Cabazitaxel

IV Compatibilities

Solution: 0.9% NaCl or dextrose 5%

IV Preparation

Use aseptic technique

2-step dilution process

Do not mix with any other drugs

Step 1 (1st dilution)

• Mix cabazitaxel 60 mg/1.5 mL vial with entire contents of supplied diluent
• Once reconstituted, resultant solution contains 10 mg/mL
• Vial contains slight overfill (ie, entire vial contains about 65 mg)
• When transferring the diluent, direct the needle onto the inside wall of vial and inject slowly to limit foaming
• Remove syringe and needle and gently mix the initial diluted solution by repeated inversions for at least 45 seconds to assure full mixing of the drug and diluent; DO NOT SHAKE
• Let solution stand for a few minutes to allow any foam to dissipate, and check that the solution is homogeneous and contains no visible particulate matter; it is not required that all foam dissipate prior to continuing the preparation process

Step 2 (2nd dilution)

• Withdraw recommended dose from reconstituted vial containing 10 mg/mL (1st dilution)
• Further dilute into sterile 250 mL PVC-free container (glass, polyolefin) of either 0.9% NaCl or dextrose 5% solution for infusion
• Final concentration should range between 0.1-0.26 mg/mL
• Thoroughly mix final infusion solution by gently inverting the bag/bottle

IV Administration

Administer IV infusion via volumetric infusion pump

Administer over 1 hr

Use an in-line filter (0.22 micron pore size) during administration

Storage

Appearance is clear, yellow to brownish-yellow, viscous solution under proper storage conditions

Store drug and diluent at room temp 25 degrees C (77 degrees F); brief exposure permitted between 15-30 degrees C (59-86 degrees F)

Do not refrigerate undiluted vial or diluent

Stability

• Do not use PVC infusion containers or polyurethane infusions sets for preparation and administration
• 1st diluted solution in vial: Use immediately (within 30 min) and discard unused portion
• 2nd (final) dilution in infusion bag: Use within 8 hr (ambient temperature, including infusion time), or for a total of 24 hr refrigerated
• Both 1st diluted solution and 2nd (final) infusion solution are supersaturated and may crystallize over time; if crystals and/or particulates appear, solutions must not be used and should be discarded

Cabazitaxel is part of the drug class:

• Taxanes

If cabazitaxel is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Many drugs can interact with cabazitaxel. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide. Tell your doctor about all medicines you use, and those you start or stop using during your treatment with cabazitaxel. Give a list of all your medicines to any healthcare provider who treats you.

Contraindications

• Known severe hypersensitivity reaction to cabazitaxel or other formulations containing polysorbate 80.1

• Baseline neutrophil count ≤1500/mm3.1

Warnings/Precautions

Warnings

Risk of severe, sometimes fatal, neutropenia.1

Monitor CBCs weekly during the first treatment cycle and prior to each treatment cycle thereafter.1 Administer recommended dose for initial cycle; adjust dosage for each subsequent cycle as needed based on hematologic recovery.1 (See Dosage Modification for Toxicity under Dosage and Administration.) Do not administer cabazitaxel until neutrophil count is >1500/mm3.1

Consider primary prophylaxis with G-CSF in patients with high-risk clinical features that could potentially increase risk of complications associated with prolonged neutropenia (e.g., age >65 years, poor performance status, prior episodes of febrile neutropenia, extensive prior radiation, poor nutritional status, other serious comorbidities).1 3

Consider therapeutic use of G-CSF and secondary prophylaxis in all patients at increased risk for neutropenic complications.1 (See Dosage Modification for Toxicity under Dosage and Administration.)

If severe prolonged neutropenia occurs despite appropriate treatment (e.g., G-CSF) or if febrile neutropenia occurs, temporary interruption of cabazitaxel therapy followed by dosage reduction or discontinuance of cabazitaxel therapy may be required.1 (See Dosage Modification for Toxicity under Dosage and Administration.)

Risk of severe hypersensitivity reactions (e.g., hypotension, bronchospasm, generalized rash/erythema).1

Premedicate all patients prior to each infusion to reduce the risk and/or severity of hypersensitivity reactions.1 (See Premedication under Dosage and Administration.)

Closely observe patient for hypersensitivity reactions, especially during the first and second infusions.1 3 Have appropriate facilities and equipment for the treatment of hypotension and bronchospasm readily available, since hypersensitivity reactions may occur within minutes following initiation of an infusion.1

If severe hypersensitivity reaction occurs, discontinue infusion immediately and institute appropriate supportive treatment.1

Cabazitaxel injection concentrate contains polysorbate 80; do not administer to patients with a history of severe hypersensitivity reactions to cabazitaxel or to other agents containing polysorbate 80.1

Other Warnings and Precautions

Risk of nausea and vomiting.1 4 Manufacturer recommends antiemetic prophylaxis (orally or IV as needed).1

Risk of severe diarrhea.1 Death related to diarrhea, dehydration, and electrolyte imbalance reported.1 2

Administer rehydration therapy and antidiarrheal and antiemetic agents as needed; intensive measures may be required for management of severe diarrhea and electrolyte imbalance.1 In patients with severe or persistent diarrhea, temporary interruption of therapy followed by dosage reduction, or discontinuance of cabazitaxel therapy, may be required.1 (See Dosage Modification for Diarrhea under Dosage and Administration.)

Renal failure reported,1 2 generally in association with sepsis, dehydration, or obstructive uropathy; some deaths due to renal failure did not have a clear etiology.1 If renal failure develops, take appropriate measures to identify the cause and treat aggressively.1

May cause fetal harm.1 Embryotoxic, fetotoxic, and abortifacient in animals.1 Avoid pregnancy during therapy.1 If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.1

Administer under the supervision of a qualified clinician experienced in the use of cytotoxic agents.1 Have appropriate diagnostic and treatment facilities readily available for management of treatment-related complications.1

Monitor CBCs weekly during first treatment cycle and prior to each treatment cycle thereafter.1

Patients must have recovered from acute toxicities (i.e., neutrophils recovered to >1500/mm3, improvement or resolution of febrile neutropenia or diarrhea) before each cycle.1

Specific Populations

Category D.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Cabazitaxel or its metabolites are distributed into milk in rats; not known whether distributed into human milk.1 Discontinue nursing or the drug.1

Safety and efficacy not established in pediatric patients.1

No overall differences in efficacy or pharmacokinetics in individuals ≥65 years of age compared with younger adults.1 However, patients ≥65 years of age had higher incidence of neutropenia, fatigue, asthenia, pyrexia, dizziness, urinary tract infection, and dehydration; also had higher rate of death within 30 days of the last cabazitaxel dose from a cause other than disease progression.1

Safety and efficacy not established.1 However, cabazitaxel is extensively metabolized, and hepatic impairment is likely to increase serum concentrations of the drug.1

Hepatic impairment increases the risk of severe or life-threatening complications of other taxanes (e.g., docetaxel).1 14 Manufacturer states that cabazitaxel should not be used in patients with hepatic impairment (serum ALT and/or AST ≥1.5 times ULN or total serum bilirubin at or above ULN).1

Safety and efficacy not studied specifically to date.1

Mild to moderate renal impairment (Clcr 30 to <80 mL/minute) does not substantially alter clearance.1

Not studied in patients with severe renal impairment (Clcr <30 mL/minute) or end-stage renal disease;1 use with caution in these patients.1

Common Adverse Effects

Myelosuppression1 2 (neutropenia,1 2 leukopenia,1 2 anemia,1 2 thrombocytopenia1 2 ), diarrhea,1 2 fatigue,1 2 nausea,1 2 vomiting,1 2 constipation,1 2 asthenia,1 2 abdominal pain,1 2 anorexia,1 back pain,1 2 hematuria,1 2 peripheral neuropathy,1 2 pyrexia,1 2 dyspnea,1 2 cough,1 dysgeusia,1 arthralgia,1 2 alopecia.1

Storage

Parenteral

25°C (may be exposed to 15–30°C); do not refrigerate.1

Diluted cabazitaxel solutions are supersaturated and may crystallize over time.1

Use initial diluted solution (10 mg/mL) within 30 minutes of preparation.1

Use final diluted solution (0.1–0.26 mg/mL) within 8 hours (including 1 hour for administration) if stored at room temperature or within 24 hours (including 1 hour for administration) if stored under refrigeration.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

• Risk of hypersensitivity reactions.1 Importance of informing clinician immediately if manifestations of severe hypersensitivity (e.g., rash, itching, dizziness or faintness, difficulty breathing, chest or throat tightness, facial swelling) occur.1 Importance of informing clinician of any history of hypersensitivity to cabazitaxel or other agents containing polysorbate 80.1

• Risk of infection, including severe or potentially fatal infection.1 Importance of patients monitoring their temperature frequently and immediately notifying clinician if fever or other manifestations of infection (e.g., cough, burning on urination, myalgia) occur.1

• Risk of dehydration.1 Importance of informing clinician if substantial vomiting or diarrhea occurs.1

• Risk of renal failure.1 Importance of informing clinician if decreased urine output occurs or if edema develops.1

• Importance of routine monitoring of blood cell counts.1

• Importance of taking the oral prednisone component of the cabazitaxel/prednisone regimen for prostate cancer as directed.1 Importance of informing clinician if not adherent to oral prednisone regimen.1

• Importance of informing geriatric patients that certain adverse effects may be more frequent or severe in older patients.1 (See Geriatric Use under Cautions.)

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Apprise patient of potential hazard to the fetus if used during pregnancy; women of childbearing potential should avoid becoming pregnant.1

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.1

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

• If you need to store cabazitaxel at home, talk with your doctor, nurse, or pharmacist about how to store it.

• RPR-116258A
• XRP6258

ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer: Utilize patient’s actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (Griggs 2012).

Antineoplastic Agents (Anthracycline, Systemic): Taxane Derivatives may enhance the adverse/toxic effect of Antineoplastic Agents (Anthracycline, Systemic). Taxane Derivatives may increase the serum concentration of Antineoplastic Agents (Anthracycline, Systemic). Taxane Derivatives may also increase the formation of toxic anthracycline metabolites in heart tissue. Consider therapy modification

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Cabazitaxel. Management: Concurrent use of cabazitaxel with strong inhibitors of CYP3A4 should be avoided when possible. If such a combination must be used, consider a 25% reduction in the cabazitaxel dose. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. 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). Consider therapy modification

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

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. Consider therapy modification

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. 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. Consider therapy modification

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). Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

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. Consider therapy modification

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Consider therapy modification

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. 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. Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

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. Consider therapy modification

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Platinum Derivatives: May enhance the myelosuppressive effect of Taxane Derivatives. Administer Taxane derivative before Platinum derivative when given as sequential infusions to limit toxicity. Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. 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. Consider therapy modification

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

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. Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

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. Consider therapy modification

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. Avoid combination

Concerns related to adverse effects:

• Bone marrow suppression: [US Boxed Warning]: Deaths due to neutropenia have been reported. Cabazitaxel is contraindicated in patients with neutrophil count ≤1,500/mm3. Monitor blood counts frequently. Neutropenia, anemia, thrombocytopenia, and/or pancytopenia may occur with use; grade 3 and 4 neutropenia was observed in over 80% of patients treated with cabazitaxel in a clinical trial. Dose reductions are recommended following neutropenic fever or prolonged neutropenia. Administration of WBC growth factors may reduce the risk of complications due to neutropenia. Consider primary WBC growth factor prophylaxis in high-risk patients (eg, >65 years of age, poor performance status, history of neutropenic fever, extensive prior radiation, poor nutrition status, other serious comorbidities); secondary prophylaxis and therapeutic WBC growth factors should be considered in all patients with increased risk for neutropenic complications. Use cautiously in patients with hemoglobin <10 g/dL. Monitor complete blood counts weekly during cycle 1 and prior to subsequent treatment cycles, or as clinically indicated.

• Gastrointestinal toxicity: Nausea, vomiting and diarrhea may occur. Diarrhea may be severe and may result in dehydration and electrolyte imbalance; fatalities have been reported. Per the manufacturer, antiemetic prophylaxis is recommended. Antidiarrheal medication and fluid and electrolyte replacement may be necessary. Diarrhea ≥ grade 3 may require treatment delay and or dosage reduction. Gastrointestinal hemorrhage and perforation, enterocolitis, neutropenic enterocolitis, and ileus (some fatal) have also been observed. Use with caution in patients at risk of developing gastrointestinal complications (eg, elderly patients, those with neutropenia or a prior history of pelvic radiation, adhesions, GI ulceration or bleeding, concomitant use of steroids, NSAIDs, antiplatelet or anticoagulant medications). Evaluate promptly if symptoms such as abdominal pain and tenderness, fever, persistent constipation, and diarrhea (with or without neutropenia) occur. May require treatment interruption and/or therapy discontinuation.

• Hypersensitivity reactions: [US Boxed Warning]: Severe hypersensitivity reactions, including generalized rash, erythema, hypotension, and bronchospasm may occur. Immediate discontinuation is required if hypersensitivity is severe; administer appropriate supportive medications. Premedicate with an IV antihistamine, corticosteroid, and H2 antagonist prior to infusion. Use in patients with history of severe hypersensitivity to cabazitaxel or other medications formulated with polysorbate 80 is contraindicated. Observe closely during infusion, especially during the first and second infusions; reaction may occur within minutes. Do not rechallenge after severe hypersensitivity reactions.

• Pulmonary toxicity: Interstitial pneumonia/pneumonitis, interstitial lung disease, and acute respiratory distress syndrome have been observed; may be fatal. Patients with underlying pulmonary disease may be at higher risk for these events. Acute respiratory distress syndrome may occur in the setting of infection. If new or worsening pulmonary symptoms develop, interrupt cabazitaxel treatment, monitor closely and promptly investigate and manage symptoms. May require discontinuation (carefully evaluate the potential benefits of treatment resumption).

• Renal failure: Renal failure (including rare fatalities) has been reported from clinical trials; generally associated with dehydration, sepsis, or obstructive uropathy. Use with caution in patients with severe renal impairment (CrCl <30 mL/minute) and end-stage renal disease.

Disease-related concerns:

• Hepatic impairment: Use is contraindicated in patients with severe hepatic impairment (total bilirubin >3 times ULN). Dose reduction is necessary in patients with mild impairment (total bilirubin >1 to ≤1.5 times ULN or AST >1.5 times ULN) and moderate impairment (total bilirubin >1.5 to ≤3 times ULN); use with caution and monitor closely. Due to extensive hepatic metabolism, cabazitaxel exposure is increased in patients with hepatic impairment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling.

Special populations:

• Elderly: Patients ≥65 years of age are more likely to experience certain adverse reactions, including grade 3 and 4 neutropenia and neutropenic fever. Fatigue, asthenia, pyrexia, dizziness, urinary tract infection, and dehydration also occurred more frequently in elderly patients compared to younger patients. Death due to causes other than disease progression (within 30 days of the last cabazitaxel dose) was higher in elderly patients versus younger patients.

Other warnings/precautions:

• Preparation for administration: Failure to properly reconstitute the concentrated vial of cabazitaxel with the correct amount of diluent may lead to higher dosage being administered and increased risk of toxicity. Follow manufacturer instructions carefully.

Use during pregnancy is considered contraindicated. (AU) Use is not recommended. (UK, US) AU TGA pregnancy category: D US FDA pregnancy category: D Comments: -Men should use effective contraception throughout treatment and for up to 6 months after the last dose. -Due to potential exposure via seminal liquid, men should prevent contact with the ejaculate by another person throughout treatment. -If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Animal studies have shown that this drug is embryotoxic, fetotoxic, and abortifacient. This drug crosses the placental barrier. There are no adequate or well-controlled studies in pregnant women. AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details. US FDA pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.