Oforta Side Effects

Generic Name: fludarabine

Note: This page contains side effects data for the generic drug fludarabine. It is possible that some of the dosage forms included below may not apply to the brand name Oforta.

It is possible that some side effects of Oforta may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

For the Consumer

Applies to fludarabine: oral tablet

As well as its needed effects, fludarabine (the active ingredient contained in Oforta) may cause unwanted side effects that require medical attention.

If any of the following side effects occur while taking fludarabine, check with your doctor immediately:

More common
  • Bloating or swelling of the face, arms, hands, lower legs, or feet
  • body aches or pain
  • burning or stinging of the skin
  • chest pain
  • cough or hoarseness
  • cough producing mucus
  • diarrhea
  • difficult or labored breathing
  • difficulty in breathing
  • ear congestion
  • fever or chills
  • general feeling of discomfort or illness
  • headache
  • joint pain
  • loss of appetite
  • loss of voice
  • lower back or side pain
  • muscle aches and pains
  • nasal congestion
  • nausea
  • painful cold sores or blisters on the lips, nose, eyes, or genitals
  • painful or difficult urination
  • rapid weight gain
  • runny nose
  • shivering
  • shortness of breath
  • sneezing
  • sore throat
  • stuffy nose
  • sweating
  • tightness in the chest
  • tingling of hands or feet
  • trouble sleeping
  • troubled breathing
  • unusual tiredness or weakness
  • unusual weight gain or loss
  • vomiting
  • wheezing
Less common
  • Bladder pain
  • bloody or cloudy urine
  • difficult, burning, or painful urination
  • frequent urge to urinate
  • pain or tenderness around the eyes and cheekbones
Incidence not known
  • Back pain
  • bloody, black, or tarry stools
  • blue lips, fingernails, or skin
  • blurred vision
  • confusion
  • convulsions
  • coughing up blood
  • difficult or fast breathing
  • dizziness
  • drowsiness
  • high fever
  • irregular, fast or slow, or shallow breathing
  • pale skin
  • sores, ulcers, or white spots on the lips or in the mouth
  • swollen glands
  • unexplained bleeding or bruising
  • unusual bleeding or bruising

Some fludarabine side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:

More common
  • Abdominal pain
  • increased sweating
  • weight loss
Less common
  • Rash

For Healthcare Professionals

Applies to fludarabine: intravenous powder for injection, intravenous solution, oral tablet

General

In general, the most common dose-limiting toxicities have been myelosuppression (60%), fever and chills (11% to 60%, sometimes without infection), infection (33%, including serious opportunistic infections), and nausea and vomiting (36%).

General side effects including pain (up to 19%), flu syndrome (up to 8%), and decreased weight (up to 6%) have been reported.[Ref]

Hematologic

Hematologic toxicity has been reported to have occurred in the majority of patients. It presents as either neutropenia, thrombocytopenia, anemia, or a combination. Fifty-nine percent of patients develop an absolute neutrophil count of less than 500/mm3, 60% develop a hemoglobin concentration decrease by at least 2 g percent, and 55% develop a platelet count decrease by 50%. Several instances of trilineage bone marrow hypoplasia or aplasia resulting in sometimes fatal pancytopenia have been reported. Rarely, bone marrow fibrosis or clinically significant hemolytic anemia have been associated with the use of fludarabine (the active ingredient contained in Oforta) A single case of pure red cell aplasia has been reported.[Ref]

Myelosuppression may be severe, cumulative, and may affect multiple cell lines.[Ref]

Immunologic

Instances of life-threatening and sometimes fatal autoimmune hemolytic anemia have been reported after one or more cycles of treatment in patients with or without a previous history of autoimmune hemolytic anemia or a positive Coombs test and who may or may not be in remission for their disease. Steroids may be effective in controlling these hemolytic episodes. The majority of affected patients developed a recurrence upon rechallenge.

An increased incidence of infections with pathogens not commonly associated with chronic lymphocytic leukemia have been associated with the use of fludarabine (the active ingredient contained in Oforta) especially when given with corticosteroids. These have included Listeria, Pneumocystis carinii pneumonia, disseminated varicella-zoster, cytomegalovirus, and unusual fungal pathogens. Fludarabine can significantly decrease the quantity of T-helper cells.[Ref]

Immunologic side effects have been reported secondary to neutropenia which predisposes patients to infection. Pneumonia has been reported in 16% to 22% of treated patients from major clinical trials. Other, less common, infections include minor bacterial and/or fungal infections of the oropharynx, upper respiratory tract, urinary tract, and soft tissue, as well as herpes zoster infections. The risk of sepsis or life-threatening infection appears greatest during the first three courses of chemotherapy with fludarabine in patients with extensive disease.[Ref]

Gastrointestinal

Gastrointestinal side effects including nausea, vomiting, and/or diarrhea have been reported in up to 36% of patients. Anorexia, stomatitis, esophagitis, mucositis, constipation, taste disturbances, abdominal pain, and gastrointestinal bleeding have been reported in less than 30% of patients.[Ref]

Nervous system

Central and peripheral nervous system toxicities have been reported, including weakness/fatigue (asthenia) (up to 31%), headache (up to 9%), hearing disturbances (6%), paresthesias (4%), confusion (1%), visual disturbances (3%), and coma (less than 1%). In postmarketing experience, cases of progressive multifocal leukoencephalopathy have been reported. Rare cases of disabling, severe, but reversible neurologic toxicity have been reported.[Ref]

Most cases of progressive multifocal leukoencephalopathy had a fatal outcome. Many of these cases were confounded by prior and/or concurrent chemotherapy. The time to onset has ranged from a few weeks to approximately one year after initiating treatment.

The early trials of fludarabine given at high doses in the treatment of acute leukemia (up to 125 mg/m2 per day for up to 7 days) revealed evidence of severe CNS toxicity. Progressive optic neuritis, cortical blindness, seizures, and paralysis developed in some patients up to 2 months after therapy ended. Use of lower doses for low-grade lymphoid malignancy has not generally been associated with these severe side effects. However, progressive headaches, paresthesias, hemiparesis, and progressive and fatal neurologic dysfunction have rarely been associated with recommended doses.[Ref]

Respiratory

Respiratory side effects have been reported including severe cases of pulmonary toxicity which resulted in adult respiratory distress syndrome, respiratory distress, pulmonary hemorrhage, pulmonary fibrosis, respiratory failure, and death. Cough (10% to 44%), upper respiratory tract infection or pneumonia (up to 22%), dyspnea (1% to 22%), rhinitis (up to 11%), increased cough (up to 6%), bronchitis (up to 5%), and sinusitis (up to 5%) have also been reported. Diffuse interstitial pneumonitis has been reported rarely.[Ref]

Rare cases of diffuse alveolar damage have been associated with tumor lysis syndrome and the use of fludarabine.

In a clinical investigation using fludarabine injection in combination with pentostatin for the treatment of refractory chronic lymphocytic leukemia in adults, there was an unacceptably high incidence of fatal pulmonary toxicity.[Ref]

Cardiovascular

Cardiovascular side effects including peripheral edema (8%) and chest pain (up to 5%) have been reported. A single case of pericardial effusion has been associated with the use of fludarabine (the active ingredient contained in Oforta) [Ref]

Genitourinary

Genitourinary side effects including dysuria, hematuria, or proteinuria have been reported in 1% to 4% of patients. Rare cases of hemorrhagic cystitis have also been reported.[Ref]

Renal

A single case of acute renal failure secondary to mesangiocapillary glomerulonephritis has been associated with the use of fludarabine (the active ingredient contained in Oforta) in a 60-year-old man who had refractory chronic lymphocytic leukemia (CLL). This lesion has rarely been associated with CLL itself.[Ref]

Renal side effects including hemolytic uremic syndrome and acute renal failure have rarely been associated with the use of fludarabine.[Ref]

Hypersensitivity

Hypersensitivity reactions--usually skin rashes-- to fludarabine (the active ingredient contained in Oforta) are relatively rare. Corticosteroid-responsive acute interstitial pulmonary infiltrates have been reported. Extremely rare cases of anaphylaxis have been reported.[Ref]

Metabolic

TLS may result in serious metabolic problems, including hyperuricemia, hyperphosphatemia, hypocalcemia, metabolic acidosis, hyperkalemia, hematuria, urate crystalluria, renal failure, and even death. (Allopurinol before and during therapy is recommended.) The onset of this syndrome may be heralded by flank pain and hematuria.[Ref]

Metabolic side effects including tumor lysis syndrome (TLS) has been reported to have occurred in approximately 1% of patients. A single case of diffuse alveolar damage has been associated with TLS and the use of fludarabine.[Ref]

Dermatologic

Most dermatologic problems are related to allergic reactions to fludarabine (the active ingredient contained in Oforta) [Ref]

Dermatologic side effects including increased sweating (up to 14%), diaphoresis (up to 8%), skin disorder (up to 6%), and rash (up to 5%) have been reported. Alopecia has been reported only rarely.[Ref]

Oncologic

Oncologic side effects have been reported in animal studies. Fludarabine phosphate was clastogenic in vitro to Chinese hamster ovary cells (chromosome aberrations in the presence of metabolic activation and induce sister chromatid exchanges both with and without metabolic activation). In addition, fludarabine (the active ingredient contained in Oforta) phosphate was clastogenic in vivo (mouse micronucleus assay).[Ref]

Hepatic

Hepatic side effects including increased lactic dehydrogenase (up to 6%) have been reported.

Musculoskeletal

Musculoskeletal side effects including back pain (up to 9%) have been reported.

References

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2. Ross SR, McTavish D, Faulds D "Fludarabine. A review of its pharmacological properties and therapeutic potential in malignancy." Drugs 45 (1993): 737-59

3. Feldman EJ, Keating MJ "Fludarabine in the treatment of lymphoproliferative malignancies." Cancer Invest 11 (1993): 314-8

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6. Maclean R, Meiklejohn D, Soutar R "Fludarabine-related autoimmune haemolytic anaemia in patients with chronic lymphocytic leukaemia." Br J Haematol 92 (1996): 768-9

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15. Bastion Y, Coiffier B, Tigaud JD, Espinouse D, Bryon PA "Pneumocystis pneumonia in a patient treated with fludarabine for chronic lymphocytic leukemia." Eur J Cancer 27 (1991): 671

16. Zinzani PL, Tabanelli M, Bendandi M, Tura S "Prolonged bone marrow aplasia of refractory prolymphocytoid variant of B-cell chronic lymphocytic leukemia related to fludarabine treatment." Eur J Haematol 53 (1994): 56-8

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