Rifater is a combination of rifampicin, isoniazid, and pyrazinamide.

It is used in the initial phase, short-course treatment of pulmonary tuberculosis.

Current treatment guidelines of adults with previously untreated tuberculosis recommend that a four-drug regimen consisting of rifampin, isoniazid, pyrazinamide, and ethambutol be given in the initial phase of treatment until drug susceptibility has been confirmed.

Rifater dose in Adults

Rifater dose in the treatment of Tuberculosis:

• Concomitant anti-tuberculosis medications should be given according to current guideline recommendations

• Weight ≤44 kg:

  • 4 tablets once daily are given

• Weight 45 to 54 kg:

  • 5 tablets once daily are given

• Weight ≥55 kg:

  • 6 tablets once daily are given

Rifater dose in Children

Dosage in the treatment of Tuberculosis:

• Adolescents ≥15 years:
  • Oral:
  • Refer to adult dosing.

Pregnancy Risk Factor: C

• This combination has not been used in animal reproduction studies. For more information, please contact individual agents.

Use of rifampin, isoniazid and pyrazinamide during breastfeeding:

• Breast milk contains rifampin, isoniazid and pyrazinamide.
• According to the manufacturer, it is recommended that the mother decide whether to stop breastfeeding or if to stop taking the drug.
• This decision should be made considering the importance of the mother's treatment.

Dose in Renal disease:

• The labelling provided by the manufacturer does not mention dosage modifications. Take care when using.

Dose in liver disease:

• The labelling provided by the manufacturer does not mention dosage modifications.
• Use cautiously;
• It is contraindicated in severe or acute impairment or in cases of previous isoniazid-associated hepatic injury.

Side effects of Rifater (Rifampicin, isoniazid, and pyrazinamide).

• Cardiovascular:

  • Angina Pectoris
  • Chest Pain
  • Chest Tightness
  • Palpitations
  • Edema

• Central Nervous System:

  • Anxiety
  • Insomnia
  • Tingling Of Extremities
  • Equilibrium Disturbance
  • Vertigo

• Dermatologic:

  • Erythema
  • Erythroderma
  • Exfoliative Dermatitis
  • Localized Rash
  • Pruritus
  • Skin Rash
  • Toxic Epidermal Necrolysis
  • Urticaria
  • Diaphoresis

• Endocrine & Metabolic:

  • Diabetic Coma
  • Increased Uric Acid

• Gastrointestinal:

  • Diarrhea
  • Gastrointestinal Pain
  • Nausea
  • Vomiting

• Hepatic:

  • Increased Serum Transaminases

• Hypersensitivity:

  • Hypersensitivity

• Neuromuscular & Skeletal:

  • Arthralgia
  • Ostealgia

• Otic:

  • Tinnitus

• Respiratory:

  • Cough
  • Hemoptysis
  • Pneumothorax

• Miscellaneous:

  • Fever

Contraindication to Rifater (Rifampin, isoniazid, and pyrazinamide) Include:

• Hypersensitivity to rifampin or other rifamycins, isoniazid, pyrazinamide, or any part of the formulation
• Hepatic injury severe
• Acute liver disease
• acute gout
• History of isoniazid-related severe reactions 

Warnings and precautions

• Cholestasis:

  • Rifampin has been shown to cause mild to severe cases of cholestasis.
  • Stop treatment for confirmed cholestasis.

• Coagulopathy

  • It might result in bleeding and vitamin K-dependent coagulation problems.
  • When treating individuals who are susceptible to vitamin K insufficiency, keep an eye on their coagulation tests (eg, chronic liver disease, poor nutritional status, prolonged use of antibacterial agents or anticoagulants).
  • If bleeding or abnormal coagulation tests occur, think about discontinuing; when necessary, think about supplementing with vitamin K.

• Dermatologic reactions

  • Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalised exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome are examples of severe cutaneous adverse reactions (SCAR).
  • If you notice any signs or symptoms of SCAR, stop treatment immediately and start the appropriate therapy.

• Flu-like syndrome:

  • A significant proportion of adverse effects, including flu-like symptoms, are linked to high dosages of rifampin >600mg once or twice weekly.

• Hematologic effects

  • It can cause anemia, thrombocytopenia, and leukopenia if you take rifampin >600mg once or twice weekly.

• Hepatitis: [US-Boxed Warning]

  • Isoniazid can cause severe and sometimes fatal liver disease.
  • Generally, transaminase levels increase within the first few months after treatment. However, it can also develop after several months.
  • Age is a factor in the risk of developing hepatitis.
  • Consuming ethanol daily can increase your risk.
  • Patients who have taken rifampin or pyrazinamide with other hepatotoxic drugs have been known to develop hepatic dysfunction.
  • Monitor patients closely for signs of hepatic dysfunction, and discontinue treatment if there is hepatocellular injury.

• Hyperbilirubinemia:

  • Because rifampin and bilirubin compete for the same excretory pathway in the liver, hyperbilirubinemia may develop early in treatment.
  • Stop therapy if hyperbilirubinemia coexists with clinical symptoms or evidence of severe hepatic injury.

• Hypersensitivity

  • Anti-tuberculosis treatment has also been associated with hypersensitivity responses.
  • Angioedema and hypotension may be symptoms of allergic reactions.
  • Hypersensitivity symptoms and signs should be monitored.
  • If you notice signs or symptoms that suggest hypersensitivity, such as fever, lymphadenopathy and eosinophilia, stop therapy, even if there is no rash.

• Peripheral neuropathies:

  • Patients at risk of peripheral neuropathies should be supplemented with pyridoxine.
  • Patients at high risk include:
    • HIV-infected patients
    • nutritional deficiency,
    • Diabetes
    • Alcoholism
    • Chronic renal failure is a condition that can lead to kidney disease.
    • Advanced age

• Superinfection

  • Extended use may result in bacterial and fungal superinfections like pseudomembranous collitis or C. difficile-associated diarrhoea (CDAD).
  • More than two months after receiving antibiotics, CDAD was monitored.

• Alcoholism

  • Patients with a history or alcoholism should be cautious (even if they stop drinking ethanol during therapy).

• Diabetes:

  • Diabetes mellitus patients need to exercise caution.
  • Patients taking rifampin may have a harder time managing diabetes.

• Gout

  • Pyrazinamide also blocks uric acid excretion
  • Acute gouty attacks were seen.
  • Patients with chronic gout should be cautious
  • It is not recommended for acute gout.
  • Patients should have baseline levels of serum uric acid and be checked periodically thereafter.

• Hepatic impairment

  • Patients with hepatic impairment should be cautious.
  • It is possible to reduce dosage.
  • Patients suffering from hepatic impairment must have their liver function tested before starting therapy. They also need to be evaluated every 2 to 4 week thereafter.
  • Stop therapy if you notice signs of hepatocellular injury.

• Porphyria

  • Patients with porphyria should be treated cautiously. Exacerbations have been reported.

• Renal impairment

  • Patients with impaired renal function should be cautious.

• Tuberculosis

  • The current guidelines for treating adults with untreated tuberculosis recommend a 4-drug regimen that includes rifampin (isoniazid), pyrazinamide and ethambutol in the initial phase until drug susceptibility is confirmed.

Monitor:

• Baseline and periodic liver function tests, serum uric acid, serum bilirubin, serum creatinine,
• CBC
• patients at higher risk for hepatitis (eg, existing hepatic impairment, older patients, ethanol consumption, alcoholism) should have liver function tests every 2 to 4 weeks.
• Monitor for prodromal signs of hepatitis
• monitor sputum cultures monthly 
• monitor chest x-ray 2 to 3 months into treatment and at completion.
• When treating individuals at risk for vitamin K deficiency, keep an eye on the results of coagulation tests.

How to administer Rifater (Rifampin, isoniazid, and pyrazinamide)?

• Give dose either 1 hour before or 2 hours after a meal with a full glass of water.

Mechanism of action of Rifater (Rifampin, isoniazid, and pyrazinamide):

• Rifampin primarily prevents transcription by attaching to the beta subunit of DNA-dependent RNA polymerase and inhibiting bacterial mRNA synthesis.
• Additionally, isoniazid prevents the production of mycolic acid, which damages the bacterial cell wall.
• Because susceptible strains of Mycobacterium convert pyrrazinamide to pyrazinoic acid, the pH of the environment is lowered.

International Brands of Rifampin, isoniazid, and pyrazinamide:

• Rifater
• Pro TB3
• Rimcure
• Rimcure 3-FDC

Rifampicin, Isoniazid, and Pyrazinamide brands in Pakistan: