Cimetidine Side Effects

Brand Names: Tagamet

Please note - some side effects for Cimetidine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Cimetidine - for the Consumer

Cimetidine

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Cimetidine:

Diarrhea; dizziness; drowsiness; headache.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); agitation; anxiety; breast enlargement; breast lumps; confusion; depression; disorientation; fatigue; hallucinations; hair loss; joint or muscle pain; pain, redness or swelling at injections site; skin flushing or redness; sexual difficulties; slow or fast heartbeat.

Cimetidine Solution

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Cimetidine Solution:

Diarrhea; dizziness; drowsiness; headache.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); agitation; anxiety; breast enlargement; breast lumps; confusion; depression; disorientation; fatigue; hallucinations; hair loss; joint or muscle pain; pain, redness or swelling at injection site; skin flushing or redness; sexual difficulties; slow or fast heartbeat.

Cimetidine Suspension

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Cimetidine Suspension:

Diarrhea; breast growth; dizziness; drowsiness; hallucinations; headache; mental confusion; sexual difficulties.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); black, tarry stools; vomit that looks like coffee grounds.

Cimetidine Side Effects - for the Professional

Cimetidine

To report SUSPECTED ADVERSE REACTIONS, contact Hi-Tech Pharmacal Co., Inc. at 1-800-262-9010 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Adverse effects reported in patients taking Cimetidine are described below by body system. Incidence figures of 1 in 100 and greater are generally derived from controlled clinical studies.

Gastrointestinal:

Diarrhea (usually mild) has been reported in approximately 1 in 100 patients.

CNS:

Headaches ranging from mild to severe have been reported in 3.5% of 924 patients taking 1600 mg/day, 2.1% of 2,225 patients taking 800 mg/day and 2.3% of 1,897 patients taking placebo. Dizziness and somnolence (usually mild) have been reported in approximately 1 in 100 patients on either 1600 mg/day or 800 mg/day.

Reversible confusional states, e.g., mental confusion, agitation, psychosis, depression, anxiety, hallucinations, disorientation, have been reported predominantly, but not exclusively, in severely ill patients. They have usually developed within 2 to 3 days of initiation of Cimetidine therapy and have cleared within 3 to 4 days of discontinuation of the drug.

Endocrine:

Gynecomastia has been reported in patients treated for one month or longer. In patients being treated for pathological hypersecretory states, this occurred in about 4% of cases while in all others the incidence was 0.3% to 1% in various studies. No evidence of induced endocrine dysfunction was found, and the condition remained unchanged or returned toward normal with continuing Cimetidine treatment.

Reversible impotence has been reported in patients with pathological hypersecretory disorders, e.g., Zollinger-Ellison Syndrome, receiving Cimetidine, particularly in high doses, for at least 12 months (range 12 to 79 months, mean 38 months). However, in large-scale surveillance studies at regular dosage, the incidence has not exceeded that commonly reported in the general population.

Hematologic:

Decreased white blood cell counts in Cimetidine-treated patients (approximately 1 per 100,000 patients), including agranulocytosis (approximately 3 per million patients), have been reported, including a few reports of recurrence on rechallenge. Most of these reports were in patients who had serious concomitant illnesses and received drugs and/or treatment know to produce neutropenia. Thrombocytopenia (approximately 3 per million patients) and, very rarely, cases of pancytopenia or aplastic anemia have also been reported. As with some other H2-receptor antagonists, there have been extremely rare reports of immune hemolytic anemia.

Hepatobiliary:

Dose-related increases in serum transaminase have been reported. In most cases they did not progress with continued therapy and returned to normal at the end of the therapy.

There have been rare reports of cholestatic or mixed cholestatic-hepatocellular effects. These were usually reversible. Because of the predominance of cholestatic features, severe parenchymal injury is considered highly unlikely. However, as in occasional liver injury with other H2-receptor antagonists, in exceedingly rare circumstances fatal outcomes have been reported.

There has been reported a single case of biopsy-proven periportal hepatic fibrosis in a patient receiving Cimetidine.

Rare cases of pancreatitis, which cleared on withdrawal of the drug, have been reported.

Hypersensitivity:

Rare cases of fever and allergic reactions including anaphylaxis and hypersensitivity vasculitis, which cleared on withdrawal of the drug, have been reported.

Renal:

Small, possibly dose-related increases in plasma creatinine, presumably due to competition for renal tubular secretion, are not uncommon and do not signify deteriorating renal function. Rare cases of interstitial nephritis and urinary retention, which cleared on withdrawal of the drug, have been reported.

Cardiovascular:

Rare cases of bradycardia, tachycardia and A-V heart block have been reported with H2-receptor antagonists.

Musculoskeletal:

There have been rare reports of reversible arthralgia and myalgia; exacerbation of joint symptoms in patients with preexisting arthritis has also been reported. Such symptoms have usually been alleviated by a reduction in Cimetidine dosage. Rare cases of polymyositis have been reported but no causal relationship has been established.

Integumental:

Mild rash and, very rarely, cases of severe generalized skin reactions including Stevens-Johnson syndrome, epidermal necrolysis, erythema multiforme, exfoliative dermatitis and generalized exfoliative erythroderma have been reported with H2-receptor antagonists. Reversible alopecia has been reported very rarely.

Immune Function:

There have been extremely rare reports of strongyloidiasis hyperinfection in immunocompromised patients.

Side Effects by Body System

Nervous system

Nervous system side effects have included headache (up to 3.5%), dizziness (1%), and somnolence (1%). Severe mental status changes, including depression, agitation, disorientation, confusion, delirium, unsteadiness, slurred speech, lethargy, hallucinations, and coma, while uncommon, have been reported frequently in the literature. Other nervous system effects reported are extrapyramidal symptoms, cerebellar syndrome with encephalopathy, and paresthesias. Critical illness, advanced age, renal, and/or liver disease appear to be associated with an increased risk for central nervous system toxicity.

The mechanism by which cimetidine induces mental status changes is not well established but appears to involve increased serum concentrations of cimetidine and, possibly, cimetidine sulfoxide. Advanced age has been implicated in many case reports of mental status changes, however, the pharmacokinetics of cimetidine correlate more closely with renal function, making renal dysfunction associated with advanced age a more likely risk factor than age itself. In addition, enhanced cimetidine penetration of the blood brain barrier has been demonstrated in patients with liver disease. Onset of symptoms have usually developed within 2 to 3 days of start of therapy, but may be delayed. Following discontinuation of cimetidine, mental status usually normalizes over several days.

Psychiatric

Psychiatric side effects may accompany other signs and symptoms of neurologic toxicity such as unsteadiness, slurred speech, and lethargy. Age, renal dysfunction, and/or liver disease may be predisposing factors in these cases.

Psychiatric side effects in the form of severe depression, suicidal ideation, paranoia, and frank psychosis have also been reported in otherwise healthy patients.

Psychiatric side effects have included depression, paranoia, agitation, mania, hallucinations, psychosis, and loss of libido. These side effects may be accompanied by other signs and symptoms of neurologic toxicity. Critical illness, advanced age, renal, and/or liver disease appear to be associated with an increased risk for central nervous system toxicity, including psychiatric disturbances.

Endocrine

Endocrine side effects have included gynecomastia, occurring in 0.3% to 1% of patients treated for nonhypersecretory conditions for 1 month or longer. In patients treated for pathologic hypersecretory conditions, this occurred in about 4% of cases. In the majority of cases, however, hormone levels remain in the normal range. In addition, galactorrhea, impotence, and transient alopecia as well as a case of possible cimetidine-induced hypoparathyroidism have been reported.

A large population-based cohort study involving 81,535 men evaluated the risk of gynecomastia associated with cimetidine, ranitidine, misoprostol, and omeprazole. Overall, 37,202 men received cimetidine. Gynecomastia developed in 86 men treated with cimetidine. The relative risk of gynecomastia during cimetidine treatment compared to a control population not treated with cimetidine was 7.2. Use of daily doses of 1000 mg or more was associated with a relative risk of 43.5.

Luteinizing hormone (LH), follicle-stimulating hormone (FSH), serum prolactin, testosterone, and estradiol levels are usually within the normal range in patients who develop gynecomastia or breast tenderness while on cimetidine. However, decreases in serum testosterone and increases in LH and estradiol as well as increases in serum prolactin have been reported on occasion.

Severe hypocalcemia was reported in an elderly woman treated with cimetidine postoperatively. There was some evidence in this case to support a possible cimetidine-induced reduction in parathyroid hormone with subsequent hypocalcemia. More study is needed to confirm this.

Cardiovascular

In a study involving medical ICU patients requiring invasive blood pressure monitoring for circulatory instability or with a need for repeated arterial blood gas draws, an average decrease of 14 mmHg in systolic and 9 mmHg in diastolic pressure was noted in 74% (50/68) of patients following administration of cimetidine 200 mg IV over 3 minutes. In 13% of patients, systolic pressure decreased by more than 30 mmHg.

Most cardiovascular side effects are noted following rapid intravenous administration. While administration by slow infusion appears to reduce the incidence of such effects, serious cardiovascular events, including sinus arrest, have been reported with continuous intravenous infusions as well as oral administration.

Cardiovascular side effects have been rarely reported. These are usually associated with rapid intravenous administration. Tachycardia, bradycardia, hypotension, QT interval prolongation, premature ventricular contractions, junctional rhythm, AV block, and sinus arrest have been reported with H2 receptor antagonist.

Hematologic

Rare cases of irreversible or fatal blood dyscrasias have been reported in the literature. While rare, hematologic abnormalities should be considered in patients treated with cimetidine who develop fever, chills, sore throat, easy bruising, and other signs or symptoms suggestive of a blood dyscrasia.

Hematologic side effects have rarely included leukopenia, eosinophilia, neutropenia, thrombocytopenia, agranulocytosis, and aplastic anemia. The manufacturer also reports extremely rare cases of autoimmune hemolytic anemia.

Hepatic

Hepatic side effects have included elevations in liver function tests and hepatitis of both cholestatic and mixed cholestatic-hepatocellular types. Some presentations of cimetidine-induced hepatitis have features suggestive of a hypersensitivity response.

Overall, serious hepatotoxicity due to cimetidine is rare. Bridging hepatic necrosis, centrilobular hepatic necrosis, and intrahepatic cholestasis have been noted on biopsy in cases of cimetidine-induced hepatitis. In some cases, liver toxicity has been associated with fever, rash, and eosinophilia, suggesting a hypersensitivity etiology.

Cimetidine-induced hepatitis in a patient with a history of famotidine-induced hepatitis has been reported in at least one case. Extreme caution is recommended when initiating cimetidine therapy in a patient with a history of other H2-antagonist-induced hepatotoxicity.

Liver injury, with fatal outcome, has been reported with the use of other H2 receptor antagonists.

Renal

Renal side effects have included elevations in serum creatinine. However, such elevations are generally due to competitive inhibition of tubular secretion of creatinine rather than a result of impaired glomerular filtration or renal toxicity. Rare cases of acute renal failure and interstitial nephritis have been reported.

Elevations in serum creatinine by as much as 20% are reported during cimetidine therapy. Cimetidine is thought to competitively inhibit the secretion of creatinine by the renal proximal tubules resulting in a reduction in creatinine clearance. Creatinine does not appear to affect cimetidine transport, except at very high concentrations.

Overt renal toxicity, such as renal failure and interstitial nephritis, is rare. In some cases, cimetidine-induced renal toxicity has been attributed to a delayed-type hypersensitivity.

Gastrointestinal

Gastrointestinal side effects have been reported rarely. These have included diarrhea (1%) which is generally mild although severe cases have been reported, nausea/vomiting (0.6%), constipation (0.2%), dry mouth, and taste changes. In addition, cases of parotitis, phytobezoars, and pancreatitis have been reported.

Dermatologic

Dermatologic side effects have included mild rash as well as severe dry skin (xerosis), seborrheic dermatitis, erythema annular centrifugum, erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, and toxic epidermal necrolysis. Reversible alopecia has also been reported rarely.

Antiandrogen and sebum-inhibitory effects are proposed mechanisms by which cimetidine causes severe xerosis and asteatotic dermatitis.

Musculoskeletal

Musculoskeletal side effects have rarely included arthralgias, inflammatory arthritis, gout-like arthritis, and myalgias. The manufacturer reports rare cases of polymyositis although causality is unknown.

Immunologic

Immunologic side effects have included a case of exacerbation of cutaneous systemic lupus erythematosus and cimetidine-induced cutaneous vasculitis. Strongyloidiasis hyperinfection has been reported rarely in immunocompromised patients.

Hypersensitivity

Hypersensitivity side effects have included urticaria, pruritus, fever, angioedema, and anaphylaxis. In addition, a case of drug fever in association with leukocytosis and abdominal pain has also been reported. Vasculitis has been reported. It resolved on discontinuation of the drug.

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