Click here to view Severity Legend:
| Severity Code | Level | Explanation |
|---|
| 0 or 1 | Contraindications
and
Therapeutic Duplications | The interaction may be life-threatening. Concomitant use of the interacting agents is contraindicated or a therapeutic duplication has occurred indicating the possibility of excessive amounts of one or more drugs. |
| 2 | Major | The interaction may be life-threatening and/or require medical intervention to minimize or prevent serious adverse effects. |
| 3 | Moderate | The interaction may result in an exacerbation of the patient's condition and/or require an alteration in therapy. |
| 4 | Minor | The interaction would have limited clinical effects. Manifestations may include an increase in the frequency or severity of side effects but generally would not require a major alteration in therapy. |
IMPORTANT:
In cases of extreme age, weight, or height minimum values are used in testing. Patient's record has actual values.
Age: 1-118 years Weight: 12-500 lbs. Height: 24-100 inches
When not indicated otherwise, tests assume a normal Serum Creatinine of "1" and test accordingly.
| Gender: | MALE | Date: | 5/9/2008 8:36:29 PM | | Age: | 66 | SCr: | 1 | | Height: | 70 in | Weight: | 185 lb | | Hepatic: | No | Smoker: | No | | Pregnant: | No | Lactating: | No |
Current Drugs:
| 00677-0678-10 | ACETAMINOPHEN - CAP, 500 MG | 2 | CAPSULE | 6 | DAY |
| 58864-0223-14 | COUMADIN - PDS, 5 MG | 1 | POWDER FOR SOLUTION | 1 | HOUR |
| 60429-0059-40 | DICLOXACILLIN SODIUM - CAP, 250 MG | 3 | CAPSULE | 6 | DAY |
| 55289-0201-30 | MINOCYCLINE HCL - CAP, 100 MG | 2 | CAPSULE | 4 | DAY |
| 00409-6062-02 | MORPHINE SULFATE IN 5% DEXTROSE - SOL, 5%-100 MG/100 ML | 1 | SOLUTION | 1 | HOUR
|
Diagnostic Indications:
| 3050 | CRYPTITIS |
| 691 | ABSCESS, BRAIN |
| 3138 | IRIDOCYCLITIS |
| 493 | CONGESTIVE HEART FAILURE |
| 1416 | NEURITIS, OPTIC |
| 3074 | EDEMA, CORNEAL |
| 3003 | ACNE
|
Allergies:
 Warning: - Congestive Heart Failure / WARFARIN SODIUM6000000 Severity: 0 - There may be a contraindication to the use of COUMADIN in patients with Congestive Heart Failure.
Warning: WARFARIN SODIUM - COUMADIN / DEXTROSE/MORPHINE SULFATE6000000 Severity: 0 - There may be a contraindication to the use of MORPHINE SULFATE IN 5% DEXTROSE in patients with Arrhythmia.
3006878 Severity: 2 - Concurrent use of ETHANOL and ACETAMINOPHEN may result in an increased risk of hepatotoxicity.Clinical Management:Caution should be used with patients who drink 3 or more alcoholic beverages per day and take acetaminophen. Patients should be advised not to exceed 4 grams of acetaminophen per 24 hours. Chronic alcoholics should avoid the use of acetaminophen. In cases of acetaminophen overdose consider treatment with acetylcysteine. Onset:DelayedSeverity:MajorDocumentation:GoodProbable Mechanism:accumulation of the hepatotoxic acetaminophen metabolite NAPQI by ethanol induction of CYP2E1; depletion of glutathioneSummary:Concurrent use of alcohol and acetaminophen may increase the CYP2E1-mediated metabolism of acetaminophen to the highly hepatotoxic metabolite NAPQI. Patients should be advised not to exceed 4 grams of acetaminophen in 24 hours and to tell their doctor if they regularly drink 3 or more alcoholic drinks per day (Prod Info Tylenol®, 2000). In chronic alcoholics, therapeutic doses or overdoses of acetaminophen are more likely to cause hepatotoxicity than in non-alcoholic patients (Barker et al, 1977; McClain et al, 1980; Johnson et al, 1981; McJunkin et al, 1976; Licht et al, 1980). In regular users of alcohol, the highest risk of acetaminophen toxicity occurs after a brief (12 hours) abstinence of alcohol, since CYP2E1 is still induced but ethanol is not present to compete for CYP2E1 (Draganov et al, 2000). Literature:Alcohol-acetaminophen syndrome is described as the development of acute toxic hepatic effects in long-term alcoholics who ingest acetaminophen in doses generally considered non-toxic. Severe hepatotoxicity can be seen in these patients after acetaminophen ingestion as low as 4 grams in 24 hours. Patients with alcohol-acetaminophen syndrome have a worse prognosis than non-alcoholic patients with acetaminophen overdose, despite the former having ingested lower doses of acetaminophen. Overall mortality in alcohol-acetaminophen syndrome is about 19%, and exceeds 75% if acute liver failure develops. Approximately 95% of acetaminophen is conjugated through glucuronide and sulfate routes, with only 5% of the drug oxidized by cytochrome P450 2E1 (CYP2E1). This oxidation results in N-acetyl-p-benzoquinoneimine (NAPQI), a compound that is highly hepatotoxic. Following ingestion of therapeutic amounts of acetaminophen in non-alcoholics, NAPQI is detoxified by conjugation with glutathione. In situations of acetaminophen overdose, glutathione stores are rapidly depleted, leaving NAPQI to cause hepatic injury. In alcoholics, alcohol competes with acetaminophen for CYP2E1 metabolism. The combination of CYP2E1 induction and glutathione depletion results in NAPQI accumulation and enhanced acetaminophen toxicity (Draganov et al, 2000). Thus far clinicians have accepted the possibility that chronic alcoholics are at increased risk of acetaminophen (paracetamol) hepatotoxicity, however, there is insufficient evidence to support the alleged major toxic interaction. Only modest (approximately two-fold) and short-lived induction of cytochrome P450 2E1 (CYP2E1) is caused by chronic alcohol ingestion and there is not a corresponding increase in the toxic metabolic activation of acetaminophen. The protective effect of alcohol is associated with inhibition of the toxic metabolic activation of acetaminophen. The timing of ethanol and acetaminophen intake is critical since the protective effect of ethanol disappears when ethanol is eliminated. Chronic alcoholics are likely to be at greatest risk to the effects of acetaminophen during the first few days of alcohol withdrawal since the metabolic activation of acetaminophen is no longer countered by the inhibitory effects of circulating ethanol. All patients who consume alcohol in excess must be considered high risk subsequent to acetaminophen overdose and be treated with N-acetylcysteine accordingly until further studies are conducted (Prescott, 2000).Reference(s):Barker JD, de Carle DJ & Anuras S: Chronic excessive acetaminophen use and liver damage. Ann Intern Med 1977; 87:299-301. Draganov P, Durrence H, Cox C et al: Alcohol-acetaminophen syndrome. Postgrad Med 2000; 107:189-195. Johnson MW, Friedman PA & Mitch WE: Alcoholism, nonprescription drugs and hepatotoxicity. The risk from unknown acetaminophen ingestion. Am J Gastroenterol 1981; 76:530-533. Licht H, Seeff LB & Zimmerman HJ: Apparent potentiation of acetaminophen hepatotoxicity by alcohol (letter). Ann Intern Med 1980; 92:511. McClain CJ, Kromhout JP, Peterson FJ et al: Potentiation of acetaminophen hepatotoxicity by alcohol. JAMA 1980; 244:251-253. McJunkin B, Barwick KW, Little WC et al: Fatal massive hepatic necrosis following acetaminophen overdose. JAMA 1976; 236:1874-1875. Prescott L: Paracetamol, alcohol and the liver. J Clin Pharmacol 2000; 49:291-301. Product Information: Tylenol(R), acetaminophen. McNeil-PPC, Inc., Fort Washington, PA, USA, 2000. Copyright© 1974-2006 Thomson MICROMEDEX. All Rights Reserved.
3011707 Severity: 2 - Concurrent use of ETHANOL and MORPHINE may result in Increased risk of respiratory depression, hypotension, profound sedation, or coma.Clinical Management:Use caution when administering morphine in patients who drink alcohol. Monitor for increased morphine side effects including reduced respiratory rate, blood pressure, and excessive sedation. Onset:RapidSeverity:MajorDocumentation:FairProbable Mechanism:additive central nervous system and respiratory depressionSummary:Concomitant administration of morphine with ethanol results in additive or synergistic central nervous system or respiratory depression (Prod Info MS Contin®, 2003; Bellville et al, 1971).Reference(s):Bellville JW, Forrest WH, Shroff P et al: The hypnotic effects of codeine and secobarbital and their interaction in man. Clin Pharmacol Ther 1971; 12:607-612. Product Information: MS Contin(R), morphine sulfate. Purdue Frederick, Stamford, CT, January, 2003. Copyright© 1974-2006 Thomson MICROMEDEX. All Rights Reserved.
 Warning: WARFARIN SODIUM - COUMADIN / 10002106 Severity: 2 - Warfarin should NOT be used in any unsupervised patient with senility. Warfarin should be used with caution in elderly patients who are at risk of hemorrhage.
2011398 Severity: 3 - Concurrent use of MINOCYCLINE and DAIRY FOODS may result in decreased minocycline concentrations.Clinical Management:Administer tetracycline derivatives one hour before or two hours after dairy foods to minimize interference on absorption. Onset:RapidSeverity:ModerateDocumentation:GoodProbable Mechanism:chelation with poor absorptionSummary:Milk and other dairy products reduce the absorption of most tetracycline derivatives by 20% to 75% (Welling et al, 1977; Neuvonen et al, 1976; Wood & Shannonhouse, 1977; Seneca, 1971). Minocycline is less affected, with 11% lower absorption, when administered with dairy products (Prod Info Minocin®, 1995). Literature:Studies have shown that a reduction in tetracycline serum levels between one-fourth and one-third of the expected level can occur if a tetracycline derivative is given concurrently with 8 ounces of whole milk, skim milk, or buttermilk, or 4 ounces of cottage cheese (Michel, 1950; Price, 1957a; Price, 1957b; Rosenblatt et al, 1966; Scheiner & Altemeier, 1962; Waisbren & Hueckel, 1950). Absorption of the antibiotic is decreased presumably by chelation with the calcium in dairy products. The intestinal interaction with divalent cations may interfere with absorption of the drug from the GI tract. In addition, interaction with both calcium and alpha-casein may result in considerable inactivation and diminished activity of the antibiotic (Scheiner & Altemeier, 1962). An antagonistic effect of milk on absorption of oxytetracycline and chlortetracycline has been reported. The authors clearly showed that ionizable salts of calcium and magnesium have considerable inhibiting effects on these analogs in vitro (Price, 1957a; Price, 1957b). Simultaneous ingestion of 8 to 10 ounces of pasteurized milk or buttermilk or cottage cheese had a marked effect on the absorption of demethylchlortetracycline in 12 healthy subjects when compared to fasting (Scheiner & Altemeier, 1962). Maximum serum drug levels were attained within 3 to 6 hours in both the fasting and non-fasting trials, but they were significantly lower in all 12 non-fasting cases than compared to those achieved with demethylchlortetracycline administered alone. Average peak levels varied from 0.4 to 0.7 mcg/ml with concomitant food as compared with 2.08 mcg/ml when demethylchlortetracycline was given alone. The average decrease in serum concentration was 50% or more. Serum concentrations at both 12 and 24 hours in the non-fasting trials were also markedly lower than those obtained with demethylchlortetracycline alone. Milk decreased the absorption of demethylchlortetracycline by about 70%, whereas non-dairy food produced about a 50% decrease in absorption (Rosenblatt et al, 1966). The relative calcium binding capacity of tetracycline derivatives in vitro was demethylchlortetracycline (74.5%); chlortetracycline (52.7%); tetracycline (39.5%); methacycline (39.5%); doxycycline (19% to 22%) (Seneca, 1971). Healthy volunteers demonstrated a 50% reduction in tetracycline serum concentrations but only a 20% reduction for doxycycline when given a variety of test meals (Welling et al, 1977). Doxycycline absorption was only minimally affected by either dairy products or food (Rosenblatt et al, 1966). Studies with the manufacturer have shown minocycline exhibits 11% reduced absorption in the presence of food or dairy products (Prod Info Minocin®, 1995).Reference(s):Michel JC: Effect of food and antacids on blood levels of aureomycin and terramycin. J Lab Clin Med 1950; 36:623. Neuvonen PJ, Penttila O, Ross M et al: Effect of long-term alcohol consumption on the half-life of tetracycline and doxycycline in man. Int J Clin Pharmacol 1976; 14:303-307. Price KE: Antibiotic inhibitors I: the effect of certain milk constituents. Antibiot Chemother 1957a; 7:672. Price KE: Antibiotic inhibitors I: the effect of certain milk constituents. Antibiot Chemother 1957a; 7:672. Price KE: Antibiotic inhibitors II: studies on the inhibitory action of selected divalent cations for oxytetracycline. Antibiot Chemother 1957b; 7:689. Product Information: Minocin(R), minocycline. Lederle Laboratories, Pearl River, NY, 1995. Rosenblatt JE, Barrett JE, Brodie JL et al: Comparison of in vitro activity and clinical pharmacology of doxycycline with other tetracyclines. Antimicrob Agents Chemother 1966; 3:134-141. Scheiner J & Altemeier WA: Experimental study of factors inhibiting absorption and effective therapeutic levels of declomycin. Surg Gynecol Obstet 1962; 114:9. Seneca H: In: Biological Basis of Chemotherapy of Infections and Infestations. FD Davis Co, Philadelphia, PA, 1971. Waisbren BA & Hueckel JS: Reduced absorption of aureomycin caused by aluminum hydroxide. Proc Soc Exp Biol Med 1950; 73:73. Welling PG, Koch PA, Lau CC et al: Bioavailability of tetracycline and doxycycline in fasted and nonfasted subjects. Antimicrob Agents Chemother 1977; 11:462-469. Wood JH & Shannonhouse WR: Milk inactivation of tetracycline. Drug Intell Clin Pharm 1977; 11:495. Copyright© 1974-2006 Thomson MICROMEDEX. All Rights Reserved.
1011697 Severity: 3 - Concurrent use of MINOCYCLINE and WARFARIN may result in an increased risk of bleeding.Clinical Management:In patients receiving oral anticoagulant therapy with warfarin, the prothrombin time ratio or international normalized ratio (INR) should be closely monitored with the addition and withdrawal of treatment with minocycline, and should be reassessed periodically during concurrent therapy. Adjustments of the warfarin dose may be necessary in order to maintain the desired level of anticoagulation. Onset:DelayedSeverity:ModerateDocumentation:FairProbable Mechanism:unknownSummary:Tetracycline therapy has been shown to reduce plasma prothrombin activity (Westfall et al, 1980; Finegold, 1970; Martin, 1968; Messinger, 1965; Searcy et al, 1964). Clinical reports of interactions with oral anticoagulants are lacking.Reference(s):Finegold SM: Interaction of antimicrobial therapy and intestinal flora. Am J Clin Nutr 1970; 23:1466. Martin WJ: Hemorrhagic diathesis induced by antimicrobials. JAMA 1968; 205:192. Messinger WJ: The effect of a bowel sterilizing antibiotic on blood coagulation mechanisms. Angiology 1965; 16:29. Searcy RL, Simms NM, Foreman JA et al: Evaluation of the blood-clotting mechanism in tetracycline-treated patients. Antimicrob Agents Chemother 1964; 10:179-183. Westfall LK, Mintzer DL & Wiser TH: Potentiation of warfarin by tetracycline (letter). Am J Hosp Pharm 1980; 37:1620. Copyright© 1974-2006 Thomson MICROMEDEX. All Rights Reserved.
 Warning: MORPHINE SULFATE - MORPHINE SULFATE IN 5% DEXTROSE / 10000463 Severity: 3 - Narcotic analgesics should be used with caution in geriatric patients. The elderly are particularly susceptible to central nervous system depression and confusion resulting from narcotic use. These effects in the elderly increase the risk of falls and subsequent fractures.
1001992 Severity: 3 - Concurrent use of WARFARIN and ACETAMINOPHEN may result in an increased risk of bleeding.Clinical Management:Patients receiving warfarin or other coumarin anticoagulants should be cautioned to limit their intake of acetaminophen; a prudent rule of thumb would be to use no more than 2 grams of acetaminophen per day for no more than a few days. Patients needing to take larger doses of acetaminophen (or for longer periods) should have intensified monitoring of prothrombin times in order to assess any effect on anticoagulant response. Onset:DelayedSeverity:ModerateDocumentation:GoodProbable Mechanism:inhibition of warfarin metabolism or interference with clotting factor formationSummary:Acetaminophen, in doses greater than 2275 mg per week, has been associated with an increased hypoprothrombinemic effect of warfarin. It has been proposed that acetaminophen may inhibit the metabolism of warfarin or acetaminophen may interfere with formation of clotting factors. Gingival bleeding and hematuria have been observed in case reports when acetaminophen is given with warfarin (Hylek et al, 1998; Bartle & Blakely, 1991; Boeijinga et al, 1982; Jones, 1976; Antlitz et al, 1968). However, due to lack of a safer alternative, acetaminophen is still the analgesic and antipyretic of choice in patients receiving warfarin therapy, as long as excessive amounts and prolonged administration are avoided (Shek et al, 1999). Literature:A prospective case-control study was developed to identify factors associated with an INR greater than 6.0 among outpatients taking warfarin whose target INR was 2.0 to 3.0. Ninety-three case patients were interviewed with an INR of greater than 6.0 and 196 controls with an INR in the range of 1.7 to 3.3. INRs increased from 3.5 for 2275-4549 mg intake of acetaminophen per week (95% confidence interval (CI), 1.2-10.0), to 6.9 for 4550 mg to 9099 mg intake per week (95% CI, 2.6-37.9). For those patients taking the highest dose of acetaminophen, 9100 mg/week or more, the odds increased 10-fold of having an INR greater than 6.0 (95% CI, 2.6-37.9). Other factors independently associated with an INR greater than 6.0 were new medication known to potentiate warfarin, advanced malignancy, recent diarrheal illness, decreased oral intake, and taking more warfarin than prescribed. Higher intake of vitamin K and alcohol consumption from 1 to 2 drinks per day were associated with decreased risk. Acetaminophen is an underrecognised cause of over anticoagulation. Regular monitoring of INR values may reduce the frequency of high levels of anticoagulation. Modification of the risk factors should reduce the frequency of overanticoagulation as well (Hylek et al, 1998). In a double-blind study, 20 patients were placed on placebo or acetaminophen 500 mg four times a day while on coumarin therapy. A significant increase in clotting times in patients taking acetaminophen was seen. The mechanism of this drug interaction is unknown and the authors of this study suggest that acetaminophen may interfere with the hepatic synthesis of factors II, VII, IX, and X (Boeijinga et al, 1982). The effect of acetaminophen on anticoagulation with warfarin-like drugs was investigated in 112 subjects by a double-blind study. All of the subjects had been receiving a stable dose of anticoagulant, and had been free of adverse reaction. Results showed a statistically significant increase in prothrombin time when acetaminophen 2.6 grams daily was added to anticoagulant therapy for a two-week period. The mean increase in prothrombin time was 3.7 seconds, and this increase became significant during the first week of acetaminophen coadministration (Antlitz et al, 1968). A 66-year-old woman experienced a three-day history of hematuria and gingival bleeding while stabilized on warfarin therapy for approximately four years. A month prior to her presentation, she had been prescribed an acetaminophen/codeine combination for lower back pain, and had taken approximately 48 tablets. Upon admission to the hospital, her PT was 96 seconds (control, 10 seconds) (Bartle & Blakely, 1991). Healthy male volunteers receiving acetaminophen 4 g daily for one day or two weeks did not show an altered disposition of either the ®- or (S)-enantiomers of warfarin. During a two-phase randomized crossover study, twenty subjects received a single dose of racemic warfarin 20 mg alone, a 22-day regimen of acetaminophen 1 gram four times daily, and a single 20 mg oral dose of warfarin administered on days 2 and 16 of acetaminophen. Acute and chronic acetaminophen dosing had no effect on the maximum serum concentrations or time to maximum serum concentration of either warfarin enantiomer. Prothrombin time (PT) changes ranged from 1.1 seconds to 6.4 seconds, with the greatest change occurring with the first exposure of warfarin. Factor VII concentrations were not significantly altered between acetaminophen treatments. Additionally, urinary excretion of acetaminophen and its metabolites was unchanged, suggesting that warfarin does not affect acetaminophen metabolism (Kwan et al, 1999). A 74-year-old patient receiving warfarin for atrial fibrillation experienced an increase in INR from 2.3 to 6.4 after acetaminophen therapy (4 g/day for 3 days). The patient's warfarin plasma concentration did not significantly change from 1.54 mcg/mL before treatment to 1.34 mcg/mL after treatment. The author concludes that acetaminophen at dosages exceeding 2g/day may cause excessive anticoagulation in patients who have previously achieved a stable INR while receiving warfarin. Patients should be advised to have additional INR measurements performed when taking acetaminophen at dosages exceeding 2 g/day (Gebauer et al, 2003).Reference(s):Antlitz AM, Mead JA Jr. & Tolentino MA: Potentiation of oral anticoagulant therapy by acetaminophen. Curr Therap Res 1968; 10:501-507. Bartle WR & Blakely JA: Potentiation of warfarin anticoagulation by acetaminophen (letter). JAMA 1991; 265:1260. Boeijinga JJ, Boerstra EE, Ris P et al: Interaction between paracetamol and coumarin anticoagulants. Lancet 1982; 1:506. Gebauer M, Nyfort-Hansen K, Henschke P et al: Warfarin and acetaminophen interaction. Pharmacotherapy 2003; 23(1):109-112. Hylek EM, Heiman H, Skates S et al: Acetaminophen and other risk factors for excessive warfarin anticoagulation. JAMA 1998; 279:657-662. Jones RV: Warfarin and distalgesic interaction. Br Med J 1976; 1:460. Kwan D, Bartle WR & Walker SE: The effects of acetaminophen on pharmacokinetics and pharmacodynamics of warfarin. J Clin Pharmacol 1999; 39:68-75. Shek KLA, Chan LN & Nutescu E: Warfarin-acetaminophen drug interaction revisited. Pharmacotherapy 1999; 19:1153-1158. Copyright© 1974-2006 Thomson MICROMEDEX. All Rights Reserved.
1000583 Severity: 3 - Concurrent use of DICLOXACILLIN and WARFARIN may result in a decrease in the anticoagulant effect of warfarin.Clinical Management:In patients receiving oral anticoagulant therapy with warfarin, the prothrombin time ratio (PT) or international normalized ratio (INR) should be monitored four to seven days after the addition of dicloxacillin and for three weeks after the discontinuation of dicloxacillin. The warfarin dosage may need to be adjusted to maintain the desired anticoagulant response. Onset:DelayedSeverity:ModerateDocumentation:GoodProbable Mechanism:hepatic microsomal enzyme inductionSummary:Dicloxacillin has been found to reduce the anticoagulant effectiveness of warfarin (Krstenansky et al, 1987; Mailloux et al, 1996; Taylor et al, 1994). Literature:Concomitant administration of dicloxacillin and warfarin was reported to result in inhibition of the hypoprothrombinemic effects of warfarin (Krstenansky et al, 1987). Prothrombin time (PT) decreased significantly (mean decrease of 1.9 seconds) when dicloxacillin was administered to seven patients receiving long-term warfarin therapy. Although the decrease in PT was not clinically significant for most of the study subjects, the PT value decreased by 5.6 seconds (24%) in one patient. A 31-year-old man with a history of rheumatic fever and aortic valve replacements was using warfarin 10 mg per day and had a PT of 21.6 seconds (Taylor et al, 1994). He was hospitalized with acute bacterial endocarditis and started on nafcillin 2 grams intravenously every four hours. Nine days later his PT was 13.3 seconds and his dose of warfarin was increased to 45 mg per day. On discharge, he began dicloxacillin 4 grams per day and warfarin 35 mg per day, which was tapered to 15 mg. After four years he did not return to his previous warfarin dose of 10 mg per day. The mechanism of action was postulated to be induction of hepatic microsomal enzymes. A 41-year-old man receiving warfarin 22 mg per week for recurrent deep vein thromboses was started on dicloxacillin 500 mg four times daily for ten days for cellulitis of the left foot. PT levels decreased from 20.4 seconds at baseline to 16.9 seconds on day 5 of dicloxacillin therapy. This represented a 17% decrease. The PT returned to baseline sometime between 9 and 22 days after dicloxacillin was discontinued (Mailloux et al, 1996). A retrospective review of seven patients who were on concurrent warfarin and dicloxacillin therapy was conducted (Mailloux et al, 1996). All patients were required to have received stable doses of warfarin for at least two weeks prior to the start of dicloxacillin therapy and could have no changes in medications known to inhibit or induce the metabolism of warfarin within the past two weeks. Five of the seven patients experienced a fall in their PT large enough to require an increase in their warfarin dose. The decrease in PT appeared to occur within 4 to 5 days after the initiation of dicloxacillin.Reference(s):Krstenansky PM, Jones WN & Garewal HS: Effect of dicloxacillin sodium on the hypoprothrombinemic response to warfarin sodium. Clin Pharm 1987; 6:804-806. Mailloux AT, Gidal BE & Sorkness CA: Potential interaction between warfarin and dicloxacillin. Ann Pharmacother 1996; 30:1402-1407. Taylor AT, Pritchard DC, Goldstein AO et al: Continuation of warfarin-nafcillin interaction during dicloxacillin therapy. J Fam Pract 1994; 39:182-185. Copyright© 1974-2006 Thomson MICROMEDEX. All Rights Reserved.
3097315 Severity: 3 - Concurrent use of ETHANOL and WARFARIN may result in increased or decreased international normalized ratio (INR) or prothrombin time.Clinical Management:Patients who use ethanol during warfarin therapy should be monitored closely for anticoagulation effect. Onset:DelayedSeverity:ModerateDocumentation:FairProbable Mechanism:inhibition or induction of warfarin metabolismSummary:Occasional consumption of low to moderate amounts of ethanol (41 to 54 g/day) does not appear to effect warfarin anticoagulation. The effect of chronic ingestion of large amounts of ethanol is less clear. More than 250 g/day of ethanol for over 3 months has been shown to prolong the half-life of warfarin, but had no effect on international normalized ratio (INR). The effect of short-term consumption of a large amount of ethanol is unknown (Cropp & Bussey, 1997). Literature:Cirrhotic patients and those who regularly consume ethanol may have an increased rate of clearance of warfarin. Social consumption of ethanol with food, in patients with normal hepatic function, does not appear to interfere with warfarin therapy (Udall, 1970; O'Reilly, 1979; O'Reilly, 1981; Kater et al, 1969).Reference(s):Cropp JS & Bussey HI: A review of enzyme induction of warfarin metabolism with recommendations for patient management. Pharmacotherapy 1997; 17:917-928. Kater RM, Roggin G, Tobon F et al: Increased rate of clearance of drugs from the circulation of alcoholics. Am J Med Sci 1969; 258:35-39. O'Reilly RA: Lack of effect of fortified wine ingested during fasting and anticoagulant therapy. Arch Intern Med 1981; 141:458-459. O'Reilly RA: Lack of effect of mealtime wine on the hypoprothrombinemia of oral anticoagulants. Am J Med Sci 1979; 277:189-194. Udall JA: Drug interference with warfarin therapy. Clin Med 1970; 77:20-25. Copyright© 1974-2006 Thomson MICROMEDEX. All Rights Reserved.
2200312 Severity: 3 - Concurrent use of WARFARIN and HIGH-PROTEIN DIET may result in reduced warfarin anticoagulant effectiveness.Clinical Management:In patients receiving oral anticoagulant therapy with warfarin, closely monitor the international normalized ratio (INR) whenever a patient begins or withdraws from a high-protein diet. Coagulation parameters should be reassessed periodically during concurrent therapy. Adjustments of the warfarin dose may be required in order to maintain the desired level of anticoagulation when a high-protein diet is initiated or when the diet is discontinued. Onset:DelayedSeverity:ModerateDocumentation:GoodProbable Mechanism:increased binding of warfarin to albumin due to increased albumin serum concentrations associated with increased protein storesSummary:The concomitant ingestion of warfarin with low-carbohydrate, high-protein diets (Atkins and South Beach variants) appeared to reduce the international normalized ratio (INR) to subtherapeutic range in 2 patients. Both patients had previously exhibited therapeutic INR values while receiving stable dose regimens of warfarin over periods of time of up to 1 year, and each patient required increases (22.2% and 30%, respectively) in warfarin dose for the duration of their compliance with their respective diets (Beatty et al, 2005). Literature:As related in a pair of case reports, the concomitant ingestion of warfarin with low-carbohydrate, high-protein diets appeared to reduce the international normalized ratio (INR) to subtherapeutic range. Both patients had previously exhibited therapeutic INR values while receiving stable dose regimens of warfarin over periods of time of up to 1 year. The first patient (a 67-year-old woman) showed a decline in INR to 1.4 from a baseline of 2.5 four weeks earlier, while receiving a weekly dose of warfarin 45 milligrams (mg)/week. The patient reported that 3 weeks previously, she had initiated consumption of an Atkins-type low carbohydrate/high-protein diet. She continued on the high-protein diet, and required a 22.2% increase in warfarin dose to 57.5 mg weekly in order to maintain a therapeutic level INR. The patient subsequently stopped the high-protein diet, resulting in a supratherapeutic INR (4.0 to 4.4) which returned to and remained within therapeutic range upon resumption of the warfarin 45 mg/week dose regimen. The second patient (a 58-year-old man) had shown a therapeutic INR (2.0 - 3.0) while receiving a stable dose regimen of warfarin 26.25 mg/week over a period of 8 months. His INR declined to 1.5 within 3 weeks of beginning a South Beach-type low-carbohydrate, high-protein diet. The warfarin dose was increased by 30% to 37.5 mg weekly, restoring the INR to therapeutic range throughout the duration of his high-protein diet. Upon withdrawal from the diet, the patient's INR increased to 3.6, requiring a reduction of dose to the baseline regimen of warfarin 26.5 mg weekly. The likelihood of interaction was given a Naranjo probability rating of 'possible' (Beatty et al, 2005).Reference(s):Beatty SJ, Mehta BH & Rodis JL: Decreased warfarin effect after initiation of high-protein, low-carbohydrate diets. Ann Pharmacother April, 2005; 39:744-747. Copyright© 1974-2006 Thomson MICROMEDEX. All Rights Reserved.
2090112 Severity: 3 - Concurrent use of WARFARIN and VITAMIN K FOODS may result in altered anticoagulant effectiveness.Clinical Management:Warfarin should be taken consistently in relation to meals. Large changes in dietary consumption of foods high in vitamin K should be avoided or accompanied by careful monitoring of the international normalized ratio (INR). Onset:DelayedSeverity:ModerateDocumentation:ExcellentProbable Mechanism:altered absorption, direct antagonism of warfarinSummary:Although serum levels of warfarin tend to be lower when administered with food, the total amount of drug absorbed is unaffected (Musa & Lyons, 1976). Foods high in vitamin K content or those foods capable of enhancing intestinal sources of vitamin K may antagonize the anticoagulant effect of warfarin (Karlson et al, 1986; Kudo, 1990). Garlic possesses antiplatelet effects which may increase the risk of bleeding in anticoagulated patients (Serlin & Breckenridge, 1983; Bordia, 1978). Literature: A study was conducted to determine the effect of single and multiple administrations of vitamin K, vitamin K-rich vegetables (e.g., spinach and broccoli), and table wine on prothrombin time in 21 patients receiving warfarin. The single administration of vitamin K-1 250 mcg, spinach 250 g, broccoli 250 g, and wine (41 g alcohol) did not significantly affect prothrombin times. However, the administration of vitamin K-1 250 or 500 mcg, spinach 250 g, or broccoli 250 g daily for one week markedly reduced the effect of warfarin. The continuous daily administration of vitamin K-1 100 mcg did not significantly affect prothrombin times. Based on these results, a single excessive dietary intake of foods rich in vitamin K should not significantly affect warfarin-induced anticoagulation; however, repeated vitamin K intake from dietary sources may require an oral anticoagulant dosage adjustment (Karlson et al, 1986). Ingestion of natto, a common soybean-based food in Japan, produced significantly elevated thrombo-test times in 10 patients who were receiving maintenance warfarin anticoagulation therapy following cardiac valve replacements. Bacillus natto, a bacterium contained in natto, was thought to produce large amounts of vitamin K in the intestine and, therefore, antagonized the effects of warfarin. Thrombo-test times increased by 32% to 100% in these patients. Based on these results, the author recommended dietary counseling in patients receiving warfarin therapy (Kudo, 1990). The following foods contain Vitamin K-1 1 to 10 mcg/100 g: cow milk, safflower oil, oleic oil, palm oil, coconut oil, apple, orange, ground beef, beet, corn, cucumber, mushroom. The following foods contain Vitamin K-1 11 to 50 mcg/100 g: dry coffee, honey, strawberry, wheat flour, wheat germ, rabbit liver, veal liver, whole egg, asparagus, carrot, green beans, natto, potato, tomato, asakusa-nori seaweed used in sushi. The following foods contain Vitamin K-1 51 to 100 mcg/100 g: corn, oats, wheat bran, chicken liver, pork liver, peas, sealettuce, watercress. The following foods contain Vitamin K-1 101 to 200 mcg/100 g: beef liver, egg yolk, broccoli, cabbage, green cauliflower, iceberg lettuce, mung beans, soybeans, fiddleheads. The following foods contain Vitamin K-1 201 to 500 mcg/100 g: garbanzo beans (chickpeas), lentils, nettle leaves, seagrass, spinach. The following foods contain over 500 mcg/100 g of Vitamin K-1: dry green tea, soybean oil, brussel sprouts, dulse seaweed, rockweed seaweed, turnip greens. There is no Vitamin K-1 in cottonseed oil, olive oil, peanut oil, safflower linoleic oil, beef heart, beef kidney, lamb liver, pigeon liver, or turkey liver (Bartle et al, 2001; Bartle & Ferland, 1998; Kudo, 1990; Pennington, 1989; Diem & Lentner, 1970).Reference(s):Bartle WR & Ferland G: Fiddleheads and the International Normalized Ratio. New Eng J Med 1998; 338(21):1550. Bartle WR, Madorin P & Ferland G: Seaweed, vitamin K, and warfarin. Am J Health Syst Pharm 2001; 58(23):2300. Bordia A: Effect of garlic on human platelet aggregation in vitro. Atherosclerosis 1978; 30:355-360. Diem K & Lentner C: Documenta Geigy Scientific Tables, (excerpts), 7th ed. Geigy Pharmaceuticals, Ardsley, NY, 1970. Karlson B, Leijd B & Hellstrom K: On the influence of vitamin K-rich vegetables and wine on the effectiveness of warfarin treatment. Acta Med Scand 1986; 220:347-350. Kudo T: Warfarin antagonism of NATTO and increase in serum vitamin K by intake of NATTO. Artery 1990; 17:189-201. Musa NM & Lyons OS: Absorption and disposition of warfarin: effects of food and liquids. Curr Ther Res 1976; 20:630. Pennington JAT: Food values of portions commonly used, 15th ed. Perennial Library, Harper & Row, New York, NY, 1989. Serlin MJ & Breckenridge AM: Drug interactions with warfarin. Drugs 1983; 25:610-620. Copyright© 1974-2006 Thomson MICROMEDEX. All Rights Reserved.
2011420 Severity: 4 - Concurrent use of ACETAMINOPHEN and FOOD may result in decreased peak acetaminophen concentrations.Clinical Management:Take on an empty stomach. Onset:RapidSeverity:MinorDocumentation:GoodProbable Mechanism:delayed absorptionSummary:When acetaminophen is coadministered with food, the absorption rate of the drug is decreased. This is thought to be the result of food altering gastrointestinal motility and transit time. For rapid relief of pain, do not take acetaminophen with food, especially if it is high in carbohydrates (Divoll et al, 1982).Reference(s):Divoll M, Greenblatt DJ, Ameer B et al: Effect of food on acetaminophen absorption in young and elderly subjects. J Clin Pharmacol 1982; 22:571-576. Copyright© 1974-2006 Thomson MICROMEDEX. All Rights Reserved.
4096117 Severity: 4 - MORPHINE may result in a falsely positive urine glucose measurement due to assay interference.
Clinical Management:Urine glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix® or Tes-Tape®) should be used by patients receiving morphine. Onset:RapidSeverity:MinorDocumentation:FairProbable Mechanism:assay interferenceSummary:The administration of morphine may result in a false-positive reaction for urine glucose using the copper reduction method (Clinitest®, Benedict's solution, or Fehling's solution) (Fischbach, 1984).Reference(s):Fischbach F: A Manual of Laboratory Diagnostic Tests, 2nd ed. J.B. Lippincott Company, Philadelphia, PA, 1984. Copyright© 1974-2006 Thomson MICROMEDEX. All Rights Reserved.
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