---

Paclitaxel medac® is:

• - Indicated in combination with cisplatin in patients with ovarian carcinoma as first-line treatment.
  - Indicated for second line treatment for metastatic carcinoma of the ovary after failure of standard therapy with platinum-containing preparations.
  - Indicated as second line treatment in Breast carcinoma as adjuvant treatment of node positive breast carcinoma.
  - Taken in combination with cisplatin for Advanced non-small-cell lung carcinoma (NSCLC) treatment.
  - Indicated in second line treatment for AIDS-related Kaposi´s sarcoma (KS)

• Pharmacology

Mechanism of Action
Natural taxane, prevents depolymerization of cellular microtubules, which results in DNA, RNA, and protein synthesis inhibition
Pharmacokinetics
Protein bound: 89-98%
Vd: 227-688 L/m²
Metabolism: Metabolized by CYP2C8, CYP3A4
Metabolites: 6-alpha-hydroxypaclitaxel (major)
Half-life elimination: 27hr terminal
Excretion: Feces (20%); urine (4%)

2. Administration

IV Incompatibilities

Additive: cisplatin (comp at low paxlitaxel conc; incomp at high paclitaxel conc)
Y-site: amphotericin B, amphotericin B cholesteryl sulfate, chlorpromazine, doxorubicin liposomal, hydroxyzine, methylprednisolone sodium succinate, mitoxantrone

IV Compatibilities

Additive: carboplatin, doxorubicin
Y-site (partial list): acyclovir, ampicillin-sulbactam, bleomycin, carboplatin, cisplatin, cytarabine, diphenhydramine, famotidine, furosemide, granisetron, heparin, linezolid, lorazepam, MgSO4, morphine SO4, ondansetron, KCl, propofol, NaHCO3, vancomycin

IV Preparation

Further dilution in NS or D5W to a concentration of 0.3-1.2 mg/mL
Standard dilution (IVPB): dose/500-1000 mL D5W or NS

IV Administration

Irritant
Mfr recommends administration over 1-24 hr
Administer taxane derivatives before platinum derivatives (cisplatin, carboplatin) in sequential infusions to limit myelosuppression and to enhance efficacy
Administer corticosteroids, H1-antagonists, H2 antagonists, prior to paclitaxel administration to minimize potential for anaphylaxis
Non-PVC tubing should be used to minimize leaching
Contact of undiluted concentrate with plasticized PVC equipment or devices is not recommended
Administer through IV tubing containing an in-line (0.22 micron) filter
Should be dispensed in either glass or Excel/PAB

3. Dosage Forms & Strengths

injectable solution

• 6mg/mL

Ovarian Cancer

Premedicate to prevent hypersensitivity reactions (eg, dexamethasone, diphenhydramine, H2 blockers)
Previously untreated: 175 mg/m² IV over 3 hours q3Weeks (follow with cisplatin), OR 
135 mg/m² IV over 24 hours q3Weeks (follow with cisplatin)
Previously treated: Various regimens exist: 135-175 mg/m² IV over 3 hours q3Weeks

Breast Cancer

Node positive (adjuvant chemotherapy): 175 mg/m² IV over 3 hours q3Weeks 4 times (with doxorubicin-containing regimen) 
Metastatic Disease (failure of initial chemotherapy or relapse within 6 months following adjuvant chemotherapy): 175 mg/m² IV over 3 hours q3Weeks

Non-small Cell Lung Cancer

135 mg/m² IV over 24 hours q3Weeks (follow with cisplatin) 

AIDS-related Kaposi's Sarcoma (2nd-line Treatment)

135 mg/m² IV over 3 hours q3Weeks; OR 
100 mg/m² IV over 3 hours q2Weeks

Pancreatic Cancer (Off-label)

Investigational:  125 mg/m² IV with gemcitabine 

Dosage Modifications

If baseline PMN <1500/m³, do not re-treat until PMN >1500/m³ and platelet count >100,000/m³
If severe neutropenia occurs (PMN <500/m³ for 7 days), reduce subsequent doses by 20%
Renal impairment: No dosage adjustment required

Hepatic Impairment

With solid carcinomas and not Kaposi sarcoma
24-hr infusion

• AST/ALT <2 x ULN and bilirubin ≤1.5 mg/dL: 135 mg/m² over 24 hr
• AST/ALT 2-<10 x ULN and bilirubin ≤1.5 mg/dL: 100 mg/m² over 24 hr
• AST/ALT <10 x ULN and bilirubin 1.6-7.5 mg/dL: 50 mg/m² over 24 hr
• AST/ALT ≥10 x ULN OR bilirubin >7.5 mg/dL: Do not administer

3-hr infusion

• AST/ALT <10 x ULN and bilirubin <1.25 x ULN: 175 mg/m² over 3 hr
• AST/ALT <10 x ULN and bilirubin 1.26-2 x ULN: 135 mg/m² over 3 hr
• AST/ALT <10 x ULN and bilirubin 2.01-5 x ULN: 90 mg/m² over 3 hr
• AST/ALT ≥10 x ULN OR bilirubin >5 x ULN: Do not administer

4. Other Indications & Uses

Off-label: head/neck cancer, small-cell lung cancer, upper GI adenocarcinoma, hormone-refractory prostate cancer, NHL, urothelium transitional cell carcinoma, stage IIB-IV melanoma

5. Side effects

>10%	<1%
Neutropenia (78-100%)	Grand mal seizures
Alopecia (55-96%)	Cardiac conduction abnormalities
Anemia (47-96%)	Frequency Not Defined
Arthralgia/myalgia (93%)	Pyrexia
Diarrhea (90%)	Dehydration
Leukopenia (90%)	Pancytopenia
Nausea/vomiting (9-88%)	Congestive heart failure
Opportunistic infections (76%)	Left ventricular dysfunction
Peripheral neuropathy (42-79%)	Stevens-Johnson syndrome, toxic epidermal necrolysis, and extravasation
Thrombocytopenia (4-68%)	Grand mal seizures
Mucositis (5-45%)