Vincristine (Dosage)

Vincristine is one of the most commonly used drugs in pediatric oncology (and is also widely used in non-pediatric oncology), and is used very frequently in therapy for acute lymphoblastic leukemia (ALL), among other types of cancers. It is an alkaloid obtained from the flower of a plant, Vinca rosae Linn periwinkle.

ACTION MECHANISM

Vinca alkaloids are classical cell mitotic spindle poisons, which bind to tubulin protein microtubules and block cells during metaphase because they prevent the polymerization of tubulin microtubules and induce the depolymerization of formed microtubules. Thus, preventing the formation of the mitotic spindle, vincristine interrupts cell division in the metaphase.

CONTRAINDICATIONS

Hypersensitivity to vincristine. Vincristine is contraindicated in patients with neuromuscular disorders (such as the demyelinating form of Charcot-Marie-Tooth syndrome); contraindicated in patients with severe liver function disorder; with constipation and iliac impediment (especially in children) and in patients treated with radiotherapy in which the liver is involved.

CAUTIONS

Precautions should be taken when prescribing vincristine in patients with hepatic insufficiency, ischemic heart problems, neurological disorders or impaired liver function.

Hepatic dysfunction may increase circulating concentrations and plasma half-life of vincristine with an increase in its adverse effects.

Risk of leukopenia and thrombocytopenia (close monitoring). There may be an acute elevation of uric acid levels in plasma; Monitor uric acid levels frequently during the first 3-4 weeks of treatment or take adequate measures to prevent uric acid neuropathy.

Both men and women should take contraceptive measures during treatment and for 6 months after the end of treatment.

SIDE EFFECTS

The main toxic effect is peripheral neurotoxicity. The first signs are usually paresthesias in the distal areas of the extremities, which can be followed by neuritic pain, loss of deep osteotendinous reflexes, and muscle cramps. A greater degree of toxicity is the appearance of motor dysfunctions, foot drop, drooping wrist, ataxia and muscle weakness.

The cranial nerves can be affected, resulting in dysphonia, diplopia, jaw pain and facial paralysis. The states of confusion, depression, hallucinations, agitation, convulsions, visual disturbances and even coma are rare. The neurotoxicity of vincristine is related to the dose and duration of treatment.

The only treatment for these neurotoxic effects is the interruption of the administration until the recovery and, in case of continuing the administration, the reduction of the dose or the increase of the intervals.

Other side effects described are:

Cardiovascular disorders: edema, hyper/hypotension, myocardial ischemia, myocardial infarction.

Dermatological manifestations: reversible alopecia in 20-50% of patients treated with vincristine. Skin rash.

Endocrine/metabolic manifestations: hyperuricemia, parotid pain, syndrome of inadequate secretion of ADH.

Gastrointestinal manifestations: abdominal pain, anorexia, constipation, diarrhea, nausea and vomiting, mucositis, paralytic ileus, necrosis and/or intestinal perforation.

Genitourinary manifestations: atony of the urinary bladder, dysuria, polyuria, urinary retention. On very rare occasions, cases of incontinence have been reported.

Hematological manifestations: vincristine is poorly medullar depressor, although anemia, thrombocytopenia and neutropenia can be observed.

Hepatobiliary disorders: Cases of hepatic veno-occlusive disease have been described, especially in children under 3 years old.

Others: deafness, optic atrophy, allergic reactions, anaphylaxis, hypersensitivity reactions, irritation at the site of injection, phlebitis, cellulitis and necrosis.

PHARMACOLOGIC INTERACTIONS

In cases of concomitant use of vincristine with oral anticoagulants closely monitor the INR ("International Normalized Ratio") and the Prothrombin Time.

Increased plasma concentrations of vincristine can be observed with the use of CYP3A4/glycoprotein P inhibitors, such as ritonavir, nelfinavir, ketoconazole, itraconazole, erythromycin, cyclosporine, nifedipine and nefazodone.

The concomitant administration of vincristine and itraconazole has been associated with an increase in the severity of neuromuscular adverse effects, by decreasing vincristine clearance: avoid concomitant use.

The use together with phenytoin/phosphophenytoin, carbamazepine: can reduce phenytoin levels and increase the risk of seizure: avoid concomitant use; if necessary, closely monitor levels of phenytoin.

Risk of severe peripheral neuropathy if used concomitantly with other neurotoxic agents (isoniazid, L-asparaginase, cyclosporin A): Monitor signs of neurotoxicity.

BRAND NAMES

  • Oncovin®
  • Vincasar Pfs®

Gene or region studied

  • CYP3A5
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