Cimetidine

We’re busy updating our review of cimetidine and will provide a rating when that’s complete. While we’re working, we share a summary from our predecessor website, Beyond Conventional Cancer Therapies. The information we share here was last updated in August 2021.

Please consider supporting our update and revision to this information.

Cimetidine

Key Points

• Cimetidine is an over-the-counter drug approved by the FDA to inhibit the secretion of stomach acid. Its use in cancer is considered off-label.
• Even though the H2 blocker drugs don’t require a prescription, consulting your oncology team about interactions with other treatments and therapies is very important. Also check that this therapy is safe for use with any other medical conditions you may have.
• Cimetidine reduces cancer growth and spread; it also enhances anticancer immunity and the effectiveness of conventional cancer treatments in some cancers. It may also reduce treatment side effects.
• Some of the benefits are seen when cimetidine is used in combination with other therapies.

Cimetidine is an antacid and antihistamine medication, in a class of medications called H2 antagonists or H2 blockers. It is used mainly to treat ulcers of the stomach and intestines and prevent their return.

Other H2 blockers include famotidine, nizatidine and ranitidine. Most of the research regarding effects in cancer involves cimetidine.

Treating the Cancer

Working against cancer growth or spread, improving survival, or working with other treatments or therapies to improve their anticancer action.

Cimetidine has shown the following effects in preventing tumor cell growth and metastasis:1

• Prevents cancer cell adhesion
• Prevents the development of blood vessels to supply tumors (anti-angiogenesis)
• Reduces cancer cell growth and spread (anti-proliferation)
• Induces cell death (apoptosis)
• Inhibits immunosuppression that typically follows surgery
• Enhances other biologically active treatments

Preclinical and clinical reports show that cimetidine may be a promising drug to repurpose for cancer treatment. It regulates the immune system, and its most promising use may be near the time of surgical removal (resection) of solid tumors in combination with other standard treatments.2

Clinical Evidence

Unspecified or Multiple Cancers

• Improved survival when combined with histamine, with reduced size of liver and lung metastases in some people with advanced cancer in whom classical anticancer therapy had been abandoned3

Brain Cancer (Glioblastoma)

Improved prognosis of people with recurrence of glioblastoma when the CLOVA cocktail of drugs (cimetidine, lithium, olanzapine, and valproate) was added to temozolomide treatment4

Breast Cancer

No effect of cimetidine use before surgery on tumor cell proliferation5

Colorectal Cancer

• May improve survival in patients with colorectal cancer6, although not all studies found benefit;7 may be more effective in those with less tumor burden and better immune function and in cancers that are more likely to trigger immune responses (have a higher antigenic potential)8
• Increased response of tumor-infiltrating white blood cells (lymphocytes) when used 10 days before and 7 days after surgery9

Kidney Cancer (Renal Cell Carcinoma)

• High-dose cimetidine: two complete remissions among 42 people with metastatic renal cell carcinoma10
• Cimetidine with interferon-alpha: favorable rates of complete or partial responses or stable disease and also of survival among people with advanced renal cell carcinoma11
• Cimetidine with interferon-alpha, a COX-2 inhibitor (meloxicam) and a renin-angiotensin-system inhibitor (candesartan) as a first-line treatment: favorable rates of objective response, clinical benefit, progression-free survival and overall survival in people with metastatic renal cell carcinoma12
• Cimetidine with a COX-2 inhibitor (meloxicam) and a renin-angiotensin system inhibitor (cilexetil): prolonged partial remissions among people with metastatic renal cell carcinoma13
• Cimetidine with coumarin: favorable response rates and disease stabilization among people with locally advanced or metastatic renal cell carcinoma in one study14 but a lower-than-expected response rate in another15

Lung Cancer

• Regression of metastasis in lung cancer16

Stomach Cancer or Gastrointestinal Cancers

• Improved survival, especially in people with stage 3 or 4 stomach cancer, when started immediately after surgery (or the decision not to operate)17
• Suppressed tumor cell proliferation18

Lab and Animal Evidence

Managing Side Effects and Promoting Wellness

Managing or relieving side effects or symptoms, reducing treatment toxicity, supporting quality of life or promoting general well-being

Clinical Evidence

• Reduced suppression of immune function that typically follows surgical removal (resection),25 including a more rapid return to pre-operative immune function after surgery26 
• Reduced cisplatin’s kidney toxicity (nephrotoxicity) without compromising the success of tumor therapy27

Lab and Animal Evidence

Optimizing Your Terrain

Creating an environment within your body that does not support cancer development, growth or spread

• Increased numbers of anticancer immune cells30
• Regulated or normalized anticancer functions of the immune system31
• Increased production of antitumor signalling proteins (cytokines)32

Access

Cimetidine is available both by prescription and as an over-the-counter drug.

Cautions

Cimetidine overall has low toxicity; however, several cautions and side effects are noted. Consult your physician and your pharmacist prior to taking this drug.

Cimetidine can interfere with vitamin D metabolism, preventing an expected rise in serum levels and the benefits from that.33

Common Side Effects/Adverse Events

Reported side effects:34

• Elevated estrogen levels; use cautiously in those with breast and gynecologic cancers;35 use can produce galactorrhea (a milky nipple discharge) in women and gynecomastia (enlargement or swelling of breast tissue) in men
• Male sexual dysfunction
• Increased potential for bone marrow suppression (myelosuppression) when used together with drugs capable of causing bone marrow suppression

Interactions with Other Treatments

From a review in 2014:36

• 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.

Dosing

CancerChoices does not recommend therapies or doses, but only provides information for patients and providers to consider as part of a complete treatment plan. Patients should discuss therapies with their physicians, as contraindications, interactions and side effects must be evaluated.

Integrative Programs, Protocols and Medical Systems

For more information about protocols, see our Protocols page.

Used in these programs and protocols:

• Block program37
• Chang strategies38

Commentary

From Clinical Pearls, Cancer Strategies Journal (Summer 2013. p.7) edited by BCCT advisor Dwight McKee, MD: “Given its low toxicity and low cost, cimetidine can probably be administered to patients with colorectal cancer and possibly other adenocarcinomas that express the Sialyl Lewis antigens to minimize metastases and recurrence and enhance survival.”

Also known by these brand names

CVS Health Heartburn Relief
Equaline Acid Reducer
Leader Heartburn Relief
Tagamet HB
Tagamet Pro

Resources

• Web MD: Cimetidine
• McKee, Dwight (editor). Clinical Pearls. Cancer Strategies Journal. Summer 2013. p.7.
• Moss Reports podcast: Repurposed Drugs for Cancer with Raymond Chang, MD
• LifeExtension Nutritional Support: Cancer Adjuvant Therapy: Repurposing Common Drugs as Adjuvant Cancer Therapies
• Raymond Chang, MD: Beyond the Magic Bullet: The Anti-Cancer Cocktail
• Keith I. Block, MD: Life over Cancer: The Block Center Program for Integrative Cancer Treatment

References

1. Antoszczak M, Markowska A, Markowska J, Huczyński A. Old wine in new bottles: drug repurposing in oncology. European Journal of Pharmacology. 2020 Jan 5;866:172784; Kubecova M, Kolostova K, Pinterova D, Kacprzak G, Bobek V. Cimetidine: an anticancer drug? European Journal of Pharmaceutical Sciences. 2011 Apr 18;42(5):439-44; Faustino-Rocha AI, Ferreira R, Gama A, Oliveira PA, Ginja M. Antihistamines as promising drugs in cancer therapy. Life Sciences. 2017 Mar 1;172:27-41.
2. Antoszczak M, Markowska A, Markowska J, Huczyński A. Old wine in new bottles: drug repurposing in oncology. European Journal of Pharmacology. 2020 Jan 5;866:172784.
3. Burtin C, Noirot C, Scheinmann P, Galoppin L, Sabolovic D, Bernard P. Clinical improvement in advanced cancer disease after treatment combining histamine and H2-antihistaminics (ranitidine or cimetidine). European Journal of Cancer & Clinical Oncology. 1988 Feb;24(2):161-7.
4. Furuta T, Sabit H et al. Biological basis and clinical study of glycogen synthase kinase- 3β-targeted therapy by drug repositioning for glioblastoma. Oncotarget. 2017 Apr 4;8(14):22811-22824.
5. Bowrey PF, King J et al. Histamine, mast cells and tumour cell proliferation in breast cancer: does preoperative cimetidine administration have an effect? British Journal of Cancer. 2000 Jan;82(1):167-70.
6. Losurdo G, Principi M et al. Histamine and histaminergic receptors in colorectal cancer: from basic science to evidence-based medicine. Anti-Cancer Agents in Medicinal Chemistry. 2018;18(1):15–20.] such as when used as adjuncts (supplementary therapy) to surgery with a curative intent,[Deva S, Jameson M. Histamine type 2 receptor antagonists as adjuvant treatment for resected colorectal cancer. Cochrane Database of Systematic Reviews. 2012;(8):CD007814; Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP. Repurposing drugs in oncology (ReDO)—cimetidine as an anti-cancer agent. Ecancermedicalscience. 2014;8:485; Kelly MD, King J et al. Randomized trial of preoperative cimetidine in patients with colorectal carcinoma with quantitative assessment of tumor-associated lymphocytes. Cancer. 1999 Apr 15;85(8):1658-63; Matsumoto S, Imaeda Y et al. Cimetidine increases survival of colorectal cancer patients with high levels of sialyl Lewis-X and sialyl Lewis-A epitope expression on tumour cells. British Journal of Cancer. 2002 Jan 21;86(2):161-7.
7. Svendsen LB, Ross C et al. Cimetidine as an adjuvant treatment in colorectal cancer. a double-blind, randomized pilot study. Diseases of the Colon and Rectum. 1995 May;38(5):514-8; Jameson MB, Michael Arendse et al. Final analysis of a randomized placebo-controlled double-blind phase II trial of perioperative cimetidine (CIM) in early colorectal cancer (CRC). Journal of Clinical Oncology. 2018;36(15_suppl):e15678-e15678; Kelly MD, King J et al. Randomized trial of preoperative cimetidine in patients with colorectal carcinoma with quantitative assessment of tumor-associated lymphocytes. Cancer. 1999 Apr 15;85(8):1658-63; Yoshimatsu K, Ishibashi K et al. [Can the survival of patients with recurrent disease after curative resection of colorectal cancer be prolonged by the administration of cimetidine?] [Article in Japanese]. Gan To Kagaku Ryoho. 2006 Nov;33(12):1730-2.
8. Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP. Repurposing drugs in oncology (ReDO)—cimetidine as an anti-cancer agent. Ecancermedicalscience. 2014;8:485.
9. Lin CY, Bai DJ, Yuan HY, et al. Perioperative cimetidine administration promotes peripheral blood lymphocytes and tumor infiltrating lymphocytes in patients with gastrointestinal cancer: results of a randomized controlled clinical trial. World Journal of Gastroenterology. 2004;10(1):136–142.
10. Inhorn L, Williams SD, Nattam S, Stephens D. High-dose cimetidine for the treatment of metastatic renal cell carcinoma. A Hoosier Oncology Group study. American Journal of Clinical Oncology. 1992 Apr;15(2):157-9.
11. Kinouchi T, Saiki S et al. Treatment of advanced renal cell carcinoma with a combination of human lymphoblastoid interferon-alpha and cimetidine. Journal of Urology. 1997 May;157(5):1604-7.
12. Tatokoro M, Fujii Y et al. Phase-II trial of combination treatment of interferon-α, cimetidine, cyclooxygenase-2 inhibitor and renin-angiotensin-system inhibitor (I-CCA therapy) for advanced renal cell carcinoma. Cancer Science. 2011 Jan;102(1):137-43.
13. Tatokoro M, Fujii Y et al. Favorable response to combination treatment of cimetidine, cyclooxygenase-2 inhibitor and renin-angiotensin system inhibitor in metastatic renal cell carcinoma: report of three cases. International Journal of Urology. 2008 Sep;15(9):848-50.
14. Marshall ME, Mendelsohn L et al. Treatment of metastatic renal cell carcinoma with coumarin (1,2-benzopyrone) and cimetidine: a pilot study. Journal of Clinical Oncology. 1987 Jun;5(6):862-6.
15. Dexeus FH, Logothetis CJ et al. Phase II study of coumarin and cimetidine in patients with metastatic renal cell carcinoma. Journal of Clinical Oncology. 1990 Feb;8(2):325-9.
16. Antoszczak M, Markowska A, Markowska J, Huczyński A. Old wine in new bottles: drug repurposing in oncology. European Journal of Pharmacology. 2020 Jan 5;866:172784.
17. Tønnesen H, Knigge UP et al. Cimetidinbehandling ved cancer ventriculi [Cimetidine treatment of stomach cancer] [Article in Danish]. Ugeskrift for Laeger. 1989 Jun 12;151(24):1549-51.
18. Kubecova M, Kolostova K, Pinterova D, Kacprzak G, Bobek V. Cimetidine: an anticancer drug? European Journal of Pharmaceutical Sciences. 2011 Apr 18;42(5):439-44; Li Y, Yang GL et al. Effects of perioperative cimetidine administration on peripheral blood lymphocytes and tumor infiltrating lymphocytes in patients with gastrointestinal cancer: results of a randomized controlled clinical trial. Hepatogastroenterology. Mar-Apr 2005;52(62):504-8.
19. Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP. Repurposing drugs in oncology (ReDO)—cimetidine as an anti-cancer agent. Ecancermedicalscience. 2014;8:485.
20. Furuta T, Sabit H et al. Biological basis and clinical study of glycogen synthase kinase- 3β-targeted therapy by drug repositioning for glioblastoma. Oncotarget. 2017 Apr 4;8(14):22811-22824.
21. Losurdo G, Principi M et al. Histamine and histaminergic receptors in colorectal cancer: from basic science to evidence-based medicine. Anti-Cancer Agents in Medicinal Chemistry. 2018;18(1):15–20; Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP. Repurposing drugs in oncology (ReDO)—cimetidine as an anti-cancer agent. Ecancermedicalscience. 2014;8:485; Eaton D, Hawkins RE. Cimetidine in colorectal cancer–are the effects immunological or adhesion-mediated? British Journal of Cancer. 2002;86(2):159–160.
22. Losurdo G, Principi M et al. Histamine and histaminergic receptors in colorectal cancer: from basic science to evidence-based medicine. Anti-Cancer Agents in Medicinal Chemistry. 2018;18(1):15–20; Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP. Repurposing drugs in oncology (ReDO)—cimetidine as an anti-cancer agent. Ecancermedicalscience. 2014;8:485.
23. Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP. Repurposing drugs in oncology (ReDO)—cimetidine as an anti-cancer agent. Ecancermedicalscience. 2014;8:485.
24. Zheng Y, Xu M et al. Cimetidine suppresses lung tumor growth in mice through proapoptosis of myeloid-derived suppressor cells. Molecular Immunology. 2013 May;54(1):74-83.
25. Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP. Repurposing drugs in oncology (ReDO)—cimetidine as an anti-cancer agent. Ecancermedicalscience. 2014;8:485; Adams WJ, Morris DL. Short-course cimetidine and survival with colorectal cancer. Lancet. 1994 Dec 24-31;344(8939-8940):1768-9; Kubecova M, Kolostova K, Pinterova D, Kacprzak G, Bobek V. Cimetidine: an anticancer drug? European Journal of Pharmaceutical Sciences. 2011 Apr18;42(5):439-44.
26. Li Y, Yang GL et al. Effects of perioperative cimetidine administration on peripheral blood lymphocytes and tumor infiltrating lymphocytes in patients with gastrointestinal cancer: results of a randomized controlled clinical trial. Hepatogastroenterology. 2005 Mar-Apr;52(62):504-8; Lin CY, Bai DJ, Yuan HY, et al. Perioperative cimetidine administration promotes peripheral blood lymphocytes and tumor infiltrating lymphocytes in patients with gastrointestinal cancer: results of a randomized controlled clinical trial. World Journal of Gastroenterology. 2004;10(1):136–142; Li B, Cao F, Zhu Q, et al. Perioperative cimetidine administration improves systematic immune response and tumor infiltrating lymphocytes in patients with colorectal cancer. Hepatogastroenterology 2013;60:244–247.
27. Ciarimboli G. Membrane transporters as mediators of cisplatin side-effects. Anticancer Research. 2014 Jan;34(1):547-50.
28. Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP. Repurposing drugs in oncology (ReDO)—cimetidine as an anti-cancer agent. Ecancermedicalscience. 2014;8:485; Ciarimboli G. Membrane transporters as mediators of cisplatin side-effects. Anticancer Research. 2014 Jan;34(1):547-50.
29. Ciarimboli G. Membrane transporters as mediators of cisplatin side-effects. Anticancer Research. 2014 Jan;34(1):547-50.
30. Kubecova M, Kolostova K, Pinterova D, Kacprzak G, Bobek V. Cimetidine: an anticancer drug? European Journal of Pharmaceutical Sciences. 2011 Apr 18;42(5):439-44; Takahashi HK, Watanabe T et al. Cimetidine induces interleukin-18 production through H2-agonist activity in monocytes. Mol Pharmacol. 2006 Aug;70(2):450-3.
31. Jafarzadeh A, Nemati M, Khorramdelazad H, Hassan ZM. Immunomodulatory properties of cimetidine: Its therapeutic potentials for treatment of immune-related diseases. International Immunopharmacology. 2019 May;70:156-166; Losurdo G, Principi M et al. Histamine and histaminergic receptors in colorectal cancer: from basic science to evidence-based medicine. Anti-Cancer Agents in Medicinal Chemistry. 2018;18(1):15–20; Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP. Repurposing drugs in oncology (ReDO)—cimetidine as an anti-cancer agent. Ecancermedicalscience. 2014;8:485; Eaton D, Hawkins RE. Cimetidine in colorectal cancer–are the effects immunological or adhesion-mediated? British Journal of Cancer. 2002;86(2):159–160; Kumar A. Cimetidine: an immunomodulator. DICP. 1990 Mar;24(3):289-95; Zhang Y, Chen Z et al. Cimetidine down-regulates stability of Foxp3 protein via Stub1 in Treg cells. Human Vaccines & Immunotherapeutics. 2016 Oct 2;12(10):2512-2518; Wang J, Su B, Ding Z, Du X, Wang B. Cimetidine enhances immune response of HBV DNA vaccination via impairment of the regulatory function of regulatory T cells. Biochemical and Biophysical Research Communications. 2008 Aug 1;372(3):491-6; Niu X, Yang Y, Wang J. Synergistic and additive effects of cimetidine and levamisole on cellular immune responses to hepatitis B virus DNA vaccine in mice. Scandinavian Journal of Immunology. 2013 Feb;77(2):84-91.
32. Losurdo G, Principi M et al. Histamine and histaminergic receptors in colorectal cancer: from basic science to evidence-based medicine. Anti-Cancer Agents in Medicinal Chemistry. 2018;18(1):15–20; Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP. Repurposing drugs in oncology (ReDO)—cimetidine as an anti-cancer agent. Ecancermedicalscience. 2014;8:485; Eaton D, Hawkins RE. Cimetidine in colorectal cancer–are the effects immunological or adhesion-mediated? British Journal of Cancer. 2002;86(2):159–160.
33. Kennedy DA, Cooley K, Skidmore B, Fritz H, Campbell T, Seely D. 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.
34. Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP. Repurposing drugs in oncology (ReDO)—cimetidine as an anti-cancer agent. Ecancermedicalscience. 2014;8:485.
35. Chang R. Beyond the Magic Bullet: The Anti-Cancer Cocktail. New York: Square One Publishers. 2012.
36. Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP. Repurposing drugs in oncology (ReDO)—cimetidine as an anti-cancer agent. Ecancermedicalscience. 2014;8:485.
37. Block KI. Life over Cancer: The Block Center Program for Integrative Cancer Treatment. New York: Bantam Dell. 2009.
38. Chang R. Beyond the Magic Bullet: The Anti-Cancer Cocktail. New York: Square One Publishers. 2012.