Does cyclophosphamide cause hepatotoxicity?

(Review of hepatotoxicity of cancer chemotherapeutic agents mentions that cyclophosphamide is an uncommon cause of liver toxicity, but in high doses, often in combination with busulfan or irradiation, can cause sinusoidal obstruction syndrome [SOS]).

Which chemotherapy drugs cause hepatotoxicity?

The major chemotherapeutic agents in this group include methotrexate, sorafenib, dactinomycin, ifosfamide, gemcitabine, etoposide, irinotecan, procarbazine, 6-mercaptopurine, cytarabine, crizotinib, and cyclophosphamide.

Which medications are most likely to induce hepatotoxicity?

The 10 most frequently implicated drugs were: amoxicillin-clavulanate, flucloxacillin, erythromycin, diclofenac, sulfamethoxazole/Trimethoprim, isoniazid, disulfiram, Ibuprofen and flutamide [12,13,14,21].

What is the toxicity unique to cyclophosphamide?

Clinically, damage to the bladder (haemorrhagic cystitis), immunosuppression (when not desired) and alopecia are the most significant toxicities associated with cyclophosphamide.

How is cyclophosphamide metabolized?

Cyclophosphamide undergoes metabolism to several intermediates with alkylating activity. The principal metabolites identified are phosphoramide mustard, and acrolein. Phosphoramide mustard can undergo dephosphoramidation to yield nornitrogen mustard, which also has alkylating activity.

How is cyclophosphamide Bioactivated?

Cyclophosphamide itself is an inactive prodrug. Approximately 70–80% of the administered drug is bioactivated by cytochrome P450 enzymes to form 4-hydroxycyclophosphamide. 4-Hydroxycyclophosphamide is unstable and decomposes into phosphoramide mustard, the ultimate alkylating metabolite.

Can chemo drugs cause liver damage?

Treatments for cancer, including certain types of chemotherapy, radiation therapy, immunotherapy and stem cell transplants, can cause liver problems.

What is drug induced hepatotoxicity?

Drug-induced hepatotoxicity is an acute or chronic liver injury secondary to drugs or herbal compounds. It is difficult to diagnose because the presentation is similar to many hepatobiliary disorders. The principle treatment is the removal of the offending agent and close observation for resolution.

What is the antidote of cyclophosphamide?

No specific antidote for cyclophosphamide is known. Overdosage should be managed with supportive measures, including appropriate treatment for any concurrent infection, myelosuppression, or cardiac toxicity should it occur.

What enzymes metabolize cyclophosphamide?

Abstract. Purpose: The anticancer agent, cyclophosphamide, is metabolized by cytochrome P450 (CYP), glutathione S-transferase (GST) and aldehyde dehydrogenase (ALDH) enzymes. Polymorphisms of these enzymes may affect the pharmacokinetics of cyclophosphamide and thereby its toxicity and efficacy.

Where is cyclophosphamide metabolized?

Cyclophosphamide is used in the treatment of chronic lymphocytic leukaemia, lymphomas, soft tissue and osteogenic sarcoma, and solid tumours. It is given orally or intravenously. Cyclophosphamide is inactive until metabolized by the liver.

How is cyclophosphamide excreted?

Cyclophosphamide is eliminated primarily in the form of metabolites. 10-20% is excreted unchanged in the urine and 4% is excreted in the bile following IV administration. Total body clearance = 63 ± 7.6 L/kg.

Is cyclophosphamide nephrotoxic?

One of the limiting effects of cyclophosphamide use is nephrotoxicity.

Is liver damage From Chemo reversible?

Chemotherapy-induced liver damage in patients with cancer may occur during chemotherapy or after the total course. Although liver function impairment may be reversed in some patients after treatment, abnormal liver function may lead to an interruption of anti-tumor therapy and jeopardize the prognosis of patients [20].

Can chemo drugs cause cirrhosis of the liver?

Conditions such as sinusoidal obstructive syndrome, steatosis, and pseudocirrhosis are more commonly associated with chemotherapy. These conditions can display clinical signs of acute hepatitis, liver cirrhosis, and even liver failure.

How is drug induced hepatotoxicity treated?

The only specific treatment for most cases of liver damage caused by taking a drug is to stop taking the drug that caused the problem. However, if you took high doses of acetaminophen, you should get treated for liver injury in the emergency department or other acute treatment setting as soon as possible.

Does cyclophosphamide (CYCP) cause hepatotoxicity?

Cyclophosphamide (CYCP), a synthetic alkylating antineoplastic, disrupts both cancerous and non-cancerous cells to cause cancer regression and multi organotoxicity respectively. CYCP-induced hepatotoxicity is rare but possible. Evidence has shown that naringin has several beneficial potentials against oxidative stress, inflammation, and fibrosis.

Is cyclophosphamide metabolite exposure associated with hematopoietic cell transplantation complications?

Engraftment and tumor relapse were not statistically significantly related to cyclophosphamide metabolite exposure. Increased exposure to toxic metabolites of cyclophosphamide leads to increased liver toxicity and nonrelapse mortality and lower overall survival after hematopoietic cell transplantation.

What is the mechanism of action of cyclophosphamide on hepatocytes?

An alternative but not mutually exclusive mechanism involves depletion of reduced glutathione in hepatocytes and sinusoidal endothelial cells by cyclophosphamide, leaving sinusoidal endothelial cells more vulnerable to damage by irradiation.

What are the side effects of cyclophosphamide?

Cyclophosphamide therapy is associated with minor transient serum enzyme elevations and has been linked to rare cases of acute liver injury. In addition, when given in high doses as a part of a myeloablative therapy, cyclophosphamide can cause acute sinusoidal obstruction syndrome.