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Since overdosage is often deliberate, patients may attempt suicide by other means during the recovery phase. Psychiatric referral may be appropriate. During maintenance, the total daily dose may be given once a day at bedtime to minimize daytime sedation. In rare instances, hemoperfusion may be beneficial in acute refractory cardiovascular instability in patients with acute toxicity. However, hemodialysis, peritoneal dialysis, exchange transfusions, and forced diuresis generally have been reported as ineffective in tricyclic poisoning. Novartis Animal Health US, Inc. toprol generic side effects toprol

Indications and usage of clomipramine

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Coadministration of haloperidol with clomipramine increases plasma concentrations of clomipramine. Coadministration of clomipramine with phenobarbital increases plasma concentrations of phenobarbital see . Younger subjects 18 to 40 years of age tolerated clomipramine better and had significantly lower steady-state plasma concentrations, compared with subjects over 65 years of age. Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil.

Does clomipramine interact with other medications

Discontinuation of therapy: Upon discontinuation of antidepressant therapy, gradually taper the dose to minimize the incidence of withdrawal symptoms and allow for the detection of re-emerging symptoms. Evidence supporting ideal taper rates is limited. APA and NICE guidelines suggest tapering therapy over at least several weeks with consideration to the half-life of the antidepressant; antidepressants with a shorter half-life may need to be tapered more conservatively. In addition for long-term treated patients, WFSBP guidelines recommend tapering over 4 to 6 months. Manufactured for: Novartis Animal Health US, Inc.

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Approximately 85% of males with sexual dysfunction chose to continue treatment. Get the help, and not just xanax, that shouldn't be anything more than a temporary fix. Anyway, good luck! The specific methods of behavioral modification used in clinical trials involved desensitization and counterconditioning techniques. Since the manifestation of separation anxiety can vary according to the individual dog, it is advised that a specific behavior modification plan be developed based on a professional assessment of each individual case. generic amitriptyline purchase now pharmacy



Clomipramine overdose

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist. Some dogs display a temporary lethargy with the first few days of Clomicalm treatment. In some cases, signs of separation anxiety, such as vocalization, may temporarily increase at the initiation of treatment. In an overdose situation, seek veterinary attention for your pet as soon as possible. Cardiovascular disease: Use with caution in patients with a history of cardiovascular disease including previous MI, stroke, tachycardia, or conduction abnormalities; the risk of conduction abnormalities with this agent is high relative to other antidepressants. The classifications below are a general guideline only. It is difficult to determine the relevance of a particular drug interaction to any individual given the large number of variables. Roth, BL; Driscol, J 12 January 2011.



Use of clomipramine

The use of MAOIs intended to treat psychiatric disorders with clomipramine hydrochloride or within 14 days of stopping treatment with clomipramine is contraindicated because of an increased risk of serotonin syndrome. Many drugs can interact with clomipramine. Not all possible interactions are listed here. Am always nice when I see her children but I know I am not the favorite grandma with these girls. They are nice girls - they don't come up to visit often as I live in a small town and they get bored. I do get very anxious when they do come during holidays - they get bored fast. To the point I am writing their other grandma on the dad's side is "cool" - they are in New York City now where their grandma and their aunt took them and pics posted on facebook every day they are there. I try not to let it bother me - I don't have the stamina and can't travel much due to my anxiety about not sleeping so that's why I'm here. Do not consider Communities as medical advice. Never delay or disregard seeking professional medical advice from your doctor or other qualified healthcare provider because of something you have read on WebMD. You should always speak with your doctor before you start, stop, or change any prescribed part of your care plan or treatment. WebMD understands that reading individual, real-life experiences can be a helpful resource, but it is never a substitute for professional medical advice, diagnosis, or treatment from a qualified health care provider. If you think you may have a medical emergency, call your doctor or dial 911 immediately. ADHD, is also widely prescribed, he says. Psychoactive Drug Screening Program PDSP. University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment. 2. Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have a particularly high risk of having suicidal thoughts or actions. These include people who have or have a family history of bipolar illness also called manic-depressive illness or suicidal thoughts or actions. 3. How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member? Store dextroamphetamine at room temperature, between 59 and 86 degrees F 15 and 30 degrees C. Store away from heat, moisture, and light. Keep in a tightly closed container. Do not store in the bathroom. Keep dextroamphetamine out of the reach of children and away from pets. Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings. Plasma concentrations of clomipramine were significantly lower in smokers than in nonsmokers. What is imipramine, and how does it work mechanism of action? cabergoline



Food and Drug Administration

In some countries, this medicine may only be approved for veterinary use. Untoward events associated with this exposure were recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of untoward events into a smaller number of standardized event categories. In a meta-analysis of various trials involving fluoxetine Prozac fluvoxamine Luvox and sertraline Zoloft to test their relative efficacies in treating OCD, clomipramine was found to be the most effective. Alpha2-Agonists Ophthalmic: Tricyclic Antidepressants may diminish the therapeutic effect of Alpha2-Agonists Ophthalmic. Electroconvulsive therapy: May increase the risks associated with electroconvulsive therapy; consider discontinuing, when possible, prior to ECT treatment. Milnacipran. Specifically, the incidence of euphoria and postural hypotension were higher in patients changing from clomipramine to milnacipran. ClomiPRAMINE may enhance the serotonergic effect of Milnacipran. This could result in serotonin syndrome. Management: Coadminister with caution. Because of its anticholinergic properties, clomipramine should be used with caution in patients with increased intraocular pressure, a history of narrow angle glaucoma, urinary retention or reduced gastrointestinal motility. Because clomipramine is principally metabolized in the liver, caution is advised in using this medication in the presence of preexisting liver disease. Nicorandil: Tricyclic Antidepressants may enhance the hypotensive effect of Nicorandil. The absolute bioavailability is approximately 25% greater in fed dogs. The apparent terminal plasma half-life ranges from approximately 2 to 9 hours in fed and 3 to 21 hours in fasted dogs. The difference and variability in apparent half-life estimates may be attributable to prolonged drug absorption in the fasted state. Separation anxiety is a complex behavior disorder displayed when the owner or other attachment figure leaves the dog. In the absence of the owner or attachment figure, dogs with separation anxiety may exhibit one or more clinical signs. The signs of separation anxiety evaluated in controlled trials were vocalization, destructive behavior, excessive salivation, and inappropriate elimination. Clomipramine is contraindicated during the acute recovery period after a myocardial infarction. Tricyclic Antidepressants. Dexmethylphenidate may increase the serum concentration of Tricyclic Antidepressants. Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. Patients and their families or other caregivers should discuss all treatment choices with the healthcare provider, not just the use of antidepressants. Modest orthostatic decreases in blood pressure and modest tachycardia were each seen in approximately 20% of patients taking clomipramine hydrochloride in clinical trials; but patients were frequently asymptomatic.



FDA approved to treat pediatric depression

Clomipramine has been found in human milk. Because of the potential for adverse reactions, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. The treatment regimens described below are based on those used in controlled clinical trials of clomipramine in 520 adults, and 91 children and adolescents with OCD. During initial titration, clomipramine should be given in divided doses with meals to reduce gastrointestinal side effects. The goal of this initial titration phase is to minimize side effects by permitting tolerance to side effects to develop or allowing the patient time to adapt if tolerance does not develop. Ocular effects: May cause mild pupillary dilation which in susceptible individuals can lead to an episode of narrow-angle glaucoma. Consider evaluating patients who have not had an iridectomy for narrow-angle glaucoma risk factors. The most commonly reported side effects were somnolence, tremor, dizziness, headache, dry mouth, constipation, and nausea. Red 40, ferrous iron oxide, gelatin, pharmaceutical glaze, propylene glycol and titanium dioxide. Adults with ADHD and a family history of and should consider the effect of ADHD drugs, both stimulants and nonstimulants, although they are considered safe in the short term. PDF. World Health Organization. Your dose may need to be gradually decreased. MAOI intended to treat psychiatric disorders. The use of MAOIs intended to treat psychiatric disorders with Anafranil or within 14 days of stopping treatment with Anafranil is also contraindicated because of an increased risk of serotonin syndrome. Tricyclic Antidepressants. FluvoxaMINE may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants TCAs including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with fluvoxamine. Clomipramine hydrochloride PH: Ph. Eur. probenecid per pill cvs



How do I get over my guilt?

Cinacalcet: May increase the serum concentration of Tricyclic Antidepressants. Management: Seek alternatives when possible. Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Clomipramine is presumed to influence obsessive and compulsive behaviors through its effects on serotonergic neuronal transmission. Hey, i bet you had some minor attacks prior to the traffic incident but maybe didnt understand it was happening. Like you, i also have had my worse attacks in traffic, however, when i think back, I've always had some signs, walking into a classroom, going into crowded place or something, i would feel nervous and sweaty, the difference was there were others around to distract my mind, and you subconsciously know theres a way out, when your stuck in traffic with anxiety you always see the worse, theres no way out! Keep this and all drugs out of reach of children. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences drug vs placebo however, were relatively stable within age strata and across indications. Antidepressants increased the risk compared to placebo of suicidal thinking and behavior suicidality in children, adolescents, and young adults in short-term studies of major depressive disorder MDD and other psychiatric disorders. Anyone considering the use of clomipramine hydrochloride or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Peginterferon Alfa-2b: May increase the serum concentration of CYP1A2 Substrates. Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. During premarket evaluation, seizure was identified as the most significant risk of clomipramine hydrochloride use. Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Caution is advised in using clomipramine with anticholinergic or sympathomimetic drugs or with other CNS-active drugs, including general anesthetics and neuroleptics. Amphetamines: Tricyclic Antidepressants may enhance the stimulatory effect of Amphetamines. Tricyclic Antidepressants may also potentiate the cardiovascular effects of Amphetamines. Källén, B; Otterblad Olausson, P Apr 2006. "Antidepressant drugs during pregnancy and infant congenital heart defect". Reproductive Toxicology.



Prescribing information for clomipramine

The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder OCD or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. Do not use clomipramine if you have used an MAO inhibitor in the past 14 days. A dangerous drug interaction could occur. MAO inhibitors include isocarboxazid, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, tranylcypromine, and others. Should I Try Psychotherapy? Is this all I need to know if my child is being prescribed an antidepressant? Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Talk to your doctor about using clomipramine safely. The 75 mg capsules are swedish orange opaque and flesh opaque imprinted on the cap and body with MYLAN over 3075 in black ink. Chichester, West Sussex, UK: Wiley-Blackwell. zocor drug



What are the possible side effects of clomipramine

They can make a change in their life, unlearn bad habits, use their organizers well, plan better, listen better. Food and Drug Administration FDA or visit www. CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Analgesics Opioid: CNS Depressants may enhance the CNS depressant effect of Analgesics Opioid. Management: Avoid concomitant use of opioid analgesics and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. What you need is therapy with goals that are specific to the behaviors and symptoms that are problematic. If you have difficulty keeping a calendar, how are you going to keep a calendar, what are the barriers? Lithium: May enhance the neurotoxic effect of Tricyclic Antidepressants. Management: This combination should be undertaken with great caution. Do not start clomipramine hydrochloride in a patient who is being treated with linezolid or intravenous methylene blue because there is increased risk of serotonin syndrome. Dose Establishment: A 12 week, placebo-controlled, multi-site clinical trial was conducted in the US and Europe to establish an effective dose of Clomicalm Tablets in dogs. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. The 25 mg capsules are medium orange opaque and flesh opaque imprinted on the cap and body with MYLAN over 3025 in black ink. NIMH-OC. Patients on placebo showed no important clinical response on either scale. If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip themissed dose and resume your usual dosing schedule. Whether it is regular therapy, group therapy, medications, or even natural remedies which you can read more about or a combination of all of these, you do have options and there is a light at the end of this seemingly never ending tunnel. What brand names are available for imipramine? Prior to elective surgery with general anesthetics, therapy with Anafranil should be discontinued for as long as is clinically feasible, and the anesthetist should be advised.



Clomipramine warnings

Precipitation of hypomania and mania has been reported in patients receiving Anafranil for the treatment of affective disorders. Activation of mania or hypomania has been reported in a small proportion of patients receiving other tricyclic antidepressants. Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. The effectiveness of clomipramine hydrochloride for the treatment of OCD was demonstrated in multicenter, placebo-controlled, parallel-group studies, including two 10-week studies in adults and one 8-week study in children and adolescents 10 to 17 years of age. Patients in all studies had moderate-to-severe OCD DSM-III with mean baseline ratings on the Yale-Brown Obsessive Compulsive Scale YBOCS ranging from 26 to 28 and a mean baseline rating of 10 on the NIMH Clinical Global Obsessive Compulsive Scale NIMH-OC. Patients taking clomipramine experienced a mean reduction of approximately 10 on the YBOCS, representing an average improvement on this scale of 35% to 42% among adults and 37% among children and adolescents. Some young people have thoughts about suicide when first taking an antidepressant. Your doctor will need to check your progress at regular visits while you are using clomipramine. Your family or other caregivers should also be alert to changes in your mood or symptoms. Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. See USP for Controlled Room Temperature. When I get in bed at night I can't sleep and I think about everything I didn't do or complete that day and somethings I can't sleep unless I get up and complete them. Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. The young woman spent a year at community college and is heading back to the university. Hello I am a female 23 yrs old and was diagnosed with anxiety about 2 yrs ago. Clomipramine is primarily metabolized in the liver. Jewelz32412 is right. You are not crazy. Do not suddenly stop taking this medication without consulting your doctor. Some conditions may become worse when the drug is abruptly stopped. Those things usually put me in that negative state. To resolve that I make sure I get some solid sack time and the minute I wake up I shower, brush my teeth, and have my coffee. cefdinir



Clomipramine drug interactions

Serious effects, including heart attack, stroke, and sudden death, have occurred with the use of stimulant medicines in patients with heart defects or other serious heart problems. If you have a heart defect or other serious heart problem, talk with your doctor about other therapies to treat your condition. Nilsson, HL; Knorring, LV. "Review. Clomipramine in acute and chronic pain syndromes". Nordic Journal of Psychiatry. Lumacaftor: May decrease the serum concentration of CYP2C19 Substrates. Greater risks for developing a discontinuation syndrome have been associated with antidepressants with shorter half-lives, longer durations of treatment, and abrupt discontinuation. For antidepressants of short or intermediate half-lives, symptoms may emerge within 2-5 days after treatment discontinuation and last 7-14 days APA 2010; Fava 2006; Haddad 2001; Shelton 2001; Warner 2006. Common adverse reactions include gastrointestinal complaints, including dry mouth, constipation, nausea, dyspepsia, and anorexia; nervous system complaints, including somnolence, tremor, dizziness, nervousness, and myoclonus; genitourinary complaints, including changed libido, ejaculatory failure, impotence, and micturition disorder; and other miscellaneous complaints, including fatigue, sweating, increased appetite, weight gain, and visual changes.



ADHD, is also widely prescribed, he says

Adverse events were observed in some animal reproduction studies. Clomipramine and its metabolite desmethylclomipramine cross the placenta and can be detected in cord blood and neonatal serum at birth Loughhead 2006; ter Horst 2011. Patients treated with clomipramine have been reported to show a variety of neuropsychiatric signs and symptoms including delusions, hallucinations, psychotic episodes, confusion, and paranoia. Because of the uncontrolled nature of many of the studies, it is impossible to provide a precise estimate of the extent of risk imposed by treatment with clomipramine. As with tricyclic antidepressants to which it is closely related, clomipramine may precipitate an acute psychotic episode in patients with unrecognized schizophrenia. Food and Drug Administration. WebMD does not endorse any specific product, service or treatment. It is unclear if it is safe for use in pregnancy. Pooled analyses of short-term 4 to 16 weeks placebo-controlled trials of 9 antidepressant drugs SSRIs and others in children and adolescents with major depressive disorder MDD obsessive compulsive disorder OCD or other psychiatric disorders a total of 24 trials involving over 4400 patients have revealed a greater risk of adverse events representing suicidal thinking or behavior suicidality during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients receiving antidepressants was 4%, twice the placebo risk of 2%. No suicides occurred in these trials. Zolpidem is for short-term use only. Tell your doctor if your insomnia symptoms do not improve, or if they get worse after using this medication for 7 to 10 nights in a row. Do not take zolpidem for longer than 4 or 5 weeks without your doctor's advice. Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults 18 to 24 years of age with major depressive disorder MDD and other psychiatric disorders; consider risk prior to prescribing. The most commonly observed adverse events associated with the use of clomipramine hydrochloride and not seen at an equivalent incidence among placebo-treated patients were gastrointestinal complaints, including dry mouth, constipation, nausea, dyspepsia, and anorexia; nervous system complaints, including somnolence, tremor, dizziness, nervousness, and myoclonus; genitourinary complaints, including changed libido, ejaculatory failure, impotence, and micturition disorder; and other miscellaneous complaints, including fatigue, sweating, increased appetite, weight gain, and visual changes. In some cases, a patient already receiving clomipramine hydrochloride therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, clomipramine hydrochloride should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Liver disease has occurred, especially in the presence of preexisting conditions or with concurrent administration of drugs metabolized by the liver. In overdoses, signs such as vomiting, lethargy or depression, weakness and incoordination, dilated pupils, and vocalization may occur. Consult with your veterinarian if your dog experiences these or any other conditions. ONLY ONE who felt this way. I wake up every morning feeling like something horrible is going to happen. SL taken only once per night if the patient has at least 4 hours of bedtime remaining before the planned time of waking. What other drugs will affect zolpidem? lamotrigine online europa



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Kraft, TB Aug 1977


PDF World Health Organization

The sublingual tablet should not be swallowed or taken with water. Thank you for sharing this very poignant and honest depiction of what it's like to live with depression and anxiety. For some, it truly does feel like a life sentence -except the jail cell is your mind. Disclaimer: Every effort has been made to ensure that the information provided by Cerner Multum, Inc. 'Multum' is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. hdis.info tindamax

Side effects of clomipramine

Cardiovascular System: Infrequent: abnormal ECG, arrhythmia, bradycardia, cardiac arrest, extrasystoles, pallor. Rare: aneurysm, atrial flutter, bundle branch block, cardiac failure, cerebral hemorrhage, heart block, myocardial infarction, myocardial ischemia, peripheral ischemia, thrombophlebitis, vasospasm, ventricular tachycardia. Use this medication regularly in order to get the most benefit from it. Continue to take it even if you feel well. To help you remember, use it at the same times each day. For some children and teenagers, the risks of suicidal actions may be especially high. Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates.

CNS depressants is not recommended

She might also have suggested a good pocket planner. As with adults, after titration, the total daily dose may be given once daily at bedtime to minimize daytime sedation. Antidepressant medicines can interact with other medicines. Know all of the medicines that you or your family member takes. Keep a list of all medicines to show the healthcare provider. Do not start new medicines without first checking with your healthcare provider. Veterinarians should be familiar with the risks and benefits of the treatment of behavioral disorders in dogs before initiating therapy. loratadine

Clomipramine dosage

If you'd like information on how to live with and manage your anxiety, then click to read more. In controlled studies of OCD, weight gain was reported in 18% of patients receiving clomipramine, compared with 1% of patients receiving placebo. In these studies, 28% of patients receiving clomipramine had a weight gain of at least 7% of their initial body weight, compared with 4% of patients receiving placebo. Several patients had weight gains in excess of 25% of their initial body weight. Conversely, 5% of patients receiving clomipramine and 1% receiving placebo had weight losses of at least 7% of their initial body weight.

After titration, the total daily dose may be given once a day at bedtime to minimize daytime sedation. If the pH response is inadequate, hyperventilation may also be used. Concomitant use of hyperventilation and sodium bicarbonate should be done with extreme caution, with frequent pH monitoring. During initial titration, this drug should be given in divided doses with meals to reduce gastrointestinal side effects.

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