Cilnidipine 10 mg/Valsartan 80 mg

DESCRIPTION

ATEDIO combination tablets is a pale-yellow elliptic film-coated tablet formulation containing per tablet 80 mg of valsartan and 10 mg of cilnidipine.

COMPOSITION

ATEDIO combination tablets contain magnesium aluminometasilicate, microcrystalline cellulose, lactose hydrate, macrogol 400, croscarmellose sodium, hydroxypropyl cellulose, hypromellose phthalate ester, hydrous silicon dioxide, magnesium stearate, hypromellose, macrogol 6000, titanium dioxide, yellow iron sesquioxide, and carnauba wax as additives.

INDICATIONS

Hypertension

DOSAGE AND ADMINISTRATION

Dosage The adult dose of ATEDIO combination tablet is one tablet once daily (80 mg as valsartan and 10 mg as cilnidipine) administered orally after breakfast. Do not use ATEDIO combination tablet as the first-line drug for hypertensive therapy.

ADVERSE REACTIONS

Japanese clinical studies that had been conducted by date of approval reported adverse reactions, including laboratory abnormalities in 55 of 459 patients (120%). The main adverse reactions were hyperuricemia in 6 patients (1.3%) and increased ALT (GPT) in 5 patients (1.1%). Clinically significant adverse reaction such as angioedema, hepatitis, hepatic dysfunction, jaundice, renal failure, hyperkalemia, shock, syncope, loss of consciousness, agranulocytosis, decreased white blood cells, decreased platelets, interstitial pneumonia, hypoglycemia, rhabdomyolysis, toxic epidermal necrolysis (TEN), oculomucocutaneous syndrome (Stevens-Johnson syndrome), erythema multiforme, pemphigus, pemphigoid were frequently unknown. Other adverse reactions were if any of the following adverse reactions occur, appropriate measures should be taken depending on the symptoms: abnormal hepatic function, increased ALT (GPT), increased AST (GOT), hyperuricemia, headache, facial flushing (hot flashes), constipation, increased blood potassium, hyperlipidemia (increased blood cholesterol, increased triglycerides).

CONTRAINDICATIONS

Do not administer ATEDIO combination tablet to the following patients: 1. Patients with a history of hypersensitivity to any of the ingredients of ATEDIO combination tablet. 2. Pregnant women or women having possibilities of being pregnant (see the section “Use During Pregnancy, Delivery, or lactation”). 3. Patients with diabetes mellitus who are receiving aliskiren (except patients with extremely poor blood pressure control with other hypotensive therapies) (An increase in the risks of nonfatal stroke, renal dysfunction, hyperkalemia, and hypotension has been reported).

PRECAUTIONS

(Precautions related to Indications) Do not use ATEDIO combination tablet as the first-line drug because it may cause an excessive decrease in blood pressure. (Precautions related to Dosage and Administration) 1. The use of ATEDIO combination tablet should be considered patient by patient on the basis of the following dosages and administrations of valsartan and cilnidipine: Valsartan: The usual adult dose is 40 to 80 mg as valsartan administered orally once daily. The dose should be adjusted appropriately depending on age and symptoms and may be increased up to 160 mg daily. Cilnidipine: Usually, for adults, 5 to 10 mg is administered as cilnidipine for orally once a day after breakfast. The dosage may be adjusted according to the patient’s age and symptoms. The dose can be increased up to 20 mg once a day, if a sufficient response does not appear. For adults with severe hypertension, ATELEC tablet should be administered 10 to 20 mg once a day for oral use after breakfast. 2. In principle, consider switching to ATEDIO combination tablet in cases in which the patient has a combination of valsartan 80 mg and cilnidipine 10 mg or blood pressure control is inadequate with either of these drugs.

Use during Pregnancy, Delivery, or Lactation (1) ATEDIO combination tablet should not be administered to pregnant women or women having possibilities of being pregnant. Discontinue administration immediately if the patient is found to be pregnant during treatment. (It has been reported that angiotensin II receptor antagonists and angiotensin converting enzyme inhibitors including valsartan caused fetal and neonatal death, oligohydramnios, fetal and neonatal hypotension, renal failure, hyperkalemia, cranial aplasia, extremity contracture presumed to be due to oligohydramnios, brain and craniofacial malformation, and hypoplasia and aplasia of the lungs in patients who received those drugs during the second to third trimester pregnancy. In addition, a retrospective epidemiological study of angiotensin converting enzyme inhibitors conducted overseas has reported that the relative risk of fetal malformation was higher in the patient group that received angiotensin converting enzyme inhibitors during the first trimester than in the patient group that received no antihypertensive drug. In addition, it has been reported that cilnidipine prolongs the gestation period and delivery time in animal experiments in rats. (2). It is advisable to avoid the administration of ATEDIO combination tablet to nursing mothers.

OVERDOSES AND TREATMENT

1. Signs and Symptoms: No information is available about an overdose of ATEDIO combination tablet. The overdose of valsartan, a component of ATEDIO combination tablet, may cause a marked decrease in blood pressure, leading to a depressed level of consciousness and circulatory collapse.

2. Treatments The following treatments should generally be taken: (1) Forced emesis and administration of activated charcoal (2) In the case of marked hypotension, immediately take appropriate measures, such as intravenous injection of physiological saline with the patient in the supine position. Note: Valsartan cannot be removed by hemodialysis because 93% or more of valsartan is bound to plasma protein.

PACKAGING

Box of 10 blisters x 10 tablets

STORAGE

Store below 30°C

SHELF-LIFE

36 months from manufacturing date.

Amino Acid Infusion for general well-being - 200 ml

DESCRIPTION

1. Composition: MORIAMIN-Ace contains the following ingredients : L-Isoleucine 1.820 g, L-Leusine 2.580 g, L-Lysine acetate 2.000 g, L-Methionine 0.880 g, L-Phenylalanine 1.400 g, L-Threonine 1.500 g, L-Tryptophan 0.260 g, L-Valine 2.800 g, L-Alanine 1.420 g, L-Arginine 1.800 g, L-Aspartic acid 0.200 g, L-Cysteine 0.070 g, L-Glutamic acid 0.100 g, L-Histidine 1.000 g, L-Proline 1.000 g, L-Serine 0.340 g, L-Tyrosine 0.080 g, Glycine 1.400 g, Total Amino Acid content: 20.650 g, Amino acid concentration: 10.325 w/v%, Sodium bisulfite: 0.060 g, Glacial acetic acid (pH adjuster): proper, Total nitrogen content: 15.2 mg/ml, Total free amino acid concentration: 10.035 w/v%, Branched chain amino acid concentration: 35.9 w/v%, EAA/NEAA: 1.71, Electrolytes Na+: <2.9 mEq/L, CH3COO-: ca. 80 mEq/L.

2. Product description: MORIAMIN-Ace is a clear and colorless aqueous solution. The pH and osmotic pressure ratio are as follow: pH 6.8-7.8, Osmotic pressure ratio Approx. 3.

3. Description containers (plastic bag): The standard of bag being used is as follows: 200 ml plastic bag, Reserve capacity of plastic bag Approx. 250 ml.

INDICATIONS

MORIAMIN-Ace is indicated for supply of amino acid in the following condition: Hypoproteinemia, Malnutrition, Pre- and Post-operation.

DOSAGE AND ADMINISTRATION

1. Administer into the peripheral vein: usually 200-400 ml is given slowly by an intravenous drip at a time for an adult. The speed of administration is preferably ca. 10g amino acids in 60 min. for their utilization in the body, usually on the standard of 200ml in ca. 120 min. for an adult, and more slowly for a child, elderly and serious patient. It may be adjusted properly depending on the age, symptom and body weight. It is desirable to be administered simultaneously with a saccharide infusion for the efficient utilization of amino acid in the body.

2. Administer into the central vein: usually 400-800 ml is given into the central vein by a continuous drip in a day for an adult by means of total parenteral nutrition. It may be adjusted properly depending on the age, symptom and body weight.

CONTRAINDICATIONS

MORIAMIN-Ace is contraindicated in the following patients:
1. Patients with hepatic coma or possibility of hepatic coma (it is possible to promote amino acid imbalance and aggravate or induce hepatic coma).
2. Patients with serious kidney disorders or azotemia (it is possible to aggravate symptoms due to nitrogen load).
3. Patients with amino acid metabolism abnormality (it is possible to promote amino acid imbalance).

PRECAUTIONS

MORIAMIN-Ace should be administered with caution in the following patients:
(1) Patients with serious acidosis (it is possible to aggravate acidosis by administration of large dose).
(2) Patients with congestive heart failure (it is possible to increase cardiac load due to an increase of the circulating blood volume).
(3) Patients with hyponatremia (Since this product scarcely contains sodium, it is possible to aggravate hyponatremia).

ADVERSE REACTIONS

Out of a total of 2,668 patients, 16 cases in 12 patients (0.45%) presented adverse reactions in including abnormality on laboratory values. The primary reactions were 5 cases of nausea (0.19%), 2 cases of vomiting (0.08%), 2 cases of hepatic functional disorder (0.08%), 1 case of vascular pain (0.04%) and 1 case of chest discomfort (0.04%).

Use in the Elderly: Since the elderly often have a physiological hypofunction, it is advisable to take such measures as the reduction in the administration speed or dose under careful supervision.

Use during Pregnancy, Delivery or Lactation: (1) The product should only be used in pregnant women, women suspected of being pregnant, and nursing mothers, provided that the expected therapeutic benefits are evaluated to outweight the possible risk of treatment. (Safety of the product in pregnant women and nursing mothers has not been established). (2) It is desirous not to administer to women who are nursing. If administration is unavoidable, avoid nursing (Safety during nursing has not been established).

Pediatric Use: Safety in children has not been established (few clinical experiences).

PACKING SIZE

Box of 30 bags x 200 ml

STORAGE

Store below 30°C

SHELF-LIFE

36 months from the manufacturing date. The product should be used before the expiration date specified on the outer package and plastic bag.

Amino Acid Infusion for Renal Failure - 200 ml

DESCRIPTION

1. Composition: NEOAMIYU contains the following ingredients : L-Isoleucine 1.500 g, L-Leusine 2.000 g, L-Lysine acetate 1.400 g, L-Methionine 1.000 g, L-Phenylalanine 1.000 g, L-Threonine 0.500 g, L-Tryptophan 0.500 g, L-Valine 1.500 g, L-Alanine 0.600 g, L-Arginine 0.600 g, L-Aspartic acid 0.050 g, L-Cysteine 0.050 g, L-Glutamic acid 0.050 g, L-Histidine 0.500 g, L-Proline 0.400 g, L-Serine 0.200 g, L-Tyrosine 0.100 g, Glycine 0.300 g, Total Amino Acid content: 12.250 g, Total Amino acid concentration: 6.100 w/v%, Sodium hydrogen sulfite: 0.050 g, Glacial acetic acid (pH adjuster): q.s, Total nitrogen content: 8.1 mg/ml, Total free amino acid concentration: 5.90 w/v%, EAA/NEAA: 3.21, Electrolytes: Na+: ca. 2 mEq/L, CH3COO-: ca. 47 mEq/L.

2. Product description: NEOAMIYU is a clear and colorless aqueous solution for infusion. The pH and osmotic pressure ratio are as follow: pH 6.6-7.6, Osmotic pressure ratio Approx. 2.

3. Description containers (plastic bag): The standard of bag being used is as follows: 200 ml plastic bag, Reserve capacity of plastic bag Approx. 250 ml.

INDICATIONS

NEOAMIYU is indicated for the provision of amino acid in the following instances in patients with acute or chronic renal failure: hypoproteinemia, malnutrition, and before and after surgery.

DOSAGE AND ADMINISTRATION

1. Chronic Renal Failure
(1). When administered via a peripheral intravenous line in adults, NEOAMIYU should be injected slowly at 200 ml once daily in patients with chronic renal failure. The usual intravenous infusion rate is 120 to 180 min. per 200 ml, and a slower rate is recommended for children, elderly patients, and patients with a serious condition. The dose may be adjusted according to the patient’s age, condition, and body weight. In patients on dialysis, NEOAMIYU should be injected into the venous side of the dialysis circuit from 90 to 60 minutes before completion of dialysis. Regarding calories, more than 1500 kcal per day is recommended to be provided for the efficiency of amino acid utilization.

(2). When administered via total parenteral nutrition in adults, NEOAMIYU should be injected in the central vein by intravenous drip at 400 ml once daily. The dose may be adjusted according to the patient’s age, condition, and body weight. More than 500 kcal of nonprotein calories should be administered per 1.6 g of nitrogen (200 ml of this product) for the efficiency of amino acid utilization.

2. Acute Renal Failure
In adults, NEOAMIYU should be administered via total parenteral nutrition in the central vein by intravenous drip at 400 ml once daily. The dose may be adjusted according to the patient’s age, condition, and body weight. More than 500 kcal of nonprotein calories should be administered per 1.6 g of nitrogen (200 ml of this product) for the efficiency of amino acid utilization.

PRECAUTIONS

1. Careful Administration (NEOAMIYU should be administered with caution in the following patients.)
(1). Patients with impaired cardiovascular function (The use of the product is associated with increased amount of blood circulation, which may lead to overload of the heart and resultant aggravation of the patient’s condition).
(2). Patients with impaired hepatic function or gastrointestinal hemorrhage (Excessive accumulation of amino acids or hyperammonemia may develop with the use of the product).
(3). Patients with marked electrolyte abnormality or abnormal acid-base balance (The patient’s condition may aggravate with the use of the product).

2. Important Precautions
(1). NEOAMIYU should be used in patients who need parenteral nutrition due to inability or insufficience of oral food intake.
(2). It has been reported that the use of essential amino acid products for renal failure may be associated with hyperammonemia or loss of consciousness if these products are used as the only source of nitrogen. Therefore, the use of this products should be discontinued immediately if poor response to voice or other abnormalities such as decreased spontaneous speech and activities are noted during treatment.

ADVERSE REACTIONS

In clinical studies of NEOAMIYU, 15 adverse reactions (4.7%) were reported in 10 (3.1%) of 318 patients. At the time of approval of the drug, main adverse reactions included nausea queasy (1.9%), vomiting (0.6%), headache (0.6%), and metabolic acidosis (0.6%). Abnormal laboratory changes included decreased bicarbonate ion level 3 events (0.9%), increased AST (GOT) 1 event (0.3%), and increased blood ammonia level 1 event (0.3%). (As of the end of approval) In post-marketing surveillance, adverse reactions (including abnormal laboratory changes) were reported in 98 (3.34%) of 2,936 patients. Main adverse reactions included increased blood urea nitrogen 23 events (0.78%), increased AST (GOT) 20 events (0.68%), increased ALT (GPT) 17 events (0.58%), hepatic disorder 13 events (0.44%), nausea 11 events (0.37%), increased blood creatinine level 8 events (0.27%), hyperammonemia 7 events (0.24%), metabolic acidosis 6 events (0.20%), vomiting 4 events (0.14%), and anorexia 4 events (0.14%). (As of the end of the re-examination)

Use in the Elderly: Since the elderly have a physiological hypofunction in general, NEOAMIYU should be carefully administered, such as reducing the dose.

Use during Pregnancy, Delivery or Lactation:
(1). NEOAMIYU should be used in pregnant women or women having possibilities of being pregnant only if the expected therapeutic benefit is evaluated to outweigh the possible risks. (The safety of this product in pregnant women has not been established.)
(2). Use of NEOAMIYU in nursing mothers is not recommended. If use of NEOAMIYU is judged to be essential, breast feeding must be discontinued during treatment. (The safety of this product in nursing mothers has not been established.)

Pediatric Use:
(1). The safety of NEOAMIYU in children has not been established. (No sufficient clinical data has been available in this population.)
(2). Infants, especially low birth weight babies and neonates, have immature amino acid metabolism. Caution should be exercised if NEOAMIYU is used in such patients, by monitoring the patient’s clinical condition and laboratory results, as well as administrating the product at a slower rate and a reduced dose.

CONTRAINDICATIONS

NEOAMIYU is contraindicated in the following patients:
1. Patients with hepatic coma or possibility of hepatic coma (it is possible to promote amino acid imbalance and aggravate or induce hepatic coma).
2. Patients with hyperammonemia (Hyperammonemia may aggravate due to nitrogen overload).
3. Patients with congenital amino acid metabolism abnormality (The condition may aggravate due to failure of the metabolism of amino acid administered).

PACKING SIZE

Box of 30 bags x 200 ml

STORAGE

Store below 30°C

SHELF-LIFE

36 months from the manufacturing date. The product should be used before the expiration date specified on the outer package and plastic bag.

Amino Acid Infusion for Hepatic Encephalopathy - 200 ml

DESCRIPTION

1. Composition: MORIHEPAMIN contains the following ingredients : L-Isoleucine 1.840 g, L-Leusine 1.890 g, L-Lysine acetate 0.790 g, L-Methionine 0.880 g, L-Phenylalanine 0.060 g, L-Threonine 0.428 g, L-Tryptophan 0.140 g, L-Valine 1.780 g, L-Alanine 1.680 g, L-Arginine 3.074 g, L-Aspartic acid 0.040 g, L-Cysteine 0.050 g, L-Histidine 0.620g, L-Proline 1.060 g, L-Serine 0.520 g, L-Tyrosine 0.080 g, Glycine 1.080 g, Total Amino Acid content: 15.170 g, Amino acid concentration: 7.585 w/v%, Sodium bisulfite: 0.050 g, Glacial acetic acid (pH adjuster): proper, Total nitrogen content: 13.18 mg/ml, Total free amino acid concentration: 7.470 w/v%, Branched chain amino acid concentration: 2.755 w/v%, Fischer’s ratio: 54.13, Electrolytes Na+: Approx. 3 mEq/L, CH3COO-: Approx. 100 mEq/L.

2.Product description: MORIHEPAMIN is a clear and colorless aqueous solution. The pH and osmotic pressure ratio are as follow: pH 6.6-7.6, Osmotic pressure ratio Approx. 3.

INDICATIONS

MORIHEPAMIN is indicated for supportive treatment for hepatic encephalopathy syndrome in patients with chronic liver disorder.

DOSAGE AND ADMINISTRATION

MORIHEPAMIN is usually intravenously drip-infused at a single dose of 500 ml in adult patients. The standard infusion rate in adults is 180 minutes or longer per 500 ml. If MORIHEPAMIN is administered via a central venous line, a 500 ml of MORIHEPAMIN should be mixed with carbohydrate-containing solution and be infused continuously via a central vein for 24 hours. The dosage may be adjusted according to the patient’s age, symptoms and body weight.

ADVERSE REACTIONS

Among 243 cases studied prior to the time of approval, 9 adverse reactions (3.7%) were reported in 9 cases (3.7%). The commonly reported adverse reactions by the time of approval included nausea/queasy (0.8% each), sweaty, transient increased blood ammonia level, vascular pain, urticaria, tremor limb by hypoglycemia (0.4% each).

CONTRAINDICATIONS

MORIHEPAMIN is contraindicated in the following patients:
1. Patients with serious renal disorder (The symptoms may be aggravated due to overload of nitrogen compounds).
2. Patients with amino acid metabolism abnormality other than liver disorder (Imbalance of amino acids may be aggravated).

PRECAUTIONS

1. Careful Administration (MORIHEPAMIN should be administered with caution in the following patients)
(1) Patients with severe acidosis (The high doses of the product may aggravate acidosis.)
(2) Patients with congestive heart failure (An increase in the circulating blood volume may worsen cardiac stress in such patients).

2. Important Precautions
If blood ammonia level increase and psychoneurotic symptoms aggravate following administration of MORIHEPAMIN which should be interrupted or changed to another therapy.

3. Use in Elderly
In general, since physiological function is decreased in the elderly, MORIHEPAMIN should be carefully administered and taking measures such as dose reduction.

4. Pediatric Use
The safety of MORIHEPAMIN in children has not been established. (No clinical experience).

5. Use in pregnancy and lactation
The safety of MORIHEPAMIN in pregnant woman and nursing mothers has not been established. Therefore, the product should not be used in pregnant woman, woman suspected of being pregnant, and nursing mothers unless the expected benefit outweigh the potential risks.

PACKING SIZE

Box of 30 bags x 200 ml

STORAGE

Store below 30°C

SHELF-LIFE

36 months from the manufacturing date. The product should be used before the expiration date specified on the outer package and plastic bag.