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.
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
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.
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.|
|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|
|Propafenone||Decrease AUC by 50% to 67%|
|Tamoxifen||Decrease AUC by 86%|
|Toremifene||Decrease steady state concentrations of toremifene in serum|
|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|
|Fluconazole||Decrease AUC by 23%|
|Itraconazole Prevention or Management: Not recommended 2 weeks before and during itraconazole treatment||Decrease exposure|
|Zopiclone||Decrease AUC by 82%|
|Zolpidem||Decrease AUC by 73%|
|Calcium Channel Blockerse|
|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|
|Oral Hypoglycemic Agents (e.g. sulfonylureas)|
|Glyburide||Decrease exposure Rifampin may worsen glucose control of glyburide|
|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%|
|Oxycodone||Decrease AUC by 86%|
|Selective 5-HT3 Receptor Antagonists|
|Statins Metabolized by CYP3A4|
|Rosiglitazone||Decrease AUC by 66%|
|Enalapril||Decrease active metabolite 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|
|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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