Many drugs can interact with clomipramine. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide. Tell your doctor about all medicines you use, and those you start or stop using during your treatment with clomipramine. Give a list of all your medicines to any healthcare provider who treats you. What should I discuss with my healthcare provider before taking escitalopram Lexapro? Take the dose you forgot as soon as you remember it. However, if it will soon be time for your next regular dose, skip the missed dose completely. Do not take two doses of this medication over a short period of time, as this may result in an overdose.
The main symptom is an uncontrolled ejaculation either before or shortly after intercourse begins. Ejaculation occurs before the person wishes it, with minimal sexual stimulation. How is premature ejaculation diagnosed? The median time to rash that resulted in discontinuation was 13 days. No such cases were observed among 380 pediatric patients who received placebo. Your doctor will tell you the right time of day to take Modafinil tablets. Discuss any withdrawal symptoms you experience with your doctor.
There was no apparent change in the elimination rate of ethinyl estradiol. Mallinckrodt, the “M” brand mark, the Mallinckrodt Pharmaceuticals logo, and other brands are trademarks of a Mallinckrodt company. If a multi-organ hypersensitivity reaction is suspected, Modafinil should be discontinued. Although there are no case reports to indicate cross-sensitivity with other drugs that produce this syndrome, the experience with drugs associated with multi-organ hypersensitivity would indicate this to be a possibility. Johnsson, G. Relationship between time of intake of grapefruit juice and its effect on pharmacokinetics and pharmacodynamics of felodipine in healthy subjects.
RxList is part of the WebMD Health Network. The opinions expressed in the WebMD User Reviews are solely those of the User, who may or may not have medical or scientific training, and do not represent the opinions of WebMD. These member reviews have not been reviewed by a WebMD physician or any member of the WebMD editorial staff for accuracy, balance, objectivity, or any other purpose except for compliance with our Terms and Conditions. Modafinil, but exposure to Modafinil acid an inactive metabolite was increased 9-fold. Breimer, D. D. Grapefruit juice and cimetidine inhibit stereoselective metabolism of nitrendipine in humans.
Digestive complaints in people with eczema. Blood levels of cyclosporine may be reduced when used with Modafinil. Monitoring of circulating cyclosporine concentrations and appropriate dosage adjustment for cyclosporine should be considered when used concomitantly with Modafinil. Signs and symptoms vary in severity depending upon factors such as the amount of drug absorbed, the age of the patient, and the time elapsed since drug ingestion. Critical manifestations of overdose include cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic toxicity. Other CNS manifestations may include drowsiness, stupor, ataxia, restlessness, agitation, delirium, severe perspiration, hyperactive reflexes, muscle rigidity, and athetoid and choreiform movements. Cardiac abnormalities may include tachycardia, signs of congestive heart failure, and in very rare cases, cardiac arrest. Respiratory depression, cyanosis, shock, vomiting, hyperpyrexia, mydriasis, and oliguria or anuria may also be present. If you are a young adult. Some components might have antioxidant effects that might help protect cells from damage or reduce cholesterol. It is not clear how the oil might work for medicinal uses. Advise patients to notify their physician if they are breastfeeding an infant. KEEP ALL MEDICINES OUT OF THE SIGHT AND REACH OF CHILDREN. Grapefruit juice might decrease how quickly the liver breaks down some medications. Drinking grapefruit juice while taking some medications that are broken down by the liver can increase the effects and side effects of some medications. Before taking grapefruit, talk to your healthcare provider if you are taking any medications that are changed by the liver. Do not use escitalopram if you are using an MAO inhibitor such as furazolidone Furoxone isocarboxazid Marplan phenelzine Nardil rasagiline Azilect selegiline Eldepryl, Emsam, Zelapar or tranylcypromine Parnate. Serious and sometimes fatal reactions can occur when these medicines are taken with escitalopram. You must wait at least 14 days after stopping an MAO inhibitor before you can take escitalopram. After you stop taking escitalopram, you must wait at least 14 days before you start taking an MAOI. Spence, J. D. Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin. Infrequent - abnormal accommodation, deafness, diplopia, earache, eye pain, foreign body sensation, hyperacusis, parosmia, photophobia, scleritis, taste loss. Rare - blepharitis, chromatopsia, conjunctival hemorrhage, exophthalmos, glaucoma, keratitis, labyrinth disorder, night blindness, retinal disorder, strabismus, visual field defect. Rare cases of serious or life-threatening rash, including SJS, Toxic Epidermal Necrolysis TEN and Drug Rash with Eosinophilia and Systemic Symptoms DRESS have been reported in adults and children in worldwide postmarketing experience. The reporting rate of TEN and SJS associated with Modafinil use, which is generally accepted to be an underestimate due to underreporting, exceeds the background incidence rate. Estimates of the background incidence rate for these serious skin reactions in the general population range between 1 to 2 cases per million-person years. Have you been diagnosed as having a low level of potassium in your blood hypokalemia? Although this medication may lessen the severity of symptoms, it cannot address the issue in the same way as a therapist or counselor, who may help you develop positive coping strategies, a good routine, and teach you more about what you are experiencing. If you are prescribed this drug, please consider with whom you can establish a good and work toward better long-term mental health. Co-administration of haloperidol with CMI increases plasma concentrations of CMI. Co-administration of CMI with phenobarbital increases plasma concentrations of phenobarbital see . Younger subjects 18 to 40 years of age tolerated CMI better and had significantly lower steady-state plasma concentrations, compared with subjects over 65 years of age.
What are nonsurgical treatments for erectile dysfunction? Your doctor has decided that you need this medicine to help treat your condition. Do you have schizophrenia or other mental disorders? Shelton MJ, Wynn HE, Hewitt RG, DiFrancesco R. Effects of grapefruit juice on pharmacokinetic exposure to indinavir in HIV-positive subjects. What should I tell my doctor before taking Modafinil tablets?
This medication may cause problems in newborns if taken during pregnancy or while breastfeeding. If you are pregnant or become pregnant while taking Anafranil, you should speak with your doctor about other possible treatments for what you are experiencing. Food and Drug Administration. WebMD does not endorse any specific product, service, or treatment. Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for clomipramine hydrochloride should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose. All medicines have side effects. But many people don't feel the side effects, or they are able to deal with them. Ask your pharmacist about the side effects of each medicine you take. Side effects are also listed in the information that comes with your medicine. Huff, M. W. Inhibition of hepatocyte apoB secretion by naringenin: enhanced rapid intracellular degradation independent of reduced microsomal cholesteryl esters.
Cigarette smoking decreases blood levels of this medication. Tell your doctor if you smoke or if you have recently stopped smoking. Clozaril can cause severe dizziness, slow heartbeats, fainting, or seizures. Do not take more of this medicine than recommended. Be careful if you drive or do anything that requires you to be alert. Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Dizziness or severe drowsiness can cause falls, fractures, or other injuries. The following table enumerates adverse events that occurred at an incidence of 1% or greater among patients with OCD who received Anafranil in adult or pediatric placebo-controlled clinical trials. Modafinil tablets has been shown to produce levels of wakefulness that permit such activities. Advise patients that Modafinil tablets are not a replacement for sleep. What happens if I overdose Anafranil? Takanaga H, Ohnishi A, Matsuo H, et al. Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model. This drug may make you dizzy or drowsy or cause temporary blurred vision. Do not drive, use machinery, or do any activity that requires alertness or clear vision until you are sure you can perform such activities safely. Limit alcoholic beverages. This list is not complete and other drugs may interact with escitalopram. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Your doctor will discuss your medical and sexual history with you.
The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. Drugs. The tablets are formulated to release the active ingredient slowly. Taking MAO inhibitors with this medication may cause a serious possibly fatal drug interaction. Avoid taking MAO inhibitors isocarboxazid, linezolid, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, selegiline, tranylcypromine during treatment with this medication. Most MAO inhibitors should also not be taken for two weeks before and after treatment with this medication. Ask your doctor when to start or stop taking this medication. Since depression is a commonly associated feature of OCD, the risk of suicide must be considered. Prescriptions for Anafranil should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose. Infrequent - endometriosis, epididymitis, hematuria, nocturia, oliguria, ovarian cyst, perineal pain, polyuria, prostatic disorder, renal calculus, renal pain, urethral disorder, urinary incontinence, uterine hemorrhage, vaginal hemorrhage. Rare - albuminuria, anorgasmy, breast engorgement, breast fibroadenosis, cervical dysplasia, endometrial hyperplasia, premature ejaculation, pyelonephritis, pyuria, renal cyst, uterine inflammation, vulvar disorder. Masi G. Pharmacotherapy of pervasive developmental disorders in children and adolescents. CNS Drugs. Modafinil is readily absorbed after oral administration, with peak plasma concentrations occurring at 2 to 4 hours. The bioavailability of Modafinil tablets is approximately equal to that of an aqueous suspension. Before taking clomipramine, tell your doctor if you have used an "SSRI" antidepressant in the past 5 weeks, such as citalopram, escitalopram, fluoxetine Prozac fluvoxamine, paroxetine Paxil sertraline Zoloft trazodone, or vilazodone Viibryd. What are surgical treatments for erectile dysfunction? Other medications can affect the removal of clomipramine from your body, which may affect how clomipramine works.
Becquemont L, Verstuyft C, Kerb R, et al. Effect of grapefruit juice on digoxin pharmacokinetics in humans. Where can people find more information about depression? This medicine may cause some people to become dizzy, drowsy, or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy, drowsy, or not alert. The criteria for narcolepsy include either: 1 recurrent daytime naps or lapses into sleep that occur almost daily for at least 3 months, plus sudden bilateral loss of postural muscle tone in association with intense emotion cataplexy; or 2 a complaint of excessive sleepiness or sudden muscle weakness with associated features: sleep paralysis, hypnagogic hallucinations, automatic behaviors, disrupted major sleep episode; and polysomnography demonstrating one of the following: sleep latency less than 10 minutes or rapid eye movement REM sleep latency less than 20 minutes. For entry into these studies, all patients were required to have objectively documented excessive daytime sleepiness, via a Multiple Sleep Latency Test MSLT with two or more sleep onset REM periods and the absence of any other clinically significant active medical or psychiatric disorder. Ioannides-Demos LL, Christophidis N, et al. Dosing implications of a clinical interaction between grapefruit juice and cyclosporine and metabolite concentrations in patients with autoimmune diseases. Anticonvulsants used to stop seizures or fits. Do not use clomipramine if you have taken an MAO inhibitor in the past 14 days. A dangerous drug interaction could occur. MAO inhibitors include furazolidone, isocarboxazid, linezolid, phenelzine, rasagiline, selegiline, and tranylcypromine. Know all of the medicines that you or your family member takes. Some medications used for high cholesterol include lovastatin Mevacor simvastatin Zocor atorvastatin Lipitor cerivastatin Baycol and others. What is amitriptyline, and how does it work mechanism of action? Do you have an overactive thyroid gland? Cerda JJ, Robbins FL, Burgin CW, et al. The effects of grapefruit pectin on patients at risk for coronary heart disease without altering diet or lifestyle. Your doctor may want to talk to your partner also. Premature ejaculation can have many causes. So your doctor may order lab tests to rule out any other medical problem. How is it treated? Fujimura, A. Effects of grapefruit juice on the pharmacokinetics of pitavastatin and atorvastatin. Do not become overheated in hot weather or while you are being active; heatstroke may occur.
Modafinil as compared to placebo. P450 2D6, they may vary in the extent of inhibition. Fluvoxamine has also been shown to inhibit P450 1A2, an isoform also involved in TCA metabolism. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite at least 5 weeks may be necessary. Concomitant use of agents in the tricyclic antidepressant class which includes Anafranil with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant agent or the other drug. Furthermore, whenever one of these drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant agent may be required. Try to take the medicine at the same time each day. Follow the directions on your prescription label. Read the Medication Guide available from your pharmacist. Consult your doctor or pharmacist if you have any questions. Delitala, G. Grapefruit juice inhibits 11beta-hydroxysteroid dehydrogenase in vivo, in man. Clin Endocrinol. Before taking clomipramine, tell your doctor if you have used an "SSRI" antidepressant in the past 5 weeks, such as citalopram Celexa escitalopram Lexapro fluoxetine Prozac, Rapiflux, Sarafem, Selfemra, Symbyax fluvoxamine Luvox paroxetine Paxil, Pexeva sertraline Zoloft trazodone Desyrel, Oleptro or vilazodone Viibryd. Store Modafinil tablets at room temperature between 20º to 25ºC 68º to 77ºF. Inactive Ingredients: croscarmellose sodium, dibasic calcium phosphate anhydrous lactose monohydrate, magnesium stearate, microcrystalline cellulose and povidone. Do not throw it away with your normal household water or waste. FDA approved for use in children. But negative emotions can be a result of chronic pain as well as a cause. What are the symptoms of erectile dysfunction? Bui, B. C. The effects of grapefruit juice on sertraline metabolism: an in vitro and in vivo study. Take this medication by mouth with or without food as directed by your doctor. To lessen side effects such as stomach upset, clomipramine may be started at a low dose, given in several doses during the day with meals, and slowly increased as your body gets used to it. After you have reached the best dose for you, the total dose can be taken once daily, usually at bedtime to prevent daytime drowsiness or as directed by your doctor. Usually, the daily dose will not be more than 250 milligrams for adults and 200 milligrams for children and teenagers. Pain patients who work with a physical therapist or occupational therapist can learn to avoid the particular ways of moving that contribute to chronic pain.
Mallinckrodt, the “M” brand mark, the Mallinckrodt Pharmaceuticals logo and other brands are trademarks of a Mallinckrodt company. This medication belongs to a class of medications called tricyclic antidepressants. It works by restoring the balance of certain natural substances serotonin, among others in the brain. Edstein, M. D. Does gender, food or grapefruit juice alter the pharmacokinetics of primaquine in healthy subjects? Anafranil for periods of several months to several years. No unusual age-related adverse events were identified in this population. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Modafinil tablets and many other medicines can interact with each other, sometimes causing side effects. Modafinil tablets may affect the way other medicines work, and other medicines may affect how Modafinil tablets work. Your dose of Modafinil tablets or certain other medicines may need to be changed. Or you can try a different position such as lying on your back during intercourse. Counseling or behavioral therapy may help reduce anxiety related to premature ejaculation. Bailey DG, Dresser GK, Kreeft JH, et al. Grapefruit juice-felodipine interaction: Effect of segments and an extract from unprocessed fruit. Do not stop taking Anafranil suddenly because this may cause withdrawal side effects. As with adults, after titration, the total daily dose may be given once daily at bedtime to minimize daytime sedation. Generally, doctors who prescribe opiod treatment monitor patients with chronic pain carefully. The side effects are usually mild and disappear as treatment continues. The brands listed are trademarks of their respective owners. Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.
Lilja JJ, Kivisto KT, Backman JT, et al. Grapefruit juice substantially increases plasma concentrations of buspirone. In Modafinil clinical studies, cardiovascular adverse reactions, including chest pain, palpitations, dyspnea, and transient ischemic T-wave changes on ECG occurred in three subjects in association with mitral valve prolapse or left ventricular hypertrophy. Some medications that are changed by the liver include diclofenac Cataflam, Voltaren ibuprofen Motrin meloxicam Mobic and piroxicam Feldene; celecoxib Celebrex; amitriptyline Elavil; warfarin Coumadin; glipizide Glucotrol; losartan Cozaar; and others. Clomipramine is used to treat symptoms of obsessive-compulsive disorder OCD such as recurrent thoughts or feelings and repetitive actions. What causes low libido? This medication packs a punch. I've been on it at 200mg daily for just over five years. It was very effective in treating my panic disorder and OCD symptoms, but I experienced all the side effects described above. The dry mouth is so bad I couldn't use my CPAP anymore. Over all I gained about 35 lbs that I could not lose not matter how hard I tried. I had constant thirst and excessive urination. My affect became flat and dull. I was rendered completely impotent. And over five years I was prescribed four other medications to treat the side effects. But I endured it all. Finally, after achieving some stability in my life, I am trying to get off it. It is a nightmare! Escitalopram may also be used for purposes not listed in this medication guide. In addition to its wake-promoting effects and ability to increase locomotor activity in animals, Modafinil produces psychoactive and euphoric effects, alterations in mood, perception, thinking, and feelings typical of other CNS stimulants in humans. Modafinil has reinforcing properties, as evidenced by its self-administration in monkeys previously trained to self-administer cocaine; Modafinil was also partially discriminated as stimulant-like. Additionally, TRUVEN HEALTH MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Truven Health does not assume any responsibility or risk for your use of the Truven Health products. Clozaril is available only from a certified pharmacy under a special program. Do not stop taking this medicine without checking first with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping it completely. This may help prevent a possible worsening of your condition and reduce the possibility of withdrawal symptoms such as dizziness, headache, nausea, vomiting, trouble sleeping, irritability, high fever, or a general feeling of discomfort or illness.
Greenblatt DJ. Analysis of drug interactions involving fruit beverages and organic anion-transporting polypeptides. Patients, their families, and their caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia psychomotor restlessness hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients should be advised to look for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient's prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication. Lab tests, including complete blood cell counts, may be performed while you use Anafranil. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia psychomotor restlessness hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. The 100 mg tablets are white to off-white, round, unscored tablets debossed with M over 573 on one side of the tablet and blank on the other side. What is erectile dysfunction? This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist. It may take 2 to 3 weeks before you notice the effect of Anafranil. Continue to use Anafranil even if you feel well. Do not miss any doses. Dijkstra, H. P. Bergamottin contribution to the grapefruit juice-felodipine interaction and disposition in humans. AUC even for patients dosed within the recommended range.
Unlike some traditional forms of psychotherapy, which focus on personal and early life experiences, cognitive behavioral therapy aims to help people think realistically about their pain and find ways to work around physical limitations. If you miss a dose of Anafranil, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once. If you take 1 dose daily at bedtime, do not take the missed dose the next morning. Be careful when drinking alcohol - it may affect you more than usual. High cholesterol. Early research suggest that taking grapefruit capsules daily for 16 weeks decreases total cholesterol and the ratio of low-density lipoprotein LDL or “bad” cholesterol to high-density lipoprotein HDL or “good” cholesterol. Eating one grapefruit daily appears to reduce total cholesterol, LDL cholesterol and in people with high cholesterol. Take clomipramine with food to reduce stomach upset. Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women. The risk increases if you are also taking other drugs that increase serotonin, so tell your doctor or pharmacist of all the drugs you take.
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Your doctor may want to do blood tests and check your heart while you are taking Anafranil. Bailey DG. Fruit juice inhibition of uptake transport: a new type of food-drug interaction. The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. Cold or allergy medicine, sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures or anxiety can add to sleepiness caused by escitalopram. Tell your doctor if you regularly use any of these medicines.
How can I get the most out of my treatment with this drug? As is the case with tricyclic antidepressants to which Anafranil is closely related, leukocyte and differential blood counts should be obtained in patients who develop fever and sore throat during treatment with Anafranil. Call a poison helpline, contact your health care provider, and seek emergency medical attention immediately. An overdose of this medication may be deadly. In some cases, a patient already receiving Anafranil 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, Anafranil should be stopped promptly, and linezolid or intravenous methylene blue can be administered.
Is it possible to prevent depression? Avoid drinking alcohol. Dangerous side effects could occur. Modafinil tablets contain Modafinil, a Schedule IV controlled substance. Anafranil 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. Tell your doctor or pharmacist if you are taking other products that cause drowsiness including alcohol, antihistamines such as cetirizine, diphenhydramine drugs for sleep or anxiety such as alprazolam, diazepam, zolpidem muscle relaxants such as carisoprodol, cyclobenzaprine and narcotic pain relievers such as codeine, hydrocodone.
Kim, R. B. Intestinal drug transporter expression and the impact of grapefruit juice in humans. The adult starting dose of Anafranil is 25 mg daily and gradually increased, as tolerated, to approximately 100 mg during the first 2 weeks. Maximum dose is 250 mg daily. Consult your doctor for pediatric or adolescent dosing. Lilja JJ, Kivisto KT, Neuvonen PJ. Duration of effect of grapefruit juice on the pharmacokinetics of the CYP3A4 substrate simvastatin. Gross AS, Goh YD, Addison RS, et al. Influence of grapefruit juice on cisapride pharmacokinetics. In addition, several intentional acute overdoses occurred; the two largest being 4500 mg and 4000 mg taken by two subjects participating in foreign depression studies. None of these study subjects experienced any unexpected or life-threatening effects. Adverse reactions that were reported at these doses included excitation or agitation, insomnia, and slight or moderate elevations in hemodynamic parameters. Other observed high-dose effects in clinical studies have included anxiety, irritability, aggressiveness, confusion, nervousness, tremor, palpitations, sleep disturbances, nausea, diarrhea, and decreased prothrombin time.