Focus on Pharm: Isoniazid

I mentioned isoniazid in this article on tuberculosis so if you’re interested in some exponential learning, make sure you review that one as soon as you’re finished here. You can also listen to that episode on any podcast player or from this link. Simply search for Straight A Nursing wherever you listen to podcasts and look for Tuberculosis Focused Review: Episode 218. 

In this article, I am teaching you what you need to know about isoniazid using the Straight A Nursing DRRUGS framework.

Listen to the below information on isoniazid in episode 233 of the Straight A Nursing podcast wherever you get your podcasts or straight from the website here

D: What DRUG CLASS is isoniazid?

Isoniazid (abbreviation INH; brand name Isotamine) is one of those medications with two classifications – therapeutic and pharmacologic. In the therapeutic class it is considered an antitubercular and in the pharmacologic class it is considered a mycolic acid inhibitor. 

Isoniazid is very selective for mycobacteria and works by inhibiting the synthesis of mycolic acid, which disrupts the cell wall. It also disrupts the synthesis of DNA and other key components in the mycobacterium. 

The medication has a peak concentration within one to two hours after dosing, but note that its absorption can be delayed by both foods and antacids so your patient will be taking this on an empty stomach. Isoniazid has a special distinction of easily crossing the blood-brain barrier, meaning CSF levels of the drug can be equal to those found in the serum. It also crosses into the placenta and breast milk and safety around its usage has not been firmly established. However, note that it may be used to treat tuberculosis in pregnant women and lactating women where the benefit outweighs the risk.

R: What ROUTES are utilized to administer isoniazid?

Isoniazid can be given PO as tablet or liquid in orange and raspberry flavor, as well as via intramuscular injection (IM). Again, make sure your patient takes the medication on an empty stomach to achieve appropriate absorption. 

When injecting isoniazid, note that it can cause some discomfort for the patient at that injection site. Be sure to rotate injection sites and massage after each administration. In addition, the medication can form crystals at low temperatures. Simply let the vial contents warm to room temperature and then re-check for any remaining crystals before administering the medication.

Anytime you are concerned about crystals, you can always take the extra step of using a filter needle to draw the medication from the vial. The filter needle is then replaced with the injection needle for administration.

IMPORTANT: Though it is not FDA approved for IV administration at this time, you could see isoniazid given via this route. If your patient has isoniazid ordered IV, there’s no harm in clarifying this with the prescriber.

R: What is the REGULAR DOSE RANGE for isoniazid?

Isoniazid dosing can be complex and vary based on its usage. For the easiest reference, note that it has a max dose of 300 mg when given daily and 900 mg when taken two or three times per week.

U: What conditions is isoniazid USED to treat?

Isoniazid is used to treat both latent and active tuberculosis. It is often used in combination with other medications (check out this article for more details). In general, active infection is treated more aggressively and with more medications than latent TB. A typical multi-drug regimen for active infection is a two-month initial phase followed by a continuation phase of four to seven months.

Because isoniazid easily crosses the blood-brain barrier, it is first line treatment in tuberculosis meningitis. This highly destructive form of extra-pulmonary tuberculosis has a mortality rate ranging from 20-69%, even with standard therapies. 

It is contraindicated in cases of pancreatitis, acute liver disease and in anyone at risk for developing hepatitis from prior usage of isoniazid.

It’s going to be used cautiously in anyone with a history of liver disease, chronic alcohol use, severe kidney disease, and pregnant/breastfeeding women. The risk for neuropathy is increased in patients with diabetes and malnourishment so it will be used cautiously in those patients as well. In addition, Black and Hispanic women are at higher risk for serious and lethal hepatotoxicity, so it is used very cautiously in these individuals.

G: What are some key GUIDELINES around isoniazid administration?

Medication adherence – The key guideline with tuberculosis treatment and the prevention of drug-resistant strains is medication adherence. The thick mycolic acid layer that surrounds the mycobacterium is very resistant to penetration by most anti-infective medications, so treatment must be consistent and persistent in order to be effective. To achieve this goal of strict medication adherence, we utilize something called “directly observed therapy” or DOT. In DOT, the individual is observed swallowing the medication. This can occur in the inpatient setting, in an outpatient clinic or even via telehealth appointments.

When to take – Because absorption can be inhibited by the presence of food in the GI tract, ensure it is taken on an empty stomach (one hour before or two hours after a meal). Antacids can also decrease absorption, so stagger their administration as well.

Dietary considerations – Foods containing tyramine can cause serious adverse reactions that include tachycardia, vomiting, shortness of breath and headache. Many foods contain tyramine, so this is a key patient-teaching area. Common foods to avoid are aged cheeses, fermented foods (sauerkraut, soy sauce, miso), cured/smoked/processed meats, fish sauce, chocolate, caffeine and beer). There are many others, so always check with a reputable drug guide, pharmacist or the prescriber when questions arise.

Ongoing assessment – Patients taking isoniazid will be assessed for the development of drug resistance prior to therapy and periodically throughout. The patient’s hepatic function will also be monitored as isoniazid can cause drug-induced hepatitis (the labs monitored are AST, ALT and serum bilirubin). In addition, monitor your patient for signs of hepatic dysfunction. This can include abdominal pain, N/V, weakness or malais, jaundice, increased bruising, facial edema).

Isoniazid can cause neurological effects, so patients should be monitored for altered mental status, seizure and peripheral neuropathy. 

Additionally, patients should be monitored for fever, unusual bleeding and signs of infection (such as sore throat or unusual fatigue).

Labs – AST, ALT, serum bilirubin, platelets, creatinine. In addition, sputum cultures will be obtained regularly until the patient has two negative results in a row.

Pregnancy – Isoniazid is in pregnancy category C, which means animal studies have shown adverse effects on the fetus but there aren’t any well-controlled or adequate studies in humans. A medication in this category could still be prescribed to a pregnant individual if the potential benefits outweigh the potential risks. Pregnant women taking isoniazid may also be prescribed pyridoxine (vitamin B6) to prevent isoniazid toxicity.

Renal disease – Patients with end-stage renal disease can still take isoniazid, but the dose should be administered after peritoneal and hemodialysis as the medication is dialyzable. Because the medication is excreted by the kidneys, reduced dosing may be needed in individuals with renal disease.

Drug interactions – Isoniazid has many drug-drug interactions, but the most common are: 

• Phenytoin – It can cause increased levels of phenytoin, which is a common medication used to treat seizure disorder.
• Theophylline – This asthma medication may have reduced elimination when taken with isoniazid leading to theophylline toxicity.
• Aluminum-containing antacids – Can decrease absorption, so stagger their administration or avoid if possible.
• Carbamazepine – Taking isoniazid with this anticonvulsant can increase the risk of hepatotoxicity.
• Warfarin – Isoniazid could inhibit the metabolism of warfarin, increasing the risk for bleeding.
• Disulfiram – Taking isoniazid with this medication that’s used as a deterrent for alcohol consumption can cause psychosis reactions and ataxia.
• General – Any medication that can cause hepatotoxicity is going to increase the risk when taken with isoniazid. This includes other antitubercular medications and acetaminophen.

Patient teaching – There is a lot of patient teaching for anyone taking isoniazid. Some key elements to ensure your patient understands are: 

• Long-term medication adherence is critical for preventing drug-resistant strains and directly observed therapy helps with that. They should understand they need to continue the medication until their doctor notifies them to stop, even if they are feeling better.
• Teach your patient to monitor for side effects and how to recognize isoniazid toxicity. Some common signs are N/V, rash, ataxia, altered mental status, slurred speech, dizziness and fever.
• Ensure your patient knows to avoid alcohol while taking the medication as alcohol increases the risk for hepatic impairment.
• Teach your patient to take the medication on an empty stomach and avoid tyramine-containing foods as consuming them could cause a serious reaction.
• Make sure your patient understands how to avoid the spread of TB. You can learn more about tuberculosis here.
• Teach your patient to recognize adverse effects of isoniazid and when to alert their MD.

S: What are the SIDE EFFECTS of isoniazid?

• CNS/Neuro – Peripheral neuropathy is the most common neurological effect. There’s a heightened risk for neuropathy in patients with renal failure, nutritional deficiencies, chronic alcohol uses, pregnancy and diabetes. Patients are often prescribed concurrent pyridoxine (vitamin B6) as it can help prevent neuropathy from occurring. Isoniazid competes with B6 as a cofactor when the body makes synaptic neurotransmitters. By supplementing with B6, the hope is that we counteract these effects.
• Other, less common neurological effects are ataxia, seizure and psychosis. 
• GI – Isoniazid can cause hepatic impairment, nausea, vomiting and life-threatening pancreatitis. Hepatic toxicity is typically observed in the first two months of treatment and is more likely in individuals using alcohol or other medications with a hepatotoxic profile. Mild cases may not necessitate discontinuation of the medication, but the patient will be monitored very closely. Isoniazid hepatitis is a severe form of lung injury that can be fatal. Signs of serious hepatic injury are fatigue, anorexia, jaundice, N/V, right upper quadrant pain, dark urine and clay-colored stool.
• Dermatologic – Rash can occur along with serious adverse effects including toxic epidermal necrolysis, Stevens-Johnson syndrome, and DRESS (drug reaction with eosinophilia and systemic symptoms).
• Other adverse effects include fever, visual disturbances, anemia and drug-induced lupus erythematosus.
• Isoniazid toxicity/poisoning occurs in cases of vitamin B6 and or GABA deficiency. Key signs are N/V, rash, ataxia, altered mental status, slurred speech, dizziness and fever. It can also cause seizures and even status epilepticus. The seizures with isoniazid toxicity often don’t respond to monotherapy with benzodiazepines, so the treatment is often benzodiazepines plus pyridoxine (vitamin B6).

I hope this review of isoniazid helps you understand this common medication used in tuberculosis treatment. For more pharmacology lessons, use this link.

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