Metronidazole/Tetracycline/Bismuth Subsalicylate

Metronidazole/Tetracycline/Bismuth Subsalicylate is a prescription medication used for the eradication of H pylori infection associated with duodenal ulcers.

• Metronidazole/Tetracycline/Bismuth Subsalicylate is available under the following different brand names:

Common side effects of Metronidazole/Tetracycline/Bismuth Subsalicylate include:

• nausea,
• vomiting,
• indigestion,
• diarrhea,
• stomach or abdominal pain,
• constipation,
• loss of appetite,
• headache,
• mouth pain,
• metallic taste in the mouth,
• trouble swallowing,
• dizziness,
• cold symptoms (stuffy nose, sneezing, sore throat),
• vaginal itching or discharge,
• swollen tongue, or
• black or "hairy" tongue.

Serious side effects of Metronidazole/Tetracycline/Bismuth Subsalicylate include:

• ringing in the ears,
• joint pain,
• numbness or tingling of arms or legs,
• frequent or painful urination,
• discolored teeth, or
• mental/mood changes (e.g., nervousness, irritability, depression).

Rare side effects of Metronidazole/Tetracycline/Bismuth Subsalicylate include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Copackaged blister card

• 14 blister packs, containing 8 chewable tablets (262.4mg/tablet) of bismuth subsalicylate plus 4 tablets (250mg/tablet) of metronidazole plus 4 capsules (500mg/capsule) of tetracycline

Duodenal Ulcer

Adult dosage

• Bismuth subsalicylate 525 mg (two 262.4 mg-chewable tablets), metronidazole 250 mg (one 250-mg tablet), and tetracycline hydrochloride 500 mg (one 500-mg capsule) orally four times daily for 14 days plus an H2 antagonist

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Metronidazole/Tetracycline/Bismuth Subsalicylate has severe interactions with the following drugs:
  • acitretin
  • dichlorphenamide
  • dronabinol
• Metronidazole/Tetracycline/Bismuth Subsalicylate has serious interactions with at least 130 other drugs.
• Metronidazole/Tetracycline/Bismuth Subsalicylate has moderate interactions with at least 193 other drugs.
• Metronidazole/Tetracycline/Bismuth Subsalicylate has minor interactions with at least 69 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Hypersensitivity to bismuth subsalicylate, metronidazole or other nitroimidazole derivatives, or tetracycline
• Coadministration with methoxyflurane
• Patients with Cockayne syndrome
• Use of disulfiram within the previous 2 weeks
• Consumption of alcohol or products containing propylene glycol within least three days of receiving metronidazole
• Pregnancy

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Metronidazole/Tetracycline/Bismuth Subsalicylate?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Metronidazole/Tetracycline/Bismuth Subsalicylate?”

Cautions

• Metronidazole has shown to be carcinogenic in mice and rats; tumors affecting the liver, lungs, mammary and lymphatic tissues were detected in several studies of metronidazole in rats and mice; unknown whether metronidazole is associated with carcinogenicity in humans
• Reports of fatal renal toxicity with concurrent use of tetracycline and methoxyflurane
• Tetracycline can cause fetal harm when administered to a pregnant woman (see Pregnancy)
• Tetracycline administered during pregnancy at high doses (above 2 g IV) is associated with rare but serious cases of maternal hepatotoxicity (see Pregnancy)
• Use of tetracyclines during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown); this adverse reaction is more common during long-term use of the drug but has been observed following repeated short-term courses
• Known or previously unrecognized candidiasis may present more prominent symptoms during therapy with metronidazole that requires treatment with an antifungal agent
• Photosensitivity, manifested by an exaggerated sunburn reaction, was observed in patients taking tetracycline
• Bismuth-containing products may cause temporary and harmless darkening of the tongue and/or black stools, generally reversible within several days after treatment is stopped
• Metronidazole is a nitroimidazole and should be used with care in patients with evidence of or history of blood dyscrasias
• Skin and subcutaneous disorders including Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS syndrome (drug rash with eosinophilia and systemic symptoms) reported
• Cases of severe hepatotoxicity/acute hepatic failure, including cases with a fatal outcome with very rapid onset after treatment initiation in patients with Cockayne syndrome reported with products containing metronidazole for systemic use
• Prescribing therapy in absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria
• Metronidazole may interfere with certain types of determinations of serum chemistry values, such as AST, SGOT, ALT, SGPT, LDH, triglycerides, and hexokinase glucose
• Bismuth absorbs x-rays and may interfere with x-ray diagnostic procedures of the gastrointestinal tract
• Severe irreversible hepatotoxicity/acute liver failure with fatal outcomes reported after initiation of metronidazole in patients with Cockayne syndrome
• Use of bismuth subsalicylate/metronidazole/tetracycline is not recommended in children and teenagers who have or who are recovering from varicella (chicken pox) or influenza due to the risk of Reye syndrome, a rare but serious illness
• Severe renal impairment; tetracyclines may increase BUN; higher tetracycline serum concentrations may lead to azotemia, hyperphosphatemia, and acidosis

Central and peripheral nervous system effects

• Metronidazole
  • Convulsive seizures, encephalopathy, aseptic meningitis, and peripheral neuropathy reported
  • Encephalopathy was reported in association with cerebellar toxicity characterized by ataxia, dizziness, and dysarthria; CNS lesions seen on MRI were described in reports of encephalopathy
  • CNS symptoms are generally reversible within days to weeks upon discontinuation of metronidazole
• Tetracycline
  • Intracranial hypertension (IH), including pseudotumor cerebri, associated with the use of tetracyclines
  • Clinical manifestations of IH include headache, blurred vision, diplopia, and vision loss; papilledema can be found on fundoscopy
  • Women of childbearing age who are overweight or have a history of IH are at greater risk for developing tetracycline-associated IH
• Bismuth-containing products
  • Cases of neurotoxicity associated with excessive doses of various bismuth-containing products reported
  • Effects have been reversible with discontinuation of bismuth therapy
  • The appearance of abnormal neurologic signs and symptoms demands the prompt evaluation of the benefit/risk ratio of the continuation of therapy

Drug interactions overview

• Avoid use with isotretinoin; both tetracycline and isotretinoin are known to cause intracranial hypertension
• Tetracyclines may decrease the effectiveness of oral contraceptives; instruct women to use backup contraception during treatment
• Coadministration with anticoagulants may alter the effects of warfarin and other oral coumarin anticoagulants; metronidazole was reported to potentiate the anticoagulant effect of warfarin, and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time; tetracycline shown to depress plasma prothrombin activity
• In patients stabilized on relatively high doses of lithium, short-term use of metronidazole may cause elevation of serum lithium concentrations and signs of lithium toxicity
• Metronidazole is reported to increase plasma concentrations of busulfan, which can result in an increased risk for serious busulfan toxicity; do not administer concomitantly with busulfan unless the benefit outweighs the risk
• Coadministration with drugs that inhibit CYP450 liver enzymes (.g, cimetidine) may result in a prolonged half-life and decreased plasma clearance of metronidazole
• Coadministration with drugs that induce CYP450 liver enzymes (.g, phenytoin, phenobarbital) may accelerate the elimination of metronidazole, resulting in reduced plasma concentrations of metronidazole
• Psychotic reactions reported with concurrent use of metronidazole and disulfiram
• Avoid alcohol or propylene glycol-containing products for at least 3 days after therapy with metronidazole-containing products is discontinued; a disulfiram-like reaction may occur

Pregnancy & Lactation

• Contraindicated in women who are pregnant because treatment of H. Pylori infection can be delayed in pregnant women
• Use of tetracyclines during the second and third-trimester pregnancy can also cause permanent discoloration of the teeth (yellow-gray brown) and possibly inhibit bone development in infant
• Administration of oral tetracycline to pregnant rats at various doses resulted in yellow fluorescence in teeth and bones in the newborn animals; maternal risks with high IV doses of tetracycline reported
• Metronidazole usage in pregnancy is associated with certain congenital anomalies
• Tetracycline administered during pregnancy at high doses (above2 g IV) was associated with rare but serious cases of maternal hepatotoxicity; the syndrome may result in stillborn or premature birth due to maternal pathology

Lactation

• Tetracycline and metronidazole are present in human milk at concentrations similar to maternal serum levels
• It is unknown whether bismuth substrate is present in human milk It is unknown if the effect of therapy have the breastfed infant or on milk production
• Tetracycline binds with calcium in human milk
• Data indicate that oral absorption of tetracycline in infants is low due to the calcium-binding in human milk
• Metronidazole transfers to human milk, and infant serum levels can be close to or comparable to infant therapeutic levels
• Because of the potential risk of the tumorigenicity shown in animal studies with metronidazole, breastfeeding women should pump and discard human milk for the duration of therapy, and for 2 days after therapy ends, and feed their infant stored human milk (collected before therapy) or formula