Side effects of cyclophopsphamide

Cyclophosphamide may cause any of the following side effects –

1. Nausea and vomiting:

The common side effect of cyclophosphamide is nausea with or without vomiting. These are dose-related and occur within 2-4 hours of therapy. These can be controlled by taking anti-emetic medications such as ondansetron, granisetron, dolasetron, palonosetron etc.

2. Diarrhea:

Cyclophosphamide can also cause diarrhea. If diarrhea occurs, appropriate amount of electrolytes containing fluids should be taken orally. Sometimes, intravenous (IV) fluids along with antidiarrheal agents such as loperamide, octreotide or opiate-based medications may be needed if severe diarrhea developed.

3. Urinary bladder toxicity:

The presentations of urinary bladder toxicity are dysuria (painful urination), hemorrhagic cystitis (blood in the urine with painful voiding due to diffuse inflammation of the urinary bladder) and increased urinary frequency. It occurs in 5% to 10% of patients and may starts within 24 hours of drug therapy or may be delayed for up to several weeks. Bladder toxicity can occur both in oral and intravenous therapy but less with intravenous therapy. After intake of cyclophosphamide, it is broken down into the phosphoramide mustard and acrolein. The byproduct acrolein causes urinary bladder injury and produces toxicity. Among bladder toxicity, hemorrhagic cystitis is the more dangerous side effect. When this drug is taken for one to several years in doses of 2 mg/kg/day, the incidence of hemorrhagic cystitis is at least 30%. To reduce the risk of bladder toxicity, all patients should intake cyclophosphamide in the morning with a large amount of liquid throughout the day and void every 2 hours. It can reduce the risk of urinary bladder injury by diluting urine. If severe hemorrhagic cystitis developed, mesna (2-mercaptoethanesulfonate) can be used that binds urotoxic metabolites of cyclophosphamide and reduce the risk of bleeding from urinary bladder.

4. Urinary bladder cancer:

The incidence of development of urinary bladder cancer is at least 6% after long term use of cyclophosphamide in doses of 2 mg/kg/day. Bladder cancer can appear several years after the discontinuation of this drug. Therefore, follow up of patients for urinary bladder cancer should continue indefinitely who have taken prolonged period of daily cyclophosphamide.

5. Bone marrow suppression:

Bone marrow suppression is an important side effect of cyclophosphamide therapy. Bone marrow is the source of all blood cells in our body. If cyclophosphamide causes bone marrow suppression, the number of blood cells can be reduced. As a result, (i) body’s defense mechanism becomes declined due to insufficient white blood cells and patient is prone to infection, (ii) anemia may develop due to insufficient red blood cells, and (iii) bleeding from different sites of body such as from nose, gum, skin, mucus membrane may occur due to reduced number of platelets (prevention and arrest of bleeding is an important function of platelet). Therefore, monitoring of blood cells count every 1-2 weeks is necessary during therapy.

6. Gonadal suppression:

Gonad means testis (in case of male) or ovary (in case of female). Cyclophosphamide can suppress the gonad that causes azoospermia (absence of sperm in semen) or anovulation (no production and discharge of an ovum), which may be permanent. Therefore, permanent infertility (inability to produce offspring) can occur in cyclophosphamide therapy that can be minimized by collection and storage of pre-treatment sperm or ova.

7. Myelodysplasia:

Myelodysplasia is a hematopoietic stem cell disorder leading to ineffective blood cell production. Myelodysplasia occur in 2% cases with chronic use of cyclophosphamide.

8. Pulmonary fibrosis:

Cyclophosphamide can cause sporadic interstitial pneumonitis that leads to fibrosis in the lung.

9. Hypogammaglobulinemia:

Rarely, cyclophosphamide causes hypogammaglobulinemia that means it lowers the level of gamamaglobulin. Gamamaglobulin is one type of antibody that plays an important role in body’s defense mechanism. When a patient with cyclophosphamide therapy develops hypogammaglobulinemia, he or she affected by frequent infections.

10. Opportunistic infection:

Opportunistic Infection is caused by opportunistic microorganisms that usually do not cause harm but do so when lowered body’s immune system. The incidence of development of life threatening opportunistic infections in cyclophosphamide therapy is low if the white blood cell count is maintained at more than 3000/µl and the patient is not taking daily glucocorticoids. However, Pneumocystis jiroveci infection and certain fungal infections can be seen with normal white blood cell count, particularly in patients taking glucocorticoids.

11. Alopecia:

Alopecia means loss of hair from head. It starts 2-3 weeks after drug therapy. Significant alopecia is unusual in chronic use of low dose cyclophosphamide. It affect the hair follicles and produces diffuse non-scarring alopecia. Most of the cases alopecia is reversible after the discontinuation of drug.

12. Hyperpigmentation:

Cyclophosphamide induces melanin pigment production that causes diffuse hyperpigmentation of skin.