Rovigon 30 chewable coated tablets

In ottemperanza all'articolo 118 “autorizzazione della pubblicità presso il pubblico” del decreto legislativo 24 aprile 2006, numero 219

INDICATIONS

Rovigon is indicated in all states of deficiency due to malabsorption, especially lipid, or malnutrition and related symptomatic pictures. Furthermore, Rovigon, as a balanced association between vitamin A and E, is indicated in functional disorders and degenerative manifestations of tissues of epithelial and mesodermal origin (for example degenerative retinopathies, inner ear disorders, etc.), especially in middle-aged and elderly people.

ACTIVE INGREDIENTS

One chewable coated tablet contains: retinol 30,000 IU (as vitamin A palmitate 1.7 MIU/g with BHA/BHT), dl–α–tocopheryl acetate 70 mg (as vitamin E 50 CWS/S). For the full list of excipients, see section 6.1.

EXCIPIENTS

Sucrose, anhydrous glucose, mannitol, cocoa powder, skimmed milk powder, cocoa butter, povidone K30, glycerol, ethyl vanillin, caramel flavouring, rice starch, talc, dried nebulised gum arabic, sodium carmellose, β-carotene (E 160a) 10% CWS, solid paraffin, light liquid paraffin.

CONTRAINDICATIONS AND SIDE EFFECTS

Hypersensitivity to the active substance or to any of the excipients. Hypervitaminosis A. Children under 12 years of age. Pregnant women or women who may become pregnant.

DOSAGE

For oral use. Unless otherwise prescribed by your doctor, the recommended dose is 1 tablet per day for a maximum of 4 weeks. The therapeutic cycle can be repeated throughout the year, at the discretion of the doctor. The dosage must be adjusted, based on serum levels of vitamin A and vitamin E. Rovigon is contraindicated in children under 12 years of age (see section 4.3).

CONSERVATION

This medicinal product does not require any special storage conditions.

WARNINGS

In order to avoid the appearance of signs and symptoms of overdose, use the product under medical supervision and for the period of time deemed strictly necessary. Preparations containing vitamin E must be used with caution in diabetics and in subjects with heart failure as this vitamin can reduce the need for insulin and digitalis. In very prolonged therapies, especially if for several years, do not exceed the number and duration of the therapeutic cycles recommended for each year, in order to avoid the risk of chronic overdose of vitamin A. Due to the presence of beta-carotene in the composition, prolonged use of the product can increase the risk of developing lung cancer in heavy smokers (twenty or more cigarettes a day). During pregnancy, a daily intake of vitamin A of up to 10,000 IU has been shown to be safe. However, doses higher than 15,000 IU/day have been associated with the possibility of malformations in humans. Therefore, during pregnancy, daily doses exceeding 10,000 IU should be avoided, especially during the first trimester (see also section 4.6). Vitamin A should not be taken together with other drugs containing vitamin A, the synthetic isomers tretinoin and etretinate or beta-carotene, since these compounds, in high doses, are considered harmful to the fetus. In women of childbearing age it is necessary to ensure that: • the patient is not pregnant when starting treatment (negative pregnancy test) • the patient understands the teratogenic risk • the patient agrees to adopt an effective contraceptive method without interruption for the entire duration of treatment and for at least one month after its cessation. Long-term treatments with vitamin A have been associated with cirrhosis, impaired hepatic circulation, hepatic fibrosis and hepatotoxicity. Patients with pre-existing liver disease are at greater risk of developing or worsening liver disease due to the reduced production capacity of retinol-binding protein. Patients taking high doses of vitamin A (above 2,500 IU/kg per day) for a prolonged period without interruption should be monitored for signs of hypervitaminosis A. A maximum daily dose of 5,000 IU/kg should not be exceeded. Before prescribing treatment, the intake of vitamin A, isotrenitoin, etretinate and beta-carotene deriving from the diet and the possible use of supplements and concomitant medications must be assessed. High doses of vitamin A have been associated with osteoporosis and osteosclerosis. This product contains sucrose and glucose. Patients with rare hereditary problems of fructose or galactose intolerance, lactase deficiency, glucose-galactose malabsorption or sucrase-isomaltase deficiency should not take this medicine.

INTERACTIONS

Vitamin E can enhance the action of digitalis or insulin. Avoid concomitant use with other drugs or supplements containing retinoids and with antibiotics belonging to the tetracycline class.

SIDE EFFECTS

The adverse reactions listed below derive from spontaneous reports and it is therefore not possible to organize them into frequency categories. Eye pathologies Visual disturbances. Gastrointestinal disorders Gastrointestinal and abdominal pain, nausea, vomiting, diarrhea. Hepatobiliary disorders Jaundice, hepatomegaly, hepatic steatosis. Cirrhosis, liver fibrosis and hepatotoxicity have been associated with long-term therapy with vitamin A (See section 4.4.). Immune system disorders Allergic reaction, allergic edema, anaphylactic reaction, anaphylactic shock. Hypersensitivity reactions and related clinical and laboratory manifestations include mild to moderate reactions that may affect the skin, respiratory tract, gastrointestinal system and cardiovascular system. Diagnostic tests Abnormal liver function tests, increased aspartate and alanine aminotransferase, increased blood triglycerides. Metabolism and nutrition disorders Hypercalcemia, disorder of lipid metabolism. Pathologies of the musculoskeletal system and connective tissue Bone pain and osteoporosis; High intake of vitamin A through diet or supplements has been associated with an increase in osteoporosis and the risk of hip fracture. Nervous system disorders Headache. A sudden onset of headache may be one of the symptoms of pseudotumor cerebri (see section 4.9). Pathologies of the skin and subcutaneous tissue Itching, urticaria, rash, dry skin, exfoliative dermatitis. The following have been associated with chronic use of vitamin A: alopecia, dermatitis, eczema, erythema, skin discoloration, changes in hair structure, hypotrichosis, dry mucous membranes, skin fragility, cheilitis. Skin changes are often among the first signs of hypervitaminosis A. Reporting of suspected adverse reactions Reporting suspected adverse reactions that occur after authorization of the medicine is important, as it allows continuous monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili.

OVERDOSE

Acute hypervitaminosis A: ingestion of excessive doses of retinol can cause acute vitamin A intoxication. Factors that influence acute retinol toxicity reactions include age, nutritional status, type of preparation taken and route of administration. However, the risk may increase in case of kidney or liver disease, low body weight, protein malnutrition, hyperlipoproteinemia, alcohol consumption or vitamin C deficiency. Acute retinol toxicity is characterized by intense headache, dizziness, hepatomegaly, vomiting, irritability, drowsiness and papilledema. After 24 hours, generalized desquamation of the skin may occur. Skin reactions associated with retinol toxicity include cheilitis, facial dermatitis, exfoliative dermatitis, dry mucous membranes, changes in hair texture, thinning hair, alopecia areata, generalized alopecia, rash, itching, skin fragility. Other manifestations of an acute massive overdose consist of gastrointestinal symptoms (abdominal pain, nausea, vomiting) and pseudotumor cerebri (increased intracranial pressure with the following symptoms: headache, dizziness, stupor, papilledema and, in newborns, transient protrusion of the fontanelles), followed within a few days by generalized skin desquamation. Generally, signs and symptoms of vitamin A toxicity disappear quickly upon cessation of intake. Chronic hypervitaminosis A: prolonged intake of vitamin A at daily doses of 10 to 20 times the maximum recommended levels can lead to the onset of hypervitaminosis A. The actual toxic dose depends on age, single doses and duration of administration. In adults, hypervitaminosis A generally results from chronic intake of more than 30 mg of retinol per day; however, mild symptoms may occur even with a chronic daily dietary intake of 10 mg of retinol. The symptoms of chronic vitamin A poisoning are varied and include headache, nausea and vomiting due to increased intracranial pressure, bone pain, signs and symptoms affecting the mucous membranes and skin, hepatomegaly, hypercalcemia, hematological alterations. Dry and itchy skin, erythematous dermatitis, fissuring of the lips, anorexia, edema, hemorrhage, irritability and asthenia may also occur. Other possible symptoms are night sweats, abdominal discomfort, growth retardation, premature closure of the epiphyses, dizziness, alopecia, skin flaking, increased skin pigmentation, inflammation of the tongue, lips and gums. Hepatotoxic reactions are present in approximately half of cases of chronic hypervitaminosis A. In addition to clinical signs, such as hepatosplenomegaly, stellate angioma, leukonychia, palmar erythema and jaundice, an increase in hepatic transaminases (aspartate and alanine aminotransferase) is observed. The increase in alkaline phosphatase may be very marked and there may be cholestasis with hyperbilirubinemia. A reversible syndrome of portal hypertension with ascites may occur. Histopathological features include stellate (Ito) cell hypertrophy and hyperplasia with perisinusoidal lipocyte accumulations associated with fibrosis. Hepatocyte atrophy and cirrhosis have been reported. It is also possible to find a picture of hepatitis and steatosis. Risk may be increased in cases of kidney or liver disease, low body weight, protein malnutrition, hyperlipoproteinemia, alcohol consumption, or vitamin C deficiency. The only diagnostic laboratory finding is increased serum retinol levels, primarily in the form of retinyl esters. The concentration of retinol binding protein (RBP) is normal and excess retinol circulates bound to a lipoprotein. Generally, the signs and symptoms of vitamin A toxicity remit quickly once intake is stopped. In patients with impaired liver function and hepatomegaly the prognosis is usually favorable. However, if portal hypertension with ascites has developed, the syndrome may persist. Vitamin E overdose: Vitamin E is usually non-toxic. However, high doses (more than 300 units per day) have caused, in rare cases, nausea, diarrhea, intestinal cramps, asthenia, weakness, headache, blurred vision, rash, gonadal dysfunction, creatinuria, increased serum levels of creatinine kinase and creatinine phosphokinase, increased serum cholesterol and triglycerides, increased urinary estrogens and androgens, and decreased serum levels of thyroxine and triiodothyronine. These effects disappeared when treatment was discontinued. A meta-analysis found that, in patients with chronic disease, doses equal to or greater than 400 units per day for a year or more were associated with an increase in mortality from any cause. The results of this data analysis were unclear about the risks and benefits of lower vitamin E doses. However, a dose–response analysis demonstrated a statistically significant relationship between vitamin E dosage and all-cause mortality, with an increased risk at doses above 150 units. These conclusions are controversial and still constitute a topic of debate in the medical and scientific community. Very high doses of vitamin E (above 800 units per day for long periods) have also been associated with increased bleeding tendency in patients with vitamin K deficiency, alterations in hormonal metabolism (thyroid, pituitary and adrenal), alterations in the immune response and compromised sexual function and may increase the thromboembolic risk in predisposed patients.

PREGNANCY AND BREASTFEEDING

Pregnancy During pregnancy, a daily intake of vitamin A of up to 10,000 IU has been shown to be safe. However, doses higher than 15,000 IU/day have been associated with the possibility of malformations in humans. Therefore, during pregnancy, daily dosages exceeding 10,000 IU should be avoided, especially during the first trimester. Vitamin A should not be taken together with other drugs containing vitamin A, the synthetic isomers tretinoin and etretinate or beta-carotene, since these compounds, in high doses, are considered harmful to the fetus. In women of childbearing age it is necessary to ensure that: • the patient is not pregnant when starting treatment (negative pregnancy test) • the patient understands the teratogenic risk • the patient agrees to adopt an effective contraceptive method without interruption for the entire duration of treatment and for at least one month after its cessation. Breastfeeding There is no adequate information available on the excretion of vitamin A and vitamin E in human and animal breast milk and a risk for the infant cannot therefore be excluded. The decision whether to discontinue breastfeeding or retinol/tocopherol therapy should be made taking into account the benefit of breastfeeding for the newborn and the benefit of retinol/tocopherol therapy for the mother.

EFFECTS ON DRIVING ABILITY

The product may cause visual disturbances. If this occurs, do not drive or operate machinery.