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● Restricted emergency use as add-on therapy for treatment of mild COVID-19
● Restricted emergency use as add-on therapy for treatment of mild COVID-19
patients with co-morbidities and moderate COVID-19 patients.<ref>{{Cite journal |last1=C R |first1=Jayanthi |last2=Swain |first2=Ashok K |last3=Ganga |first3=Ranganath T |last4=Halnor |first4=Dnyaneshwar |last5=Avhad |first5=Ajit |last6=Khan |first6=Mohd. Saif |last7=Ghosh |first7=Ayan |last8=Choudhary |first8=Sumer Sanjiv |last9=Yannawar |first9=Anand Namdevrao |last10=Despande |first10=Shubhangi |last11=Patel |first11=Manish |last12=Anne |first12=Krishna Prasad |last13=Bangar |first13=Yogesh |date=12 September 2022 |title=Efficacy and Safety of Inosine Pranobex in COVID-19 Patients: A Multicenter Phase 3 Randomized Double-Blind, Placebo-Controlled Trial |journal=Advanced Therapeutics |language=en |volume=5 |issue=12 |doi=10.1002/adtp.202200159 |issn=2366-3987 |pmc=9539257 |pmid=36246300}}</ref>
patients with co-morbidities and moderate COVID-19 patients.<ref>{{Cite journal |last1=C R |first1=Jayanthi |last2=Swain |first2=Ashok K |last3=Ganga |first3=Ranganath T |last4=Halnor |first4=Dnyaneshwar |last5=Avhad |first5=Ajit |last6=Khan |first6=Mohd. Saif |last7=Ghosh |first7=Ayan |last8=Choudhary |first8=Sumer Sanjiv |last9=Yannawar |first9=Anand Namdevrao |last10=Despande |first10=Shubhangi |last11=Patel |first11=Manish |last12=Anne |first12=Krishna Prasad |last13=Bangar |first13=Yogesh |date=12 September 2022 |title=Efficacy and Safety of Inosine Pranobex in COVID-19 Patients: A Multicenter Phase 3 Randomized Double-Blind, Placebo-Controlled Trial |journal=Advanced Therapeutics |language=en |volume=5 |issue=12 |doi=10.1002/adtp.202200159 |issn=2366-3987 |pmc=9539257 |pmid=36246300}}</ref>

==Dosage and Administration==
Before starting treatment with inosine pranobex your doctor will ask you, about your own medical history, if necessary he may perform physical examination and advice lab investigations. The drug can be taken orally and the dosage is prescribed by your doctor.<ref>https://www.trinjurylaw.com/blog/2021/07/everything-you-should-know-before-starting-a-new-medication/</ref>


==Contraindications==
==Contraindications==

Revision as of 15:19, 19 January 2024

Isoprinosine
INN: Inosine acedoben dimepranol
Chemical structures of the three components of inosine pranobex (from top to bottom: inosine, acedoben and dimethylamino isopropanol)
Combination of
InosineImmunostimulant
DimethylaminoisopropanolImmunostimulant
AcedobenImmunostimulant
Clinical data
Trade namesImunovir, Delimmun, Isoprinosine, Isojol 500, Viruxan
Other namesMethisoprinol
AHFS/Drugs.comhttps://www.drugs.com/international/isoprinosine-500mg.html
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Identifiers
PubChem CID
ChemSpider
UNII
KEGG
ECHA InfoCard100.048.313 Edit this at Wikidata
Chemical and physical data
FormulaC52H78N10O17
Molar mass1115.249 g·mol−1
3D model (JSmol)
  • CC(CN(C)C)O.CC(CN(C)C)O.CC(CN(C)C)O.CC(=O)NC1=CC=C(C=C1)C(=O)O.CC(=O)NC1=CC=C(C=C1)C(=O)O.CC(=O)NC1=CC=C(C=C1)C(=O)O.C1=NC2=C(C(=O)N1)N=CN2C3C(C(C(O3)CO)O)O

Inosine pranobex (BAN; also known as inosine acedoben dimepranol (INN) or methisoprinol) is an antiviral drug that is a combination of inosine and dimepranol acedoben (a salt of acetamidobenzoic acid and dimethylaminoisopropanol) in a ratio of 1 to 3. Inosine pranobex has no effect on viral particles itself.[citation needed] Instead, it acts as an immunostimulant, an analog of thymus hormones.[1]

Inosine pranobex has been used in SSPE, herpes simplex virus, human papillomavirus, HIV, influenza virus, and airway virus infections, cytomegalovirus, and Epstein-Barr virus infections.[2] The effect on SSPE is unclear, it is not a cure for it.

Medical Uses

Inosine pranobex is an immunostimulant and antiviral drug indicated for:[3]

● Mucocutaneous infections due to herpes simplex virus (type I and/ or type II).

● Genital warts as adjunctive therapy to podophyllin or carbon dioxide laser.

● Subacute Sclerosing Panencephalitis (SSPE).

● Influenza and other Acute Viral Respiratory Infections (AVRI).

● Restricted emergency use as add-on therapy for treatment of mild COVID-19 patients with co-morbidities and moderate COVID-19 patients.[4]

Contraindications

If there is a known hypersensitivity to product components, inosine pranobex should not be used. Also, it should not be prescribed in cases where the patient is presently suffering from gout or elevated uric acid blood levels.[5]

Special warnings and precautions for use

Inosine pranobex may cause a transient elevation of baseline serum and urinary uric acid, usually remaining within the normal range (using 8 mg % as the upper limit), particularly in males and in the ageing population of both sexes. The elevation of uric acid levels is due to the catabolic metabolism of the inosine moiety in this product in humans to uric acid. It is not due to a fundamental drug-induced alteration of enzyme or renal clearance function. Therefore, Inosine pranobex may be administered with caution in patients with a history of gout, Hyperuricemia, urolithiasis, or to patients with impaired renal function. During treatment, uric acid levels in these patients should be monitored closely.[6]

In the case of long term treatment (3 months or longer), the serum and/or urine uric acid levels, liver function, blood count and renal functions should be checked on a regular basis in all patients. There is a possibility that ureteric and biliary calculi may occur when patients receive long term treatment. In some people acute hypersensitivity reactions (urticaria, angioedema, anaphylaxis and anaphylactic shock) may occur. Treatment with Inosine pranobex should be withdrawn in these cases.[7]

Controlled trials monitoring fetal risk and impairment of fertility in humans are not available. It is not known if inosine pranobex is excreted in human milk. Therefore, inosine pranobex should not be administered during pregnancy or lactation unless the physician decides the benefits outweigh the potential risk. Although animal tests have shown no teratogenic effect, the use of inosine pranobex in women where pregnancy is suspected or confirmed should be avoided.[8]

Side effects

Common side effects include: nausea with or without vomiting, discomfort in the stomach, increased liver enzymes and blood urea nitrogen, itching, skin rashes, headaches, vertigo, fatigue or malaise (feeling unwell), and painful joints. Uncommon side effects include: diarrhea, constipation, nervousness, drowsiness or insomnia.[9][10][11]

System Organ Class[12] Frequency Adverse Reaction
Immune system disorders: Not known Angioedema, Hypersensitivity, Urticaria, Anaphylactic reaction
Psychiatric disorders Uncommon Nervousness
Nervous system disorders Common Headache, Vertigo
Uncommon Somnolence (Drowsiness), Insomnia
Not Known Dizziness
Gastrointestinal disorders: Common Vomiting, Nausea, Epigastric discomfort, Epigastric pain
Uncommon Diarrhea, Constipation
Not known Abdominal pain upper
Skin and subcutaneous tissue disorders Common Rash, Pruritus (Itching)
Not known Erythema
Musculoskeletal and connective tissue disorders Common Arthralgia
Renal and urinary disorders Uncommon Polyuria
General disorders and administration site conditions Commmon Fatigue, Malaise
Investigations Very common Blood uric acid increased,

Urine uric acid increased

Common Blood urea increased, Transaminases increased, Blood alkaline phosphate increased
  • Very common: ≥1/10;
  • Common: ≥1/100, <1/10;
  • Uncommon: ≥1/1,000, <1/100;
  • Rare: ≥1/10,000, <1/1,000;
  • Very rare: <1/10,000, including isolated reports;
  • Not Known: Cannot be estimated from the available data.

Overdose

There has been no experience of overdose with inosine pranobex. However, serious adverse effects apart from increased levels of uric acid in the body, seem unlikely in view of the animal toxicity studies. Treatment should be restricted to symptomatic and supportive measures.[13]

Drug interactions

It is not advisable take xanthine oxidase inhibitors drugs (drugs reducing production of uric acid), uricosuric agents (drugs which increase excretion of uric acid), diuretics (drugs which helps to excrete excess amount of water from body), immunosuppressive drugs (drugs which suppresses immune system) and zidovudine.[14] Some other drugs that interact with inosine pranobex and could increase higher serum level in a patient include:[15]

Pharmacology

Mechanism of Action

The broad spectrum antiviral activity of Inosine pranobex in vivo is due to its immunomodulating effect. It positively impacts host's immune system, by enhancing T-cell lymphocyte proliferation and activity of natural killer cells, increasing levels of pro-inflammatory cytokines, and thereby restoring deficient responses in immunosuppressed patients. It has been shown that it can affect viral RNA levels and hence inhibit growth of several viruses.[3]

Pharmacodynamics

Inosine pranobex 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.

In clinical studies Inosine pranobex has been shown to normalize (to the patient's baseline) a deficient or dysfunctional cell-mediated immunity by evoking a Th1 type response which initiates T lymphocyte maturation and differentiation and potentiation of induced lymphoproliferative responses, in mitogen or antigen-activated cells. Similarly, the drug has been shown to modulate T lymphocyte and natural killer cell cytotoxicity, T8 suppressor and T4 helper cell functions and also to increase the number of IgG and complement surface markers.[14]

Inosine pranobex increases cytokine IL-1 production and enhances IL-2 production, up regulating the expression of the IL-2 receptor in vitro. It significantly increases endogenous IFN -γ secretion and decreases the IL-4 production in vivo. It has also been shown to potentiate neutrophil, monocyte and macrophage chemotaxis and phagocytosis.[16]

In vivo, inosine acedoben dimeparanol enhances potentiation of depressed lymphocytic mRNA protein synthesis and translational ability while inhibiting viral RNA synthesis achieved by yet-to-be-clarified degrees of (1) incorporation of inosine-mediated orotic acid into polyribosomes; (2) inhibition of polyadenylic acid attachment to viral messenger RNA and (3) molecular reorganization of lymphocyte intramembrane plasma particles (IMP) which take part in emitting signals via specific T cells receptor (TcR) that results in a nearly threefold increase in density. Inosine pranobex inhibits cGMP phosphodiesterase only at high concentrations in vitro and at levels not involved in the in vivo immunopharmacological effects. In vitro, inosine pranobex exhibits inhibitory activity on the replication of herpes virus type 1 (HSV-1).[17][18]

Pharmacokinetics

Each moiety of the drug exhibits separate pharmacological properties.

Absorption: When administered orally in man, inosine pranobex is rapidly and completely absorbed (≥ 90%) from the gastrointestinal tract and appears in the blood. Similarly, 94-100% of IV values of DIP [N,N-dimethylamino-2-propanol] and PacBA [p-acetamidobenzoic acid] components are recovered in urine after oral administration in Rhesus monkeys.[19]

Distribution: Radiolabelled material was found in the following tissues in order of decreasing specific activity when drug was administered to monkeys: kidneys, lung, liver, heart, spleen, testes, pancreas, brain and skeletal muscle.

Metabolism: In human subjects following a 1 g oral dose of inosine pranobex, the following plasma levels were found for DIP and PAcBA, respectively: 3.7μg/ml (2 hours) and 9.4μg/ml (1 hour). In human dose tolerance studies, peak post-dose elevation of uric acid levels as a measurement of drug-derived inosine are not linear and can vary±10% between 1–3 hours.

Excretion: The 24-hour urinary excretion of PAcBA and its major metabolite under steady-state conditions at 4g per day amounted to approximately 85% of the administered dose. 95% of the DIP-derived radioactivity in urine was recovered as unchanged DIP and DIP N-oxide. The elimination half-life is 3.5 hours for DIP and 50 minutes for PAcBA. The major metabolites in humans are the N-oxide for DIP and the o-acylglucuronide for PAcBA. Because the inosine moiety is degraded by the purine degradation pathway to uric acid, radiolabelled experiments in humans are inappropriate. In animals up to about 70% of the administered inosine can be recovered as urinary uric acid following oral tablet administration and the remainder as the normal metabolites, xanthine and hypoxanthine.

Bioavailability/AUC: Urinary recoveries under steady state conditions of the PAcBA moiety and its metabolite were found to be > 90% of the expected value from solution. The recovery of the DIP moiety and its metabolite was >76%. The plasma AUC was >88% for DIP and > 77% for PAcBA.[20]

Researches

There are multiple researches shown that Inosine Pranobex 500 mg is effective drug in various infectious diseases.

  • Inosine pranobex. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy[21]
  • Inosine Pranobex: A Key Player in the Game Against a Wide Range of Viral Infections and Non-Infectious Diseases[22]
  • Inosine pranobex is safe and effective for the treatment of subjects with confirmed acute respiratory viral infections: analysis and subgroup analysis from a Phase 4, randomized, placebo-controlled, double-blind study[23]
  • Genotoxicity and Mutagenicity of Inosine Pranobex[24]
  • The efficacy of inosine pranobex in preventing the acquired immunodeficiency syndrome in patients with human immunodeficiency virus infection. The Scandinavian Isoprinosine Study Group[25]
  • [Immunological and clinical study on therapeutic efficacy of inosine pranobex][26]

References

Public Domain This article incorporates text from this source, which is in the public domain: https://pdf.hres.ca/dpd_pm/00017981.PDF

  1. ^ "Inosine Pranobex". American Cancer Society. Archived from the original on 23 August 2010. Retrieved 31 July 2013.
  2. ^ Hashimoto K, Hosoya M (January 2021). "Advances in Antiviral Therapy for Subacute Sclerosing Panencephalitis". Molecules. 26 (2): 427. doi:10.3390/molecules26020427. PMC 7830519. PMID 33467470.
  3. ^ a b Sliva, Jiri; Pantzartzi, Chrysoula N.; Votava, Martin (2019-08-01). "Inosine Pranobex: A Key Player in the Game Against a Wide Range of Viral Infections and Non-Infectious Diseases". Advances in Therapy. 36 (8): 1878–1905. doi:10.1007/s12325-019-00995-6. ISSN 1865-8652. PMC 6822865. PMID 31168764.
  4. ^ C R, Jayanthi; Swain, Ashok K; Ganga, Ranganath T; Halnor, Dnyaneshwar; Avhad, Ajit; Khan, Mohd. Saif; Ghosh, Ayan; Choudhary, Sumer Sanjiv; Yannawar, Anand Namdevrao; Despande, Shubhangi; Patel, Manish; Anne, Krishna Prasad; Bangar, Yogesh (12 September 2022). "Efficacy and Safety of Inosine Pranobex in COVID-19 Patients: A Multicenter Phase 3 Randomized Double-Blind, Placebo-Controlled Trial". Advanced Therapeutics. 5 (12). doi:10.1002/adtp.202200159. ISSN 2366-3987. PMC 9539257. PMID 36246300.
  5. ^ https://www.pharmadoor.com.br/images/medicamentos/bulas/pharmadoor_-_Isoprinosine_bula.pdf
  6. ^ "Imunovir 500mg Tablets - Summary of Product Characteristics (SMPC) - (Emc)".
  7. ^ "Imunovir 500mg Tablets - Summary of Product Characteristics (SmPC) - (emc)". www.medicines.org.uk. Retrieved 2023-12-15.
  8. ^ "Isoprinosine Full Prescribing Information, Dosage & Side Effects | MIMS Philippines". www.mims.com. Retrieved 2023-12-15.
  9. ^ "Inosine pranobex: Indication, Dosage, Side Effect, Precaution | MIMS Malaysia". www.mims.com. Retrieved 2023-12-15.
  10. ^ "INOSINE ACEDOBEN DIMEPRANOL: Uses, Side Effects and Medicines | Apollo Pharmacy". www.apollopharmacy.in. Retrieved 2023-12-15.
  11. ^ "Inosine Pranobex | Memorial Sloan Kettering Cancer Center". www.mskcc.org. Retrieved 2023-12-15.
  12. ^ "PRESCRIBING INFORMATION PrIMUNOVIR® Inosine Pranobex Tablets, 500mg" (PDF). pdf.hres.ca. June 30, 2020. Archived (PDF) from the original on May 18, 2022. Retrieved June 30, 2020.
  13. ^ https://pdf.hres.ca/dpd_pm/00057022.PDF
  14. ^ a b Beran, Jiří; Šalapová, Eva; Špajdel, Marian; on behalf of the Isoprinosine Study (EWO ISO-2014/1) Team (2016-11-07). "Inosine pranobex is safe and effective for the treatment of subjects with confirmed acute respiratory viral infections: analysis and subgroup analysis from a Phase 4, randomised, placebo-controlled, double-blind study". BMC Infectious Diseases. 16 (1): 648. doi:10.1186/s12879-016-1965-5. ISSN 1471-2334. PMC 5100179. PMID 27821093. This article incorporates text from this source, which is available under the CC BY 4.0 license.
  15. ^ "Inosine pranobex". go.drugbank.com. Retrieved 2023-12-19.
  16. ^ Ompico, Melissa G. (2013). "Methisoprinol for children with early phase dengue infection: A pilot study". Paediatrica Indonesiana. 53 (6): 320. doi:10.14238/PI53.6.2013.320-7. S2CID 71954060.
  17. ^ Hussein, Abdel Maksoud; Mahmoud, Omnia; Khalifa, Mahmoud; Hussein, Abdel Maksoud; Mahmoud, Omnia; Khalifa, Mahmoud (2019). "Biochemical study on immunomodulation and safety margin of inosine acedoben dimepranol before and after vaccination". GSC Advanced Research and Reviews. 1 (1): 017–025. doi:10.30574/gscarr.2019.1.1.0008. ISSN 2582-4597.
  18. ^ https://gsconlinepress.com/journals/gscarr/sites/default/files/GSCARR-2019-0008.pdf
  19. ^ Tobólska, Sylwia; Terpiłowska, Sylwia; Jaroszewski, Jerzy; Siwicki, Andrzej Krzysztof (20 Jun 2018). "Genotoxicity and Mutagenicity of Inosine Pranobex". Journal of Veterinary Research. 62 (2): 207–213. doi:10.2478/jvetres-2018-0030. ISSN 2450-7393. PMC 6200294. PMID 30364916.
  20. ^ "Isoprinosine Full Prescribing Information, Dosage & Side Effects | MIMS Philippines".
  21. ^ Campoli-Richards, D. M.; Sorkin, E. M.; Heel, R. C. (November 1986). "Inosine pranobex. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy". Drugs. 32 (5): 383–424. doi:10.2165/00003495-198632050-00001. ISSN 0012-6667. PMID 2431857.
  22. ^ Sliva, Jiri; Pantzartzi, Chrysoula N.; Votava, Martin (August 2019). "Inosine Pranobex: A Key Player in the Game Against a Wide Range of Viral Infections and Non-Infectious Diseases". Advances in Therapy. 36 (8): 1878–1905. doi:10.1007/s12325-019-00995-6. ISSN 1865-8652. PMC 6822865. PMID 31168764.
  23. ^ Beran, Jiří; Šalapová, Eva; Špajdel, Marian; Isoprinosine Study (EWO ISO-2014/1) Team (2016-11-07). "Inosine pranobex is safe and effective for the treatment of subjects with confirmed acute respiratory viral infections: analysis and subgroup analysis from a Phase 4, randomised, placebo-controlled, double-blind study". BMC Infectious Diseases. 16 (1): 648. doi:10.1186/s12879-016-1965-5. ISSN 1471-2334. PMC 5100179. PMID 27821093.{{cite journal}}: CS1 maint: numeric names: authors list (link)
  24. ^ Tobólska, Sylwia (2018-10-24). "Genotoxicity and Mutagenicity of Inosine Pranobex". Journal of Veterinary Research. 62 (2): 207–213. doi:10.2478/jvetres-2018-0030. PMC 6200294. PMID 30364916.
  25. ^ Pedersen, C.; Sandström, E.; Petersen, C. S.; Norkrans, G.; Gerstoft, J.; Karlsson, A.; Christensen, K. C.; Håkansson, C.; Pehrson, P. O.; Nielsen, J. O. (1990-06-21). "The efficacy of inosine pranobex in preventing the acquired immunodeficiency syndrome in patients with human immunodeficiency virus infection. The Scandinavian Isoprinosine Study Group". The New England Journal of Medicine. 322 (25): 1757–1763. doi:10.1056/NEJM199006213222501. ISSN 0028-4793. PMID 1693173.
  26. ^ Gołebiowska-Wawrzyniak, Maria; Markiewicz, Katarzyna; Kozar, Agata; Derentowicz, Piotr; Czerwińska-Kartowicz, Iwona; Jastrzebska-Janas, Krystyna; Wacławek, Jolanta; Wawrzyniak, Zbigniew M.; Siwińska-Gołebiowska, Henryka (September 2005). "[Immunological and clinical study on therapeutic efficacy of inosine pranobex]". Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego. 19 (111): 379–382. ISSN 1426-9686. PMID 16358878.
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