All about L-Aspara (L-Asparaginase) injection

Name of Medicine: L-Aspara

Active Ingredient: L-Asparaginase

Chemical Formula: C1377H2208N382O442S17

Description: L-Aspara is an established formulation of L-Asparaginase, an antineoplastic agent. It is administered as an injection.

What is L-Aspara?

L-Aspara is an anticancer formulation of a chemotherapeutic agent namely L-Asparaginase. This drug belongs to the family of medications known as antineoplastic agents. It is used in the treatment of Blood Cancer, in general. The prescription drug is available in the form of an injection in the strength of 10,000 IU.

Clinical Relevance 

L-Asparaginase is indicated to patients with Acute Lymphoblastic Leukemia (ALL) as first-line therapy and a component of a multi-agent chemotherapy regimen. It works by making the tumor cells starve of essential nutrients. This slows the growth of tumor cells and results in apoptosis. 

Clinical Pharmacology

Pharmacodynamics 

Asparaginase therapy reduced plasma asparagine levels from an average of 41 μM to less than 3 μM in clinical trials of patients with previously untreated, standard-risk ALL. The natural asparaginase whose plasma enzyme activity was more than 0.1 International Units/mL before therapy. In this investigation, asparaginase-treated patients’ cerebral fluid asparagine levels reduced from 2.8 μM (pretreatment) to 1.0 μM and 0.3 μM on days 7 and 28 after induction, respectively. Asparagine depletion occurs 14 to 23 days after delivery of native E. coli asparaginase.

Mechanism of Action 

Asparagine is a non-essential amino acid that helps cells thrive by maintaining DNA, RNA, and protein synthesis. While healthy and normal cells can receive asparagine from food or synthesize it from aspartate via asparagine synthetase activity, lymphoblastic leukemic cells lack the asparagine synthetase enzyme and are unable to create asparagine from scratch. As a result, for protein synthesis and cell survival, leukemic cells rely on an exogenous source of asparagine. By converting L-asparagine to L-aspartic acid and ammonia, E. coli depletes plasma levels of asparagine in leukemic cells, resulting in decreased DNA, RNA, and protein synthesis, suppression of cell growth, and activation of apoptotic cell-death processes. However, normal cells are affected less by the rapid depletion (caused by treatment with the enzyme asparaginase) since they can synthesize asparagine.

Absorption 

Daily intravenous treatment of L-asparaginase produced from E. coli resulted in a cumulative increase in plasma levels in patients with metastatic cancer and leukemia in research. Peak plasma levels of asparaginase were reached 14 to 24 hours after intramuscular injection in metastatic cancer and leukemia patients.

The asparaginase activity of native E. coli asparaginase reaches its maximum in 24 to 48 hours after treatment.

Toxicity

There has been no research on E. coli’s mutagenic or carcinogenic potential. People have been researching E. coli L-asparagine. When tested against Salmonella typhimurium strains in the Ames testing, no mutagenic effect was seen. There also has been no research on the effects of infertility. In rabbits, edema and necrosis of pancreatic islets were observed after the administration of a single intravenous injection of 12,500 to 50,000 International Units of L-asparagine/kg. This observation has very little clinical significance because it does not imply pancreatitis.

Clinical Trial 

Five USSR institutes collaborated to conduct phase II clinical studies of L-asparaginase on 49 patients with diverse kinds of hemoblastosis, including 15 children aged 1 to 15 and 34 adults aged 16 to 75. The medicine was given in a daily dose of 200 IU per 1 kg of body weight as intravenous drips twice a day for two to three weeks. The daily dose was split into two doses, each given at a 12-hour interval. The effectiveness of the medication was unaffected by the gender of the patients. In children with acute lymphoblastic leukemia, leunase efficiency was shown to be quite high (85.7 percent). The drug’s effectiveness in treating people with systemic malignant blood diseases was lower. Some of the symptoms seen in patients with widespread hematosarcoma were just temporary. Nausea and vomiting were reported in eight children and thirteen adults, allergic reactions in the form of pruritus and rashes in eight adults, and impairment of liver and pancreatic functions in two children and one adult. One youngster was diagnosed with acute pancreatonecrosis. On the other hand, the effect on the peripheral blood was negligible. In comparison to other L-asparaginase preparations, Leunase is unlikely to provide any significant benefits.

Interactions 

Drug-Drug Interactions 

• Adalimumab: The concomitant use of L-Aspara injection with Adalimumab may increase the risk of serious bacterial infections. It can also result in certain severe effects. 
• Lomitapide: The concomitant use of L-Aspara injection with Lomitapide may cause liver problems and lead to adverse reactions, including liver impairment. 
• Natalizumab: The concomitant use of L-Aspara injection with Natalizumab may cause serious infections. Consult your medical team to know the ways of managing/avoiding interactions. 

Alcohol Interactions 

The consumption of alcohol with L-Asparaginase can lead to severe reactions in the body. It is advisable to contact your medical team regarding other consequences of alcohol during the treatment period.

Drug-Disease Interactions

• Hepatic Dysfunction:- Patients can experience liver failure or other hepatic reactions like – hepatitis and increased liver enzymes during treatment with L-Asparaginase. 
• Bleeding Disorders:- Risk of severe bleeding may be increased in patients since L-Aspara (L-Asparaginase) interferes with coagulation factors. It is advisable to immediately report your signs and symptoms of bleeding to your medical practitioner. 
• Pancreatic Dysfunction:- Extreme caution is advised in patients who have a medical history of pancreatitis or some related condition. L-Asparaginase injection tends to decrease the insulin synthesis or inflammation and necrosis of cells of the pancreas. 

Drug Category

• Antineoplastic Agents: Medications belonging to this category work by rapidly killing cancer cells. Through such a mechanism, the drugs lower a load of tumors in the patient’s body.
• Amidohydrolases: This is a category of enzymes that are responsible for catalyzing the hydrolysis of amide or amine bonds. L-Asparaginase belongs to this diverse superfamily. 
• Asparaginases: These compounds work by starving cancer cells of essential nutrients while slowing or stopping tumor cell growth and spread in the patient’s body. It is approved and hence commonly used in treating a number of cancers.

Adverse Reactions 

Certain negative effects may occur after using L-Aspara (Peg L-Asparaginase injection). During the course of treatment, some persons may have a mild, moderate, or severe reaction. Such reactions should be thoroughly monitored, and patients should get supportive care. L-Aspara injection should be stopped if side effects remain longer than expected.

Some individuals receiving L-Aspara (Peg L-Asparaginase injection) may develop injection site responses such as skin rash, dry skin, swelling of the hands and legs, itching, and irritability. Fever, cough, and other flu-like symptoms may accompany these reactions.

Several people who take L-Asparaginase may develop pancreatitis. Stomach pain, nausea, vomiting, a racing heart, and tenderness while touching the abdomen should not be overlooked.

Patients receiving L-Asparaginase may also experience severe thrombosis, particularly sagittal sinus thrombosis. It’s important to keep an eye on side effects like throbbing or cramping pain, swelling in one leg, enlarged veins, and heated skin surrounding the uncomfortable areas.

Frequent dyspepsia (discomfort or pain in the upper abdomen), anal fissure, ileus, pancreatitis, dysphagia (difficulty swallowing), gastritis, and colitis are all possible side effects of L-Aspara (Peg L-Asparaginase injection). Malaise and temperature intolerance are two more common side effects that patients may experience.

Tinnitus and vertigo; sleeplessness, sadness, anxiety, confusional state; palpitations, angina pectoris, cardiomegaly, and myocardial infarction might also occur during the course.

Warnings and Precautions 

Pancreatitis

Pancreatitis may be experienced by some patients receiving therapy with L-Aspara (L-Asparaginase injection). Stomach or pelvic pain during the course of this injection should be monitored and tested for Pancreatitis. 

Thrombosis

Serious thrombotic effects, including sagittal sinus thrombosis, may occur in some patients receiving therapy with L-Aspara (L-Asparaginase injection). L-Aspara injection should be permanently discontinued if such a reaction continues.

Coagulopathy

Coagulopathy is a condition in which the individual loses his blood’s ability to clot. The patient receiving therapy with L-Aspara (L-Asparaginase injection) should be closely monitored for such reactions.

Serious Allergic Reactions

Serious allergic reactions may occur in patients who receive L-Aspara (L-Asparaginase injection). This condition is quite common in patients who are hypersensitive. L-Aspara injection should be permanently discontinued if such a reaction continues.

Pregnant Women

L-Aspara injection may lead to fetal harm when given to a woman during pregnancy. This injection may not be absolutely safe for use in patients who are pregnant or are planning to become pregnant. Women with child-bearing potential are highly recommended to make use of proper contraception for at least 28 days prior to the course of L-Aspara.

Nursing Mothers

It is not yet known whether L-Aspara (L-Asparaginase injection) is excreted in human milk. As many other medications are excreted in breast milk, it becomes important to undertake precautions for avoiding adverse events. Hence, breastfeeding should be discontinued while receiving L-Asparaginase injection.

Packaging

L-Aspara (L-Asparaginase injection) is supplied as a sterile solution in a Type I single-use vial containing 10,000 IU of L-Asparaginase, a lyophilized enzyme therapeutic agent. Store the injection in a refrigerator between 2°C and 8ºC. Do not shake or freeze the solution. Do not place the injectable solution under direct light or moisture. Protect the injection from heat. Know the methods of disposing of the used or expired packs of L-Aspara injection from a medical professional. Pregnant women should not handle such medications without wearing gloves.