Drug Interactions between isoniazid / pyrazinamide / rifampin and tretinoin

Using isoniazid together with rifAMPin can cause serious side effects that may affect your liver. You should avoid or limit the use of alcohol while being treated with these medications. Your doctor may already be aware of the risks but has determined that this is the best course of treatment for you, has taken appropriate precautions, and is monitoring you closely for any potential complications. If you develop severe liver problems, you may need a dose adjustment or an interruption in therapy. Call your doctor immediately if you have fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, abdominal pain, dark colored urine, light colored stools, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage. Talk to your healthcare provider if you have any questions or concerns. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Ask your doctor before using rifAMPin together with pyrazinamide. This can cause damage to the liver. Liver function and drug levels in the blood may be monitored with blood tests during treatment. Call your doctor if you experience fever, rash, loss of appetite, nausea, vomiting, fatigue, right upper abdominal pain, dark urine, and jaundice. You may need a dose adjustment or special tests to safely take both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Concomitant use of strong CYP450 3A4 inducers with tretinoin (systemic) may decrease the plasma concentration of tretinoin, which is a CYP450 3A4 substrate. Reduced efficacy of tretinoin may occur. Studies document the interaction between endogenous retinoids and CYP450 3A4 inducers (e.g., carbamazepine, phenytoin, phenobarbital) showing decreased concentration of the retinoids and reduced efficacy. While clinical data specific to tretinoin are not available, similar effects may occur.

MONITOR CLOSELY: Coadministration of rifampin with agents known to induce hepatotoxicity may potentiate the risk of liver injury. There are various possible mechanisms related to rifampin-associated hepatotoxicity described in product labeling and medical literature, however no consensus has been made. These include increased mitochondrial oxidative stress, apoptotic liver cell injury (in rodent studies), the development of cholestasis, hepatic lipid accumulation, and elevated toxic metabolites caused by rifampin-mediated induction of cytochrome P450 enzymes. Cases of drug-induced liver injury (including fatal cases) have been reported within the first few days to months following rifampin treatment initiation. Additional data suggests that 1-2% of patients receiving rifampin monotherapy for tuberculosis prophylaxis experience hepatotoxicity. The severity of hepatotoxicity from rifampin ranges from asymptomatic elevations in liver enzymes, jaundice and/or hyperbilirubinemia, and symptomatic self-limiting hepatitis to fulminant liver failure and death. In most cases, liver function recovers upon on discontinuation of rifampin treatment, however, progression to acute liver failure requiring liver transplantation is possible. Known risk factors that may predispose the patient to rifampin related hepatotoxicity include: coadministration with other hepatotoxic agents, alcoholism, existing liver disease, malnutrition, extensive liver tuberculosis, liver adenocarcinoma and biliary tract neoplasm. Clinical data have been reported with concurrent use of rifampin with other antituberculosis agents (e.g., isoniazid, pyrazinamide), acetaminophen, antiretroviral agents (e.g., saquinavir/ritonavir) and halothane. Data with other hepatotoxic agents are limited.

MANAGEMENT: The manufacturer recommends avoiding concomitant use of tretinoin with strong CYP450 3A4 inducers due to a potentially significant reduction in its efficacy. If concurrent use cannot be avoided, pharmacologic response to the retinoid should be monitored more closely whenever rifampin is added to or withdrawn from therapy, and the retinoid dosage adjusted as necessary. Caution and close clinical monitoring should be considered if rifampin is coadministered with other hepatotoxic medications. In addition, the manufacturer recommends patients with impaired liver function only be given rifampin in cases of necessity and then under strict medical supervision. Some authorities consider rifampin treatment in patients with existing liver injury contraindicated (Canada). In cases where coadministration of rifampin with hepatotoxic agents is required, careful monitoring of liver function, especially ALT and AST, should be done prior to therapy and then every 2 to 4 weeks during therapy. If hepatic damage is suspected, rifampin should be immediately discontinued. Furthermore, if hepatitis is attributed to rifampin in patients with tuberculosis, alternative agents should be considered. Patients should be instructed to contact their physician immediately if they experience symptoms such as itching, weakness, loss of appetite, nausea, vomiting, abdominal pain, yellowing of the eyes or skin or dark urine.

Isoniazid may cause liver problems and using it with other medications that can also affect the liver, such as pyrazinamide, may increase that risk. You should avoid or limit the use of alcohol while being treated with these medications. Your doctor may already be aware of the risks but has determined that this is the best course of treatment for you, has taken appropriate precautions, and is monitoring you closely for any potential complications. If you develop severe liver problems, you may need a dose adjustment or an interruption in therapy. Call your doctor immediately if you have fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, abdominal pain, dark colored urine, light colored stools, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage. Talk to your healthcare provider if you have any questions or concerns. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Isoniazid may cause liver problems and using it with other medications that can also affect the liver, such as tretinoin, may increase that risk. You should avoid or limit the use of alcohol while being treated with these medications. Your doctor may already be aware of the risks but has determined that this is the best course of treatment for you, has taken appropriate precautions, and is monitoring you closely for any potential complications. If you develop severe liver problems, you may need a dose adjustment or an interruption in therapy. Call your doctor immediately if you have fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, abdominal pain, dark colored urine, light colored stools, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage. Talk to your healthcare provider if you have any questions or concerns. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.