Drug: Alemtuzumab (Campath®)

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Usual Diluents

NS , D5W

Dilution Data

[Amount of drug] [Infusion volume] [Infusion rate]

Admixture:
[Prescribed dose] [100 ml ] [2 hours]

Inject syringe contents into 100 mL sterile 0.9% Sodium Chloride USP or 5% Dextrose in Water USP. Gently invert the bag to mix the solution. Discard syringe. The vial contains no preservatives and is intended for single use only. DISCARD VIAL including any unused portion after withdrawal of dose.
Use within 8 hours after dilution. Store diluted Campath at room temperature (15-30°C) or refrigerated (2-8°C). Protect from light.

Unlabeled route: subcutaneous - see specialized reference e.g. [Solimando, DA. Drug Information Handbook for Oncology: A Complete Guide to Combination Chemotherapy Regimens, 8th ed. Hudson, OH: Lexi-Comp, Inc.; 2010.]

Recommended Concomitant Medications: [1] Premedicate with diphenhydramine (50 mg) and acetaminophen (500-1000 mg) 30 minutes prior to first infusion and each dose escalation. Institute appropriate medical management (e.g. steroids, epinephrine, meperidine) for infusion reactions as needed. [2 ] Administer trimethoprim/sulfamethoxazole DS twice daily (BID) three times per week (or equivalent) as Pneumocystis jiroveci pneumonia (PCP) prophylaxis. [3 ] Administer famciclovir 250 mg BID or equivalent as herpetic prophylaxis. Continue PCP and herpes viral prophylaxis for a minimum of 2 months after completion of Campath or until the CD4+ count is

200 cells/µL, whichever occurs later.

Dose escalation is required at initiation of dosing - See DOSAGE AND ADMINISTRATION

Stability / Miscellaneous

WARNINGS	CLINICAL PHARMACOLOGY	INDICATIONS
DOSAGE AND ADMINISTRATION	RECONSTITUTION / DILUTION	HOW SUPPLIED
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WARNING
WARNING: CYTOPENIAS, INFUSION REACTIONS, and INFECTIONS
Cytopenias: Serious, including fatal, pancytopenia/marrow hypoplasia, autoimmune idiopathic thrombocytopenia, and autoimmune hemolytic anemia can occur in patients receiving Campath. Single doses of Campath greater than 30 mg or cumulative doses greater than 90 mg per week increase the incidence of pancytopenia [see PACKAGE INSERT FOR WARNINGS AND PRECAUTIONS (5.1)].

Infusion Reactions: Campath administration can result in serious, including fatal, infusion reactions. Carefully monitor patients during infusions and withhold Campath for Grade 3 or 4 infusion reactions. Gradually escalate Campath to the recommended dose at the initiation of therapy and after interruption of therapy for 7 or more days [see PACKAGE INSERT FOR DOSAGE AND ADMINISTRATION (2) and WARNINGS AND PRECAUTIONS (5.2)].

Infections: Serious, including fatal, bacterial, viral, fungal, and protozoan infections can occur in patients receiving Campath. Administer prophylaxis against Pneumocystis jiroveci pneumonia (PCP) and herpes virus infections [see PACKAGE INSERT FOR DOSAGE AND ADMINISTRATION (2.2) and WARNINGS AND PRECAUTIONS (5.3)].

CLINICAL PHARMACOLOGY
Mechanism of Action
Campath binds to CD52, an antigen present on the surface of B and T lymphocytes, a majority of monocytes, macrophages, NK cells, and a subpopulation of granulocytes. A proportion of bone marrow cells, including some CD34+ cells, express variable levels of CD52. The proposed mechanism of action is antibody-dependent cellular-mediated lysis following cell surface binding of Campath to the leukemic cells.

Pharmacokinetics
Campath pharmacokinetics were characterized in a study of 30 previously treated B-CLL patients in whom Campath was administered at the recommended dose and schedule. Campath pharmacokinetics displayed nonlinear elimination kinetics. After the last 30 mg dose, the mean volume of distribution at steady-state was 0.18 L/kg (range 0.1 to 0.4 L/kg). Systemic clearance decreased with repeated administration due to decreased receptor-mediated clearance (i.e., loss of CD52 receptors in the periphery). After 12 weeks of dosing, patients exhibited a seven-fold increase in mean AUC. Mean half-life was 11 hours (range 2 to 32 hours) after the first 30 mg dose and was 6 days (range 1 to 14 days) after the last 30 mg dose.

Comparisons of AUC in patients

65 years (n=6) versus patients < 65 years (n=15) suggested that no dose adjustments are necessary for age. Comparisons of AUC in female patients (n=4) versus male patients (n=17) suggested that no dose adjustments are necessary for gender.

The pharmacokinetics of Campath in pediatric patients have not been studied. The effects of renal or hepatic impairment on the pharmacokinetics of Campath have not been studied

INDICATIONS AND USAGE
Campath is indicated as a single agent for the treatment of B-cell chronic lymphocytic leukemia (B-CLL).

DOSAGE AND ADMINISTRATION
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2.1 Dosing Schedule and Administration

Administer as an IV infusion over 2 hours. Do not administer as intravenous push or bolus.
Recommended Dosing Regimen
- Gradually escalate to the maximum recommended single dose of 30 mg. Escalation is required at initiation of dosing or if dosing is held 7 days during treatment. Escalation to 30 mg ordinarily can be accomplished in 3 - 7 days.
- Escalation Strategy:
  - Administer 3 mg daily until infusion reactions are grade 2 [see PACKAGE INSERT - ADVERSE REACTIONS (6.1)].
  - Then administer 10 mg daily until infusion reactions are grade 2.
  - Then administer 30 mg/day three times per week on alternate days (e.g., Mon-Wed-Fri). The total duration of therapy, including dose escalation, is 12 weeks.
Single doses of greater than 30 mg or cumulative doses greater than 90 mg per week increase the incidence of pancytopenia

2.2 Recommended Concomitant Medications
        -Premedicate with diphenhydramine (50 mg) and acetaminophen (500-1000 mg) 30 minutes prior to first infusion and each dose escalation. Institute appropriate medical management (e.g. steroids, epinephrine, meperidine) for infusion reactions as needed [see PACKAGE INSERT -BOXED WARNING, WARNINGS AND PRECAUTIONS (5.2) and ADVERSE REACTIONS (6.1)].
       -Administer trimethoprim/sulfamethoxazole DS twice daily (BID) three times per week (or equivalent) as Pneumocystis jiroveci pneumonia (PCP) prophylaxis.
      -Administer famciclovir 250 mg BID or equivalent as herpetic prophylaxis.
Continue PCP and herpes viral prophylaxis for a minimum of 2 months after completion of Campath or until the CD4+ count is

200 cells/µL, whichever occurs later [see PACKAGE INSERT - BOXED WARNING and WARNINGS AND PRECAUTIONS (5.3)].

2.3 Dose Modification

Withhold Campath during serious infection or other serious adverse reactions until resolution.
Discontinue Campath for autoimmune anemia or autoimmune thrombocytopenia.
There are no dose modifications recommended for lymphopenia.

Dose Modification for Neutropenia or Thrombocytopenia [see PACKAGE INSERT -WARNINGS AND PRECAUTIONS (5.1)]

Hematologic Values	Dose Modification*
ANC < 250/µL and/or platelet count 25,000/µL
For first occurrence:	Withhold Campath therapy. Resume Campath at 30 mg when ANC 500/µL and platelet count 50,000/µL.
For second occurrence:	Withhold Campath therapy. Resume Campath at 10 mg when ANC 500/µL and platelet count 50,000/µL.
For third occurrence:	Discontinue Campath therapy.
50% decrease from baseline in patients initiating therapy with a baseline ANC 250/µL and/or a baseline platelet count 25,000/µL
For first occurrence:	Withhold Campath therapy. Resume Campath at 30 mg upon return to baseline value(s).
For second occurrence:	Withhold Campath therapy. Resume Campath at 10 mg upon return to baseline value(s).
For third occurrence:	Discontinue Campath therapy.
*Dose Modification for Neutropenia or Thrombocytopenia [see WARNINGS AND PRECAUTIONS (5.1)] If the delay between dosing is 7 days, initiate therapy at Campath 3 mg and escalate to 10 mg and then to 30 mg as tolerated [see DOSAGE AND ADMINISTRATION (2.1)].

2.4 Preparation and Administration
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. If particulate matter is present or the solution is discolored, the vial should not be used. DO NOT SHAKE VIAL.

Use aseptic technique during the preparation and administration of Campath. Withdraw the necessary amount of Campath from the vial into a syringe.

To prepare the 3 mg dose, withdraw 0.1 mL into a 1 mL syringe calibrated in increments of 0.01 mL.
To prepare the 10 mg dose, withdraw 0.33 mL into a 1 mL syringe calibrated in increments of 0.01 mL.
To prepare the 30 mg dose, withdraw 1 mL in either a 1 mL or 3 mL syringe calibrated in 0.1 mL increments.

Reference(s)