Prevention of the Spread and Recurrence of Cancer by Coumarins and Fibrinolytic Agents
László Muszbek in Hemostasis and Cancer, 2019
Cimetidine is a histamine antagonist used in the treatment of peptic ulceration. It has been shown to affect the cellular immune system by lowering suppressor/cytotoxic T lymphocytes. Three patients with advanced melanoma on treatment with coumarin for several months were given cimetidine in addition, and there was a dramatic reduction in tumor within 7 days. The next patient, however, when cimetidine and coumarin were started simultaneously, had a rapid enhancement of tumor growth.33 Five more patients on long-term treatment with coumarin (100 mg daily) were given cimetidine (1000 mg daily) and only one patient responded. She had an absolute lymphocyte count of 3.86 × 109/ℓ (T cells 46%, helper cells 27%, suppressor/cytotoxic cells 20%) prior to cimetidine. After 2 weeks her absolute lymphocyte count had fallen to 1.94 × 109/ℓ (T cells 57%, helper cells 40%, suppressor/cytotoxic cells 18%). Three of the nonresponding patients had low lymphocyte counts below 0.9 × 109/ℓ and low suppressor/cytotoxic cell levels. The remaining patient who failed to respond had cerebral metastasis. Cimetidine given alone to seven other patients with melanoma was ineffective. It appears that the immune system needs to be primed by coumarin and only if suppressor cells are raised could cimetidine be expected to produce a response. The most interesting feature of the tumor reduction was its rapidity without toxicity. The mechanism needs to be further elucidated, but an immunological pathway would seem most likely.
Miscellaneous Drugs
Sarah Armstrong, Barry Clifton, Lionel Davis in Primary FRCA in a Box, 2019
The oral drugs used in diabetes are sulfonylureas, biguanides and other antidiabeticsSulfonylureas include first generation (e.g. tolbutamide) and second generation (e.g. glibenclamide, gliclazide, glipizide) drugs which increase insulin release from the pancreas. Cimetidine inhibits their metabolism increasing their effect. Thiazides, corticosteroids and phenothiazines antagonise their effectMetformin is the only biguanide available in the UK. It delays gut glucose uptake, increases peripheral insulin sensitivity and inhibits renal and hepatic gluconeogenesis. It may cause severe lactic acidosis especially in renal impairment or alcohol abusersAcarbose delays intestinal glucose absorption, pioglitazone (a thiazolidinedione) improves insulin sensitivity and meglitinides (e.g. repaglinide and metiglinide) increase insulin secretion by the pancreas
Tetracyclines
Thomas T. Yoshikawa, Shobita Rajagopalan in Antibiotic Therapy for Geriatric Patients, 2005
Studies of the interaction of tetracycline and the hepatic enzyme inhibitor cime-tidine have yielded conflicting results. In one study, the simultaneous administration of single doses of cimetidine and tetracycline resulted in mean reductions in peak plasma concentration, area under the plasma concentration vs. time curve, and 72 hr urinary excretion of 1.2mg/L, 40%, and 30%, respectively. In contrast, multiple-dose cimetidine exerted no significant effect on tetracycline disposition. In the second study, 3 days of cimetidine pretreatment reduced tetracycline bioavailability by a mean of 30% (from the capsule formulation only, not the solution formulation). In the third study, simultaneous administration of single doses of cimetidine and tetracycline resulted in no significant alteration in tetracycline pharmacokinetics.
Verification of a cocktail approach for quantitative drug–drug interaction assessment: a comparative analysis between the results of a single drug and a cocktail drug
Published in Xenobiotica, 2021
Motoyasu Miura, Shinya Uchida, Shimako Tanaka, Chiaki Kamiya, Naoki Katayama, Akio Hakamata, Keiichi Odagiri, Naoki Inui, Junichi Kawakami, Hiroshi Watanabe, Noriyuki Namiki
The cocktail study had an open-label, single-sequence design, and was divided into four phases: a control phase, a rifampicin phase, a cimetidine phase, and a fluvoxamine phase. Each phase was separated by a washout period of at least 2 w. During the control phase, subjects were simultaneously administered five probe drugs as the cocktail drug. Caffeine 100 mg (caffeine; Mylan, Tokyo, Japan), losartan 25 mg (Nu-Lotan; MSD, Tokyo, Japan), omeprazole 20 mg (Omepral; AstraZeneca, Osaka, Japan), dextromethorphan 30 mg (Medicon; Shionogi, Osaka, Japan), and midazolam 15 µg/kg (Dormicum; Astellas Pharma, Tokyo, Japan) were used as reported by Inui et al. (2013). During the rifampicin phase, subjects were administered rifampicin 450 mg (Rifadin capsules, Daiichi Sankyo, Tokyo, Japan) once a day in the morning for 6 d until the day before the study. During the cimetidine phase, the subjects were administered cimetidine 400 mg (Tagamet tablet, Sumitomo Dainippon Pharma, Tokyo, Japan) twice a day before the cocktail study, morning and evening. On the day of the cocktail study, the subjects were administered cimetidine with the cocktail drug. During the fluvoxamine phase, fluvoxamine 25 mg (Depromel tablet, Meiji Seika Pharma, Tokyo, Japan) was administered on the same administration schedule as for the cimetidine phase.
Capecitabine for the treatment of pancreatic cancer
Published in Expert Opinion on Pharmacotherapy, 2019
Nauman S. Siddiqui, Amandeep Godara, Margaret M. Byrne, Muhammad Wasif Saif
In addition to warfarin, few other agents warrant revision here. Allopurinol metabolites can lead to the decreased conversion of capecitabine to 5-FU and hence potentially can decrease 5-FU antitumor activity [63]. Consideration should be given to use of alternate agent rather than the continuation of allopurinol while on capecitabine [64]. Cimetidine, an over the counter H2 blocker can decrease the clearance of 5-FU. Therefore, cimetidine should be discontinued or replaced with other anti-acid medications such as ranitidine if necessary [65]. 5-bromovinyluracil, a metabolite of two antivirals agents, named sorivudine and brivudine is known to be a potent inhibitor of DPD. Patients should not receive concurrent therapy with either of these antiviral agents while receiving capecitabine. If a patient has received prior sorivudine or brivudine, then at least four weeks must elapse before the patient receives capecitabine therapy [66]. Finally, capecitabine can lead to higher phenytoin levels in the plasma. Patients on active treatment should b routinely monitored for phenytoin toxicity and drug levels [66].
Pharmacological treatments for functional nausea and functional dyspepsia in children: a systematic review
Published in Expert Review of Clinical Pharmacology, 2018
Pamela D. Browne, Sjoerd C. J. Nagelkerke, Faridi S. van Etten-Jamaludin, Marc A. Benninga, Merit M. Tabbers
H2RAs have been shown safe and effective in adults with FD [69]. However, to date, there is limited evidence to support the efficacy H2RAs in children with upper gastro-intestinal complaints [70]. Additionally, a previous study in children with GERD found that the use of H2RAs was related to more adverse events (i.e. gastroenteritis and pneumonia) compared with PPI use [60,71]. Other side effects reported in children due to H2RAs include irritability, headache, anorexia, somnolence, and headache. Particularly cimetidine may cause side effects, because of an increased risk on multiple drug interactions and interference with endocrine functioning [72]. By selectively blocking the histamine-2 receptor in the parietal cells, H2RAs decrease the production of gastric acid and pepsin and consequently increase gastric pH [73].