SHYNDEC XINRAN Nifedipine Controlled Release Tablets For Hypertension 30mg*6

[Trade Name]
Xinran

[Generic Name]
Nifedipine Controlled-Release Tablets

[English Name]
Nifedipine Controlled-Release Tablets

[Main Ingredients]
Main ingredient: Nifedipine.

[Properties and Dosage Form]
This product is a film-coated tablet. After removing the coating, the core tablet is a yellow and red bilayer tablet.

[Indications]
1. Hypertension. 2. Coronary heart disease. 3. Chronic stable angina (exertional angina).

[Specifications]
30mg x 6 tablets

[Dosage and Administration]
Treatment should be tailored to individual patient needs. A different basal dose should be administered based on the patient's clinical condition. Patients with liver impairment should be carefully monitored, and the dose should be reduced in severe cases. Unless otherwise directed by a physician, the following dosages are recommended for adults: 1. Hypertension: 30mg tablets of Benzedrine, 30mg (1 tablet at a time), once daily. 60mg tablets of Benzedrine, 60mg (1 tablet at a time), once daily. 2. Coronary Artery Disease: Chronic Stable Angina (Exertional Angina): 30mg tablets of Benzedrine, 30mg (1 tablet at a time), once daily. 60mg tablets of Benzedrine, 60mg (1 tablet at a time), once daily. The usual initial dose for treatment is 30mg daily. Duration of treatment: The duration of medication should be determined by the physician. Dosage: Generally, the tablet should be swallowed whole with a small amount of liquid, and medication can be taken at any time, regardless of mealtimes.

[Adverse Reactions]
The most common adverse reactions in clinical practice, based on the frequency of occurrence and different human body systems (n=9566, October 13, 1998): 1.1%≤Incidence <10%: (1) Whole body: weakness (fatigue), edema, headache (2) Cardiovascular system: peripheral edema, palpitations, vasodilation (flushing, hot sensation) (3) Digestive system: constipation (4) Nervous system: dizziness 2.0.1%≤Incidence <1%: (1) Whole body: abdominal pain, chest pain, leg pain, discomfort, pain (2) Cardiovascular system: hypotension, orthostatic hypotension, syncope, tachycardia (3) Digestive system: diarrhea, dry mouth, indigestion, flatulence, nausea (4) Musculoskeletal system: leg muscle cramps (5) Nervous system: insomnia, tension, paresthesia, drowsiness, dizziness (6) Respiratory system: dyspnea, rhinitis (7) Skin and its appendages: itching, rash (8) Urogenital system: nocturia, polyuria, impotence 3.0.01%≤Incidence <0.1%: (1) Whole body: allergic reaction, substernal pain, chills, facial edema, fever, cellulitis, neck pain, pelvic pain, pain (2) Cardiovascular system: angina pectoris (except unstable type), cardiac discomfort, atrial fibrillation, bradycardia, cardiac arrest, premature contraction, phlebitis, cutaneous vascular ectopy (3) Digestive system: anorexia, belching, gastrointestinal discomfort, gingivitis, gingival hyperplasia, increased GGT, abnormal liver function, vomiting, abdominal pain, esophagitis, gastrointestinal bleeding (4) Musculoskeletal system: joint pain, joint discomfort, muscle pain, joint pain, arthritis (5) Nervous system: dysesthesia, sleep disturbance, tremor, anxiety, mental confusion, loss of libido, depression, hypertonia (6) Respiratory system: epistaxis, cough, rales, pharyngitis (7) Skin and its appendages: angioedema, polymorphic rash, pustular rash, sweating, urticaria, bullous rash (8) Special senses: visual disturbances, eye discomfort, eye pain, amblyopia, conjunctivitis, diplopia, tinnitus (9) Genitourinary system: dysuria, frequent urination, urinary stones, enuresis (10) Hemolymphatic system: lymphadenopathy (11) Nutritional metabolism: gout (12) Most common spontaneous reports: see adverse drug reactions (13) Calculated according to CIOMSIII frequency classification and COSTART human body system names (5th ed. mod., Bayer): (n=2886, status: September 15, 1998) 4. Incidence rate <0.01% (1) Whole body: allergic reaction (2) Digestive system: fecal stones, dysphagia, esophagitis, gingival discomfort, intestinal obstruction, intestinal ulcer, jaundice, increased SGPT (3) Hemolymphatic system: leukopenia, purpura (4) Metabolic and nutritional disorders: hyperglycemia, weight loss (5) Musculoskeletal system: muscle spasms (6) Skin and its appendages: exfoliative dermatitis, gynecomastia, photosensitive dermatitis (7) Special senses: blurred vision (8) For dialysis patients with malignant hypertension and hypovolemia, vasodilation may cause a significant drop in blood pressure.

[Contraindications]
1. This product is contraindicated in patients with known hypersensitivity to nifedipine or any of its ingredients. 2. Nifedipine is contraindicated in cardiogenic shock. 3. It is contraindicated in patients with KOCK capsules (ileostomy after proctocolectomy). 4. Due to enzyme induction, nifedipine cannot reach an effective blood concentration when used in combination with rifampicin. Therefore, it should not be used in combination with rifampicin. 5. Nifedipine is contraindicated in women within 20 weeks of pregnancy and breastfeeding women.

[Precautions]
1. Patients with heart failure and severe aortic stenosis should be very cautious when taking nifedipine when their blood pressure is very low (severe hypotension with systolic blood pressure <90 mmHg). 2. Nifedipine contains non-deformable substances. Therefore, patients with severe gastrointestinal stenosis should be cautious when using nifedipine because obstructive symptoms may occur. Gastric stones are very rare and may require surgical treatment if they occur. 3. There have been case reports of patients without gastrointestinal diseases experiencing obstructive symptoms. 4. Nifedipine may cause false positive results during X-ray barium meal imaging (mistaken for polyps due to filling defects). 5. Patients with impaired liver function must be strictly monitored and the dose should be reduced if the condition is severe. 6. Nifedipine is metabolized and eliminated through the cytochrome P450 system. Therefore, drugs that inhibit or induce the cytochrome P450 3A4 system may alter the first-pass effect or clearance rate of nifedipine (see [Drug Interactions] for details). Therefore, weak to moderate inhibitors of the cytochrome P450 3A4 system may increase the plasma concentration of nifedipine. For example (1) Macrolide antibiotics (e.g. erythromycin) (2) Anti-HIV protease inhibitors (e.g. ritonavir) (3) Azole antifungals (e.g. ketoconazole) (4) Antidepressants nefazodone and fluoxetine (5) Quinupristin/dalfopristin (6) Valproic acid (7) Cimetidine Blood pressure should be monitored when nifedipine is used in combination with the above drugs. If necessary, the dose of nifedipine should be reduced. 7. Effects on the ability to drive and operate machines. Individual responses to drugs vary and may affect the ability to drive and operate machines. This effect is particularly evident when changing drugs or drinking alcohol in the early stages of treatment. 8. Bispivir has a non-absorbable shell that allows the drug to be slowly released into the body for absorption. When this process is complete, the intact, empty tablets can be found in the feces. 9. Nifedipine controlled-release tablets contain a photosensitive active ingredient. Therefore, they should be stored away from light and moisture. Tablets should be taken immediately after removal from the aluminum-plastic sheet.

[Use during Pregnancy and Lactation]
This product is contraindicated in pregnant and lactating women. Nifedipine is teratogenic in rats and rabbits, including toe abnormalities. These abnormalities may be the result of bleeding from a damaged uterus. Nifedipine administration has been associated with embryotoxic, placental, and fetotoxic effects, including slowed fetal growth (rats, mice, and rabbits), small placentas, or chorionic dysgenesis (monkeys). ), embryonic and fetal death (rats, mice, and rabbits), prolonged pregnancy, and decreased neonatal survival (rats; other species have not been evaluated). All drug doses that caused these teratogenic, embryotoxic, and fetotoxic effects in animals were toxic to the mothers and were several times the maximum recommended human dose. Nifedipine can enter breast milk. Because there are no reports of potential effects on infants, if nifedipine is taken during breastfeeding, breastfeeding must be discontinued.

[Pediatric Use]
There are no data on the use of this drug in children.

[Geriatric Use]
Although small pharmacokinetic studies have shown increases in t½, Cmax, and AUC, clinical studies of nifedipine have not included sufficient patients over 65 years of age to determine whether responses differ between elderly and younger patients. Reported clinical experience has also failed to confirm differences in responses between elderly and younger patients. Generally, due to decreased liver, kidney, or cardiac function, comorbidities, or concomitant medication use in elderly patients, caution should be exercised in elderly patients, often starting with a low dose.

[Drug Interactions]
1. Combination with nitrates to control angina attacks and is well tolerated. 2. Combination with beta-blockers: While this drug is well tolerated and effective in most patients, it may induce and worsen hypotension, heart failure, and angina in some patients. 3. Combination with digitalis may increase blood digoxin concentrations, urging monitoring of digoxin blood levels during initial use, dose adjustments, or discontinuation of this drug. 4. Concomitant use with highly protein-bound drugs, such as dicoumarols, phenytoin, quinidine, quinine, and warfarin, often alters the free concentration of these drugs. 5. Concomitant use with cimetidine increases the peak plasma concentration of this drug; therefore, adjust the dose accordingly. 6. Concomitant administration of grapefruit juice increases the Cmax and AUC of this drug.

[Overdose]
Symptoms: Severe nifedipine poisoning may include the following: impaired consciousness or even coma, decreased blood pressure, tachycardia/bradycardia with a normal heart rhythm, hyperglycemia, metabolic acidosis, hypoxemia/cardiogenic shock with pulmonary edema. Treatment of adult overdose: 1. In the treatment of nifedipine overdose, elimination of the active ingredient and restoration of cardiovascular stability should be prioritized. 2. After oral lavage, small bowel enema may be administered if necessary. Especially for patients poisoned by nifedipine extended-release tablets, treatment should be as comprehensive as possible, including enema measures, to prevent absorption of other active ingredients. 3. Hemodialysis is not effective because it cannot eliminate nifedipine, but plasma exchange (which results in high plasma protein and relatively low blood volume) can be performed. 4. Bradycardiac arrhythmias can be treated with beta-sympathomimetic drugs, and life-threatening bradycardia can be treated with a temporary pacemaker. 5. Hypotension caused by cardiogenic shock and arterial dilation can be treated with calcium supplements (10ml-20ml of 10% calcium gluconate slowly administered intravenously, repeated as necessary). Serum calcium may reach the upper limit of normal or be slightly elevated. If blood pressure does not increase significantly after administration of calcium supplements, sympathomimetic vasoconstrictors such as dopamine or norepinephrine should be considered. The dose should be determined based on the efficacy. 6. Due to the risk of cardiac overload, fluid or blood volume replacement should be used with caution.

[Pharmacology and Toxicology]
1. Pharmacological Action: (1) Nifedipine is a 1,4-dihydropyridine calcium ion antagonist. Calcium ion antagonists can reduce the entry of calcium ions into cells through slow calcium channels. Nifedipine specifically acts on myocardial cells, coronary arteries, and smooth muscle cells of peripheral resistance vessels. (2) Nifedipine can dilate coronary arteries, especially large blood vessels, and can even dilate healthy blood vessels in incompletely blocked areas. Nifedipine can also reduce the tension of coronary artery smooth muscle and prevent vasospasm. Ultimately, it increases blood flow in narrowed blood vessels and improves oxygen supply. At the same time, nifedipine reduces oxygen demand by reducing peripheral resistance (afterload). Long-term use of nifedipine can prevent the occurrence of new coronary atherosclerotic lesions. (3) Nifedipine can reduce increased peripheral resistance and blood pressure by reducing the tension of arterial smooth muscle. In the early stages of nifedipine treatment, a short-term reflex increase in heart rate may occur, leading to an increase in cardiac output. However, this increase is not enough to compensate for the dilation of blood vessels. In addition, short-term or long-term use of nifedipine can increase the excretion of sodium and water. Nifedipine's antihypertensive effect is particularly significant in patients with hypertension. (4) A multinational, randomized, double-blind, prospective study that followed 6,321 hypertensive patients with at least one additional risk factor for 3-4.8 years showed that nifedipine controlled-release tablets can reduce the incidence of cardiovascular and cerebrovascular events, which is equivalent to the effect of combined use with standard diuretics. 2. Toxicological studies: (1) Genetic toxicity The Ames test, micronucleus test and dominant lethality test were all negative. (2) Reproductive toxicity Nifedipine administered before mating can reduce fertility in rats at approximately 30 times the maximum recommended human dose. There are reports that the ability of sperm from infertile men to bind to fertile eggs in vitro is reversibly reduced after using the recommended dose of nifedipine. In rodents, rabbits and monkeys, nifedipine has shown a variety of embryotoxic, placental and fetal toxicity, including slow fetal growth (rats, mice and rabbits), toe abnormalities (rats and rabbits), rib deformities (mice), cleft palate (mice), small placenta and chorionic dysgenesis (monkeys), embryonic and fetal death (rats, mice and rabbits), and prolonged pregnancy (rats, other species have not been evaluated). The doses associated with the above toxicity all showed maternal toxicity and were several times the maximum recommended dose for humans. (3) Carcinogenicity: Rats were given nifedipine orally for 2 years without any carcinogenic effect. (4) Long-term toxicity: Dogs were given nifedipine orally once daily for 1 year at a dose of 100 mg/kg body weight without any toxicity symptoms. In rat studies, toxic reactions occurred when the drug concentration in the feed exceeded 100 pppm (about 5-7 mg/kg body weight).

[Pharmacokinetics]
Baixintong's formulation enables a near-constant release of nifedipine over 24 hours, utilizing a membrane-regulated push-pull osmotic pump mechanism for zero-order release. It is unaffected by gastrointestinal motility and pH. After administration, the inactive ingredients in the tablet pass intact through the gastrointestinal tract and are excreted in the stool as an insoluble outer shell.

[Storage] Store in a cool, dry place (not exceeding 20°C) away from light.
[Packaging] 30mg x 6 tablets
[Expiry Life] 12 months
[Approval Number] National Medicine Standard H20000079
[Manufacturer] Shanghai Modern Pharmaceutical Co., Ltd.