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  • CLASSES

    Actinomycines

    BOXED WARNING

    New primary malignancy

    New primary malignancy has been reported (e.g., leukemia) following treatment with radiation and chemotherapy, including dactinomycin. Patients receiving multimodal therapy require long-term and careful observation. DNA damage and cytogenetic effects have been demonstrated in the animal studies.

    Extravasation

    Extravasation resulting in severe soft tissue damage has been reported with intravenous dactinomycin use; surgery and skin grafting may be necessary in severe cases. Extravasation may occur with or without a burning or stinging sensation and even if there is good blood return on needle aspiration. Immediately discontinue the injection or infusion if any signs or symptoms of extravasation occur; restart dactinomycin administration in another vein. Apply intermittent ice to the site for 15 minutes 4-times daily for 3 days if extravasation is suspected. If severe extravasation occurs, observe the patient closely and consult a plastic surgeon.[63445] [61766]

    Accidental exposure, ocular exposure, requires an experienced clinician

    Dactinomycin is highly toxic and its administration requires an experienced clinician knowledgeable in the use of chemotherapy agents. Dactinomycin demonstrates toxic properties such as corrosivity, carcinogenicity, mutagenicity, and teratogenicity; exercise usual cautions for handling, preparing, and administering cytotoxic drugs. Use care to avoid accidental exposure to dactinomycin such as inhaling dust vapors, contact with skin or mucous membranes, or ocular exposure. If accidental exposure occurs, seek medical attention immediately. For ocular exposure, rinse the eyes immediately and thoroughly for at least 15 minutes with water, normal saline, or balanced salt ophthalmic irrigation solution; promptly obtain an ophthalmologic consultation. For accidental skin contact, irrigate the affected area immediately with large amounts of water for at least 15 minutes; remove contaminated clothing and shoes.[63445]

    Pregnancy

    Dactinomycin is classified as FDA pregnancy risk category D. Due to its potential for teratogenesis, dactinomycin should be avoided during pregnancy.[63445] Dactinomycin may cause fetal harm when administered during pregnancy, based on its mechanism of action and data from animal studies. Females of reproductive potential should avoid pregnancy during and after treatment with dactinomycin. Advise pregnant women of the potential risk to the fetus. Embryotoxicity and fetal malformations were observed in pregnant rats, rabbits, and hamsters following dactinomycin administered during organogenesis at doses that were as low as 0.2-times the clinical dose of 1,250 mcg/m2.[61766]

    DEA CLASS

    Rx

    DESCRIPTION

    A cytotoxic antitumor antibiotic
    Used in Wilms tumor, rhabdomyosarcoma, Ewing sarcoma, testicular cancer, gestational trophoblastic neoplasia, and certain locally recurrent or locoregional solid malignancies
    Fatal sinusoidal obstruction syndrome has been reported

    COMMON BRAND NAMES

    Cosmegen

    HOW SUPPLIED

    Cosmegen/Dactinomycin Intravenous Inj Pwd F/Sol: 500mcg

    DOSAGE & INDICATIONS

    For the treatment of gestational trophoblastic disease.
    For the treatment of nonmetastatic or low-risk metastatic gestational trophoblastic disease, as a single-agent.
    Intravenous dosage
    Female Adults and Post-Menarchal Adolescents and Children

    12 mcg/kg IV daily for 5 days.

    For high-risk gestational trophoblastic disease in combination with methotrexate, leucovorin, etoposide, cyclophosphamide, and vincristine (EMA-CO regimen).
    Intravenous dosage
    Female Adults and Post-Menarchal Adolescents and Children

    500 mcg IV daily on days 1 and 2 repeated every 2 weeks for up to 8 weeks in combination with multi-agent chemotherapy.[61766] Dactinomycin has been evaluated in combination with methotrexate, leucovorin, etoposide, cyclophosphamide, and vincristine (EMA-CO regimen) in clinical studies; cure rates have ranged from 70% to 90% in women with high-risk gestational trophoblastic disease. Results are typically better in women who receive EMA-CO as primary therapy and in women without metastatic disease. Growth-factor support should be considered to maintain dose-intensity and prevent hematological toxicity. Complete response is typically defined as three consecutive weekly human chorionic gonadotropin (hCG) levels that are undetectable or less than the upper limit of normal. In studies, treatment was continued for 2 to 3 additional courses after complete hCG response.[33966] [33967]

    For high-risk gestational trophoblastic disease in combination with methotrexate, leucovorin, etoposide, and cisplatin (EMA-EP regimen).
    Intravenous dosage
    Female Adults and Post-Menarchal Adolescents and Children

    500 mcg IV daily on days 1 and 2 repeated every 2 weeks for up to 8 weeks in combination with multi-agent chemotherapy. Dactinomycin has been evaluated in combination with methotrexate, leucovorin, etoposide, and cisplatin (EMA-EP regimen) in a clinical study. Studies in patients with chemotherapy-refractory, high-risk gestational trophoblastic disease have shown response rates of more than 90% with salvage treatment with EMA-EP. Growth-factor support should be considered to maintain dose-intensity and prevent hematological toxicity.

    For the treatment of metastatic nonseminomatous testicular cancer, as part of a multiphase combination chemotherapy regimen.
    Intravenous dosage
    Male Adults, Adolescents, and Children

    1,000 mcg/m2 IV once every 3 weeks for 12 weeks in combination with cisplatin-based, multi-agent chemotherapy. Dactinomycin has been evaluated in combination with cyclophosphamide, bleomycin, vinblastine, and cisplatin (VAB-6 regimen).

    For the treatment of Wilms' tumor, as part of a multiphase combination chemotherapy regimen.
    Intravenous dosage
    Adults, Adolescents, Children, and Infants

    45 mcg/kg IV once every 3 to 6 weeks for up to 26 weeks in combination with multi-agent chemotherapy.[61766] An alternative regimen is dactinomycin 15 mcg/kg IV daily for 5 days in combination with other chemotherapy agents.

    For the treatment of malignant melanoma.
    For the treatment of malignant melanoma as a single-agent or in combination with other chemotherapy†.
    Intravenous dosage
    Adults

    1.2 mg/m2 IV on day 1 every 3 weeks has been given in combination with a single-dose of dacarbazine 800 mg/m2 IV on day 1 of the first course. In a small study of 18 patients, the ORR was 22% with this combination.Single-agent dacarbazine alone has produced response rates of 20%. In another study, dactinomycin in combination with bleomycin, dacarbazine, and vindesine produced an ORR of 33%.

    Intra-arterial dosage (isolated limb perfusion)
    Adults

    50 mcg/kg for the legs or 35 mcg/kg for the arms in combination with hyperthermia has been utilized.

    For the treatment of rhabdomyosarcoma.
    For the treatment of rhabdomyocarcoma, as part of a multiphase combination chemotherapy regimen.
    Intravenous dosage
    Adults, Adolescents, Children, and Infants

    15 mcg/kg IV once daily for 5 days every 3 to 9 weeks for up to 112 weeks in combination with multi-agent chemotherapy. An alternative regimen is dactinomycin 15 mcg/kg IV daily for 5 days in combination with other chemotherapy agents.[63445]

    For the first-line treatment of rhabdomyosarcoma, in combination with vincristine, ifosfamide, and doxorubicin.
    Intravenous dosage
    Adolescents and Children

    Ifosfamide 6,000 mg/m2 continuous IV infusion (CIV) over 48 hours on days 1, 29, and 50 in combination with mesna 6,000 mg/m2/day CIV over 48 hours on days 1, 29, and 50, doxorubicin 40 mg/m2/day IV on days 29 and 30, dactinomycin 0.5 mg/m2/day IV on days 1 through 3 and 50 through 52, and vincristine 1.5 mg/m2 IV on days 1, 8, 15, and 22. The duration of therapy was dependent on stage at diagnosis (stage I: 16 weeks; II: 26 weeks; III: 40 weeks; IV: 48 weeks).

    For the treatment of osteogenic sarcoma†.
    Intravenous dosage
    Adults, Adolescents, and Children

    0.6 mg/m2/day IV on days 1 and 2 or on days 1, 2, and 3 in combination with bleomycin and cyclophospamide (BCD regimen) has been incorporated into multiple treatment protocols. In the POG-8651 protocol, 106 patients (younger than 30 years old) with previously untreated nonmetastatic high-grade osteogenic sarcoma were randomized to receive 3 days of BCD each cycle as part of a multiagent chemotherapy regimen in sequence with doxorubicin and cisplatin, and high-dose methotrexate, either before or after surgical resection. Event-free survival (EFS), the primary endpoint, was not significantly different between the treatment arms, and reached 69% at 5 years in the post-operative group. In a comparison of the Memorial Sloan-Kettering Cancer Center T-10 and T-12 protocols, 73 patients (ages 4.6 to 36.4 years) with previously untreated, high-grade osteogenic sarcoma received BCD on days 1 and 2 of each cycle as part of a multiagent chemotherapy regimen in sequence with doxorubicin and cisplatin, high-dose methotrexate, and surgical resection. The 5-year EFS was 78% and 73% in the T-12 and T-10 protocols, respectively. The use of BCD alone has also been studied in 8 patients (ages 9.1 to 16.4 years) with previously treated metastatic osteogenic sarcoma. Patients received 1 to 5 courses of BCD. No tumor regression could be measured for any of the patients, and progressive tumor enlargement was demonstrated in 2 patients. Use in patients older than 40 years of age has not been adequately assessed.

    For the treatment of Kaposi's sarcoma†.
    Intravenous dosage
    Adults and Adolescents

    0.42 mg/m2/day IV on days 1 through 5, every 3 or 4 weeks (after recovery from myelosuppression) has been studied. Dactinomycin has been given with or without vincristine 1.4 mg/m2 IV weekly until the end of the second course of dactinomycin, then vincristine was given on days 1 and 5 of each subsequent course. In a small study, 9/10 patients (5 CR, 4 PR) receiving dactinomycin achieved a response, and 13/14 patients (10 CR, 3 PR) receiving dactinomycin/vincristine achieved a response.

    †Indicates off-label use

    MAXIMUM DOSAGE

    NOTE: The correct dose of dactinomycin will vary based on specific protocol used. Clinicians should consult the appropriate references to verify the dose.

    Adults

    15 mcg/kg or 400 to 600 mcg/m2 IV daily for 5 days; 45 mcg/kg or 1,250 mcg/m2 IV as a single dose.

    Geriatric

    15 mcg/kg or 400 to 600 mcg/m2 IV daily for 5 days; 45 mcg/kg or 1,250 mcg/m2 IV as a single dose.

    Adolescents

    15 mcg/kg or 400 to 600 mcg/m2 IV daily for 5 days; 45 mcg/kg or 1,250 mcg/m2 IV as a single dose.

    Children

    15 mcg/kg or 400 to 600 mcg/m2 IV daily for 5 days; 45 mcg/kg or 1,250 mcg/m2 IV as a single dose.

    Infants

    15 mcg/kg IV daily for 5 days; 45 mcg/kg or 1,250 mcg/m2 IV as a single dose.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not provided by the manufacturer; however, a 50% dactinomycin dosage reduction has been suggested in patients with hepatic impairment (e.g., any level of elevated hepatic enzymes).[53549]

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Hazardous Drugs Classification
    NIOSH 2016 List: Group 1
    NIOSH (Draft) 2020 List: Table 1
    Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
    Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
    Emetic Risk
    Doses of 1.35 mg/m2/dose or greater: High
    Doses of 10 mcg/kg/dose: Moderate
    Administer routine antiemetic prophylaxis prior to treatment.
    Extravasation Risk
    Vesicant
    Administer drug through a central venous line.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Monitor patients for signs or symptoms of extravasation; stop the injection or infusion immediately if extravasation occurs.
    Reconstitution:
    Add 1.1 mL of preservative-free sterile water for injection to the 500-mcg lyophilized, single-dose vial for a final vial concentration of 500 mcg/mL.
    The reconstituted vial solution should be clear and gold-colored.
    Discard any unused portion of the vial.
    Storage: store reconstituted vials or the diluted solution at room temperature (20 to 25 degrees C; 68 to 77 degrees F) for up to 4 hours from vial reconstitution (includes infusion time).[63445] [61766]
    Intravenous (IV) Injection:
    Withdraw the appropriate amount of dactinomycin and directly inject it into the tubing of a running IV infusion of 5% dextrose injection or 0.9% sodium chloride injection.
    If dactinomycin is injected directly into a vein, use a two-needle technique; use one sterile needle to remove the calculated dose from the vial and another sterile needle for direct injection into the vein.[63445]
    IV Infusion:
    Withdraw the appropriate amount of dactinomycin and dilute it in 5% dextrose injection or 0.9% sodium chloride injection for a final concentration greater than 10 mcg/mL.
    Administer as an IV infusion over 10 to 15 minutes.
    Do not use an in-line filter with a cellulose ester membrane.[61766]

    STORAGE

    Cosmegen:
    - Avoid excessive humidity
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Keep away from heat and flame
    - Protect from moisture
    - Reconstituted product must be used within 4 hours
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in a cool, well ventilated, dry place
    - Store in the original carton to protect from light

    CONTRAINDICATIONS / PRECAUTIONS

    Serious rash

    Use is contraindicated in patients with a history of hypersensitivity with dactinomycin or any component of the product.[63445] Serious rash, such as Steven-Johnson syndrome and toxic epidermal necrolysis have been reported with dactinomycin use. Permanently discontinue therapy in patients who experience a severe mucocutaneous reaction.[61766]

    New primary malignancy

    New primary malignancy has been reported (e.g., leukemia) following treatment with radiation and chemotherapy, including dactinomycin. Patients receiving multimodal therapy require long-term and careful observation. DNA damage and cytogenetic effects have been demonstrated in the animal studies.

    Anemia, bone marrow suppression, geriatric, neutropenia, thrombocytopenia

    Severe myelosuppression/bone marrow suppression (e.g., anemia, neutropenia, and thrombocytopenia) has been reported with dactinomycin therapy; some cases were fatal. Monitor complete blood counts prior to each treatment cycle; delay the next dactinomycin dose if severe myelosuppression persists. Consider a dose reduction in patients who with prolonged myelosuppression based on the severity of the reactions and disease being treated.[61766] Geriatric patients may have an increased risk of myelosuppression compared with younger patients based on a published meta-analysis of all studies performed by the Eastern Cooperative Oncology Group (ECOG) over a 13-year period.[63445]

    Herpes infection, infection

    Use of dactinomycin is contraindicated in patients with an active herpes infection (i.e., chickenpox or herpes zoster infection), due to a risk of death from these infections.[63445]

    Extravasation

    Extravasation resulting in severe soft tissue damage has been reported with intravenous dactinomycin use; surgery and skin grafting may be necessary in severe cases. Extravasation may occur with or without a burning or stinging sensation and even if there is good blood return on needle aspiration. Immediately discontinue the injection or infusion if any signs or symptoms of extravasation occur; restart dactinomycin administration in another vein. Apply intermittent ice to the site for 15 minutes 4-times daily for 3 days if extravasation is suspected. If severe extravasation occurs, observe the patient closely and consult a plastic surgeon.[63445] [61766]

    Children, hepatotoxicity, infants, sinusoidal obstruction syndrome (SOS), veno-occlusive disease (VOD)

    Veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) and hepatotoxicity (e.g., hepatic failure) have been reported with dactinomycin therapy; some cases were fatal. Obtain liver function tests prior to and during therapy; monitor patients for symptoms of VOD (e.g., weight gain and ascites). Consider delaying the next dactinomycin dose if VOD occurs. Resume, dose reduce, or permanently discontinue dactinomycin therapy based on the severity of the reactions and disease being treated. Children younger than 4 years of age may be at increased risk for developing VOD.[61766] Consider using dactinomycin only in infants older than 6 to 12 months due to the risk of increased toxicity.[63445]

    Radiation therapy

    Concomitant use of dactinomycin and radiation therapy may increase the risk of gastrointestinal toxicity, myelosuppression, skin or mucous membrane toxicity, and veno-occlusive disease/sinusoidal obstruction syndrome. Therefore, reduce the dactinomycin dose by 50% if it is used together with radiation. Use dactinomycin with caution in patients who have had prior radiation therapy due to a risk of a radiation recall reaction in the previously treated radiation fields; this risk appears highest if dactinomycin is administered within 2 months of prior radiation therapy.[61766] Administer dactinomycin concomitantly with radiotherapy in patients with Wilms' tumor only after risk versus benefit of therapy assessment.[63445]

    Accidental exposure, ocular exposure, requires an experienced clinician

    Dactinomycin is highly toxic and its administration requires an experienced clinician knowledgeable in the use of chemotherapy agents. Dactinomycin demonstrates toxic properties such as corrosivity, carcinogenicity, mutagenicity, and teratogenicity; exercise usual cautions for handling, preparing, and administering cytotoxic drugs. Use care to avoid accidental exposure to dactinomycin such as inhaling dust vapors, contact with skin or mucous membranes, or ocular exposure. If accidental exposure occurs, seek medical attention immediately. For ocular exposure, rinse the eyes immediately and thoroughly for at least 15 minutes with water, normal saline, or balanced salt ophthalmic irrigation solution; promptly obtain an ophthalmologic consultation. For accidental skin contact, irrigate the affected area immediately with large amounts of water for at least 15 minutes; remove contaminated clothing and shoes.[63445]

    Nephrotoxicity

    Nephrotoxicity (e.g., renal failure) has been reported with dactinomycin therapy. Monitor renal function tests (i.e., serum creatinine) and serum electrolytes frequently during dactinomycin therapy.[61766]

    Vaccination

    Avoid vaccination with live viral vaccines prior to and during dactinomycin therapy.[61766]

    Laboratory test interference

    Dactinomycin may cause laboratory test interference for the determination of antibacterial drug levels.[63445]

    Pregnancy

    Dactinomycin is classified as FDA pregnancy risk category D. Due to its potential for teratogenesis, dactinomycin should be avoided during pregnancy.[63445] Dactinomycin may cause fetal harm when administered during pregnancy, based on its mechanism of action and data from animal studies. Females of reproductive potential should avoid pregnancy during and after treatment with dactinomycin. Advise pregnant women of the potential risk to the fetus. Embryotoxicity and fetal malformations were observed in pregnant rats, rabbits, and hamsters following dactinomycin administered during organogenesis at doses that were as low as 0.2-times the clinical dose of 1,250 mcg/m2.[61766]

    Contraception requirements, male-mediated teratogenicity, pregnancy testing, reproductive risk

    Counsel patients about the reproductive risk and contraception requirements during dactinomycin treatment. Pregnancy testing should be performed prior to starting dactinomycin in female patients of reproductive potential. These patients should use effective contraception and avoid pregnancy during and for at least 6 months after dactinomycin therapy. Women who become pregnant while receiving dactinomycin should be apprised of the potential hazard to the fetus. Additionally, male patients with a female partner of reproductive potential should use effective contraception during and for 3 months after dactinomycin therapy due to the risk of male-mediated teratogenicity.[61766]

    Breast-feeding

    It is not known if dactinomycin or its metabolites are secreted in human milk or if it has effects on the breast-fed infant or milk production. Due to the risk of serious adverse reactions in nursing infants, women should discontinue breast-feeding during dactinomycin therapy and for 14 days after the last dose.[61766]

    ADVERSE REACTIONS

    Severe

    pancytopenia / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    sinusoidal obstruction syndrome (SOS) / Delayed / Incidence not known
    hepatic failure / Delayed / Incidence not known
    disseminated intravascular coagulation (DIC) / Delayed / Incidence not known
    veno-occlusive disease (VOD) / Delayed / Incidence not known
    peptic ulcer / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    thrombosis / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    tissue necrosis / Early / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    new primary malignancy / Delayed / Incidence not known
    leukemia / Delayed / Incidence not known
    pneumothorax / Early / Incidence not known
    tumor lysis syndrome (TLS) / Delayed / Incidence not known
    nephrotoxicity / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    visual impairment / Early / Incidence not known

    Moderate

    neutropenia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    anemia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    ascites / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    hepatomegaly / Delayed / Incidence not known
    hyperbilirubinemia / Delayed / Incidence not known
    proctitis / Delayed / Incidence not known
    esophagitis / Delayed / Incidence not known
    dysphagia / Delayed / Incidence not known
    oral ulceration / Delayed / Incidence not known
    stomatitis / Delayed / Incidence not known
    skin ulcer / Delayed / Incidence not known
    erythema / Early / Incidence not known
    edema / Delayed / Incidence not known
    impaired wound healing / Delayed / Incidence not known
    radiation recall reaction / Delayed / Incidence not known
    hypocalcemia / Delayed / Incidence not known
    pneumonitis / Delayed / Incidence not known
    growth inhibition / Delayed / Incidence not known
    bleeding / Early / Incidence not known
    phlebitis / Rapid / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known

    Mild

    weight gain / Delayed / Incidence not known
    abdominal pain / Early / Incidence not known
    nausea / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    vomiting / Early / Incidence not known
    cheilitis / Delayed / Incidence not known
    diarrhea / Early / Incidence not known
    pharyngitis / Delayed / Incidence not known
    alopecia / Delayed / Incidence not known
    injection site reaction / Rapid / Incidence not known
    rash / Early / Incidence not known
    acne vulgaris / Delayed / Incidence not known
    skin hyperpigmentation / Delayed / Incidence not known
    lethargy / Early / Incidence not known
    malaise / Early / Incidence not known
    fatigue / Early / Incidence not known
    fever / Early / Incidence not known
    myalgia / Early / Incidence not known
    infection / Delayed / Incidence not known

    DRUG INTERACTIONS

    Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
    Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
    Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents.
    Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity.
    SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
    Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.

    PREGNANCY AND LACTATION

    Pregnancy

    Dactinomycin is classified as FDA pregnancy risk category D. Due to its potential for teratogenesis, dactinomycin should be avoided during pregnancy.[63445] Dactinomycin may cause fetal harm when administered during pregnancy, based on its mechanism of action and data from animal studies. Females of reproductive potential should avoid pregnancy during and after treatment with dactinomycin. Advise pregnant women of the potential risk to the fetus. Embryotoxicity and fetal malformations were observed in pregnant rats, rabbits, and hamsters following dactinomycin administered during organogenesis at doses that were as low as 0.2-times the clinical dose of 1,250 mcg/m2.[61766]

    Counsel patients about the reproductive risk and contraception requirements during dactinomycin treatment. Pregnancy testing should be performed prior to starting dactinomycin in female patients of reproductive potential. These patients should use effective contraception and avoid pregnancy during and for at least 6 months after dactinomycin therapy. Women who become pregnant while receiving dactinomycin should be apprised of the potential hazard to the fetus. Additionally, male patients with a female partner of reproductive potential should use effective contraception during and for 3 months after dactinomycin therapy due to the risk of male-mediated teratogenicity.[61766]

    MECHANISM OF ACTION

    Dactinomycin is a cell cycle-phase nonspecific, antibiotic that is more active in actively proliferating cells. It complexes with DNA by intercalating between DNA residues, causing the helix to uncoil and thereby inhibiting DNA synthesis and DNA-dependent RNA synthesis. Dactinomycin selectively inhibits messenger RNA synthesis.

    PHARMACOKINETICS

    Dactinomycin is administered intravenously (IV); additionally, it may be administered via regional perfusion. Radiolabeled dactinomycin did not penetrate the blood-brain barrier in 3 adult patients with malignant melanoma. It is minimally metabolized and is concentrated in nucleated cells. Approximately 30% of radiolabeled dactinomycin was recovered in urine and feces within 1 week. The terminal plasma half-life was about 36 hours.[63445] [61766]
    Affected cytochrome P450 isoenzymes or drug transporters: P-gp, OATP1B3Dactinomycin is a substrate of P-glycoprotein and OATP1B3 transporters in vitro.[61766]