Cimetidine and Other H2 Blockers: Safety and precautions - CancerChoices



H2 blockers, used to treat gastrointestinal ulcers and/or reduce stomach acid, may improve survival among people with cancer, especially after colorectal cancer resection.

Safety and precautions

Cimetidine has low toxicity overall; however, several cautions, side effects, and interactions with other drugs are noted. Proton-pump inhibitors (PPIs) are the most commonly prescribed drugs to treat stomach-acid issues,1Gardner A. Should you be afraid of stomach-acid medicine? Penn Medicine News. July 02, 2019. Viewed May 1, 2023. but H2 blockers are also commonly used to reduce stomach acid. Because they are often used without a prescription, their use is not always monitored by a health professional. We strongly recommend that you tell your oncologist if you are using H2 blockers.

Cancer risk

Increased risk of breast cancer, squamous cell carcinoma, or adenocarcinoma and are noted among people using H2 blockers. No rise in esophageal or stomach (gastric) cancer has been seen.

Breast cancer

Substantially higher risk of estrogen receptor-positive/progesterone receptor-positive ductal carcinoma among current users of ranitidine, but no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on risk of breast cancer among people using H2 blockers overall, cimetidine, or famotidine

Gastrointestinal cancer

No evidence of a rise in incidence of esophageal or stomach (gastric) cancer among people who had been prescribed cimetidine in a large study

Lung cancer

Modest evidencesignificant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observational studies), or several small studies aggregated into a meta-analysis (this is the CancerChoices definition; other researchers and studies may define this differently) of a moderately higher risk of squamous cell carcinoma or adenocarcinoma among people with type 2 diabetes using histamine-2 receptor blockers

Interactions with cancer treatment

Good evidencesignificant effects in one large or several mid-sized and well-designed clinical studies (randomized controlled trials (RCTs) with an appropriate placebo or other strong comparison control or observational studies that control for confounds) (this is the CancerChoices definition; other researchers and studies may define this differently) links use of acid suppressants (either PPIs or H2 blockers) to worse survival among people with non-small-cell lung cancer treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors or PD-1/PD-L1 inhibitors, but no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on survival among people treated with gefitinib.

Studies have found no adverse effects from histamine blockers on treatment with gefitinib, interleukin-2 (IL-2), or ALA-PDT.

Use of either proton pump inhibitors or H2 blockers can also lead to an inaccurate fasting plasma gastrin assay for diagnosing a gastrinoma.10Dhillo WS, Jayasena CN et al. Plasma gastrin measurement cannot be used to diagnose a gastrinoma in patients on either proton pump inhibitors or histamine type-2 receptor antagonists. Annals of Clinical Biochemistry. 2006 Mar;43(Pt 2):153-5.

Common side effects/adverse events

Common side effects include headache, dizziness, diarrhea, and rash. Other less common but more serious side effects include these:11Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP. Repurposing drugs in oncology (ReDO)—cimetidine as an anti-cancer agent. Ecancermedicalscience. 2014;8:485.

  • Reversible suppression of white blood cells (leukopenia) or platelets (thrombocytopenia)
  • Elevated estrogen levels; use can produce galactorrhea (a milky nipple discharge) in women and gynecomastia (enlargement or swelling of breast tissue) in men
  • Male sexual dysfunction which resolves with discontinued use
  • Increased potential for bone marrow suppression (myelosuppression) when used together with drugs capable of causing bone marrow suppression

One elderly user experienced reversible mental confusion from cimetidine.12Marshall ME, Butler K, Hermansen D. Treatment of hormone-refractory stage D carcinoma of prostate with coumarin (1,2-benzopyrone) and cimetidine: a pilot study. Prostate. 1990;17(2):95-9. 

Interactions with other treatments

Cimetidine may interact with several medications and therapies:13Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP. Repurposing drugs in oncology (ReDO)—cimetidine as an anti-cancer agent. Ecancermedicalscience. 2014;8:485.

  • Hydroxychloroquine: cimetidine may interact with the antimalarial medication hydroxychloroquine (another drug used off-label for some types of cancer). 
  • Methadone and opioids: cimetidine affects the metabolism of methadone, sometimes resulting in higher blood levels and a higher incidence of side effects. Cimetidine is also known to increase the effects of several opioids and can lead to extreme plasma levels of these drugs and a fatal overdose. 
  • Psychoactive medications: cimetidine can interact with a number of different psychoactive medications, including tricyclic antidepressants and selective serotonin reuptake inhibitors, causing increased blood levels of these drugs and subsequent toxicity.

Cimetidine can interfere with vitamin D metabolism, preventing an expected rise in serum levels and the benefits from that.14Kennedy DA, Cooley K et al. Vitamin D: pharmacokinetics and safety when used in conjunction with the pharmaceutical drugs used in cancer patients: a systematic review. Cancers (Basel). 2013 Mar 11;5(1):255-80. You might want to have your vitamin D levels checked before, during, and after using cimetidine. If your levels are low before starting cimetidine, talk with your doctor about using vitamin D supplements.

Do not use/contraindications

Due to possible elevated estrogen levels from use, people with estrogen-sensitive cancers, including some breast cancers and gynecologic cancers, should use H2 blockers with caution.15Chang R. Beyond the Magic Bullet: The Anti-Cancer Cocktail. New York: Square One Publishers. 2012; Mathes RW, Malone KE, Daling JR, Porter PL, Li CI. Relationship between histamine2-receptor antagonist medications and risk of invasive breast cancer. Cancer Epidemiology, Biomarkers & Prevention. 2008 Jan;17(1):67-72.

Due to suppression of white blood cells or platelets, use during chemotherapy should also be approached with caution.16Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP. Repurposing drugs in oncology (ReDO)—cimetidine as an anti-cancer agent. Ecancermedicalscience. 2014;8:485.

Keep reading about H2 blockers

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Nancy Hepp, MS

Lead Researcher
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Ms. Hepp is a researcher and communicator who has been writing and editing educational content on varied health topics for more than 20 years. She serves as lead researcher and writer for CancerChoices and also served as the first program manager. Her graduate work in research and cognitive psychology, her master’s degree in instructional design, and her certificate in web design have all guided her in writing and presenting information for a wide variety of audiences and uses. Nancy’s service as faculty development coordinator in the Department of Family Medicine at Wright State University also provided experience in medical research, plus insights into medical education and medical care from the professional’s perspective.

Nancy Hepp, MS Lead Researcher

Laura Pole, MSN, RN, OCNS

Senior Clinical Consultant
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Laura Pole is senior clinical consultant for CancerChoices. Laura is an oncology clinical nurse specialist who has been providing integrative oncology clinical care, navigation, consultation, and education services for over 40 years. She is the co-creator and co-coordinator of the Integrative Oncology Navigation Training at Smith Center for Healing and the Arts in Washington, DC. Laura also manages the “Media Watch Cancer News That You Can Use” listserv for Smith Center/Commonweal. In her role as a palliative care educator and consultant, Laura has served as statewide Respecting Choices Faculty for the Virginia POST (Physician Orders for Scope of Treatment) Collaborative as well as provided statewide professional education on palliative and end-of-life care for the Virginia Association for Hospices and Palliative Care.

For CancerChoices, Laura curates content and research, networks with clinical and organizational partners, brings awareness and education of integrative oncology at professional and patient conferences and programs, and translates research into information relevant to the patient experience as well as clinical practice.

Laura sees her work with CancerChoices as a perfect alignment of all her passions, knowledge and skills in integrative oncology care. She is honored to serve you.

Laura Pole, MSN, RN, OCNS Senior Clinical Consultant

Reviewer

Susan Yaguda, MSN, RN

Manager at Atrium Health’s Levine Cancer Institute and CancerChoices Clinical Consultant
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Susan Yaguda, MSN, RN, has been a nurse for nearly 40 years, working in a variety of healthcare settings. She currently works in Charlotte, North Carolina, at Atrium Health’s Levine Cancer Institute as the manager for Integrative Oncology and Cancer Survivorship. She works with a multidisciplinary team to deliver holistic, evidence-based support and education for patients and care partners at any point along the trajectory of cancer care. She completed the Integrative Oncology Scholars Program through the University of Michigan in 2020, is certified as an Integrative Health Coach through Duke Integrative Medicine and has a post-graduate certificate in Nursing Education from the University of North Carolina, Charlotte. Susan also was awarded the Planetree International Scholar’s Award in 2018 and was recognized by the Daisy Foundation for Nurse Leadership in 2021. Susan has a particular interest in empowering patients and care partners with knowledge to help drive informed decision making and educating nurses on the benefits of integrative care for patients and self-care. She has presented nationally and internationally on integrative oncology and nursing education.

She and her husband, Mark, have two adult children and a very spoiled foxhound. She enjoys hiking, knitting, cooking, and pickleball.

“As a frequent consumer of Beyond Conventional Cancer Therapies, and now CancerChoices, for both professional education and patient support, it is an honor to have the opportunity to engage with the dedicated team at CancerChoices to serve those impacted by this disease.”  

 

Susan Yaguda, MSN, RN Manager at Atrium Health’s Levine Cancer Institute and CancerChoices Clinical Consultant

Last update: May 9, 2024

Last full literature review: May 2023

CancerChoices provides information about integrativein cancer care, a patient-centered approach combining the best of conventional care, self care, and evidence-informed complementary care in an integrated plan cancer care. We review complementaryin cancer care, complementary care involves the use of therapies intended to enhance or add to standard conventional treatments; examples include supplements, mind-body approaches such as yoga or psychosocialtherapy, and acupuncture therapies and self carelifestyle actions and behaviors that may impact cancer outcomes; examples include eating health-promoting foods, limiting alcohol, increasing physical activity, and managing stress practices to help patients and professionals explore and integrate the best combination of conventionalthe cancer care offered by conventionally trained physicians and most hospitals; examples are chemotherapy, surgery, and radiotherapy and complementary therapies and practices for each person.

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