
Mitotane	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane.
Nivolumab	Immunosuppressants may diminish the therapeutic effect of Nivolumab.
Palifermin	May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy.
Pitolisant	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant.
Platinum Derivatives	May enhance the myelosuppressive effect of Taxane Derivatives. Administer Taxane derivative before Platinum derivative when given as sequential infusions to limit toxicity.
Roflumilast	May enhance the immunosuppressive effect of Immunosuppressants.
St John's Wort	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.
Stiripentol	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring.
Tofacitinib	Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants.
Vaccines (Inactivated)	Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation.
Risk Factor X (Avoid combination)
BCG (Intravesical)	Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical).
BCG (Intravesical)	Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical).
Cladribine	May enhance the immunosuppressive effect of Immunosuppressants.
Cladribine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Conivaptan	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Deferiprone	Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone.
Dipyrone	May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased
Fusidic Acid (Systemic)	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Idelalisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Natalizumab	Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
Pimecrolimus	May enhance the adverse/toxic effect of Immunosuppressants.
Tacrolimus (Topical)	May enhance the adverse/toxic effect of Immunosuppressants.
Vaccines (Live)	Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants.

Monitoring parameters:

Blood Tests

• Complete Blood Count (CBC): Check before every treatment cycle.
• Liver Function: Check bilirubin, ALT, AST, and alkaline phosphatase levels before every treatment cycle.
• Kidney Function: Regularly monitor.

Watch Out For:

• Allergic Reactions: Especially in patients who had reactions to paclitaxel before. Monitor closely when starting the treatment.
• Nerve Symptoms: Look for sensations like tingling or numbness.
• Stomach & Gut Issues: This includes diarrhea, mouth sores, inflammation of the intestines, and colitis especially when white blood cell count is low.
• Skin Reactions: Observe for any changes or irritations on the skin.
• Eye Issues: Check for any vision problems, excessive tearing, or narrowing of tear ducts.
• Fluid Build-Up: Look for signs like swelling or weight gain.

How to administer Docetaxel (Taxotere)?

Infusion Process:

• Infuse docetaxel over 1 hour.
• Use tubing that doesn't absorb the drug (non-DEHP, polyethylene lined).

Pre-Medication:

• Take corticosteroids for 3 days, starting a day before the docetaxel treatment. This helps reduce allergic reactions and fluid buildup.

Alcohol Content:

• Some docetaxel versions contain alcohol. This could be a concern for certain patients. If needed, there's a version without alcohol available.

Filter Use:

• Don't use an in-line filter for Taxotere; the manufacturer hasn't tested it for compatibility.
• Don't use an in-line filter for the non-alcohol version of docetaxel either.

Avoiding Extravasation (drug leakage into the surrounding tissue):

• Docetaxel can irritate or damage tissue if it leaks out of the vein.
• Make sure the needle or catheter is properly placed before starting the infusion.

If Extravasation Happens:

• Stop the infusion immediately but leave the needle/cannula in place.
• Gently pull out the leaked solution without flushing the line.
• Remove the needle/cannula and raise the affected limb.
• There's some debate about whether to use a warm or cold compress.

Mechanism of action of Docetaxel (Taxotere):

• Docetaxel works by helping to build structures called microtubules in the cell, and making sure they stay stable.
• These microtubules are important for cell function.
• By stabilizing them, docetaxel stops the cell from making DNA, RNA, and proteins, which the cell needs to grow.
• This action mainly affects a specific phase in the cell's life cycle, called the M phase.
• When given at the suggested doses, the way the body processes docetaxel is consistent and predictable.

Protein binding:

• Docetaxel spreads widely in the body, mostly outside the blood vessels, and it binds a lot to body tissues. On average, the volume it spreads in the body is 113 liters.

Metabolism

• It sticks to proteins in the blood: about 94% to 97% of it binds to specific proteins like alpha-acid glycoprotein, albumin, and some fats in the blood.
• Our liver processes docetaxel, mainly using a system called CYP3A4, which turns it into different products.

Half-life elimination:

• About half of the drug is removed from the body in roughly 11 hours.

Excretion:

• When the body gets rid of docetaxel, about 75% of it goes out in the feces (poop), and only a tiny part of that is the unchanged drug.
• Around 6% is removed in the urine (pee).

Docetaxel Brand Names (International):

• Docefrez
• Taxotere
• Adenex SV
• Asodoc
• Belotaxel
• Brexel
• Camitotic
• Daxotel
• Decexan
• Dexotel
• Docegrix
• Docetax
• Docetex
• Docexan
• Dolectran
• Doletran
• Donataxel
• Dotaxel
• Doxecal
• Doxestad
• Doxetal
• Doxetasan
• Eutaxer
• Hentaxel
• Isotera
• Monotaxel
• Newtaxel-A
• Newtaxell
• Novotaxel
• Oncodocel
• Oncotaxel
• Pacancer
• Qvidadotax
• Taceedo
• Taxanit
• Taxanit RTU
• Taxelo
• Taxespira
• Taxomed
• Taxotere
• Taxozen
• Tedocad
• Texot
• Tyxan
• Vexdo
• Zytax

Docetaxel Brand Names in Pakistan:

Docetaxel Injection 20 mg
Daxotel	Atco Laboratories Limited
Docetax	A. J. Mirza Pharma (Pvt) Ltd
Docetaxel Varifarma	Medinet Pharmaceuticals
Donataxel	Ferozsons Laboratoies Ltd.
Dozep	Pharmedic (Pvt) Ltd.
Mebrexel	Consolidated Chemical Laboratories (Pvt) Ltd.
Taxotere	Sanofi Aventis (Pakistan) Ltd.
Texot	Atco Laboratories Limited

Docetaxel Injection 80 mg
Daxotel	Atco Laboratories Limited
Docetax	A. J. Mirza Pharma (Pvt) Ltd
Mebrexel	Consolidated Chemical Laboratories (Pvt) Ltd.

Docetaxel Injection 20 mg/0.5ml
Docekabir	Oncogene Pharmaceuticals Karachi
Docetaxel	Al-Habib Pharmaceuticals.
Ebedoce	Novartis Pharma (Pak) Ltd

Docetaxel Injection 80 mg/0.5ml
Docekabir	Oncogene Pharmaceuticals Karachi
Docetaxel	Al-Habib Pharmaceuticals.
Ebedoce	Novartis Pharma (Pak) Ltd

Docetaxel Infusion 20 Mg
Taxotere Concentrate	Sanofi Aventis (Pakistan) Ltd.

Docetaxel Infusion 80 mg
Taxotere Concentrate	Sanofi Aventis (Pakistan) Ltd.