Rifadin

Last updated on RxList: 6/30/2021
Rifadin Side Effects Center

What Is Rifadin?

Rifadin (rifampin, isoniazid and pyrazinamide) is an antibiotic used to treat or prevent tuberculosis (TB). Rifadin may also be used to eliminate a type of bacteria from your nose and throat that may cause meningitis or other infections, even if you do not have an infection.

What Are Side Effects of Rifadin?

Common side effects of Rifadin include:

  • upset stomach,
  • heartburn,
  • nausea,
  • menstrual changes,
  • headache,
  • drowsiness,
  • tired feeling, or
  • dizziness.

Rifadin may also produce a harmless, red or orange coloration of urine, stools, sweat, saliva, or tears. Soft contact lenses may be permanently stained. Tell your doctor if you have unlikely but serious side effects of Rifadin including:

  • flu-like symptoms (fever, chills, headache, muscle aches),
  • changes in amount of urine,
  • persistent nausea or vomiting,
  • stomach or abdominal pain,
  • dark urine,
  • yellowing eyes or skin,
  • mental/mood changes (e.g., confusion, unusual behavior),
  • unusual tiredness,
  • easy bruising or bleeding,
  • small red spots on the skin, or
  • joint pain and swelling.

Dosage for Rifadin

To treat tuberculosis, the adult dose of Rifadin is 10 mg/kg, in a single daily administration, not to exceed 600 mg/day, oral or IV. The pediatric dose 10-20 mg/kg, not to exceed 600 mg/day, oral or IV.

What Drugs, Substances, or Supplements Interact with Rifadin?

Rifadin may interact with acetaminophen, blood thinners, barbiturates, diazepam or similar medicines, beta-blockers, clofibrate, steroids, birth control pills or estrogen hormone replacement, heart medicines, HIV medicines, ketoconazole, itraconazole, fluconazole, methadone, phenytoin, ethotoin, mephenytoin, sulfa drugs, oral diabetes medication, cyclosporine, or theophylline. Rifadin can interact with many drugs. Tell your doctor all medications you use.

Rifadin During Pregnancy and Breastfeeding

During pregnancy, Rifadin should be used only prescribed. When this drug is taken during the last few weeks of pregnancy, the risk of bleeding in both mother and infant may be increased. Tell your doctor if you notice bleeding in your newborn. This medication passes into breast milk. Consult your doctor before breastfeeding.

Additional Information

Our Rifadin (rifampin, isoniazid and pyrazinamide) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Get emergency medical help if you have signs of an allergic reaction (hives, rash, feeling light-headed, wheezing, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning in your eyes, skin pain, red or purple skin rash that spreads and causes blistering and peeling).

Seek medical treatment if you have a serious drug reaction that can affect many parts of your body. Symptoms may include: skin rash, fever, swollen glands, muscle aches, severe weakness, unusual bruising, or yellowing of your skin or eyes.

Call your doctor at once if you have:

  • severe stomach pain, diarrhea that is watery or bloody;
  • chest pain, cough, shortness of breath;
  • a light-headed feeling, like you might pass out;
  • easy bruising, unusual bleeding (nosebleeds, bleeding gums);
  • pounding heartbeats or fluttering in your chest;
  • flu symptoms--fever, chills, body aches, headache, weakness, nausea, vomiting; or
  • liver problems--upper stomach pain, tiredness, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

  • red discoloration of your teeth, sweat, urine, saliva, and tears;
  • heartburn, gas, upset stomach, loss of appetite;
  • nausea, vomiting, diarrhea;
  • fever;
  • headache, dizziness, drowsiness, tiredness;
  • muscle weakness, pain in your arms or legs;
  • problems with balance or muscle movement;
  • numbness; or
  • confusion, changes in behavior, trouble concentrating.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Rifadin (Rifampin)

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Rifadin Professional Information

SIDE EFFECTS

Gastrointestinal

Heartburn, epigastric distress, anorexia, nausea, vomiting, jaundice, flatulence, cramps, and diarrhea have been noted in some patients. Although Clostridium difficile has been shown in vitro to be sensitive to rifampin, pseudomembranous colitis has been reported with the use of rifampin (and other broad-spectrum antibiotics). Therefore, it is important to consider this diagnosis in patients who develop diarrhea in association with antibiotic use. Tooth discoloration (which may be permanent) may occur.

Hepatic

Hepatotoxicity including transient abnormalities in liver function tests (e.g., elevations in serum bilirubin, alkaline phosphatase, serum transaminases, gamma-glutamyl transferase), hepatitis, a shock-like syndrome with hepatic involvement and abnormal liver function tests, and cholestasis have been reported (see WARNINGS).

Hematologic

Thrombocytopenia has occurred primarily with high dose intermittent therapy but has also been noted after resumption of interrupted treatment. It rarely occurs during well-supervised daily therapy. This effect is reversible if the drug is discontinued as soon as purpura occurs. Cerebral hemorrhage and fatalities have been reported when rifampin administration has been continued or resumed after the appearance of purpura.

Rare reports of disseminated intravascular coagulation have been observed.

Leukopenia, hemolytic anemia, decreased hemoglobin, bleeding, and vitamin K–dependent coagulation disorders (abnormal prolongation of prothrombin time or low vitamin K–dependent coagulation factors) have been observed.

Agranulocytosis has been reported very rarely.

Central Nervous System

Headache, fever, drowsiness, fatigue, ataxia, dizziness, inability to concentrate, mental confusion, behavioral changes, muscular weakness, pains in extremities, and generalized numbness have been observed.

Psychoses have been rarely reported.

Rare reports of myopathy have also been observed.

Ocular

Visual disturbances have been observed.

Endocrine

Menstrual disturbances have been observed.

Rare reports of adrenal insufficiency in patients with compromised adrenal function have been observed.

Renal

Elevations in BUN and serum uric acid have been reported. Rarely, hemolysis, hemoglobinuria, hematuria, interstitial nephritis, acute tubular necrosis, renal insufficiency, and acute renal failure have been noted. These are generally considered to be hypersensitivity reactions. They usually occur during intermittent therapy or when treatment is resumed following intentional or accidental interruption of a daily dosage regimen, and are reversible when rifampin is discontinued and appropriate therapy instituted.

Dermatologic

Cutaneous reactions are mild and self-limiting and do not appear to be hypersensitivity reactions. Typically, they consist of flushing and itching with or without a rash. More serious cutaneous reactions which may be due to hypersensitivity occur but are uncommon.

Hypersensitivity Reactions

Occasionally, pruritus, urticaria, rash, pemphigoid reaction, erythema multiforme, acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, Drug Reaction with Eosinophilia and Systemic Symptoms syndrome (see WARNINGS), vasculitis, eosinophilia, sore mouth, sore tongue, and conjunctivitis have been observed.

Anaphylaxis has been reported rarely.

Miscellaneous

Edema of the face and extremities has been reported. Other reactions which have occurred with intermittent dosage regimens include "flu syndrome" (such as episodes of fever, chills, headache, dizziness, and bone pain), shortness of breath, wheezing, decrease in blood pressure and shock. The "flu syndrome" may also appear if rifampin is taken irregularly by the patient or if daily administration is resumed after a drug-free interval.

DRUG INTERACTIONS

Pharmacodynamic Interactions

Healthy subjects who received rifampin 600 mg once daily concomitantly with saquinavir 1000 mg/ritonavir 100 mg twice daily (ritonavir-boosted saquinavir) developed severe hepatocellular toxicity. Therefore, concomitant use of these medications is contraindicated. (See CONTRAINDICATIONS.)

When rifampin is given concomitantly with other hepatotoxic medications such as halothane or isoniazid, the potential for hepatotoxicity is increased. The concomitant use of rifampin and halothane should be avoided. Patients receiving both rifampin and isoniazid should be monitored closely for hepatotoxicity.

Effect Of Rifampin On Other Drugs

Induction Of Drug Metabolizing Enzymes And Transporters

Drug metabolizing enzymes and transporters affected by rifampin include cytochromes P450 (CYP) 1A2, 2B6, 2C8, 2C9, 2C19, and 3A4, UDP-glucuronyltransferases (UGT), sulfotransferases, carboxylesterases, and transporters including P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2). Most drugs are substrates for one or more of these enzyme or transporter pathways and these pathways may be induced by rifampin simultaneously. Therefore, rifampin may increase the metabolism and decrease the activity of certain coadministered drugs or increase the activity of a coadministered pro-drug (where metabolic activation is required) and has the potential to perpetuate clinically important drug drug interactions against many drugs and across many drug classes (Table 1).

Table 1 summarizes the effect of rifampin on other drugs or drug classes. Adjust dosages of concomitant drugs based on approved drug labeling and if applicable, therapeutic drug monitoring, unless otherwise specified.

Table 1: Drug Interactions with Rifampin that Affect Concomitant Drug Concentrationsa

Drug or Drug Class and Prevention or Management Clinical Effect
Antiretrovirals
Prevention or Management: Concomitant use is contraindicated (See CONTRAINDICATIONS)
Atazanavir Decrease AUC by 72%
Darunavirb
Tipranavir Substantial decrease in exposure, which may result in loss of therapeutic effect and development of resistance.
Fosamprenavirc Decrease AUC by 82%
Saquinavir Decrease AUC by 70% Coadministration may result in severe hepatocellular toxicity
Antiretrovirals
Prevention or Management: Avoid concomitant use
Zidovudine Decrease AUC by 47%
Indinavir Decrease AUC by 92%
Efavirenz Decrease AUC by 26%
Hepatitis C Antiviral
Prevention or Management: Avoid concomitant use
Daclatasvir Decrease AUC by 79%
Simeprevir Decrease AUC by 48%
Sofosbuvirb Decrease AUC by 72% Coadministration of sofosbuvir with rifampin, may decrease sofosbuvir plasma concentrations, leading to reduced therapeutic effect of sofosbuvir.
Telaprevir Decrease AUC by 92%
Systemic Hormonal Contraceptives
Prevention or Management: Advise patients to change to non-hormonal methods of birth control during rifampin therapy
Estrogens Decrease exposure
Progestins
Anticonvulsants
Phenytoind Decrease exposured
Antiarrhythmics
Disopyramide Decrease exposure
Mexiletine Decrease exposure
Quinidine Decrease exposure
Propafenone Decrease AUC by 50%-67%
Tocainide Decrease exposure
Antiestrogens
Tamoxifen Decrease AUC by 86%
Tamoxifen Decrease steady state concentrations of toremifene in serum
Antithrombotic Agents
Clopidogrel
Prevention or Management: Concomitant use of clopidogrel and rifampin should be discouraged
Increase active metabolite exposure and risk of
bleeding
Ticagrelor
Prevention or Management: Avoid use
Decrease exposure
Antipsychotics
Haloperidol Decrease plasma concentrations by 70%
Oral Anticoagulants
Prevention or Management: Perform prothrombin time daily or as frequently as necessary to establish and maintain the required dose of anticoagulant
Warfarin Decrease exposure
Antifungals
Fluconazole Decrease AUC by 23%
Itraconazole
Prevention or Management: Not recommended 2 weeks before and during itraconazole treatment
Decrease exposure
Ketoconazole Decrease exposure
Beta-blockers
Metoprolol Decrease exposure
Propranolol Decrease exposure
Benzodiazepines
Diazepama,e Decrease exposure
Benzodiazepine-related drugs
Zopiclone Decrease AUC by 82%
Zolpidem Decrease AUC by 73%
Calcium Channel Blockerse
Diltiazem Decrease exposure
Nifedipinef Decrease exposure
Verapamil Decrease exposure
Corticosteroidsg
Prednisolone Decrease exposure
Cardiac Glycosides
Digoxin
Prevention or Management: Measure serum digoxin
concentrations before initiating rifampin. Continue monitoring and increase digoxin dose by
approximately 20%-40% as necessary.
Decrease exposure
Digitoxin Decrease exposure
Fluoroquinolones
Pefloxacinh Decrease exposure
Moxifloxacina,d Decrease exposure
Oral Hypoglycemic Agents (e.g. sulfonylureas)
Glyburide Decrease exposure Rifampin may worsen glucose control of glyburide
Glipizide Decrease exposure
Immunosuppressive Agents
Cyclosporine Decrease exposure
Tacrolimus
Prevention or Management: Monitoring of whole blood concentrations and appropriate dosage
adjustments of tacrolimus are recommended when
rifampin and tacrolimus are used concomitantly.
Decrease AUC by 56%
Narcotic Analgesics
Oxycodone Decrease AUC by 86%
Morphine Decrease exposure
Selective 5-HT3 Receptor Antagonists
Ondansetron Decrease exposure
Statins Metabolized by CYP3A4
Simvastatin Decrease exposure
Thiazolidinediones
Rosiglitazone Decrease AUC by 66%
Tricyclic Antidepressants
Nortriptylinei Decrease exposure
Other Drugs
Enalapril Decrease active metabolite exposure
Chloramphenicolj Decrease exposure
Clarithromycin Decrease exposure
Dapsone Decrease exposure
Doxycyclinek Decrease exposure
Irinotecanl
Prevention or Management: Avoid the use of rifampin, strong CYP3A4 inducer, if possible. Substitute non-enzyme inducing therapies at least 2 weeks prior to initiation of irinotecan therapy
Decrease irinotecan and active metabolite exposure
Levothyroxine Decrease exposure
Losartan Parent Decrease AUC by 30%
Active metabolite (E3174) Decrease AUC by 40%
Methadone In patients well-stabilized on methadone, concomitant administration of rifampin resulted in a marked reduction in serum methadone levels and a concurrent appearance of withdrawal symptoms.
Praziquantel
Prevention or Management: Concomitant use is contraindicated (See CONTRAINDICATIONS)
Decrease plasma praziquantel concentrations to undetectable levels.
Quinine
Prevention or Management: Avoid concomitant use
Decrease AUC by 75%-85%
Telithromycin Decrease AUC by 86%
Theophylline Decrease exposure by 20% to 40%
a Administered with rifampin 600 mg daily, unless otherwise specified
b Rifampin dosage used concomitantly with the drug(s) is not specified in the proposed package insert.
c Administered with rifampin 300 mg daily
d Administered with rifampin 450 mg daily
e Administered with rifampin 1200 mg daily
f Rifampin 1200 mg administered as a single oral dose 8 hours before administering a single oral dose of nifedipine 10 mg
g Numerous cases in the literature describe a decrease in glucocorticoid effect when used concomitantly with rifampin. The literature contains reports of acute adrenal crisis or adrenal insufficiency induced by the combination of rifampin-isoniazid-ethambutol or rifampin-isoniazid in patients with Addison’s disease
h Administered with rifampin 900 mg daily
i A tuberculosis treatment regimen including rifampin (600 mg/day) isoniazid (300 mg/day), pyrazinamide (500 mg 3× per day), and pyridoxine (25 mg) was associated with higher than expected doses of nortriptyline were required to obtain a therapeutic drug level. Following the discontinuation of rifampin, the patient became drowsy and the serum nortriptyline levels rose precipitously (3-fold) into the toxic range.
j Concomitant use with rifampin in 2 children
k Administered with rifampin (10 mg/kg daily)
l Administered with an antibiotic regimen including rifampin (450 mg/day), isoniazid (300 mg/day), and streptomycin (0.5 g/day) IM
AUC = area under the time-concentration curve

Effect Of Other Drugs On Rifampin

Concomitant antacid administration may reduce the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of antacids.

Concomitant use with probenecid and cotrimoxazole increases the concentration of rifampin which may increase the risk of RIFADIN toxicities. Monitor for adverse reactions associated with RIFADIN during coadministration.

Other Interactions

Atovaquone

Concomitant use of rifampin with atovaquone decrease concentrations of atovaquone and increase concentrations of rifampin which may increase the risk of RIFADIN toxicities. Coadministration of rifampin with atovaquone is not recommended.

Read the entire FDA prescribing information for Rifadin (Rifampin)

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© Rifadin Patient Information is supplied by Cerner Multum, Inc. and Rifadin Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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