Levamisole: Anthelminthic agent

Group: anthelminthic agent
Tablet 40 mg, 50 mg (as hydrochloride)
Syrup 40 mg/5 ml

General information

Levamisole, the (-)-isomer of tetramisole, acts by paralysing the musculature of susceptible nematodes. Unable to maintain their anchorage, the worms are ejected by normal peristaltic action, usually within 24 hours.

Levamisole is rapidly and almost completely absorbed from the gastrointestinal tract

Levamisole is rapidly and almost completely absorbed from the gastrointestinal tract. Peak plasma concentrations occur within 2 hours and the plasma half-life is about 4 hours. It is extensively metabolized in the liver and is excreted in the urine as metabolites and unchanged drug.

Levamisole is used with another cancer medicine (fluorouracil) to help make it work better against cancer of the colon.

Levamisole is available only with your doctor's prescription.

Dosing

The dose of levamisole will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of levamisole. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

Missed Dose

If you miss a dose of levamisole, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Indication

For adjuvant treatment in combination with fluorouracil after surgical resection in patients with Dukes' stage C colon cancer. Also used to treat malignant melanoma and head/neck cancer. Levamisole was originally used as an antihelminthic to treat worm infestations in both humans and animals.

Colorectal cancer

P.J.J van Genderen, in Side Effects of Drugs Annual, 2008

Levamisole is used as an immunomodulating drug in colorectal cancer, usually in combination with 5-fluorouracil. The IGCS-COL multicenter randomized phase III study partly addressed the role of levamisole in the modulation of 5-fluorouracil as adjuvant systemic chemotherapy in patients with colorectal cancer. There was no evidence of improvement of disease-free survival or overall survival advantage by adding levamisole; nor did the addition of levamisole produce any statistically significant effect on the adverse effects profile of 5-fluorouracil.

In another study in 598 patients with stage III colon cancer the addition of levamisole to adjuvant fluorouracil significantly worsened the prognosis.

 

Antihelminthic drugs

P.J.J. van Genderen, in Side Effects of Drugs Annual, 2009

Comparative studies

Levamisole has been studied as an immunomodulator in the treatment of frequently relapsing steroid-dependent idiopathic nephrotic syndrome in a controlled study. Levamisole 2.5 mg/kg on alternate days for 1 year (n = 32) was compared with low-dose prednisolone 0.5 mg/kg on alternate days for 1 year (n = 24). The mean relapse rate was reduced more by levamisole as was the mean cumulative dose of steroids. Therapy failed in three levamisole-treated individuals compared with 12 controls. There were no major adverse effects of levamisole, and in particular significant leukopenia was not encountered. One patient taking levamisole reported a mild transient gastrointestinal upset.

Immunotherapy

Anahid Jewett, Han-Ching Tseng, in Pharmacology and Therapeutics for Dentistry (Seventh Edition), 2017

Levamisole

Levamisole is an anthelmintic drug that possesses nonspecific immunostimulatory properties. In deficient animals and humans, it restores many different immunologic functions, suggesting that it acts on multiple populations of cells, including neutrophils, macrophages, and T cells (but not B cells). Its effects on the immune response and its pharmacologic activity indicate that levamisole is a thymomimetic agent.

Levamisole has been used in the treatment of tumors and other diseases in which there are manifestations of immune dysfunction, including rheumatoid arthritis and Crohn disease. Several investigators have used it successfully in the treatment of recurrent aphthous stomatitis and herpes labialis. It has been suggested that the therapeutic effect of levamisole in aphthous stomatitis, which may have an autoimmune etiology, results from enhancement of suppressor T cells that normally prevent autoimmune responses. It is currently approved for use in the United States as an adjunct to fluorouracil in the treatment of colorectal carcinoma. The combination of levamisole with fluorouracil led to reduced colorectal cancer reoccurrence in comparison with no adjuvant therapy. Treatment with levamisole alone has shown no significant effect on the reduced reoccurrence of the colorectal carcinoma.

 

 

 

Antiparasitic drugs

Stephen W Page, in Small Animal Clinical Pharmacology (Second Edition), 2008

Levamisole

(-)-(S)-2,3,5,6-tetrahydro-6-phenylimidazol[2,1-b]thiazole].

Clinical applications

Levamisole, the levorotatory and biologically active isomer of the racemic tetramisole, was discovered by Janssen Pharmaceutica in 1966 and developed as a broad-spectrum anthelmintic for use in a variety of mammalian and avian species. While widely used as an antiparasitic agent in ruminants, with a number of immunomodulatory uses still under development in humans and other species, levamisole has not found wide application as an anthelmintic in dogs and cats, principally because of the narrow therapeutic index.

Pharmacodynamics

Levamisole is a synthetic imidazothiazole derivative that has been widely used in treatment of worm infestations in both humans and animals. As an anthelmintic, it probably works by targeting the nematode nicotinergic acetylcholine receptor. As an immunomodulator, it appears that Levamisole is an immunostimulant which has been shown to increase NK cells and activated T-cells in patients receiving this adjuvantly along with 5FU for Stage III colon cancer.

Mechanism of action

The mechanism of action of levamisole as an antiparasitic agent appears to be tied to its agnositic activity towards the L-subtype nicotinic acetylcholine receptors in nematode muscles. This agonistic action reduces the capacity of the males to control their reproductive muscles and limits their ability to copulate. The mechanism of action of Levamisole as an anticancer drug in combination with fluorouracil is unknown. The effects of levamisole on the immune system are complex. The drug appears to restore depressed immune function rather than to stimulate response to above-normal levels. Levamisole can stimulate formation of antibodies to various antigens, enhance T-cell responses by stimulating T-cell activation and proliferation, potentiate monocyte and macrophage functions including phagocytosis and chemotaxis, and increase neutrophil mobility, adherence, and chemotaxis.

Levamisole Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Less common

  • Fever or chills
  • unusual feeling of discomfort or weakness

Rare

  • Black, tarry stools
  • blood in urine or stools
  • cough or hoarseness
  • lower back or side pain
  • painful or difficult urination
  • pinpoint red spots on skin
  • unusual bleeding or bruising

Check with your doctor as soon as possible if any of the following side effects occur:

Less common

  • Sores in mouth and on lips

Rare

  • Blurred vision
  • confusion
  • convulsions (seizures)
  • lip smacking or puffing
  • numbness, tingling, or pain in face, hands, or feet
  • paranoia (feelings of persecution)
  • puffing of cheeks
  • rapid or worm-like movements of tongue
  • trembling or shaking
  • trouble in walking
  • uncontrolled movements of arms and legs

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

  • Diarrhea
  • metallic taste
  • nausea

Less common

  • Anxiety or nervousness
  • dizziness
  • headache
  • mental depression
  • nightmares
  • pain in joints or muscles
  • skin rash or itching
  • trouble in sleeping
  • unusual tiredness or sleepiness
  • vomiting

Levamisole may cause a temporary loss of hair in some people. After treatment has ended, normal hair growth should return.

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Interactions
Albendazole: The bioavailability of Albendazole can be increased when combined with Levamisole
Ivermectin: The bioavailability of Ivermectin can be increased when combined with Levamisole.

Food Interactions

·  Take on an empty stomach.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

 

 

References

·         https://www.drugbank.ca/drugs/DB00848

·         https://www.drugs.com/cons/levamisole.html

·         http://apps.who.int/medicinedocs/en/d/Jh2922e/3.2.2.html

·         https://www.sciencedirect.com/topics/neuroscience/levamisole

  •      Stephen W Page, in Small Animal Clinical Pharmacology (Second Edition), 2008
  •      Anahid Jewett, Han-Ching Tseng, in Pharmacology and Therapeutics for Dentistry (Seventh Edition), 2017

·  P.J.J. van Genderen, in Side Effects of Drugs Annual, 2009

· P.J.J. van Genderen, in Side Effects of Drugs Annual, 2008

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