See also Frequently Asked Questions About Heroin, Morphine, and the Opiates - Heroin/Morphine FAQ

If safe values for effect equivalence, minimal deadly dose, tolerance formation, loss of tolerance, half-life value and resorption were known, the safe dose could be worked out at any time. But these parameters have only been partly looked into for people plus they show an inter-individual distribution.

From the scientific data, from theoretical considerations and from experienced values, practical assumptions can be made and limiting parameters are appropriate ruling-sizes for formulating dosing-guidelines:

Minimal deadly doses in intolerant people are well known. A safe first-dose can be given on grounds of experiences made. The first consumption should always be taken under supervision so that the effect and the extent of the effect of the first dose can be observed. This way, when there is insufficient effect, the dose can be safely increased thus avoiding over- and underdoses.

Half-Life Value: the cumulation is determined by the half-life value and the interval between doses. A reasonable interval between doses can be worked out from the half-life value. The velocity for cumulation, formation of tolerance and loss of tolerance should be sufficient to theoretically calculate the maximum possible increase of the daily opioid dose. The dose-effect relationships have only been partly researched in people. Quantitative data especially concerning the development of tolerance is not yet available. With mixed consumptions of different opioids there is, for each substance, other cumulation thus different tolerance developments.

The tolerance dose is the daily opioid dose where the maximum tolerance is reached in comparison to additionally administered opioids. The tolerance dose corresponds to the maximum achievable effect (Efficacy, see Chapter 2.10 and 3.6).

Resorption: these data have been well researched. The waiting time until the next consumption can be calculated from this. Only after the full effect of the previous consumption is visible, can the safety for the next dose be guessed.

Equivalence doses were discussed in chapter 11.1. The doses of different opioids in mixed consumption or when changing from one opioid to another, can be effect-equivalent calculated with the conversion factors given in Tab.28.

The limit-parameters shown in Tab.29 are transformations of the pharmacological parameters. They are appropriate help when formulating dose guidelines and example prescriptions. Safe doses can be directly derived from the limit-parameters already mentioned. Simple example-prescriptions are purposeful for practical necessity for the personnel.

Too high and too fast increases in doses can lead to overdoses.

Too delayed increases in dose and persistent small doses provoke illegal opioid buying and consumptions.

One cannot do without a clinical judgement of the patient when doing the individual prescription and again when administering to the patient.

Special effects of first-doses and increases in doses need to be observed.

Information from (blamed on addiction compulsions) patients concerning illegal consumption should not be taken as a basis when calculating the dose!

The following prescription-parameters and prescription patterns are suggestions, which should be understood as extreme- and limiting variants. This also counts for the examples. The usual prescription should be done with more care.

First-dose: the safe first dose of 40mg should never be exceeded because there recorded cases of death from swallowed methadone starting at 50 mg. The average lethal dose of oral methadone for opioid-intolerant persons is 1-1.5 mg / kg body weight. A reliable, alternative course of action is a first dose of 30 mg and at the earliest, after 3 hours, a one time supplement of maximum 20 mg. So that the effect of the first dose can be judged, it should be consumed under supervision of the personnel. This second method was tried thousands of times in the AruD-outpatient clinics.

The daily increase in dose should not exceed 10mg, due to the very definite cumulation. The cumulated dose can ‘overtake’ the development of tolerance, especially on the second and third day, due to the large half-life value and then lead to overdoses.

The tolerance dose of oral methadone is reached through daily doses of 80 to 120mg a day in opioid tolerant people. The therapeutically necessary levels of methadone in the blood, of 150 to 600ng/ml are reached with daily methadone doses of 80 to120 mg/ day. (Dole 1988). Further increases in dose would hardly have an additional effect. Doses less than 70 mg/d are usually, in the long run, insufficient.

Minimum Waiting Time: 3 hours. The intestinal resorption can be delayed so that the maximum effect is only observed after 3 hours.

The first dose of 15 mg methadone i.v. was presumed safe in the Prove-trials. If the first dose of 15 mg under supervision of the medical personnel, was bearable without problems, up to maximum 30 mg methadone was then slowly injected i.v..

The daily dose increase should not increase the 10mg due to the prominent cumulation as a result of the large half-life value.

The tolerance dose and thus the maximum effect is reached with 80 to 120mg of methadone/day in opioid tolerant people, with i.v. application.

Minimum Waiting Time: with each intravenous injection of opioids it is recommended that one waits a minimum of half an hour before the next consumption.

A first-dose of 15 mg heroin i.v. is bearable for opioid intolerant people. All the same, an intravenous first dose of 20 mg heroin can lead to breathing arrest in intolerant, not addicted people. When the first dose is intravenously applied under supervision and it is coped with well, 15mg can be immediately injected. In the course of the first day, injectable heroin can be administered more than once in small, bearable doses of 30 mg (theoretically up until a maximum each half an hour) under supervision.

Daily Increases in Dose are safe up to maximum of 50%.
The safe dose can be calculated, where the first dose is calculated thus giving the daily dose: the maximum single dose of heroin can be 50% of the whole dose consumed the previous day. If 30 mg heroin is injected five times on the first day, 75 mg can be administered in one syringe on the second day and this dose can be consumed more than once, which even allows for a safe increase in dose over the 50% given in Tab.29.
Once again:: effects of first-doses and increases in dose must be observed!

Tolerance Dose: the maximum effect of heroin seems to be reached at 600mg/day in tolerant heroin addicts. Increases in dose over 600 mg/day, lead to an increasing flattening of the flash effect (Fig.27). The withdrawal-preventing saturation of the opioid hunger and the analgesic effect is reached with considerably less daily doses.

Minimum Waiting Time: it is recommended that there is a minimum half an hour waiting time before the next heroin injection. The maximum effect can only be safely ascertained after half an hour. The resorption and the maximum effect can be delayed for over half an hour with paravenous injections.