Adrucil Side Effects
Generic name: fluorouracil
Note: This document contains side effect information about fluorouracil. Some of the dosage forms listed on this page may not apply to the brand name Adrucil.
Some side effects of Adrucil may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.
For the Consumer
Applies to fluorouracil: intravenous solution
Get emergency medical help if you have any of these signs of an allergic reaction while taking fluorouracil (the active ingredient contained in Adrucil) hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Call your doctor at once if you have:
signs of infection such as fever, chills, sore throat, flu symptoms;
white patches or sores inside your mouth or throat, or on your lips;
pale skin, easy bruising or bleeding (nosebleeds, bleeding gums, or any bleeding that will not stop);
weakness or fainting;
bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;
coughing up blood or vomit that looks like coffee grounds;
watery diarrhea, ongoing or severe vomiting;
pain, redness, numbness, and peeling skin on your hands or feet;
numbness or tingling anywhere in your body, loss of muscle control; or
sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance.
Common side effects may include:
temporary hair loss;
mild to moderate nausea and vomiting, loss of appetite;
mild, itchy skin rash;
eye dryness, watering, or increased sensitivity to light; or
temporary loss of your fingernails or toenails.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.
For Healthcare Professionals
Applies to fluorouracil: compounding powder, intravenous solution
Gastrointestinal side effects can be severe and life-threatening with fluorouracil (the active ingredient contained in Adrucil) Stomatitis and esophagopharyngitis, diarrhea, anorexia, nausea and emesis are commonly seen during therapy. The mucositis and diarrhea are dose-limiting and occur with both bolus and continuous infusion schedules. Mucositis may be preceded by a sensation of dryness, followed by erythema and formation of white, patchy membrane, ulceration, and necrosis. Lesions may occur anywhere in the gastrointestinal tract and result in dysphagia, retrosternal burning, watery diarrhea and proctitis. The diarrhea may be bloody. Profuse nausea, vomiting and diarrhea can lead to dehydration and hypotension. If diarrhea occurs, supportive care and aggressive hydration should be instituted.
Patients should be examined prior to each dose of fluorouracil and questioned about mouth soreness and/or watery stools. Treatment should be withheld in the face of ongoing mucositis or diarrhea. Antidiarrheal agents may provide symptomatic relief from mild diarrhea; however, be less effective in the setting of moderate to severe diarrhea. Octreotide has been shown to be more effective than loperamide for the treatment of fluorouracil-induced diarrhea.
An oral hygiene program is often instituted to help reduce the severity of mucositis, and topical anesthetics can provide local pain relief. Allopurinol mouthwashes have shown little benefit in the amelioration of fluorouracil-induced mucositis. Mouth cooling (oral cryotherapy) with ice chips or popsicles for 30 minutes prior to bolus infusions of fluorouracil has been shown to reduce the severity of mucositis.
Hematologic side effects including leukopenia have been reported. Leukopenia usually follows every course of fluorouracil (the active ingredient contained in Adrucil) however, it may be less severe with continuous infusion therapy. The lowest white blood cell counts are seen between the 9th and 14th days after the first course of treatment. Pancytopenia, thrombocytopenia, agranulocytosis and anemia are also seen with fluorouracil therapy.
Dermatologic side effects occur with both bolus and continuous infusion schedules. Loss of hair, which may progress to total alopecia, nail changes (onycholysis and pigmentation), dermatitis, and increased pigmentation and atrophy of the skin may occur. Fluorouracil is capable of enhancing the cutaneous toxicity of radiation which typically occurs within 7 days of radiation and presents as erythema followed by dry desquamation or in severe cases, erythema. Increased reactions with ultraviolet light may occur with exaggerated sunburn reactions. Photosensitivity may also occur along with pigmentation over the veins into which fluorouracil (the active ingredient contained in Adrucil) was administered. Actinic keratoses may develop an erythematous inflammatory reaction following systemic administration of fluorouracil. With continuous infusion and high dose bolus fluorouracil, palmar-plantar erythrodysesthesia ("hand-foot syndrome") is particularly common.
Palmar-plantar erythrodysesthesia syndrome consists of a dysesthesia affecting the hands and feet followed 3 to 4 days later by symmetrical swelling of the palms and soles of the feet in combination with erythema and tenderness of the distal phalanges. The swelling and erythema progress with continued therapy with the development of a central pallor over the tufts of the distal phalanges. Sometimes the face may also be involved. Patients with an underlying skin disorder may be more prone to such toxicity. This condition resolves after 7 days of discontinuation of therapy and recurs upon reinstitution of treatment. Pyridoxine may provide remission of this complication and allow continuation of fluorouracil treatment.
A 65-year-old woman developed hyperpigmentation of the hands and feet, desquamating erythema of the palms and slight pitting of the nails while receiving continuous infusion fluorouracil. After application of a 7 mg nicotine patch one hour prior to drug infusion, the desquamation, erythema, and hyperpigmentation resolved even with continued chemotherapy. This improvement may be due to the vasoconstricting properties of the nicotine patch.
Cardiac side effects associated with fluorouracil (the active ingredient contained in Adrucil) therapy are characterized by chest pain, arrhythmia, and electrocardiogram (ECG) changes. ECG changes consisted of diffuse ST segment elevations (or depression), tall peaked T waves, T-wave inversions, and sinus tachycardia. Other changes seen include prolongation of the QT interval, atrial fibrillation, ventricular extrasystoles, sustained and nonsustained ventricular tachycardia, and ventricular fibrillation. In some patients, chest pain was accompanied by ECG and serum enzyme changes suggestive of myocardial ischemia. Studies suggest the incidence of cardiac toxicity to be less than 10%. Cardiac toxicity has been observed with both the bolus and infusional schedules; however, is more common with the continuous infusion. A case of late-onset severe cardiotoxicity from fluorouracil therapy resulting in death has been reported.
The mechanism of cardiac toxicity with fluorouracil is unknown but proposed mechanisms include direct toxicity to the myocardium, coronary vasospasm, autoimmune phenomena, and thrombogenic effects. Another theory has suggested an impurity, fluoroacetaldehyde, generated in the alkaline solution of fluorouracil vials during storage which may be converted to a cardiotoxic substance, fluoroacetate.
Most arrhythmias caused by fluorouracil are treatable. Ischemic symptoms, such as chest pain and ECG changes, usually disappear when the fluorouracil infusion is stopped. If the symptoms respond to nitrate therapy, the infusion may be continued cautiously. The use of calcium-channel blockers or steroids has not been shown to protect against cardiotoxicity.
Risk factors for fluorouracil-related cardiotoxicity include advanced age, a history of cardiac disease, continuous infusion regimens, high doses, combination chemotherapy, or concomitant irradiation of the mediastinum. Sex and concomitant use of leucovorin were not shown to be risk factors for fluorouracil toxicity.
A cerebellar syndrome has also been reported with a variety of treatment schedules and doses of fluorouracil (the active ingredient contained in Adrucil) however, the incidence increases with higher weekly doses or after intensive daily treatment regimens. This syndrome may present with gross dysmetria, slurred speech, ataxia of the trunk or extremities, and dizziness. The cerebellar dysfunction appears to be reversible with symptoms abating after discontinuation of therapy, decreasing the fluorouracil dose or increasing the interval between treatment courses.
Neurotoxicity with fluorouracil can also present as an acute encephalopathy or a multifocal leukoencephalopathy. Features of the latter include white-matter lesions on MRI and symptoms such as mental decline, memory loss, motor signs, seizures, speech disturbances, and ataxia. Cessation of chemotherapy and treatment with steroids may be beneficial.
The cause of fluorouracil neurotoxicity is not known but may be associated with the formation of metabolites (fluoroacetate or fluorocitrate) that inhibit the Krebs cycle in the cerebellum, concurrent administration of levamisole, thiamine deficiency, or dihydropyrimidine dehydrogenase deficiency.
Nervous system side effects including somnolence, cerebellar ataxia, and upper motor neuron signs have rarely been reported. These symptoms are more common with intracarotid arterial infusions, high doses or intensive daily schedules and usually reverse upon discontinuation of the drug.
Ocular side effect including excessive lacrimation (most common), epiphora, blepharitis, conjunctivitis, cicatricial ectropion, tear duct stenosis, blurred vision, keratitis, and punctal stenosis have been reported. Excessive lacrimation usually improves with dose reduction of fluorouracil (the active ingredient contained in Adrucil) and conjunctivitis is reversible with discontinuation of therapy at an early point. Surgical correction of dacrystenosis and ectropion, however, may be required.
A small pilot study has suggested that ocular ice pack therapy may lessen fluorouracil-induced toxicity to a moderate degree when applied 5 minutes prior to chemotherapy.
More Adrucil resources
- Adrucil Prescribing Information (FDA)
- Adrucil injection Concise Consumer Information (Cerner Multum)
- Adrucil Monograph (AHFS DI)
- Adrucil MedFacts Consumer Leaflet (Wolters Kluwer)
- Adrucil Advanced Consumer (Micromedex) - Includes Dosage Information
- Fluorouracil Professional Patient Advice (Wolters Kluwer)
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