Drug Interaction Report
11 potential interactions and/or warnings found for the following 2 drugs:
- Fiortal (aspirin / butalbital / caffeine)
- Levora (ethinyl estradiol / levonorgestrel)
Interactions between your drugs
ethinyl estradiol butalbital
Applies to: Levora (ethinyl estradiol / levonorgestrel), Fiortal (aspirin / butalbital / caffeine)
ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with a barbiturate may reduce the efficacy of contraceptive hormones. There have been numerous case reports of menstrual abnormalities (e.g., breakthrough bleeding, amenorrhea, irregular menses) and unintended pregnancy occurring in women who received oral contraceptives with phenobarbital. In a study of four women treated chronically with a contraceptive pill containing 50 mcg of ethinyl estradiol, coadministration with phenobarbital (30 mg twice a day) was associated with breakthrough bleeding and a greater than 60% reduction in plasma ethinyl estradiol concentration in two of the women. The interaction stems from accelerated clearance of contraceptive hormones as well as decreased plasma concentrations of unbound (active) hormones due to induction of hepatic CYP450 enzymatic activity and enhancement of hormone-binding globulin capacity by phenobarbital. Since all barbiturates are believed to possess enzyme-inducing capabilities, the interaction should be expected with agents in the class other than phenobarbital.
MANAGEMENT: Women using hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy with barbiturates. Alternative or additional methods of birth control should be used during and for at least one week after short-term and 4 weeks after long-term (greater than 4 weeks) barbiturate therapy. No precautions or recommendations are available for women using hormone-releasing intrauterine systems, but a significant interaction with these systems is thought to be unlikely due to their local action. Injectable progestin-only contraceptives are also thought to be unaffected by barbiturates. Input from a gynecologist or similar expert on adequate contraception, including emergency contraception, should be sought as needed.
References
- Baciewicz AM (1985) "Oral contraceptive drug interactions." Ther Drug Monit, 7, p. 26-35
- Mumford JP (1974) "Letter: Drugs affecting oral contraceptives." Br Med J, 2, p. 333-4
- Back DJ, Bates M, Bowden A, et al. (1980) "The interaction of phenobarbital and other anticonvulsants with oral contraceptive steroid therapy." Contraception, 22, p. 495-503
- Dossetor J (1975) "Drug interactions with oral contraceptives." Br Med J, 4, p. 467-8
- Furlan AJ, Rothner AD (1974) "Anti-epileptic drugs and failure of oral contraceptives." Lancet, 1, p. 1113
- Coulam CB, Annegers JF (1979) "Do anticonvulsants reduce the efficacy of oral contraceptives?" Epilepsia, 20, p. 519-26
- Szoka PR, Edgren RA (1988) "Drug interactions with oral contraceptives: compilation and analysis of an adverse experience report database." Fertil Steril, 49, s31-8
- Mattson RH, Cramer JA, Darney PD, Naftolin F (1986) "Use of oral contraceptives by women with epilepsy." JAMA, 256, p. 238-40
- Laengner H, Detering K (1974) "Letter: Anti-epileptic drugs and failure of oral contraceptives." Lancet, 2, p. 600
- Curran MA (1986) "Drug interactions with the pill." Med J Aust, 144, p. 670-1
- Back DJ, Orme ML (1990) "Pharmacokinetic drug interactions with oral contraceptives." Clin Pharmacokinet, 18, p. 472-84
- D'Arcy PF (1986) "Drug interactions with oral contraceptives." Drug Intell Clin Pharm, 20, p. 353-62
- Kleier DJ, Tucker JE (1987) "Oral contraceptive failure secondary to dentally prescribed drugs: fact or fiction?" J Colo Dent Assoc, 66, p. 5-6
- Back DJ, Breckenridge AM, Crawford FE, MacIver M, Orne ML, Rowe PH (1981) "Interindividual variation and drug interactions with hormonal steroid contraceptives." Drugs, 21, p. 46-61
- Shane-McWorter L, Cerveny JD, MacFarlane LL, Osborn C (1998) "Enhanced metabolism of levonorgestrel during phenobarbital treatment and resultant pregnancy." Pharmacotherapy, 18, p. 1360-4
- Haukkamaa M (1986) "Contraception by Norplant subdermal capsules is not reliable in epileptic patients on anticonvulsant treatment." Contraception, 33, p. 559-65
- (2001) "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories
- Back DJ, Grimmer SF, Orme ML, Proudlove D, Mann RD, Breckenridge AM (1988) "Evaluation of Committee on Safety of Medicines yellow card reports on oral contraceptive-drug interactions with anticonvulsants and antibiotics." Br J Clin Pharmacol, 25, p. 527-32
- O'Brien MD, Guillebaud J (2006) "Contraception for women with epilepsy." Epilepsia, 47, p. 1419-22
- Faculty of Sexual & Reproductive Healthcare (2016) "FSRH Clinical Guidance: Drug Interactions with Hormonal Contraception. file:///C:/Users/df033684/Downloads/ceuguidancedruginteractionshormonal.pdf"
levonorgestrel butalbital
Applies to: Levora (ethinyl estradiol / levonorgestrel), Fiortal (aspirin / butalbital / caffeine)
ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with a barbiturate may reduce the efficacy of contraceptive hormones. There have been numerous case reports of menstrual abnormalities (e.g., breakthrough bleeding, amenorrhea, irregular menses) and unintended pregnancy occurring in women who received oral contraceptives with phenobarbital. In a study of four women treated chronically with a contraceptive pill containing 50 mcg of ethinyl estradiol, coadministration with phenobarbital (30 mg twice a day) was associated with breakthrough bleeding and a greater than 60% reduction in plasma ethinyl estradiol concentration in two of the women. The interaction stems from accelerated clearance of contraceptive hormones as well as decreased plasma concentrations of unbound (active) hormones due to induction of hepatic CYP450 enzymatic activity and enhancement of hormone-binding globulin capacity by phenobarbital. Since all barbiturates are believed to possess enzyme-inducing capabilities, the interaction should be expected with agents in the class other than phenobarbital.
MANAGEMENT: Women using hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy with barbiturates. Alternative or additional methods of birth control should be used during and for at least one week after short-term and 4 weeks after long-term (greater than 4 weeks) barbiturate therapy. No precautions or recommendations are available for women using hormone-releasing intrauterine systems, but a significant interaction with these systems is thought to be unlikely due to their local action. Injectable progestin-only contraceptives are also thought to be unaffected by barbiturates. Input from a gynecologist or similar expert on adequate contraception, including emergency contraception, should be sought as needed.
References
- Baciewicz AM (1985) "Oral contraceptive drug interactions." Ther Drug Monit, 7, p. 26-35
- Mumford JP (1974) "Letter: Drugs affecting oral contraceptives." Br Med J, 2, p. 333-4
- Back DJ, Bates M, Bowden A, et al. (1980) "The interaction of phenobarbital and other anticonvulsants with oral contraceptive steroid therapy." Contraception, 22, p. 495-503
- Dossetor J (1975) "Drug interactions with oral contraceptives." Br Med J, 4, p. 467-8
- Furlan AJ, Rothner AD (1974) "Anti-epileptic drugs and failure of oral contraceptives." Lancet, 1, p. 1113
- Coulam CB, Annegers JF (1979) "Do anticonvulsants reduce the efficacy of oral contraceptives?" Epilepsia, 20, p. 519-26
- Szoka PR, Edgren RA (1988) "Drug interactions with oral contraceptives: compilation and analysis of an adverse experience report database." Fertil Steril, 49, s31-8
- Mattson RH, Cramer JA, Darney PD, Naftolin F (1986) "Use of oral contraceptives by women with epilepsy." JAMA, 256, p. 238-40
- Laengner H, Detering K (1974) "Letter: Anti-epileptic drugs and failure of oral contraceptives." Lancet, 2, p. 600
- Curran MA (1986) "Drug interactions with the pill." Med J Aust, 144, p. 670-1
- Back DJ, Orme ML (1990) "Pharmacokinetic drug interactions with oral contraceptives." Clin Pharmacokinet, 18, p. 472-84
- D'Arcy PF (1986) "Drug interactions with oral contraceptives." Drug Intell Clin Pharm, 20, p. 353-62
- Kleier DJ, Tucker JE (1987) "Oral contraceptive failure secondary to dentally prescribed drugs: fact or fiction?" J Colo Dent Assoc, 66, p. 5-6
- Back DJ, Breckenridge AM, Crawford FE, MacIver M, Orne ML, Rowe PH (1981) "Interindividual variation and drug interactions with hormonal steroid contraceptives." Drugs, 21, p. 46-61
- Shane-McWorter L, Cerveny JD, MacFarlane LL, Osborn C (1998) "Enhanced metabolism of levonorgestrel during phenobarbital treatment and resultant pregnancy." Pharmacotherapy, 18, p. 1360-4
- Haukkamaa M (1986) "Contraception by Norplant subdermal capsules is not reliable in epileptic patients on anticonvulsant treatment." Contraception, 33, p. 559-65
- (2001) "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories
- Back DJ, Grimmer SF, Orme ML, Proudlove D, Mann RD, Breckenridge AM (1988) "Evaluation of Committee on Safety of Medicines yellow card reports on oral contraceptive-drug interactions with anticonvulsants and antibiotics." Br J Clin Pharmacol, 25, p. 527-32
- O'Brien MD, Guillebaud J (2006) "Contraception for women with epilepsy." Epilepsia, 47, p. 1419-22
- Faculty of Sexual & Reproductive Healthcare (2016) "FSRH Clinical Guidance: Drug Interactions with Hormonal Contraception. file:///C:/Users/df033684/Downloads/ceuguidancedruginteractionshormonal.pdf"
aspirin caffeine
Applies to: Fiortal (aspirin / butalbital / caffeine), Fiortal (aspirin / butalbital / caffeine)
One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.
References
- Yoovathaworn KC, Sriwatanakul K, Thithapandha A (1986) "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet, 11, p. 71-6
Drug and food interactions
butalbital food
Applies to: Fiortal (aspirin / butalbital / caffeine)
GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.
MANAGEMENT: The combination of ethanol and barbiturates should be avoided.
References
- Gupta RC, Kofoed J (1966) "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J, 94, p. 863-5
- Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS (1971) "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med, 51, p. 346-51
- Saario I, Linnoila M (1976) "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh), 38, p. 382-92
- Stead AH, Moffat AC (1983) "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol, 2, p. 5-14
- Seixas FA (1979) "Drug/alcohol interactions: avert potential dangers." Geriatrics, 34, p. 89-102
levonorgestrel food
Applies to: Levora (ethinyl estradiol / levonorgestrel)
MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.
MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.
References
- Edgar B, Bailey D, Bergstrand R, et al. (1992) "Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics on felodipine and its potential clinical relevance." Eur J Clin Pharmacol, 42, p. 313-7
- Jonkman JH, Sollie FA, Sauter R, Steinijans VW (1991) "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther, 49, p. 248-55
- Bailey DG, Arnold JM, Munoz C, Spence JD (1993) "Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin." Clin Pharmacol Ther, 53, p. 637-42
- Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
- Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A (1994) "Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation." Pharmazie, 49, p. 522-4
- Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD (1993) "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther, 54, p. 589-94
- Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG (1995) "Drug-food interactions in clinical practice." J Fam Pract, 40, p. 376-84
- (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
- Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
- Min DI, Ku YM, Geraets DR, Lee HC (1996) "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol, 36, p. 469-76
- Majeed A, Kareem A (1996) "Effect of grapefruit juice on cyclosporine pharmacokinetics." Pediatr Nephrol, 10, p. 395
- Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS (1996) "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol, 42, p662
- Josefsson M, Zackrisson AL, Ahlner J (1996) "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol, 51, p. 189-93
- Kantola T, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther, 63, p. 397-402
- Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A (1998) "Interaction between grapefruit juice and diazepam in humans." Eur J Drug Metab Pharmacokinet, 23, p. 55-9
- Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
- Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR (1998) "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther, 64, p. 248-56
- Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
- Lilja JJ, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther, 64, p. 477-83
- Fuhr U, Maier-Bruggemann A, Blume H, et al. (1998) "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther, 36, p. 126-32
- Lilja JJ, Kivisto KT, Neuvonen PJ (1999) "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther, 66, p. 118-27
- Eagling VA, Profit L, Back DJ (1999) "Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-I protease inhibitor saquinavir by grapefruit juice components." Br J Clin Pharmacol, 48, p. 543-52
- Damkier P, Hansen LL, Brosen K (1999) "Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine." Br J Clin Pharmacol, 48, p. 829-38
- Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC (1999) "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther, 21, p. 1890-9
- Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57
- Gunston GD, Mehta U (2000) "Potentially serious drug interactions with grapefruit juice." S Afr Med J, 90, p. 41
- Takanaga H, Ohnishi A, Maatsuo H, et al. (2000) "Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model." Br J Clin Pharmacol, 49, p. 49-58
- Libersa CC, Brique SA, Motte KB, et al. (2000) "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol, 49, p. 373-8
- Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
- Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E (2001) "Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers." Ther Drug Monit, 23, p. 369-73
- Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K (1993) "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol, 44, p. 295-8
- Flanagan D (2005) "Understanding the grapefruit-drug interaction." Gen Dent, 53, 282-5; quiz 286
aspirin food
Applies to: Fiortal (aspirin / butalbital / caffeine)
GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.
MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.
References
- (2002) "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn
ethinyl estradiol food
Applies to: Levora (ethinyl estradiol / levonorgestrel)
Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.
References
- Weber A, Jager R, Borner A, et al. (1996) "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception, 53, p. 41-7
- Schubert W, Eriksson U, Edgar B, Cullberg G, Hedner T (1995) "Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17B-estradiol." Eur J Drug Metab Pharmacokinet, 20, p. 219-24
caffeine food
Applies to: Fiortal (aspirin / butalbital / caffeine)
The effect of grapefruit juice on the pharmacologic activity of caffeine is controversial. One report suggests that grapefruit juice increases the effect of caffeine. The proposed mechanism is inhibition of cytochrome P-450 metabolism of caffeine. However, a well-conducted pharmacokinetic/pharmacodynamic study did not demonstrate this effect. The clinical significance of this potential interaction is unknown.
References
- (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
- Maish WA, Hampton EM, Whitsett TL, Shepard JD, Lovallo WR (1996) "Influence of grapefruit juice on caffeine pharmacokinetics and pharmacodynamics." Pharmacotherapy, 16, p. 1046-52
ethinyl estradiol food
Applies to: Levora (ethinyl estradiol / levonorgestrel)
The central nervous system effects and blood levels of ethanol may be increased in patients taking oral contraceptives, although data are lacking and reports are contradictory. The mechanism may be due to enzyme inhibition. Consider counseling women about this interaction which is unpredictable.
References
- Hobbes J, Boutagy J, Shenfield GM (1985) "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther, 38, p. 371-80
levonorgestrel food
Applies to: Levora (ethinyl estradiol / levonorgestrel)
The central nervous system effects and blood levels of ethanol may be increased in patients taking oral contraceptives, although data are lacking and reports are contradictory. The mechanism may be due to enzyme inhibition. Consider counseling women about this interaction which is unpredictable.
References
- Hobbes J, Boutagy J, Shenfield GM (1985) "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther, 38, p. 371-80
aspirin food
Applies to: Fiortal (aspirin / butalbital / caffeine)
One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.
References
- Yoovathaworn KC, Sriwatanakul K, Thithapandha A (1986) "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet, 11, p. 71-6
Therapeutic duplication warnings
No duplication warnings were found for your selected drugs.
Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
No interaction information available. |
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