Monitoring Patients on Anti-TB Medications

1. Monitoring Patients on Anti-TB Medications Reynard J. McDonald, MD Medical Director, Lattimore Practice Northeast National Tuberculosis Center at NJMS

2. Adverse Side Effect • Any unexplained, unintended, undesired, or excessive response to a medication, used at recommended doses that may require: • Discontinuation of the medication (therapeutic or diagnostic) • Modifying the dose (except for minor dosage adjustments) • Prolonging treatment

3. Adverse Side Effects Cont’d • Adverse drug reactions may lead to complications: • Prevents optimal drug use in some patients • Necessitates supportive care • Significantly complicates treatment • Decreases patient’s quality of life • Results in temporary or permanent harm, disability, or death

4. Scope of Problem • The fourth leading cause of death in the US is adverse drug reactions (ADRs) • Only heart disease, cancer, and stroke kill more Americans than ADRs • The number of deaths from ADRs is three times the number of deaths from people killed by automobile accidents

5. Risk Factors for Developing an ADR • Multiple drug therapy • Over the counter medications • Alcohol • Drugs of abuse • Number of drugs • Age • Very young • Very old • Pregnancy • Risk to fetal development (first trimester, phenytoin) • Co-morbidity/chronic diseases – can alter a drug’s absorption, distribution, metabolism or elimination • Hereditary factors – slow acetylators

6. Monitoring for Adverse Reactions • Health care workers should be educated about: • Name(s) of medication • Common side effects • More serious reactions • What to do if symptoms occur • What to do if patients have other behaviors that may interfere with their treatment • What to do if a dose is missed • How to report an ADR

7. Monitoring for Adverse Reactions • During treatment, patients should be questioned and evaluated for: • Signs and symptoms of possible side effects • Use open-ended questions to obtain more information • While in the field, health care workers should: • Make observations about the patient and the surrounding environment • Take appropriate action to address and correct the adverse reaction

8. How Do I Report an ADR? • Depends on each individual TB program • e.g., telephone, email, fax, or mail • Follow the TB Program’s standard procedure for reporting ADRs • Ensure complete documentation of all pertinent information

9. TB Medications That Can Cause an ADR • First-Line Anti-TB Medications • Isoniazid (INH) • Rifampin (RIF) • Rifabutin (RFB) • Rifapentine (RPT) • Ethambutol (EMB) • Pyrazinamide (PZA) • Second-Line Anti-TB Medications

10. Isoniazid (INH) • Adverse effects: • Hepatic enzyme elevation • Hepatitis • Peripheral neuropathy • CNS effects • SLE-like symptoms • Hypersensitivity reaction • Monoamine (Histamine/tyramine poisoning) • Diarrhea

11. INH Drug Interactions & Monitoring • Drug Interaction • Phenytoin • Monitoring • Routine monitoring is not necessary • For patients with pre-existing liver disease or who develop abnormal liver function test should be measured monthly and when symptoms occur • Prevention • Vitamin B6 may prevent peripheral neuropathy and CNS effects

12. Rifampin (RIF) • Adverse effects: • Cutaneous reactions • Gastrointestinal reactions • Flu-like syndrome • Hepatotoxicity • Severe immunologic reactions • Orange discoloration of bodily fluids • Patients should be informed in advance of urine and contact lens discoloration

13. RIF Drug Interactions • Drug Interactions • Antiinfectives • Hormone therapy • Narcotics • Anticoagulants • Immunosuppressive agents • Anticonvulsants • Cardiovascular agents • Bronchodilators • Sulfonylurea hypoglycemics • Hypolipidemics • Psychotropic drugs

14. RIF Monitoring • Monitoring • No routine monitoring required • When given with drugs that interact, may necessitate regular measurements of the serum concentrations of the drugs in question

15. Rifabutin (RFB) • Adverse effects: • Hematologic toxicity • Uveitis • GI symptoms • Polyarthralgia • Hepatitis • Rash • Orange discoloration of bodily fluids • Drug interactions and monitoring – see RIF

16. Rifapentine (RPT) • Adverse effects: • Similar to those associated with RIF • May increase metabolism of co-administered drugs that are metabolized by hepatic enzymes • Drug Interactions: • Are likely to be similar to those of RIF • Monitoring: • Similar to that for RIF

17. Ethambutol (EMB) • Adverse effect: • Optic neuritis (impaired perception of the red and green colors) • Cutaneous reactions • Monitoring • Baseline and monthly tests of visual acuity and color vision • Educate patient about self monitoring their vision and reporting any visual changes to their physician immediately

18. Pyrazinamide (PZA) • Adverse effects: • Hepatotoxicity • GI symptoms • Non-gouty polyarthralgia • Hyperuricemia • Acute gouty arthritis • Rash • Monitoring • Serum uric acid measurements are not routinely recommended • Liver function tests should be performed when the drug is used in patients with underlying liver disease

19. Second-Line Anti-TB Medications • Cycloserine • Ethionamide • Levofloxacin • Moxifloxacin • Gatifloxacin • p-Aminosalicylic acid (PAS) • Streptomycin • Amikacin/Kanamycin • Capreomycin

20. Second-Line Anti-TB Medications • Cycloserine • Psychosis, seizures • Ethionamide and PAS • GI upset • Fluoroquinolones • Tendon rupture • Aminoglycosides • Deafness • Renal failure

21. Patient Education • Health care workers must clearly explain to patients the following: • When the medication should be taken • How much • How often • All patients should be educated about: • TB • Medication dosages • Possible side effects • Importance of taking the medication

22. Additional Challenges • Close supervision is necessary for patients who abuse alcohol and other drugs to: • Ensure adherence • Monitor for medication side effects and adverse reactions • Directly observed therapy (DOT) and case management can produce the best results

23. Questions To Ask • How do you feel? • Do you have any of the following: • Abdominal pain • Fatigue • Unusual breathing • Rash • Joint pains/swellings • Other unusual symptoms

24. Questions Cont’d • Are you taking any medications other than anti-TB medications? • Prescription medications, herbal remedies or vitamins • How is your appetite? • How do you feel after you take the medications? • Have you had any weight gain or loss? • What color is your urine (should be orange for patients on rifampin)? • Do you have any fever?

25. Patient Observation • Does the patient have signs and symptoms of hepatitis including any of the following: • Yellow eyes • Yellow skin • Nausea or vomiting • Does the patient have any rash? • Is the patient gaining weight? • Are you having any problems taking the anti-TB medications?

26. Importance of Monitoring • Close monitoring of patients throughout treatment can: • Prevent serious complications • Promote continuity of care • Improve patient-health care provider relationship • Encourage adherence • Ensure successful completion of treatment