Description

Simple

A birth control drug used to prevent pregnancy or as a component of hormone replacement therapy in patients having symptoms of menopause.

Clinical

A synthetic second-generation progestin used for contraception, prevention of endometrial hyperplasia in hormone replacement therapy, and in the treatment of other hormone-mediated illnesses such as endometriosis.

Overview

Norethisterone, also known as norethindrone, is a synthetic progestational hormone belonging to the 19-nortestosterone-derived class of progestins.[8] It is further classified as a second-generation progestin, along with [levonorgestrel] and its derivatives, and is the active form of several other progestins including [norethynodrel] and [lynestrenol].[8] Norethisterone mimics the actions of endogenous [progesterone], albeit with a greater potency,[5] and is used on its own or in combination with estrogen derivatives in a variety of applications including contraception and hormone replacement therapy.[14,15,Read more

Pharmacology

Indication

Norethisterone is indicated as an oral contraceptive when given as monotherapy[14] or in combination with an estrogen component, such as [ethinylestradiol] or [estradiol].[ Read more

Pharmacodynamic

Norethisterone is a synthetic oral progestin used for contraception or to treat other hormone-related conditions such as menopausal symptoms and endometriosis. As a synthetic progestin, norethisterone acts similarly to endogenous progesterone but with a much higher potency - it acts at the pelvic le... Read more

Mechanism of action

On a molecular level, progestins like norethisterone exert their effects on target cells via binding to progesterone receptors that result in downstream changes to target genes.[16] Target cells... Read more

Absorption

The Cmax of norethisterone following oral administration of a single dose ranges from 5.39 to 7.36 ng/mL with a Tmax of 1-2 hours.[14, Read more

Protein binding

Norethisterone is 38% bound to sex hormone-binding globulin and 61% bound to albumin.[ Read more

Volume of distribution

The volume of distribution of norethisterone is approximately 4 L/kg.[ Read more

Clearance

The plasma clearance of norethisterone has been estimated as 0.4 L/hr/kg,[ Read more

Half life

The half-life of norethisterone has been variably estimated as 8-10 hours.[ Read more

Route of elimination

Following administration of radio-labeled norethisterone, slightly more than 50% of the administered dose was eliminated in the urine and 20-40% was eliminated in the feces.[ Read more

Toxicity

The oral LD50 in mice 6 g/kg and the TDLo in human women is 42 mg/kg.[20] There have been no reports of serious ill effects following overdose of oral contraceptives, including following ingestio... Read more

Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Hot Flashes US
  • Kind: experimental
    • Percent: 87
  • Clinical Trial
    Headache US
  • Kind: experimental
    • Percent: 51
  • Clinical Trial
    Metrorrhagia Canada
  • Kind: experimental
    • Percent: 34.3
  • Clinical Trial
    Breast Pain US
  • Kind: experimental
    • Percent: 31
  • Kind: placebo
    • Percent: 7
  • Clinical Trial
    Nausea and vomiting US
  • Kind: experimental
    • Percent: 29
  • Clinical Trial
    Pain US
  • Kind: experimental
    • Percent: 29
  • Clinical Trial
    Emotional Lability US
  • Kind: experimental
    • Percent: 27
  • Clinical Trial
    Breast Pain US
  • Kind: experimental
    • Percent: 25
  • Kind: placebo
    • Percent: 7
  • Clinical Trial
    Dysmenorrhea US
  • Kind: experimental
    • Percent: 21
  • Kind: placebo
    • Percent: 5
  • Clinical Trial
    Dysmenorrhea US
  • Kind: experimental
    • Percent: 20
  • Kind: placebo
    • Percent: 5
  • Clinical Trial
    Headache US
  • Kind: experimental
    • Percent: 20
  • Kind: placebo
    • Percent: 20
  • Clinical Trial
    Headache US
  • Kind: experimental
    • Percent: 18
  • Kind: placebo
    • Percent: 20
  • Clinical Trial
    Asthenia US
  • Kind: experimental
    • Percent: 18
  • Clinical Trial
    Vaginitis US
  • Kind: experimental
    • Percent: 15
  • Clinical Trial
    Altered bowel habit US
  • Kind: experimental
    • Percent: 15
  • Clinical Trial
    Breast Pain US
  • Kind: experimental
    • Percent: 13
  • Clinical Trial
    Sleep Disorder US
  • Kind: experimental
    • Percent: 13
  • Clinical Trial
    Weight Gain US
  • Kind: experimental
    • Percent: 13
  • Clinical Trial
    Vaginitis US
  • Kind: experimental
    • Percent: 13
  • Kind: placebo
    • Percent: 5
  • Clinical Trial
    Rhinitis US
  • Kind: experimental
    • Percent: 13
  • Kind: placebo
    • Percent: 9
  • Clinical Trial
    Menstrual disorder US
  • Kind: experimental
    • Percent: 12
  • Kind: placebo
    • Percent: 2
  • Clinical Trial
    Respiratory disorder US
  • Kind: experimental
    • Percent: 12
  • Kind: placebo
    • Percent: 7
  • Clinical Trial
    Asthenia US
  • Kind: experimental
    • Percent: 12
  • Kind: placebo
    • Percent: 4
  • Clinical Trial
    Dizziness US
  • Kind: experimental
    • Percent: 11
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: 11
  • Kind: placebo
    • Percent: 7
  • Clinical Trial
    Back Pain US
  • Kind: experimental
    • Percent: 11
  • Kind: placebo
    • Percent: 5
  • Clinical Trial
    Pharyngitis US
  • Kind: experimental
    • Percent: 10
  • Kind: placebo
    • Percent: 2
  • Clinical Trial
    Skin reaction US
  • Kind: experimental
    • Percent: 9
  • Clinical Trial
    Neuromuscular Disorder US
  • Kind: experimental
    • Percent: 9
  • Clinical Trial
    Edema US
  • Kind: experimental
    • Percent: 9
  • Clinical Trial
    Injection site reaction US
  • Kind: experimental
    • Percent: 9
  • Clinical Trial
    Sinusitis US
  • Kind: experimental
    • Percent: 9
  • Kind: placebo
    • Percent: 9
  • Clinical Trial
    Sinusitis US
  • Kind: experimental
    • Percent: 4
  • Kind: placebo
    • Percent: 9
  • Clinical Trial
    Rhinitis US
  • Kind: experimental
    • Percent: 7
  • Kind: placebo
    • Percent: 9
  • Clinical Trial
    Depression US
  • Kind: experimental
    • Percent: 5
  • Kind: placebo
    • Percent: 9
  • Clinical Trial
    Depression US
  • Kind: experimental
    • Percent: 3
  • Kind: placebo
    • Percent: 9
  • Clinical Trial
    Pain US
  • Kind: experimental
    • Percent: 4
  • Kind: placebo
    • Percent: 9
  • Clinical Trial
    Pain US
  • Kind: experimental
    • Percent: 6
  • Kind: placebo
    • Percent: 9
  • Clinical Trial
    Flu syndrome US
  • Kind: experimental
    • Percent: 9
  • Kind: placebo
    • Percent: 7
  • Clinical Trial
    Back Pain US
  • Kind: experimental
    • Percent: 9
  • Kind: placebo
    • Percent: 5
  • Clinical Trial
    Nausea and vomiting US
  • Kind: experimental
    • Percent: 8.8
  • Clinical Trial
    Nausea Canada
  • Kind: experimental
    • Percent: 8.7
  • Clinical Trial
    Papanicolaou smear suspicious US
  • Kind: experimental
    • Percent: 8
  • Kind: placebo
    • Percent: 5
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: 8
  • Kind: placebo
    • Percent: 7
  • Clinical Trial
    Asthenia US
  • Kind: experimental
    • Percent: 8
  • Kind: placebo
    • Percent: 4
  • Clinical Trial
    Accidental injury US
  • Kind: experimental
    • Percent: 5
  • Kind: placebo
    • Percent: 8
  • Clinical Trial
    Accidental injury US
  • Kind: experimental
    • Percent: 4
  • Kind: placebo
    • Percent: 8
  • Clinical Trial
    Headaches US
  • Kind: experimental
    • Percent: 7.5
  • Clinical Trial
    GI Disturbance US
  • Kind: experimental
    • Percent: 7
  • Clinical Trial
    Breast enlargement US
  • Kind: experimental
    • Percent: 7
  • Clinical Trial

    Contraindications

    • Route:
      • Transdermal
    • Dose Form:
      • Patch
    • Sex Group: female
    • Regions: US
    • Patient Conditions:
        • Name: Thromboembolic Events
        • Drugbank Id: DBCOND0056086
    • With Drugs:
        • Name: Estradiol
        • Drugbank Id: DB00783
    • Route:
      • Transdermal
    • Dose Form:
      • Patch
    • Sex Group: female
    • Regions: US
    • Patient Conditions:
        • Name: Thrombophilic disorders
        • Drugbank Id: DBCOND0107564
    • With Drugs:
        • Name: Estradiol
        • Drugbank Id: DB00783
    • Route:
      • Oral
    • Dose Form:
      • Tablet
    • Hypersensitivity:
      • true
    • Regions: Canada
    • Route:
      • Oral
    • Dose Form:
      • Tablet
    • Regions: Canada
    • Patient Conditions:
        • Name: Undiagnosed abnormal vaginal bleeding
        • Drugbank Id: DBCOND0107909
    • Route:
      • Oral
    • Dose Form:
      • Tablet
    • Regions: Canada
    • Patient Conditions:
        • Name: Breast Carcinoma
        • Drugbank Id: DBCOND0031124
    • Route:
      • Oral
    • Dose Form:
      • Tablet
    • Regions: Canada
    • Patient Conditions:
        • Name: Malignant Liver Tumour
        • Drugbank Id: DBCOND0123730
        • Modification Of:
          • Condition Stage: malignant
          • Base:
            • Name: Liver Tumour
            • Drugbank Id: DBCOND0046698
    • Route:
      • Oral
    • Dose Form:
      • Tablet
    • Regions: Canada
    • Patient Conditions:
        • Name: Benign Liver Tumour
        • Drugbank Id: DBCOND0123729
        • Modification Of:
          • Base:
            • Name: Liver Tumour
            • Drugbank Id: DBCOND0046698
          • Severity:
            • Includes:
              • benign
    • Route:
      • Oral
    • Dose Form:
      • Tablet
    • Regions: Canada
    • Patient Conditions:
        • Name: Active liver disease
        • Drugbank Id: DBCOND0107507
        • Modification Of:
          • Condition Status: active
          • Base:
            • Name: Liver Disease
            • Drugbank Id: DBCOND0028338
    • Route:
      • Oral
    • Dose Form:
      • Tablet
    • Regions: Canada
    • Patient Conditions:
        • Name: Pregnancy
        • Drugbank Id: DBCOND0018394

    Food Interactions

    Take with or without food. Co-administration with food slightly alters pharmacokinetics, but not to a clinically significant extent.