Rifapentine

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications:

• Latent tuberculosis infection caused by M. tuberculosis

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to rifamycins (e.g. rifampicin, rifabutin)
• Acute or chronic hepatic disease
• Porphyria

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment 
• Concomitant use with contact lenses
• Concomitant use with dentures
• Coadministration with other hepatotoxic agents
• Coadministration with antacids
  (See additional prescribing points)

Forms avail. in SA and covered in this monograph: tab

Infections caused by M. tuberculosis

Rifapentine should be administered once-weekly in combination with isoniazid for 12 weeks as directly observed therapy (DOT)
See additional prescribing points

Latent tuberculosis infection (Additional agent required)
- At high risk of progression to tuberculosis disease (including those in close contact with active tuberculosis patients, recent conversion to a positive tuberculin skin test, HIV-infected patients, or those with pulmonary fibrosis on radiograph)

• Oral (tab): Recommended dose: Based on weight (see table below), weekly; Treatment duration: 12 weeks; Max: 900mg/week

Active tuberculosis disease should be ruled out before initiating treatment for latent tuberculosis infection

Rifapentine, in combination with isoniazid, should be given with food (See additional prescribing points)

Paed. Forms avail. in SA and covered in this monograph: tab

Infections caused by M. tuberculosis

Rifapentine should be administered once-weekly in combination with isoniazid for 12 weeks as directly observed therapy (DOT)
See additional prescribing points

Latent tuberculosis infection (Additional agent required)
- At high risk of progression to tuberculosis disease (including those in close contact with active tuberculosis patients, recent conversion to a positive tuberculin skin test, HIV-infected patients, or those with pulmonary fibrosis on radiograph)

Younger than 2 years

• No information available

2 years and older

• See adult dosage

Active tuberculosis disease should be ruled out before initiating treatment for latent tuberculosis infection

Rifapentine, in combination with isoniazid, should be given with food (See additional prescribing points)

Pregnancy 

• Caution; not recommended
• Women who are pregnant should not be treated with rifapentine
• Rifapentine might have a similar effect as rifampicin which is known to cause postnatal haemorrhages in the mother and infant when taken during the last few weeks of pregnancy, appropriate coagulation testing should be performed when pregnant women are inadvertently exposed to rifapentine during late pregnancy. Treatment with vitamin K may be indicated

Breastfeeding

• Caution; not recommended 
• Mothers on treatment with rifapentine should not breastfeed their babies. It is not known whether rifapentine is excreted in human milk
• May produce a red-orange discolouration of body fluids, including breast milk

Renal Impairment

• Caution; no dose adjustment recommended 

Hepatic Impairment

• Caution; no dose adjustment recommended 
• Patients with abnormal hepatic tests and/or hepatic disease should only be given rifapentine if no safer alternative is available, and then with caution and under strict medical supervision

Elderly

• No dose adjustment recommended 

Porphyria Information

• Porphyrinogenic (P) 

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Fatigue

Respiratory Disorders

• Influenza
• Pneumonia

Gastrointestinal Disorders

• Nausea
• Upper abdominal pain
• Oesophageal irritation
• Clostridium difficile-associated diarrhoea
  - Pseudomembranous colitis

Hepatobiliary Disorders

• Hepatitis
• Hepatotoxicity
  (See additional prescribing points)

Endocrine and Metabolic Disorders

• Pancreatitis

Musculoskeletal Disorders

• Myalgia

Skin and Subcutaneous Tissue Disorders

• Skin reaction
  - Skin rash
  - Mucosal lesions
• Severe cutaneous adverse reactions (SCARs)
  - Stevens-Johnson Syndrome (SJS)
• Drug reaction with eosinophilia and systemic symptoms (DRESS)

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity
  - Hypotension
  - Urticaria
  - Angioedema
  - Acute bronchospasm
  - Conjunctivitis
  - Thrombocytopenia
  - Neutropenia
• Influenza-like illness
  - Weakness
  - Muscle pain
  - Aches
  - Itching
  - Sweats
  - Dizziness
  - Shortness of breath
  - Chest pain
  - Cough
  - Syncope
  - Palpitations
• Pyrexia
• Chills

Others

• Red-orange discolouration of body tissues and/or fluids

• CYP3A4 substrates
• CYP2C8/9 substrates
• Protease inhibitors
• Indinavir
• Darunavir
• Lopinavir
• Saquinavir
• Ritonavir
• Non-nucleoside reverse transcriptase inhibitors
• Rilpivirine
• Nucleoside reverse transcriptase inhibitor
• Zidovudine
• Antifungals
• Itraconazole
• Ketoconazole
• Voriconazole
• Narcotic analgesics
• Methadone
• Alfentanil
• Buprenorphine
• Hypoglycaemic agents
• Repaglinide
• Calcium channel blockers
• Felodipine
• Diltiazem
• Verapamil
• Nifedipine
• Alpha-adrenergic antagonists
• Beta-adrenergic antagonists
• Alfuzosin
• Propranolol
• Ergot alkaloid derivatives
• Ergotamine
• Oral anti-vitamin K anticoagulant
• Warfarin
• Hormonal contraceptives
• Immunosuppressants
• Ciclosporin
• Tacrolimus
• Sirolimus
• Benzodiazepines
• Midazolam
• P-gp substrates
• Digoxin
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Sulfonylureas
• Oral anticoagulants

None routine. Specific cases may require

• Hepatic function 
  - Serum transaminases
  - Bilirubin
• Digoxin levels
  (See additional prescribing points)

Method of administration

• Patients should be informed that adherence to the treatment regimen for rifapentine and other substances is essential for effective treatment, and the importance of not missing any doses must be stressed
• Rifapentine, in combination with isoniazid, should be given with food
• For patients who cannot swallow tablets, the tablets may be crushed and added to a small amount of semi-solid food, all of which should be consumed immediately

Interactions

• Rifapentine is an inducer of CYP3A4 and CYP2C8/9. Concomitant use of rifapentine with other medicines metabolised by these enzymes, may cause a significant decrease in plasma concentrations and loss of therapeutic effect of these medicines
• Interactions with antacids have not been studied. However, in the clinical efficacy study, patients were advised to take rifapentine at least 1 hour before or 2 hours after the ingestion of antacids
• Rifapentine has also been shown to inhibit and to induce P-gp which could modify plasma exposure of digoxin (a P-gp substrate with narrow therapeutic index). Appropriate monitoring and dose adjustment of digoxin may be necessary in case of coadministration with rifapentine

Adverse reactions

• Rifapentine may cause serious hepatic disease/injury
• Patients with abnormal hepatic function tests and/or hepatic disease should only be given rifapentine if no safer alternative is available, and then with caution and under strict medical supervision. In such patients, careful monitoring of hepatic parameters (especially serum transaminases and bilirubin) should be carried out prior to therapy and then every 2 to 4 weeks during therapy
• If there are indications of a liver reaction or if the hepatic condition worsening, rifapentine should be discontinued
• Hepatotoxicity of other antituberculosis medicines (e.g. isoniazid, pyrazinamide) used in combination with rifapentine should also be taken into account 

Rifapentine must always be used in combination with isoniazid as a 12-week once-weekly regimen for the treatment of latent tuberculosis infection

Dosing of isoniazid
- Adults and children>12 years

• The recommended dose of isoniazid is 15mg/kg (rounded to the nearest 50mg or 100mg) up to a maximum of 900mg once-weekly for 12 weeks

- Children 2-11 years

• The recommended dose of isoniazid is 25mg/kg (rounded to the nearest 50mg or 100mg) up to a maximum of 900mg once-weekly for 12 weeks

Rifapentine belongs to the rifamycin class of antibiotics which exert their antibacterial action by selectively inhibiting the DNA-dependent RNA polymerase of susceptible bacteria. It forms a stable complex with bacterial DNA-dependent RNA polymerase, leading to repression of RNA synthesis and cell death. Rifapentine and its 25-desacetyl metabolite accumulate in human monocyte-derived macrophages and are bactericidal to both intracellular and extracellular Mycobacterium tuberculosis organisms at concentrations achievable by the recommended oral dosing regimens. 25-Desacetyl rifapentine, the active metabolite, is almost as active as rifapentine. Rifapentine shows cross-resistance with rifampicin.

Spectrum of activity: Mycobacterium tuberculosis

Film-coated tablet 150mg

• Priftin (Sanofi Aventis) originator