Selective Endothelin-A Receptor Antagonist (Diabetic Nephropathy) Pregnancy: Contraindicated in pregnancy. 'Based on data from animal reproductive toxicity studies, VANRAFIA may cause fetal harm, including birth defects and fetal death, when administered to a pregnant patient and is contraindicated during pregnancy.' There are no available data on use in pregnancy; exclude pregnancy before initiation, advise effective contraception before, during and for two weeks after discontinuation, and discontinue as soon as possible when pregnancy is detected (US label §8.1, §5.1).

Atrasentan

Brand names: Zenaro

Atrasentan is a selective endothelin receptor antagonist investigated for reducing proteinuria in chronic kidney disease, including IgA nephropathy and diabetic kidney disease.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 0.75 mg

Route: Oral, with or without food. 'Swallow tablets whole. Do not cut, crush, or chew.'

Frequency: Once daily

SOURCE: no UK SPC (eMC) record was fetched for this drug (providers.emc is null). The dose above is from the US prescribing information for VANRAFIA (atrasentan), Novartis Pharmaceuticals Corporation, label date 2026-06-12 (https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=48384e66-f6ff-4b6e-81e2-0a7ac05e8627) — verify against UK labelling before use. VERBATIM §2.2: 'The recommended dose of VANRAFIA is 0.75 mg administered orally once daily with or without food.' Only one tablet strength is listed (§3: 0.75 mg film-coated tablet). BEFORE STARTING (§2.1): 'Exclude pregnancy before initiating VANRAFIA' — VANRAFIA is contraindicated in pregnancy; advise effective contraception before, during, and for two weeks after discontinuation of treatment. MISSED DOSE: 'If a dose or doses are missed, take the prescribed dose at the next scheduled time. Do not double the dose to make up for a missed dose.' MONITORING (§5.2): obtain liver enzyme testing before initiating and repeat during treatment as clinically indicated. INDICATION CONTEXT: the safety population described in the label is adults with IgA nephropathy (IgAN) studied in ALIGN (NCT04573478) — consistent with the renal page. No renal-impairment dose adjustment and no maximum dose were stated in the fetched sections. §5, §6.1 and §8.1 text was truncated at the source-fetch limit.

Dose auto-extracted from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Pregnancy — 'Use of VANRAFIA is contraindicated in patients who are pregnant' (§4.1)
Hypersensitivity — 'contraindicated in patients with a history of a hypersensitivity reaction to atrasentan or any component of the product' (§4.2)

Side effects

Most common adverse reactions (incidence ≥ 5%): peripheral oedema and anaemia
Fluid retention (§5.3)
Hepatotoxicity — 'Asymptomatic and transient transaminase elevations have been observed with VANRAFIA'; some endothelin receptor antagonists have caused elevations of aminotransferases, hepatotoxicity and liver failure (§5.2)
Decreased sperm counts (§5.4, §8.3)
Embryo-fetal toxicity (§5.1)

Interactions

Strong or moderate CYP3A inducers — avoid concomitant use; atrasentan is a CYP3A substrate and concomitant use is expected to decrease atrasentan exposure, which may reduce efficacy (§7.1)
OATP1B1/1B3 inhibitors — avoid concomitant use; atrasentan is an OATP1B1/1B3 substrate and concomitant use increases atrasentan exposure, which may increase the risk of adverse reactions (§7.1)

Clinical monograph

How it works

It selectively blocks the endothelin A receptor, reducing endothelin-1-mediated vasoconstriction, mesangial proliferation and glomerular injury, thereby lowering proteinuria.

Prescribing in practice

Endothelin receptor antagonists carry a class risk of fluid retention and oedema, which can precipitate or worsen heart failure.
This class is teratogenic, so pregnancy must be excluded and effective contraception used.
It is generally used as an adjunct to standard renin-angiotensin system blockade rather than as monotherapy.

Monitoring

Monitor for fluid retention, weight gain and signs of heart failure, along with proteinuria and renal function.

Counselling the patient

Report rapid weight gain, ankle swelling or breathlessness promptly.
Effective contraception is essential because of the risk of harm to a pregnancy.
Continue your other kidney-protective medicines as directed.

Evidence & guidelines

Endothelin receptor antagonists have shown reductions in proteinuria in chronic kidney disease in clinical trials, with cardiovascular safety guiding their use.

Reference: Heerspink et al. Lancet 2019 (SONAR trial); MHRA conditional approval SPC Zenaro 2024; KDIGO Diabetic Kidney Disease Guidelines 2022; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways