Product Monograph - Imunovir
INDICATIONS:
May be beneficial in retarding neurological deterioration and prolonging life in patients with slowly progressive subacute sclerosing panencephalitis (SSPE). Inosine pranobex is not indicated for any condition other than SSPE.
CONTRAINDICATIONS:
Inosine Pranobex is contraindicated in patients who are:
- hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see SUPPLIED.
- currently suffering with gout
- currently presenting with elevated uric acid blood levels
WARNINGS:
Isoprinosine may cause a transient elevation of baseline serum and urinary uric acid, usuallyremaining 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, Isoprinosine 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
In the case of long term treatment, 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) may occur. Treatment with Inosine Pranobex should be withdrawn in these cases.
Imunovir contains wheat starch. Suitable for people with coeliac disease. Patients with wheat allergy (different from coeliac disease) should not take this medicine.
PRECAUTIONS:
Pregnancy: Specific studies on the effects of inosine pranobex on animal reproduction have been performed and were negative. However, well-controlled trials concerning fetal risk and impairment of fertility in humans are not available. Therefore, care should be taken in the use of inosine pranobex by pregnant women and women of childbearing age, and the risks involved should be assessed.
It is not known if inosine acedoben dimepranol is excreted in human milk. Imunovir should not be administered to pregnant women unless the benefits outweigh the potential risks.
Isoprinosine® should not be administered with immunosuppressive agents due to its potentially antagonistic immunostimulatory effects. Isoprinosine® raises plasma uric levels and so should be used with caution with xanthine oxidase inhibitors or uricosuric agents whose action it may antagonize and also with diuretics as their effect on raising plasma uric acid levels may be increased.
Concomitant use with AZT increases AZT nucleotide formation through multiple mechanisms involving increased plasma AZT bioavailability and increased intracellular phosphorylation in human blood monocytes.
As a result Imunovir increases the effect of AZT.
ADVERSE EFFECTS:
Imunovir tablets may cause unwanted side effects but these are infrequent and are usually of a mild and brief nature. The most consistent side effect is increased uric acid levels in the blood and urine, which return to pre-treatment levels after the dosing is finished.
During treatment with Isoprinosine, the only consistently observed drug-related side effect in adults as well as paediatric population is a transient elevation (usually remaining within normal range) of urine and serum uric acid levels, which usually return to baseline values a few days after the end of treatment.
Frequency convention (MedDRA):
| 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 estimate from the available data |
| System Organ Class | Frequency of detailed adverse effect |
| Gastrointestinal disorders: | Common: Vomiting, nausea, epigastric discomfort. |
| Uncommon: Diarrhea, constipation. |
| General disorders and administration site conditions: | Common: Fatigue, Malaise. |
| Investigations: | Very Common: Blood uric acid increased, urine uric acid increased. |
| Common: Blood urea increased, transaminases increased, blood alkaline phosphatase increased. | |
| Musculoskeletal and connective tissue disorders: | Common: Arthralgia. |
| Nervous system disorders: | Common: Headache, vertigo. |
| Uncommon: Somnolence, insomnia. | |
| Psychiatric disorders: | Uncommon: Nervousness. |
| Renal and urinary disorders: | Uncommon: Polyuria. |
| Skin and subcutaneous tissue disorders: | Common: Rash, pruritus. |
Post-Marketing Experience:
The following undesirable effects have been reported in post-marketing surveillance. The frequency with which they occur is not known (cannot be estimated from available data):
| System Organ Class | Reported adverse effect |
| Gastrointestinal disorders: | Abdominal pain upper. |
| General disorders and administration site conditions: | Hyperpyrexia. |
| Hepatobiliary disorders | Biliary calculi. |
| Immune system disorders: | Angioedema, hypersensitivity, urticarial, anaphylactic reaction. |
| Metabolism and Nutrition disorders: | Hyperuricaemia. |
| Nervous system disorders: | Disturbances in attention, dizziness. |
| Renal and urinary disorders | Ureteric calculi, nephrolithiasis |
| Respiratory disorders | Dyspnoea |
| Skin and subcutaneous tissue disorders: | Erythema |
DOSAGE:
Adults and Children: The recommended dosage is 50 mg/kg/day, up to a maximum of 3 g/day, administered orally in 3 to 4 equally divided doses during waking hours.
OVERDOSE:
Treatment: Toxic effects from an overdose of inosine pranobex have not been observed. Since the drug is rapidly metabolized, reduction in dosage or withdrawal from treatment with symptomatic general management of signs and symptoms would generally suffice should any untoward reaction occur. Similar management would apply to an accidental overdose.
For management of a suspected drug overdose, contact your regional poison control centre.
PHARMACOLOGY:
Mechanism(s) that might explain the results of the clinical studies employing inosine pranobex have not been completely elucidated. However, possible antiviral and immunomodulating properties of this drug may be involved.
Serum uric acid concentration rose with increasing inosine pranobex doses. Hyperuricemic levels (greater than 7.5 mg%) were seen at doses equal to or exceeding 3 g/day. At doses of 4 g/day, about 60% of the subjects had serum uric acid levels in excess of 7 mg%; 30% of the subjects exceeded 7.5 mg%. Urinary uric acid excretion was also elevated after inosine pranobex administration. The time for urine normalization was usually longer than that required for normalization of serum uric acid level. In 1 case, uricosuria was found to last more than 9 days, and another case was reported in which 3 weeks were required to restore uric acid excretion to normal level.
Inosine pranobex is composed of inosine and the p-acetamidobenzoic acid salt of N, N-dimethylamido-2-propanol. The principal metabolite (about 80%) of p-acetamidobenzoic acid is O-acylglucuronide and the principal metabolite of N, N-dimethylamine-2-propanol is N, N-dimethylamino- 2-propanol-N-oxide. Virtually 100% of the metabolites was recovered in urine within 8 through 24 hours postadministration period. Each of the components of inosine pranobex is rapidly metabolized, the inosine and p-acetamidobenzoic acid more extensively than N, N-dimethylamino-2-propanol.
HOW SUPPLIED:
Each white, oblong tablet, engraved D N on one side and with a breakline on the reverse contains inosine pranobex 500 mg. Nonmedicinal ingredients: magnesium stearate, mannitol, microcrystalline cellulose, povidone and wheat starch. Tartrazine free. Cartons of 100 tablets packed as 5 blister strips of 20 tablets. Store at room temperature.