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Several drug interactions involving amantadine and rimantadine are clinically significant. Anticholinergic drugs can potentiate the toxicity of amantadine. Thiazide-triamterene, trimethoprim-sulfamethoxazole, quinine, and quinidine increase plasma amantadine levels. Cimetidine decreases rimantadine clearance, and aspirin and acetaminophen decrease rimantadine plasma levels.
Sildenafil has other minor adverse effects, such as headache, nasal congestion, and flushing. There are no clinically significant drug interactions between sildenafil and apomorphine. Apomorphine, like sildenafil, is orally active. However, unlike sildenafil, it exerts its action through the central nervous system. Apomorphine can produce dizziness, nausea, pallor, and hypotension, and in the presence of ethanol, it purportedly increases
Gabapentin is a narrow-spectrum drug. It is useful only in patients with partial epilepsy, that is those with simple or complex partial seizures, or partial-onset generalized tonic-clonic convulsions. Gabapentin is felt to be more useful in newly diagnosed patients with mild epilepsy and in the elderly, who benefit from the relatively mild side-effect profile and lack of drug interactions, but less useful in patients with refractory epilepsy. Although gabapentin can be initiated at a therapeutic dose of 1200-2400 mg day, it appears to be better tolerated when titrated 57 . Typically, 300 mg two times a day is well tolerated as a starting dose, but lower starting doses are needed in some patients. Clinical trials have only tested efficacy to 2400 mg day 46 . However, in clinical experience, higher doses can be useful. However, gabapentin displays dose-dependent, saturable absorption. At higher doses, less may be absorbed across the gut, leading to diminishing returns 58 . The amount of...
Not clear if this is clinically necessary. In one study 82 , levetiracetam was started at 4000 mg day, and was well tolerated. Serum levels are typically within the range of 10-40 mg l, but will vary substantially over the course of a day, because of the short half-life of the drug. Another advantage of levetiracetam is that it is associated with no drug interactions because it is predominantly renally excreted, and shows limited metabolism in humans. As with other renally excreted drugs, lower doses should be used in the elderly, because they have a reduced creatinine clearance 83 .
The kidney is the most commonly transplanted organ, usually as a result of hypertensive disease, diabetes or glomerulonephritis, all of which cause uraemia and may be associated with seizures. The immunosuppressant agents most often used in renal transplantation are cyclosporine, tacrolimus, azathioprine and mycophenolate most patients are also on steroids. Cyclosporine and tacrolimus are well known to be associated with posterior leukoencephalopathy and seizures 33, 34 . Cyclosporine has also been shown to reduce seizure threshold 35 . These immunosuppressants are mainly metabolized by the liver. Enzyme-inducing AEDs such as phenytoin, carbamazepine and phenobarbital may reduce the plasma concentration of cyclosporine it is therefore particularly important to monitor cyclosporine levels in such patients. It has been reported that phenytoin and phenobarbital reduce renal allograft survival, possibly due to increased metabolism of immunosuppressive agents 36, 37 . Owing to fewer...
Pregabalin is better tolerated when titrated. A recent study indicated that starting at the highest dose of 600 mg, while safe, led to 32 dropouts 93 . Pregabalin can be initiated at 50-75 mg twice daily, and titrated by 50-75 mg every week or two weeks. There are very few clinical data available regarding the safety and tolerability of doses above 600 mg day. Twice-daily dosing is commonly used, despite the short half-life of the drug. A study comparing efficacy and tolerability of the same total daily dose, given as twice daily or thrice daily showed no statistically significant difference, but there was a trend to both better efficacy and tolerability when thrice daily was used 94 . Therefore, it is reasonable to start off with a twice-daily regimen, and switch to thrice daily only if side-effects are present and or breakthrough seizures are occurring. Pregabalin levels have only recently become available, and their clinical utility is unknown. Common dose-related...
A Avoidance of nonsteroidal antiinflammatory drugs and treatment with alternative modalities ie oral or intraarticular
These occur either through competition for albumin binding or overlapping drug effects. With oral anticoagulants, the effect of warfarin (Coumadin) can be increased, and an NSAID-induced platelet defect can further increase the risk for bleeding. Gastrointestinal bleeding can occur in the setting of NSAID-related gastric mucosal defects. Decreased renal clearance resulting from NSAIDs and albumin-binding competition can lead to increased levels of lithium and an increased risk for hypoglycemia in patients taking oral hypoglycemic drugs.
Constipation, cramps, vomiting, flatulence, decreased appetite. CNS Headache, nervousness, insomnia, drowsiness, anxiety, dizziness, fa-tique, sedation, agitation. CV Hot flashes, palpitations. Pulmonary Infection, pharyngitis, nasal congestion, sinus headache, sinusitis, cough, dyspnea, bronchitis. GU Decreased libido, delayed ejaculation. Eyes Visual changes, eye pain, photophobia. Miscellaneous Sweating, rash, pruritus, urticaria, pain, asthenia, viral infection, fever, allergy, chills. Drug Interactions See individual agents.
Pharmacogenetics covers a new aspect of drug development, which will apply to discovery, development, and marketed programs. To date, benchmarkingtype information is not available. However, it is expected to play an important role in the near future for many pharmaceutical companies. To associate polymorphism with drug effects, DNA samples are obtained from both drug- and placebo-treated patients. To associate polymorphism with disease risk (i.e., target discovery validation), DNA from patients affected by a specific disease should be compared with DNA from patients unaffected by that disease. The latter group may be affected with other disease states hence, patient DNA samples from one trial may serve as controls in another, provided that they have been obtained from a population of comparable ethnic composition. In effect, supplementary DNA collection will not be necessary to effect properly controlled pharmacogenetic and target validation studies. Moreover, power simulations...
Special Concerns Use with caution during lactation and in elderly clients. There are no efficacy studies in children. GI disorders may limit absorption of atovaquone. Side Effects Since many clients taking atovaquone have complications of HIV disease, it is often difficult to distinguish side effects caused by atovaquone from symptoms caused by the underlying medical condition. Dermatologic Rash (including maculopapular), pruritus. Oral Can-didiasis, taste perversion. GI Nausea, diarrhea, vomiting, abdominal pain, constipation, dyspepsia. CNS Headache, fever, insomnia, dizziness, anxiety, anorexia. Respiratory Cough, sinusitis, rhinitis. Hematologic Anemia, neutropenia. Miscellaneous Asthenia, pain, sweating, hypo-glycemia, hypotension, hyperglyce-mia, hyponatremia. Drug Interactions Since atova-quone is highly bound to plasma proteins ( 99 9 ), caution should be exercised when giving the drug with other highly plasma protein-bound
Contraindications Myeloprolifera-tive disorders. Use with other agents known to suppress bone marrow function. Severe CNS depression or coma due to any cause. Lactation. Special Concerns Use with caution in clients with known CV disease, prostatic hypertrophy, narrow angle glaucoma, hepatic or renal disease. Side Effects Hematologie Agranu-locytosis, leukopenia, neutropenia, eosinophilia. CNS Seizures (appear to be dose dependent), drowsiness or sedation, dizziness, vertigo, headache, tremor, restlessness, nightmares, hypokinesia, akinesia, agitation, akathisia, confusion, rigidity, fatigue, insomnia, hyperkinesia, weakness, lethargy, slurred speech, ataxia, depression, anxiety, epilepti-form movements. CV Orthostatic hypotension (especially initially), tachycardia, syncope, hypertension, angina, chest pain, cardiac abnormalities, changes in ECG. Neuroleptic malignant syndrome Hyperpyrexia, muscle rigidity, altered mental status, irregular pulse or BP, tachycardia, diaphoresis,...
The clinical presentation of benzodiazepine intoxication is nonspecific. Clinical assessment also may be difficult because of the frequent coingestion of other agents. Except for additive effects, drug interactions of benzodiazepines with other sedative-hypnotics are unusual.
Drug Interactions Alprazolam T Alprazolam levels and l psychomotor performance Carbamazepine T Serum levels of carbamazepine toxicity Diazepam Fluoxetine T half-life of diazepam excessive sedation or impaired psychomotor skills MAO inhibitors MAO inhibitors should be discontinued 14 days before initiation of fluoxetine therapy due to the possibility of symptoms resembling a neuroleptic malignant syndrome or fatal reactions Phenytoin Fluoxetine may T phenytoin levels
Special Concerns Use with caution during lactation. Geriatric clients are at greater risk of developing bradycardia. Aortic or mitral valve disease, asthma, COPD, diabetes mellitus, major surgery, renal disease, thyroid disease, well-compensated heart failure. Side Effects Oral Dry mouth. CV Bradycardia, dysrhythmias, hypotension. CNS Depression, dizziness, fatigue, insomnia, lethargy. GI Diarrhea, dyspepsia, vomiting. Hematologic Aranulocytosis, throm-bocytopenia. Skin Pruritus, rash, increased skin pigmentation, sweating, dry skin, alopecia, skin irritation, psoriasis. Ophthalmic Dry, burning eyes, conjunctivitis, kerati-tis. GU Impotence. Respiratory Bronchospasm, dyspnea, pharyngitis. Drug Interactions See also Drug Interactions of concern to the dental
Oral Dry mouth. GI N&V, abdominal discomfort, constipation, anorexia, dysphagia. CNS Confusion, hallucinations, fainting, drowsiness, dizziness, insomnia, depression, vertigo, anxiety, fatigue, headache, lethargy, nightmares. GU Urinary incontinence, urinary retention, urinary frequency. Other Abnormal involuntary movements, asthenia, visual disturbances, ataxia, hypotension, SOB, edema of feet and ankles, blepharospasm, erythromelalgia, skin mottling, nasal stuffiness, paresthe-sia, skin rash. Drug Interactions Alcohol T Chance of GI toxicity alcohol intolerance Butyrophenones i Effect of bromocriptine because butyrophe-nones are dopamine antagonists Erythromycins T Levels of bromocriptine T pharmacologic and toxic effects Phenothiazines i Effect of bromocriptine because phenoth-iazines are dopamine antagonists Sympathomimetics T Side effects of bromocriptine, including ventricular tachycardia and cardiac dysfunction
CNS Dizziness, headache. Dermatologie. Rash, urticaria. Drug Interactions Inhibition of platelet adhesiveness by guaifenesin may result in bleeding tendencies. How Supplied Capsule 200 mg Capsule, extended release 300 mg Liquid 100 mg 5 mL, 200 mg 5 mL Syrup 50 mg 5 mL, 100 mg 5 mL Tablet 100 mg, 200 mg Tablet, extended release 600 mg, 800 mg, 1,200 mg
Side Effects CNS Sedation (transient), weakness, headache, asthenia, dizziness, paresthesias, Parkinson-like symptoms, psychic disturbances, symptoms of CV impairment, choreoathetotic movements, Bell's palsy, decreased mental acuity, verbal memory impairment. CV Bradycardia, orthostatic hypotension, hypersensitivity of carotid sinus, worsening of angina, paradoxical hypertensive response (after IV), myocarditis, CHF, pericarditis, vasculitis. Oral Dry mouth, bleeding, lichenoid drug reaction, sore or black tongue, sialoadenitis. GI N&V, abdominal distention, diarrhea or constipation, flatus, colitis, pancreatitis. Hematologic Hemolytic anemia, leukopenia, granulocytopenia, thrombocytopenia, bone marrow depression. Endocrine Gynecomas-tia, amenorrhea, galactorrhea, lactation, hyperprolactinemia. GU Impotence, failure to ejaculate, decreased libido. Dermatologie Rash, toxic epidermal necrolysis. Hepatic Jaundice, hepatitis, liver disorders, abnormal liver function tests. Miscellaneous...
Dermatologic Erythema, pruritus, or burning at the site of application cutaneous hypersensitivity, sweating, rash at application site. Body as a whole Allergy, back pain. Oral Dry mouth. GI Diarrhea, dyspepsia, abdominal pain, constipation, N&V. Musculoskeletal Arthralgia, myalgia. CNS Abnormal dreams, somnolence, dizziness, impaired concentration, headache, insomnia. CV Tachycardia, hypertension. Respiratory Increased cough, pharyngitis, sinusitis. GU Dysmenorrhea. Drug Interactions Propoxyphene l Metabolism of propoxyphene
Use with caution during lactation. Safety and efficacy in children have not been established. Side Effects Commonly, dizziness, lightheadedness, N&V, and sedation these effects are more common in ambulatory clients than nonam-bulatory clients. Other side effects include euphoria, dysphoria, constipation, skin rash, and pruritus. See also individual components. Drug Interactions Anticholinergic drugs Production of paralytic ileus
The calcium channel blockers block the movement of calcium across L-type calcium channels. The main drugs that share this action are verapamil (a phenylalkylamine), diltiazem (a benzthiazepine), and the dihydropyridines, which include amlodipine, darodipine, felodipine, isradi-pine, lacidipine, lercanidipine, manidipine, nicardipine, nifedipine, nimodipine, nisoldipine, and nitrendipine. Other agents, for example prenylamine and lidoflazine, are now rarely used, and perhexiline, having failed to reach the market at all in some countries, was withdrawn in the UK after continuing concerns about its safety (1). Mibefradil blocks T type calcium channels it was withdrawn within 1 year of marketing because of multiple drug interactions, emphasizing the need for rigorous drug assessment before release and the importance of postmarketing surveillance of new drugs (2).
Ergot problems can be exacerbated by caffeine, by tobacco cigarettes, by the HIV AIDS drug ritonavir, and possibly by the antidepressant fluoxetine (Prozac). A case report relates instances of bad reactions occurring when people used ergot products along with beta blockers, a type of drug that is typically prescribed for heart problems.
P450, or inducing specific isoforms of this enzyme system. However, drug interactions involving these isoenzymes and omeprazole or lansoprazole are uncommon and generally appear to be clinically unimportant. Pantoprazole seems to have a lower drug interaction potential than either omeprazole or lansoprazole.
A meta-analysis of 20 short-term studies of five SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline) has been published (11). There were no overall differences in efficacy, but fluoxetine had a slower onset of action. Analysis of tolerability showed the expected adverse effects profile, the most common adverse event being nausea, followed by headache, dizziness, and tremor. The rate of withdrawal from treatment because of adverse effects was significantly greater with fluvoxamine (RR 1.9 CI 1.2, 3.0). Data available from the UK Committee on Safety of Medicines suggested that withdrawal reactions were most common with paroxetine and least common with fluoxetine (presumably because of the long half-life of its active metabolite norfluoxetine). There were more gastrointestinal reactions to fluvoxamine and paroxetine. This pattern was reflected in prescription-event monitoring data. Citalopram and sertraline were least likely to cause drug interactions, but citalopram...
Drug interactions may include increased cholinergic effects with bethanecol increased plasma tacrine levels with cimetidine or fluvoxamine. This may occur by inhibition of P450 1A2. The association of tacrine with haloperidol may increase parkinsonism and tacrine increases theophylline concentration.
Venlafaxine hydrochloride has few currently known significant drug interactions and is therefore easier to use with patients on complicated drug regimens. A potential disadvantage of venlafaxine hydrochloride is its very short half-life 4 hours for the parent drug and 10 hours for the active metabolite. This short half-life is associated with rapid excretion of the drug if patients miss a day's doses, and some patients then develop a withdrawal syndrome manifested by dysphoria, anxiety, dizziness, and complaints of peripheral electrical sensations. The withdrawal syndrome may occur even with the sustained-release formulation.
Affect liver metabolism, in this case by stimulating the CYP3A enzyme pathway that metabolizes many drugs. Aside from various drug interactions, the other side effects are mainly neurological, in particular, dizziness, vivid dreams, and euphoria. These symptoms usually, but do not always, recede after the first month. They can be ameliorated by taking efavirenz at bedtime. one odd neurological side effect is indicated by reports that those on efavirenz can test positive for marijuana use. This can pose serious problems for individuals in certain jobs. other major efavirenz side effects involve skin rashes, which are almost always mild to moderate and transient. There have been concerns about fetal outcomes of pregnant women exposed to efavirenz. Because of findings in studies with animals, DuPont has issued warnings that women on efavirenz use two methods of birth control (one a barrier method) to prevent pregnancy. Finally, note that a major fear about efavirenz use is its tendency...
Pharmacokinetic and pharmacodynamic factors, comor-bid medical illnesses, and concurrent medications increase side effects and drug interactions in this population. The geriatric psychopharmacology maxim start low and go slow should be followed in the use of these medications. The appropriate starting dose of antipsychotics in the elderly is 25 of the adult dose and daily maintenance dose is 30 to 50 . Antipsychotic medications in the elderly can require 6 weeks or longer for optimum therapeutic effects. Patients with Dementia generally require smaller doses of an-tipsychotics than patients with Schizophrenia.
The emergence of concerns regarding the long-term safety of PIs, particularly elevations in plasma lipids and fat redistribution (lipodystrophy syndrome), and their propensity to cause drug interactions have led to a reevaluation of the role of these agents as life-long therapies for persons with HIV-1 infection. This has heralded much debate in the HIV community regarding the choice of initial therapy, between PI-containing and PI-sparing regimens, and the relative tolerability of the various therapies has become an important focus in this debate.
Drug prophylaxis against opportunistic infections has become a cornerstone of treatment for AIDS patients. However, it is important to note that as HIV infection progresses to advanced and late-stage disease, there may be cases in which the advantages and disadvantages of prophylactic or suppressive drugs for some opportunistic infections should be discussed with a physician. The advantages of prophylactic therapy include prevention of disease, decreased severity of disease, decreased risk of and necessity for hospitalization, probable decrease in the number of sick days and lost wages, potential psychological benefits, and preservation of health insurance benefits by staying healthier. The disadvantages of prophylactic or suppressive therapy for some infections can include the following additional drug side effects the risk of harmful drug interactions, which becomes a growing consideration as the number of drugs taken increases the possibility that use of the drug will produce...
Drug interactions that may lead to an enhanced effect. Reproduced from Seymour RM, Routledge PA (1998). Important drug - drug interactions in the elderly. Drugs & Ageing 12, 485 - 94 by permission of Adis International Ltd, Auckland, New Zealand. Reproduced from Seymour RM, Routledge PA (1998). Important drug - drug interactions in the elderly. Drugs & Ageing 12, 485 - 94 by permission of Adis International Ltd, Auckland, New Zealand. Despite the many ways in which drug-drug interactions may occur, it is likely that only about 10 of potential interactions result in clinically significant events. However, while death or serious clinical consequences are rare, low grade, clinical morbidity in the elderly may be much more common (Seymour and Routledge, 1998). Non-specific complaints such as confusion, lethargy, weakness, dizziness, incontinence, depression and falling may indicate an underlying drug-drug interaction. The drug interactions of clinical importance in the elderly...
Increases in AST, ALT, bilirubin, alkaline phosphatase. Hematologic Thrombocytopenia, eosinophilia, hemolysis, leukopenia, hemolytic anemia. Allergic Flu-like symptoms, dyspnea, wheezing, SOB, purpura, pruritus, urticaria, skin rashes, sore mouth and tongue, conjunctivitis. Renal Hematuria, hemoglobinuria, renal insufficiency, acute renal failure. Miscellaneous Visual disturbances, muscle weakness or pain, arthralgia, decreased BP, osteomalacia, menstrual disturbances, edema of face and extremities, adrenocorti-cal insufficiency, increases in BUN and serum uric acid. NOTE Body fluids and feces may be red-orange. Drug Interactions Acetaminophen i Effect of acetaminophen due to T breakdown by liver
Appropriate prescribing Elderly patients often receive multiple drugs for their multiple diseases. This greatly increases the risk of drug interactions as well as adverse reactions, and may affect compliance (see Taking medicines to best effect under General guidance). The balance of benefit and harm of some medicines may be altered in the elderly. Therefore, elderly patients' medicines should be reviewed regularly and medicines which are not of benefit should be stopped. Non-pharmacological measures may be more appropriate for symptoms such as headache, sleeplessness, and lightheadedness when associated with social stress as in widowhood, loneliness, and family dispersal. In some cases prophylactic drugs are inappropriate if they are likely to complicate existing treatment or
The selective effects of drugs on specific neurotransmitter systems may be additive or competitive. This potential for drug interaction must be considered whenever such drugs are administered concurrently. To minimize such interactions, a drug-free period may be required when modifying therapy, and development of desensitized and supersensitive states with prolonged therapy may limit the speed with which one drug may be halted and another started. An excitatory effect is commonly observed with low concentrations of certain depressant drugs due either to depression of inhibitory systems or to a transient increase in the release of excitatory transmitters. Examples are the stage of excitement during induction of general anesthesia and the effects of alcohol to relieve inhibitions. The excitatory phase occurs only with low concentrations of the depressant uniform depression ensues with increasing drug concentration. The excitatory effects can be minimized, when appropriate, by...
Venlafaxine is metabolized by the liver to an equipotent metabolite, O-desmethylvenlafaxine. The half-life of venlafaxine is four hours, but the active metabolite has a half-life of ten hours. Duloxetine is hepatically metabolized and 70 percent renally excreted. The dose should be reduced in patients with impaired renal function and is contraindicated for use by patients with alcohol use disorders. Milnacipran does not significantly inhibit or induce P450 isoenzymes, thereby reducing the potential for adverse drug-drug interactions.85
Many H1 antihistamines are metabolized by CYPs. Thus, inhibitors of CYP activity such as macrolide antibiotics (e.g., erythromycin) or imidazole antifungals (e.g., ketoconazole) can increase H1 antihistamine levels, leading to toxicity. Some newer antihistamines, such as cetirizine, fexofe-nadine, levocabastine, and acrivastine, are not subject to these drug interactions.
Gabapentin and pregabalin are structually related compounds and have similar side effect profiles. They are usually well tolerated with no contraindications except for known hypersensitivity to their components and lack drug interactions although additive side effects may be seen. Dose reduction is needed in patients with impaired renal function. The most common adverse reactions are dose-related somnolence, which seems to be higher in the SCI population (41 in the pregabalin group and 9 in the placebo group 23 ) than in peripheral pain trials, and dizziness (occurring in 20 - 40 ). These side effects pose a risk for accidental injury in the elderly. Other adverse reactions include dry mouth, asthenia, blurred vision, ataxia, peripheral edema, and weight gain.
Drug Interactions Because sertraline is highly bound to plasma proteins, its use with other drugs that are also highly protein bound may lead to displacement, resulting in higher plasma levels of the drug and possibly increased side effects. Alcohol Concurrent use is not recommended in depressed clients Benzodiazepines l Clearance of benzodiazepines metabolized by hepatic oxidation Cimetidine T Half-life and blood levels of sertraline Diazepam T Plasma levels of de-smethyldiazepam (significance not known)
Dose (adult) benzodiazepine overdose first dose 0.2 mg IV over 15 seconds, second dose 0.3 mg IV over 30 seconds, if no adequate response give third dose 0.5 mg IV over 30 seconds, may repeat at 1 minute intervals up to a total dose of 3 mg reversal of conscious sedation 0.2 mg IV over 15 seconds, may repeat at 1 minute intervals to a total dose of 1 mg. Dose (ped) 0.01 mg kg IV (max 0.2 mg kg), then 0.005-0.01 mg kg dose given at 1 minute intervals up to a max total dose of 1 mg. Clearance 100 hepatic metabolism 90 -95 renal elimination of metabolite. Adverse effects seizures, acute withdrawal, nausea, dizziness, agitation, arrhythmias, hypertension. Drug interactions do not use in suspected tricyclic drug overdose, seizure-prone patients, unknown drug overdoses.
Few drug interactions have been reported with amantadine. Ethanol in combination with amantadine can increase central nervous system (CNS) side effects, such as dizziness, confusion, and orthostatic hypotension (13). Antimuscarinics and medication with significant anticholinergic activity may increase the anticholinergic side effects of amantadine (13). A potential interaction of amantadine with bupropion has been reported (13,14). Affected patients develop restlessness, agitation, gait disturbance, and dizziness, and may require hospitalization depending upon severity. There is also a case report, suggesting amantadine toxicity from an interaction with hydrochlorothiazide-triamterene (15).
Side Effects Body as a whole Headache, infection, asthenia, back pain, chest pain. CV Postural hypotension, syncope. GI Diarrhea, nausea, tooth disorder. CNS Dizziness, vertigo, somnolence, insomnia, decreased libido. Respiratory Rhinitis, pharyngitis, increased cough, sinusitis. GU Abnormal ejaculation. Miscellaneous Amblyopia. Drug Interactions Cimetidine causes significant l in clearance of tamsulosin.
Older patients frequently take multiple medications, which makes the potential for drug interactions with antidepressant medications a concern. The potential for interaction is generally higher with older antidepressant compounds (such as TCAs and MAOIs), which are associated with clinically significant interactions with many medications frequently prescribed to elderly patients (Spina et al, 2002). New antidepressants have a more selective mechanism of action and a lower potential for pharmacodynamic drug interactions.
Pregabalin, the successor drug of gabapentin was shown to be efficacious in PHN, DPN and spinal cord injury (until now 7 published studies) 22, 23 . Its mechanism of action has now been solved a modulating action on the a28-subunit of central Ca-channels located presynaptically at the nociceptive terminal in the dorsal horn spinal cord. Pregabalin has a low potential for drug-drug interactions, and no negative impact on cardiac function. In addition, pregabalin was noted considerably to improve sleep disturbances in neuropathic pain
Significant drug-drug interactions may be encountered when Ca2+ channel blockers are used to treat hypertension. Concurrent use of a p receptor antagonist with a nondihydropyridine drug may magnify negative chronotropic and inotropic effects of these drugs or cause heart block in susceptible patients. Verapamil blocks the P-glycoprotein drug transporter in kidney and liver and inhibits the elimination of digoxin and other drugs (see Chapter 2). When used with quinidine, Ca2+ channel blockers may cause excessive hypotension, particularly in patients with idiopathic hypertrophic subaortic stenosis.
John's wort use is the numerous clinically significant herb-drug interactions that have been reported. St. John's wort appears to be a major inducer of the cytochrome P450 3A4 (CYP3A4) enzyme system in the liver. This first came to light following acute heart transplant rejection in a person taking cyclosporin and St. John's wort. The cy-closporin levels remained subtherapeutic until St. John's wort was discontinued. A similar phenomenon was noted with AIDS patients taking protease inhibitors and nonnucleoside reverse transcriptase inhibitors (NNRTIs). Concomitant use of St. John's wort reduced the effectiveness of these medicines as well. Since then, St. John's wort has been shown to reduce plasma levels of digoxin, warfarin, theophylline, and oral contraceptives. Breakthrough bleeding has been observed in young women taking this herb, and patients starting oral contraceptives should be counseled to use backup contraception if they take St. John's wort...
Drug Interactions SSRIs interact with other drugs that have effects on 5-HT neurotransmission, including TCAs, buspirone, sumatriptan and tryptophan, but particularly important is the interaction with MAOIs that can lead to a syner-gistic increase in synaptic serotonin. This can result in the serotonin syndrome, comprising restlessness, irritability, tremor, sweating and hyperreflexia. The syndrome can be lethal (Sternbach 1991). In general clinical practice, there should be a washout of 2 weeks between discontinuing MAOI therapy and starting SSRI a washout of 1-2 weeks should follow SSRI discontinuation (5 weeks for fluoxetine). The drugs have variable potential for drug interactions via hepatic CYP450 enzymes (Table 5). Escitalopram has the lowest potential for interactions.
Action Kinetics Competitively inhibits gastric acid secretion by blocking the effect of histamine on histamine H2 receptors. Weak inhibitor of cytochrome P-450 (drug-metabolizing enzymes) thus, drug interactions involving inhibition of hepatic metabolism are not expected to occur. Food increases the bio-availability. Peak effect PO, 1-3 hr Drug Interactions Antacids Antacids may l the absorption of ranitidine Diazepam l Effect of diazepam due to l absorption from GI tract How Supplied Capsule 150 mg, 300 mg Granule for reconstitution 150 mg Injection 1 mg mL, 25 mg mL Syrup 15 mg mL Tablet 75 mg, 150 mg, 300 mg Tablet, effervescent 150 mg
Drug drug interactions Drug interactions can be either metabolic or pharmacological. Drugs interact because they share the same metabolic (chemical breakdown) pathways, or directly interact with each other chemically. The chemical interaction of drugs can create totally different compounds in the body and can be dangerous. Also, these chemical combinations can be additive as one drug potentiates or increases the effects of another. Marinol is no exception. It has several notable drug drug interactions, though none life-threatening. Since Cannabis is chemically similar to Marinol it is reasonable to consider the following drug interactions in connection with Cannabis. Any person taking other pharmaceuticals along with Marinol or Cannabis should research interactions and consult with the prescriber.
From the time of its introduction in 1965, indomethacin (Indocin) has been widely used as an analgesic to relieve inflammatory pain associated with RA, OA and ankylosing spondylitis, and, to a lesser extent, in gout. Although both its analgesic and anti-inflammatory activities are well established, its use is often limited because of frequent GI distress and potential drug interactions, especially with warfarin furosemide, and lithium (i.e., it elevates blood levels of
Side Effects CV Orthostatic hypotension, hypotension, MI, angina pectoris, palpitations, paradoxical pressor reaction, tachycardia. CNS Headache, dizziness, psychoses, tremors, depression, anxiety, disorientation. GI N&V, diarrhea, anorexia, constipation, paralytic ileus. Allergic Rash, urticaria, fever, chills, arthralgia, pruritus, eosinophilia. Rarely, hepatitis, obstructive jaundice. Hematologic Decrease in hemoglobin and RBCs, purpura, agranulocytosis, leukope-nia. Other Peripheral neuritis (paresthesias, numbness, tingling), dyspnea, impotence, nasal congestion, edema, muscle cramps, lacrimation, flushing, conjunctivitis, difficulty in urination, lupus-like syndrome, lym-phadenopathy, splenomegaly. Side effects are less severe when dosage is increased slowly. NOTE Hydrala-zine may cause symptoms resembling system lupus erythematosus (e.g., arthralgia, dermatoses, fever, splenomegaly, glomerulonephritis). Residual effects may persist for several years and long-term treatment with...
Drug-Drug Interactions The efficacy of St John's wort in major depression has not been established. There is evidence to suggest it may be effective in milder forms of depression. Its clinical use is limited by uncertainty concerning its active components, propensity for drug-drug interactions, and paucity of safety data. Currently, there is no available literature on using St John's wort in children and adolescents, in patients with major psychiatric comorbidities, or in pregnant or lactating women. The drug-drug interactions associated with St John's wort limit its use in patients with other medical or psychiatric comorbidities. Its efficacy is not established in moderate to severe major depression. Further research and well-designed clinical trials are needed to determine the efficacy of St John's wort in the treatment of mood disorders.
Cause a profound drop in BP following the first dose initiate therapy under close medical supervision. Use with caution in renal disease (especially renal artery stenosis) as increases in BUN and serum creatinine have occurred. Use with caution in clients with aortic stenosis due to possible decreased coronary perfusion following vasodilator use. With the exception of fosinopril (contraindicated), use with caution during lactation. Geriatric clients may show a greater sensitivity to the hypotensive effects of ACE inhibitors although these drugs may preserve or improve renal function and reverse LV hypertrophy. For most ACE inhibitors, safety and effectiveness have not been determined in children. Side Effects See individual entries. Side effects common to most ACE inhibitors include the following. Oral Dry mouth, loss of taste, oral ulceration. GI Abdominal pain, N&V, diarrhea, constipation, dry mouth. CNS Sleep disturbances, insomnia, headache, dizziness, fatigue, nervousness,...
Potential drug-to-drug interactions are a concern. Concomitant use of sibutramine with CNS drugs, especially serotonergic agents, has not been studied. Caution is advised when simultaneously prescribing sibutramine with serotonin selective reuptake inhibitors (SSRI). Also, use of sibutramine and migraine headache medication like sumatriptan succinate (Imitrex), as well as other common migraine headache medications like dihydroergotamine, fentanyl, lithium, tryptophan or meperidine, must be approached with caution. Combining these medications with sibutramine may precipitate a potentially fatal serotonin syndrome reaction 11 . The orlistat package insert lists as a precaution low vitamin A, D, E, and beta-carotene values in some patients who use the medication the manufacturer recommends patients take a fat-soluble multivitamin daily. Contraindications for use of orlistat are malabsorption syndrome, cholestasis, and hypersensitivity to components within the pill. Minimal drug-to-drug...
After ophthalmic use Transient ocular burning or discomfort, stinging, redness, itching, photophobia, tearing, and dryness. Drug Interactions Antacids l Effects of antacids How Supplied Injection 4 mg mL, 20 mg mL, 40 mg mL Ophthalmic solution 0.3 Tablet 200 mg, 300 mg, 400 mg
Duction defects, sinus pause, junc-tional rhythm, AV block palpitations, sustained ventricular tachycardia, cardiac chest pain, CHF, cardiac death, hypotension, hypertension, atrial fibrillation, atrial flutter, syncope, bradycardia, cardiac arrest, MI, pulmonary embolism, vasodilation, thrombophlebitis, cerebrovascular events. CNS Dizziness (common), anxiety, headache, fatigue, nervousness, paresthesias, sleep disorders, tremor, anxiety, hypoesthesias, depression, euphoria, somnolence, agitation, confusion, seizures, hallucinations, loss of memory, vertigo, coma. Oral Dry mouth, bitter taste. GI Nausea, abdominal pain, vomiting, diarrhea, dyspepsia, anorexia, ileus, flatulence, dysphagia. Musculoskeletal Asthenia, abnormal gait, akathisia, ataxia, abnormal coordination, dys-kinesia, pain. GU Urinary retention, dysuria, urinary incontinence, urinary frequency, impotence, kidney pain, decreased libido. Respiratory Dyspnea, apnea, asthma, hyperventilation, pharyngitis, cough, sinusitis....
Gabapentin and pregabalin act at the a28-subunit of presynaptic calcium channels on primary nociceptive endings.56,57 Dizziness and drowsiness are the most commonly reported adverse events, especially during upward titration to targeted doses. Both drugs have a low potential for drug interactions, and no negative impact on cardiac function. Peripheral edema occurs in some patients. Both drugs have been shown to be effective in the management of PHN. Pregabalin has superior bio-availability and dose titration-to-effect seems to produce fewer side effects than gabapentin.58 Gabapentin and pregabalin improve sleep disturbance, overall mood, and other measures of quality of life in neuropathic pain patients.56,59 I
Successful opioid therapy requires that the benefits of analgesia clearly outweigh treatment-related adverse effects. This implies that a detailed understanding of adverse opioid effects and the strategies used to prevent and manage them are essential skills for all involved in postoperative pain management. The pathophysiological mechanisms contributing to adverse opioid effects are incompletely understood. The appearance of these effects depends on a number of factors, including patient age, extent of disease, concurrent organ dysfunction, prior opioid exposure, the route of drug administration, and the adverse drug interactions. The potential for additive side effects and serious toxicity from drug combinations must be recognized. The sedative effect of an opioid may add to that produced by numerous other centrally acting drugs, such as anxiolytics, neuroleptics and antidepressants. Likewise, drugs with anticholinergic effects probably worsen the constipatory effects of opioids. As...
DEPENDENCE AND TOLERANCE All drugs of this group are addictive. Psychologic and physical dependence and tolerance develop even when clients use clinical doses. Tolerance is characterized by the fact that the client requires shorter periods of time between doses or larger doses for relief of pain. Tolerance usually develops faster when the narcotic analgesic is administered regularly and when the dose is large. Drug Interactions Alcohol, ethyl Potentiation or addition of CNS depressant effects concomitant use may lead to drowsiness, lethargy, stupor, respiratory collapse, coma, or death Anesthetics, general See Alcohol Antianxiety drugs See Alcohol Antidepressants, tricyclic T Narcotic-induced respiratory depression Antihistamines See Alcohol Barbiturates See Alcohol CNS depressants See Alcohol MAO inhibitors Possible potentia-tion of either MAO inhibitor (excitation, hypertension) or narcotic (hypotension, coma) effects death has resulted
Side Effects GI N&V, anorexia, abdominal cramps and pain, diarrhea, altered sensation of taste. CNS Headache, dizziness, insomnia, drowsiness, confusion, nervousness. Hypersensitivity Rash, pruritus, urticaria, edema, angioedema, eosinophilia, anaphylaxis (rare), toxic epidermal necrolysis (rare), erythema multiforme, Stevens-Johnson syndrome. Other Tingling sensation, photophobia, perineal burning, tinnitus, thrombocytopenia. Drug Interactions Probenecid i Excretion of cinoxacin i concentration in the urine.
Vigabatrin (Sabril) is an enzyme-induced irreversible inhibitor of GABA aminotransferase resulting in increased cerebral GABA levels. It is rapidly absorbed, unaffected by food consumption. It is not protein-bound and is excreted unmetabolized by the renal system. It has no significant drug interactions. Blood levels are not useful in determining therapeutic effect or toxicity. Abnormalities of cerebral myelin have not been substantiated in humans however, recently investigators identified visual changes in adults using vigabatrin. Dosage is initated at 30 mg kg day and gradually increased over 4 weeks to a maximum of 100 mg kg day (bid dosage) if necessary for improved seizure control. European studies initially found it very effective in the treatment of infantile spasms associated with tuberous sclerosis. More common side effects include dizziness, ataxia, and behavioral changes in children. As with all AEDs, seizure activation has been reported but cannot be predicted with any...
GU Vaginal moniliasis, urinary incontinence, renal failure. Hematologic Eosinophilia, leukopenia, increased or decreased platelets, decreased hemoglobin, leukocytosis. Miscellaneous Gluco-suria, pyuria, increased or decreased potassium, asthenia, back or chest pain, myalgia, arthralgia, purpura, vertigo, tinnitus, conjunctivitis. Additional Drug Interactions Bismuth subsalicylate Bioavailability of enoxacin is l when bismuth subsalicylate is given within 1 hr should not use together How Supplied Tablet 200 mg, 400 mg
Hematologic Anemia, lym-phadenopathy, spleen disorder. Respiratory Cough, dyspnea, halitosis, pharyngeal hyperemia, pharyngitis, pneumonia, rales, rhonchi, respiratory failure, sinus disorder, sinusitis, URI. Dermatologie. Body odor, contact dermatitis, dermatitis, dry skin, flushing, folliculitis, herpes simplex, herpes zoster, night sweats, pruritus, seborrhea, skin disorder, skin infection, sweating, urticaria. GU Nephrolithiasis, dysuria, hematuria, hydronephrosis, nocturia, PMS, proteinuria, renal colic, urinary frequency, UTI, uterine abnormality, urine sediment abnormality, urolithiasis. Ophthalmic Accommodation disorder, blurred vision, eye pain, eye swelling, orbital edema. Miscellaneous Asymptomatic hyperbilirubinemia, food allergy, taste disorder. Drug Interactions Astemizole i Metabolism of astem-izole possibility of cardiac arrhythmias and prolonged sedation Clarithromycin T Plasma levels of both indinavir and clarithromycin Fluconazole i Plasma levels of in-dinavir
Urinary frequency, acute urinary retention, oliguria with hypertension, impotence, renal failure, azotemia, albuminuria, glycosuria, increased BUN, microscopic deposits in urine. Pulmonary Pulmonary hypersensi-tivity characterized by fever, dyspnea, pneumonitis, or pneumonia. Dermatologic Pruritus, urticaria, photosensitivity, exfoliative dermatitis, erythematous rashes, alterations in pigmentation, alopecia, sweating, purpura, toxic epidermal necrolysis (Lyell's syndrome), Stevens-Johnson syndrome, aggravation of disseminated lupus erythematosus, alopecia, erythema nodosum or multiforme. Ophthalmologic Nystagmus, double vision, blurred vision, oculomotor disturbances, conjunctivitis scattered, punctate lens opacities. Hepatic Abnormal liver function tests, cholestatic or hepatocellular jaundice, hepatitis, acute intermittent porphyria. Other Peripheral neuritis, paresthesias, tinnitus, fever, chills, joint and muscle aches and leg cramps, adenopathy or lymphade-nopathy, inappropriate...
Special Concerns Diabetes mellitus, hyperthyroidism, lactation, myasthe-nia gravis, peripheral vascular disease, renal disease. Side Effects Oral Dry mouth, taste disturbances. CV AV block, bradycardia, CHF, hypotension, palpitations. CNS Depression, dizziness, drowsiness, fatigue, hallucinations, headache, lethargy, paresthesias. GI Colitis, constipation, cramps, diarrhea, flatulence, hepatomegaly, nausea, vomiting. Hematologic Agranulocytosis, thrombocytopenia. Allergie fever, sore throat, respiratory distress, rash, pharyngitis, laryngos-pasm, anaphylaxis. Skin pruritus, rash, fever. Ophthalmic Dry, burning eyes. GU Dysuria, impotence, noctu-ria. Other Hypoglycemia or hyper-glycemia. Respiratory Broncho-spasm, cough, dyspnea, laryngos-pasm, nasal stuffiness, pharyngitis, respiratory dysfunction, wheezing. Drug Interactions See also Drug Interaetions for Beta-Adrenergie Blocking Agents and Antihyperten-sive Agents.
Some recreational users combine butorphanol with the common cold and allergy remedy diphenhydramine to produce a typical opiate-type stupor. Users of that combination sometimes report loss of interest in other drugs. Unwanted results can include emotional flip-flops, dizziness, nausea, vomiting, breathing difficulty, and general reduction of mental and physical abilities. Withdrawal symptoms from the combination may involve impaired concentration, mental restlessness and unease, and emotional instability and peevishness.
Metabolized in the liver by either glucuronidation or beta-oxidation. Valproic acid is not enzyme inducer, but it may cause clinically relevant drug interactions by inhibiting the metabolism of selected substrates such as phenobarbital and lamotrigine (39). Side effects of valproic acid include nausea or dyspepsia, sedation, headaches, dizziness, and tremors.
DRUG INTERACTIONS Do not use if you take Antihypertensives, as they may combine to lower blood pressure excessively antihistamines, phenothi-azines, or tricyclic antidepressants, as they may combine to produce pronounced dry mouth, blurry vision, constipation, low blood pressure, rapid heart rate, and even mental confusion.
DRUG INTERACTIONS Use with extra caution if you take Albuterol (Combivent, Ventolin) for asthma or other breathing problems, as atomoxetine can increase the effect of albuterol on the cardiovascular system, raising heart rate and blood pressure MAOI antidepressants, as their use with atomoxetine can cause a
DRUG INTERACTIONS Do not use if you take Other SSRIs, St. John's wort, or tryptophan, as their use with citalopram can cause the serotonin syndrome MAOI antidepressants, as their use with citalopram can cause a serious, sometimes fatal, reaction of agitation, fever, cardiovascular changes and mental status changes.
Drug interactions The serotonin syndrome was reported in 45-year-old white man who received intravenous linezolid (600 mg 12 hourly) and sertraline (205A). Drug interactions There may be difficulty in reversing neuromuscular blockade if polymyxin is given in combination with neuromuscular blocking drugs (208R).
DRUG INTERACTIONS Don't use if you take Other SSRIs, St. John's wort, or tryptophan or other serotonin reuptake inhibitors, as duloxetine can cause the serotonin syndrome, which consists of potentially dangerous alterations in pulse, blood pressure, hyperactivity, and mental status changes (see chapter 19) MAOI antidepressants, as their use with duloxetine can cause a serious, sometimes fatal, reaction of agitation, fever, cardiovascular changes, and mental status changes.
DRUG INTERACTIONS Don't use if you take Other SSRIs, St. John's wort, or tryptophan, as their use with escitalopram can cause the serotonin syndrome MAOI antidepressants, as their use with escitalopram can cause a serious, sometimes fatal, reaction of agitation, fever, cardiovascular changes, and mental status changes.
DRUG INTERACTIONS Use with extra caution if you take Clarithromicin (Biaxin), itraconozole (Sporonox), ketoconozole (Nizoril), nefazodone (Serzone), nelfinavir (Viracept), ritonavir (Norvir), or troleandomycin (Tao) because the breakdown of eszopiclone may be impaired, leading to a more intense effect anticonvulsants, antidepressants, antihistamines, antipsychotics, barbiturates, benzodiazepines, or any drug that causes sedation or central nervous system depression, because the combination with eszopiclone can cause pronounced sedation.
DRUG INTERACTIONS Use with extra caution if you take Tricyclic an-tidepressants, as the combination may cause irregular heart rhythms that are potentially fatal anticonvulsants, antidepressants, antihistamines, antipsychotics, barbiturates, benzodiazepines, or any drug that causes sedation or central nervous system depression, because the combination can cause pronounced sedation antihypertensive medication, as fluphenazine may combine to lower blood pressure excessively antihistamines, or antiparkinsonian agents, as they may combine to produce pronounced dry mouth, blurry vision, constipation, low blood pressure, rapid heart rate, and mental confusion.
DRUG INTERACTIONS Don't use if you take MAOI antidepressants, as their use with maprotiline can cause pronounced hypertension and the potential for strokes. Use with extra caution if you take Antihypertensives, as maprotiline may lower blood pressure excessively antihistamines, phenothiazines, or tri-cyclic antidepressants, as they may combine to produce pronounced dry mouth, blurry vision, constipation, low blood pressure, rapid heart rate, and even mental confusion anticonvulsants, antidepressants, antihistamines, antipsychotics, barbiturates, benzodiazepines, or any drug that causes sedation or central nervous system depression, because the combination can cause pronounced sedation ben-zodiazepines, because the risk of seizures is elevated if you taper the benzodi-azepine quickly phenothiazines, as the combination puts you at a higher risk of developing seizures.
DRUG INTERACTIONS Don't use if you take Other SSRIs, St. John's wort, or tryptophan as their use with paroxetine can cause the serotonin syndrome MAOI antidepressants, as their use with paroxetine can cause a serious, sometimes fatal, reaction of agitation, fever, cardiovascular changes, and mental status changes.
DRUG INTERACTIONS Use with extra caution if you take Tricyclic antidepressants, as the combination may cause irregular heart rhythms that are potentially fatal anticonvulsants, antidepressants, antihistamines, antipsy-chotics, barbiturates, benzodiazepines, or any drug that causes sedation or central nervous system depression, because the combination can cause pronounced sedation antihypertensive medication, as perphenazine may combine to lower blood pressure excessively antihistamines or antiparkinsonian agents, as they may combine to produce pronounced dry mouth, blurry vision, constipation, low blood pressure, rapid heart rate, and mental confusion.
DRUG INTERACTIONS Do not use if you take Fluvoxamine (Luvox) because the breakdown of ramelteon may be impaired, leading to a more intense effect. Use with extra caution if you take Itraconozole (Sporonox) or ketoconozole (Nizoril), because the breakdown of ramelteon may be impaired, leading to a more intense effect Anticonvulsants, antidepressants, antihistamines, antipsychotics, barbiturates, benzodiazepines, other hypnotics, or any drug that causes sedation or central nervous system depression, because the combination with ramelteon can cause pronounced sedation.
DRUG INTERACTIONS Don't use if you take Other SSRIs, St. John's wort, or tryptophan, as their use with sertraline can cause the serotonin syndrome MAOI antidepressants, as their use with sertraline can cause a serious, sometimes fatal, reaction of agitation, fever, cardiovascular changes, and mental status changes.
DRUG INTERACTIONS Use with extra caution if you take Anticonvul-sants, antidepressants, antihistamines, antipsychotics, barbiturates, benzodi-azepines, or any drug that causes sedation or central nervous system depression, because the combination can cause pronounced sedation antihypertensive medication, as thiothixene may combine to lower blood pressure excessively antihist-amines or antiparkinsonian agents, as they may combine to produce pronounced dry mouth, blurry vision, constipation, low blood pressure, rapid heart rate, and mental confusion.
DRUG INTERACTIONS Use with extra caution if you take Anticonvul-sants, antidepressants, antihistamines, antipsychotics, barbiturates, benzodi-azepines, or any drug that causes sedation or central nervous system depression, because the combination with topiramate can cause pronounced sedation pheny-toin (Dilantin), as the combination may require lower doses of phenytoin and higher doses of topiramate than would otherwise be expected oral contraceptives (birth control pills), because topiramate may make them less effective.
DRUG INTERACTIONS Don't use if you take Itraconazole, ketocona-zole, or nefazodone, as they may significantly intensify the effects of triazolam. Use with extra caution if you take Anticonvulsants, antidepressants, antihista-mines, antipsychotics, barbiturates, benzodiazepines, or any drug that causes sedation or central nervous system depression, because the combination with triazolam can cause pronounced sedation.
DRUG INTERACTIONS Don't use if you take MAOI antidepressants, as their use with trimipramine can cause pronounced hypertension and the potential for strokes. Use with extra caution if you take Phenothiazines, as the combination may cause irregular heart rhythms that are potentially fatal antihyperten-sives, as they may combine to lower blood pressure excessively antihistamines, phenothiazines, and antiparkinsonian agents, as they may combine to produce pronounced dry mouth, blurry vision, constipation, low blood pressure, rapid heart rate, and even mental confusion guanethadine to lower blood pressure, as trimipramine may block its effects.
DRUG INTERACTIONS Do not use if you take Other SSRIs, St. John's wort, or tryptophan or other serotonin reuptake inhibitors, as their use with venlafaxine can cause the serotonin syndrome, which consists of potentially dangerous alterations in pulse, blood pressure, hyperactivity, and mental status changes (see chapter 19) MAOI antidepressants, as their use with venlafaxine can cause a serious, sometimes fatal, reaction of agitation, fever, cardiovascular changes, and mental status changes.
The role of medications, especially antidepressants, in the treatment of panic disorder is well established. Both TCAs and SSRIs have been used successfully, with over two-thirds of patients reporting remission of symptoms after 12 weeks of treatment. If a TCA is selected, nortriptyline hydrochlo-ride or desipramine hydrochloride should be used because these have fewer side effects than other medications in their class. Initial doses are 10 mg po qhs for nortriptyline hydrochloride and 25 mg po qhs for desipramine hydrochloride. Serum drug levels should be monitored as doses are increased to maintenance ranges of 50-100 mg qhs for nortriptyline hydrochloride and 100-200 mg qhs for desipramine hydrochloride. The approximate monthly cost for nortriptyline hydrochloride, 100 mg qhs, is 50 for desipramine hydrochloride, 200 mg qhs, it is 40. The SSRIs do not require monitoring of serum levels, but they can cause significant drug-drug interactions (see Table 2.1). Maintenance doses of...
Pharmacogenetics and pharmacogenomics are beginning to be integrated more into early clinical development programs and as important components in plans to achieve the overall goals of Phase I and II trials, such as safety, tolerability, pharmacokinetics phar-macodynamics (PK PD), dose ranging, drug-drug interactions, and potentially proof of concept for efficacy hypotheses.
Nefazodone and trazodone possess antidepressive and anxiolytic properties. Both agents antagonize 5-HT receptors and modestly inhibit the reuptake of norep-inephrine and 5-HT. In a controlled comparative study (n 16), nefazodone and fluoxetine were similarly effective at improving depression, with nefazodone also producing a notable improvement in motor symptoms (142). However, the use of nefazodone may be limited by reports of hepatoxicity and significant hepatic CYP450 3A4-mediated drug-drug interactions. Trazodone has not been studied in PD depression however, low-dose trazodone is commonly used as a sedative hypnotic. Of note, a metabolite of trazodone, m-chlorophenylpiperazine, is anxiogenic and a subset of patients may experience irritability and enhanced anxiety, especially if trazodone is used in the presence of a potent CYP450 2D6 isoenzyme inhibitor (e.g., fluoxetine and paroxetine) (160). Common side effects of both nefazodone and tra-zodone include dizziness, orthostatic...
Drug Interactions Ritonavir is expected to produce large increases in the plasma levels of a number of drugs, including astemizole, bupro-prion, cisapride, erythromycin, me-peridine, phenothiazines, piroxicam, propoxyphene, tefenadine. This may lead to an increased risk of arrhythmias, hematologic complications, seizures, or other serious adverse effects.
One unique property of this medication is that it is not metabolized by the CYP450 enzyme system, thus there are no drug-drug interactions reported. Absorption of this drug is fast and rapid and is complete within one hour of administration. About 40 protein bound. It is extensively metabolized by cholinesterase-mediated hydrolysis in the brain. It has an elimination half life of 1.5 h. 97 of the metabolite is excreted in the urine. 3. Other side effects may include dizziness, headache, fatigue, insomnia. Drug interactions 11
Drug Interactions Barbiturates combine with other CNS depressants to cause severe depression ethanol is the most frequent offender, and interactions with first-generation antihistamines also are common. Isoniazid, methylphenidate, and monoamine oxidase inhibitors also increase the CNS-depressant effects. Other prominent drug interactions occur as a result of the induction of hepatic drug-metabolizing enzymes by barbiturates (see above).
Drug response is just as complex as disease genetics, resulting not only from underlying genotypic variation at several mostly unknown loci, but also from variation in gene expression, post-translational modification of proteins, drug dose, drug interactions, diet, and other non-genetic factors. Therefore, we expect to see relatively slight effects of individual genes regarding drug response as well. In fact, pharmacogenomic markers reported on to date confer only about a twofold increased likelihood of response (Poirier 1995 Drazen 1999).
Hypertension ED is commonly seen in patients with hypertension (6). In a retrospective analysis, Kloner et al. (52) examined the effect of antihypertensive medication on the efficacy of sildenafil. They found that sildenafil is effective in patients taking antihypertensives and is comparable to results seen in the general population of men taking sildenafil. There were no significant drug interactions between sildenafil and antihypertensive medications noted in the clinical trials that included men taking diuretics, beta-blockers, angiotensin converting
DRUG INTERACTIONS Use with extra caution if you take Anticonvul-sants, antidepressants, antihistamines, antipsychotics, barbiturates, benzodiazepines, or any drug that causes sedation or central nervous system depression, because the combination can cause pronounced sedation antihypertensive medication, as loxa-pine may combine to lower blood pressure excessively antihistamines, or antiparkin-sonian agents, as they may combine to produce pronounced dry mouth, blurry vision, constipation, low blood pressure, rapid heart rate, and mental confusion.
Drug interactions are not a prominent problem with entacapone, although the capability of entacapone to chelate iron in the gastrointestinal tract has been noted (70), and it has been suggested that an interval of two to three hours be allowed between entacapone and iron ingestion (18). Although animal studies have suggested that COMT inhibition may increase apomorphine bioavailability (71), such an effect has not been demonstrated in humans, even when administering a double dose of 400 mg entacapone (72).
Pharmacokinetic drug interactions are relatively uncommon with trazodone. Trazodone levels may be increased by concurrent fluoxetine administration. Increased serum digoxin and phenytoin levels have been reported in patients receiving trazodone. Elderly patients have a predisposition for developing elevated plasma trazodone levels at any given therapeutic dose. Pharmacodynamic interactions are most common with coingestants such as ethanol, central nervous system (CNS) depressants, or a-adrenergic blockers.
Vaginal Use Symptomatic candida vaginitis, N&V. Drug Interactions Barbiturates Possible therapeutic failure of metronidazole Ethanol or ethanol-containing products Possible disulfiram-like reaction, including flushing, palpitations, tachycardia, and N&V How Supplied Capsule 375 mg Cream 0.75 Gel jelly 0.75 Injection 500 mg 100 mL Tablet 250 mg, 500 mg
DRUG INTERACTIONS Use with extra caution if you take Antihyperten-sives, as diphenhydramine may lower blood pressure excessively antihistamines, phenothiazines, or tricyclic antidepressants, as they may combine to produce pronounced dry mouth, blurry vision, constipation, low blood pressure, rapid heart rate, and even mental confusion MAOI antidepressants, as they can intensify the side effects of diphenhydramine anticonvulsants, antidepressants, antihistamines, antipsy-chotics, barbiturates, benzodiazepines, or any drug that causes sedation or central nervous system depression, because the combination can cause pronounced sedation.
The following side effects are common to each of the fluoroquinolone antibiotics. Oral Dry or painful mouth. GI N&V, diarrhea, abdominal pain or discomfort, heartburn, dyspepsia, flatulence, constipation, pseudomembranous colitis. CNS Headache, dizziness, malaise, lethargy, fatigue, drowsiness, somnolence, depression, insomnia, seizures, pa-resthesia. Dermatologic Rash, pho-tosensitivity, pruritus (except for cip-rofloxacin). Hypersensitivity reactions Facial or pharyngeal edema, dyspnea, urticaria, itching, tingling, loss of consciousness, CV collapse. Other Visual disturbances and oph-thalmologic abnormalities, hearing loss, superinfection, phototoxicity, eosinophilia, crystalluria, Achilles and other tendon inflammation and rupture. Fluoroquinolones, except norfloxacin, may also cause vagin-itis, syncope, chills, and edema. Drug Interactions Antacids i Serum levels of fluoroquinolones due to i absorption from the GI tract
Neuropathic pain therapeutic blood levels are in the range of 10 to 20 mg ml. There are numerous potential drug interactions, including induction of cytochrome P450 enzymes, which may accelerate the metabolism of other drugs. Because of side effects and toxicity, phenytoin is not a first-line drug for neuropathic pain.
DRUG INTERACTIONS Use with extra caution if you take Tricyclic an-tidepressants, as the combination may cause irregular heart rhythms that are potentially fatal anticonvulsants, antidepressants, antihistamines, antipsychotics, barbiturates, benzodiazepines, or any drug that causes sedation or central nervous system depression, because the combination can cause pronounced sedation. Antihypertensive medication, as thioridazine may combine to lower blood pressure excessively antihistamines or antiparkinsonian agents, as they may combine to produce pronounced dry mouth, blurry vision, constipation, low blood pressure, rapid heart rate, and mental confusion.
DRUG INTERACTIONS Do not use if you take MAOI antidepressants, as their use with clomipramine can cause pronounced hypertension and the potential for strokes. Use with extra caution if you take Phenothiazines, as the combination may cause irregular heart rhythms that are potentially fatal antihyperten-sives, as they may combine to lower blood pressure excessively antihistamines, phenothiazines, and antiparkinsonian agents, as they may combine to produce pronounced dry mouth, blurry vision, constipation, low blood pressure, rapid heart rate, and even mental confusion guanethadine to lower blood pressure, as clomipramine may block its effects.