Skip to main content

Advertisement

SpringerLink
Log in

Influence of oral magnesium-containing supplement and antacid administration on hypomagnesemia induced by panitumumab

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Hypomagnesemia is a common side effect of panitumumab. The effect of magnesium-containing supplement as a laxative and concomitant antacid (proton pump inhibitor and histamine H2 antagonist) administration on panitumumab-induced hypomagnesemia was retrospectively investigated.

Methods

Patients with advanced or recurrent colorectal cancer who received panitumumab were included in this study. Serum magnesium levels were extracted from the electronic medical records of 1753 administrations in 221 patients who received panitumumab. Serum magnesium levels in patients with or without oral magnesium-containing supplement and antacid treatment were compared using analysis of covariance as the number of panitumumab administration up to 16 times for covariates.

Results

The mean serum magnesium levels were significantly decreased with increasing number of panitumumab administrations (2.13 mg/dL at 1st vs. 1.55 mg/dL at 16th, p < 0.001). The use of oral magnesium-containing supplement significantly inhibited the decline in mean serum magnesium level (1.98 mg/dL vs. 1.78 mg/dL, p < 0.001). However, antacid use in patients receiving oral magnesium-containing supplement significantly decreased the effectiveness of the magnesium supplement on serum magnesium level (2.02 mg/dL vs. 1.93 mg/dL, p < 0.05).

Conclusion

The use of oral magnesium-containing supplement might function as magnesium supplement based on the finding that use of oral magnesium-containing supplement during panitumumab administration decreased hypomagnesemia. However, combination of antacid decreased the supplemental effect of oral magnesium on hypomagnesemia. These results suggest the possibility that use of antacids during anti-EGFR antibody administration may promote hypomagnesemia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Kim TW, Elme A, Kusic Z et al (2014) A phase 3 trial evaluating panitumumab plus best supportive care vs best supportive care in chemorefractory wild-type KRAS or RAS metastatic colorectal cancer. Br J Cancer 115:1206–1214

    Article  CAS  Google Scholar 

  2. Price TJ, Peeters M, Kim TW et al (2014) Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol 15:569–579

    Article  CAS  PubMed  Google Scholar 

  3. Douillard JY, Siena S, Cassidy J et al (2014) Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol 25:1346–1355

    Article  CAS  PubMed  Google Scholar 

  4. Fakih M, Wilding G, Lombardo J (2006) Cetuximab-induced hypomagnesemia in patients with colorectal cancer. Clin Colorectal Cancer 6:152–156

    Article  CAS  PubMed  Google Scholar 

  5. Tejpar S, Piessevaux H, Claes K, Piront P, Hoenderop JG, Verslype C, Van Cutsem E (2007) Magnesium wasting associated with epidermal-growth-factor receptor-targeting antibodies in colorectal cancer: a prospective study. Lancet Oncol 8:387–394

    Article  CAS  PubMed  Google Scholar 

  6. Fakih M (2008) Management of anti-EGFR-targeting monoclonal antibody-induced hypomagnesemia. Oncology (Williston Park) 22:74–76

    Google Scholar 

  7. Schrag D, Chung KY, Flombaum C, Saltz L (2005) Cetuximab therapy and symptomatic hypomagnesemia. J Natl Cancer Inst 97:1221–1224

    Article  CAS  PubMed  Google Scholar 

  8. Yoshimura Y, Fujisaki K, Yamamoto T, Shinohara Y (2017) Pharmacokinetic studies of orally administered magnesium oxide in rats. Yakugaku Zasshi 137:581–587

    Article  CAS  PubMed  Google Scholar 

  9. Ibuka H, Ishihara M, Suzuki A, Kagaya H, Shimizu M, Kinosada Y, Itoh Y (2016) Antacid attenuates the laxative action of magnesia in cancer patients receiving opioid analgesic. J Pharm Pharmacol 68:1214–1221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Yamasaki M, Funakoshi S, Matsuda S, Imazu T, Takeda Y, Murakami T, Maeda Y (2014) Interaction of magnesium oxide with gastric acid secretion inhibitors in clinical pharmacotherapy. Eur J Clin Pharmacol 70:921–924

    Article  CAS  Google Scholar 

  11. Yamamoto Y, Watanabe K, Tsukiyama I, Yabushita H, Matsuura K, Wakatsuki A (2016) Hydration with 15 mEq magnesium is effective at reducing the risk for cisplatin-induced nephrotoxicity in patients receiving cisplatin (≥ 50 mg/m2) combination chemotherapy. Anticancer Res 36:1873–1877

    CAS  PubMed  Google Scholar 

  12. Bodnar L, Wcislo G, Gasowska-Bodnar A, Synowiec A, Szarlej-Wcisło K, Szczylik C (2008) Renal protection with magnesium subcarbonate and magnesium sulphate in patients with epithelial ovarian cancer after cisplatin and paclitaxel chemotherapy: a randomised phase II study. Eur J Cancer 44:2608–2614

    Article  CAS  PubMed  Google Scholar 

  13. Willox JC, McAllister EJ, Sangster G, Kaye SB (1986) Effects of magnesium supplementation in testicular cancer patients receiving cis-platin: a randomised trial. Br J Cancer 54:19–23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ranade VV, Somberg JC (2001) Bioavailability and pharmacokinetics of magnesium after administration of magnesium salts to humans. Am J Ther 8:345–357

    Article  CAS  PubMed  Google Scholar 

  15. Lindberg JS, Zobitz MM, Poindexter JR, Pak CY (1990) Magnesium bioavailability from magnesium citrate and magnesium oxide. J Am Coll Nutr 9:48–55

    Article  CAS  PubMed  Google Scholar 

  16. FDA Drug Safety Communication. Low magnesium levels can be associated with long-term use of Proton Pump Inhibitor drugs (PPIs). https://www.fda.gov/drugs/drugsafety/ucm245011.htm. Accessed 7 Dec 2018 (Updated 8 Apr 2017)

  17. Eom CS, Park SM, Myung SK, Yun JM, Ahn JS (2011) Use of acid-suppressive drugs and risk of fracture: a meta-analysis of observational studies. Ann Fam Med 9:257–267

    Article  PubMed  PubMed Central  Google Scholar 

  18. Merki HS, Wilder-Smith CH (1994) Do continuous infusions of omeprazole and ranitidine retain their effect with prolonged dosing? Gastroenterology 106:60–64

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was funded by a research grant of Shizuoka Cancer Center.

Author information

Authors and Affiliations

  1. Department of Pharmacy, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka Prefecture, 411-8777, Japan

    Junya Sato, Hiroshi Ishikawa, Rei Tanaka & Michihiro Sino

Authors
  1. Junya Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroshi Ishikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rei Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michihiro Sino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Junya Sato.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sato, J., Ishikawa, H., Tanaka, R. et al. Influence of oral magnesium-containing supplement and antacid administration on hypomagnesemia induced by panitumumab. Cancer Chemother Pharmacol 83, 673–679 (2019). https://doi.org/10.1007/s00280-019-03772-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-019-03772-y

Keywords

Search

Navigation