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Drug Interactions between Asthmacon and Kelnor 1/35

This report displays the potential drug interactions for the following 2 drugs:

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Moderate

amobarbital ethinyl estradiol

Applies to: Asthmacon (aminophylline / amobarbital / ephedrine) and Kelnor 1 / 35 (ethinyl estradiol / ethynodiol)

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

  1. Baciewicz AM "Oral contraceptive drug interactions." Ther Drug Monit 7 (1985): 26-35
  2. Mumford JP "Letter: Drugs affecting oral contraceptives." Br Med J 2 (1974): 333-4
  3. Back DJ, Bates M, Bowden A, et al. "The interaction of phenobarbital and other anticonvulsants with oral contraceptive steroid therapy." Contraception 22 (1980): 495-503
  4. Dossetor J "Drug interactions with oral contraceptives." Br Med J 4 (1975): 467-8
  5. Furlan AJ, Rothner AD "Anti-epileptic drugs and failure of oral contraceptives." Lancet 1 (1974): 1113
  6. Coulam CB, Annegers JF "Do anticonvulsants reduce the efficacy of oral contraceptives?" Epilepsia 20 (1979): 519-26
  7. Szoka PR, Edgren RA "Drug interactions with oral contraceptives: compilation and analysis of an adverse experience report database." Fertil Steril 49 (1988): s31-8
  8. Mattson RH, Cramer JA, Darney PD, Naftolin F "Use of oral contraceptives by women with epilepsy." JAMA 256 (1986): 238-40
  9. Laengner H, Detering K "Letter: Anti-epileptic drugs and failure of oral contraceptives." Lancet 2 (1974): 600
  10. Curran MA "Drug interactions with the pill." Med J Aust 144 (1986): 670-1
  11. Back DJ, Orme ML "Pharmacokinetic drug interactions with oral contraceptives." Clin Pharmacokinet 18 (1990): 472-84
  12. D'Arcy PF "Drug interactions with oral contraceptives." Drug Intell Clin Pharm 20 (1986): 353-62
  13. Kleier DJ, Tucker JE "Oral contraceptive failure secondary to dentally prescribed drugs: fact or fiction?" J Colo Dent Assoc 66 (1987): 5-6
  14. Back DJ, Breckenridge AM, Crawford FE, MacIver M, Orne ML, Rowe PH "Interindividual variation and drug interactions with hormonal steroid contraceptives." Drugs 21 (1981): 46-61
  15. Shane-McWorter L, Cerveny JD, MacFarlane LL, Osborn C "Enhanced metabolism of levonorgestrel during phenobarbital treatment and resultant pregnancy." Pharmacotherapy 18 (1998): 1360-4
  16. Haukkamaa M "Contraception by Norplant subdermal capsules is not reliable in epileptic patients on anticonvulsant treatment." Contraception 33 (1986): 559-65
  17. "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories PROD (2001):
  18. Back DJ, Grimmer SF, Orme ML, Proudlove D, Mann RD, Breckenridge AM "Evaluation of Committee on Safety of Medicines yellow card reports on oral contraceptive-drug interactions with anticonvulsants and antibiotics." Br J Clin Pharmacol 25 (1988): 527-32
  19. O'Brien MD, Guillebaud J "Contraception for women with epilepsy." Epilepsia 47 (2006): 1419-22
  20. Faculty of Sexual & Reproductive Healthcare "FSRH Clinical Guidance: Drug Interactions with Hormonal Contraception. file:///C:/Users/df033684/Downloads/ceuguidancedruginteractionshormonal.pdf" (2016):
View all 20 references

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Moderate

amobarbital aminophylline

Applies to: Asthmacon (aminophylline / amobarbital / ephedrine) and Asthmacon (aminophylline / amobarbital / ephedrine)

MONITOR: Barbiturates may decrease serum levels and therapeutic effects of the methylxanthines. The mechanism is barbiturate induction of CYP450 3A4 and 1A2 hepatic metabolism of methylxanthines.

MANAGEMENT: Close observation for clinical and laboratory evidence of decreased methylxanthine effect is indicated if these drugs must be used together. Patients should be advised to notify their physician if they experience a worsening of their respiratory symptoms.

References

  1. Upton RA "Pharmacokinetic interactions between theophylline and other medication (Part I)." Clin Pharmacokinet 20 (1991): 66-80
  2. Bukowskyj M, Nakatsu K, Munt PW "Theophylline reassessed." Ann Intern Med 101 (1984): 63-73
  3. Landay RA, Gonzalez MA, Taylor JC "Effect of phenobarbital on theophylline disposition." J Allergy Clin Immunol 62 (1978): 27-9
  4. Dahlqvist R, Steiner E, Koike Y, von Bahr C, Lind M, Billing B "Induction of theophylline metabolism by pentobarbital." Ther Drug Monit 11 (1989): 408-10
View all 4 references

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Moderate

ethinyl estradiol aminophylline

Applies to: Kelnor 1 / 35 (ethinyl estradiol / ethynodiol) and Asthmacon (aminophylline / amobarbital / ephedrine)

MONITOR: The coadministration with contraceptive steroids may increase the plasma concentrations of theophylline and other methylxanthines. The proposed mechanism is inhibition of methylxanthine metabolism via hepatic microsomal enzymes, of which estrogens and progestins are also substrates. In one study, theophylline clearance was approximately 30% lower in oral contraceptive users than in nonusers. However, clinical data have been conflicting.

MANAGEMENT: Caution is advised during concomitant therapy with methylxanthines and hormonal contraceptives. Serum theophylline levels and pharmacologic response should be monitored and the dosage adjusted accordingly, particularly following initiation or discontinuation of hormonal contraceptives in patients who are stabilized on their theophylline regimen. Patients should be advised to notify their physician if they experience signs and symptoms of theophylline toxicity such as nausea, vomiting, diarrhea, headache, restlessness, insomnia, and irregular heartbeat.

References

  1. Tornatore KM, Kanarkowski R, McCarthy TL, et al. "Effect of chronic oral contraceptive steroids on theophylline disposition." Eur J Clin Pharmacol 23 (1982): 129-34
  2. Gardner MJ, Tornatore KM, Jusko WJ, Kanarkowski R "Effects of tobacco smoking and oral contraceptive use on theophylline disposition." Br J Clin Pharmacol 16 (1983): 271-80
  3. Roberts RK, Grice J, McGuffie, Heilbronn L "Oral contraceptive steroids impair the elimination of theophylline." J Lab Clin Med 101 (1983): 821-25

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Moderate

amobarbital ethynodiol

Applies to: Asthmacon (aminophylline / amobarbital / ephedrine) and Kelnor 1 / 35 (ethinyl estradiol / ethynodiol)

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

  1. Baciewicz AM "Oral contraceptive drug interactions." Ther Drug Monit 7 (1985): 26-35
  2. Mumford JP "Letter: Drugs affecting oral contraceptives." Br Med J 2 (1974): 333-4
  3. Back DJ, Bates M, Bowden A, et al. "The interaction of phenobarbital and other anticonvulsants with oral contraceptive steroid therapy." Contraception 22 (1980): 495-503
  4. Dossetor J "Drug interactions with oral contraceptives." Br Med J 4 (1975): 467-8
  5. Furlan AJ, Rothner AD "Anti-epileptic drugs and failure of oral contraceptives." Lancet 1 (1974): 1113
  6. Coulam CB, Annegers JF "Do anticonvulsants reduce the efficacy of oral contraceptives?" Epilepsia 20 (1979): 519-26
  7. Szoka PR, Edgren RA "Drug interactions with oral contraceptives: compilation and analysis of an adverse experience report database." Fertil Steril 49 (1988): s31-8
  8. Mattson RH, Cramer JA, Darney PD, Naftolin F "Use of oral contraceptives by women with epilepsy." JAMA 256 (1986): 238-40
  9. Laengner H, Detering K "Letter: Anti-epileptic drugs and failure of oral contraceptives." Lancet 2 (1974): 600
  10. Curran MA "Drug interactions with the pill." Med J Aust 144 (1986): 670-1
  11. Back DJ, Orme ML "Pharmacokinetic drug interactions with oral contraceptives." Clin Pharmacokinet 18 (1990): 472-84
  12. D'Arcy PF "Drug interactions with oral contraceptives." Drug Intell Clin Pharm 20 (1986): 353-62
  13. Kleier DJ, Tucker JE "Oral contraceptive failure secondary to dentally prescribed drugs: fact or fiction?" J Colo Dent Assoc 66 (1987): 5-6
  14. Back DJ, Breckenridge AM, Crawford FE, MacIver M, Orne ML, Rowe PH "Interindividual variation and drug interactions with hormonal steroid contraceptives." Drugs 21 (1981): 46-61
  15. Shane-McWorter L, Cerveny JD, MacFarlane LL, Osborn C "Enhanced metabolism of levonorgestrel during phenobarbital treatment and resultant pregnancy." Pharmacotherapy 18 (1998): 1360-4
  16. Haukkamaa M "Contraception by Norplant subdermal capsules is not reliable in epileptic patients on anticonvulsant treatment." Contraception 33 (1986): 559-65
  17. "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories PROD (2001):
  18. Back DJ, Grimmer SF, Orme ML, Proudlove D, Mann RD, Breckenridge AM "Evaluation of Committee on Safety of Medicines yellow card reports on oral contraceptive-drug interactions with anticonvulsants and antibiotics." Br J Clin Pharmacol 25 (1988): 527-32
  19. O'Brien MD, Guillebaud J "Contraception for women with epilepsy." Epilepsia 47 (2006): 1419-22
  20. Faculty of Sexual & Reproductive Healthcare "FSRH Clinical Guidance: Drug Interactions with Hormonal Contraception. file:///C:/Users/df033684/Downloads/ceuguidancedruginteractionshormonal.pdf" (2016):
View all 20 references

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Moderate

aminophylline ethynodiol

Applies to: Asthmacon (aminophylline / amobarbital / ephedrine) and Kelnor 1 / 35 (ethinyl estradiol / ethynodiol)

MONITOR: The coadministration with contraceptive steroids may increase the plasma concentrations of theophylline and other methylxanthines. The proposed mechanism is inhibition of methylxanthine metabolism via hepatic microsomal enzymes, of which estrogens and progestins are also substrates. In one study, theophylline clearance was approximately 30% lower in oral contraceptive users than in nonusers. However, clinical data have been conflicting.

MANAGEMENT: Caution is advised during concomitant therapy with methylxanthines and hormonal contraceptives. Serum theophylline levels and pharmacologic response should be monitored and the dosage adjusted accordingly, particularly following initiation or discontinuation of hormonal contraceptives in patients who are stabilized on their theophylline regimen. Patients should be advised to notify their physician if they experience signs and symptoms of theophylline toxicity such as nausea, vomiting, diarrhea, headache, restlessness, insomnia, and irregular heartbeat.

References

  1. Tornatore KM, Kanarkowski R, McCarthy TL, et al. "Effect of chronic oral contraceptive steroids on theophylline disposition." Eur J Clin Pharmacol 23 (1982): 129-34
  2. Gardner MJ, Tornatore KM, Jusko WJ, Kanarkowski R "Effects of tobacco smoking and oral contraceptive use on theophylline disposition." Br J Clin Pharmacol 16 (1983): 271-80
  3. Roberts RK, Grice J, McGuffie, Heilbronn L "Oral contraceptive steroids impair the elimination of theophylline." J Lab Clin Med 101 (1983): 821-25

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Minor

ePHEDrine aminophylline

Applies to: Asthmacon (aminophylline / amobarbital / ephedrine) and Asthmacon (aminophylline / amobarbital / ephedrine)

Ephedrine-methylxanthine combinations are used for the treatment of asthma but the efficacy of the combination has been questioned. This combination may lead to increased xanthine side effects. The mechanism is unknown, but may be related to synergistic pharmacologic effects. Patients using this combination should be closely monitored for side effects such as nausea, vomiting, tachycardia, nervousness, or insomnia. If side effects are noted, the dosage of the xanthine may need to be decreased.

References

  1. Weinberger M, Bronsky E, Bensch GW, Bock GN, Yecies JJ "Interaction of ephedrine and theophylline." Clin Pharmacol Ther 17 (1975): 585-92
  2. Sims JA, doPico GA, Reed CE "Bronchodilating effect of oral theophylline-ephedrine combination." J Allergy Clin Immunol 62 (1978): 15-21
  3. Tinkelman DG, Avner SE "Ephedrine therapy in asthmatic children. Clinical tolerance and absence of side effects." JAMA 237 (1977): 553-7
  4. Weinberger MM, Brousky EA "Evaluation of oral bronchodilator therapy in asthmatic children: bronchodilators in asthmatic children." J Pediatr 84 (1974): 421-7
  5. Badiei B, Faciane J, Sly M "Effect of throphylline, ephedrine and theri combination upon exercise-induced airway obstruction." Ann Allergy 35 (1975): 32-6
View all 5 references

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Drug and food interactions

Major

amobarbital food

Applies to: Asthmacon (aminophylline / amobarbital / ephedrine)

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

  1. Gupta RC, Kofoed J "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J 94 (1966): 863-5
  2. Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med 51 (1971): 346-51
  3. Saario I, Linnoila M "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh) 38 (1976): 382-92
  4. Stead AH, Moffat AC "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol 2 (1983): 5-14
  5. Seixas FA "Drug/alcohol interactions: avert potential dangers." Geriatrics 34 (1979): 89-102
View all 5 references

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Moderate

ePHEDrine food

Applies to: Asthmacon (aminophylline / amobarbital / ephedrine)

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

References

  1. Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res 1 (1979): 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther 11 (1970): 656
  3. "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc PROD (2001):
  4. "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals PROD (2001):
  5. "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals PROD (2001):
  6. "Product Information. Focalin (dexmethylphenidate)." Mikart Inc (2001):
  7. "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company (2002):
View all 7 references

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Moderate

aminophylline food

Applies to: Asthmacon (aminophylline / amobarbital / ephedrine)

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

References

  1. Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res 1 (1979): 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther 11 (1970): 656
  3. "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc PROD (2001):
  4. "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals PROD (2001):
  5. "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals PROD (2001):
  6. "Product Information. Focalin (dexmethylphenidate)." Mikart Inc (2001):
  7. "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company (2002):
View all 7 references

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Minor

ethinyl estradiol food

Applies to: Kelnor 1 / 35 (ethinyl estradiol / ethynodiol)

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

  1. Weber A, Jager R, Borner A, et al. "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception 53 (1996): 41-7
  2. Schubert W, Eriksson U, Edgar B, Cullberg G, Hedner T "Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17B-estradiol." Eur J Drug Metab Pharmacokinet 20 (1995): 219-24

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Minor

ethinyl estradiol food

Applies to: Kelnor 1 / 35 (ethinyl estradiol / ethynodiol)

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

  1. Hobbes J, Boutagy J, Shenfield GM "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther 38 (1985): 371-80

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Minor

ethynodiol food

Applies to: Kelnor 1 / 35 (ethinyl estradiol / ethynodiol)

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

  1. Hobbes J, Boutagy J, Shenfield GM "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther 38 (1985): 371-80

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Therapeutic duplication warnings

No 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.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor 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.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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