Patient Group Direction (PGD) for the administration of norethisterone 5mg tablets for period delay

1. Clinical condition or situation to which the direction applies

Indication

• Norethisterone 5mg tablets are indicated for the postponement of menstruation.

Objectives of care

• To temporarily postpone menstruation based on the patient’s needs.

Inclusion criteria

• Valid consent has been obtained from the patient/carer who does not want to consult with their GP and would prefer to access treatment from the PGD user.

• Patients from 16 years of age.

• Patients who wish to delay their period for a particular situation, such as holidays, exams, weddings etc.

Exclusion criteria

(Refer to current and relevant SmPC (Great Britain or Northern Ireland) and online British National Formulary (BNF) guidance for additional details)

• Patients for whom no valid consent has been received.

• Hypersensitivity to the active substance(s) or to any of the excipients or trace residuals in the selected product of norethisterone 5mg tablets. See section 2 and 6.1 of the relevant Summary of Product Characteristics (SmPC).

• Patients under 16 years of age.

• Known or suspected pregnancy.

• Women of childbearing potential who are not willing to take measures to avoid pregnancy (e.g. by using barrier contraception) during treatment.

• Breast-feeding patients.

• Patients taking medications that would contraindicate the supply of norethisterone 5mg tablets (see Product interactions).

• Male patients.

  Patients with:

• Previous idiopathic or current venous thromboembolism (deep vein thrombosis, pulmonary embolism).

• Active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction), or those at high risk of venous or arterial thrombosis.

• Presence or a history of prodromi of a thrombosis (e.g. transient ischaemic attack, angina pectoris).

• History of migraine with focal neurological symptoms.

• Diabetes mellitus with vascular involvement.

• Disturbance of liver function or jaundice.

• Previous or existing liver tumours (benign or malignant).

• Known, past or suspected sex hormone-dependent malignancies, including breast cancer.

• History during pregnancy of idiopathic jaundice, severe pruritus or pemphigoid gestationis.

• Undiagnosed genital bleeding.

• Endometrial hyperplasia.

• Porphyria.

• Papilloedema or retinal vascular lesions.

• Hypertension.

• Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

• Patients with severe depression, generalized anxiety disorder, psychosis, schizophrenia, suicide attempts, suicidal thoughts, self-endangering behaviour or any other psychiatric disorder.

• Patients with prolonged immobilisation.

1. Clinical condition or situation to which the direction applies – continued

Cautions

(including any relevant action to be taken)

Adverse reactions

• Therapy should be discontinued if the following occur (1) (2) (3):

  ̵ Jaundice or deterioration in liver function

  ̵ Significant increase in blood pressure

  ̵ New onset of migraine-type headache or more frequent occurrence of unusually severe headaches

  ̵ Pregnancy

  ̵ Sudden perceptual disorders (e.g. disturbances of vision or hearing)

  ̵ First signs of thrombophlebitis or thromboembolic symptoms

• Norethisterone should be withdrawn immediately if venous thromboembolism (VTE) develops in the patient. Patients should be advised to contact their doctor immediately if they become aware of a potential thromboembolic symptom, including (1) (2) (3):

  • Painful swelling in the leg

  • Sudden pain in the chest

  • Dyspnoea

• Any patient who develops an acute impairment of vision, proptosis, diplopia or migraine headache should be referred for an ophthalmology evaluation to exclude papilloedema or retinal vascular lesions (1) (2) (3).

• Liver tumours have been reported in users of hormonal substances such as the one contained in norethisterone. If severe upper abdominal complaints, liver enlargement or signs of intra-abdominal haemorrhage occur, discontinue treatment and refer the patient to their GP (1).

  Pregnancy

• If menstrual bleeding should fail to follow a course of norethisterone, the possibility of pregnancy must be excluded before a further course is given (1) (2) (3).

  Surgery

• Where prolonged immobilisation is likely to follow elective surgery, particularly abdominal or orthopaedic surgery to the lower limbs, consideration should be given to stopping norethisterone treatment 4-6 weeks pre-operatively. Treatment should not be

restarted until the patient is fully remobilised (1) (2) (3).

1. Clinical condition or situation to which the direction applies – continued

Cautions

(including any relevant action to be taken)

Combined oral contraceptives

• As partial metabolisation of norethisterone to ethinylestradiol has been observed, similar pharmacological effects as combined oral contraceptives (COCs) may occur. Therefore, precautions associated with the use of COCs should also be considered (1). Thromboembolism

• Personal or strong family history of thromboembolism or recurrent spontaneous abortion should be investigated to exclude a thrombophillic predisposition. Until a thorough evaluation of thrombophillic factors has been made, the use of norethisterone is contraindicated (1) (2) (3).

• Risk of venous thromboembolism (VTE). Risk factors for VTE include a personal history or family history, obesity (BMI >30 kg/m2), systemic lupus erythematosus and patients being treated with steroid hormones. The risk of VTE may be temporarily increased with prolonged immobilisation, major trauma or major surgery (1) (2) (3).

• The risk of thromboembolic events may also be increased by the presence of other predisposing factors such as smoking, dyslipoproteinaemia, hypertension, diabetes and increasing age (over 35 years) (1).

  Concomitant conditions

• Treatment is not recommended when administering norethisterone in patients with conditions which might be aggravated by fluid retention (1) (2) (3):

  ̵ Epilepsy

  ̵ Migraine

  ̵ Asthma

  ̵ Cardiac dysfunction

  ̵ Renal dysfunction

• Individuals with a history of chloasma should minimise exposure to the sun or ultraviolet radiation when taking norethisterone (1).

  Other considerations

• Healthcare professionals must not delegate their responsibility and have the right to refuse treatment to eligible patients based on their own clinical judgement.

• Where there is doubt, treatment should not be initiated until the patient has sought

advice from the appropriate healthcare professional.

1. Clinical condition or situation to which the direction applies – continued

Product interactions

• Prior to supply and where indicated, medication that the patient is using should be checked for product interactions using the British National Formulary (BNF) and SmPC. This includes checking that the patient’s medication does not suggest conditions that are excluded from treatment under this PGD.

• Norethisterone is not recommended for patients taking anticoagulants, and the risks and benefits of norethisterone should be carefully considered (1) (2) (3).

• Concurrent administration with other sex hormones is not recommended, as it may affect treatment (1).

• Concurrent administration with a contraceptive pill or hormone injections is not recommended.

• The metabolism of progestogens may be increased by concomitant administration of compounds known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes (e.g. anticonvulsants and anti-infectives). Therefore, concurrent administration is not recommended (2) (3).

• Concurrent administration with antiviral medicines to treat HIV (e.g. ritonavir, nelfinavir) is not recommended (1) (2) (3).

• Herbal preparations containing St John’s Wort (Hypericum perforatum) are not recommended to taken whilst on norethisterone treatment (2) (3).

• Concurrent administration of norethisterone and ciclosporin (for suppressing the immune system) is not recommended (1).

• Aminoglutethimide has been reported to decrease plasma levels of some progestogens, hence concurrent administration with norethisterone is not recommended (2) (3).

• Concurrent administration with other drugs which also cause fluid retention (e.g. NSAIDs and vasodilators) are not recommended (2) (3).

• Norethisterone may reduce the haematological toxicity of chemotherapy (2) (3).

Action if patient is excluded from the service

• Discuss with patient and document the reasons for exclusion from treatment under the PGD.

• If the patient has consented, refer them to their GP and/or inform their GP.

• Signpost to other services if appropriate.

• Document the reasons for exclusion and any action taken, in the patient’s medication

  record.

• When treatment is postponed reschedule as appropriate.

Action if patient declines the service

• Ensure patient/carer fully understands the risks of declining the service.

• Advise the patient/carer about the benefits of the service.

• Refer patient to GP if appropriate.

• Document the reasons for declining the service and any action taken, including advice given to the patient.

• Reschedule treatment if appropriate.

• Explain NHS eligibility for this service where appropriate.

2. Description of treatment

Name, strength & formulation of drug

Supplier

Name of product

Composition

Pharmaceutical

form

Excipients

Age indications

Bayer plc

*Primolut N®

5 milligrams of norethisterone

Tablet

• Lactose

• Maize starch

• Magnesium stearate

16 years and over

Pfizer Ltd

*Utovlan®

5 milligrams of norethisterone

Tablet

• Maize starch

• Polyvidone

• Magnesium stearate

• Lactose monohydrate

16 years and over

Wockhardt UK Ltd

*Norethisterone

5 milligrams of norethisterone

Tablet

• Lactose

• Maize starch

• Magnesium stearate

16 years and over

• *Any appropriate 5mg norethisterone tablets can be supplied under this PGD (excipients may vary).

• For a full list of excipients, see section 2 and 6.1 of the relevant SmPC.

Legal status

• POM – Prescription Only Medicine

Dose/dose range

• One 5mg tablet (1) (2) (3).

Use of PGD outside terms of SmPC

• This PGD covers treatment in England, Scotland, Wales and Northern Ireland. Please note that Northern Ireland may have a separate SmPC from Great Britain and guidance may differ. Please refer to the relevant SmPC for more information.

• Although healthcare professionals have the right to refuse treatment even where a

patient is eligible, they cannot override PGD exclusions.

Route/method of

administration

• For oral administration (1) (2) (3).

Frequency of administration

• One tablet three times daily, starting three days before the expected onset of menstruation (1) (2) (3).

• Menstruation usually follows within three days of finishing the treatment (1) (2) (3).

Quantity to supply

• A sufficient quantity of tablets should be supplied to cover the treatment period.

• A maximum supply of 17 days treatment can be provided.

Follow up / minimum or maximum period

• The treatment should start 3 days before the expected onset of menstruation and continued for no longer than 10 to 14 days (1).

• Norethisterone 5mg tablets can be used to delay your period by up to 14 days in any 6-month period.

• Women who wish to delay their period more than once every 6 months should

consult their GP.

3. Further aspects of treatment

Adverse reactions and their management

• Follow local SOP on adverse reactions and their management.

• Very common (≥1/10) or common (≥1/100 to <1/10) side effects include: Menstrual cycle irregularities (4).

• Uncommon side effects include (≥ 1/1,000 to < 1/100): Breast tenderness (4).

• Frequency of side effects not known: Hepatic cancer, thromboembolism, appetite change, depression, fatigue, gastrointestinal disorder, headaches, hypertension, libido disorder, nervousness, rash and weight change (4).

• For a comprehensive list of all warnings, cautions and potential adverse reactions, refer

to the current BNF and SmPC (Great Britain or Northern Ireland).

Reporting procedure of adverse reactions

• Report to GP if appropriate & document in patient’s medication records.

• Follow local SOP for reporting of adverse events.

• All suspected adverse reactions must be reported via the Yellow Card scheme to the MHRA or on the website at https://yellowcard.mhra.gov.uk/

• An adverse reaction should be reported even if it is not certain that the medicine has caused it, if it is well recognised, or if other drugs were given at the same time.

• Further information is available online from https://yellowcard.mhra.gov.uk/

Advice to patient / carer

Patient information

• Provide a patient information leaflet and discuss as required.

• Provide advice on & explain potential warnings & side effects and request to report them if they occur.

• Advise on possible side effects and their management. If the symptoms persist, or the patient experiences other severe symptoms then they should be advised to contact their GP, call NHS 111 or visit A&E.

• Advise patients if menstrual bleeding should fail to follow a course of norethisterone, they should not take any more until they are certain they are not pregnant (1) (2) (3).

• Women of childbearing potential must be advised to use barrier contraception for the duration of treatment.

• Patients should contact the health care professional if they start taking any new medical products that may be contraindicated with norethisterone.

  Adverse reactions

• Any patient who develops an acute impairment of vision, proptosis, diplopia or migraine headache should be advised to contact the supplier and stop taking norethisterone (1) (2) (3).

• Patients should stop treatment immediately if venous thromboembolism (VTE) develops. Potential thromboembolic symptoms include (1) (2) (3):

  ̵ Painful swelling in the leg

  ̵ Sudden pain or tightness in the chest

  ̵ Dyspnoea

• Patients should be advised to discontinued treatment immediately and seek medical advice from their doctor, if the following occur (1) (2) (3):

̵ New onset of migraine-type headaches or more frequent occurrence of unusually severe headaches

̵ Sudden perceptual disorders (e.g. disturbances of vision or hearing)

̵ First signs of thrombophlebitis or thromboembolic symptoms (listed above)

̵ Pending operations (six weeks beforehand), immobilisation (e.g. after accidents)

̵ Onset of jaundice or deterioration in liver function, anicteric hepatitis, general pruritus

̵ Significant increase in blood pressure

̵ Suspected pregnancy

3. Further aspects of treatment – continued

Records to be kept

• In all cases manual records including any risk assessment forms or computerised records should include:

  ̵ Patient’s name, address and date of birth;

  ̵ Name of supplier;

  ̵ Dose, site and route of administration;

  ̵ Date of administration/supply;

  ̵ Brand name, batch number & expiry date of product;

  ̵ Confirmation that there are no contraindications; that side effects have been discussed; support literature given (if applicable) and any other advice given;

  ̵ That valid informed consent was given prior to administration/supply;

  ̵ Signature and printed name and designation (in black ink) for paper records. For computer records, ensure data authentication of practitioner delivering care;

• GP may be notified, so long as the patient has consented for personalised information to be shared. Pharmacy/clinic records should be stored in line with relevant legislation and local policies. Generally, records should be kept for 8 years in adults and until 25 years of

age in children.

3. Further aspects of treatment – continued

Additional facilities / requirements

• Medication supplied using this PGD must be labelled with the same labelling requirements which patients would otherwise have received if the medicine had been supplied against a prescription and indicate in the patient’s medication record that the medicine was supplied via a PGD.

• Access to medical support (this may be via telephone).

  PGD user must:

• Be familiar with and have online access to the most recent information regarding norethisterone 5mg tablets, such as information from the product SmPC and the BNF.

• Be able to assess the patient’s capacity to understand the nature and purpose of the

  supply in order for the patient to give or refuse consent.

• Be aware of current clinical recommendations and be able to undertake supply and discuss any issues that may arise.

• Have been trained in the delivery of this medicine covered by this PGD.

• Maintain their skills, knowledge and their own professional level of competence in this area according to their individual code of professional conduct.

• Possess appropriate professional indemnity.

• Agree to work within the terms of the implementing PGD.

• Be aware of medicine handling, storage and supply guidelines.

• Have an SOP for providing a private PGD service at the pharmacy/clinic, with the appropriate procedures and policies in place, including consent, record keeping, competency and training requirements.

  The superintendent/clinical lead of the implementing pharmacy/clinic will be responsible for:

• Providing adequate up-to-date clinical resources.

• Ensuring that staff using the PGD, have access to up-to-date resources.

• Ensuring that staff have received adequate training in all areas relevant to this PGD.

  Requirements for Continuing Professional Development (CPD)

• All staff involved in the implementation of this PGD should participate in adequate and appropriate CPD to ensure procedures follow the most up to date clinical guidance. Facilities and supplies to be available

• Consultations carried out under the authorisation of this PGD should be completed in a private space, physically closed off from interruption such as a pharmacy consultation room, in order to ensure patient confidentiality.

• The following should be available:

  1. Safe storage areas for medicines and equipment

  2. Clean and tidy clinical rooms that allow confidentiality and patient privacy

  3. Copies of the current PGD

  4. Access to a current BNF and relevant SmPC

     Audit

• All health risk assessment, advice and medicine supply record forms should be stored in the pharmacy/clinic and will be audited by the implementing pharmacy/clinic in order to analyse service delivery. If the service is deemed insufficient, management staff, the superintendent/clinical lead and implementing healthcare professional will be informed

and an action plan drawn up to remedy the service.

3. Further aspects of treatment – continued

Consent

• Prior to the administration and/or supply of a medicine, consent must be obtained, preferably written, from the patient, and documented either in the patient’s medical records/notes or on an administration form.

  The key points include:

• If a patient’s fitness and suitability cannot be established, supply should be deferred.

• There is no legal requirement for consent to be in writing but written consent serves to record the decision and the discussions that have taken place.

• Consent - either written or verbal - is required at the time of each supply.

• Consent remains valid unless the patient who gave it withdraws it. If there is new information between the time consent was given and when the supply is offered, including new evidence of risk, new medicines becoming available or where there is a significant change in the patient’s condition, it may be necessary for the patient to reconfirm their consent.

• Written and verbal information should be available in a form that can be easily understood by the person who will be giving the consent. Where English is not easily understood, translations and properly recognised interpreters should be used in order that they can make informed consent.

• The attendance of a patient for the supply/administration of treatment after an invitation to attend for this purpose may be viewed as acceptance that the patient may have the treatment/administration.

• Patients should also be informed about how data on the supply will be stored, who will be able to access that information and how that data may be used.

• Where consent is either refused or withdrawn, this decision must be documented.

• Consent obtained before the occasion upon which a patient attends for the

supply/administration is only an agreement for the patient to be included in this instance and does not mean that consent is in place for each future supply/administration.

4. References & Resources

For a comprehensive list of all warnings, cautions and potential adverse reactions, refer to the current BNF and SmPCs.

References

1. Summary of Product Characteristics; Primolut N. emc (Great Britain). [Online] 11 January 2019. [Cited: 27 July 2023.] https://www.medicines.org.uk/emc/product/1135.

2. Summary of Product Characteristics; Utovlan Tablets. emc (Great Britain). [Online] 28 January 2019. [Cited: 27 July 2023.] https://www.medicines.org.uk/emc/product/1717.

3. Summary of Product Characteristics; Norethisterone 5mg Tablets. emc (Great Britain). [Online] 21 February 2017. [Cited: 27 July 2023.] https://www.medicines.org.uk/emc/product/1494/smpc.

4. Norethisterone. BNF; The National Institute for Health and Care Excellence. [Online] [Cited: 27 July 2023.] https://bnf.nice.org.uk/drug/norethisterone.html#interactions.

Additional resources

1. How can I delay my period? NHS. [Online] August 17, 2022. [Cited: July 27, 2023.] https://www.nhs.uk/common-health- questions/travel-health/how-can-i-delay-my-period/.

1. Norethisterone. BNF; The National Institute for Health and Care Excellence. [Online] [Cited: July 27, 2023.] https://bnf.nice.org.uk/drug/norethisterone.html?msclkid=24a91301cf7711ec888213541995996b

2. Patient Group Direction; Medicines practice guideline [MPG2]. National Institute for Health and Care Excellence. [Online] March 27, 2017. [Cited: July 27, 2023.] https://www.nice.org.uk/Guidance/MPG2.

3. Competency framework for health professionals using Patient Group Directions. National Institute for Health and Care Excellence.

[Online] January 4, 2018. [Cited: July 27, 2023.] https://www.nice.org.uk/guidance/mpg2/resources.