Missed Dose Management

Introduction

The vast majority of patients occasionally miss a dose of their medication. Hence, it seems logical to counsel patients on what to do about a missed dose at the time of dispensing.



General Advice

In general, always look first in the manufacturer's Patient Information Leaflet (PI) or Consumer Medicine Information (CMI). They may have a section entitled "What to do if you miss a dose".

If the information is not available, you may then follow:

  • If the dose is less than 2 hours late, take the missed dose as soon as they remember, and resume the next dose at usual time.
  • If the dose is more than 2 hours late, the advice depends on how often the medicine is taken.
    • If taken once or twice a day, patient should usually take the dose as soon as they remember as long as the next dose is not due within a few hours. Patients should then continue taking the medicine at the usual times.
    • If taken more often than twice a day, it is usually safer to omit the missed dose, and wait until the next dose is due, then continue as normal. Do not double the dose.
Exceptions that do not follow the advice above include drugs that must be taken at specific times (e.g. phosphate binders, pancreatic enzymes, orlistat and prandial insulin).

To decide the most appropriate strategy following a missed dose, we should consider

  • The severity of the patient's condition
  • Whether clinically significant breakthrough effects are likely to be observed
  • The characteristics of the medication, e.g. half-life, pro-drug or not (if yes, consider the half-life of active metabolite)
For instance, extra precautions should be taken when the patient missed doses of



Bisphosphonates

Alendronate 70 mg Tablet
  • If patient misses a weekly dose, it can be taken the next day. If more than 1 day has elapsed, that dose is skipped until the next scheduled ingestion.
Ibandronic acid 150 mg Tablet
  • If patient misses a monthly dose, it can be taken up to 7 days before the next administration.
Risedronate 35 mg Once Weekly Tablet
  • If patient misses a weekly dose, it can be taken the next day. If more than 1 day has elapsed, that dose is skipped until the next scheduled ingestion.
Risedronate 150 mg Once Monthly Tablet
  • If patient misses a monthly dose, it can be taken up to 7 days before the next administration.



Combined Oral Contraceptive Pills

If you are less than 24 hours taking on an active pill, take it as soon as you remember and take the next pill at the usual time; contraception will not be affected.

If you are more than 24 hours late taking an active pill, the pill will not be as effective.

  • If you are late taking an active pill, take it as soon as you remember and take the next pill at the usual time (this may mean taking 2 pills on the same day or at the same time).
  • Continue with the daily pill and use another contraceptive method until you have taken active pills for 7 days in a row.
    • If the missed pill was in the last 7 days of active pills, finish the active pills in your present pack, then start the active pills in a new pack without any break.
    • If the missed pill was in the first 7 days of active pills and you had unprotected sex during or after that time, seek emergency contraception.



GLP-1 Receptor Agonists

Dulaglutide Weekly Injection
  • Missed dose should be administered as soon as possible within 3 days; resume usual schedule thereafter. If there are <3 days until next scheduled dose, omit the missed dose and resume administration at the next scheduled weekly dose.
Exenatide Immediate Release Daily Injection
  • Missed dose should be skipped; resume at the next scheduled dose
Exenatide Extended Release Weekly Injection
  • Missed dose should be administered as soon as possible if the next scheduled dose is due in ≥3 days; resume usual schedule thereafter. If there are <3 days until next scheduled dose, omit the missed dose and resume administration at the next scheduled weekly dose.
Liraglutide Daily Injection
  • In the event of a missed dose, the once-daily regimen can be resumed with the next scheduled dose (an extra dose or an increase in the next dose should not be attempted); if >3 days have passed since the last liraglutide dose, reinitiate therapy at the initial dose.
Lixisenatide Daily Injection
  • If dose is missed, administer within one hour of next meal.
Semaglutide Weekly Injection
  • Missed dose should be administered as soon as possible within 5 days; resume usual schedule thereafter. If >5 days have elapsed, skip the missed dose and resume administration at the next scheduled weekly dose.



Methotrexate 2.5 mg Tablet

  • If a weekly dose is missed, it can be taken as soon as it is remembered if this is within 2 days. However, if the dose is three or more days late then a doctor or the rheumatology clinic should be contacted for advice. A double dose should not be taken to make up for a missed dose. It is unlikely that a disease flare-up would occur as result of single missed dose.



Progestin Only Contraceptive Pills

Norethisterone 0.35 mg Tablet (Noriday)
  • If you forget a pill, take it as soon as you remember and carry on with the next pill at the right time. If the pill was more than 3 hours overdue, you are not protected. Continue normal pill-taking but you must also use another method, such as the condom, for the next 2 days.
Desogestrel 0.075 mg Tablet (Cerazette)
  • If you forget a pill, take it as soon as you remember and carry on with the next pill at the right time. If the pill was more than 12 hours overdue, you are not protected. Continue normal pill-taking but you must also use another method, such as the condom, for the next 2 days.
NOTE: If you have unprotected sex during the next 2 days after missed pill, seek emergency contraception.



Miscellaneous - More Examples

Acalabrutinib 100 mg Capsule

  • If a dose is more than 3 hours late, the missed dose should not be taken and the next dose should be taken at the normal time.

Alectinib 150 mg Capsule

  • Manufacturer advises if a dose is more than 6 hours late, the missed dose should not be taken and the next dose should be taken at the normal time.

Alpelisib 200 mg Tablet

  • Manufacturer advises if dose is more than 9 hours late, the missed dose should not be taken and the next dose should be taken at the usual time.

Bedaquiline 100 mg Tablet

  • If a dose is missed during the first two weeks of treatment, the missed dose should not be taken and the next dose should be taken at the usual time; If a dose is missed during weeks 3-24 of treatment, the missed dose should be taken as soon as possible and then the usual regimen resumed.

Ceritinib 150 mg Capsule

  • Manufacturer advises if a patient vomits during a course of treatment or if a dose is more than 12 hours late, the replacement or missed dose should not be taken and the next dose should be taken at the normal time.

Cobimetinib 20 mg Tablet

  • Manufacturer advises if a dose is more than 12 hours late, the missed dose should not be taken and the next dose should be taken at the normal time.

Dienogest 2 mg Tablet

  • Manufacturer advises if one or more tablets are missed, or if vomiting and/or diarrhea occurs within 3-4 hours of taking a tablet, another tablet should be taken as soon as possible and the next dose taken at the normal time.

Dolutegravir 50 mg Tablet

  • If a dose is more than 20 hours late on the once-daily regimen (or more than 8 hours late on the twice-daily regimen), the missed dose should not be taken and the next dose should be taken at the normal time

Clozapine 25 mg and 100 mg tablet

  • If, for any reason, a patient misses fewer than 2 days' clozapine, restart at the dose prescribed before the event. Do not administer extra tablets to catch up.
  • If more than 2 days are missed, restart at 12.5 mg daily and increase slowly (but at a faster rate than in drug-naïve patients).

Etravirine 100 mg Tablet

  • If a dose is more than 6 hours late, the missed dose should not be taken and the next dose should be taken at the normal time.

Lenalidomide 5, 10, 15 and 25 mg Capsule

  • May administer a missed dose if within 12 hours of usual dosing time. If greater than 12 hours, patient should skip dose for that day and resume usual dosing the following day. Patient should not take 2 doses to make up for a missed dose.

Lenvatinib 4 mg and 10 mg Capsule

  • Manufacturer advises if a dose is more than 12 hours late, the missed dose should not be taken and the next dose should be taken at the normal time.

Lorlatinib 25 mg and 100 mg Tablet

  • Manufacturer advises if a dose is more than 20 hours late, the missed dose should not be taken and the next dose should be taken at the normal time

Molnupiravir 200 mg Capsule

  • If a dose is more than 10 hours late, the missed dose should not be taken and the next dose should be taken at the normal time.

Nevirapine 200 mg Tablet

  • If a dose is more than 8 hours late with the “immediate-release” preparation (or more than 12 hours late with the modified-release preparation), the missed dose should not be taken and the next dose should be taken at the usual time.

Osimertinib 40 mg and 80 mg Tablet

  • Manufacturer advises if a dose is more than 12 hours late, the missed dose should not be taken and the next dose should be taken at the normal time

Rilpivirine 25 mg Tablet

  • If an oral dose is more than 12 hours late, the missed dose should not be taken and the next dose should be taken at the normal time.

Rivastigmine 1.5, 3, 4.5 and 6 mg Capsule

  • If dosing is interrupted for ≤3 days, restart the treatment at the same or lower dose and titrate every 2 weeks based on tolerability (maximum recommended dose: 6 mg twice daily). If interrupted for >3 days, reinitiate at 1.5 mg twice daily and titrate every 2 weeks based on tolerability (maximum recommended dose: 6 mg twice daily)

Rivastigmine 4.6, 9.5 and 13.3 mg/24 hour Transdermal Patch

  • If dosing is interrupted for ≤3 days, restart treatment with the same or a lower strength patch. If interrupted for >3 days, reinitiate at 4.6 mg/24 hours and titrate (no sooner than every 4 weeks) to lowest effective maintenance dose.

Selxipag 200, 400, 600, 800, 1000, 1200, 1400, 1600 mcg Tablet

  • Manufacturer advises if a dose is more than 6 hours late, the missed dose should not be taken and the next dose should be taken at the normal time; if a dose is missed for 3 days or more, treatment should be restarted at a lower dose and then increased.

Siponimod 0.25 and 2 mg Tablet

  • Manufacturer advises if a dose is missed during treatment initiation (days 1-6), the initial titration regimen should be restarted. If a maintenance dose is missed (after day 6), the missed dose should not be taken, and the next dose should be taken at the normal time. If 4 or more consecutive doses are missed, the initial titration regimen should be used to restart treatment.

Sofosbuvir 400 mg Tablet

  • Manufacturer advises if a dose is more than 18 hours late, the missed dose should not be taken and the next dose should be taken at the normal time.

Venetoclax 10, 50 and 100 mg Tablet

  • If a dose is more than 8 hours late, the missed dose should not be taken and the next dose should be taken at the normal time.



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Comments

  1. For methotrexate I think need to mention to the patient to not take folate on the day he/she remembers to take the missed dose, however most patient probably already understand if he/she has been taking methotrexate for some time

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