(proe pran' oh lole)
P / L - Contraindicated in pregnancy and Caution during lactation
|| See TERMINOLOGY & ABBREVIATIONS ||
|Description||Propranolol hydrochloride is a synthetic beta-adrenergic receptor blocking agent chemically described as 2-Propanol, 1-[(1-methylethyl) amino]-3-(1-naphthalenyloxy)-, hydrochloride,(±)-. Propranolol hydrochloride is a stable, white, crystalline solid which is readily soluble in water and ethanol. Its molecular weight is 295.80. Propranolol is available as 10 mg, 20 mg, 40 mg, 60 mg, and 80 mg tablets for oral administration. The inactive ingredients contained in Propranolol Tablets may be: lactose, magnesium stearate, microcrystalline cellulose, and stearic acid. In addition, Propranolol 10 mg and 80 mg Tablets contain FD&C Yellow No. 6 and D&C Yellow No. 10; Propranolol 20 mg Tablets contain FD&C Blue No. 1; Propranolol 40 mg Tablets contain FD&C Blue No. 1, FD&C Yellow No. 6, and D&C Yellow No. 10; Propranolol 60 mg Tablets contain D&C Red No. 30.|
|Indication(s) & Dosage||Hypertension
Adult: As conventional tablet or oral solution: Initially, 40-80 mg bid. Usual range: 160-320 mg daily. As extended release tablet: Initially, 80 mg once daily. Usual range: 120-160 mg once daily. Max: 640 mg daily.
Child: Initially, 1 mg/kg daily in divided doses, may increase to 2-4 mg/kg daily in 2 divided doses.
Adult: 60 mg daily given on the 3 days before the operation with Î±-blockade. Prolonged treatment of 30 mg daily may be given if tumour is inoperable.
Child: 250-500 mcg/kg 3-4 times daily.
Adult: 40 mg 4 times daily for 2-3 days followed by 80 mg bid. Alternatively, 180-240 mg daily in divided doses. Doses to be given within 5-21 days of MI.
Adult: 30-160 mg daily in divided doses.
Child: 250-500 mcg/kg 3-4 times daily.
Prophylaxis of migraine
Adult: Initially, 40 mg bid-tid increased to 160 mg daily. Up to 240 mg daily may be necessary. Discontinue therapy if satisfactory response not obtained within 4-6 wk after reaching max dose.
Child: <12 yr: 20 mg bid-tid.
Adult: Initially, 40 mg bid increased up to 160 mg bid.
Adult: As conventional tablet or oral solution: 40 mg bid-tid, may increase to 120-240 mg daily, up to 320 mg daily may be required in some patients. As extended release tablet: 80 mg once daily, increased as needed every 3-7 days, average dose 160 mg once daily, max: 320 mg daily.
Adult: 10-40 mg, given 3-4 times daily.
Adult: 10-40 mg, given 3-4 times daily.
Adult: 40 mg once daily, may increase to bid-tid.
Adult: 40 mg bid-tid. May increase at wkly intervals to 160 mg daily. Up to 320 mg daily may be necessary.
Emergency treatment of cardiac arrhythmias
Adult: 1 mg injected over a period of 1 minute, repeated every 2 minutes, if needed. Max: 10 mg in conscious patients and 5 mg in patients underanaesthesia.
Child: 25-50 mcg/kg via slow inj, may be repeated 3-4 times daily.
Adult: 1 mg, given over 1 minute, may repeat at 2-minute intervals until response is observed or a max of 10 mg is used in conscious patients or 5 mg in patients who are under anaesthesia.
|Administration||Tab: Should be taken on an empty stomach. Take before meals.
Cap: May be taken with or without food. Take consistently either always w/ or always w/o meals.
|Overdosage||Severe and occasionally fatal CV depression.|
|Contraindications||Sinus bradycardia, cardiogenic shock, pulmonary oedema, severe hyperactive airway disease, compensated cardiac failure, Raynaud's disease, hypoglycaemia, severe haemorrhage, metabolic acidosis, severe peripheral arterial disease, 2nd or 3rd degree heart block. Pregnancy (2nd and 3rd trimesters).|
Hypersensitivity reactions, including anaphylactic/anaphylactoid reactions, have been associated with the administration of propranolol and hydrochlorothiazide.
Cardiac Failure: Sympathetic stimulation is a vital component supporting circulatory function in congestive heart failure, and inhibition with beta blockade always carries the potential hazard of further depressing myocardial contractility and precipitating cardiac failure. Propranolol acts selectively without abolishing the inotropic action of digitalis on the heart muscle (i.e., that of supporting the strength of myocardial contractions). In patients already receiving digitalis, the positive inotropic action of digitalis may be reduced by propranolol's negative inotropic effect.
Patients Without a History of Heart Failure: Continued depression of the myocardium over a period of time can, in some cases, lead to cardiac failure. In rare instances, this has been observed during propranolol therapy. Therefore, at the first sign or symptom of impending cardiac failure, patients should be fully digitalized and/or given additional diuretic, and the response observed closely: a) if cardiac failure continues, despite adequate digitalization and diuretic therapy, propranolol therapy should be withdrawn (gradually, if possible); b) if tachyarrhythmia is being controlled, patients should be maintained on combined therapy and the patient closely followed until threat of cardiac failure is over.
Angina Pectoris: There have been reports of exacerbation of angina and, in some cases, myocardial infarction following abrupt discontinuation of propranolol therapy. Therefore, when discontinuance of propranolol is planned, the dosage should be gradually reduced and the patient should be carefully monitored. In addition, when propranolol is prescribed for angina pectoris, the patient should be cautioned against interruption or cessation of therapy without the physician's advice. If propranolol therapy is interrupted and exacerbation of angina occurs, it usually is advisable to reinstitute propranolol therapy and take other measures appropriate for the management of unstable angina pectoris. Since coronary artery disease may be unrecognized, it may be prudent to follow the above advice in patients considered at risk of having occult atherosclerotic heart disease, who are given propranolol for other indications.
Nonallergic Bronchospasm (e.g., chronic bronchitis, emphysema):
PATIENTS WITH BRONCHOSPASTIC DISEASES SHOULD, IN GENERAL, NOT RECEIVE BETA BLOCKERS. Propranolol should be administered with caution since it may block bronchodilation produced by endogenous and exogenous catecholamine stimulation of beta receptors.
Major Surgery: Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery, however the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.
Diabetes and Hypoglycemia: Beta-adrenergic blockade may prevent the appearance of certain premonitory signs and symptoms (pulse rate and pressure changes) of acute hypoglycemia in labile insulin-dependent diabetes. In these patients, it may be more difficult to adjust the dosage of insulin. Hypoglycemic attack may be accompanied by a precipitous elevation of blood pressure in patients on propranolol.
Propranolol therapy, particularly in infants and children, diabetic or not, has been associated with hypoglycemia especially during fasting as in preparation for surgery. Hypoglycemia also has been found after this type of drug therapy and prolonged physical exertion and has occurred in renal insufficiency, both during dialysis and sporadically, in patients on propranolol.
Acute increases in blood pressure have occurred after insulin-induced hypoglycemia in patients on propranolol.
Thyrotoxicosis: Beta blockade may mask certain clinical signs of hyperthyroidism. Therefore, abrupt withdrawal of propranolol may be followed by an exacerbation of symptoms of hyperthyroidism, including thyroid storm. Propranolol may change thyroid-function tests, increasing T4and reverse T3, and decreasing T3.
Wolff-Parkinson-White Syndrome: Several cases have been reported in which, after propranolol, the tachycardia was replaced by a severe bradycardia requiring a demand pacemaker. In one case this resulted after an initial dose of 5 mg propranolol.
Skin Reactions: Cutaneous reactions, including Stevens-Johnson Syndrome, toxic epidermal necrolysis, exfoliative dermatitis, erythema multiforme, and urticaria, have been reported with use of propranolol.
Compensated heart failure, peripheral vascular disease, diabetes. Switching from conventional to sustained-release preparations, elderly. Ischaemic heart disease, congestive cardiac failure, renal or hepatic dysfunction. Increased risk of bradycardia and hypotension in patients with underlying cardiac disorders. 1st degree heart block. May mask symptoms of hyperthyroidism and hypoglycaemia. May unmask myasthenia gravis. Abrupt withdrawal may lead to angina, MI, ventricular arrhythmias and death. Lactation.
Elevated blood urea levels in patients with severe heart disease, elevated serum transaminase, alkaline phosphatase, lactate dehydrogenase.
Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Combinations of propranolol and hydrochlorothiazide have not been evaluated for carcinogenic or mutagenic potential or for potential to adversely affect fertility.
In dietary administration studies in which mice and rats were treated with propranolol for up to 18 months at doses of up to 150 mg/kg/day, there was no evidence of drug-related tumorigenesis.
In a study in which both male and female rats were exposed to propranolol in their diets at concentrations of up to 0.05%, from 60 days prior to mating and throughout pregnancy and lactation for two generations, there were no effects on fertility. Based on differing results from Ames Tests performed by different laboratories, there is equivocal evidence for a genotoxic effect of propranolol in bacteria (S.typhimurium strain TA 1538).
Two-year feeding studies in mice and rats conducted under the auspices of the National Toxicology Program (NTP) uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in female mice (at doses of up to approximately 600 mg/kg/day) or in male and female rats (at doses of up to approximately 100 mg/kg/day). The NTP, however, found equivocal evidence for hepatocarcinogenicity in male mice.
Hydrochlorothiazide was not genotoxic in vitro in the Ames bacterial mutagen assay (S.typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538) or in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations. Nor was it genotoxic in vivo in assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and theDrosophila sex-linked recessive lethal trait gene. Positive test results were obtained in the in vitro CHO Sister Chromatid Exchange (clastogenicity), Mouse Lymphoma Cell (mutagenicity) and Aspergillus nidulans non-disjunction assays.
Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diet, to doses of up to 100 mg/kg and 4 mg/kg, respectively, prior to mating and throughout gestation.
|Adverse Drug Reaction(s)||
The following adverse reactions have been observed, but there is not enough systematic collection of data to support an estimate of their frequency. Within each category, adverse reactions are listed in decreasing order of severity. Although many side effects are mild and transient, some require discontinuation of therapy.
Cardiovascular: Congestive heart failure; hypotension; intensification of AV block; bradycardia; thrombocytopenic purpura; arterial insufficiency, usually of the Raynaud type; paresthesia of hands.
Central Nervous System: Reversible mental depression progressing to catatonia; mental depression manifested by insomnia, lassitude, weakness, fatigue; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, decreased performance on neuropsychometrics; hallucinations; visual disturbances; vivid dreams; light-headedness. Total daily doses above 160 mg (when administered as divided doses of greater than 80 mg each) may be associated with an increased incidence of fatigue, lethargy, and vivid dreams.
Gastrointestinal: Mesenteric arterial thrombosis; ischemic colitis; nausea, vomiting, epigastric distress, abdominal cramping, diarrhea, constipation.
Allergic: Hypersensitivity reactions, including anaphylactic/anaphylactoid reactions; laryngospasm and respiratory distress; pharyngitis and agranulocytosis; fever combined with aching and sore throat; erythematous rash.
Hematologic: Agranulocytosis; nonthrombocytopenic purpura; thrombocytopenic purpura.
Autoimmune: In extremely rare instances, systemic lupus erythematosus has been reported.
Miscellaneous: Male impotence. Alopecia, LE-like reactions, psoriasiform rashes, dry eyes, and Peyronie's disease have been reported rarely. Oculomucocutaneous reactions involving the skin, serous membranes, and conjunctivae reported for a beta blocker (practolol) have not been associated with propranolol.
Skin: Stevens-Johnson Syndrome; toxic epidermal necrolysis; exfoliative dermatitis; erythema multiforme; urticaria.
Cardiovascular: Orthostatic hypotension (may be aggravated by alcohol, barbiturates or narcotics).
Central Nervous System: Dizziness, vertigo, headache, xanthopsia, paresthesias.
Gastrointestinal: Pancreatitis; jaundice (intrahepatic cholestatic jaundice); sialadenitis; anorexia, nausea, vomiting, gastric irritation, cramping, diarrhea, constipation.
Hypersensitivity: Anaphylactic reactions; necrotizing angiitis (vasculitis, cutaneous vasculitis); respiratory distress including pneumonitis; fever; urticaria, rash, purpura, photosensitivity.
Hematologic: Aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia.
Skin: Erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis.
Miscellaneous: Hyperglycemia, glycosuria; hyperuricemia; muscle spasm; weakness; restlessness; transient blurred vision.
Whenever adverse reactions are moderate or severe, thiazide dosage should be reduced or therapy withdrawn.
|Drug Interactions||Decreased effect with aluminum and calcium salts, NSAIDs, ampicillin,rifampicin. Concurrent use with chlorpromazine results in raised blood levels of both drugs and additive hypotensive effect. Hypotensive effect reduced byindometacin. Additive effect with other antihypertensives and diuretics. May reduce the clearance of bupivacaine. Plasma levels may be increased by hydralazine and propafenone. Increased serum levels of thioridazine when used with propranolol.
Potentially Fatal: Marked hypertension and bradycardia with adrenaline. Rebound hypertension due to abrupt withdrawal of clonidine is potentiated. Severe bradycardia may occur with digitalis.
|Lab Interference||Metabolite may interfere with bilirubin and metanephrine measurements.|
|Pregnancy Category (FDA)||Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.
|Storage||Intravenous: Store at 20-25°C. Oral: Store at 20-25°C.|
Propranolol is a nonselective beta-adrenergic receptor blocking agent possessing no other autonomic nervous system activity. It specifically competes with beta-adrenergic receptor agonist agents for available receptor sites. When access to beta-receptor sites is blocked by propranolol, the chronotropic, inotropic, and vasodilator responses to beta-adrenergic stimulation are decreased proportionately. At dosages greater than required for beta blockade, propranolol also exerts a quinidine-like or anesthetic-like membrane action, which affects the cardiac action potential. The significance of the membrane action in the treatment of arrhythmias is uncertain.
Mechanism of Action
The mechanism of the antihypertensive effect of propranolol has not been established. Factors that may contribute to the antihypertensive action include: (1) decreased cardiac output, (2) inhibition of renin release by the kidneys, and (3) diminution of tonic sympathetic nerve outflow from vasomotor centers in the brain. Although total peripheral resistance may increase initially, it readjusts to or below the pretreatment level with chronicuse of propranolol. Effects of propranolol on plasma volume appear to be minor and somewhat variable.
In angina pectoris, propranolol generally reduces the oxygen requirement of the heart at any given level of effort by blocking the catecholamine-induced increases in the heart rate, systolic blood pressure, and the velocity and extent of myocardial contraction. Propranolol may increase oxygen requirements by increasing left ventricular fiber length, end diastolic pressure, and systolic ejection period. The net physiologic effect of beta-adrenergic blockade is usually advantageous and is manifested during exercise by delayed onset of pain and increased work capacity.
Propranolol exerts its antiarrhythmic effects in concentrations associated with beta-adrenergic blockade, and this appears to be its principal antiarrhythmic mechanism of action. In dosages greater than required for beta blockade, propranolol also exerts a quinidine-like or anesthetic-like membrane action, which affects the cardiac action potential. The significance of the membrane action in the treatment of arrhythmias is uncertain.
The mechanism of the antimigraine effect of propranolol has not been established. Beta-adrenergic receptors have been demonstrated in the pial vessels of the brain.
The specific mechanism of propranolol's antitremor effects has not been established, but beta-2 (noncardiac) receptors may be involved. A central effect is also possible. Clinical studies have demonstrated that Propranolol is of benefit in exaggerated physiological and essential(familial) tremor.
Pharmacokinetics And Drug Metabolism
Propranolol is highly lipophilic and almost completely absorbed after oral administration. However, it undergoes high first-pass metabolism by the liver and on average, only about 25% of propranolol reaches the systemic circulation. Peak plasma concentrations occur about 1 to 4 hours after an oral dose.
Administration of protein-rich foods increase the bioavailability of propranolol by about 50% with no change in time to peak concentration, plasma binding, half-life, or the amount of unchanged drug in the urine.
Approximately 90% of circulating propranolol is bound to plasma proteins (albumin and alphai acid glycoprotein). The binding is enantiomer-selective. The S(-)-enantiomer is preferentially bound to alpha1 glycoprotein and the R(+)-enantiomer preferentially bound to albumin. The volume of distribution of propranolol is approximately 4 liters/kg.
Propranolol crosses the blood-brain barrier and the placenta, and is distributed into breast milk.
Metabolism and Elimination
Propranolol is extensively metabolized with most metabolites appearing in the urine. Propranolol is metabolized through three primary routes: aromatic hydroxylation (mainly 4-hydroxylation), N-dealkylation followed by further side-chain oxidation, and direct glucuronidation. It has been estimated that the percentage contributions of these routes to total metabolism are 42%, 41% and 17%, respectively, but with considerable variability between individuals. The four major metabolites are propranolol glucuronide, naphthyloxylactic acid and glucuronic acid, and sulfate conjugates of 4-hydroxy propranolol.
In vitro studies have indicated that the aromatic hydroxylation of propranolol is catalyzed mainly by polymorphic CYP2D6. Side-chain oxidation is mediated mainly by CYP1A2 and to some extent by CYP2D6. 4-hydroxy propranolol is a weak inhibitor of CYP2D6.
Propranolol is also a substrate of CYP2C19 and a substrate for the intestinal efflux transporter, p-glycoprotein (p-gp). Studies suggest however that p-gp is not dose-limiting for intestinal absorption of propranolol in the usualtherapeutic dose range.
In healthy subjects, no difference was observed between CYP2D6 extensive metabolizers (EMs) and poor metabolizers (PMs) with respect to oral clearance or elimination half-life. Partial clearance of 4-hydroxy propranolol was significantly higher and of naphthyloxyactic acid significantly lower in EMs than PMs.
The plasma half-life of propranolol is from 3 to 6 hours.
Propranolol is a racemic mixture of two enantiomers, R(+) and S(-). The S(-)-enantiomer is approximately 100 times as potent as the R(+)-enantiomer in blocking beta adrenergic receptors. In normal subjects receiving oral doses of racemic propranolol, S(-)-enantiomer concentrations exceeded those of the R(+)-enantiomer by 40-90% as a result of stereoselective hepatic metabolism. Clearance of the pharmacologically active S(-)-propranolol is lower than R(+)-propranolol after intravenous and oral doses.
In a study of 12 elderly (62-79 years old) and 12 young (25-33 years old) healthy subjects, the clearance of S(-)-enantiomer of propranolol was decreased in the elderly. Additionally, the half-life of both the R(+)- and S(-)-propranolol were prolonged in the elderly compared with the young (11 hours vs. 5 hours).
Clearance of propranolol is reduced with aging due to decline in oxidation capacity (ring oxidation and side-chain oxidation). Conjugation capacity remains unchanged. In a study of 32 patients age 30 to 84 years given a single 20-mg dose of propranolol, an inverse correlation was found between age and the partial metabolic clearances to 4-hydroxypropranolol (40HP-ring oxidation) and to naphthoxylactic acid (NLA-side chain oxidation). No correlation was found between age and the partial metabolic clearance to propranolol glucuronide (PPLG-conjugation).
In a study of 9 healthy women and 12 healthy men, neither the administration of testosterone nor the regular course of the menstrual cycle affected the plasma binding of the propranolol enantiomers. In contrast, there was a significant, although non-enantioselective diminution of the binding of propranolol after treatment with ethinyl estradiol. These findings are inconsistent with another study, in which administration of testosterone cypionate confirmed the stimulatory role of this hormone on propranolol metabolism and concluded that the clearance of propranolol in men is dependent on circulating concentrations of testosterone. In women, none of the metabolic clearances for propranolol showed any significant association with either estradiol or testosterone.
A study conducted in 12 Caucasian and 13 African-American male subjects taking propranolol, showed that at steady state, the clearance of R(+)- and S(-)-propranolol were about 76% and 53% higher in African-Americans than in Caucasians, respectively.
Chinese subjects had a greater proportion (18% to 45% higher) of unbound propranolol in plasma compared to Caucasians, which was associated with a lower plasma concentration of alpha1 acid glycoprotein.
In a study conducted in 5 patients with chronic renal failure, 6 patients on regular dialysis, and 5 healthy subjects, who received a single oral dose of 40 mg of propranolol, the peak plasma concentrations (Cmax) of propranolol in the chronic renal failure group were 2 to 3-fold higher (161±41 ng/mL) than those observed in the dialysis patients (47±9 ng/mL) and in the healthy subjects (26±1 ng/mL). Propranolol plasma clearance was also reduced in the patients with chronic renal failure.
Studies have reported a delayed absorption rate and a reduced half-life of propranolol in patients with renal failure of varying severity. Despite this shorter plasma half-life, propranolol peak plasma levels were 3-4 times higher and total plasma levels of metabolites were up to 3 times higher in these patients than in subjects with normal renal function.
Chronic renal failure has been associated with a decrease in drug metabolism via downregulation of hepatic cytochrome P450 activity resulting in a lower "first-pass" clearance.
Propranolol is not significantly dialyzable.
Propranolol is extensively metabolized by the liver. In a study conducted in 7 patients with cirrhosis and 9 healthy subjects receiving 80-mg oral propranolol every 8 hours for 7 doses, the steady-state unbound propranolol concentration in patients with cirrhosis was increased 3-fold in comparison to controls. In cirrhosis, the half-life increased to 11 hours compared to 4 hours.
Interactions with Substrates, Inhibitors or Inducers of Cytochrome P-450 Enzymes Because propranolol's metabolism involves multiple pathways in the cytochrome P-450 system (CYP2D6, 1A2, 2C19), co-administration with drugs that are metabolized by, or effect the activity (induction or inhibition) of one or more of these pathways may lead to clinically relevant drug interactions.
Substrates or Inhibitors of CYP2D6
Blood levels and/or toxicity of propranolol may be increased by co-administration with substrates or inhibitors of CYP2D6, such as amiodarone, cimetidine, delavudin, fluoxetine, paroxetine, quinidine, and ritonavir. No interactions were observed with either ranitidine or lansoprazole.
Substrates or Inhibitors of CYP1A2
Blood levels and/or toxicity of propranolol may be increased by co-administration with substrates or inhibitors of CYP1A2, such as imipramine, cimetidine, ciprofloxacin, fluvoxamine, isoniazid, ritonavir, theophylline, zileuton, zolmitriptan, and rizatriptan.
Substrates or Inhibitors of CYP2C19
Blood levels and/or toxicity of propranolol may be increased by co-administration with substrates or inhibitors of CYP2C19, such as fluconazole, cimetidine, fluoxetine, fluvoxamine, tenioposide, and tolbutamide. No interaction was observed with omeprazole.
Inducers of Hepatic Drug Metabolism
Blood levels of propranolol may be decreased by co-administration with inducers such as rifampin, ethanol, phenytoin, and phenobarbital. Cigarette smoking also induces hepatic metabolism and has been shown to increase up to 77% the clearance of propranolol, resulting in decreased plasma concentrations.
Cardiovascular Drugs Antiarrhythmics
The AUC of propafenone is increased by more than 200% by co-administration of propranolol.
The metabolism of propranolol is reduced by co-administration of quinidine, leading to a two-three fold increased blood concentration and greater degrees of clinical beta-blockade.
The metabolism of lidocaine is inhibited by co-administration of propranolol, resulting in a 25% increase in lidocaine concentrations.
Calcium Channel Blockers
The mean Cmax and AUC of propranolol are increased, respectively, by 50% and 30% by co-administration of nisoldipine and by 80% and 47%, by co-administration of nicardipine.
The mean Cmax and AUC of nifedipine are increased by 64% and 79%, respectively, by co-administration of propranolol.
Propranolol does not affect the pharmacokinetics of verapamil and norverapamil. Verapamil does not affect the pharmacokinetics of propranolol.
Administration of zolmitriptan or rizatriptan with propranolol resulted in increased concentrations of zolmitriptan (AUC increased by 56% and Cmax by 37%) or rizatriptan (the AUC and Cmax were increased by 67% and 75%, respectively).
Co-administration of theophylline with propranolol decreases theophylline oral clearance by 30% to 52%.
Propranolol can inhibit the metabolism of diazepam, resulting in increased concentrations of diazepam and its metabolites. Diazepam does not alter the pharmacokinetics of propranolol.
The pharmacokinetics of oxazepam, triazolam, lorazepam, and alprazolam are not affected by co-administration of propranolol.
Co-administration of long-acting propranolol at doses greater than or equal to 160 mg/day resulted in increased thioridazine plasma concentrations ranging from 55% to 369% and increased thioridazine metabolite (mesoridazine) concentrations ranging from 33% to 209%.
Co-administration of chlorpromazine with propranolol resulted in a 70% increase in propranolol plasma level.
Co-administration of propranolol with cimetidine, a non-specific CYP450 inhibitor, increased propranolol AUC and Cmax by 46% and 35%, respectively. Co-administration with aluminum hydroxide gel (1200 mg) may result in a decrease in propranolol concentrations.
Co-administration of metoclopramide with the long-acting propranolol did not have a significant effect on propranolol's pharmacokinetics.
Lipid Lowering Drugs
Co-administration of cholestyramine or colestipol with propranolol resulted in up to 50% decrease in propranolol concentrations.
Co-administration of propranolol with lovastatin or pravastatin, decreased 18% to 23% the AUC of both, but did not alter their pharmacodynamics. Propranolol did not have an effect on the pharmacokinetics of fluvastatin.
Concomitant administration of propranolol and warfarin has been shown to increase warfarin bioavailability and increase prothrombin time.
Concomitant use of alcohol may increase plasma levels of propranolol.
Pharmacodynamics And Clinical Effects
In a retrospective, uncontrolled study, 107 patients with diastolic blood pressure 110 to 150 mmHg received propranolol 120 mg t.i.d. for at least 6 months, in addition to diuretics and potassium, but with no other antihypertensive agent. Propranolol contributed to control of diastolic blood pressure, but the magnitude of the effect of propranolol on blood pressure cannot be ascertained.
In a double-blind, placebo-controlled study of 32 patients of both sexes, aged 32 to 69 years, with stable angina, propranolol 100 mg t.i.d. was administered for 4 weeks and shown to be more effective than placebo in reducing the rate of angina episodes and in prolonging total exercise time.
In a report examining the long-term (5-22 months) efficacy of propranolol, 10 patients, aged 27 to 80, with atrial fibrillation and ventricular rate >120 beats per minute despite digitalis, received propranolol up to 30 mg t.i.d. Seven patients (70%) achieved ventricular rate reduction to <100 beats per minute.
The Beta-Blocker Heart Attack Trial (BHAT) was a National Heart, Lung and Blood Institute-sponsored multicenter, randomized, double-blind, placebo-controlled trial conducted in 31 U.S. centers (plus one in Canada) in 3,837 persons without history of severe congestive heart failure or presence of recent heart failure; certain conduction defects; angina since infarction, who had survived the acute phase of myocardial infarction. Propranolol was administered at either 60 or 80 mg t.i.d. based on blood levels achieved during an initial trial of 40 mg t.i.d. Therapy with Propranolol , begun 5 to 21 days following infarction, was shown to reduce overall mortality up to 39 months, the longest period of follow-up. This was primarily attributable to a reduction in cardiovascular mortality. The protective effect of Propranolol was consistent regardless of age, sex, or site of infarction. Compared with placebo, total mortality was reduced 39% at 12 months and 26% over an average follow-up period of 25 months. The Norwegian Multicenter Trial in which propranolol was administered at 40 mg q.i.d. gave overall results which support the findings in the BHAT.
Although the clinical trials used either t.i.d. or q.i.d. dosing, clinical, pharmacologic, and pharmacokinetic data provide a reasonable basis for concluding that b.i.d. dosing with propranolol should be adequate in the treatment of postinfarction patients.
In a 34-week, placebo-controlled, 4-period, dose-finding crossover study with a double-blind randomized treatment sequence, 62 patients with migraine received propranolol 20 to 80 mg 3 or 4 times daily. The headache unit index, a composite of the number of days with headache and the associated severity of the headache, was significantly reduced for patients receiving propranolol as compared to those on placebo.
In a 2 week, double-blind, parallel, placebo-controlled study of 9 patients with essential or familial tremor, propranolol, at a dose titrated as needed from 40-80 mg t.i.d. reduced tremor severity compared to placebo.
Hypertrophic Subaortic Stenosis
In an uncontrolled series of 13 patients with New York Heart Association (NYHA) class 2 or 3 symptoms and hypertrophic subaortic stenosis diagnosed at cardiac catheterization, oral propranolol 40-80 mg t.i.d. was administered and patients were followed for up to 17 months. Propranolol was associated with improved NYHA class for most patients.
In an uncontrolled series of 3 patients with norepinephrine-secreting pheochromocytoma who were pretreated with an alpha adrenergic blocker (prazosin), perioperative use of propranolol at doses of 40-80 mg t.i.d. resulted in symptomatic blood pressure control.
|ATC Classification||C07AA05 - propranolol; Belongs to the class of non-selective beta-blocking agents. Used in the treatment of cardiovascular diseases.|
Search Google: Propranolol
|Brand Name||Manufacturer/Marketer||Composition||Dosage Form||Pack Size & Price|
|ADLOCK||Sonear Laboratories Ltd.||Propranolol hydrochloride 10 & 40mg||Tablet||100's each: 50.00 & 46.00 MRP|
|BETACAP TR||Sun Pharmaceutical (Bangladesh) Ltd.||Propranolol hydrochloride 40mg||Tablet (extended release)||40mg x 50's: 125.00 MRP|
|G-PROPRANOLOL||Gonoshasthaya Pharmaceuticals Ltd||Propranolol hydrochloride 40mg||Tablet||40mg x 100's: 35.00 MRP|
|INDEVER||ACI Ltd.||Propranolol hydrochloride 10 & 40mg||Tablet||100's: 51.00 & 150.00 MRP|
|INDEVER SR||ACI Ltd.||Propranolol hydrochloride 40mg & 80mg||Capsule (sustained release)||100's: 92.00 & 155.00 MRP|
|PROPRANOL||Opsonin Pharma Limited||Propranolol hydrochloride 10 & 40mg||Tablet||10mg x 200's, 40mg x 100's: 42.00 & 31.00 MRP|
Why this medicine?
Propranolol helps to keep your blood pressure under control. It may also be used to treat certain heart diseases such as angina pectoris (chest pain) and arrhythmia (irregular heart beats).
How to use this medicine?
Take Propranolol exactly as directed by your doctor. Do not take more or less than instructed by your doctor.
What should be done if I have forgotten to use this medicine?
Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and return to your normal schedule.
When not to use this medicine?
Alert your doctor if you suffer from heart disease, asthma or other lung diseases.
What should be noted while using this medicine?
Alert your doctor if you have liver, kidney or thyroid disease, diabetes, any disease that affects your blood vessels or blood circulation as well as other illnesses such as myasthenia gravis and phaeochromocytoma. You should also inform your doctor if you are seeing a psychiatrist.
What side effects could appear?
Propranolol may cause dizziness or drowsiness. If you feel dizzy or drowsy, do not drive or take part in any activity in which you need to be alert.
Can it be taken this with other medicines?
Alert your doctor if you are taking any other medicines, especially those listed here:
How to store this medicine?
Store in a cool, dry place away from the reach of children. Medicines must not be used past the expiry date.
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