Can Labetalol cause premature baby?

ADVERSE REACTIONS Most adverse effects are mild and transient and occur early in the course of treatment. In controlled clinical trials of 3 to 4 months' duration, discontinuation of labetalol hydrochloride due to one or more adverse effects was required in 7% of all patients. In these same trials, other agents with solely beta-blocking activity used in the control groups led to discontinuation in 8% to 10% of patients, and a centrally acting alpha-agonist led to discontinuation in 30% of patients. The incidence rates of adverse reactions listed in the following table were derived from multicenter, controlled clinical trials comparing labetalol hydrochloride, placebo, metoprolol, and propranolol over treatment periods of 3 and 4 months. Where the frequency of adverse effects for labetalol hydrochloride and placebo is similar, causal relationship is uncertain. The rates are based on adverse reactions considered probably drug related by the investigator. If all reports are considered, the rates are somewhat higher (e.g., dizziness, 20%; nausea, 14%; fatigue, 11%), but the overall conclusions are unchanged. Labetalol HCl (N=227) % Placebo (N=98) % Propranolol (N=84) % Metoprolol (N=49) % Body as a whole Fatigue 5 0 12 12 Asthenia 1 1 1 0 Headache 2 1 1 2 Gastrointestinal Nausea 6 1 1 2 Vomiting <1 0 0 0 Dyspepsia 3 1 1 0 Abdominal pain 0 0 1 2 Diarrhea <1 0 2 0 Taste distortion 1 0 0 0 Central and Peripheral Nervous Systems Dizziness 11 3 4 4 Paresthesias <1 0 0 0 Drowsiness <1 2 2 2 Autonomic Nervous System Nasal stuffiness 3 0 0 0 Ejaculation failure 2 0 0 0 Impotence 1 0 1 3 Increased sweating <1 0 0 0 Cardiovascular Edema 1 0 0 0 Postural hypotension 1 0 0 0 Bradycardia 0 0 5 12 Respiratory Dyspnea 2 0 1 2 Skin Rash 1 0 0 0 Special Senses Vision abnormality 1 0 0 0 Vertigo 2 1 0 0 The adverse effects were reported spontaneously and are representative of the incidence of adverse effects that may be observed in a properly selected hypertensive patient population, i.e., a group excluding patients with bronchospastic disease, overt congestive heart failure, or other contraindications to beta-blocker therapy. Clinical trials also included studies utilizing daily doses up to 2,400 mg in more severely hypertensive patients. Certain of the side effects increased with increasing dose, as shown in the following table that depicts the entire U.S. therapeutic trials data base for adverse reactions that are clearly or possibly dose related. Labetalol Hydrochloride Daily Dose (mg) 200 300 400 600 800 Number of Patients 522 181 606 608 503 Dizziness (%) 2 3 3 3 5 Fatigue 2 1 4 4 5 Nausea <1 0 1 2 4 Vomiting 0 0 <1 <1 <1 Dyspepsia 1 0 2 1 1 Paresthesias 2 0 2 2 1 Nasal Stuffiness 1 1 2 2 2 Ejaculation Failure 0 2 1 2 3 Impotence 1 1 1 1 2 Edema 1 0 1 1 1 Labetalol Hydrochloride Daily Dose (mg) 900 1,200 1,600 2,400 Number of Patients 117 411 242 175 Dizziness (%) 1 9 13 16 Fatigue 3 7 6 10 Nausea 0 7 11 19 Vomiting 0 1 2 3 Dyspepsia 0 2 2 4 Paresthesias 1 2 5 5 Nasal Stuffiness 2 4 5 6 Ejaculation Failure 0 4 3 5 Impotence 4 3 4 3 Edema 0 1 2 2 In addition, a number of other less common adverse events have been reported: Body as a Whole: Fever. Cardiovascular: Hypotension, and rarely, syncope, bradycardia, heart block. Central and Peripheral Nervous Systems: Paresthesia, most frequently described as scalp tingling. In most cases, it was mild and transient and usually occurred at the beginning of treatment. Collagen Disorders: Systemic lupus erythematosus, positive antinuclear factor. Eyes: Dry eyes. Immunological System: Antimitochondrial antibodies. Liver and Biliary System: Hepatic necrosis, hepatitis, cholestatic jaundice, elevated liver function tests. Musculoskeletal System: Muscle cramps, toxic myopathy. Respiratory System: Bronchospasm. Skin and Appendages: Rashes of various types, such as generalized maculopapular, lichenoid, urticarial, bullous lichen planus, psoriaform, and facial erythema; Peyronie's disease, reversible alopecia. Urinary System: Difficulty in micturition, including acute urinary bladder retention. Hypersensitivity: Rare reports of hypersensitivity (e.g., rash, urticaria, pruritus, angioedema, dyspnea) and anaphylactoid reactions. Following approval for marketing in the United Kingdom, a monitored release survey involving approximately 6,800 patients was conducted for further safety and efficacy evaluation of this product. Results of this survey indicate that the type, severity, and incidence of adverse effects were comparable to those cited above. Potential Adverse Effects In addition, other adverse effects not listed above have been reported with other beta-adrenergic blocking agents. Central Nervous System: Reversible mental depression progressing to catatonia, an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance on psychometrics. Cardiovascular: Intensification of A-V block (see CONTRAINDICATIONS ). Allergic: Fever combined with aching and sore throat, laryngospasm, respiratory distress. Hematologic: Agranulocytosis, thrombocytopenic or nonthrombocytopenic purpura. Gastrointestinal: Mesenteric artery thrombosis, ischemic colitis. The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with labetalol hydrochloride. Clinical Laboratory Tests There have been reversible increases of serum transaminases in 4% of patients treated with labetalol hydrochloride and tested and, more rarely, reversible increases in blood urea. To report SUSPECTED ADVERSE REACTIONS, contact Northstar Rx LLC at 1-800-206-7821 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

WARNINGS AND PRECAUTIONS Monitor patients for symptomatic postural hypotension and syncope after initial dosing or dose increments. ( 5.1 ) Monitor heart rate and rhythm for bradycardia, including sinus pause, heart block, severe bradycardia, and cardiac arrest in patients receiving Labetalol Hydrochloride Tablets. ( 5.2 ) Beta-blockade can depress myocardial contractility and precipitating more severe failure. Avoid use in patients with overt heart failure. ( 5.3 ). Monitor heart rate and rhythm for bradycardia, including sinus pause, heart block, severe bradycardia, and cardiac arrest in patients receiving Labetalol Hydrochloride Tablets. ( 5.2 ) Beta-blockade can depress myocardial contractility and precipitating more severe failure. Avoid use in patients with overt heart failure. ( 5.3 ) Acute exacerbation of coronary artery disease upon cessation of therapy. Do not abruptly discontinue. ( 5.4 ) Avoid use in patients with bronchospastic disease. ( 5.5 ) Beta‑adrenergic blockade may prevent the appearance of premonitory signs and symptoms (e.g., tachycardia) of acute hypoglycemia. ( 5.6 ) Exacerbation of pheochromocytoma: Paradoxical increases in blood pressure may occur. ( 5.7 ) Hepatic necrosis and death have been reported. If the patient develops signs or symptoms of liver injury, institute appropriate treatment and investigate the probable cause. ( 5.8 ) Do not routinely withdraw chronic beta blocker therapy prior to surgery. ( 5.10 ) 5.1 Hypotension Monitor patients for symptomatic postural hypotension and syncope after initial dosing or dose increments with Labetalol Hydrochloride Tablets. Elderly patients are generally more likely than younger patients to experience orthostatic symptoms [see Dosage and Administration (2.1) , Use in Specific Populations (8.5) , Clinical Pharmacology (12.2) ]. 5.2 Bradycardia Bradycardia, including sinus pause, heart block, severe bradycardia, and cardiac arrest have occurred with the use of beta blockers. Monitor heart rate and rhythm in patients receiving Labetalol Hydrochloride Tablets. 5.3 Cardiac Failure Sympathetic stimulation is a vital component supporting circulatory function in congestive heart failure. Beta‑blockade carries a potential hazard of further depressing myocardial contractility and precipitating more severe failure. Avoid Labetalol Hydrochloride Tablets in patients with overt congestive heart failure. If patients develop signs or symptoms of heart failure during administration, discontinue Labetalol Hydrochloride Tablets and treat appropriately. 5.4 Ischemic Heart Disease Abrupt cessation of therapy with beta blocking agents in patients with coronary artery disease can cause exacerbations of angina pectoris and, in some cases, myocardial infarction has been reported. Therefore, even in the absence of overt angina pectoris, after the discontinuation of Labetalol Hydrochloride Tablets observe patients for development or worsening of angina. If patient experiences angina or angina markedly worsens or if acute coronary insufficiency develops, promptly reinstitute Labetalol Hydrochloride Tablets and manage as unstable angina. 5.5 Reactive Airway Disease and Nonallergic Bronchospasm Avoid use in patients with reactive airways disease. If Labetalol Hydrochloride Tablets are used, use the smallest effective dose, to minimize inhibition of endogenous or exogenous beta agonists. 5.6 Hypoglycemia Beta-blockers may prevent early warning signs of hypoglycemia, such as tachycardia, and increase the risk for severe or prolonged hypoglycemia at any time during treatment, especially in patients with diabetes mellitus or children and patients who are fasting (i.e., surgery, not eating regularly, or are vomiting). If severe hypoglycemia occurs, patients should be instructed to seek emergency treatment. 5.7 Use in Patients with Pheochromocytoma Labetalol hydrochloride has been shown to be effective in lowering blood pressure and relieving symptoms in patients with pheochromocytoma; higher than usual doses may be required. However, paradoxical hypertensive responses have been reported in a few patients with this tumor; therefore, blood pressure when administering labetalol hydrochloride to patients with pheochromocytoma. 5.8 Hepatic Injury Severe hepatocellular injury occurs rarely with labetalol therapy. The hepatic injury is usually reversible, but hepatic necrosis and death have been reported. If the patient develops signs or symptoms of liver injury, institute appropriate treatment and investigate the probable cause. Do not restart labetalol in patients without another explanation for the observed liver injury. 5.9 Use in Patients at Risk of Severe Acute Hypersensitivity Reactions Patients at risk of anaphylactic reactions may be more reactive to allergen exposure (accidental, diagnostic, or therapeutic). Patients using beta-blockers may be unresponsive to the usual doses of epinephrine used to treat anaphylactic or anaphylactoid reactions. Avoid Labetalol Hydrochloride Tablets in patients at high risk of anaphylactic reactions. 5.10 Major Surgery Do not routinely withdraw chronic beta blocker therapy prior to surgery. The effect of labetalol’s alpha adrenergic activity has not been evaluated in this setting. A synergism between labetalol hydrochloride and halothane anesthesia has been shown [ see Drug Interactions (7.3) ]. 5.11 Intraoperative Floppy Iris Syndrome (IFIS) IFIS has been observed during cataract surgery in some patients treated with alpha-1 blockers (labetalol is an alpha/beta blocker). This variant of small pupil syndrome is characterized by the combination of a flaccid iris that billows in response to intraoperative irrigation currents, progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs, and potential prolapse of the iris toward the phacoemulsification incisions. Inform the patient’s ophthalmologist to be prepared for possible modifications to the surgical technique, such as the utilization of iris hooks, iris dilator rings, or viscoelastic substances. 5.1 Hypotension Monitor patients for symptomatic postural hypotension and syncope after initial dosing or dose increments with Labetalol Hydrochloride Tablets. Elderly patients are generally more likely than younger patients to experience orthostatic symptoms [see Dosage and Administration (2.1) , Use in Specific Populations (8.5) , Clinical Pharmacology (12.2) ]. 5.2 Bradycardia Bradycardia, including sinus pause, heart block, severe bradycardia, and cardiac arrest have occurred with the use of beta blockers. Monitor heart rate and rhythm in patients receiving Labetalol Hydrochloride Tablets. 5.3 Cardiac Failure Sympathetic stimulation is a vital component supporting circulatory function in congestive heart failure. Beta‑blockade carries a potential hazard of further depressing myocardial contractility and precipitating more severe failure. Avoid Labetalol Hydrochloride Tablets in patients with overt congestive heart failure. If patients develop signs or symptoms of heart failure during administration, discontinue Labetalol Hydrochloride Tablets and treat appropriately. 5.4 Ischemic Heart Disease Abrupt cessation of therapy with beta blocking agents in patients with coronary artery disease can cause exacerbations of angina pectoris and, in some cases, myocardial infarction has been reported. Therefore, even in the absence of overt angina pectoris, after the discontinuation of Labetalol Hydrochloride Tablets observe patients for development or worsening of angina. If patient experiences angina or angina markedly worsens or if acute coronary insufficiency develops, promptly reinstitute Labetalol Hydrochloride Tablets and manage as unstable angina. 5.5 Reactive Airway Disease and Nonallergic Bronchospasm Avoid use in patients with reactive airways disease. If Labetalol Hydrochloride Tablets are used, use the smallest effective dose, to minimize inhibition of endogenous or exogenous beta agonists. 5