Paclitaxel is a chemotherapeutic drug used in the treatment of various types of cancer, including ovarian, breast, and non-small cell lung cancer, among others. It's derived from the Pacific yew tree (Taxus brevifolia).

Paclitaxel (Taxol) is a chemotherapeutic agent, a plant alkaloid, that is used in the treatment of various cancers including breast, ovarian, lung, cervical cancer, and Kaposi's sarcoma.

Paclitaxel (Taxol) Uses:

• Breast cancer:
  • Adjuvant treatment of node-positive breast cancer; treatment of metastatic breast cancer after failure of combination chemotherapy or relapse within 6 months of adjuvant chemotherapy (previous therapy must include an anthracycline)
• Kaposi sarcoma (AIDS-related):
  • Second-line treatment of AIDS-related Kaposi sarcoma
• Non-small cell lung cancer:
  • First-line treatment of non-small cell lung cancer (in combination with cisplatin) in patients who are not candidates for potentially curative surgery and/or radiation therapy
• Ovarian cancer:
  • Subsequent therapy for the treatment of advanced ovarian cancer; first-line therapy of ovarian cancer (in combination with cisplatin)
• Off Label Use of Paclitaxel in Adults:
  • Bladder cancer, advanced or metastatic
  • Cervical cancer, advanced
  • Esophageal/gastric cancer, preoperative chemoradiation
  • Head and neck cancers, advanced
  • Ovarian cancer, intraperitoneal (offlabel route)
  • Penile cancer, metastatic
  • Small cell lung cancer, relapsed/refractory
  • Soft tissue sarcoma (angiosarcoma), advanced/unresectable
  • Testicular germ cell tumors, relapsed/refractory
  • Thymoma/thymic carcinoma, advanced
  • Unknown primary adenocarcinoma
  • Endometrial carcinoma
  • Esophageal cancer (metastatic/unresectable)
  • Gastric cancer (metastatic/unresectable)
  • Melanoma
  • Thyroid cancer (anaplastic).

Paclitaxel (Taxol) Dose in Adults

Note:

• Before getting the paclitaxel treatment, it's advised to take some pre-medications to prevent potential side effects.
• You should take a pill called dexamethasone twice, first 12 hours before and then 6 hours before your treatment (if you have advanced HIV, take a smaller dose).
• Also, about half an hour to an hour before your treatment, you'll be given an injection of diphenhydramine and another medicine, which could be cimetidine, famotidine, or ranitidine.
• These helps prepare your body for the paclitaxel treatment.

Paclitaxel (Taxol) Dose in the treatment of Breast cancer, adjuvant treatment:

• For breast cancer adjuvant treatment, paclitaxel is given intravenously (through an IV).
• The dose is 175 mg/m^2, and it's administered over a span of 3 hours.
• This treatment is given every 3 weeks, and the patient goes through 4 cycles of this therapy.
• It's important to note that this paclitaxel regimen is typically given after a regimen that contains an anthracycline (another type of chemotherapy drug).

Paclitaxel (Taxol) Dose in the treatment of metastatic or relapsed Breast cancer: 

• For the treatment of metastatic or relapsed breast cancer, paclitaxel is given intravenously (IV). The recommended dose is 175 mg/m^2, administered over a duration of 3 hours. This treatment is repeated every 3 weeks.

Paclitaxel (Taxol) Dose in the treatment of AIDS-related Kaposi sarcoma, : 

For the treatment of AIDS-related Kaposi sarcoma, paclitaxel is given through an IV. Two dosing options are available:

• 135 mg/m^2, administered over 3 hours, and repeated every 3 weeks.
• 100 mg/m^2, administered over 3 hours, and repeated every 2 weeks. This lower dose is recommended for patients who aren't as physically robust or have a lower performance status because of the potential for stronger side effects.

It's also important to note that for these patients, the premedication with dexamethasone should be reduced to a dose of 10 mg.

Paclitaxel (Taxol) Dose in the treatment of non-small cell lung cancer:

• Standard Regimen: Administer paclitaxel at a dose of 135 mg/m^2 over 24 hours every 3 weeks. This treatment is usually combined with another drug called cisplatin.
• Off-label combinations:
  • Pembrolizumab and Carboplatin: Give paclitaxel at a dose of 200 mg/m^2 on the first day, repeated every 3 weeks for 4 cycles. This regimen is combined with pembrolizumab and carboplatin. After these cycles, continue treatment with pembrolizumab as a maintenance therapy. (Based on Paz-Ares 2018 study)
  • Atezolizumab, Bevacizumab, and Carboplatin: Administer paclitaxel at a dose of 200 mg/m^2 (or 175 mg/m^2 for Asian patients) on the first day, repeated every 3 weeks for 4 to 6 cycles. This combination includes atezolizumab, bevacizumab, and carboplatin. After these cycles, continue with atezolizumab and bevacizumab as maintenance therapy. (Based on Socinski 2018 study)

Paclitaxel (Taxol) Dose in the treatment of advanced ovarian cancer:

Previously Treated:

• IV (Intravenous) treatment: 135 or 175 mg/m^2 over 3 hours, every 3 weeks.

Previously Untreated:

• IV: 175 mg/m^2 over 3 hours every 3 weeks, combined with cisplatin.
• Alternatively, IV: 135 mg/m^2 over 24 hours every 3 weeks, combined with cisplatin.

Intraperitoneal (Off-label route):

• 60 mg/m^2 on day 8 in a 21-day treatment cycle for 6 cycles. This is combined with IV paclitaxel (135 mg/m^2 over 24 hours on day 1) and intraperitoneal cisplatin. Standard premedication for paclitaxel is needed.

Previously Untreated (Off-label combinations):

• IV: 175 mg/m^2 over 3 hours every 3 weeks, combined with carboplatin, for 6 cycles.
• Or IV: 60 mg/m^2 over 1 hour weekly, combined with carboplatin, for 18 weeks.
• Another regimen includes 175 mg/m^2 on day 1 every 3 weeks, combined with bevacizumab (from cycle 2) and carboplatin, for up to 6 cycles. This is followed by bevacizumab alone for up to 22 cycles or until disease progression.

Neoadjuvant Therapy (Off-label):

• Only select patients should receive this treatment, especially those with a suspected stage IIIC or IV ovarian cancer, who have a high surgical risk or are less likely to achieve optimal cytoreduction.
• Regimens:
  • IV: 175 mg/m^2 over 3 hours on day 1 every 3 weeks, combined with carboplatin, for 3 neoadjuvant cycles. After that, undergo debulking surgery, followed by 3 more chemotherapy cycles.
  • Or IV: 175 mg/m^2 on day 1 every 3 weeks, combined with carboplatin, for 3-4 neoadjuvant cycles. Post this, undergo debulking surgery, then 2-3 additional chemotherapy cycles, totaling 6 cycles.

Paclitaxel (Taxol) Dose in the treatment of advanced or metastatic Bladder cancer (off-label): 

• Regimen based on Sternberg 2001:
  • IV (Intravenous) treatment: 150 mg/m^2 every 2 weeks, combined with gemcitabine.
• Regimen based on Meluch 2001:
  • IV: 200 mg/m^2 over 1 hour every 3 weeks, combined with gemcitabine, for a total of 6 cycles.

Paclitaxel (Taxol) Dose in the treatment of advanced cervical cancer (off-label):

• Regimen based on Tewari 2014:
  • IV (Intravenous) treatment: 135 or 175 mg/m^2 every 3 weeks, combined with bevacizumab and cisplatin, until the disease progresses or the side effects become too severe.
  • Alternatively, IV: 175 mg/m^2 every 3 weeks, combined with bevacizumab and topotecan, until either the disease progresses or side effects are too severe.
• Regimen based on Monk 2009 & Moore 2004:
  • IV: 135 mg/m^2 over 24 hours every 3 weeks, combined with cisplatin, for a total of 6 cycles.

Paclitaxel (Taxol) Dose in the treatment of preoperative chemoradiation of esophageal/ gastric cancer (off-label): 

Treatment Regimen:

• IV (Intravenous) administration of paclitaxel at a dose of 50 mg/m^2 on days 1, 8, 15, 22, and 29. This is combined with carboplatin and radiation therapy.
• After the chemotherapy and radiation treatment, surgery is typically performed within a timeframe of 4 to 6 weeks.

Paclitaxel (Taxol) Dose in the treatment of head and neck cancers, advanced (off-label):

Treatment Regimen:

• IV (Intravenous) administration of paclitaxel at a dose of 175 mg/m^2, given over 3 hours, every 3 weeks. This is combined with cisplatin.
• The treatment typically lasts for at least 6 cycles.

Paclitaxel (Taxol) Dose in the treatment of metastatic Penile cancer (off-label):

Treatment Regimen:

• IV (Intravenous) administration of paclitaxel at a dose of 175 mg/m^2, given over 3 hours, every 3 to 4 weeks.
• This is combined with ifosfamide and cisplatin.
• The treatment is typically carried out for 4 cycles.

Paclitaxel (Taxol) Dose in the treatment of relapsed/ refractory small cell lung cancer (off-label): 

Based on Smit 1998:

• Treatment Regimen:
  • IV (Intravenous) administration of paclitaxel at a dose of 175 mg/m^2, given over 3 hours, every 3 weeks. This is used as a single agent.
  • The treatment typically lasts for up to 5 cycles.

Based on Yamamoto 2006:

• Treatment Regimen:
  • IV administration of paclitaxel at a dose of 80 mg/m^2, given over 1 hour, weekly for 6 weeks within an 8-week treatment cycle. This is used as a single agent.
  • Treatment continues until the disease progresses or side effects become too severe (unacceptable toxicity).

Paclitaxel (Taxol) Dose in the treatment of advanced/ unresectable soft tissue sarcoma (angiosarcoma),  (off-label): 

Based on Penel 2008:

• Treatment Regimen:
  • IV (Intravenous) administration of paclitaxel at a dose of 80 mg/m^2, given over 1 hour on days 1, 8, and 15 within a 4-week treatment cycle. It's used as a single agent.
  • The treatment is typically carried out for up to 6 cycles.

Based on Schlemmer 2008:

• Treatment Regimens:
  • IV administration of paclitaxel at a dose of 135 to 175 mg/m^2, given over 3 hours, every 3 weeks. This is used as a single agent.
  • Alternatively, IV administration of paclitaxel at a dose of 75 to 100 mg/m^2, given once weekly. This is also used as a single agent.

Paclitaxel (Taxol) Dose in the treatment of relapsed or refractory testicular germ cell tumors (off-label):

Based on Bokemeyer 2008:

• Treatment Regimen:
  • IV (Intravenous) administration of paclitaxel at a dose of 80 mg/m^2, given over 1 hour on days 1 and 8 of a 3-week treatment cycle. This is combined with gemcitabine and oxaliplatin.
  • Treatment continues for 2 cycles beyond the best response observed, up to a maximum of 8 cycles.

Based on Kondagunta 2005:

• Treatment Regimen:
  • IV administration of paclitaxel at a dose of 250 mg/m^2, given over 24 hours on day 1 of a 3-week treatment cycle. This is combined with ifosfamide, mesna, cisplatin, and filgrastim.
  • The treatment typically lasts for 4 cycles.

Based on Einhorn 2007:

• Treatment Regimen:
  • IV administration of paclitaxel at a dose of 100 mg/m^2, given over 1 hour on days 1, 8, and 15 within a 4-week treatment cycle. This is combined with gemcitabine.
  • Treatment is typically carried out for up to 6 cycles.

Paclitaxel (Taxol) Dose in the treatment of advanced Thymoma or thymic carcinoma, (off-label):

Treatment Regimen:

• IV (Intravenous) administration of paclitaxel at a dose of 225 mg/m^2, given over 3 hours, every 3 weeks. This is combined with carboplatin.
• The treatment typically lasts for up to 6 cycles.

Paclitaxel (Taxol) Dose in the treatment of Unknown primary adenocarcinoma (off-label):

Based on Briasoulis 2000:

• Treatment Regimen:
  • IV (Intravenous) administration of paclitaxel at a dose of 200 mg/m^2, given over 3 hours, every 3 weeks. This is combined with carboplatin.
  • The treatment is usually carried out for 6 to 8 cycles.

Based on Greco 2000:

• Treatment Regimen:
  • IV administration of paclitaxel at a dose of 200 mg/m^2, given over 1 hour, every 3 weeks. This regimen combines paclitaxel with both carboplatin and etoposide.
  • Treatment typically ranges from 4 to 8 cycles.

Use in Children:

Not indicated.

Pregnancy Risk Factor D

• Studies on animals have shown that paclitaxel can cause problems during reproduction.
• When tested on a human placenta model, it was found that paclitaxel can cross over to the baby, especially at the end of pregnancy.
• The drug's movement to the baby is less when there's more albumin, a protein in the blood.
• Also, how this drug behaves might change in pregnant women.
• So, women who can become pregnant should be told to avoid getting pregnant while on this drug.

Use of paclitaxel while breastfeeding

• A study found that paclitaxel, a drug used for cancer treatment, can get into breast milk.
• In one case, a mother who was treated for thyroid cancer had paclitaxel in her milk even several days after getting the drug.
• The amount of drug that the baby might get from the milk was found to be about 17% of what the mother took.
• By about 13 days (316 hours) after the treatment, the drug couldn't be found in the milk anymore.
• Because this drug can harm the baby, it's advised that mothers don't breastfeed while on this treatment.

Paclitaxel (Taxol) Dose in Kidney Disease:

The manufacturer's instructions don't provide specific dosage adjustments for certain conditions, but experts have made recommendations.

• If someone's kidney function is below a certain level (CrCl <50 mL/minute), they usually don't need a dosage adjustment for paclitaxel.
• For patients on hemodialysis, paclitaxel can still be used because it's not removed by the dialysis process. So, it can be given before or after dialysis as needed.

Paclitaxel (Taxol) Dose in Liver Disease:

Note:

• The manufacturer's dosage recommendations are mainly based on the patient's initial treatment and how their body reacts.
• For future treatments, the dosage may vary depending on the patient's response.

For a 24-hour infusion of paclitaxel:

• If liver enzymes are less than twice the normal limit and bilirubin (a liver function marker) is up to 1.5 mg/dL: the dose is 135 mg/m.
• If liver enzymes are 2 to 9 times the normal limit, but bilirubin is still up to 1.5 mg/dL: the dose is 100 mg/m.
• If liver enzymes are less than 10 times the normal limit and bilirubin is between 1.6 to 7.5 mg/dL: the dose is 50 mg/m.
• If liver enzymes are 10 times or more than the normal limit or bilirubin is more than 7.5 mg/dL: paclitaxel should not be used.

For a 3-hour infusion of paclitaxel:

• If liver enzymes are less than 10 times the normal limit and bilirubin is up to 1.25 times the normal limit: the dose is 175 mg/m.
• If liver enzymes are less than 10 times the normal limit and bilirubin is between 1.26 to 2 times the normal limit: the dose is 135 mg/m.
• If liver enzymes are less than 10 times the normal limit and bilirubin is between 2.01 to 5 times the normal limit: the dose is 90 mg/m.
• If liver enzymes are 10 times or more than the normal limit or bilirubin is more than 5 times the normal limit: paclitaxel should not be used.

Common Side Effects of Paclitaxel (Taxol):

• Cardiovascular:
  • Flushing
  • ECG Abnormality
  • Edema
  • Hypotension
• Central Nervous System:
  • Peripheral Neuropathy
• Dermatologic:
  • Alopecia
  • Skin Rash
• Gastrointestinal:
  • Nausea
  • Vomiting
  • Diarrhea
  • Mucositis
  • Stomatitis
  • Abdominal Pain
• Hematologic & Oncologic:
  • Neutropenia
  • Leukopenia
  • Anemia
  • Thrombocytopenia
  • Hemorrhage
• Hepatic:
  • Increased Serum Alkaline Phosphatase
  • Increased Serum AST
• Hypersensitivity:
  • Hypersensitivity Reaction
• Infection:
  • Infection
• Local:
  • Injection Site Reaction
• Neuromuscular & Skeletal:
  • Arthralgia
  • Myalgia
  • Weakness
• Renal:
  • Increased Serum Creatinine

Less Common Side Effects Of Paclitaxel (Taxol):

• Cardiovascular:
  • Bradycardia
  • Tachycardia
  • Hypertension
  • Cardiac Arrhythmia
  • Syncope
  • Venous Thrombosis
• Dermatologic:
  • Changes In Nails
• Hematologic & Oncologic:
  • Febrile Neutropenia
• Hepatic:
  • Increased Serum Bilirubin
• Respiratory:
  • Dyspnea

Contraindications to Paclitaxel (Taxol):

Paclitaxel shouldn't be used in people who:

• Are allergic to paclitaxel itself, a substance called polyoxyl 35 or another substance called Cremophor EL, or any other ingredient in the paclitaxel mixture.
• Are being treated for solid tumors and have very low levels of a type of white blood cell called neutrophils (less than 1,500 per tiny drop of blood).
• Are being treated for Kaposi sarcoma and have even lower levels of neutrophils (less than 1,000 per tiny drop of blood).

These conditions can make the treatment risky or less effective.

Warnings and precautions

Suppression of bone marrow: [US Boxed Warning]

• Paclitaxel can seriously decrease the number of a certain type of white blood cells called neutrophils in the bone marrow, which can increase the risk of infections.
• It's crucial to frequently check blood counts during treatment.
• Don't start paclitaxel if these neutrophils are too low: below 1,500 per tiny drop of blood for solid tumors, or below 1,000 for those with Kaposi sarcoma related to AIDS.
• This decrease in neutrophils often happens about 11 days after treatment and is the main reason to limit or adjust the drug dosage.
• Before giving the next dose, ensure that neutrophil counts have recovered to safer levels.
• If neutrophil counts drop too low for a long time, consider reducing the drug dosage by 20% in future treatments and think about giving other treatments to support and boost these counts.

Cardiovascular effects

• When paclitaxel is given, there's a chance of blood pressure changes, like it going too low or too high, and the heart rate slowing down.
• It's important to frequently check vital signs, especially in the first hour of the drug being given.
• There have been rare cases where paclitaxel caused serious heart rhythm problems.
• If someone has had these problems with paclitaxel before, they should have continuous heart monitoring during future treatments.
• The American Heart Association has also said that paclitaxel might harm the heart directly or make existing heart problems worse.
• Always be cautious and monitor the heart closely when using this medication.

Extravasation

• When giving paclitaxel, be very careful as it can harm the skin and tissues around where it's injected.
• Before and during the treatment, make sure the needle or tube is correctly placed in the vein.
• If the drug leaks outside the vein, it can cause mild reactions like skin color changes, soreness, redness, or swelling.
• These reactions might show up a week or more after the treatment, especially if the drug is given over a longer time, like 24 hours.
• In some cases, the reactions can be more severe, causing skin peeling, dead tissue, hardening, or redness and swelling of the skin.
• Sometimes, even if the drug is given through a different vein the next time, the skin might still react.
• Always be cautious and check the injection site regularly.

Hypersensitivity reactions: [US Boxed Warning]

• Some people have severe allergic reactions when getting paclitaxel.
• Symptoms can include difficulty breathing needing treatment, low blood pressure that requires intervention, swelling, and skin rashes.
• These reactions have happened to 2% to 4% of patients in studies, even with precautionary medications given beforehand.
• In rare cases, these reactions can be deadly.
• To lower the risk, patients are given medications like steroids, antihistamines, and others before paclitaxel.
• If a severe allergic reaction does happen, the infusion should be stopped immediately, and the patient shouldn't get paclitaxel again.
• Smaller allergic reactions, like skin redness, breathing issues, changes in blood pressure, or fast heartbeat, don't usually require stopping the treatment.

Peripheral neuropathy

• Paclitaxel can often cause issues with the nerves, leading to symptoms like tingling or numbness, especially in the hands and feet.
• People who've had nerve problems from other cancer treatments or those with conditions like diabetes might be more likely to experience these issues.
• If someone has severe nerve symptoms with paclitaxel, the dose should be reduced by 20%.
• Always keep an eye out for any signs of nerve problems and talk to the doctor if they appear.

Hepatic impairment

• Be very careful when using paclitaxel in patients with liver problems.
• Those with high levels of bilirubin (a substance the liver produces) might have worsened bone marrow side effects, which can affect the blood.
• If a patient has liver problems, a lower dose of paclitaxel is recommended.
• Always monitor patients with liver issues closely when they're on this medication.

Paclitaxel (conventional): Drug Interaction

Risk Factor C (Monitor therapy)
Abiraterone Acetate	May increase the serum concentration of CYP2C8 Substrates (High risk with Inhibitors).
Alfuzosin	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Antipsychotic Agents (Second Generation [Atypical])	Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]).
Aprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Barbiturates	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Benperidol	May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bexarotene (Systemic)	PACLitaxel (Conventional) may increase the serum concentration of Bexarotene (Systemic). Bexarotene (Systemic) may decrease the serum concentration of PACLitaxel (Conventional).
Blood Pressure Lowering Agents	May enhance the hypotensive effect of HypotensionAssociated Agents.
Bosentan	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Brimonidine (Topical)	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Chloramphenicol (Ophthalmic)	May enhance the adverse/toxic effect of Myelosuppressive Agents.
Clofazimine	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Clopidogrel	May increase the serum concentration of PACLitaxel (Conventional).
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.
CYP2C8 Inhibitors (Moderate)	May decrease the metabolism of CYP2C8 Substrates (High risk with Inhibitors).
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).
Deferasirox	May increase the serum concentration of CYP2C8 Substrates (High risk with Inhibitors).
Denosumab	May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
Diazoxide	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
DULoxetine	Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine.
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.
Fosaprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Fosnetupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Herbs (Hypotensive Properties)	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Hypotension-Associated Agents	Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents.
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).
Levodopa-Containing Products	Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products.
Lormetazepam	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Mesalamine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Molsidomine	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Naftopidil	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Netupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Nicergoline	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nicorandil	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nitroprusside	Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside.
Ocrelizumab	May enhance the immunosuppressive effect of Immunosuppressants.
Palbociclib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Pentoxifylline	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
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.).
Pholcodine	Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine.
Phosphodiesterase 5 Inhibitors	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Pidotimod	Immunosuppressants may diminish the therapeutic effect of Pidotimod.
Promazine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Prostacyclin Analogues	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Quinagolide	May enhance the hypotensive effect of Blood Pressure Lowering 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.
Tertomotide	Immunosuppressants may diminish the therapeutic effect of Tertomotide.
Tocilizumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Trastuzumab	May decrease the serum concentration of PACLitaxel (Conventional). PACLitaxel (Conventional) may increase the serum concentration of Trastuzumab.
Vinorelbine	PACLitaxel (Conventional) may enhance the neurotoxic effect of Vinorelbine.
Risk Factor D (Consider therapy modification)
Amifostine	Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered.
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.
CYP2C8 Inhibitors (Strong)	May decrease the metabolism of CYP2C8 Substrates (High risk with Inhibitors).
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 decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors).
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).
Dabrafenib	May decrease the serum concentration of CYP2C8 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP2C8 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects).
Deferiprone	Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely.
DOXOrubicin (Conventional)	Taxane Derivatives may decrease the metabolism of DOXOrubicin (Conventional). Management: Consider using docetaxel instead of paclitaxel as a way to avoid this potential interaction, and monitor closely for toxic effects of doxorubicin. Administer doxorubicin prior to paclitaxel when used concomitantly.
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 CYP2C8 Substrates (High risk with Inhibitors). Management: Use CYP2C8 substrates at the lowest recommended dose, and monitor closely for adverse effects (including myopathy), during and in the 2 weeks following mifepristone treatment.
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.
Obinutuzumab	May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion.
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.
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.
Sipuleucel-T	Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy.
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)
Atazanavir	May increase the serum concentration of PACLitaxel (Conventional). Management: Use of paclitaxel or other narrow therapeutic index CYP2C8 substrates with atazanavir without concurrent ritonavir is not recommended. If paclitaxel is used with ritonavir-boosted atazanavir, no significant interaction is expected.
BCG (Intravesical)	Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical).
BCG (Intravesical)	Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical).
Bromperidol	Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents.
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).
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.
SORAfenib	May enhance the adverse/toxic effect of PACLitaxel (Conventional). Management: Concurrent sorafenib with carboplatin and paclitaxel in patients with squamous cell lung cancer is contraindicated. Use in other settings is not specifically contraindicated but should be approached with added caution.
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:

• Check the complete blood count (CBC) to see different types of blood cells.
• Specifically, look at the platelet count.
• Monitor liver and kidney function.

Allergic Reactions:

• Watch out for signs of allergic reactions.

Vital Signs:

• Regularly check things like blood pressure, heart rate, and temperature, especially during the first hour of the infusion.

Heart Monitoring:

• If the patient has heart rhythm problems, use continuous cardiac monitoring.

Infusion Site:

• Keep an eye on the spot where the medicine is being infused to make sure there are no problems or reactions.

How to administer Paclitaxel (Taxol)?

• How to Administer:
  • Give through an IV (drip into the vein).
  • The infusion can take 3 or 24 hours, depending on the medical condition and treatment plan. Some special cases might need only a 1-hour infusion.
  • Use a special filter (0.22-micron) and a specific tube (polyethylene-lined) for the infusion.
• Order of Medications:
  • When used with other chemotherapy drugs, the sequence of giving them can vary. Always refer to the specific treatment plan.
• Preparation Before Infusion:
  • Give dexamethasone (a steroid) 12 and 6 hours before the paclitaxel dose.
    • The standard dose is 20 mg, either by mouth or IV.
    • For patients with advanced HIV, reduce this to 10 mg.
  • Give diphenhydramine (an antihistamine) 30 to 60 minutes before the paclitaxel dose. The dose is 50 mg IV.
  • Give one of the stomach medications (cimetidine 300 mg, famotidine 20 mg, or ranitidine 50 mg) IV 30 to 60 minutes before the paclitaxel dose.
• Caution During Infusion:
  • Paclitaxel can be harmful to skin and tissues if it leaks out of the vein.
  • Always make sure the needle or tube is correctly placed in the vein.
• What to Do if There's a Leak (Extravasation):
  • If the drug leaks, stop the infusion and don't remove the needle.
  • Try to pull out the leaked drug without flushing the line.
  • Consider using hyaluronidase (an antidote) to help manage the leak.
    • If the needle is still in place, give 1 mL of hyaluronidase for each 1 mL of leaked drug through the IV.
    • If the needle is out, inject it around the leak area.
  • Elevate the affected limb (arm or leg).
• Using Paclitaxel in the Abdomen (Intraperitoneal):
  • This is an off-label use, meaning it's not the standard method.
  • Prepare the solution in warm saline and give it quickly through a special tube placed in the abdomen.

Mechanism of action of Paclitaxel (Taxol):

• Paclitaxel works by boosting the actions of certain cell parts called microtubules, making them more stable and preventing them from falling apart.
• This messes with a specific phase of cell division, stopping cells from multiplying.
• The drug can also cause cell structures to be out of shape, leading to broken chromosomes.
• Apart from this, paclitaxel might slow down cell growth and affect the body's immune response.

Distribution:

• After being given, paclitaxel spreads widely in the body.
• The amount it spreads can change based on the dose and how long it's given for.
• The average spread is between 227 to 688 L/m.
• At first, it moves quickly to some parts of the body, and later, it slowly comes out of those parts.

Binding to Proteins:

• Between 89% to 98% of paclitaxel in the body attaches to proteins.

Breaking Down in the Body:

• The liver breaks down paclitaxel, mainly using pathways called CYP2C8 and 3A4. This process creates new substances, with 6α-hydroxypaclitaxel being the main one.

How Long it Stays in the Body:

• In children: It takes around 4.6 to 17 hours for half of the drug to leave the body. This can change based on the dose and how long the drug is given.
• In adults:
  • For a 3-hour infusion: On average, about 13 to 20 hours.
  • For a 24-hour infusion: On average, about 16 to 53 hours.

Getting Rid of the Drug:

• Most of paclitaxel (about 71%) leaves the body through poop, with only about 5% unchanged. A smaller part (about 14%) goes out in pee.

International Brand Names of Paclitaxel:

• APO-Paclitaxel
• Aclipak
• Aclixel
• Acoexel
• Alzene
• Anzatax
• Asotax
• Bristaxol
• Britaxol
• Celtax
• Clitaxel
• Cryoxet
• Dalys
• Ebetaxel
• Genaxol
• Genetaxyl
• Intaxel
• Meditaxel
• Mitotax
• Ofoxel
• Pacli-One
• Pacliavenir
• Paclitaxin
• Paclitero
• Paclitex
• Pacxel
• Padexol
• Panataxel
• Parexel
• Paxel
• Paxene
• Paxol
• Paxomed
• Praxel
• Santotaxel
• Sindaxel
• Taxocris
• Taxol
• Vexel
• Xelpac

Paclitaxel Brand Names in Pakistan:

Paclitaxel Injection 210 mg in Pakistan
Paclitaxel Ebewe	Novartis Pharma (Pak) Ltd

Paclitaxel Injection 6 mg/ml in Pakistan
Anzatax	Atco Laboratories Limited
Ebetaxel	Bio Pharma
Ebetaxel	Bio Pharma
Paclitax	Pharmedic (Pvt) Ltd.
Paclitaxel	Inno Pharm
Paclitaxel Varifarma	Medinet Pharmaceuticals
Panataxel	Ferozsons Laboratoies Ltd.
Taxol	Glaxosmithkline
Unitaxel	Al-Habib Pharmaceuticals.

Paclitaxel Injection 30 mg/ml in Pakistan
Anzatax	Atco Laboratories Limited
Intaxel	Atco Laboratories Limited
Metaplaxel	Consolidated Chemical Laboratories (Pvt) Ltd.
Oncotaxel	Pharmevo (Pvt) Ltd.
Paclikebir	Oncogene Pharmaceuticals Karachi
Paclitaxfil	Atco Laboratories Limited
Paclixil	A. J. Mirza Pharma (Pvt) Ltd

Paclitaxel Injection 100 mg/ml in Pakistan
Intaxel	Atco Laboratories Limited
Paclitax	Pharmedic (Pvt) Ltd.
Paclixil	A. J. Mirza Pharma (Pvt) Ltd

Paclitaxel Injection 150 mg/ml in Pakistan
Anzatax	Atco Laboratories Limited
Metaplaxel	Consolidated Chemical Laboratories (Pvt) Ltd.
Paclikebir	Oncogene Pharmaceuticals Karachi
Paclitax	Pharmedic (Pvt) Ltd.
Paclitaxel Ebewe	Novartis Pharma (Pak) Ltd

Paclitaxel Injection 260 mg/ml in Pakistan
Intaxel	Atco Laboratories Limited
Paclixil	A. J. Mirza Pharma (Pvt) Ltd

Paclitaxel Injection 300 mg/ml in Pakistan
Intaxel	Atco Laboratories Limited
Paclikebir	Oncogene Pharmaceuticals Karachi
Paclitaxel Ahp	A. J. Mirza Pharma (Pvt) Ltd
Paclitaxel Ebewe	Novartis Pharma (Pak) Ltd