Name of the Antimetabolites Drugs
- Cytarabine
- Fluorouracil, 5- FU
- Methotrexate
- Hydroxyurea
- Azacitidine
1.Cytarabine
| Cytarabine |
| Availability : Injection, Powder for Reconstitution (Conventional): 100 mg, 500 mg, 1 g. Injection, Solution (Conventional): 20 mg/mL, 100 mg/mL. Injection, Suspension (Liposomal): 10 mg/mL. |
| Administration/handling: May give by subcutaneous, IV push, IV infusion, intrathecal routes at concentration not to exceed 100 mg/mL. May be carcinogenic, mutagenic, teratogenic (embryonic deformity). Handle with extreme care during preparation/administration. Liposomal for intrathecal use only. |
| IV, Intrathecal: Reconstitution : Conventional: Reconstitute with Bacteriostatic Water for Injection. • Dose may be further diluted with 250–1,000 mL D5W or 0.9% NaCl for IV infusion. • Intrathecal: reconstitute vial with preservative-free 0.9% NaCl or pt’s spinal fluid. Dose usually administered in 5–15 mL of solution, after equivalent volume of CSF removed. • Liposomal: No reconstitution required. Rate of administration :• Conventional: For IV infusion, give over 1–3 hrs or as continuous infusion. Storage : Conventional: Store at room temperature. • Reconstituted solution is stable for 48 hrs at room temperature. • Use diluted solution within 24 hrs. • Discard if slight haze develops. • Liposomal: Refrigerate; use within 4 hrs following withdrawal from vial. |
| Follow facility procedures for safe handling, administration, and disposal of chemotherapeutic drugs. For I.V. injection, reconstitute each 100 mg with 5 ml of diluent (if necessary), and give each 100-mg dose over 1 to 3 minutes. For I.V. infusion, dilute further with 50 to 100 ml of dextrose 5% in water or normal saline solution, and infuse over 30 minutes to 24 hours (depending on dosage and concentration).; Be aware that conventional and liposomal forms can be administered intrathecally. Don’t use intrathecal route for formulations containing benzyl alcohol. |
| When giving conventional form intrathecally, reconstitute with autologous spinal fluid or preservative-free normal saline solution for injection. Use immediately; Patients receiving intrathecal cytarabine should be treated concurrently with dexamethasone to mitigate symptoms of chemical arachnoiditis. |
| Usual Dosage for Induction (Conventional) (Refer to Individual Protocols) IV: Adults, elderly, children: (Induction): 100 mg/m2/day continuous infusion for 7 days or 200 mg/m2/day continuous infusion (as 100 mg/m2 over 12 hrs q12h) for 7 days. |
| To induce remission of acute nonlymphocytic leukemia: Adults: Injection (conventional form)—100 mg/m2/day by continuous I.V. infusion on days 1 through 7, or 100 mg/m2 I.V. q 12 hours on days 1 through 7, given with other antineoplastics |
| Meningeal leukemia: Adults: Injection (conventional form)—5 to 75 mg/m2/day intrathecally for 4 days, or once q 4 days. Most common dosage is 30 mg/m2 q 4 days until cerebrospinal fluid is normal |
| Lymphomatous meningitis : Adults: Liposomal injection—50 mg intrathecally q 14 days for two doses (at weeks 1 and 3); then q 14 days for three doses (at weeks 5, 7, and 9), with one additional dose at week 13; then q 28 days for four doses |
Mechanism of Action:
Inhibits DNA polymerase. Cell cycle–specific for S phase of cell division. Therapeutic Effect: Inhibits DNA synthesis.
Potent immunosuppressive activity.
Indications:
- To induce remission of acute nonlymphocytic Leukemia
- Meningeal leukemia
- Lymphomatous meningitis
- Refractory Leukemia
Cautions & Contraindications:
- •Hypersensitivity to cytarabine.
- •Liposomal: Active meningeal infection.
- •Cautions: Renal/hepatic impairment, prior drug-induced bone marrow suppression.
Metabolism and Half- Life:
Widely distributed; moderate amount crosses blood-brain barrier. Protein binding: 15%. Primarily excreted in urine. Half-life: 1–3 hrs
Drug Interactions:
- May decrease therapeutic effect of BCG (intravesical), vaccines (live).
- May increase adverse effects of vaccines (live).
- May increase adverse effects of natalizumab.
- Echinacea may decrease therapeutic effect.
- May increase serum alkaline phosphatase, bilirubin, uric acid, AST.
Side- Effects:
Frequent:
- IV: Asthenia, fever, pain, altered taste/smell, nausea, vomiting (risk greater with IV push than with continuous IV infusion).
- Intrathecal: Headache, asthenia, altered taste/smell, confusion, drowsiness, nausea, vomiting.
Occasional:
- IV: Abnormal gait, drowsiness, constipation, back pain, urinary incontinence, peripheral edema, headache, confusion.
- Intrathecal: Peripheral edema, back pain, constipation, abnormal gait, urinary incontinence.
Nursing Considerations
Baseline assessment
- Monitor liver function test results, CBC with differential, platelet count, blood urea nitrogen, and serum creatinine and uric acid levels.
- Leukocyte count decreases within 24 hrs after initial dose, continues to decrease for 7–9 days followed by brief rise at 12 days, decreases again at 15–24 days, then rises rapidly for next 10 days.
- Platelet count decreases 5 days after drug initiation to its lowest count at 12–15 days, then rises rapidly for next 10 days.
- Observe for signs and symptoms of cytarabine syndrome (malaise, fever, muscle ache, bone pain, occasional chest pain, maculopapular rash, and conjunctivitis).
- When giving liposomal form, assess for signs and symptoms of chemical arachnoiditis, such as neck rigidity and pain, nausea, vomiting, headache, fever, and back pain.
- Observe closely for signs and symptoms of infection, which could become severe and fatal.
Intervention/evaluation
- Monitor BMP, LFT, serum uric acid.
- Monitor CBC for evidence of myelosuppression.
- Monitor for blood dyscrasias (fever, sore throat, signs of local infection, unusual bruising/bleeding from any site), symptoms of anemia (excessive fatigue, weakness).
- Monitor for signs of neuropathy (gait disturbances, handwriting difficulties, paresthesia).
Patient/family teaching
- Increase fluid intake (may protect against hyperuricemia).
- Do not have immunizations without physician’s approval (drug lowers resistance).
- Avoid contact with those who have recently received live virus vaccine.
- Promptly report fever, sore throat, signs of local infection, unusual bruising/bleeding from any site
- Tell patient to contact prescriber immediately if he develops signs or symptoms of infection, cytarabine syndrome (malaise, fever, muscle ache, bone pain, chest pain, rash, eye infection), or chemical arachnoiditis (neck rigidity or pain, nausea, vomiting, headache, fever, or back pain).
- Tell patient that drug makes him more susceptible to infection. Advise him to avoid crowds and exposure to illness.
- Advise patient to increase fluid intake, to promote uric acid excretion.
2.Fluorouracil, 5-FU
| Fluorouracil, 5-FU |
| Availability : Cream, Topical: (Carac): 0.5%. (Tolak): 4%, (Efudex): 5%. (Fluoroplex): 1%. Injection Solution: (Adrucil): 50 mg/mL. Solution, Topical: (Efudex): 2%, 5% |
| Administration/handling: Give by IV injection or IV infusion. Do not add to other IV infusions. Avoid small veins, swollen/edematous extremities, areas overlying joints, tendons. May be carcinogenic, mutagenic, teratogenic. Handle with extreme care during preparation/administration. IV Reconstitution • IV push does not need to be diluted or reconstituted. • Inject through Y-tube or 3-way stopcock of free-flowing solution. • For IV infusion, further dilute with 50–1,000 mL D5W or 0.9% NaCl. Rate of administration: Give IV push slowly over 1–2 min. • IV infusion is administered over 30 min–24 hrs (refer to individual protocols). • Extravasation produces immediate pain, severe local tissue damage. Storage: Store at room temperature. • Solution appears colorless to faint yellow. Slight discoloration does not adversely affect potency or safety. • If precipitate forms, redissolve by heating, shaking vigorously; allow to cool to body temperature. • Diluted solutions stable for 72 hrs at room temperature. |
| Usual Range: IV bolus: Adults, elderly: 200–1000 mg/m2/day for 1–21 days or 500–600 mg/m2/dose q3–4wks. IV infusion: Adults, elderly: 15 mg/kg/day or 500 mg/m2/day over 4 hrs for 5 days or 800–1200 mg/m2 over 24–120 hrs. |
| Multiple Actinic or Solar Keratoses : Topical: (Carac 0.5%): Adults, elderly: Apply once daily for up to 4 wks. (Efudex 5%): Adults, elderly: Apply twice daily for 2–4 wks. (Fluoroplex 1%): Apply twice daily for 2–6 wks. (Tolak 4%): Apply once daily for 4 wks. |
| Basal Cell Carcinoma: Topical: (Efudex 5%): Adults, elderly: Apply twice daily for 3–6 wks up to 10–12 wks. |
Mechanism of action:
Blocks formation of thymidylic acid. Cell cycle–specific for S phase of cell division. Therapeutic Effect: Inhibits DNA, RNA synthesis. Topical: Destroys rapidly proliferating cells.
Indications:
- Parenteral: Treatment of carcinoma of colon, rectum, breast, stomach (gastric), pancreas.
- Topical: Treatment of multiple actinic or solar keratoses, superficial basal cell carcinomas.
OFF-LABEL:
Parenteral: Treatment of carcinoma of bladder, cervical, endometrial, head/neck, anal, esophageal, renal cell, unknown primary cancer
Cautions & Contraindications:
- Hypersensitivity to fluorouracil.
- Myelosuppression
- Poor nutritional status
- Potentially serious infections.
- Cautions: History of high-dose pelvic irradiation, hepatic/renal impairment, palmar-plantar erythrodysesthesia syndrome (hand and foot syndrome), previous use of alkylating agents. Pts with widespread metastatic marrow involvement
Metabolism and Half- Life:
Widely distributed. Crosses blood-brain barrier. Metabolized in liver. Primarily excreted by lungs as carbon dioxide. Removed by hemodialysis. Half-life: 16 min.
Drug Interactions:
- Bone marrow depressants (e.g., cladribine) may increase risk of myelosuppression.
- Live virus vaccines may potentiate virus replication, increase vaccine side effects, decrease pt’s antibody response to vaccine.
- May decrease serum albumin.
- Topical: May cause eosinophilia, leucocytosis, thrombocytopenia, toxic granulation
Side- Effects:
- Parenteral: Frequent: Alopecia, dermatitis, anorexia, diarrhea, esophagitis, dyspepsia, stomatitis.
- Occasional: Cardiotoxicity (angina, ECG changes), skin dryness, epithelial fissuring, nausea, vomiting, excessive lacrimation, blurred vision.
- Rare: Headache, photosensitivity, somnolence, allergic reaction, dyspnea, hypotension, MI, pulmonary edema.
- Topical: Occasional: Erythema, skin ulceration, pruritus, hyperpigmentation, dermatitis, insomnia, stomatitis, irritability, photosensitivity, excessive lacrimation, blurred vision
Nursing Considerations
Baseline assessment
- Obtain baseline CBC with differential, serum renal function, LFT and monitor during therapy.
- Question history of hypersensitivity reaction, hepatic/renal impairment.
Intervention/evaluation
- Monitor for rapidly falling WBC, platelet count; intractable diarrhea, GI bleeding (bright red or tarry stool).
- Assess oral mucosa for stomatitis.
- Drug should be discontinued if intractable diarrhea, stomatitis, GI bleeding occurs.
- Assess skin for rash.
Patient/family teaching
- Maintain strict oral hygiene.
- Report signs/symptoms of infection, unusual bruising/bleeding, visual changes, nausea, vomiting, diarrhea, chest pain, palpitations.
- Avoid sunlight, artificial light sources; wear protective clothing, sunglasses, sunscreen.
- Topical: Apply only to affected area.
- Do not use occlusive coverings.
- Be careful near eyes, nose, mouth.
- Wash hands thoroughly after application.
- Treated areas may be unsightly for several weeks after therapy.
3.Methotrexate
| Methotrexate |
| Availability: Injection, Powder for Reconstitution: 1 g. Injection, Autoinjector: (Rasuvo): 7.5 mg, 10 mg, 12.5 mg, 15 mg, 17.5 mg, 20 mg, 22.5 mg, 25 mg, 27.5 mg, 30 mg. Injection Solution: 25 mg/mL. Injection, Syringe: (Otrexup): 7.5 mg/0.4 mL, 10 mg/0.4 mL, 15 mg/0.4 mL, 20 mg/0.4 mL, 25 mg/0.4 mL. Solution, Oral: (Xatmep): 2.5 mg/mL. Tablets: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg. |
| Administration/handling: May be carcinogenic, mutagenic, teratogenic. Handle with extreme care during preparation/administration. Wear gloves when preparing solution. If powder or solution comes in contact with skin, wash immediately, thoroughly with soap, water. May give IM, IV, intraarterially, intrathecally. IV: Reconstitution • Reconstitute powder with D5W or 0.9% NaCl to provide concentration of 25 mg/mL or less. For intrathecal use, dilute with preservative-free 0.9% NaCl to provide a concentration not greater than 2–4 mg/mL. Rate of administration: Give IV push at rate of 10 mg/min. Give IV infusion at rate of 4–20 mg/hr (refer to specific protocol). Storage: Store vials at room temperature. Diluted solutions stable for 24 hrs at room temperature. |
| Oncology Uses: Refer to individual specific protocols for optimum dosage, sequence of administration |
| Head/Neck Cancer: PO, IV, IM: Adults, elderly: 40 mg/m2 once wkly. Continue until disease progression or unacceptable toxicity |
| Breast Cancer: IV: Adults, elderly: 40 mg/m2 days 1 and 8 q4wks in combination with cyclophosphamide and fluorouracil |
| Mycosis Fungoides: IM, PO: Adults, elderly: 5–50 mg once weekly or 15–37.5 mg twice wkly. |
| Rheumatoid Arthritis (RA): PO: Adults: Initially, 10–15 mg once wkly. May increase by 5 mg q2–4wks to a maximum dose of 20–30 mg once weekly. SQ/IM: Initially, 7.5 mg/wk. Adjust dose gradually to optimal response. Elderly: Initially, 5–7.5 mg/wk. Maximum: 20 mg/wk. |
| Juvenile Rheumatoid Arthritis (JRA): PO, IM, SQ: CHILDREN: Initially, 10 mg/m2 once weekly, then 20–30 mg/m2/wk as a single dose |
| Psoriasis: PO: Adults, elderly: Initially, 10–25 mg once weekly or 2.5–5 mg q12h for 3 doses once wkly. IM/SQ: 10–25 mg once wkly. Adjust dose gradually to optimal response. Titrate to lowest effective dose. |
Mechanism of Action:
Competes with enzymes necessary to reduce folic acid to tetrahydrofolic acid, a component essential to DNA synthesis, repair, and cellular replication. Therapeutic Effect: Inhibits DNA, protein synthesis. Possesses anti-inflammatory and immune-modulating activity.
Indications:
Oncology-related:
- Treatment of breast, head/neck, non–small-cell lung, small-cell lung carcinomas
- Trophoblastic tumors
- Acute lymphocytic, meningeal leukemias
- Non-hodgkin’s lymphomas (lymphosarcoma, burkitt’s lymphoma)
- Carcinoma of gastrointestinal tract
- Mycosis fungoides
- Osteosarcoma.
Non-oncology uses:
- Psoriasis
- Rheumatoid arthritis (including juvenile idiopathic arthritis).
OFF-LABEL:
Treatment of acute myelocytic leukemia, bladder carcinoma, ectopic pregnancy, management of abortion, systemic lupus erythematosus, treatment of and maintenance of remission in Crohn’s diseasese
Cautions & Contraindications:
- Hypersensitivity to methotrexate.
- Breastfeeding.
- For pts with psoriasis, juvenile idiopathic arthritis or rheumatoid arthritis
- Pregnancy, hepatic disease
- Alcoholism
- Immunodeficiency syndrome
- Preexisting blood dyscrasias.
- Cautions: Peptic ulcer, ulcerative colitis, preexisting myelosuppression, history of chronic hepatic disease, alcohol consumption, obesity, diabetes, hyperlipidaemia, use with other hepatotoxic medications, concomitant use of proton pump inhibitors.
- Use of NSAIDs or aspirin with lower methotrexate doses for rheumatoid arthritis.
Metabolism and Half- Life:
Variably absorbed from GI tract. Completely absorbed after IM administration. Protein binding: 50%–60%. Widely distributed. Metabolized in liver. Primarily excreted in urine. Removed by hemodialysis but not by peritoneal dialysis. Half-life: 3–10 hrs (large doses, 8–15 hrs).
Drug Interactions:
- Alcohol, hepatotoxic medications (e.g., acetaminophen, acitretin) may increase risk of hepatotoxicity.
- Bone marrow depressants (e.g., cladribine) may increase myelosuppression.
- May decrease the therapeutic effect of vaccines (live).
- May increase adverse effects of natalizumab, vaccines (live).
- NSAIDs (e.g., ibuprofen, ketorolac, naproxen) may increase risk of toxicity.
- Probenecid, salicylates (e.g., aspirin) may increase concentration, risk of toxicity.
- May increase serum uric acid, AST.
Side – Effects:
- Frequent: Nausea, vomiting, stomatitis, burning/erythema at psoriatic site (in pts with psoriasis).
- Occasional: Diarrhea, rash, dermatitis, pruritus, alopecia, dizziness, anorexia, malaise, headache, drowsiness, blurred vision.
Nursing Considerations
Baseline assessment
- Rheumatoid arthritis: Assess pain, range of motion.
- Obtain baseline CBC, BMP, LFT, rheumatoid factor.
- Psoriasis: Assess skin lesions.
- Question for possibility of pregnancy in pts with psoriasis, rheumatoid arthritis (RA).
- Obtain all functional tests before therapy, repeat throughout therapy.
- Antiemetics may prevent nausea, vomiting.
Intervention/evaluation
- Monitor CBC, BMP, LFT, urinalysis, chest X-rays, serum uric acid.
- Monitor for hematologic toxicity (fever, sore throat, signs of local infection, unusual bruising/bleeding from any site), symptoms of anemia (excessive fatigue, weakness).
- Assess skin for evidence of dermatologic toxicity.
- Keep pt well hydrated, urine alkaline.
- Avoid rectal temperatures, traumas that induce bleeding.
- Apply 5 full min of pressure to IV sites.
Patient/family teaching
- Maintain strict oral hygiene.
- Do not have immunizations without physician’s approval (drug lowers resistance).
- Avoid crowds, those with infection.
- Avoid alcohol, aspirin.
- Avoid ultraviolet sunlight exposure.
- Use contraceptive measures during therapy and for 3 mos (males) or 1 ovulatory cycle (females) after therapy.
- Promptly report fever, sore throat, signs of local infection, unusual bruising/ bleeding from any site, diarrhea.
- Hair loss is reversible, but new hair growth may have different color, texture.
- Report persistent nausea/vomiting
- Instruct patient to drink 2 to 3 L of fluid each day.
- Advise patient to take oral doses 1 hour before or 2 hours after meals.
- Tell patient to take temperature daily and to report fever or other signs or symptoms of infection.
4.Hydroxyurea
| Hydroxyurea |
| Availability: capsule: 200mg,300mg, 400mg, 500mg; Tablet: 100mg,1000mg (tripled scored) |
| Administration and Handling: Oral administration: Capsules: Swallow capsule whole; do NOT open, break, or chew capsule because hydroxyurea is a cytotoxic drug. Prophylactic administration of folic acid is recommended Tablets: Administer dose qDay, with a glass of water. Do not split the 100-mg tablets into smaller parts; Patients unable to swallow tablets: Disperse tablets immediately before use in a small quantity of water in a teaspoon; Hydroxyurea is a cytotoxic drug; follow applicable special handling and disposal procedures. |
| Oral solution: May take with or without food. Do not shake solution Oral syringes for accurate measurement: Red 3-mL oral syringe: Marked from 0.5-3 mL for measuring doses ≤3 mL; each graduation of 0.1 mL contains 10 mg of hydroxyurea; White 12-mL oral syringe: Marked from 1-12 mL for measuring doses >3 mL; each graduation of 0.25 mL contains 25 mg of hydroxyurea. |
| Missed dose: Take missed dose as soon as possible, but only on the same day. If this is not possible, skip the dose and continue with the next dose as prescribed. Do not take 2 doses to make up for a missed dose |
| Storage: Capsules: Store at room temperature, 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF); Keep tightly closed. Tablets: Store at room temperature, 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF); Keep tightly closed. Store broken 1000-mg tablets in the bottle and use within 3 months |
| Head and neck cancer; ovarian cancer; malignant melanoma: Adults: 60 to 80 mg/kg (2 to 3 g/m2)P.O. as a single daily dose q 3 days, or 20 to 30 mg/kg/day P.O. as a single dose. Begin therapy 7 days before radiation. |
| Resistant chronic myelogenous leukemia: Adults: 20 to 30 mg/kg/day P.O. in one or two divided doses |
| Sickle cell anemia : Adults and children: 15 mg/kg/day P.O. as a single dose. May increase by 5 mg/kg/day P.O. q 12 weeks, up to 35 mg/kg/day. |
| Thrombocythemia, Essential (Off-label): 15 mg/kg PO qDay .Titrate to control platelets & maintain WBC count |
| HIV, Adjunct Treatment (Off-label): 500 mg PO BID. Use with antiretrovirals |
| Psoriasis (Off-label): 1000-1500 mg/day PO qDay-BID |
Mechanism of Action:
May inhibit enzyme necessary for DNA synthesis without disrupting RNA or protein synthesis.
The precise mechanism by which hydroxyurea produces its cytotoxic and cytoreductive effects is not known. However, various studies support the hypothesis that hydroxyurea causes an immediate inhibition of DNA synthesis by acting as a ribonucleotide reductase inhibitor, without interfering with the synthesis of ribonucleic acid or of protein.
The mechanisms by which hydroxyurea produces its beneficial effects in patients with sickle cell anemia (SCA) are uncertain. Known pharmacologic effects of hydroxyurea that may contribute to its beneficial effects include increasing hemoglobin F levels in red blood cells (RBCs), decreasing neutrophils, increasing the water content of RBCs, increasing deformability of sickled cells, and altering the adhesion of RBCs to endothelium.
Indications:
- Chronic Myelogenous Leukemia
- Sickle Cell Anemia
- Polycythaemia Vera/Thrombocythemia, Essential
- Cervical Cancer
- Solid Tumors
- Head and Neck Cancer
- Melanoma
- Ovarian Cancer
- HIV, Adjunct Treatment
- Psoriasis
Cautions & Contraindications:
- Hypersensitivity to drug or tartrazine
- Bone marrow depression
- Severe anemia or thrombocytopenia
- Use cautiously in:
- Renal or hepatic impairment, obese patients, females of childbearing age, elderly patients.
Metabolism and Half- Life:
- Duration: up to 24 hr ; Protein binding: 75-80%
- Metabolized (60%) by liver and GI tract
- Elimination Half-Life: 2-4 hr
- Excretion: Urine (40% of administered dose in sickle cell anemia patients)
Drug Interactions:
- Live-virus vaccines: decreased antibody response to vaccine, increased risk of adverse reactions
- Myelo-suppressants: additive bone marrow depression
- Hemoglobin, platelets, red blood cells, white blood cells: decreased values
- Mean corpuscular volume: transient increase
Side- Effects:
- CNS: drowsiness, malaise, confusion, dizziness, headache
- GI: nausea, vomiting, diarrhea, constipation, stomatitis, anorexia
- GU: dysuria, hyperuricemia, infertility, renal tubular dysfunction
- Hematologic: anemia, megaloblastosis, leukopenia, thrombocytopenia, bone marrow depression
- Hepatic: hepatitis
- Metabolic: hyperuricemia
- Skin: alopecia, erythema, pruritus, rash, urticaria, exacerbation of post-radiation erythema
- Other: chills, fever
Nursing Considerations
Interventions/evaluations
- Assess CBC weekly
- Closely monitor patient with renal or hepatic impairment. Check kidney and liver function tests often.
- Assess fluid status. Make sure patient drinks 10 to 12 glasses of water daily.
Patient teaching
- Advise patient to mark dates for drug doses, diagnostic tests, and treatments on calendar.
- Instruct patient to immediately report easy bruising, bleeding, unusual tiredness, or yellowing of skin or eyes.
- Tell patient to report such adverse effects as appetite loss, nausea, vomiting, oral lesions, constipation, diarrhea, confusion, dizziness, headache, and rash.
- Instruct female patient to use barrier contraception.
- Tell patient he will undergo regular blood testing to monitor drug effects.
- As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.
5.Azacitidine
| Azacitidine |
| Availability: injection, lyophilized powder for reconstitution: 100mg/single-dose vial; Tablet: 200mg, 300mg |
| Administration and Handling: IV Preparation: Reconstitute each vial with 10 mL sterile water for injection Vigorously shake or roll vial until all solids are dissolved; resulting concentration is 10 mg/mL; solution should appear clear. Visually inspect parenteral drug product for particulate matter and discoloration before administration, whenever solution and container permit Adults: Withdraw required amount and inject into a 50 -100 mL infusion bag of either 0.9% NaCl or Lactated Ringer Pediatric patients: Withdraw required amount of drug solution and inject into an infusion bag (volume up to 100 mL) of either 0.9% NaCl or Lactated Ringer to achieve a final concentration of 0.9-4 mg/mL IV Administration: IV administration only when reconstituted with 10 mL of sterile water Administer total dose over a period of 10 – 40 min; complete administration within 1 hr of reconstitution |
| SC Preparation: Reconstitute with 4 mL room temperature sterile water for injection for immediate use and refrigerated sterile water (2-8C, 36-46F) for delayed use; inject diluent slowly into vial. Vigorously shake or roll the vial until a uniform suspension is achieved; suspension will be cloudy; resulting concentration is 25 mg/mL Do not filter suspension after reconstitution; filtering could remove the active substance. For doses requiring >1 vial, divide dose equally between the syringes (eg, dose 150 mg = 6 mL, 2 syringes with 3 mL in each syringe) and inject into 2 separate sites. Due to retention in vial and needle, it may not be feasible to withdraw all of the suspension from vial. SC Administration: SC administration only when reconstituted with 4 mL of sterile water Resuspend the contents of syringe to provide a homogeneous suspension immediately before administration. To resuspend, vigorously roll syringe between the palms until a uniform, cloudy suspension is achieved. Rotate sites for each injection (thigh, abdomen, or upper arm). Administer new injections at least 1 inch from an old site and never into areas where the site is tender, bruised, red, or hard. |
| Oral Administration: Hazardous drug; follow applicable special handling and disposal procedure; Do not split, crush, or chew tablets. Take a dose about the same time each day. Do not substitute IV or SC azacitidine Indications and dosing regimen differ from that of IV or SC azacitidine Premedication: Administer an antiemetic 30 min before each dose for the first 2 cycles; Omit antiemetics after 2 cycles if no nausea and vomiting has occurred Missed dose: Take dose as soon as possible on the same day, and resume the normal schedule the following day; do not take 2 doses on the same day Vomited dose: If dose is vomited, do not take another dose on the same day. Resume normal schedule the following day |
| Storage: Cytotoxic drug; follow applicable special handling and disposal procedures Unused vials: Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF) Reconstituted vial or diluted IV infusion bag: Store for up to 1 hr at 25ºC (77ºF) Reconstituted suspension or prepared SC syringes: Reconstituted with non-refrigerated water for injection: Store for up to 1 hr at 25ºC (77ºF) or for up to 8 hr between 2-8ºC (36-46ºF); Reconstituted with refrigerated (2-8ºC, 36-46ºF) water for injection: Store for 22 hr at 2-8ºC (36-46ºF) Tablets: Store bottles at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF); Keep bottle tightly closed; Store and dispense in the original bottle (with 2 desiccant canisters) |
| Treatment of the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusion), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia Adults: For first treatment cycle: 75mg/m2 subcutaneously or I.V. daily for 7 days; for subsequent treatment cycles, repeat cycle every 4 weeks. Dosage may be increased to 100mg/m2 if beneficial effect doesn’t occur after two cycles and no toxicity (other than nausea and vomiting) develops. Patient should be treated for at least four cycles. Continue therapy as long as patient benefits from it. |
| Myelodysplastic Syndromes : Vidaza only: Indicated for myelodysplastic syndromes in patients with the following French-American-British (FAB) subtypes: Refractory anemia (RA) or RA with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), chronic myelomonocytic leukemia (CMMoL) Each cycle is 4 weeks; 75 mg/m2 IV or SC qDay for 7 days; repeat cycle every 4 weeks. May increased to 100 mg/m2 if no benefit observed after 2 treatment cycles and if no toxicity other than nausea and vomiting. Treat for minimum of 4-6 cycles. Continue treatment as long as patient continues to benefit |
| Acute Myeloid Leukemia: Onureg only: Indicated for continued treatment of adults with acute myeloid leukemia who achieved first complete remission (CR) or CR with incomplete blood count recovery following intensive induction chemotherapy and are not able to complete intensive curative therapy Each cycle is 28 days; 300 mg PO qDay on Days 1-14. Continue until disease progression or unacceptable toxicity |
Mechanism of Action:
Thought to exert antineoplastic effect by causing DNA hypomethylation and direct cytotoxicity on abnormal hematopoietic bone marrow cells. Cytotoxicity causes death of rapidly growing cells, including cancer cells no longer responsive to normal growth control mechanisms
Indications:
Treatment of the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusion), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia
Cautions & Contraindications:
- Hypersensitivity to drug or mannitol
- Advanced malignant hepatic tumor
- Use cautiously in:
- Impaired renal or hepatic function, myelodysplastic syndrome
- Pregnant or breastfeeding patients
- Children (safety and efficacy not established)
Metabolism and Half- Life:
- Undergoes spontaneous hydrolysis and deamination mediated by cytidine deaminase.
- Peak plasma time: SC: 0.5 hr , PO: 1 hr
- Half-life: PO: ~0.5 hr, SC or IV: 4 hr
- Excretion: PO: <2% unchanged (urine), IV: 85% (urine); <1% (feces), SC: 50% (urine)
Drug Interactions:
- Antiretroviral agents (didanosine, stavudine) : Potentially fatal pancreatitis and hepatotoxicity reported in patients with HIV infection receiving concomitant therapy
- Myelosuppressive agents: Possible additive bone marrow depression
- Uricosuric agents: Potential increased serum uric acid concentrations
Side- Effects:
- Injection site reactions (redness, pain, bruising, irritation)
- Tiredness
- Weakness
- Diarrhea
- Headache
- Dizziness
- Anxiety
- Trouble sleeping (insomnia)
- Constipation
- Stomach pain
- Nausea and vomiting (may be severe)
- Loss of appetite
- Joint or muscle pain
- Cold symptoms such as stuffy nose, sneezing, or sore throat.
Nursing Considerations
Patient monitoring
- Monitor CBC during therapy.
- Monitor liver function tests and serum creatinine frequently.
- Watch for renal tubular acidosis (serum bicarbonate level below 20mEq/L associated with alkaline urine and hypokalemia, and serum potassium level below 3 mEq/L).
- Monitor patient for signs and symptoms of tumor lysis syndrome (such as irregular heartbeat, shortness of breath, high potassium level, high uric acid level, impaired mental ability, kidney failure).
Patient teaching
- Instruct patient to call prescriber immediately if shortness of breath, high potassium level, impaired mental ability, rash, easy bruising or bleeding, or respiratory symptoms develop.
- Advise male patient not to father a child during therapy.
- Caution female of childbearing potential to avoid pregnancy and breastfeeding during therapy.
REFERENCES
- Robert Kizior, Keith Hodgson, Saunders Nursing Drug handbook,1st edition 2024, Elsevier Publications. ISBN-9780443116070
- McGraw Hill- Drug Handbook, Seventh Edition, 2013, McGraw Hill Education Publications,9780071799430.
- April Hazard, Cynthia Sanoski, Davi’s Drug Guide for Nurses -Sixteenth Edition 2019, FA Davis Company Publications,9780803669451.
- Jones and Bartlet, Pharmacology for Nurses, Second Edition, 2020, Jones and Bartlet Learning Publications, ISBN 9781284141986.
- Nursebro.com, Search – Nursebro
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