Tenofovir Disoproxil Fumarate

Registered South African indications:

• HIV-1 infection

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients

Cautions

• Breastfeeding
• Moderate to severe renal impairment
• Hepatic impairment
• Elderly
• Cirrhosis
• Hepatitis B co-infection
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption

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

HIV infection
HIV infected pregnant women
Chronic hepatitis B

• Oral (tab): 300mg, dly

In HIV infected women: In combination with emtricitabine (or lamivudine) and efavirenz

Hepatitis B: Discontinue treatment when

•  HBeAG-positive patients: 12 months after HBeAg seroconversion and in association with persistently normal ALT levels and undetectable HBV DNA levels
• HBeAg-negative patients: long term therapy unless HBsAg seroconversion is achieved
• Cirrhotic patients: lifelong treatment

Unbooked pregnant women diagnosed at labour

• Oral (tab): 300mg as single dose

See EML: Care of HIV infected pregnant women

Taken in combination with emtricitbine (or lamivudine) and efavirenz (or nevirapine) 

HIV post exposure prophylaxis

• Oral (tab): 300mg, dly; Treatment duration: 4 weeks

In combination with emtricitabine OR lamivuding OR zidovudine  AND lamivudine AND atazanavir/ritonavir OR lopinavir/ritonavir

See EML: HIV prophylaxis

Do not use as monotherapy

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

HIV infection

< 40kg

• No suitable preparation available in SA  

Older than 15 years and > 40kg

• See adult dosage

Do not use as monotherapy

Consult HIV/infectious disease specialists prior to any decisions related to ARV regimen termination/switch

Pregnancy

• Compatible
• A large amount of data on pregnant women (more than 1,000 pregnancy outcomes) indicate no malformations or foetal/neonatal toxicity associated with tenofovir disoproxil. Animal studies do not indicate reproductive toxicity. The use of tenofovir disoproxil may be considered during pregnancy if necessary

Breastfeeding

• Caution
• Tenofovir has been shown to be excreted in human milk. There is insufficient information on the effects of tenofovir in newborns/infants
• As a general rule, it is recommended that HIV and HBV infected women do not breastfeed their infants in order to avoid transmission of HIV and HBV to the infant
• South African HIV guidelines strongly recommend exclusive breastfeeding for the first 6 months, after which the nutritional needs of the child will require the introduction of complementary foods, while breastfeeding continues
• Mothers failing second or third line regimens should not breastfeed, provided the mother fulfils the AFASS (affordable, feasible, acceptable, sustainable and safe) criteria

Renal Impairment

• CrCl >50ml/min: No dose adjustment recommended
• CrCl ≤50ml/min: Caution; dose adjustment recommended
  Avoid use

Hepatic Impairment

• Caution; no dose adjustment recommended
  In patients with chronic hepatitis B with or without HIV co-infection; Close monitoring for evidence of exacerbation of hepatitis is recommended

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Dizziness
• Headache

Gastrointestinal Disorders

• Diarrhoea
• Nausea and vomiting
• Abdominal pain
• Abdominal distension
• Flatulence
• Pancreatitis

Hepatobiliary Disorders

• Increased transaminases
• Hepatic steatosis
• Hepatitis

Genitourinary Disorders

• Increased creatinine
• Proximal renal tubulopathy
• Acute renal failure
• Renal failure
• Acute tubular necrosis
• Nephritis
• Nephrogenic diabetes insipidus

Endocrine and Metabolic Disorders

• Hypophosphataemia
• Hypokalaemia
• Lactic acidosis

Musculoskeletal Disorders

• Rhabdomyolysis
• Muscular weakness
• Osteomalacia 
• Myopathy

Skin and Subcutaneous Tissue Disorders

• Rash
• Angioedema

Others

• Asthenia
• Fatigue

• Adefovir 
• Didanosine
• Medicinal products that reduce renal function
• OAT1 substrates
• OAT3 substrates
• MRP4 substrates
• Nephrotoxic medicinal products
• Tacrolimus
• Hepatitis C virus antiviral agents
• Atazanavir
• Lopinavir/ritonavir

• Full blood count
• Renal function - before initiation, 1 month, 2 month, 3 month, 6 monthly thereafter

Specific cases may require

• Lactate levels
• Bone density
• Hepatic function

Tenofovir disoproxil fumarate, a prodrug, is converted to tenofovir. Tenofovir is a nucleotide reverse transcriptase inhibitor (NRTIs).  It is an analogue of the naturally occurring deoxynucleotides required to synthesize the viral DNA. Tenofovir inhibits HIV-1 reverse transcriptase and the HBV polymerase by direct binding competition with the natural deoxyribonucleotide substrate and, after incorporation into DNA, by DNA chain termination.

Tablet 300mg

• Adco Tenofovir (Adcock)
• Aspen Tenofovir (Pharmacare)
• Cipla Tenofovir (Cipla)
• Hetero Tenofovir (Hetero)
• Ricovir (Mylan)
• Riovex 300 Macleods Pharmaceuticals
• Sonke Tenofovir fct (Ranbaxy)
• Tenofovir Winthrop (Winthrop) (Discontinued: 11/06/2018)
• Viread (Pharmacare)
• Zefin (Novagen)

COMBINATION PREPARATIONS

Emtricitabine/  Tenofovir Disoproxil Fumurate

Tablet 200mg/300mg

• Adco Emtevir (Adcock)
• Didivir (Cipla)
• Emtewin (Winthrop)
• Emtroc (Macleods)
• Hetemcit (Hetero)
• Temecit (Adcock)
• Tencitab (Pharmacare)
• Tenemcom (Specpharm)
• Tenemine (Mylan)
• Truvada (Pharmacare)
• Tyricten (Novagen)

Lamivudine/ Tenofovir Disoproxil Fumurate

Tablet 300mg/300mg

• Cipla Lamivudine & Tenofovir (Cipla)

Efavirenz/ Emtricitabine/ Tenofovir Disoproxil Fumurate

Tablet 600mg/200mg/300mg

• Atenef (Sonke)
• Atreslawin (Sanofi)
• Atripla (MSD) originator
• Atroiza (Mylan)
• Citenvir (Novagen)
• Odimune (Cipla)
• Rizene (Adcock)
• Trenvir (Cipla)
• Tribuss (Pharmacare)
• Triolar (Macleods)
• Trivenz (Adcock)
• Truno 600/200/300 (Aurobindo)

Efavirenz/ Lamivudine/ Tenofovir Disoproxil Fumurate

Tablet 600mg/300mg/300mg

• Arion (Novagen)
• Eflaten (Mylan)
• Tenarenz (Pharmacare)
• Virlaten (Sandoz)