Mixavit Drops is indicated as a multivitamin supplement for infants and newborn babies to prevent or to correct vitamin deficiency due to inadequate diet, malabsorption syndrome, or other reasons.

Posology:

Half to full dropper (0.3 - 0.6mL) daily, or as directed by the physician.

Note: Mixavit drops may be given in the baby formula or mixed with cereals or fruit juice.

Method of administration:

For oral administration

The recommended dose should not be exceeded without medical advice.

When prescribing Mixavit, as with all multi-vitamin preparations, allowance should be made for vitamins obtained from other sources to prevent hypervitaminosis occurring.

Vitamin D has the following interaction information:

Note: Vitamin D belongs to Vitamins but Vitamins has no interactions information.

Ascorbic acid has the following interaction information:

Vitamin A has the following interaction information:

Note: Vitamin A belongs to Vitamins but Vitamins has no interactions information.

Not indicated.

None known

Mixavit drops are generally well-tolerated when taken within the recommended doses. Vitamin A (palmitate)

Adverse effects are extremely rare at daily doses of less than 9mg (16363.6IU).

Vitamin D

The only known adverse effects of vitamin D occur when excessive doses are taken. Ascorbic Acid (C), Nicotinamide, Pyridoxine (B₆), Riboflavin (B₂) & Thiamine (B₁)

These water soluble vitamins are generally non toxic compounds with a wide margin of safety, the excess amounts being rapidly excreted in the urine.

To report any side effect(s):

The National Pharmacovigilance and Drug Safety Centre (NPC)

Fax: +966-11-205-7662

Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.

Toll free phone: 8002490000

E-mail: npc.drug@sfda.gov.sa

Website: www.sfda.gov.sa/npc

Symptoms and signs

Mixavit contains levels of vitamins which present little risk in overdose.

Vitamin A (palmitate)

Acute administration of high doses of vitamin A can cause headache, nausea, vomiting and irritability. In infants acute toxicity can lead to transient hydrocephalus. All these effects disappear within 24 hours of taking retinol.

Vitamin D

Excessive doses of vitamin D, 60 000 units per day, can result in hypercalcaemia and hypercalciuria. Adverse effects of hypercalcaemia may include muscle weakness, apathy, headache, anorexia, nausea and vomiting, hypertension and cardiac arrhythmias.

Thiamine (Vitamin B₁)

When taken orally, thiamine is non-toxic. If large doses are ingested they are not stored by the body but excreted unchanged by the kidneys.

Riboflavin (Vitamin B₂)

Riboflavin has been found to be practically non-toxic.

Pyridoxine (Vitamin B₆)

Acute doses less than 500mg per day appear to be safe. Excessive doses may lower serum folate concentrations. Sensory neuropathy has been described with chronic dosing of 200mg daily.

Nicotinamide

A single large overdose of nicotinamide is unlikely to have serious ill effects, though transient abnormalities of liver function might occur.

Ascorbic acid (Vitamin C)

Ascorbic acid is not stored to a great extent by the body; any excess amounts are eliminated in the urine. Ascorbic acid is thought to become toxic at chronic doses in excess of 6 g.

Treatment

Treatment should be supportive and symptomatic.

Vitamin A (palmitate)

Vitamin A plays an essential role in the function of the retina, the growth and function of epithelial tissue, bone growth, reproduction and embryonic development.

Vitamin D

Vitamin D is a regulator of both calcium and phosphate homeostasis.

Thiamine (Vitamin B₁)

Vitamin B₁ is essential for proper carbohydrate metabolism and plays an essential role in the decarboxylation of alpha keto acids.

Riboflavin (Vitamin B₂)

Riboflavin is essential for the utilisation of energy from food. It is a component of co-enzymes which play an essential role in oxidative/reductive metabolic reactions. Riboflavin is also necessary for the functioning of pyridoxine and nicotinic acid.

Nicotinamide

Nicotinamide is an essential component of co-enzymes responsible for proper tissue respiration.

Pyridoxine (Vitamin B₆)

Vitamin B₆ is a constituent of the co-enzymes, pyridoxal pyrophosphate and pyridoxamine phosphate, both of which play an important role in protein metabolism.

Ascorbic acid (Vitamin C)

Ascorbic acid is a water soluble vitamin and a powerful antioxidant.

It is a cofactor in numerous biological processes, such as the metabolism of folic acid, amino acid oxidation and the absorption and transport of iron.

It is also required for the formation, maintenance and repair of intercellular cement material. Ascorbic acid is important in the defence against infection, the normal functioning of T-lymphocytes and for the effective phagocytic activity of leucocytes. It also protects cells against oxidation damage to essential molecules.

Absorption

Vitamins A, B₁, B₂, B_6, C, D and nicotinamide are well absorbed from the gastro-intestinal tract.

Distribution

These vitamins are widely distributed to all tissues in the body.

Metabolism and Elimination

Vitamin A (palmitate)

Vitamin A (palmitate) is hydrolysed in the intestinal lumen to retinol which is then absorbed.

Retinol circulates in the blood bound to retinol binding protein which protects it from glomerular filtration.

The complex circulates to target tissues where the vitamin is released, permeates the cell and binds intracellularly to cellular retinol binding protein. Of the absorbed retinol 20 - 50% is either conjugated or oxidised to various products and excreted over a matter of days in the urine and faeces, while the remainder is stored. This stored retinol is gradually metabolised by the liver and peripheral tissues.

Vitamin D

The pharmacokinetics of vitamin D is also well known. Vitamin D is well absorbed from the gastro-intestinal tract in the presence of bile. It is hydroxylated in the liver to form
25-hydroxycholecalciferol and then undergoes further hydroxylation in the kidney to form the active metabolite 1, 25 dihydroxycholecalciferol (calcitriol). The metabolites circulate in the blood bound to a specific α - globin. Vitamin D and its metabolites are excreted mainly in the bile and faeces.

Thiamine (Vitamin B₁)

Thiamine has a plasma half life of 24 hours and is not stored to any great extent in the body. Excess ingested thiamine is excreted in the urine as either the free vitamin or as the metabolite, pyrimidine.

Riboflavin (Vitamin B₂)

Following absorption riboflavin is converted into the co-enzymes: flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD).

Riboflavin is not stored in body tissues to any great extent and amounts in excess of the body's requirements are excreted in the urine largely unchanged.

Pyridoxine (Vitamin B₆)

The half life of pyridoxine ranges from 15 - 20 days. Once absorbed vitamin B₆ is converted to its active co-enzyme form pyridoxal 5-phosphate. Muscle is the major storage site for pyridoxal 5-phosphate. It is degraded in the liver to 4-pyridoxic acid which is eliminated by the kidneys.

Nicotinamide

Nicotinamide is readily taken up into tissues and utilised for the synthesis of the
co-enzyme forms nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). Nicotinamide is degraded in the liver and other organs to a number of products that are excreted in the urine, the major metabolites being
n-methyl-2-pyridone-5-carboxamide and n-methylnicotinamide.

Ascorbic acid (Vitamin C)

Ascorbic acid reaches a maximum plasma concentration 4 hours following oral administration after which there is rapid urinary excretion. Following oral administration 60 % of the dose is excreted in 24 hours either as ascorbic acid or its metabolite dihydroascorbic acid.

Pharmacokinetics in Renal Impairment

No specific studies.

Pharmacokinetics in the Elderly

Not appropriate.

Mutagenicity

There is insufficient information to determine the mutagenic potential of the active ingredients. However very large doses of vitamin C are claimed to be mutagenic

Carcinogenicity

There is insufficient information to determine the carcinogenic potential of the active ingredients.

Teratogenicity

High doses of vitamin D are known to be teratogenic in experimental animals, but direct evidence for this is lacking in humans.

The teratogenicity of vitamin A in animals is well known, both high and low levels of the vitamin result in defects. But the significance of this for humans is in dispute. Synthetic versions of vitamin A (Isotretinoin and Etretinate) have been shown to be powerful teratogens.

There is insufficient information to determine the teratogenic potential of the other active ingredients.

Fertility

Not appropriate.

* Vitamin E used as antioxidant

None known

Store below 30^oC, protected from light.

·   15mL or 25mL solution in an amber coloured glass bottle with dropper, packed in a printed carton along with a leaflet.

No special requirements