procarbazine

ROUTE	ONSET	PEAK	DURATION
PO	14 days	2–8 wk	28 days or more (up to 6 wk)

Derm: alopecia, photosensitivity, pruritus, rash

EENT: nystagmus, photophobia, retinal hemorrhage

GI: nausea, vomiting, anorexia, ascites, diarrhea, dry mouth, dysphagia, hepatic impairment, stomatitis

GU: gonadal suppression

Hemat: anemia, leukopenia, thrombocytopenia

Neuro: confusion, dizziness, drowsiness, hallucinations, headache, mania, mental depression, neuropathy, nightmares, paresthesia, psychosis, SEIZURES, syncope, tremor

Resp: cough, pleural effusion

Misc: SECONDARY MALIGNANCY

Interactions ⬆ ⬇

Drug-drug:

Concurrent use with sympathomimetics, including methylphenidate, may produce life-threatening hypertension; avoid concurrent use during and for 14 days following procarbazine.
Deep coma and death may result from concurrent use of opioid analgesics; avoid concurrent use of meperidine. Use small incremental doses of other agents and titrate to effect.
↑bone marrow depression may occur with other antineoplastics or radiation therapy.
Seizures and hyperpyrexia may occur with concurrent use of MAO inhibitors, tricyclic antidepressants, SSRI antidepressants (should not be used within 5 wk of fluoxetine), or carbamazepine.
May ↓ digoxin levels and effectiveness.
Concurrent use with levodopa may result in flushing and hypertension.
↑CNS depression with other CNS depressants, including alcohol, antidepressants, antihistamines, opioid analgesics, phenothiazines, and sedative/hypnotics.
Disulfiram-like reaction may occur with alcohol.
Cigarette smoking may ↑ the risk of secondary lung cancer.

Ingestion of foods high in tyramine content (see Food Sources for Specific Nutrients) may result in hypertension.
Ingestion of foods high in caffeine content may result in arrhythmias.

Route/Dosage ⬆ ⬇

PO (Adults ): 2–4 mg/kg/day as a single dose or in divided doses for 1 wk; then 4–6 mg/kg/day until response is obtained; then maintenance dose of 1–2 mg/kg/day. Dosage should be rounded off to the nearest 50 mg.
PO (Children ): 50 mg/m²/day for 7 days; then 100 mg/m²/day; maintenance dose of 50 mg/m²/day.

Availability ⬆ ⬇

Assessment ⬆ ⬇

Monitor BP, HR, and respiratory rate periodically during therapy. Report significant changes to health care professional.
Assess nutritional status (appetite, intake and output ratios, weight, frequency and amount of emesis). Anorexia and weight loss can be ↓ by feeding light, frequent meals. Nausea and vomiting can be minimized by administering an antiemetic ≥1 hr prior to receiving medication. Phenothiazine antiemetics should be avoided.
Monitor for bone marrow depression. Assess for bleeding (bleeding gums; bruising; petechiae; guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for ↑ fatigue, dyspnea, and orthostatic hypotension.
Concurrent ingestion of tyramine-rich foods and many medications may result in life-threatening hypertensive crisis. Signs and symptoms of hypertensive crisis include chest pain, severe headache, nausea and vomiting, photosensitivity, and enlarged pupils. Treatment includes IV phentolamine.
Monitor for CNS signs or symptoms such as paresthesias, neuropathies, or confusion; discontinue immediately if these signs/symptoms occur.
Monitor for any of the following side effects: leukopenia, thrombocytopenia, hypersensitivity reactions, stomatitis (including small ulcers or persistent soreness), diarrhea, hemorrhage, or bleeding tendencies. Discontinue procarbazine until those side effects resolve; then it may be resumed at a lower dose. If leukopenia develops, hospitalization may be necessary.

Lab Test Considerations:

Monitor CBC with differential prior to and every 3–4 days during therapy. Notify physician if WBC <4000/mm³ or platelet count <100,000/mm³. Therapy should be discontinued and resumed at a lower dose when counts improve. The nadir of leukopenia and thrombocytopenia occurs in approximately 2–8 wk, and recovery usually occurs in about 6 wk. Anemia also may occur.
- Assess hepatic and renal function prior to therapy. Monitor urinalysis, AST, ALT, alkaline phosphatase, BUN, and serum creatinine at least weekly during therapy.
- Closely monitor serum glucose in patients with diabetes. Oral hypoglycemics or insulin dosage may need to be ↓ because hypoglycemic effects are enhanced.
- Bone marrow aspiration studies are recommended prior to initiation of therapy and at time of maximum hematologic response to ensure adequate bone marrow reserve.

Implementation ⬆ ⬇

If radiation or a chemotherapeutic agent known to have marrow-depressant activity has been used, an interval of >1 mo without such therapy is recommended before starting treatment with procarbazine.
PO: Administer with food or fluids if GI irritation occurs. Confer with pharmacist regarding opening of capsules if patient has difficulty swallowing.
- Handle intact tablets or capsules with single gloves; use double gloves, respiratory protection, and a protective gown in the preparation of tablets or capsules, including cutting, crushing, or manipulating, or the handling of uncoated tablets; optimally prepare in a ventilated control device.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of procarbazine to patient. Instruct them to take medication as directed. Take missed doses as soon as remembered within a few hr, but not if several hr have passed or if almost time for next dose. Health care professional should be consulted if vomiting occurs shortly after a dose is taken. Advise patient on the proper handling and disposal of chemotherapy drugs. Do not share medication with others, even if they have similar symptoms; may be harmful. Keep out of children's reach. Advise patient to read Patient Information sheet before starting therapy and with each Rx refill in case of changes.
Emphasize the importance of regular follow-up physical exams and lab tests to monitor for efficacy and side effects.
Instruct patient to notify health care professional promptly if signs of infection (fever, fatigue, sore throat, chills, cough, ↑ mucus, hoarseness, pain in lower back or side, difficult or painful urination) occur. Caution patient to avoid crowds and persons with known infections.
Instruct patient to notify health care professional promptly if signs of bleeding (bleeding gums, bruising, petechiae, blood in stool or urine, vomiting that looks like coffee grounds) occur. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Patient should not receive IM injections or rectal temperatures. Caution patient not to drink alcoholic beverages or take medication containing aspirin or NSAIDs, which may precipitate gastric bleeding.
Caution patient to avoid alcohol, caffeinated beverages, and foods or beverages containing tyramine (see Food Sources for Specific Nutrients for foods included) during therapy and for ≥2 wk after therapy has been discontinued, because they may precipitate a hypertensive crisis.
Advise patient that an additional interaction of alcohol with procarbazine is a disulfiram-like reaction (flushing, nausea, vomiting, headache, abdominal cramps).
Instruct patient to inspect oral mucosa for erythema and ulceration. Emphasis and teach about oral hygiene. If ulceration occurs, advise patient to notify health care professional and to use sponge brush and rinse mouth with water after eating and drinking. Topical agents may be used if mouth pain interferes with eating. Stomatitis pain may require treatment with opioid analgesics.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications or having surgery to avoid potential drug interactions.
May cause drowsiness or dizziness. Caution patient to avoid driving or other activities that require alertness until response to medication is known.
Discuss the possibility of hair loss with patient. Explore methods of coping.
Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
Instruct patient not to receive any vaccinations without advice of health care professional.
Advise patient to notify health care professional of medication regimen prior to treatment or surgery. This therapy usually should be withdrawn ≥2 wk prior to surgery.
Instruct patient to inform health care professional if muscle or joint pain, nausea, vomiting, sweating, tiredness, weakness, constipation, headache, difficulty swallowing, or loss of appetite becomes pronounced.
Advise patient to carry identification describing medication regimen at all times.
Rep: May cause fetal harm. Advise females of reproductive potential to notify health care professional immediately if pregnancy is planned or suspected and to avoid breastfeeding. Advise females of reproductive potential to use effective contraception during and for 4 mo after final dose of therapy. May impair infertility in males and females.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇