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What is Ranitidine (Zantac®)? + Side Effects & Interactions

Written by Carlos Tello, PhD (Molecular Biology) | Last updated:
Jonathan Ritter
Puya Yazdi
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD | Written by Carlos Tello, PhD (Molecular Biology) | Last updated:

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Ranitidine is a best-selling drug used to reduce high stomach acid, and because of its long history of use, a great deal of data is available on its safety profile. Read on to learn more about the potential side effects and interactions of ranitidine as well as genetic factors that may change the way people respond to this drug.

Disclaimer: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the scientific literature. Please discuss your medications with your doctor.

What Is Ranitidine (Zantac)?

Ranitidine is a drug that decreases stomach acid production and is therefore employed in the treatment and prevention of disorders related to excessive stomach acid [1].

Developed in 1977, ranitidine was first introduced into the market in 1981 and quickly became the best-selling drug worldwide [2].

The main brand names for ranitidine are Zantac® and Taladine®.

Ranitidine is a histamine blocker. By binding to the H2-receptors on the stomach acid-producing cells, it prevents their activation by histamine [3].

Prescription ranitidine comes as tablets (oral and effervescent), capsules, and syrup. This medication is mainly used to treat [1]:

  • Ulcers of the stomach and bowel
  • Esophagus inflammation
  • Gastroesophageal reflux disease (GERD)
  • Zollinger-Ellison syndrome

It is also sold over-the-counter (OTC) as 75 mg and 150 mg tablets to prevent symptoms of excessive acid in the stomach such as [4, 5]:

  • Heartburn
  • Acid indigestion
Ranitidine decreases stomach acid production by blocking the H2 histamine receptor in the stomach. Developed in 1977, ranitidine is prescribed to treat stomach ulcers, esophageal inflammation, GERD, and Zollinger-Ellison syndrome.

Side Effects

Ranitidine is frequently used worldwide and generally well tolerated.

A review of 21 trials concluded that ranitidine doses of 150 to 600 mg/day are equally safe in elderly and non-elderly patients [6].

Frequency of the main adverse effects of ranitidine in elderly and non-elderly patients [6].

Adverse effects can, however, occur in up to 5% of patients. Those most frequently reported are [1]:

1) Stomach and Bowel

The most frequent events in this system are [7]:

  • Nausea and/or vomiting (2.6-6.8%)
  • Diarrhea (1.4-4.1%)
  • Stomach pain (1.3-1.8%)

These effects tend to improve with continuous treatment. Other, less frequent (up to 2%) side effects include:

  • Constipation
  • Heartburn
  • Dry mouth
  • Gas
  • Pancreas inflammation

Stomach and bowel cancer occurred at a rate of 0.2 per million patients treated, but cannot be associated with ranitidine intake [8].

Occasionally, people taking ranitidine may experience nausea, vomiting, or stomach pain. Even less frequently, other gastrointestinal side effects may include constipation and gas.

2) Brain

The most common effects of ranitidine on the brain are [7]:

  • Confusion (2.1 events per million)
  • Headache (2.1 events per million)
  • Dizziness (1.7 events per million)

The proportion increases with age and among hospitalized patients, as well as in those with liver or kidney failure. The symptoms are quickly reversed by stopping the treatment [9].

Less frequently reported reactions include:

  • Sleepiness
  • Insomnia
  • Disorientation
  • Hallucinations
  • Agitation
  • Delirium
Rare neurological side effects of ranitidine have been reported. These include confusion, headache, and dizziness.

3) Skin

Skin reactions associated with ranitidine intake include [7]:

  • Rash (2.9 events per million)
  • Itching (1.9 events per million)
  • Hives (1.7 events per million)
  • Baldness (1.3 events per million)

The following reactions have been observed less frequently:

Rare skin side effects have been associated with ranitidine, including rash, itching, hives, and hair loss.

4) Liver

Liver injuries caused by the use of ranitidine are rare [12].

The most common liver abnormalities associated with ranitidine are [7]:

  • Increased levels of liver enzymes (5.9 events per million)
  • Hepatitis (1.1 events per million)

5) Hormone Production

Ranitidine does not alter the function of the thyroid, hypothalamus, pituitary, or sex glands [13, 14].

Breast growth has been reported in 0.2 to 1.3 male patients per million [1].

A small rise in prolactin release during ranitidine treatment was observed in 2 studies [15, 16].

6) Heart

The most common effects (0.2 to 0.3 events per million) on the heart include [7]:

However, no differences were found between the ranitidine and placebo treatment groups [17].

7) Blood Composition

No evidence of change in hemoglobin concentration and red blood counts has been found with ranitidine [7].

In very rare cases, patients taking ranitidine had lower counts of white blood cells and platelets. However, the incidence was lower than that found in the general population [18].

8) Kidneys

Although ranitidine is mostly eliminated through the urine, no evidence of kidney damage associated with this drug has been found. Dose reduction is only recommended in patients with strong kidney failure [7].

9) Other

Because it reduces stomach acid, ranitidine may impair iron absorption [19, 20].

On very rare occasions, patients taking ranitidine have developed a gout-like joint inflammation [21].

One patient with eye nerve damage suffered from increased eye pressure after taking cimetidine and ranitidine [22].

One patient suffered from airway narrowing, breath shortness, and cough after taking ranitidine [23].

One case of a male patient suffering from impotence during treatment with ranitidine was reported [24].

Anaphylaxis (a fast, life-threatening allergic reaction) can occur in 0.86 patients per million [25].

Injection of ranitidine has caused 3 cases of heart arrest [26, 27, 28].

A very rare allergy to ranitidine has been recorded. Ranitidine may also impair iron absorption. Other side effects are extremely rare.

Other Safety Concerns

Drug Interactions

To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. Talk to your healthcare provider to find out how ranitidine might interact with something else you are taking.

Due to its acid-blocking activity, ranitidine reduces the absorption of drugs requiring acid in the stomach, such as:

  • HIV medication (Atazanavir, Delavirdine, and Fosamprenavir) [29, 30, 31]
  • Antifungal drugs (Itraconazole and Ketoconazole) [32, 33]
  • Cancer medication (Gefitinib, Dasatinib, and Erlotinib ) [34, 35, 36]
  • Antibiotics (Enoxacin, Cefpodoxime, Bacampicillin, and Cefuroxime) [37, 38, 39]

Conversely, it increases the absorption of drugs requiring low acid, such as the sedatives:

  • Triazolam [40]
  • Midazolam [41]

In a small trial on 12 healthy volunteers, ranitidine increased absorption of the HIV medication saquinavir. However, the effect was independent of ranitidine’s activity against acid production [42].

Absorption of ranitidine and other H2-receptor blockers is reduced by:

  • Antacids [43]
  • Cisapride (enhancer of stomach and bowel movements) [44]
  • Sucralfate (ulcer medication) [45]

Ranitidine binds to the cytochrome P450, thus slowing down the elimination of the following drugs through the kidneys and liver [46]:

  • Procainamide (treatment of irregular heart rates) [47]
  • Triamterene (treatment of hypertension and fluid retention) [48]
  • Midazolam (sedative) [49]

It is thus important to adjust the doses of these medications when used in combination with ranitidine.

The fact that ranitidine also decreases nicotine elimination can be especially relevant to smokers trying to give up or reduce this habit [50].

Ranitidine reduced the breakdown of warfarin (blood thinner medication) in a small trial on 10 patients, but 6 other studies failed to reproduce this result [51, 7].

In conditions mimicking social drinking, ranitidine increased blood alcohol levels by accelerating stomach emptying [52, 53].

In a small study on 12 diabetic patients, ranitidine enhanced the effect of glipizide (drug lowering blood sugar levels) [54].

In contrast, ranitidine increased both blood sugar and insulin levels when combined with glibenclamide (a drug that lowers blood sugar levels) in another study on 15 healthy volunteers [55].

Ranitidine may decrease the absorption of drugs that require stomach acid to be absorbed, such as HIV medication and some antibiotics. Other interactions are also possible. Your doctor may adjust the dosage of certain medications if you are taking ranitidine at the same time.

Contraindications

The safety and efficiency of this drug have not been sufficiently described in patients younger than 1 month [56].

In a small trial on 29 children aged 4 to 11 years old with stomach acidity, 75 mg/day ranitidine was both effective and safe [4].

The incidence of the most common side effects on the nervous system (confusion, headaches, and dizziness) increased in elderly and chronically ill patients, as well as in those with kidney failure [57, 9].

In critically ill patients, ranitidine may increase the risk of developing pneumonia [58].

In rare occasions, ranitidine has been reported to cause:

  • Porphyria [59]
  • Stomach cancer [60]

Therefore, it should be avoided in people already suffering from these conditions.

Because ranitidine is mostly eliminated through urine and partly broken down in the liver, patients with severe kidney and liver diseases should avoid or moderate its intake [61].

Ranitidine is significantly removed by hemodialysis and therefore should be taken after this procedure [62].

Finally, ranitidine must be avoided by patients with an allergy to H2-receptor blockers [63].

The safety profile of ranitidine in infants is unknown. Side effects may be more common in the elderly and chronically ill patients.

Use During Pregnancy and Breastfeeding

A study of pregnancy databases including over 1000 women exposed to H2-receptor blockers concluded that these drugs are safe, given their lack of association with [64]:

  • Infant risk of dying
  • Premature delivery
  • Low birth weight
  • Poor infant wellness (low APGAR scores)

Ranitidine is transported into breast milk. Because the peak concentration occurs 12 hours after intake, breastfeeding is recommended 1 to 2 hours after drug use to reduce exposure to the baby [65].

Drug Comparisons

PPIs Versus H2-Receptor Blockers

Stomach acid is produced by the presence of protons (H+).

The hydrogen potassium (H+/K+) ATPase is the enzyme that accumulates acid in the stomach by exchanging potassium from the stomach with protons from the parietal cells [66].

This enzyme is found inside parietal cells in the inner lining of the stomach. Upon binding of histamine to the H2-receptors on these cells, the H+/K+ ATPase moves to the cell surface and turns into its activated shape [67].

As opposed to H2-receptor blockers, which inactivate one of the signals that trigger acid production, proton pump inhibitors (PPIs) block the main enzyme of the process: H+/K+ ATPase [68, 69].

Because they target the last step of acid production and block the enzyme, the effect of PPIs is stronger and lasts longer than that of H2-receptor blockers [70].

PPIs are sold as inactive, neutrally charged drugs that cross membranes and accumulate in parietal cells. The high acidity in these cells then transforms PPIs into their active form, which binds to the H+/K+ ATPase and blocks it [71].

The main commercial drugs belonging to this category are [67]:

  • Omeprazole (Losec®)
  • Lansoprazole (Prevacid®)
  • Pantoprazole (Protonix®)
  • Rabeprazole (Aciphex®)
  • Esomeprazole (Nexium®)
  • Dexlansoprazole (Dexilant®)

While H2-receptor blockers have a rapid action of short (less than 12 hours) duration, PPIs have a stronger and more durable (up to 3 days) action that also takes longer to start working [72, 73].

H2-receptor blockers are thus preferred to treat mild, occasional symptoms (episodic heartburn and acid indigestion, or acid aspiration during surgery), while PPIs are used with stronger, chronic disorders (chronic gastroesophageal reflux disease, erosive esophagitis, and ulcers) [74, 75, 76].

Because of their stronger action, PPIs showed increased efficiency over H2-receptor blockers in clinical trials on people with:

  • Gastroesophageal reflux disease [77]
  • Acid indigestion [78]
  • Erosive esophagitis [79]
  • Stress-induced ulcer [80]

Although both H2-receptor blockers and PPIs are usually well tolerated, it is important to take their differential adverse effects into consideration. Some risks associated with long-term treatment with PPIs include:

  • Magnesium deficiency [81]
  • Increased risk of hip fracture [82]
  • Bacterial infections in the digestive system [83, 84, 85]
  • Pneumonia [86]
  • Chronic kidney disease [87]
  • Dementia [88]
H2 receptor blockers like ranitidine are alternatives to proton pump inhibitors (PPIs) like omeprazole. They may be more or less effective for different conditions and for different people.

Ranitidine vs. Other H2-Receptor Blockers

Besides ranitidine, the commercial H2-receptor blockers most widely employed are [89]:

  • Cimetidine (Tagamet®)
  • Famotidine (Pepcid®)
  • Nizatidine (Axid®)

Ranitidine vs. Cimetidine

Cimetidine is available in 200, 300, 400, and 800 mg tablets, as a syrup (200 mg/5 ml), as a 100 or 200 mg/5 ml suspension, as intravenous injection (100 mg/ml), and as intravenous infusion (4 mg/ml). Cimetidine is 4 to 5 times less powerful than ranitidine [46].

As opposed to ranitidine, which is also broken down in the liver, cimetidine is almost exclusively eliminated in the urine [90, 91].

Because it binds to the male sex hormone (testosterone) receptors, long-term use of cimetidine can cause loss of libido, impotence, and breast growth in men [46].

In a trial on over 1000 people with gastroesophageal reflux, a 200-mg dose of cimetidine was as efficient as 75 mg of ranitidine in reducing heartburn symptoms [92].

In another trial on almost 200 children with acid indigestion, treatments with ranitidine (1 to 2 mg/kg per dose) and cimetidine (10 mg/kg per dose) were equally effective in relieving the symptoms [93].

Additionally, 7.8 g cimetidine/day reduced the symptoms as efficiently as 2.1 g ranitidine/day in a small trial on 9 people with Zollinger-Ellison syndrome [94].

Cimetidine (200 mg 3 times per day) was as effective as ranitidine (150 mg twice per day) in healing stomach ulcers in one trial on 260 people [95].

Ramitidine appears to have fewer side effects than cimetidine despite being more powerful.

Ranitidine vs. Famotidine

Famotidine is available in 20- and 40-mg tablets, and is approximately 7.5 times more potent than ranitidine [46, 96].

In a small trial on 9 people with Zollinger-Ellison syndrome, 0.24 g famotidine/day was as efficient at reducing the symptoms as 2.1 g ranitidine/day, and its effects lasted 30% longer [94].

However, famotidine (40 mg/day) was less effective in treating stomach ulcers than ranitidine (150 mg twice per day) in one trial on 69 people [97].

Both ranitidine and famotidine showed similar effectiveness against acid aspiration in a trial on 50 people undergoing surgery [98].

Famotidine is orders of magnitude more potent than ranitidine, though ranitidine is still preferred for some conditions.

Ranitidine vs. Nizatidine

Nizatidine is as potent as ranitidine and is available as 150- and 300-mg capsules [46].

In a small trial on 10 elderly people, repeated intake of nizatidine caused lower accumulation of the drug in blood than the same treatment with ranitidine. Nizatidine was thus concluded to be safer for the repeated treatment of elderly patients [99].

In 2 trials on over 400 people with gastroesophageal reflux, ranitidine 150 mg was as effective as nizatidine 150 mg at relieving the heartburn and acid regurgitation symptoms [100].

Ranitidine and nizatidine are of similar potency, but some clinical research suggests that nizatidine may be safer for patients at risk of side effects, like the elderly.

Genetics Related to Ranitidine

OCT1

OCT1 is responsible for transporting ranitidine into the liver for its subsequent degradation. Alleles with poor or absent ranitidine uptake capacity may reduce the breakdown of this drug [101].

FMO3

FMO3 and the cytochromes CYP2C19, CYP1A2, and CYP2D6 degrade ranitidine in the liver before its elimination in urine [102].

SNPs associated with lower abundance of FMO3 (rs2064074, rs28363536, rs2266782, rs909530, rs2266780, and rs909531) may reduce ranitidine breakdown [103].

CYP2C19

The CYP2C19 variant CYP2C19*17 (rs12248560) is associated with increased abundance of this enzyme and may enhance ranitidine breakdown [104].

CYP1A2

CYP1A2 alleles may be less efficient at breaking down ranitidine based on their reduced activity on other drugs. In turn, the CYP1A2*1F variant caused increased activity of this enzyme [105, 106, 107, 108].

CYP2D6

CYP2D6 alleles classified as having reduced or null activity may be less efficient at breaking down ranitidine [109].

Variations in certain genes may change a person’s response to ranitidine. Research is ongoing to identify relevant variants.

If You Have Food Sensitivities

A note from Joe:

“I recommend following my lectin avoidance diet, named as such because I think that lectins are the single major trigger of autoimmune disease. However, they are not the only trigger. And this diet is not a one-size-fits-all regimen. It may not suit EVERYONE’s needs, but it’s a good template from which to build a personalized diet.

If you suffer from food sensitivities, the Lectin Avoidance Diet helps you figure out which foods are inflammatory, and which are less inflammatory for you.”

Takeaway

Ranitidine, sold under the brand name Zantac®, is an H2 histamine receptor blocker that is prescribed to treat disorders caused by too much stomach acid production, such as gastric ulcers, GERD, heartburn, and erosive esophagitis.

Ranitidine is generally very well tolerated, though some side effects have been recorded. The most common of these are nausea, vomiting, diarrhea, and stomach pain. More rarely, people may experience confusion, headache, rash, or other side effects. Ranitidine may interfere with the absorption of some drugs, and your doctor may alter the dosage of your prescriptions while you are on ranitidine.

Ranitidine is only one member of the H2 blocker class of drugs, which also includes cimetidine, famotidine, and nizatidine. Some genetic variants may change the way people respond to or metabolize ranitidine.

Further Reading

About the Author

Carlos Tello

Carlos Tello

PhD (Molecular Biology)
Carlos received his PhD and MS from the Universidad de Sevilla.
Carlos spent 9 years in the laboratory investigating mineral transport in plants. He then started working as a freelancer, mainly in science writing, editing, and consulting. Carlos is passionate about learning the mechanisms behind biological processes and communicating science to both academic and non-academic audiences. He strongly believes that scientific literacy is crucial to maintain a healthy lifestyle and avoid falling for scams.

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