Rifampin (Page 3 of 5)

Laboratory Tests

Adults treated for tuberculosis with rifampin should have baseline measurements of hepatic enzymes, bilirubin, serum creatinine, a complete blood count, and a platelet count (or estimate). Baseline tests are unnecessary in pediatric patients unless a complicating condition is known or clinically suspected.

Patients should be seen at least monthly during therapy and should be specifically questioned concerning symptoms associated with adverse reactions. All patients with abnormalities should have follow-up, including laboratory testing, if necessary. Routine laboratory monitoring for toxicity in people with normal baseline measurements is generally not necessary.

Drug 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 accelerate the metabolism and reduce the activity of certain coadministered drugs, 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

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

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 Substantial decrease in exposure, which may result in loss of therapeutic effect and development of resistance.
Tipranavir
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% to 67%
Tocainide Decrease exposure
Antiestrogens
Tamoxifen Decrease AUC by 86%
Toremifene Decrease steady state concentrations of toremifene in serum
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% to 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% to 85%
Telithromycin Decrease AUC by 86%
Theophylline Decrease exposure by 20% to 40%

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