Felypressin

Summary

Felypressin is a synthetic nonapeptide vasopressin analogue used as a vasoconstrictor in combination with the local anaesthetic prilocaine (often marketed as Citanest with Octapressin). It is prescribed for local infiltration in procedures such as cervical biopsy, loop excision of the cervix, and dental extractions, where it helps reduce procedural pain and limits bleeding.

Mechanism of Action

Felypressin acts on vasopressin V1 receptors, producing smooth‑muscle contraction in blood vessels and the uterus. The resulting vasoconstriction limits local blood flow, prolonging the effect of the co‑administered anaesthetic and reducing bleeding. Its oxytocic activity, also mediated via V1 receptors, can stimulate uterine contractions, which underlies its contraindication in pregnancy.

What the Research Shows

Randomised trials have shown that intracervical injection of prilocaine with felypressin markedly lowers pain scores during cervical punch biopsy and loop excision, abolishing severe pain and reducing moderate pain to under 7 % of participants. In a dental study, the prilocaine‑felypressin mix increased sympathetic activity (higher LF/HF ratio) compared with lidocaine‑epinephrine, while both regimens raised systolic pressure during extraction. A cervical excision trial reported fewer side‑effects such as faintness and shaking with felypressin versus lignocaine‑adrenaline, though blood loss was slightly higher. A Cochrane review found no difference in analgesic efficacy between felypressin‑prilocaine and lidocaine‑adrenaline, with low‑quality evidence supporting its use. Systematic safety reviews flag felypressin as contraindicated in pregnancy because of its uterine‑contracting properties. Immunological studies suggest the felypressin‑prilocaine combination can modulate neutrophil and macrophage functions, but clinical relevance remains unclear.

Reported Benefits

Evidence from controlled trials indicates that felypressin, when combined with prilocaine, provides effective pain relief for cervical procedures, often eliminating severe pain. Compared with lignocaine‑adrenaline, it is associated with fewer subjective side‑effects such as faintness and shaking, making it a preferred option for some gynecological surgeries. Its vasoconstrictive action also helps limit local bleeding, though not as effectively as adrenaline in all settings.

Limitations of the Evidence

The clinical data are limited to relatively small, procedure‑specific trials, many of which are of low methodological quality. Comparative effectiveness against other vasoconstrictors shows mixed results, with some studies noting higher sympathetic activation and slightly greater blood loss. No large‑scale safety data exist beyond pregnancy‑related contraindications, and the immunomodulatory findings are pre‑clinical. Consequently, broader generalisation of benefits remains uncertain.

Safety Considerations

Felypressin’s vasoconstrictive and oxytocic actions raise concerns for uterine contraction, leading to a contraindication in pregnancy. Reported side‑effects include faintness, shaking, and increased sympathetic tone during dental extraction. No serious adverse events were recorded in the cited trials, but autonomic changes and potential impacts on natural immunity have been observed in laboratory studies. Caution is advised in patients with cardiovascular instability or those at risk of uterine hyperstimulation.

How It Is Administered

Felypressin is supplied as a vasoconstrictor component of a prilocaine solution (e.g., Citanest with Octapressin). It is administered by subcutaneous or submucosal injection, typically directly into the tissue to be treated—such as intracervical injection for gynecologic procedures or infiltration for dental extractions. The formulation is a sterile aqueous solution intended for single‑use injection.

Routes of Administration

Goals & Uses

• Prolongation of local anaesthesiaAnaesthesiaHigh
• Safe vasoconstriction in patients with cardiovascular contraindications to adrenalineCardiovascular Risk ReductionModerate
• Control intra‑operative bleedingSurgicalModerate
• Haemostasis in dental proceduresSurgical HaemostasisModerate
• Prolong local anesthetic effectAnestheticModerate

Contraindications

• Raynaud's disease / peripheral vascular diseaseVascularModerate
• PregnancyPopulationModeratePotential fetal risk or insufficient safety data
• Severe cardiovascular diseaseCardiovascularModerate
• Known hypersensitivity to felypressin or vasopressin analoguesAllergy / ImmunologyHigh
• Severe hypertensionCardiovascularHigh

Adverse Effects

• Hypersensitivity / allergic reactionImmunologicalRare
• Uterine contractionsObstetricUnknown
• HypertensionCardiovascularCommonHigh blood pressure
• HeadacheNeurologicCommonPain in the head or upper neck
• Local tissue ischaemiaVascularUncommon
• TachycardiaCardiovascularUncommonAbnormally fast heart rate
• Pallor at injection siteVascularCommon
• BradycardiaCardiovascularRare

Drug Interactions

• Other vasopressors / vasoconstrictorsModerate
• Tricyclic antidepressantsLow
• OxytocinHigh
• MAO inhibitorsHigh
• EpinephrineModerate

Population Constraints

• Elderly patients with cardiovascular diseaseCardiovascularRelative
• Pediatric patients (<12 y)AgeRelative
• Patients with renal impairmentOrgan ImpairmentRelative
• Paediatric patientsAgeRelative
• Patients with severe hypertensionCardiovascularRelative
• Pregnant womenReproductiveAbsolute

Regulatory Status

• European UnionUnapprovedNo centralized marketing authorization
• United StatesUnapprovedNot FDA‑approved; used off‑label in dentistry
• BRApprovedApproved: local dental anesthesiaApproved for use as vasoconstrictor in Brazil
• United KingdomApprovedApproved: Vasoconstrictor in dental local anaesthetic formulations (e.g., prilocaine 3% with felypressin 0.03 IU/mL)Available as Citanest with Octapressin; licensed for dental use.

Approved and in clinical use in the UK, EU, and various other countries as a component of dental local anaesthetic formulations. Not widely approved or marketed in the United States. Regulatory status varies by jurisdiction.

Evidence & Sources

• A double-blind, randomized, placebo-controlled trial of prilocaine and felypressin (Citanest and Octapressin) for the relief of pain associated with cervical biopsy and treatment with the Semm coagulator
  Journal ArticleModerateDuncan ID, et al.2005-01-01T00:00:00.000000Z
• Difference in the Effects of Lidocaine With Epinephrine and Prilocaine With Felypressin on the Autonomic Nervous System During Extraction of the Impacted Mandibular Third Molar: A Randomized Controlled Trial
  Journal ArticleModerateYamashita K, et al.2020-01-01T00:00:00.000000Z
• A comparison of the side effects of prilocaine with felypressin and lignocaine with adrenaline in large loop excision of the transformation zone of the cervix: results of a randomised trial
  Journal ArticleModerateHowells RE, et al.2000-01-01T00:00:00.000000Z
• Review of the Safety and Clinical Considerations of Vasoconstrictor Agents in Dental Anesthesia During Pregnancy
  Journal ArticleModerateUrîtu A, et al.2025-01-01T00:00:00.000000Z
• Immunological modulation by lidocaine-epinephrine and prilocaine-felypressin on the functions related to natural immunity in neutrophils and macrophages
  Journal ArticleModerateAzuma Y, Ohura K2004-01-01T00:00:00.000000Z
• Pain relief for women with cervical intraepithelial neoplasia undergoing colposcopy treatment
  Journal ArticleHighGajjar K, et al.2016-01-01T00:00:00.000000Z

Frequently Asked Questions