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Interactions between Kyleena and Somatrem

1 drug interaction and 27 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

levonorgestrel somatrem

Applies to: Kyleena (levonorgestrel) and somatrem
Monitor

Coadministration with human growth hormone (hGH) receptor agonists may alter the clearance and plasma concentrations of estrogens and progestins that are metabolized by CYP450 isoenzymes. The mechanism of this interaction may be mediated via the effects of hGH receptor agonists on different CYP450 isoenzymes. The labeling of some hGH receptor agonists specify that this interaction may be the most significant for substrates of CYP450 3A4, which may be involved in the metabolism of estrogen and progestin, as well as CYP450 1A2 and their clearance may be increased. However, clinical data are limited, and clinical significance is unknown. In a study of 11 growth hormone (GH)-deficient adults randomized to GH or placebo for 6 months followed by 3 months of GH for all subjects, antipyrine clearance, a non-specific marker of hepatic CYP450 activity, increased in all subjects who received GH treatment compared to placebo. In vitro studies have indicated that GH enhanced CYP450 3A4 gene expression; however, other studies have suggested that when administered in a pulsatile fashion, CYP450 3A4 activity is reduced. A study in healthy elderly men did not reveal any effects on CYP450 3A4 or 2D6 but did demonstrate induction of 1A2 and inhibition of 2C19. Given that studies have varied in the type of growth hormone used, dosing regimens, ages and sexes of the patients and/or cell lines utilized, it is difficult to predict how coadministration may affect the CYP450 substrate.

Management

Careful monitoring is advised when estrogens and progestins that are metabolized by CYP450 isoenzymes are used in combination with hGH receptor agonists. If the sex steroid in question is being used for hormonal contraception, additional or alternative non-hormonal birth control may necessary. The label of the specific hGH receptor agonist and estrogen and/or progestin being coadministered should be consulted for more specific guidance. Patients should be advised to monitor for both reductions in the efficacy of their estrogen and/or progestin as well as side effects of those medications and report any concerns to their healthcare provider.

References (19)
  1. Dossetor J (1975) "Drug interactions with oral contraceptives." Br Med J, 4, p. 467-8
  2. 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
  3. (2003) "Product Information. Humatrope (somatropin)." Lilly, Eli and Company
  4. (2004) "Product Information. Zorbtive (somatropin)." Serono Laboratories Inc
  5. Faculty of Sexual & Reproductive Healthcare (2016) "FSRH Clinical Guidance: Drug Interactions with Hormonal Contraception. file:///C:/Users/df033684/Downloads/ceuguidancedruginteractionshormonal.pdf"
  6. (2025) "Product Information. Skytrofa (lonapegsomatropin)." Ascendis Pharma, Inc., DailyMed
  7. (2025) "Product Information. Norditropin (somatropin)." Novo Nordisk Pharmaceuticals Inc
  8. (2024) "Product Information. Norditropin FlexPro (somatropin)." Novo Nordisk Ltd
  9. (2020) "Product Information. Genotropin Miniquick (somatropin)." Pfizer Canada ULC
  10. (2025) "Product Information. Ngenla (somatrogon)." Pfizer U.S. Pharmaceuticals Group
  11. (2025) "Product Information. Ngenla (somatrogon)." Pfizer Canada ULC
  12. (2026) "Product Information. Ngenla (somatrogon)." Pfizer Australia Pty Ltd
  13. (2026) "Product Information. Ngenla (somatrogon)." Pfizer Ltd
  14. Cheung NW, Liddle C, Coverdale S, Lou JC, boyages sc (1996) "Growth hormone treatment increases cytochrome P450-mediated antipyrine clearance in man" The Journal of Clinical Endocrinology & Metabolism, 81, p. 1996-2001
  15. Dhir RN, Dworakowski W, Thangavel C, Shapiro BH (2006) "Sexually dimorphic regulation of hepatic isoforms of human cytochrome P450 by growth hormone" The Journal of Pharmacology and Experimental Therapeutics, 316, p. 87-94
  16. Jurgens G, Lange KHW, Reuther LO, et al (2002) "Effect of growth hormone on hepatic cytochrome P450 activity in healthy elderly men" Clin Pharmacol and Therapeutic, 71, p. 162-8
  17. jaffe ca, turgeon dk, Demott-Friberg R, Watkins PB (2002) "Growth hormone secretion pattern is an independent regulator of growth hormone actions in humans" American Journal of Physiology-Endocrinology and Metabolism, 283, E1008-E1015
  18. (2025) "Product Information. Saizen (somatropin)." Merck Serono Australia Pty Ltd, A015-0925
  19. (2025) "Product Information. Skytrofa (lonapegsomatropin)." Specialised Therapeutics Pharma Pty Ltd

Food/lifestyle interactions

Moderate food/lifestyle interactions

Moderate:

levonorgestrel Food/Lifestyle

Applies to: Kyleena (levonorgestrel)
Monitor

Grapefruit or 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 (32)
  1. 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
  2. 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
  3. 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
  4. Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
  5. 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
  6. 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
  7. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG (1995) "Drug-food interactions in clinical practice." J Fam Pract, 40, p. 376-84
  8. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  9. 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
  10. 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
  11. Majeed A, Kareem A (1996) "Effect of grapefruit juice on cyclosporine pharmacokinetics." Pediatr Nephrol, 10, p. 395
  12. 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
  13. 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
  14. 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
  15. 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
  16. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  17. 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
  18. 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
  19. 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
  20. 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
  21. 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
  22. 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
  23. 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
  24. 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
  25. Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57
  26. Gunston GD, Mehta U (2000) "Potentially serious drug interactions with grapefruit juice." S Afr Med J, 90, p. 41
  27. 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
  28. 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
  29. 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
  30. 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
  31. 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
  32. Flanagan D (2005) "Understanding the grapefruit-drug interaction." Gen Dent, 53, 282-5; quiz 286
Moderate:

somatrem Alcohol (Ethanol)

Applies to: somatrem
Monitor

Coadministration with human growth hormone (hGH) receptor agonists may alter the clearance and plasma concentrations of medicinal products that are metabolized by CYP450 isoenzymes. The mechanism of this interaction may be mediated via the effects of hGH receptor agonists on expression of different CYP450 isoenzymes. The labeling of some hGH receptor agonists specify that this interaction may be the most significant for substrates of CYP450 3A4 and/or 1A2 and indicate that their clearance may be increased. However, clinical data are limited, and clinical significance is unknown. In a study of 11 growth hormone (GH)-deficient adults randomized to GH or placebo for 6 months followed by 3 months of GH for all subjects, antipyrine clearance, a non-specific marker of hepatic CYP450 activity, increased in all subjects who received GH treatment compared to placebo. In vitro studies have indicated that GH enhanced CYP450 3A4 gene expression; however, other studies have suggested that when administered in a pulsatile fashion, CYP450 3A4 activity is reduced. A study in healthy elderly men did not reveal any effects on CYP450 3A4 or 2D6 but did demonstrate induction of 1A2 and inhibition of 2C19. Given that studies have varied in the type of growth hormone used, dosing regimens, ages and sexes of the patients and/or cell lines utilized, it is difficult to predict how coadministration may affect the CYP450 substrate.

Management

Careful monitoring is advised when drugs that are metabolized by CYP450 isoenzymes are used in combination with hGH receptor agonists. As this interaction's clinical significance is unknown, the label of the specific hGH receptor agonist and CYP450 substrate(s) being coadministered should be consulted for more specific guidance.

References (20)
  1. (2003) "Product Information. Humatrope (somatropin)." Lilly, Eli and Company
  2. (2004) "Product Information. Zorbtive (somatropin)." Serono Laboratories Inc
  3. (2025) "Product Information. Skytrofa (lonapegsomatropin)." Ascendis Pharma, Inc., DailyMed
  4. (2025) "Product Information. Norditropin (somatropin)." Novo Nordisk Pharmaceuticals Inc
  5. (2024) "Product Information. Norditropin FlexPro (somatropin)." Novo Nordisk Ltd
  6. (2020) "Product Information. Genotropin Miniquick (somatropin)." Pfizer Canada ULC
  7. (2025) "Product Information. Ngenla (somatrogon)." Pfizer U.S. Pharmaceuticals Group
  8. (2025) "Product Information. Ngenla (somatrogon)." Pfizer Canada ULC
  9. (2026) "Product Information. Ngenla (somatrogon)." Pfizer Australia Pty Ltd
  10. (2025) "Product Information. Sogroya (somapacitan)." Novo Nordisk Pharmaceuticals Pty Ltd
  11. (2025) "Product Information. Sogroya (somapacitan)." Novo Nordisk Pharmaceuticals Inc
  12. (2023) "Product Information. Sogroya (somapacitan)." Novo Nordisk Canada Inc
  13. (2025) "Product Information. Sogroya (somapacitan)." Novo Nordisk Ltd, 2
  14. (2026) "Product Information. Ngenla (somatrogon)." Pfizer Ltd
  15. Cheung NW, Liddle C, Coverdale S, Lou JC, boyages sc (1996) "Growth hormone treatment increases cytochrome P450-mediated antipyrine clearance in man" The Journal of Clinical Endocrinology & Metabolism, 81, p. 1996-2001
  16. Dhir RN, Dworakowski W, Thangavel C, Shapiro BH (2006) "Sexually dimorphic regulation of hepatic isoforms of human cytochrome P450 by growth hormone" The Journal of Pharmacology and Experimental Therapeutics, 316, p. 87-94
  17. Jurgens G, Lange KHW, Reuther LO, et al (2002) "Effect of growth hormone on hepatic cytochrome P450 activity in healthy elderly men" Clin Pharmacol and Therapeutic, 71, p. 162-8
  18. jaffe ca, turgeon dk, Demott-Friberg R, Watkins PB (2002) "Growth hormone secretion pattern is an independent regulator of growth hormone actions in humans" American Journal of Physiology-Endocrinology and Metabolism, 283, E1008-E1015
  19. (2025) "Product Information. Saizen (somatropin)." Merck Serono Australia Pty Ltd, A015-0925
  20. (2025) "Product Information. Skytrofa (lonapegsomatropin)." Specialised Therapeutics Pharma Pty Ltd
Moderate:

somatrem Alcohol (Ethanol)

Applies to: somatrem
Monitor

Coadministration with human growth hormone (hGH) receptor agonists may alter the clearance and plasma concentrations of medicinal products that are metabolized by CYP450 isoenzymes. The mechanism of this interaction may be mediated via the effects of hGH receptor agonists on expression of different CYP450 isoenzymes. The labeling of some hGH receptor agonists specify that this interaction may be the most significant for substrates of CYP450 3A4 and/or 1A2 and indicate that their clearance may be increased. However, clinical data are limited, and clinical significance is unknown. In a study of 11 growth hormone (GH)-deficient adults randomized to GH or placebo for 6 months followed by 3 months of GH for all subjects, antipyrine clearance, a non-specific marker of hepatic CYP450 activity, increased in all subjects who received GH treatment compared to placebo. In vitro studies have indicated that GH enhanced CYP450 3A4 gene expression; however, other studies have suggested that when administered in a pulsatile fashion, CYP450 3A4 activity is reduced. A study in healthy elderly men did not reveal any effects on CYP450 3A4 or 2D6 but did demonstrate induction of 1A2 and inhibition of 2C19. Given that studies have varied in the type of growth hormone used, dosing regimens, ages and sexes of the patients and/or cell lines utilized, it is difficult to predict how coadministration may affect the CYP450 substrate.

Management

Careful monitoring is advised when drugs that are metabolized by CYP450 isoenzymes are used in combination with hGH receptor agonists. As this interaction's clinical significance is unknown, the label of the specific hGH receptor agonist and CYP450 substrate(s) being coadministered should be consulted for more specific guidance.

References (20)
  1. (2003) "Product Information. Humatrope (somatropin)." Lilly, Eli and Company
  2. (2004) "Product Information. Zorbtive (somatropin)." Serono Laboratories Inc
  3. (2025) "Product Information. Skytrofa (lonapegsomatropin)." Ascendis Pharma, Inc., DailyMed
  4. (2025) "Product Information. Norditropin (somatropin)." Novo Nordisk Pharmaceuticals Inc
  5. (2024) "Product Information. Norditropin FlexPro (somatropin)." Novo Nordisk Ltd
  6. (2020) "Product Information. Genotropin Miniquick (somatropin)." Pfizer Canada ULC
  7. (2025) "Product Information. Ngenla (somatrogon)." Pfizer U.S. Pharmaceuticals Group
  8. (2025) "Product Information. Ngenla (somatrogon)." Pfizer Canada ULC
  9. (2026) "Product Information. Ngenla (somatrogon)." Pfizer Australia Pty Ltd
  10. (2025) "Product Information. Sogroya (somapacitan)." Novo Nordisk Pharmaceuticals Pty Ltd
  11. (2025) "Product Information. Sogroya (somapacitan)." Novo Nordisk Pharmaceuticals Inc
  12. (2023) "Product Information. Sogroya (somapacitan)." Novo Nordisk Canada Inc
  13. (2025) "Product Information. Sogroya (somapacitan)." Novo Nordisk Ltd, 2
  14. (2026) "Product Information. Ngenla (somatrogon)." Pfizer Ltd
  15. Cheung NW, Liddle C, Coverdale S, Lou JC, boyages sc (1996) "Growth hormone treatment increases cytochrome P450-mediated antipyrine clearance in man" The Journal of Clinical Endocrinology & Metabolism, 81, p. 1996-2001
  16. Dhir RN, Dworakowski W, Thangavel C, Shapiro BH (2006) "Sexually dimorphic regulation of hepatic isoforms of human cytochrome P450 by growth hormone" The Journal of Pharmacology and Experimental Therapeutics, 316, p. 87-94
  17. Jurgens G, Lange KHW, Reuther LO, et al (2002) "Effect of growth hormone on hepatic cytochrome P450 activity in healthy elderly men" Clin Pharmacol and Therapeutic, 71, p. 162-8
  18. jaffe ca, turgeon dk, Demott-Friberg R, Watkins PB (2002) "Growth hormone secretion pattern is an independent regulator of growth hormone actions in humans" American Journal of Physiology-Endocrinology and Metabolism, 283, E1008-E1015
  19. (2025) "Product Information. Saizen (somatropin)." Merck Serono Australia Pty Ltd, A015-0925
  20. (2025) "Product Information. Skytrofa (lonapegsomatropin)." Specialised Therapeutics Pharma Pty Ltd
Moderate:

somatrem Caffeine

Applies to: somatrem
Monitor

Coadministration with human growth hormone (hGH) receptor agonists may alter the clearance and plasma concentrations of medicinal products that are metabolized by CYP450 isoenzymes. The mechanism of this interaction may be mediated via the effects of hGH receptor agonists on expression of different CYP450 isoenzymes. The labeling of some hGH receptor agonists specify that this interaction may be the most significant for substrates of CYP450 3A4 and/or 1A2 and indicate that their clearance may be increased. However, clinical data are limited, and clinical significance is unknown. In a study of 11 growth hormone (GH)-deficient adults randomized to GH or placebo for 6 months followed by 3 months of GH for all subjects, antipyrine clearance, a non-specific marker of hepatic CYP450 activity, increased in all subjects who received GH treatment compared to placebo. In vitro studies have indicated that GH enhanced CYP450 3A4 gene expression; however, other studies have suggested that when administered in a pulsatile fashion, CYP450 3A4 activity is reduced. A study in healthy elderly men did not reveal any effects on CYP450 3A4 or 2D6 but did demonstrate induction of 1A2 and inhibition of 2C19. Given that studies have varied in the type of growth hormone used, dosing regimens, ages and sexes of the patients and/or cell lines utilized, it is difficult to predict how coadministration may affect the CYP450 substrate.

Management

Careful monitoring is advised when drugs that are metabolized by CYP450 isoenzymes are used in combination with hGH receptor agonists. As this interaction's clinical significance is unknown, the label of the specific hGH receptor agonist and CYP450 substrate(s) being coadministered should be consulted for more specific guidance.

References (20)
  1. (2003) "Product Information. Humatrope (somatropin)." Lilly, Eli and Company
  2. (2004) "Product Information. Zorbtive (somatropin)." Serono Laboratories Inc
  3. (2025) "Product Information. Skytrofa (lonapegsomatropin)." Ascendis Pharma, Inc., DailyMed
  4. (2025) "Product Information. Norditropin (somatropin)." Novo Nordisk Pharmaceuticals Inc
  5. (2024) "Product Information. Norditropin FlexPro (somatropin)." Novo Nordisk Ltd
  6. (2020) "Product Information. Genotropin Miniquick (somatropin)." Pfizer Canada ULC
  7. (2025) "Product Information. Ngenla (somatrogon)." Pfizer U.S. Pharmaceuticals Group
  8. (2025) "Product Information. Ngenla (somatrogon)." Pfizer Canada ULC
  9. (2026) "Product Information. Ngenla (somatrogon)." Pfizer Australia Pty Ltd
  10. (2025) "Product Information. Sogroya (somapacitan)." Novo Nordisk Pharmaceuticals Pty Ltd
  11. (2025) "Product Information. Sogroya (somapacitan)." Novo Nordisk Pharmaceuticals Inc
  12. (2023) "Product Information. Sogroya (somapacitan)." Novo Nordisk Canada Inc
  13. (2025) "Product Information. Sogroya (somapacitan)." Novo Nordisk Ltd, 2
  14. (2026) "Product Information. Ngenla (somatrogon)." Pfizer Ltd
  15. Cheung NW, Liddle C, Coverdale S, Lou JC, boyages sc (1996) "Growth hormone treatment increases cytochrome P450-mediated antipyrine clearance in man" The Journal of Clinical Endocrinology & Metabolism, 81, p. 1996-2001
  16. Dhir RN, Dworakowski W, Thangavel C, Shapiro BH (2006) "Sexually dimorphic regulation of hepatic isoforms of human cytochrome P450 by growth hormone" The Journal of Pharmacology and Experimental Therapeutics, 316, p. 87-94
  17. Jurgens G, Lange KHW, Reuther LO, et al (2002) "Effect of growth hormone on hepatic cytochrome P450 activity in healthy elderly men" Clin Pharmacol and Therapeutic, 71, p. 162-8
  18. jaffe ca, turgeon dk, Demott-Friberg R, Watkins PB (2002) "Growth hormone secretion pattern is an independent regulator of growth hormone actions in humans" American Journal of Physiology-Endocrinology and Metabolism, 283, E1008-E1015
  19. (2025) "Product Information. Saizen (somatropin)." Merck Serono Australia Pty Ltd, A015-0925
  20. (2025) "Product Information. Skytrofa (lonapegsomatropin)." Specialised Therapeutics Pharma Pty Ltd
Moderate:

somatrem Caffeine

Applies to: somatrem
Monitor

Coadministration with human growth hormone (hGH) receptor agonists may alter the clearance and plasma concentrations of medicinal products that are metabolized by CYP450 isoenzymes. The mechanism of this interaction may be mediated via the effects of hGH receptor agonists on expression of different CYP450 isoenzymes. The labeling of some hGH receptor agonists specify that this interaction may be the most significant for substrates of CYP450 3A4 and/or 1A2 and indicate that their clearance may be increased. However, clinical data are limited, and clinical significance is unknown. In a study of 11 growth hormone (GH)-deficient adults randomized to GH or placebo for 6 months followed by 3 months of GH for all subjects, antipyrine clearance, a non-specific marker of hepatic CYP450 activity, increased in all subjects who received GH treatment compared to placebo. In vitro studies have indicated that GH enhanced CYP450 3A4 gene expression; however, other studies have suggested that when administered in a pulsatile fashion, CYP450 3A4 activity is reduced. A study in healthy elderly men did not reveal any effects on CYP450 3A4 or 2D6 but did demonstrate induction of 1A2 and inhibition of 2C19. Given that studies have varied in the type of growth hormone used, dosing regimens, ages and sexes of the patients and/or cell lines utilized, it is difficult to predict how coadministration may affect the CYP450 substrate.

Management

Careful monitoring is advised when drugs that are metabolized by CYP450 isoenzymes are used in combination with hGH receptor agonists. As this interaction's clinical significance is unknown, the label of the specific hGH receptor agonist and CYP450 substrate(s) being coadministered should be consulted for more specific guidance.

References (20)
  1. (2003) "Product Information. Humatrope (somatropin)." Lilly, Eli and Company
  2. (2004) "Product Information. Zorbtive (somatropin)." Serono Laboratories Inc
  3. (2025) "Product Information. Skytrofa (lonapegsomatropin)." Ascendis Pharma, Inc., DailyMed
  4. (2025) "Product Information. Norditropin (somatropin)." Novo Nordisk Pharmaceuticals Inc
  5. (2024) "Product Information. Norditropin FlexPro (somatropin)." Novo Nordisk Ltd
  6. (2020) "Product Information. Genotropin Miniquick (somatropin)." Pfizer Canada ULC
  7. (2025) "Product Information. Ngenla (somatrogon)." Pfizer U.S. Pharmaceuticals Group
  8. (2025) "Product Information. Ngenla (somatrogon)." Pfizer Canada ULC
  9. (2026) "Product Information. Ngenla (somatrogon)." Pfizer Australia Pty Ltd
  10. (2025) "Product Information. Sogroya (somapacitan)." Novo Nordisk Pharmaceuticals Pty Ltd
  11. (2025) "Product Information. Sogroya (somapacitan)." Novo Nordisk Pharmaceuticals Inc
  12. (2023) "Product Information. Sogroya (somapacitan)." Novo Nordisk Canada Inc
  13. (2025) "Product Information. Sogroya (somapacitan)." Novo Nordisk Ltd, 2
  14. (2026) "Product Information. Ngenla (somatrogon)." Pfizer Ltd
  15. Cheung NW, Liddle C, Coverdale S, Lou JC, boyages sc (1996) "Growth hormone treatment increases cytochrome P450-mediated antipyrine clearance in man" The Journal of Clinical Endocrinology & Metabolism, 81, p. 1996-2001
  16. Dhir RN, Dworakowski W, Thangavel C, Shapiro BH (2006) "Sexually dimorphic regulation of hepatic isoforms of human cytochrome P450 by growth hormone" The Journal of Pharmacology and Experimental Therapeutics, 316, p. 87-94
  17. Jurgens G, Lange KHW, Reuther LO, et al (2002) "Effect of growth hormone on hepatic cytochrome P450 activity in healthy elderly men" Clin Pharmacol and Therapeutic, 71, p. 162-8
  18. jaffe ca, turgeon dk, Demott-Friberg R, Watkins PB (2002) "Growth hormone secretion pattern is an independent regulator of growth hormone actions in humans" American Journal of Physiology-Endocrinology and Metabolism, 283, E1008-E1015
  19. (2025) "Product Information. Saizen (somatropin)." Merck Serono Australia Pty Ltd, A015-0925
  20. (2025) "Product Information. Skytrofa (lonapegsomatropin)." Specialised Therapeutics Pharma Pty Ltd

Minor food/lifestyle interactions

Minor:

levonorgestrel Alcohol (Ethanol)

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

Disease interactions

21 potential interactions Applies to: 20 conditions, including High Blood Pressure, High Cholesterol, Depression, Migraine, and Underactive Thyroid.

Abnormal Uterine Bleeding

Major:

Kyleena

The levonorgestrel in Kyleena has a major potential interaction with Abnormal Uterine Bleeding.

The use of contraceptives is contraindicated when there is an undiagnosed abnormal genital bleeding. Adequate diagnostic measures should be undertaken to rule out the presence of any malignancy.

Asthma

Moderate:

Kyleena

The levonorgestrel in Kyleena has a moderate potential interaction with Asthma.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

Breast Cancer

Major:

Kyleena

The levonorgestrel in Kyleena has a major potential interaction with Breast Cancer.

The use of progestogens is considered by manufacturers to be contraindicated in patients with existing or suspected malignancy of the breast. Some supportive data are available for medroxyprogesterone. Specifically, medroxyprogesterone treatment may be associated with breast cancer, primarily when the drug is administered intramuscularly. A pooled analysis of two case-control studies, one from the World Health Organization and the other from New Zealand, revealed a small overall relative risk of breast cancer in women who have ever used intramuscular medroxyprogesterone acetate. The relative risk was higher in the subgroup of women who had initiated therapy within the previous 5 years. Thus, an increased risk (approximately 2-fold) is associated with intramuscular medroxyprogesterone use in the first 5 years. A more recent U.S. study also found a statistically significant increase in breast cancer risk among recent users (defined as last use within the past five years) who used depo-medroxyprogesterone acetate for 12 months or longer.

Cerebral Vascular Disorder

Moderate:

Kyleena

The levonorgestrel in Kyleena has a moderate potential interaction with Cerebral Vascular Disorder.

The use of levonorgestrel requires careful assessment and caution in conditions of arterial disease, including stroke and myocardial infarction, and also, in patients with increased blood pressure and coagulopathies.

Depression

Moderate:

Kyleena

The levonorgestrel in Kyleena has a moderate potential interaction with Depression.

The use of oral contraceptives has been associated with an increased incidence of depression. It is uncertain whether this effect is related to the estrogenic or the progestogenic component of the contraceptive, although excess progesterone activity is associated with depression. Patients with a history of depression receiving estrogen and/or progestogen therapy should be followed closely. The manufacturer of medroxyprogesterone recommends monitoring patients who have a history of depression and to not re- administer medroxyprogesterone if depression recurs.

Diabetes Mellitus

Moderate:

Kyleena

The levonorgestrel in Kyleena has a moderate potential interaction with Diabetes Mellitus.

Impaired glucose tolerance has been observed in some patients administered oral contraceptives and appears to be related primarily to the estrogen dose. However, progestogens can increase insulin secretion and produce insulin resistance to varying degrees, depending on the agent. Caution and close monitoring are recommended in patients with diabetes mellitus during therapy with estrogens and/or progestogens, and adjustments made accordingly in their antidiabetic regimen.

Moderate:

somatrem

Somatrem has a moderate potential interaction with Diabetes Mellitus.

The use of growth hormone has been associated with resistance to insulin. Patients with diabetes mellitus or impaired glucose tolerance should be observed closely during therapy. The dose of antihyperglycemic drugs (insulin or oral/injectable agents) may require adjustment.

Fluid Retention

Moderate:

Kyleena

The levonorgestrel in Kyleena has a moderate potential interaction with Fluid Retention.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

Heart Failure

Moderate:

Kyleena

The levonorgestrel in Kyleena has a moderate potential interaction with Heart Failure.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

Hepatic Tumor

Major:

Kyleena

The levonorgestrel in Kyleena has a major potential interaction with Hepatic Tumor.

The use of oral contraceptives is contraindicated in patients with liver tumors. An increased risk of benign hepatic adenomas and hepatocellular carcinomas has been associated with long-term, oral estrogen- progestin contraceptive use of at least 4 years and 8 years, respectively. Although these tumors are rare and have not been reported with other types of estrogen or progestogen therapies, any preparation containing estrogens and/or progestogens should probably be avoided in patients with existing tumors of the liver. Hepatic hemangiomas and nodular hyperplasia of the liver have been reported with isolated estrogen therapy.

High Blood Pressure

Moderate:

Kyleena

The levonorgestrel in Kyleena has a moderate potential interaction with High Blood Pressure.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

High Cholesterol

Moderate:

Kyleena

The levonorgestrel in Kyleena has a moderate potential interaction with High Cholesterol.

Some progestogenic agents may elevate plasma LDL levels and/or lower HDL levels, although data have been inconsistent. Patients with preexisting hyperlipidemia may require closer monitoring during progestogen therapy, and adjustments made accordingly in their lipid-lowering regimen.

History, Thrombotic/Thromboembolic Disorder

Moderate:

Kyleena

The levonorgestrel in Kyleena has a moderate potential interaction with History, Thrombotic/Thromboembolic Disorder.

The use of levonorgestrel requires careful assessment and caution in conditions of arterial disease, including stroke and myocardial infarction, and also, in patients with increased blood pressure and coagulopathies.

Liver Disease

Major:

Kyleena

The levonorgestrel in Kyleena has a major potential interaction with Liver Disease.

The use of progestogens, in general, is contraindicated in patients with impaired hepatic function or liver disease. There are little or no data concerning the pharmacokinetic disposition of the different progestogens in patients with hepatic disease. However, most hormones, including progestational hormones, are known to be extensively metabolized by the liver. Medroxyprogesterone should not be used by women with significant liver disease and should be discontinued if jaundice or disturbances of liver function occur.

Migraine

Moderate:

Kyleena

The levonorgestrel in Kyleena has a moderate potential interaction with Migraine.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

Renal Dysfunction

Moderate:

Kyleena

The levonorgestrel in Kyleena has a moderate potential interaction with Renal Dysfunction.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

Seizures

Moderate:

Kyleena

The levonorgestrel in Kyleena has a moderate potential interaction with Seizures.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

Thrombotic/Thromboembolic Disorder

Moderate:

Kyleena

The levonorgestrel in Kyleena has a moderate potential interaction with Thrombotic/Thromboembolic Disorder.

The use of levonorgestrel requires careful assessment and caution in conditions of arterial disease, including stroke and myocardial infarction, and also, in patients with increased blood pressure and coagulopathies.

Thyroid Disease

Moderate:

Kyleena

The levonorgestrel in Kyleena has a moderate potential interaction with Thyroid Disease.

When administering estrogen and/or progestogen therapy in patients with thyroid disorders, clinicians should be aware that these hormones may affect thyroid function tests. Patients on thyroid replacement therapy may require higher doses of thyroid hormone and appropriate monitoring. Changes have mostly been reported with the use of combination oral contraceptives. Specifically, thyroid-binding globulin (TBG) may be increased, resulting in elevated circulating total thyroid hormone, as measured by PBI (protein-bound iodine), T4 by column or radioimmunoassay, or T3 by radioimmunoassay. Free T3 resin uptake may be decreased. On the contrary, a decrease in TBG and, consequently, thyroxine concentration, has been reported by the manufacturers of the progestin-only (norethindrone) oral contraceptives.

Underactive Thyroid

Moderate:

somatrem

Somatrem has a moderate potential interaction with Underactive Thyroid.

The use of growth hormone has been associated with the development of hypothyroidism. Patients should be monitored baseline and periodically for adequate thyroid function. Inadequate treatment of hypothyroidism may inhibit the optimal response to growth hormone.

Weight Loss

Minor:

Kyleena

The levonorgestrel in Kyleena has a minor potential interaction with Weight Loss.

Progestogens can cause weight gain, which may be significant (as is the case with parenteral medroxyprogesterone) and undesirable in obese patients attempting to lose weight.

More resources

Kyleena

A total of 277 drugs are known to interact with Kyleena.

somatrem

A total of 654 drugs are known to interact with somatrem.

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.