Intafol-D

Mecobalamin (Intafol-D) also contains the following inactive ingredients: Lactose, maize starch, microcrystalline cellulose, povidone (K-30), purified talc, anhydrous colloidal silica, hypromellose, macrogol, titanium dioxide, isopropyl alcohol, dicholoromethane, red iron oxide and yellow iron oxide.

Vitamin D3 (Intafol-D) (Vitamin D2) is a derivative of ergosterol formed by ultraviolet rays breaking of the C9-C10 bond. It differs from cholecalciferol in having a double bond between C22 and C23 and a methyl group at C24.

Oral

Nutritional supplementation

Adult: Usual dose range: 125-250 mg 1-2 times daily. Dosing instruction may vary according to the product used.

Mecobalamin (Intafol-D) (doxacurium chloride) is a long-acting neuromuscular blocking agent, indicated to provide skeletal muscle relaxation as an adjunct to general anesthesia, for endotracheal intubation or to facilitate mechanical ventilation.

Vitamin D3 (Intafol-D) has an important role in energize the intestinal absorption for calcium and phosphor, to regulate their metabolism and balance in blood. It helps bone calcification. Deficiency of Vitamin D3 (Intafol-D) in the body causes deficiency of the calcium in the bone, weakness of its resistance and deformity.

Cholecalciferol is a Vitamin D3 (Intafol-D). Vitamin D is important for the absorption of calcium from the stomach and for the functioning of calcium in the body.

Cholecalciferol is used to treat or prevent many conditions caused by a lack of vitamin D, especially conditions of the skin or bones.

Cholecalciferol may also be used for purposes not listed in this medication guide.

Oral

Nutritional supplementation

Adult: Usual dose range: 125-250 mg 1-2 times daily. Dosing instruction may vary according to the product used.

Mecobalamin (Intafol-D) SHOULD ONLY BE ADMINISTERED INTRAVENOUSLY.

Mecobalamin (Intafol-D), like other long-acting neuromuscular blocking agents, displays variability in the duration of its effect. The potential for a prolonged clinical duration of neuromuscular block must be considered when Mecobalamin (Intafol-D) is selected for administration. The dosage information provided below is intended as a guide only. Doses should be individualized. Factors that may warrant dosage adjustment include: advancing age, the presence of kidney or liver disease, or obesity (patients weighing ≥ 30% more than ideal body weight for height). The use of a peripheral nerve stimulator will permit the most advantageous use of Mecobalamin (Intafol-D), minimize the possibility of overdosage or underdosage, and assist in the evaluation of recovery.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Adults

Initial Doses

When administered as a component of a thiopental/narcotic induction-intubation paradigm as well as for production of long-duration neuromuscular block during surgery, 0.05 mg/kg (2 × ED95) Mecobalamin (Intafol-D) produces good-to-excellent conditions for tracheal intubation in 5 minutes in approximately 90% of patients. Lower doses of Mecobalamin (Intafol-D) may result in a longer time for development of satisfactory intubation conditions. Clinically effective neuromuscular block may be expected to last approximately 100 minutes on average (range: 39 to 232) following 0.05 mg/kg Mecobalamin (Intafol-D) administered to patients receiving balanced anesthesia.

An initial Mecobalamin (Intafol-D) dose of 0.08 mg/kg (3 × ED95) should be reserved for instances in which a need for very prolonged neuromuscular block is anticipated. In approximately 90% of patients, good-to-excellent intubation conditions may be expected in 4 minutes after this dose; however, clinically effective block may be expected to persist for as long as 160 minutes or more (range: 110 to 338).

If Mecobalamin (Intafol-D) is administered during steady-state isoflurane, enflurane, or halothane anesthesia, reduction of the dose of Mecobalamin (Intafol-D) by one third should be considered.

When succinylcholine is administered to facilitate tracheal intubation in patients receiving balanced anesthesia, an initial dose of 0.025 mg/kg (ED95) Mecobalamin (Intafol-D) provides about 60 minutes (range: 9 to 145) of clinically effective neuromuscular block for surgery. For a longer duration of action, a larger initial dose may be administered.

Maintenance Doses

Maintenance dosing will generally be required about 60 minutes after an initial dose of 0.025 mg/kg Mecobalamin (Intafol-D) or 100 minutes after an initial dose of 0.05 mg/kg Mecobalamin (Intafol-D) during balanced anesthesia. Repeated maintenance doses administered at 25% T1 recovery may be expected to be required at relatively regular intervals in each patient. The interval may vary considerably between patients. Maintenance doses of 0.005 and 0.01 mg/kg Mecobalamin (Intafol-D) each provide an average 30 minutes (range: 9 to 57) and 45 minutes (range: 14 to 108), respectively, of additional clinically effective neuromuscular block. For shorter or longer desired durations, smaller or larger maintenance doses may be administered.

Children

When administered during halothane anesthesia, an initial dose of 0.03 mg/kg (ED95) produces maximum neuromuscular block in about 7 minutes (range: 5 to 11) and clinically effective block for an average of 30 minutes (range: 12 to 54). Under halothane anesthesia, 0.05 mg/kg produces maximum block in about 4 minutes (range: 2 to 10) and clinically effective block for 45 minutes (range: 30 to 80). Maintenance doses are generally required more frequently in children than in adults. Because of the potentiating effect of halothane seen in adults, a higher dose of Mecobalamin (Intafol-D) may be required in children receiving balanced anesthesia than in children receiving halothane anesthesia to achieve a comparable onset and duration of neuromuscular block. Mecobalamin (Intafol-D) has not been studied in pediatric patients below the age of 2 years.

Compatibility

Y-site Administration

Mecobalamin (Intafol-D) Injection may not be compatible with alkaline solutions with a pH greater than 8.5 (e.g., barbiturate solutions).

Mecobalamin (Intafol-D) is compatible with:

• 5% Dextrose Injection, USP
• 0.9% Sodium Chloride Injection, USP
• 5% Dextrose and 0.9% Sodium Chloride Injection, USP
• Lactated Ringer's Injection, USP
• 5% Dextrose and Lactated Ringer's Injection
• Sufenta® (sufentanil citrate) Injection, diluted as directed
• Alfenta® (alfentanil hydrochloride) Injection, diluted as directed
• Sublimaze® (fentanyl citrate) Injection, diluted as directed

Mecobalamin (Intafol-D) diluted up to 1:10 in 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP has been shown to be physically and chemically stable when stored in polypropylene syringes at 5° to 25°C (41° to 77°F), for up to 24 hours. Since dilution diminishes the preservative effectiveness of benzyl alcohol, aseptic techniques should be used to prepare the diluted product. Immediate use of the diluted product is preferred, and any unused portion of diluted Mecobalamin (Intafol-D) should be discarded after 8 hours.

1 tab daily.

Mecobalamin (Intafol-D) (doxacurium chloride) is contraindicated in patients with known hypersensitivity to the product and its components. Mecobalamin (Intafol-D) (doxacurium chloride) is contraindicated for use in premature infants because the formulation contains benzyl alcohol.

Contraindications for vitamin D analogues (Vitamin D2, Vitamin D3 (Intafol-D), Calcitriol, and Calcidiol)

Vitamin D should not be given to patients with hypercalcemia or evidence of vitamin D toxicity. Use of vitamin D in patients with known hypersensitivity to vitamin D (or drugs of the same class) or any of the inactive ingredients is contraindicated.

Docosahexaenoic acid (Intafol-D) (DHA) is used to prevent age related macular degeneration (loss of vision due to aging), coronary artery disease (blockage in arteries supplying blood to the heart), high cholesterol, type II diabetes, attention deficit hyperactive disorder (a type of brain disorder in which there are problems paying attention, excessive activity or difficulty controlling behavior), stroke, menstrual pain (dysmenorrhea) and memory disorders. DHA in combination with Eicosapentaenoic acid (EPA) is prescribed for the treatment of heart diseases, bipolar disorders (a mental condition marked by alternating periods of elation and depression), rheumatoid arthritis (a chronic progressive disease causing inflammation in the joints), renal diseases, Systemic lupus erythematosus (a type of autoimmune disorder), asthma and ulcerative colitis (disease causing inflammation and ulcer in the colon).

Vitamin D3 (Intafol-D) is used for the prevention and treatment of vitamin D deficiency. Vitamin D3 (Intafol-D) is important for absorption of calcium in the body. It is also used to prevent bone disorders such as osteomalacia and rickets.

Monitor prothrombin time when used with anticoagulant medications (including warfarin), aspirin or aspirin-containing products, NSAIDs, antiplatelet agents (e.g. ticlopidine, clopidogrel, dipyridamole). May increase hypotension when used with antihypertensive medications.

Antibiotics: The use of antibiotics may alter the intestinal microflora and may decrease the possible contribution of Mecobalamin (Intafol-D) by certain inhabitants of the microflora (eg, Lactobacillus spp) to the body's requirement for the vitamin. This may particularly be a problem for vegetarians. Garlic, onions, leeks, bananas, asparagus and artichokes, among other vegetables and fruits, contain inulins which promote the growth of certain colonic bacteria including Lactobacillus spp.

Cholestyramine:

Colchicine: Colchicine may cause decreased absorption of Mecobalamin (Intafol-D).

Colestipol:

H₂-Blockers (Cimetidine, Famotidine, Nizatidine, Ranitidine): Chronic use of H₂-blockers may result to decreased absorption of Mecobalamin (Intafol-D). They are unlikely to affect the absorption of supplemental B₁₂.

Metformin: Metformin may decrease the absorption of Mecobalamin (Intafol-D). This possible effect may be reversed with oral calcium supplementation.

Nitrous Oxide: Inhalation of the anesthetic agent nitrous oxide (not to be confused with nitric oxide) can produce a functional deficiency. Nitrous oxide forms a complex with cobalt in Mecobalamin (Intafol-D), the cofactor for methionine synthase, resulting in inactivation of the enzyme.

Para-Amino Salicylic Acid: Chronic use of the anti-tuberculosis drug may decrease the absorption of Mecobalamin (Intafol-D).

Potassium Chloride: It has been reported that potassium chloride may decrease the absorption of Mecobalamin (Intafol-D).

Proton Pump Inhibitors (Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole): Chronic use of proton pump inhibitors may result in decreased absorption, naturally found in food sources.

Interactions for vitamin D analogues (Vitamin D2, Vitamin D3 (Intafol-D), Calcitriol, and Calcidiol)

Cholestyramine

Cholestyramine has been reported to reduce intestinal absorption of fat soluble vitamins; as such it may impair intestinal absorption of any of vitamin D

Phenytoin/Phenobarbital

The coadministration of phenytoin or phenobarbital will not affect plasma concentrations of vitamin D, but may reduce endogenous plasma levels of calcitriol/ergocalcitriol by accelerating metabolism. Since blood level of calcitriol/ergocalcitriol will be reduced, higher doses of Rocaltrol may be necessary if these drugs are administered simultaneously

Thiazides

Thiazides are known to induce hypercalcemia by the reduction of calcium excretion in urine. Some reports have shown that the concomitant administration of thiazides with vitamin D causes hypercalcemia. Therefore, precaution should be taken when coadministration is necessary

Digitalis

Vitamin D dosage must be determined with care in patients undergoing treatment with digitalis, as hypercalcemia in such patients may precipitate cardiac arrhythmias

Ketoconazole

Ketoconazole may inhibit both synthetic and catabolic enzymes of vitamin D. Reductions in serum endogenous vitamin D concentrations have been observed following the administration of 300 mg/day to 1200 mg/day ketoconazole for a week to healthy men. However, in vivo drug interaction studies of ketoconazole with vitamin D have not been investigated

Corticosteroids

A relationship of functional antagonism exists between vitamin D analogues, which promote calcium absorption, and corticosteroids, which inhibit calcium absorption

Phosphate-Binding Agents

Since vitamin D also has an effect on phosphate transport in the intestine, kidneys and bones, the dosage of phosphate-binding agents must be adjusted in accordance with the serum phosphate concentration

Vitamin D

The coadministration of any of the vitamin D analogues should be avoided as this could create possible additive effects and hypercalcemia

Calcium Supplements

Uncontrolled intake of additional calcium-containing preparations should be avoided

Magnesium

Magnesium-containing preparations (eg, antacids) may cause hypermagnesemia and should therefore not be taken during therapy with vitamin D by patients on chronic renal dialysis.

GI disturbances (especially at high doses) e.g. nausea, eructation, vomiting, abdominal distension, diarrhoea and constipation.

The most frequent adverse effect of nondepolarizing blocking agents as a class consists of an extension of the pharmacological action beyond the time needed for surgery and anesthesia. This effect may vary from skeletal muscle weakness to profound and prolonged skeletal muscle paralysis resulting in respiratory insufficiency and apnea which require manual or mechanical ventilation until recovery is judged to be clinically adequate. Inadequate reversal of neuromuscular block from Mecobalamin (Intafol-D) (doxacurium chloride) is possible, as with all nondepolarizing agents. Prolonged neuromuscular block and inadequate reversal may lead to postoperative complications.

Observed in Clinical Trials

Adverse experiences were uncommon among the 1034 surgical patients and volunteers who received Mecobalamin (Intafol-D) (doxacurium chloride) and other drugs in US clinical studies in the course of a wide variety of procedures conducted during balanced or inhalational anesthesia. The following adverse experiences were reported in patients administered Mecobalamin (Intafol-D) (doxacurium chloride) (all events judged by investigators during the clinical trials to have a possible causal relationship):

Incidence Greater than 1%

None

Incidence Less than 1%

Observed During Clinical Practice

There have been post-marketing reports of severe allergic reactions (anaphylactic and anaphylactoid reactions) with the use of neuromuscular blocking agents of which Mecobalamin (Intafol-D) (doxacurium chloride) is a member. These reactions, in some cases, have been life threatening and fatal. Because these reactions were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency.

Applies to cholecalciferol: oral capsule, oral capsule liquid filled, oral solution, oral tablet, oral tablet chewable, oral wafer

As well as its needed effects, cholecalciferol (the active ingredient contained in Vitamin D3 (Intafol-D)) may cause unwanted side effects that require medical attention.

Major Side Effects

If any of the following side effects occur while taking cholecalciferol, check with your doctor immediately:

Incidence not known:

• Cough
• difficulty swallowing
• dizziness
• fast heartbeat
• hives or itching
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• skin rash
• tightness in the chest
• unusual tiredness or weakness