Adverse Events During Treatment

Patients on treatment for latent TB infection (LTBI) or TB disease should report any signs and symptoms of adverse drug reactions to their health care provider, including

• Unexplained loss of appetite, nausea or vomiting, brown urine*, or jaundice (yellowing of skin or eyes)
• Persistent tingling, numbness, or burning of hands or feet
• Persistent weakness, fatigue, fever, or abdominal tenderness
• Easy bruising or bleeding
• Blurred vision or changed vision

*Patients taking rifampin (RIF) or rifapentine (RPT) should be informed that they will notice an orange discoloration of urine and possibly other body fluids. This is normal.

Patients should provide a list of current medications to avoid drug interactions. Some interactions to note:

• Isoniazid (INH) increases blood levels of phenytoin (Dilantin) and disulfiram (Antabuse)
• RIF and RPT decrease blood levels of many drugs including oral contraceptives, warfarin and some other anticoagulants (“blood thinners”), sulfonylureas (used for diabetes), and methadone
• RIF and RPT are contraindicated in HIV-infected individuals being treated with protease inhibitors (PIs) and most nonnucleoside reverse transcriptase inhibitors (NNRTIs)

Healthcare providers treating patients with the combination regimen of isoniazid and rifapentine in 12 once-weekly doses (3HP) should

• Inform the patient (parents/legal guardians of pediatric patient) about possible adverse effects and instruct them to seek medical attention when symptoms of possible adverse effects first appear.
• Conduct monthly evaluations for the findings of treatment-associated adverse events (e.g., symptoms suggestive of systemic drug reactions, loss of appetite, vomiting, yellow eyes, tenderness of the liver, easy bruising, rash).
• Order baseline liver chemistry blood tests (at least alanine or aspartate aminotransferase [ALT or AST, respectively]) for patients with specific conditions: HIV infection, liver disorders, postpartum period (≤3 months after delivery), regular alcohol usage, injection drug usage, or taking medications with known possible interactions with either isoniazid or rifapentine. Consider a baseline liver chemistry blood test for older patients on an individual basis, especially for those taking medications for chronic medical conditions.
• Conduct blood tests at the next clinical visit for patients whose baseline testing is abnormal and for others at risk for liver disease. Discontinue 3HP if a serum ALT/AST concentration is ≥5 times the upper limit of normal in the absence of symptoms, or ≥3 times the upper limit of normal in the presence of symptoms.
• Be vigilant for drug hypersensitivity reactions, particularly hypotension or thrombocytopenia.
• In case of a possible severe adverse reaction (e.g., hypotension requiring intravenous fluid support), discontinue 3HP and provide supportive medical care.
• In case of mild to moderate adverse reaction (e.g., dizziness), use conservative management (e.g., treat dizziness with rest, oral fluids), conduct clinical and laboratory monitoring, and consider continuing 3HP treatment under observation.