I missed taking medicine in the morning. Can I take the double dose in the evening?

It is not uncommon to miss taking drug once or twice during our continuous drug regimen. It happens rarely if the drug is prescribed once a day. But if the drug is prescribed twice or thrice a day then there is high chance that you forget to take your medication at least once especially during work hours. What we are going to discuss here is that when you missed out on a medication and remember it few hours later, can you take the drug and if you remember it during the next dosing, can you take double the dose of drug prescribed.

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Can we take double of the recommended dose

Before we could really talk about this, we should know few basic ideas on what our body does to the drug that is administered. The administered drug is processed by the body by the process which we call Pharmacokinetics. This involves

1.       Absorption – From site of administration to plasma (Intravenous dosage doesn’t involve absorption as the drug is already administered in plasma)

2.       Distribution – From plasma the drug is distributed to its site of action.

3.       Metabolism- The drug is metabolized to make it excrete out of body.

4.       Excretion- Especially via urine.

To get the answer to our question we should know about the mechanics of elimination of drug from the body. Most of the drug follows First order Kinetics while Aspirin, Phenytoin and Ethanol in high dose follows zero order kinetics.

When I say first order kinetics what I mean by that is constant fraction of drug is eliminated from body in some time. Let’s make this clear with some real numbers. Suppose you are administered with 80 mg drug and 50% is eliminated in every 4 hours then the amount of drug in the body after 4 hours will be 40 mg. In the next 4 hour it will be 20 mg. In the next 4 hour it will be 10 mg and so on.

80 mg--------- Initially

40 mg--------- After 4 hours

20 mg--------- After 8 hours

10 mg ---------- After 12 hours

Here we see the drug is becoming half in every 4 hours. So we call that the half life of drug is 4 hours.

 

The difference in zero order kinetics is that the constant amount (not fraction) of drug in eliminated in a specific time. Let’s give some real number. Suppose you have 80mg drug in your body then after every 4 hours every 10 mg (10 mg is taken as example only) is eliminated.

80 mg ------------ Initially

70 mg------------- After 4 hours

60 mg ------------ After 8 hours

50 mg-------------- After 12 hours.

In this case we can’t find out the exact time when the drug will be half. So half life is variable.

 

Now after understanding the concept of half life, let’s try to understand therapeutic index of the drug so that we can really answer our question. For a drug to show its action in the body, it should achieve some minimum concentration in the plasma. Below this concentration the drug doesn’t show its effect. This is known as minimum effective concentration of the drug. Only above this concentration, the therapeutic effect of any drug is seen. As the concentration of drug gets higher and higher, it can reach a certain concentration above which it start showing toxic effects. The concentration of the drug at which it start showing toxic effect is called minimum toxic concentration. To make a drug therapeutically beneficial our goal should be to keep concentration of the drug steady in the plasma and at this steady concentration, we should make sure the concentration achieved is higher than minimum effective concentration and lower than minimum toxic concentration. The gap or the difference between minimum effective concentration and minimum toxic concentration determines therapeutic index of the drug. Higher the therapeutic index, safer it is. Few drugs have very narrow therapeutic index and we should be really conscious about drug dosing for such drugs.

After understanding the concept of first order kinetic, half life and therapeutic index, lets try to answer our question by playing with some numbers. Suppose you have been injected 100mcg/ml of some drug intravenously. Let’s say this drug has minimum effective concentration 40mcg/ml and minimum toxic concentration 230 mcg/ml. Let’s just say that the drug has a half life of 8 hours and the drug is recommended thrice a day(every 8 hours) every day. The example has been taken only for our simplicity sake.

Initial dosing of the drug------------------------------------------------- 100 mcg/ml

After 1^st half-life (8 hours) ---------------------------------------------- 50 mcg/ml

100 mcg/ml drug re-administered after 8 hrs of initial dosing------ 150 mcg/ml

After 2^nd half-life (16 hours) -------------------------------------------- 75 mcg/ml

100 mcg/ml drug re-administered after 8 hrs of second dosing ------175 mcg/ml

After 3^rd half-life (24 hours) ----------------------------------------------87.5mcg/ml

100 mcg/ml re-administered after 8 hrs of 3^rd dosing------------------187.5mcg/ml

After 4^th half life (32 hours) -----------------------------------------------93.75 mcg/ml

100 mcg/ml re-administered after 8 hours of 4^th dosing--------------- 193.75mcg/ml

After 5^th half-life (40 hours) ------------------------------------------96.875mcg/ml

100 mcg/ml re-administered after 8 hours of 5^th dosing -------------- 196.875mcg/ml

After 6^th half life (48 hours) ----------------------------------------- 98.4375 mcg/ml

100 mcg/ml re-administered after 8 hours of 6^th dosing-------------- 198.4375mcg/ml

After 7^th half life (56 hours) -----------------------------------------99.21875 mcg/ml

Mathematically we can keep going down and it will take very long to reach a steady state. But clinically what we see here is that after 4^th and 5^th half life the drug concentration hasn’t changed to significant concentration. It is around 200 mcg/ml when the drug is administered and decreases over time till it reaches around 100 mcg/ml and at this time we re-administer 100 mcg/ml of drug. Here we have achieved a steady state plasma concentration in between 100 and 200 mcg/ml.

Now let’s see what happens when we miss the dosage of drug after reaching steady state. The drug concentration we have achieved after taking drug is 200mcg/ml. After 8 hours it decreases to 100 mcg/ml. We were supposed to re-administer drug at this time but we forget. In this case, the drug concentration keeps decreasing below 100 mcg/ml. In the next 8 hours (which is the half life of drug), its concentration will be 50 mcg/ml. Luckily in our example this is still above minimum effective concentration i.e. 40 mcg/ml. If we miss to take drug again then then the drug concentration will further decrease below 50 mcg/ml and when it is less than 40mcg/ml, the therapeutic effect of drug is lost.

Lets suppose this patient only miss one dose of the drug and the concentration of drug in the plasma has decreased down from 100 mcg/ml to 50 mcg/ml. Patient is supposed to take drug now but the patient remember that he forgets to take one dose of the drug during office and takes double the recommended dose of drug i.e. 200 mcg/ml. Then the concentration of the drug is the plasma reaches 250mcg/ml. This is greater than the minimum toxic effect of the drug and the patient suffers from numerous toxic effects.

 

Conclusion

It is strongly recommended to follow the drug dosage and frequency recommended by your physician. Make sure you don’t forget to take medication in time. You can set an alarm or a reminder in your smartphone. But in case you forget to take the drug in time and remember it an hour later or so then take the prescribed dose of drug as soon as you remember. In case you remember too late; let’s say you were supposed to take one dose of drug in the morning and one dose in the evening and in the evening you realize that you missed morning dose of drug then in this case you only take the evening dose of the drug and take morning dose next morning. NEVER take double the recommended dose of drug because some drug may have very narrow therapeutic index and that can be toxic to you.

 

I hope this was useful.