Case Review Focus Areas:
- Whether the patient took Zantac (Ranitidine)?
- Did the patient develop cancer
- When and where was the injury diagnosed?
- The extent and duration of the cancer injury from Zantac
- Treatment/management of the Adverse Events (AE’s) as a result of the exposure to the Zantac
- Follow-up visits for management of complications/AEs
- Outcome/prognosis
- Any medical/surgical history, social history that could have had an effect on the injury
Zantac (Ranitidine) – Case Review – Focus Blocks
Ranitidine, sold under the trade name Zantac among others, is a medication which decreases stomach acid production. It is commonly used in treatment of heart burn, peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–Ellison syndrome. There is also tentative evidence of benefit for hives. It can be taken by mouth, by injection into a muscle, or into a vein.
Ranitidine was discovered in 1976, and came into commercial use in 1981. It is on the World Health Organization’s List of Essential Medicines, the safest and most effective medicines needed in a health system. It is available as a generic medication. The 2015 wholesale price in the developing world was about US$ 0.01–0.05 per pill. In the United States it is about $0.05 per dose. In 2016, it was the 50th most prescribed medication in the United States with more than 15 million prescriptions. In September 2019, the toxin N-nitrosodimethylamine was discovered to occur in Ranitidine from a number of manufacturers, resulting in distribution stops and recalls.
It is generally safe in pregnancy. Ranitidine is an H2 histamine receptor antagonist that works by blocking histamine and thus decreasing the amount of acid released by cells of the stomach.
Dosing:
For ulcer treatment, a night-time dose is especially important — as the increase in gastric/duodenal pH promotes healing overnight when the stomach and duodenum are empty. Conversely, for treating reflux, smaller and more frequent doses are more effective. Ranitidine used to be administered long-term for reflux treatment, sometimes indefinitely. However, Proton-Pump Inhibitors (PPIs) have taken over this role. In addition, a fairly rapid Tachyphylaxis can develop within six weeks of initiation of treatment, further limiting its potential for long-term use. People with Zollinger–Ellison syndrome have been given very high doses without any harm.
Contraindication:
Ranitidine is contraindicated for patients known to have hypersensitivity to the drug.
Cancer-causing impurities:
In September 2019, the U.S. Food and Drug Administration (FDA) learned that some Ranitidine medicines, including some products sold under the brand name Zantac, contained a Nitrosamine impurity called N-nitrosodimethylamine (NDMA), classified as a probable human carcinogen, at low levels causing cancer. Health Canada announced that it was assessing NDMA in Ranitidine and requested that manufacturers stop the distribution of Ranitidine products in Canada until the NDMA levels in the products are found to be safe. Health Canada announced that Ranitidine drugs were being recalled by Sandoz Canada, Apotex Inc., Pro Doc Limitee, Sanis Health Inc., and Sivem Pharmaceuticals ULC. The European Medicines Agency (EMA) started an EU-wide review of Ranitidine medicines at the request of the European Commission.
In September 2019, Sandoz issued a “precautionary distribution stop” of all medicines containing Ranitidine followed a few days later by a recall of Ranitidine Hydrochloride capsules in the United States. The Italian Medicines Agency, AIFA, recalled all Ranitidine that uses an active pharmaceutical ingredient (API) from Saraca Laboratories. The German Pharmacists Committee (AMK) published a list of recalled products. The Therapeutic Goods Administration (TGA) in Australia published a list of recalled products.
In September 2019, Apotex recalled all Over-The-Counter (OTC) Ranitidine tablets sold in the United States at Walmart, Rite Aid, and Walgreens. Subsequently, Walmart, Rite Aid, Walgreens, and CVS pulled Zantac and some generics from their shelves.
In October 2019, the U.S. Food and Drug Administration (FDA) observed that a third-party laboratory was using higher temperatures in its tests to look for nitrosamine impurities. The NDMA was generated by the added heat but the higher temperatures were recommended for using a gas chromatography–mass spectrometry (GC/MS) method to test for NDMA in valsartan and angiotensin II receptor blockers (ARBs). The FDA stated that it recommends using a liquid chromatography-high resolution mass spectrometry (LC-HRMS) testing protocol to test samples of Ranitidine. Its LC-HRMS testing method does not use elevated temperatures and has shown the presence of much lower levels of NDMA in Ranitidine medicines than reported by the third-party laboratory. International regulators using similar LC-MS testing methods have also shown the presence of low levels of NDMA in ranitidine samples.
In October 2019, Sanofi recalled all over-the-counter Zantac in the United States and Canada
Long term Side effects:
- Serious side effects may include liver problems
- Constipation
- Diarrhea
- Fatigue
- Headache (may be severe)
- Drowsiness
- Dizziness
- Sleep problems (insomnia)
- Decreased sex drive
Lawsuit Focus:
Allegations raised against Zantac (Ranitidine):
- Zantac, which has been found to contain a carcinogenic chemical at 26,000 times the FDA-approved limit.
- Zantac contains the active ingredient ranitidine. When ingested, ranitidine metabolizes into N-nitrosodimethylamine (NDMA) which the FDA, EPA and World Health Organization (WHO) classify as a carcinogen.
- Start date and total duration of consumption of Zantac
- Date of diagnosis of cancer (any type)
Specific Focus:
Identify and report cases with the following scenario:
- No injuries: Patient exposed to Zantac but did not develop any injury (In that scenario we will provide a case screening).
Identify and report on missing medical records:
Apart from identifying critical missing records that are important for the case, provide a detailed outline on what records are needed, why we need them, how did we get a clue that these records are missing and whether the records missing are confirmatory/probable. This will also help in following up and retrieving the records.