Terlakiren

Summary

Terlakiren (CP-80,794) is an orally active peptidomimetic renin inhibitor developed in the early 1990s by Pfizer. It demonstrated effective RAAS blockade in early clinical trials for hypertension but was ultimately discontinued due to poor oral bioavailability and pharmacokinetic limitations compared to competing agents. It never reached regulatory approval.

Mechanism of Action

Competitive inhibitor of renin, the rate-limiting enzyme in the renin-angiotensin-aldosterone system (RAAS). Blocks cleavage of angiotensinogen to angiotensin I, reducing downstream production of angiotensin II and aldosterone, thereby lowering blood pressure.

Routes of Administration

Goals & Uses

• Antihypertensive effectCardiovascularModerate
• RAAS blockadeMechanistic/pharmacodynamicModerate

Contraindications

• Hypersensitivity to renin inhibitors or peptidomimeticsImmunologicHigh
• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• Bilateral renal artery stenosisVascular/RenalHigh

Adverse Effects

• Gastrointestinal disturbancesGastrointestinalUnknown
• HypotensionCardiovascularUncommonLow blood pressure
• Renal impairmentRenalUncommon

Drug Interactions

• Angiotensin Receptor Blockers (ARBs)Moderate
• ACE inhibitorsModerate
• Potassium-sparing diureticsModerate

Population Constraints

• Pregnant womenReproductiveAbsolute
• Patients with severe renal impairmentOrgan ImpairmentRelative
• Volume-depleted patientsCardiovascularRelative

Regulatory Status

• European UnionUnapprovedNo EMA approval sought or granted.
• United StatesUnapprovedNever submitted for or granted FDA approval. Development discontinued in the mid-1990s.
• United KingdomUnapprovedNo regulatory approval in the UK.

Never approved by any regulatory agency. Development was discontinued by Pfizer in the mid-1990s. Superseded by later small-molecule renin inhibitors such as aliskiren, which achieved regulatory approval.

Evidence & Sources

No sources recorded yet.