Viralex ® (Inosine pranobex 500mg tablet) is indicated for:

• 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.

Posology

Adults and the Elderly:

The recommended dosage is 50mg/kg bd wt/day, rounded to the nearest multiple of 500mg (usually 3g/day, up to a maximum of 4g/day), administered orally in 3-4 divided doses during waking hours.

• Mucocutaneous herpes simplex: 1 g administered orally 4 times daily, for 7 -14 days.
• Genital warts: 1g administered orally 3 times daily, for 14-28 days as adjunctive therapy to podophyllin or carbon dioxide laser.
• Subacute sclerosing panencephalitis (SSPE): 50-100mg/kg daily, up to a maximum of 3-4 g, in divided doses every 4 hours, with regular monitoring to evaluate patient status and requirement for extended treatment
• Influenza and other Acute Viral Respiratory Infections (AVRI): 1 g administered orally 3 times daily, for 7 days.
• In mild COVID-19 patients with co-morbidities and moderate COVID-19 patients: 1 g administered orally 3 times daily, for 10 days

Children above the age of 1 year

50 mg/kg of body weight per day, administered in 3-4 divided doses.

Method of administration

For oral use.

To make ingestion easier, the tablets may be crushed and dissolved in a small amount of flavored liquid at the time of administration.

• Hypersensitivity to the active substance.
• Acute gout or elevated blood uric acid blood levels.

1. Inosine pranobex may cause a transient elevation of baseline serum and urinary uric acid, usually remaining within the normal range (using 8mg % 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, hyperuricaemia, urolithiasis, or to patients with impaired renal function. During treatment, uric acid levels in these patients should be monitored closely.
2. 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.

The drug should be used with caution with xanthine oxidase inhibitors (e.g. allopurinol)or uricosuric agents, including diuretics(e.g. hydrochlorothiazide, chlorthalidone, indapamide) and loop diuretics (furosemide, torasemide, ethacrynic acid)..

Inosine pranobex may be administered after but not concomitantly with immunosuppressive agents, as there may be a pharmacokinetic influence on the desired therapeutic effects.

Concomitant use with zidovudine (AZT) increases AZT nucleotide formation through multiple mechanisms involving increased plasma AZT bioavailability and increased intracellular phosphorylation in human blood monocytes.

As a result Inosine pranobex increases the effect of AZT.

Controlled trials monitoring foetal 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.

Inosine pranobex has no or negligible influence on the ability to drive and use machines.

Frequency convention – 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.

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.

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 Tcell lymphocyte proliferation and activity of natural killer cells, increasing levels of proinflammatory 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.

Pharmacotherapeutic group: Other antivirals, ATC code: J05AX05

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 normalise (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.

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.

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 reorganisation 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).

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 [pacetamidobenzoic acid] components are recovered in urine after oral administration in Rhesus monkeys.

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 oacylglucuronide 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.

Inosine pranobex showed a low toxicity profile in multivariate acute, subacute and chronic toxicology in mice, rats, dogs, cats and monkeys in doses up to 1500mg/kg/day and produced the lowest acute oral LD50 at 50 times the maximum therapeutic dosage level of 100mg/kg/day.

Long-term toxicology studies in mice and rats have shown no indication of carcinogenic potential.

Standard mutagenicity assays and in vivo studies in mice and rats and in vitro studies in human peripheral blood lymphocytes revealed no aberrant properties.

No evidence of perinatal toxicity, embryotoxicity, teratogenicity or impaired reproductive function in mice, rats and rabbits could be demonstrated in studies with continuous parental dosing of up to 20 times the maximum therapeutically recommended human dose (100 mg/kg/day) (See also item 4.6 for usage recommendations in pregnancy).

Povidone K-25 IP, Potato Starch IP, Magnesium Stearate IP

Not Applicable

24 months

Aluminum/PVC/PE/PVDC blisters in carton box.

Package contains 10 tablets.

Store below 30°C.

Inosine pranobex is an immunostimulant and antiviral drug indicated for

• 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.

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.

You should not take Inosine pranobex if you have a history of gout (accumulation of uric acid in smaller joints), hyperuricaemia (increased in blood uric acid level), urolithiasis (kidney stone), or to patients with impaired kidney function.

Inosine pranobex is to be taken as directed by your treating physician.

You should stop using inosine pranobex -

1. If your serum and urine uric acid level start increasing above normal level.
2. If you start experiencing any allergic reaction

You should not 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.

The possible side effects of inosine pranobex are, increased in blood and urine uric acid level, increased blood urea level, increased blood transaminases level, increased blood alkaline phosphate, fatigue, malaise (illness), arthralgia (joint pain), rash (red, bumpy, scaly or itchy patches of skin), pruritus (itching), vomiting, nausea, epigastric discomfort (stomach discomfort), headache, vertigo (a sensation of whirling and loss of balance), Somnolence (excessive sleepiness), Insomnia (trouble falling asleep), Nervousness, Diarrhoea, Constipation, Polyuria( excessive urination), Angioedema, Hypersensitivity (swelling of the area beneath the skin), Urticaria (round, red welts on the skin that itch), Anaphylactic reaction (A severe, potentially life-threatening allergic reaction),Dizziness (lightheadedness), upper Abdominal pain, Erythema (superficial reddening of the skin).

If any adverse events occurred please report to following

• Email: drugsafety@themismedicare.com

Link to download form - https://www.themismedicare.com/adverse-events/

• Toll Free No: 18001034746