RIFADIN

What it is

Rifadin is available as 150 mg and 300 mg capsules, a syrup containing 100 mg per 5 mL, and an intravenous infusion containing 600 mg per vial. Rifadin is a semisynthetic antibiotic derivative of rifamycin B, specifically the hydrazone 3-(4-methylpiperazinyliminomethyl) rifamycin SV.

Approved indications

— Treatment of tuberculosis in initial treatment and re-treatment of patients, used in conjunction with at least one other antituberculosis drug. — Management of lepromatous leprosy and dimorphous leprosy to effect speedy conversion of the infectious state to the noninfectious state. — Alternative drug in lepromatous, dimorphous, indeterminate and tuberculoid leprosy resistant to sulfones and other antileprosy drugs. — Alternative drug in patients having true drug allergy to more commonly used antileprosy drugs. — Prophylaxis of meningococcal disease in close contacts of known cases and in carriers. — Prophylaxis of household contacts of patients with *Haemophilus influenzae* type B.

Dosing overview

Oral Rifadin should be administered once daily on an empty stomach either 30 minutes before or two hours after a meal. In treatment of tuberculosis, Rifadin must be used with at least one other antituberculous agent; similarly in leprosy treatment, rifampicin should always be used with at least one other antileprosy drug.

Key safety warnings

**Hepatotoxicity.** Rifampicin has been shown to produce liver dysfunction, with fatalities associated with jaundice reported in patients with liver disease or receiving rifampicin with other hepatotoxic agents. Rifampicin should only be given to patients with liver disease in cases of necessity and under strict medical supervision, with periodic liver function monitoring (especially ALT and AST) prior to therapy and then every 2 to 4 weeks during therapy, with dosage adjustment made if necessary. Patients should contact their physician immediately if experiencing symptoms such as itching, weakness, loss of appetite, nausea, vomiting, abdominal pain, yellowing of the eyes or skin or dark urine; if cholestasis is confirmed, rifampicin should be discontinued. Drug-induced liver injury including fatal cases (especially when used in combination with other anti-tuberculosis drugs) has been reported, with signs including elevated serum hepatic enzymes, cholestatic jaundice, hepatitis and hepatotoxicity; though most patients recovered on discontinuation, progression to acute liver failure requiring liver transplantation can occur. **Interactions and enzyme induction.** Rifampicin has been observed to increase the requirement for anticoagulant drugs of the coumarin type; prothrombin time should be performed daily or as frequently as necessary to maintain the required dose of anticoagulant. Rifampicin is a potent inducer of drug metabolising enzymes and transporters that might decrease or increase concomitant drug exposure, safety and efficacy; patients should be advised not to take any other medication without medical advice. **Hypersensitivity and immunological reactions.** Rifadin is not recommended for intermittent therapy because of the possibility of immunological reactions including anaphylaxis; patients should be cautioned against interruption of the daily dosage regimen since rare renal hypersensitivity reactions have been reported when therapy was resumed, and if thrombocytopenia, purpura, haemolytic anaemia or renal failure develops, treatment should be stopped at once and not reinstituted. **Severe bullous reactions and DRESS syndrome.** Cases of severe bullous skin reactions such as Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and acute generalised exanthematous pustulosis (AGEP) have been reported; if symptoms or signs are present, rifampicin treatment must immediately be discontinued. Severe systemic hypersensitivity reactions including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome have been observed; early manifestations of hypersensitivity such as fever, lymphadenopathy or biological abnormalities may be present even without rash, and if such signs occur the patient should consult their physician immediately and rifampicin should be discontinued if an alternative etiology cannot be established. **Interstitial lung disease.** Reports of interstitial lung disease (ILD) or pneumonitis have occurred in tuberculosis patients; ILD/pneumonitis is a potentially fatal disorder and careful assessment of patients with acute onset and unexplained worsening of pulmonary symptoms (dyspnoea accompanied by dry cough) and fever should be performed, with Rifadin permanently discontinued in severe cases and appropriate treatment initiated. **Coagulopathy.** Rifampicin may cause vitamin K dependent coagulopathy and severe bleeding, with monitoring of coagulopathy occurrence recommended for patients at particular bleeding risk; supplemental vitamin K administration should be considered when appropriate.

Contraindications

Jaundice. History of hypersensitivity to any of the rifamycins. Rifadin use is contraindicated when given concurrently with the combination of saquinavir/ritonavir, with cabotegravir, fostemsavir and lenacapavir, and with lurasidone as it markedly decreases the exposure of lurasidone.

PBS listing

Rifadin syrup 100 mg per 5 mL (60 mL) is listed on the PBS with one item, restriction type restricted, with an ex-manufacturer price of A$12.22.

Regulatory history

Rifadin oral liquid (20 mg/mL) was first listed on the ARTG on 8 July 1991, the powder for injection (600 mg) was first listed on 21 January 2009, and the 150 mg and 300 mg capsules were both first listed on 17 June 2015. Rifadin was first approved on 22 August 1996.