Khapzory Side Effects Center

Last updated on RxList: 9/15/2022
Khapzory Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Khapzory?

Khapzory (levoleucovorin) is a folate analog indicated for rescue after high-dose methotrexate therapy in patients with osteosarcoma; diminishing the toxicity associated with overdosage of folic acid antagonists or impaired methotrexate elimination; and treatment of patients with metastatic colorectal cancer in combination with fluorouracil.

What Are Side Effects of Khapzory?

Common side effects of Khapzory include:

  • swelling and sores on the mouth and lips,
  • vomiting,
  • diarrhea,
  • nausea,
  • indigestion,
  • shortness of breath,
  • skin rash and itching,
  • confusion,
  • nerve pain,
  • abnormal kidney function, and
  • changes in taste

Seek medical care or call 911 at once if you have the following serious side effects:

  • Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
  • Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheartedness, or passing out;
  • Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors.

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

Dosage for Khapzory

The dose of Khapzory depends on the condition it is used to treat.

What Drugs, Substances, or Supplements Interact with Khapzory?

Khapzory may interact with fluorouracil. Tell your doctor all medications and supplements you use.

Khapzory During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Khapzory; it is administered in combination with methotrexate or fluorouracil, which can harm a fetus. It is unknown if Khapzory passes into breast milk. Khapzory is administered in combination with methotrexate or fluorouracil, which are not recommended for use while breastfeeding. Consult your doctor before breastfeeding.

Additional Information

Our Khapzory (levoleucovorin) for Injection, for Intravenous Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.


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Khapzory Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Tell your doctor or caregivers at once if you have:

  • blisters or ulcers in your mouth, red or swollen gums, trouble swallowing;
  • severe or ongoing diarrhea;
  • a light-headed feeling, like you might pass out;
  • seizure (convulsions);
  • dehydration symptoms--feeling very thirsty or hot, being unable to urinate, heavy sweating, or hot and dry skin; or
  • kidney problems--little or no urination; painful or difficult urination; swelling in your feet or ankles.

Common side effects may include:

  • diarrhea, nausea, vomiting; or
  • pain or sores in your mouth.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Khapzory Professional Information


The following clinically significant adverse reactions are described elsewhere in the labeling:

  • Increased gastrointestinal toxicities with fluorouracil [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

High-Dose Methotrexate Therapy

Table 2 presents the frequency of adverse reactions which occurred during the administration of 58 courses of high-dose methotrexate 12 grams/m² followed by levoleucovorin rescue, for osteosarcoma in 16 patients aged 6 to 21 years. Most patients received levoleucovorin 7.5 mg every 6 hours for 60 hours or longer, beginning 24 hours after completion of methotrexate administration.

Table 2 : Adverse Reactions with High-Dose Methotrexate Therapy

Adverse Reactions Levoleucovorin
All Grades (%) Grade 3-4 (%)
Stomatitis 38 6
Vomiting 38 0
Nausea 19 0
Diarrhea 6 0
Dyspepsia 6 0
Typhlitis 6 6
Dyspnea 6 0
Skin and Appendages
Dermatitis 6 0
Confusion 6 0
Neuropathy 6 0
Renal function abnormal 6 0
Taste perversion 6 0

Combination With Fluorouracil In Colorectal Cancer

Table 3 presents the frequency of adverse reactions which occurred in 2 arms of a randomized controlled trial conducted by the North Central Cancer Treatment Group (NCCTG) in patients with metastatic colorectal cancer. The trial failed to show superior overall survival with fluorouracil + levoleucovorin compared to fluorouracil + d,l-leucovorin. Patients were randomized to fluorouracil 370 mg/m² intravenously and levoleucovorin 100 mg/m² intravenously, both daily for 5 days, or to fluorouracil 370 mg/m² intravenously and d,l-leucovorin 200 mg/m² intravenously, both daily for 5 days. Treatment was repeated week 4 and week 8, and then every 5 weeks until disease progression or unacceptable toxicity.

Table 3 : Adverse Reactions Occurring in ≥ 10% of Patients in Either Arm

Adverse Reactions Levoleucovorin/ fluorouracil
d,l-Leucovorin/ fluorouracil
Grades 1-4 (%) Grades 3-4 (%) Grades 1-4 (%) Grade 3-4 (%)
Gastrointestinal Disorders
Stomatitis 72 12 72 14
Diarrhea 70 19 65 17
Nausea 62 8 61 8
Vomiting 40 5 37 6
Abdominal Pain* 14 3 19 3
General Disorders
Asthenia/Fatigue/Malaise 29 5 32 11
Skin Disorders
Dermatitis 29 1 28 1
Alopecia 26 0.3 28 1
Metabolism and Nutrition
Anorexia/Decreased Appetite 24 4 25 2
*Includes abdominal pain, upper abdominal pain, lower abdominal pain, and abdominal tenderness

Postmarketing Experience

The following adverse reactions have been identified during post approval use of levoleucovorin products. Because these adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following have been reported:

  • Dermatologic: pruritus, rash
  • Respiratory: dyspnea
  • Other Clinical Events: temperature change, rigors, allergic reactions


Effects Of Leucovorin Products On Other Drugs

Antiepileptic Drugs

Folic acid in large amounts may counteract the antiepileptic effect of phenobarbital, phenytoin and primidone and increase the frequency of seizures in susceptible children. It is not known whether folinic acid has the same effects; however, both folic and folinic acids share some common metabolic pathways. Monitor patients taking folinic acid in combination with antiepileptic drugs.


Leucovorin products increase the toxicity of fluorouracil. Do not initiate or continue therapy with Fusilev and fluorouracil in patients with symptoms of gastrointestinal toxicity until those symptoms have resolved. Monitor patients with diarrhea until the diarrhea has resolved, as rapid deterioration leading to death can occur [see WARNINGS AND PRECAUTIONS].


The concomitant use of d,l-leucovorin with trimethoprim-sulfamethoxazole for the acute treatment of Pneumocystis jiroveci pneumonia in patients with HIV infection was associated with increased rates of treatment failure and morbidity in a placebo-controlled study [see WARNINGS AND PRECAUTIONS].

Read the entire FDA prescribing information for Khapzory (Levoleucovorin Injection)

© Khapzory Patient Information is supplied by Cerner Multum, Inc. and Khapzory Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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