Maxiliv Injection

Glutathione for injection 600 mg/via

Each vial contains :

Glutathione BP 600 mg

Excipients q.s.

Injection 600 mg

4.1 Therapeutic indication

• Alcoholic fatty liver
• Alcoholic liver fibrosis
• Alcoholic liver cirrhosis
• Alcoholic hepatitis
• As an add-on to the standard of care in moderate COVID-19 patients

4.2 Posology & method of administration Alcoholic fatty liver, Alcoholic liver fibrosis, Alcoholic liver cirrhosis, Alcoholic hepatitis

The dose of Glutathione injection is dependent on the severity of the disease. In mild to moderate disease : 300 mg to 600 mg daily by slow intramuscular or intravenous injection.

Intravenous drip : Dissolve with 5 ml sterile water for injections; the solution is further diluted into 250 ml or 500 ml with normal saline or 5% glucose solution for intravenous infusion respectively.

Intramuscular injection : Dissolve with 5 ml sterile water for injections. Inject the solution intramuscularly, preferably in the gluteal region.

As an add-on to the standard of care in moderate COVID19 patients

Loading dose : 4 vials of Glutathione (600 mg x 4) followed by.

Maintenance dose : 2 vials (600 mg x 2) every 12 hourly as intravenous injection for maximum of 7 days or earlier till the clinical improvement

4.3 Contraindications

Glutathione injection is contraindicated in the patients who show hypersensitivity to reduced Glutathione.

4.4 Warning And precautions

• Administer Glutathione injection under the supervision of a doctor.

• Keep out of reach of children.

• Administer Glutathione injection intramuscularly only when the need arises. Avoid injecting at the same site repeatedly.

• The products for parenteral use should be visually inspected before administration, in order to detect the presence of particles or an abnormal colour. Do not use in case of turbidity or precipitates.

• Use immediately after reconstitution

4.5 Drug interactions

Vitamin K, Vitamin B12, Calcium pantothenate, and antihistamines can affect the bioavailability of Glutathione.

4.6 Special populations

Pregnancy And Lactation

Glutathione injection should not be administered to a pregnant and lactating woman unless the clinical benefit outweighs the risks.

Pediatric

Glutathione injection should be used with caution in neonates, premature infants, and children, especially when it is administered by intramuscular injection.

Geriatric

For elderly patients, appropriate dose reduction and strict monitoring is required during therapy

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.

4.8 Undesirable effects

After intramuscular administration of Glutathione, rare instances of skin rash have been reported which have disappeared after discontinuation of treatment. Mild pain at the injection site has also been reported. As is the case with all intravenous infusions, febrile reactions, infections at the site of injection, venous thrombosis or phlebitis and extravasation may occur.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to : medico@zuventus.com

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

No adverse events have been reported after Glutathione intravenous infusion up to 50 mg/kg dosage. No specific antidote is available for the treatment of Glutathione overdosage. Symptomatic treatment should be provided.

5.1 Mechanism of action

Glutathione is an extremely important cell protectant which directly quenches reactive hydroxyl free radicals, other oxygen-centered free radicals, and radical centers on DNA and other biomolecules. It is an essential cofactor for many enzymes which require thiol-reducing equivalents, and helps to keep redox-sensitive active sites on enzymes in the necessary reduced state. Higher-order thiol cell system like metallothioneins, thioredoxins, and other redox regulator proteins are ultimately regulated by reduced form of Glutathione (GSH) levels and the ratio of GSH / GSSG (oxidized GSH). GSH / GSSG balance is crucial for homeostasis, stabilizing cellular biomolecular spectrum, and facilitating cellular performance and survival.

5.2 Pharmacodynamic properties

Glutathione (GSH) and its metabolites also interface with energetics and neurotransmitter synthesis, through several prominent metabolic pathways. GSH availability downregulates the pro-inflammatory potential of leukotrienes and other eicosanoids. Recently discovered S-nitroso metabolites generated in-vivo from GSH and NO (Nitric Oxide) further diversity GSH’s impact on metabolism.

5.3 Pharmacokinetic properties

Af 2 ter intravenous infusion of 2 g/m of Glutathione, the plasma concentration increases from an average of 6.9 mmol/L to a peak plasma concentration of approximately 334mmol/L. The volume of distribution is approximately 15 L, plasma half-life is approximately 10 minutes, 2 and the average clearance rate is 850 ml/mint/m . After 90 minutes of the first infusion, urinary excretion Glutathione and cysteine increases by 300% and 10% respectively. In addition, after high-dosage intravenous administration (50 mg/kg of body weight), Glutathione shows the following pharmacokinetic parameters in healthy volunteers.

After intramuscular injection, Glutathione reaches peak plasma concentration within 5 hours. Data shows that Glutathione is well distributed in all the organs within a short period of time, with higher concentration in liver, kidney and spleen then in other organs. While the distribution (measured in unit body weight) of GSH in hearts skeletal muscle and brain is not as high as in other organs, the excretion of GSH via these organs is slower. 7 days after the injection, 24 ± 4.2 % of the GSH is excreted in the urine

6.1 Animal Toxicology or Pharmacology

No known animal toxicology data

Glutathione (GSH) is a physiological tripeptide- a chain of three amino acid- cysteine, glycine and glutamic acid. It is used for the detoxification of electrophilic metabolites. It is a very efficient free radical scavenger, preventing damage to important cellular components caused by reactive oxygen species such as free radicals and peroxides.

Chemical Name : (2S) -2- Amino-4-[1- (carboxymethyl) carbamoyl-(2R)-2-sulfanylethylcarbamoyl] butanoic acid.

Molecular Formula : C₁₀H₁₇N₃O₆S

Molecular Weight : 307.32 g/mol

8.1 Incompatibilities

Not applicable

8.2 Shelf Life

Refer on the pack

8.3 Packaging information

A vial of 600 mg with SWFI IP 5 ml.

8.4 Storage and handing Instructions Store below 25°C. Protect from light.

Keep out of reach of children.

After reconstitution, do not use in case any foreign particulate matter is observed inside the vial.

• Not to exceed the stated recommended daily dose.

• In case of overdosage, consult your physician.