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Isoprinosine Review Article

 

Isoprinosine, also known as Imunovir has been recommended as an adjuvant treatment for cancer, age-associated immune impairments and AIDS. There have been more than 60 articles published on Isoprinosine and cancer since 1972. Isoprinosine is an immunostimulator, which besides its immunomodulatory effect also has antiviral properties. It is used in the treatment of acute and chronic viral infections. Isoprinosine acts on the immune system to restore impaired cell-mediated immune response to its baseline level, in addition to enhancing humoral immune response. The drug also has a direct antiviral activity. Isoprinosine can reduce the intensity of symptoms and shorten the duration of the viral infection. In addition, the occurrence of complications is reduced and the frequency and severity of recurrences is minimised. Isoprinosine has been found to have an immunoenhancing effect in old persons. Isoprinosine also available in SYRUP form.

Isoprinosine can also be administered for immunorestoration after chemotherapy, surgery or radiation.

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Immunostimulator with antiviral action. Isoprinosine - synthetic purine complex derivative having immunostimulatory activity and non-specific antiviral effect. Isoprinosine restores the function of lymphocytes in immunosuppression, increases blastogenesis in population of monocytic cells, stimulates the expression of membrane receptors on the surface of T-helper cells, prevents the decrease of activity of lymphocyte cells under the influence of glucocorticoids, normalizes them thymidine incorporation. Isoprinosine has a stimulating effect on the activity of cytotoxic T lymphocytes and natural killer cells, T-suppressor function and T-helper cells, and also increases the production of IgG, interferon-gamma, interleukin (IL) -1, IL-2, reduces the formation of pro-inflammatory cytokines - IL-4 and IL-10, potentiates the chemotaxis of neutrophils, monocytes and macrophages.

Isoprinosine is an immunomodulator and is approved for immunorestoration in chemotherapy in some countries. Patients on chemotherapy are particularly susceptible to different viral infections as a result of chemotherapy-induced immunodepression. Adjuvant therapy with Isoprinosine can restore the cell-mediated immune response to the individual's baseline levels.

It can therefore be prescribed during chemotherapy to restore the immune response and as a prophylaxis against reactivation of latent herpes simplex or herpes varicelliform zoster (shingles) infections, or for treatment or management of other secondary viral infections.

In these instances, the dosage used is the standard 50 mg/kg/day of lean body weight, up to a maximum of 3g daily (6x 500 mg tablets), divided evenly during waking hours. Schedule of treatment depends on the type of chemotherapeutic agent used. Isoprinosine is only administered after the infusion and only when the desired immune suppression against the cancerous cells has taken effect. At that point between infusions when it is desirable for the immune system to normalise, Isoprinosine treatment is initiated in order to enhance the normal immune response recovery. The number of treatment days depends on the length of time between infusions and also the immune profile of the individual patient.

Isoprinosine can also be administered for immunorestoration after chemotherapy, surgery or radiation.

How Does Isoprinosine work?
Isoprinosine is a synthetic purine derivative with immunomodulatory and antiviral properties, which result from an apparent in vivo enhancement of host immune responses due to the drug.
The action of Isoprinosine can be summarized as follows:
--- Normalizes the cell-mediated immunity by stimulating the differentiation of T-lymphocytes into T-cytotoxic cells and T-helper cells and increasing lymphokine production
--- Increases production of IL-1 (interleukin-1) and IL-2 (interleukin-2) and IFN-? (gamma interferon)
--- Increases NK cell (natural killer cell) function
--- Increases the humoral immune response by stimulating the differentiation of B- lymphocytes into plasma cells and by enhancing antibody production
--- Increases the number of IgG and complement surface markers
--- Potentiates neutrophil, monocyte and macrophage chemotaxis and phagocytosis
--- Inhibits viral growth by suppressing viral RNA synthesis while potentiating depressed lympocytic
--- RNA synthesis and translational ability

The drug exhibits antiviral activity against viruses Herpes simplex, cytomegalovirus and measles virus, T-cell lymphoma type III, polio, influenza A and B, echovirus (enterotsitopatogenny human virus), encephalomyocarditis and equine encephalitis in vivo. Isoprinosin’s mechanism of antiviral action is associated with inhibition of viral RNA and digidropteroatsintetazy enzyme involved in the replication of some viruses, increases mRNA synthesis of viral suppression of lymphocytes, which is accompanied by inhibition of the biosynthesis of RNA and translation of viral proteins, increases the production of lymphocytes possess antiviral properties of interferons alpha and gamma.

Other benefits of Isoprinosine treatment: Studies have documented the ability of Isoprinosine to slow the progression of AIDS in HIV-infected persons by increasing the total number and activity of T-cells, T-helper cells and NK (natural killer) cells. The largest study, which was published in The New England Journal of Medicine on June 21, 1990 found that HIV infected people with CD4 cells count over 500 experienced significant benefits from Isoprinosine therapy. T-lymphocyte defects are common in cancer and AIDS patients according to a study in Medical Oncological Tumor Pharmacotherapy in 1989, which found that Isoprinosine and levamisole (another immune-boosting drug) mimic the actions of the thymic hormones to promote T-cell development. Combinations of Isoprinosine, low-dose Interleukin 1 and 2, and other immune-modulating hormones such as Melatonin are suggested as possibly effective cancer therapies.

Isoprinosine Could Help in Chronic Fatigue Syndrome (ME/CFS) Doctors Report: In 1999 Dr. Byron Hyde reported that a small Isoprinosine study was 'milestone' in the treatment of ME/CFS. Dr. Paul Cheney calls Isoprinosine a 'very good immune-modulator' and appears to have used it extensively to boost NK cell functioning and reduce Th2 dominance in the immune system. In 2007 Dr. De Meirleir stated that he felt that Inosine - an amino acid available in health food stores - was as effective as Isoprinosine.

Chronic Fatigue Syndrome (ME/CFS) studies - Few studies have assessed Isoprinosine's effectiveness in ME/CFS. After a small single blind, placebo-controlled trial of 16 patients in 1999 Dr.Hyde's published study (2003) indicated that 6/10 patients improved and that their natural killer cell activity and T-helper cell numbers increased but no changes were seen in IFN-y, IL-1@, IL-10 and IL-12 levels. At the 2009 IACFS/ME conference Dr. Hone reported that Isoprinsine conferred 'significant (clinical)improvement' and increased NK cell functioning and reduced Epstein-Barr Virus levels in patients with reduced natural killer cell activity.

Indications for use

- Treatment of influenza and other acute respiratory viral infections
- Infections caused by Herpes simplex virus types 1, 2, 3 and 4: genital and labial herpes, herpes keratitis, herpes zoster, varicella;
- Infectious mononucleosis caused by Epstein-Barr virus;
- CMV infection;
- Measles severe;
- HPV infection: HPV larynx / vocal cords (fibrous type), genital HPV infection in men and women, the warts;
- Molluscum contagiosum.
Contraindications
- Hypersensitivity to the drug
- Gout
- Urolithiasis
- Arrhythmia
- Chronic renal failure
- Children under 3 years of age (body weight 15-20 kg)

Isoprinosine notes:

Isoprinosine effect on serum levels of cytokines in healthy adults.

J Interferon Cytokine Res. 2010 Apr;30(4):223-8.
Medical Institute Ministry of Interior, Sofia, Bulgaria
Petrova M Zhelev D, Ivanova A, Krastev Z.

Summary: Isoprinosine has immunomodulating and antiviral properties, resulting in increased immune response. We measured the levels of certain cytokines during and after treatment with isoprinosine. 10 healthy volunteers received 1 g Isoprinosine 3 times a day, 5 days a week.

Both treatment and follow-up phase last 3 weeks. Interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-10, and tumor necrosis factor-alpha (TNF-alpha) were measured in serum using commercial ELISA kits at baseline, 7th, 10th, 14th, 21st, 28th, 35th, and 42nd day.

There was an increase in the serum levels of all measured cytokines for 7-10 days.

The levels of IL-2 had another raise at 42nd day after drop to initial values (P < 0.05; P < 0.001, respectively). Those of IL-10 held up enhanced from 7th to 28th day of measurement (P < 0.01). There was a nearly flat line of values of TNF-alpha after initial slight increase at 10th day. We found a moderate negative correlation between IFN-gamma and IL-2, IL-10, and TNF-alpha (Spearman's r: -0.63, -0.62, -0.63; P < 0.05, respectively)

Conclusion: it was demonstrated immunomodulatory properties of isoprinosine in healthy adults. We advise to resume studies using modern techniques to elucidate the mechanisms of action of Isoprinosine, and possibly other compounds in various clinical conditions.

-------

Isoprinosine having generic name Inosiplex (or Immunovir) is an old drug that has been extensively used for herpes, genital warts, influenza, melanomas, other tumors, hepatitis B, a rare brain inflammation in children caused by the zoster virus (subacute sclerosing panencephalitis) and cancer.

This medication is approved in Canada and many other countries as an anti-viral drug. It is also used to treat chronic fatigue syndrome called as fibromyalgia.

According to a clinical study, Isoprinosine was successfully used to treat viral infections in patients with acute leukemia, chronic leukemia and Hodgkin’s disease. It was also used to evaluate the immune function in cancer patients receiving pelvic radiation. Many studies have published indicating Isoprinosine’s antiviral and immunostimulatory effects benefiting AIDS patients.

Isoprinosine is reported to have fewer side effects. Some of them are dizziness, stomach pain, digestion problem and itching. When this medication is given with ribavarin it causes drop in the white blood cells count of patient. Intake of Isoprinosine may results in certain allergic reactions like tightness in the chest or throat, skin hives, rashes, chest pain and itchy skin.

The recommended dosage of Isoprinosine is as prescribed by doctor. Generally it is taken as 1 – 4 gms per day i.e. 2 – 8 tablets per day. Isoprinosine is available in 500 mg tablets form. This medication can also be given as syrup. The price of Isoprinosine syrup for 150ml package is USD 67.

Consult doctor before taking this medication if you are pregnant or planning to become pregnant during the treatment. Physician's advice is necessary for lactating women if taking Isoprinosine. This medicine should not be taken by children.

Store Isoprinosine in a dry and cool place within a tight container.



Isoprinosine: Scientific update:

Article N 1

Urologiia. 2012 Mar-Apr;(2):35-6, 38.
The role of human papilloma virus in development of chronic urethritis and vulvodynia in females: perspectives of immunomodulating therapy.
Neĭmark AI, Shelkovnikova NV, Neĭmark BA, Sizovv KA.
Abstract:
The article is devoted to combined affection of the lower urinary tracts and genitalia in women with human papilloma virus (HPV) infection which manifests with persistent recurrent urethritis, pelvic pain syndrome. The colposcopic and urethrocystoscopic features, disturbed microcirculation of urethral and vaginal mucosa in virus infection promoting recurrences and persistence of HPV are discussed. Immunomodulators (inosin pranobex-groprinosin) are recommended for more effective treatment.


Article N 2

Gig Sanit. 2012 May-Jun;(3):33-4.
Efficacy of immunomodulators in children with respiratory diseases in environmentally poor areas.
Abstract:
The authors evaluated the clinical efficacy and safety of the antiviral and immunomodulatory drug Isoprinosine (inosine pranobex, Teva Pharmaceutical Industries, Ltd) in the treatment of bronchopulmonary diseases in children. One hundred and fifty-two children with acute respiratory diseases and an exacerbation of recurrent respiratory diseases were followed up. The use of Isoprinosine in their combined treatment showed both positive clinical changes and a better immunogram.


Article N 3

Dev Med Child Neurol. 2010 Oct;52(10):901-7. doi: 10.1111/j.1469-8749.2010.03717.x. Epub 2010 Jun 15.
Subacute sclerosing panencephalitis: an update.
Gutierrez J, Issacson RS, Koppel BS.
Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Abstract:
Subacute sclerosing panencephalitis (SSPE) is a chronic encephalitis occurring after infection with measles virus. The prevalence of the disease varies depending on uptake of measles vaccination, with the virus disproportionally affecting regions with low vaccination rates. The physiopathology of the disease is not fully understood; however, there is evidence that it involves factors that favour humoral over cellular immune response against the virus. As a result, the virus is able to infect the neurons and to survive in a latent form for years. The clinical manifestations occur, on average, 6 years after measles virus infection. The onset of SSPE is insidious, and psychiatric manifestations are prominent. Subsequently, myoclonic seizures usually lead to a final stage of akinetic mutism. The diagnosis is clinical, supported by periodic complexes on electroencephalography, brain imaging suggestive of demyelination, and immunological evidence of measles infection. Management of the disease includes seizure control and avoidance of secondary complications associated with the progressive disability. Trials of treatment with interferon, ribavirin, and isoprinosine using different methodologies have reported beneficial results. However, the disease shows relentless progression; only 5% of individuals with SSPE undergo spontaneous remission, with the remaining 95% dying within 5 years of diagnosis.

Caution! Before starting to take this medicine, it is vital that you should consult your doctor! Do not use it on your own initiative, without medical advice.


 

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