Methods & formulas

LDL-C was lowered by an additional 6.2% (5.6% after adjustment for covariates) of the original pretreatment LDL-C for each doubling of the statin dose.

Reductions in LDL cholesterol (in the 164 trials) were 2.8 mmol/l (60%) with rosuvastatin 80 mg/day, 2.6 mmol/l (55%) with atorvastatin 80 mg/day, 1.8 mmol/l (40%) with atorvastatin 10 mg/day, lovastatin 40 mg/day, simvastatin 40 mg/day, or rosuvastatin 5 mg/day, all from pretreatment concentrations of 4.8 mmol/l.

The standard deviation of LDL-C reduction for all statins and doses ranged from 12.8 to 17.9%.

Rosuvastatin 5 mg reduced LDL-C by 39% … Equivalent reductions in LDL-C required atorvastatin 15 mg or simvastatin 39 mg. Rosuvastatin 10 mg reduced LDL-C by 44% … Equivalent reductions in LDL-C required atorvastatin 29 mg or simvastatin 72 mg. Rosuvastatin 20 mg reduced LDL-C by 50% … [equivalent reductions] required atorvastatin 70 mg … and were not achieved with the maximum 80 mg dose of simvastatin. Rosuvastatin 40 mg reduced LDL-C by 55% … Comparable reductions were not achieved with the maximum 80 mg doses of atorvastatin or simvastatin … each rosuvastatin dose is equivalent to doses 3–3.5 times higher for atorvastatin and 7–8 times higher for simvastatin.

In the primary analysis, fluoxetine 40mg/day was equivalent to paroxetine dosage of 34.0mg/day, … escitalopram 18.0mg/day, … mirtazapine 50.9mg/day, … sertraline 98.5mg/day, … and venlafaxine 149.4mg/day.

Table 1 (Current study column): "Citalopram 20" — i.e. citalopram 20 mg = 1 unit = 20 mg fluoxetine, so citalopram 40 mg ≈ fluoxetine 40 mg (fluoxetine-40-equivalent = 40.0). Efficacy plateau: "the dose-efficacy curve showed a gradual increase up to doses between 20 mg and 40 mg fluoxetine equivalents, and a flat to decreasing trend through the higher licensed doses up to 80 mg."

This warning advised against prescribing citalopram at doses >40 mg/day due to 'dose-dependent QT interval prolongation.' This safety warning also decreased the maximum dose to 20 mg in patients ≥60 years old, those with hepatic impairment, those who are CYP2C19 poor metabolizers, and/or those taking cimetidine or other CYP2C19 inhibitors.

Doses below or at the lower end of the usually recommended dose range (citalopram: 10–20 mg, paroxetine: 10 mg; sertraline: 50 mg) were superior to placebo but inferior to higher doses, hence confirming a dose-dependency to be at hand.

the dose–response curve with ARBs was shallow with decrease of 10.3/6.7 (systolic/diastolic), 11.7/7.6, and 13.0/8.3 mmHg with 25% max dose, 50% max dose, and with the max dose of ARBs, respectively. … doubling the dose merely increased the antihypertensive efficacy by <2 mmHg systolic or diastolic.

Olmesartan had the highest surface under the cumulative ranking in reducing office systolic (91.4%) and diastolic blood pressure (87.2%). … Valsartan and losartan were less effective in lowering blood pressure than other drugs.

After 8 weeks of treatment, mean reductions from baseline in supine systolic/diastolic pressure 24 hours after dosing (trough) for losartan potassium 10, 25, 50, 100, and 150 mg, enalapril maleate 20 mg, and placebo were 7.6/7.9, 7.8/6.8, 13.0/10.1, 8.9/9.9, 10.5/9.7, 14.7/11.2, and 3.8/5.6 mm Hg, respectively.

placebo-subtracted mean changes from baseline to end point for valsartan 10, 20, 40, 80, 160, and 320 mg, respectively: SDBP, -0.8, -2.8, -2.6, -3.9, -5.1, and -6.4 mm Hg; SSBP, -1.3, -5.7, -5.3, -6.8, -8.6, and -9.0 mm Hg

The optimal dose range is 80 to 160 mg, given once daily.

Patients received either placebo or candesartan cilexetil 2, 4, 8, 16, or 32 mg once daily for 8 weeks. … Mean changes in BP were -10.7/-7.8 mm Hg and -12.6/-10.2 mm Hg in the 16- and 32-mg groups, respectively, versus -0.3/-2.6 mm Hg in the placebo group.

The placebo-corrected mean reductions in sitting diastolic BP were approximately 2.5 mm Hg with 2 mg, 4.5 mm Hg with 4 mg, 6 mm Hg with 8 mg, and 8 mm Hg with 16 mg of candesartan cilexetil.

After a placebo lead-in phase, all patients were randomized to 8 weeks of double-blind therapy with either placebo (n = 158) or irbesartan at doses of 1, 5, 10, 25, 50, 100, 200, or 300 mg (n = 731 total) orally once daily. … Reductions from baseline in trough seated diastolic blood pressure ranged from 7.5 mm Hg for 50 mg irbesartan to 11.6 mm Hg for 300 mg irbesartan.

After 8 weeks of treatment, reductions from baseline in trough seated diastolic blood pressure (SeDBP) and trough seated systolic blood pressure (SeSBP) with 300 mg irbesartan were greater than with 100 mg losartan (P < .01 for both comparisons), by 3.0 and 5.1 mm Hg, respectively

Telmisartan 20 to 160 mg once daily produced mean reductions in supine trough systolic blood pressure and diastolic blood pressure of up to 15.5 and 10.5 mm Hg, respectively. … Maximum blood pressure reduction occurred with a dosage of 40 to 80 mg/day.

After a 28-day placebo run-in period, patients were randomized to 28 days of once-daily, double-blind, double-dummy treatment with telmisartan 40, 80, or 120 mg; enalapril 20 mg; or placebo.

Treatment with olmesartan medoxomil resulted in a significant placebo-adjusted reduction of mean 24-hour ambulatory diastolic blood pressure of 9.6 mm Hg, 12.2 mm Hg, and 10.6 mm Hg in the 5-, 20-, and 80-mg q.d. groups, respectively. … Corresponding reductions in mean ambulatory systolic blood pressure were 14.5 mm Hg, 16.5 mm Hg, and 15.4 mm Hg.

BP-lowering efficacy defined as Emax was superior with olmesartan, (DBP/SBP mmHg: -9.0/-12.4)

Losartan in the dose of 50 mg lowered ABP less well than other ARBs at 50% max dose by 2.5 mmHg systolic (P < 0.0001) and 1.8 mmHg diastolic (P = 0.0003). … Blood pressure reduction with losartan at starting dose and at max dose was consistently inferior to the other ARBs.

The WHO Defined Daily Dose (DDD) values, oral, group C09AA: captopril 50 mg, enalapril 10 mg, lisinopril 10 mg, perindopril 4 mg, ramipril 2.5 mg.

The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. … The DDD is a unit of measurement and does not necessarily reflect the recommended or Prescribed Daily Dose. … The DDD is sometimes a 'dose' that is rarely if ever prescribed.

However, these agents' pharmacodynamics and pharmacokinetics suggest that once-daily administration may not lead to a 24-hour effect.

We calculated the mean doses of each drug weighted by sample size and divided them by the weighted mean olanzapine dose to obtain olanzapine equivalents. … The doses equivalent to 1 mg/d olanzapine were: amisulpride 38.3 mg/d, aripiprazole 1.4 mg/d, asenapine 0.9 mg/d, chlorpromazine 38.9 mg/d, clozapine 30.6 mg/d, haloperidol 0.7 mg/d, quetiapine 32.3mg/d, risperidone 0.4 mg/d, sertindole 1.1 mg/d, ziprasidone 7.9 mg/d, zotepine 13.2 mg/d. … Table 1 (mean, SD): risperidone 0.38 (0.12), haloperidol 0.74 (0.22), chlorpromazine 38.88 (16.9), quetiapine 32.27 (7.4), aripiprazole 1.41 (0.3), ziprasidone 7.92 (1.56), amisulpride 38.33 (8.76), clozapine 30.62 (18.64), sertindole 1.08 (0.2), asenapine 0.89, zotepine 13.24.

Clinical trials have reported dose-dependent bioavailabilities ranging from 73.8 +/- 18.3 to 35.7 +/- 18.3% when the dose was increased from 100 to 1600 mg. … The permeability of gabapentin … was consistent with carrier-mediated absorption, i.e., a 75 to 80% decrease in permeability when the drug concentration was increased from 0.01 to 50 mM.

The absolute bioavailability of gabapentin drops from 60% to 33% as the dosage increases from 900 to 3600 mg/day, while the absolute bioavailability of pregabalin remains at > or = 90% irrespective of the dosage.

The statistically significant relationship between dose and F was described using an Emax relationship.

V0 = Vm × C / (Km + C).

The Bateman function, A"(e-k(e)t--e-k(a)t), quantifies the time course of a first-order invasion (rate constant ka) to, and a first-order elimination (rate constant ke) from, a one-compartment body model where A" = (gamma Dose)ka/(ka-ke)V.

The Bateman function, A"(e-k(e)t--e-k(a)t), quantifies the time course of a first-order invasion (rate constant ka) to, and a first-order elimination (rate constant ke) from, a one-compartment body model where A" = (gamma Dose)ka/(ka-ke)V.

The area under the plasma concentration–time curve is commonly estimated by the trapezoidal rule, in which the area between successive sampling times is approximated by that of a trapezoid.

For drugs that follow linear pharmacokinetics, the area under the curve (AUC) is directly proportional to the dose; deviation from dose proportionality indicates nonlinear (capacity-limited) pharmacokinetics.

V0 = Vm × C / (Km + C).

Molar concentration (mol/L) is obtained by dividing the mass concentration by the molecular weight of the drug.

The half-life is related to the elimination rate constant by the equation t1/2 = 0.693/k.

Clearance is the product of the volume of distribution and the elimination rate constant, CL = k · V.

Since k(e)tmax = ln m/(m-1), m can be determined from the given table relating m and k(e)tmax.

The Bateman function, A"(e-k(e)t--e-k(a)t), quantifies the time course of a first-order invasion (rate constant ka) to, and a first-order elimination (rate constant ke) from, a one-compartment body model where A" = (gamma Dose)ka/(ka-ke)V.

The total area under the plasma concentration–time curve following a single dose is AUC = F·Dose/CL, where CL is clearance.

When a drug has 100% bioavailability, regression of Dose/V/C on AUC/C in the nonabsorption phase gives ke no matter what is the ratio of m = ka/ke.

At plateau, the average concentration is Cav = F·Dose/(CL·τ), where τ is the dosing interval.

The Bateman function and "feathering" fail when the rate constants are equal. The time course is then expressed by C = gamma Dtk e-kt.

The determination of the Michaelis-Menten kinetic parameters (Vmax and Km) was calculated using the formula (equation) (Shargel & Yu, 2022): R = V max − Km.R/Css … Css: Steady level of drug in plasma … R: Dosage/day or rate of dosing … Vmax: The maximum rate of drug metabolism … Km: Michaelis-Menten constant.

For each subject the Cpss values were fitted to a rearranged Michaelis-Menten equation Cpss =KmR/(Vm-R).

This system applies the Michaelis-Menten equation to the initial data pair (D1-Css1) and solves for (a) maximum metabolic rate constant (Vmax) assuming the population mean for the Michaelis constant (Km) (method 1).

Accurate predictions of the Css error within 5 micrograms/ml were obtained in 84% of the 25 cases, and in 30% of the 10 cases excluded.

For gabapentin enacarbil, a power model was most suitable, with a power of 0.925 for bioavailable dose or 0.844 for steady-state concentration.

The accumulation index, Rac = 1/(1 − e^(−k·τ)), expresses the extent of accumulation on repeated dosing relative to a single dose.

Golden-section search locates the extremum of a unimodal function on an interval by successively narrowing the bracket using the golden ratio.

A method is described for the minimization of a function of n variables, which depends on the comparison of function values at the (n+1) vertices of a general simplex, followed by the replacement of the vertex with the highest value by another point.

Computerized analysis of the time-plasma concentration profiles using a two-compartment Michaelis-Menton elimination model yielded a median absorption constant of 1.29 h-1; volume of distribution of 0.47 l/kg; Vmax of 0.12 g h-1 kg-1; and Km of 0.03 g/l.

The crushing error rate decreased from 3.1% (21 wrongly crushed medicines out of 681 administrations) to 0.5% (3/636), RR=0.15 (95% CI 0.05 to 0.51) … Medications which were erroneously crushed included enteric-coated formulations (eg, omeprazole), medication with regulated release systems (eg, Persantin; dipyridamol) and toxic substances (eg, finasteride).

Evidence does support … the inappropriateness of splitting sustained-release preparations, given the potential for alteration of the rate of drug release for some products … sustained-release tablets, which should not be split.

the administration of medications unsuitable for enteral feeding tubes (33.3%), predominantly due to the use of controlled release or enteric-coated formulations.

No eligible studies concerning manipulation of oral capsules or liquids, rectal enemas, nebuliser solutions, injections or transdermal patches were identified … The results cannot be extrapolated between dosage forms, methods of manipulation or between different brands of the same drug.

A total of 52 of 320 half tablets (16.2%) and 48 of 320 half tablets (15.0%) fell outside of the proxy United States Pharmacopeia (USP) specification for weight and drug content … Bromazepam, carvedilol, bisoprolol, losartan, digoxin, and meloxicam half tablets failed the weight and content uniformity test … Tablets containing drugs with a wide therapeutic index and long half-life might be more suitable candidates for division.

Clinical studies report that the use of uncoated, sugar-coated, or film-coated tablets with the same dose of crushed forms and their use as a whole tablet has the same efficacy and safety data. … Physical manipulations on drugs with these coating properties do not cause any change in bioavailability and pharmacokinetic data.

Medications which were erroneously crushed included enteric-coated formulations (eg, omeprazole), medication with regulated release systems (eg, Persantin; dipyridamol) and toxic substances (eg, finasteride).

In this list, NIOSH established that crushing tablets or making solutions from them causes an unacceptable risk at hospitals. Furthermore, United States Pharmacopeia <800> and European regulations impose the use of closed system devices and plastic pouches to contain any dust or particles generated during these operations.

in over 60% of sustained-release drugs pharmaceutical companies use specific suffixes in their drug names such as SR, chrono or prolong to highlight specific galenic formulations. Thus, these suffixes may provide a first hint that a drug is potentially inappropriate for drug modification. … Most summaries of product characteristics do not list information regarding drug modification or safety aspects.

the area under the curve for verapamil during the initial 24 h period was 1.7 and 1.3 times greater in the crushed and simple suspension groups, respectively, than in the tablet group.

The dosage range is 10 mg to 80 mg once daily.

The dosage range for CRESTOR is 5 to 40 mg orally once daily.

The maximum recommended dosage is ZOCOR 40 mg once daily. An 80 mg daily dosage of ZOCOR is restricted to patients who have been taking simvastatin 80 mg daily chronically (e.g., for 12 months or more) without evidence of muscle toxicity.

The recommended starting dosage is pravastatin sodium tablets 40 mg to 80 mg once daily.

The recommended dosing range is 10 to 80 mg/day in single or two divided doses; the maximum recommended dose is 80 mg/day.

The recommended dosage for LESCOL XL is 80 mg once daily.

The maximum recommended dosage is LIVALO 4 mg once daily.

The dosage range for CRESTOR is 5 to 40 mg orally once daily.

The dosage range is 10 mg to 80 mg once daily.

For patients with severe renal impairment [creatinine clearance (CLcr) 15 – 29 mL/min], the recommended starting dosage of simvastatin is 5 mg once daily.

In patients with severe renal impairment, the recommended starting dosage is pravastatin sodium 10 mg once daily.

The recommended dosing range is 10 to 80 mg/day in single or two divided doses; the maximum recommended dose is 80 mg/day.

Lescol is supplied as capsules containing fluvastatin sodium, equivalent to 20 mg or 40 mg of fluvastatin, for oral administration.

For patients with renal impairment, the recommended starting dosage for patients with moderate and severe renal impairment and patients with end-stage renal disease receiving hemodialysis is LIVALO 1 mg once daily.

Pitavastatin doses (1–4 mg) reduced LDL-C by 28–47%, comparable to atorvastatin, rosuvastatin, and simvastatin. The 2 mg dose matched atorvastatin's 10 mg dose in efficacy for both short-term (35–42%) and long-term (28–36%) use.

In combining trial data we specified equivalent daily doses of different drugs as the 'usual maintenance dose' in reference pharmacopoeias. We call this the standard dose. … All five categories of drug produced similar reductions in blood pressure. … The average reduction was 9.1 mm Hg systolic and 5.5 mm Hg diastolic at standard dose and 7.1 mm Hg systolic and 4.4 mm Hg diastolic (20% lower) at half standard dose.

In patients with coronary disease, the use of short-acting nifedipine in moderate to high doses causes an increase in total mortality. … Other calcium antagonists may have similar adverse effects, in particular those of the dihydropyridine type.

Even within the dihydropyridine subgroup, there are significant differences in formulations, pharmacokinetics, durations of action and their effects on blood pressure, heart rate, end organs and the sympathetic nervous system. … Amlodipine has an inherently long pharmacokinetic half-life, whereas, in contrast, nifedipine has an inherently short half-life but in the GITS formulation the sophisticated delivery system allows for once-daily dosing. … However, it has long been known that potent arterial vasodilators evoke a baroreceptor-mediated reflex increase in heart rate that is mediated via the sympathetic nervous system.

This study indicates the amlodipine dosage of 5 or 10 mg once daily can be used when nifedipine ER is converted to amlodipine in the treatment of hypertension. … Dosing titration of amlodipine was required in 16 of 27 patients after the switch.

When converting patients from amlodipine, dosages usually should be equal to those of felodipine; if converting to other calcium channel antagonists, the need for adjustments should be anticipated. … Conversion to calcium channel antagonists other than felodipine or less than equal dosages of felodipine may require dosage titration.

This was a double-blind, double-dummy, randomized clinical trial comparing nifedipine GITS (30 mg) and amlodipine (5 mg) for 24 weeks following a placebo run-in. … There were no significant differences between active treatment groups in the blood pressure changes (systolic blood pressure: nifedipine GITS -15.5 mmHg; amlodipine -15.7 mmHg).

In a randomized crossover design, 42 patients were randomized to receive amlodipine (5-10 mg) or the GITS formulation of nifedipine (nifedipine GITS) (30-60 mg) once daily for 12 weeks, then vice versa. … When compliance was not perfect, i.e. when one or two doses were missed, DBP was maintained at a significantly lower level with amlodipine compared with nifedipine GITS.

Eligible patients were randomly assigned to amlodipine 5-10 mg/day or nifedipine-GITS 30-60 mg/day. … After 8-week treatment, BP was similarly reduced in the amlodipine (n = 257) and nifedipine-GITS groups (n = 248) for both clinic and ambulatory (24-hour systolic/diastolic BP 10.3/6.5 vs 10.9/6.3 mm Hg, P ≥ 0.24) measurements.

The usual initial antihypertensive oral dose of NORVASC is 5 mg once daily, and the maximum dose is 10 mg once daily.

The usual initial antihypertensive oral dose of levamlodipine is 2.5 mg once daily, and the maximum dose is 5 mg once daily.

The recommended starting dose is 5 mg once a day. … The recommended dosage range is 2.5 - 10 mg once daily. … In clinical trials, doses above 10 mg daily showed an increased blood pressure response but a large increase in the rate of peripheral edema and other vasodilatory adverse events.

In mild to moderate hypertension, the recommended initial dose is one 20 mg tablet once-daily. In severe hypertension, the recommended initial dose is one 30 mg tablet once-daily. … If necessary, the dosage can be increased according to individual requirements up to a maximum of 90 mg once-daily.

The recommended initial dose is 2 mg once daily. The dose may be increased to 4 mg (and then, if necessary, to 6 mg) after adequate time has been allowed for the full pharmacological effect to occur. … Daily doses above 6 mg have not been shown to be significantly more effective.

Richtdosis für Erwachsene: 2-mal täglich (morgens und abends) 1 Tablette Nitrendipin-ratiopharm® 10 mg Tabletten oder 1-mal täglich (morgens) 1 Tablette Nitrendipin-ratiopharm® 20 mg Tabletten (entspr. 20 mg Nitrendipin). … Die maximale Tagesdosis beträgt 40 mg Nitrendipin.

The recommended dosage is 10 mg orally once a day at least 15 minutes before meals; the dose may be increased to 20 mg depending on the individual patient's response. … Since the dose-response curve is steep with a plateau at doses between 20-30 mg, it is unlikely that efficacy will be improved by higher doses; whereas side effects may increase.

Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 2.5 mg once daily.

Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 1.25 mg once daily and this dose may be used when adding levamlodipine to other antihypertensive therapy.

Patients whose mild to moderate essential hypertension is controlled with nifedipine GITS 30 mg once daily may be able to switch to 20 mg once daily with continued antihypertensive efficacy.

nitrendipine is suitable for monotherapy of mild arterial hypertension in the dosage of 10 mg once daily used in this study.

Amlodipine did not increase cardiovascular morbidity or mortality in patients with severe heart failure.

The drug appears to be safe but not clearly efficacious in patients with heart failure.

Uncompensated heart failure

Left ventricular failure with pulmonary stasis

Among those with a baseline EF of less than 0.40, late CHF appeared in 12% (39/326) receiving placebo and 21% (61/297) receiving diltiazem (p = 0.004).

Second or third degree atrioventricular block (except in patients with a functioning artificial pacemaker)… Sick sinus syndrome… Bradycardia of less than 50 beats/minute

Sick sinus syndrome, 2nd or 3rd degree AV block in patients without a functioning pacemaker… Severe bradycardia (less than 50 beats per minute).

DHP-CCBs are vascular-selective and function as potent vasodilators, whereas non-DHP-CCBs are cardiac-selective… acting on… the sinoatrial (SA) node and atrioventricular (AV) node.

In mild to moderate hepatic impairment, the recommended starting dose should be lowered to the minimum therapeutic effective dose. … Felodipine is contraindicated in patients with severe hepatic impairment.

Owing to the duration of action of the formulation, Adalat LA should not be administered to patients with hepatic impairment. … no dose adaptation in elderly people above 65 years is necessary.

the bioavailability of MOTENS may be increased and the hypotensive effect enhanced… in severe cases, a dose reduction may be necessary.

Patienten mit Leberfunktionsstörungen können verstärkte oder verlängerte Wirkungen… aufweisen.

The mean felodipine bioavailability with grapefruit juice was 284 (range 164-469)% of that with water.

Cmax and AUC increased 8-fold and 6-fold… The combination with strong CYP3A4 inhibitors should be avoided. … with carbamazepine, phenytoin or phenobarbital, the Cmax and AUC of felodipine were decreased by 82% and 96% respectively.

Co-administration with: strong inhibitors of CYP3A4… grapefruit or grapefruit juice

The use of nifedipine in combination with rifampicin is therefore contraindicated. … blood pressure should be monitored and, if necessary, a reduction of the nifedipine dose should be considered.

may give rise to significant increase in Amlodipine exposure… more pronounced in the elderly.

Most common adverse reaction… is edema which occurred in a dose related manner.

doses above 10 mg daily showed an increased blood pressure response but a large increase in the rate of peripheral edema… age and dose related… discontinuation… in about 3%.

Nifedipine is 7.17 times more likely to cause peripheral edema compared to lacidipine

Peripheral edema is a common adverse effect of calcium channel blockers.

The incidence of peripheral edema with calcium channel blocker/renin-angiotensin system blocker combination was 38% lower than that with calcium channel blocker monotherapy (P<.00001) (relative risk [RR] 0.62; 95% confidence interval [CI], 0.53-0.74).

They should not be used in clinically significant aortic stenosis…

Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis.

The anti-inflammatory potency of cortisol (hydrocortisone) is conventionally equal to 1; hence, based on the relative potencies of various corticosteroids, it is possible to identify the equivalent doses of every single steroid. … Conversion of corticosteroid doses. Elaboration of data from [1] and [3]

this study… shows that currently used dosing tables reflect reasonable dose equivalency relationships for four corticosteroids.

prednisolone, which has four times the anti-inflammatory potency as hydrocortisone but less salt-retaining properties, a longer plasma disappearance half-life.

This hierarchy [non-genomic] is completely different from that for the classical effects… of crucial relevance for… glucocorticoid high-dose therapy.

Diazepam Milligram Equivalency Algorithm … The recommended total daily dose described in product labels was used to adjust for differences in dosing intervals and to standardize total daily dose exposure across medication types.

clinicians should not discontinue BZDs abruptly in patients who are likely to be physically dependent and at risk of withdrawal symptoms. … Clinicians should tailor tapering strategies to each individual patient and adjust tapering based on patient response.

Kirchheiner et al reported the relative potencies were 0.23, 0.90, 1.00, 1.60, and 1.82 for pantoprazole, lansoprazole, omeprazole, esomeprazole, and rabeprazole, respectively

Based on the mean 24-h gastric pH, the relative potencies of the five PPIs compared to omeprazole were 0.23, 0.90, 1.00, 1.60, and 1.82 for pantoprazole, lansoprazole, omeprazole, esomeprazole, and rabeprazole, respectively.

Relative intravenous potency (mg): Furosemide 40, Torsemide 20, Bumetanide 1 … Oral : intravenous dosing: Furosemide 1 : 2, Torsemide 1 : 1, Bumetanide 1 : 1 … Torsemide and bumetanide have an oral bioavailability of 80–100 %, while furosemide has a wide variant bioavailability of 10–100 %.

High intensity, which typically lowers LDL-C by 50% or more; Moderate intensity, which lowers LDL-C by 30% to 49%; Low intensity, which lowers LDL-C by 30% or less.

risk was significantly greater for high compared with moderate intensity statin therapy for any muscle problem (RR=1.04, 95% CI 1.00 to 1.07; I2=0%), myalgia (RR=1.04, 95% CI 1.00 to 1.08; I2=0%, number needed to harm (NNH)=173), attrition due to muscle problems (RR=1.37, 95% CI 1.09 to 1.73, I2=0%, NNH=218) and elevated CK (RR=4.69, 95% CI 2.50 to 8.80; I2=7%, NNH=527). There were no significant differences in risk between moderate intensity therapy and placebo for all outcomes.

Myopathy was confirmed in 53 (1%) participants allocated 80 mg simvastatin compared with two (0·03%) allocated 20 mg simvastatin. Rhabdomyolysis was diagnosed in seven participants allocated 80 mg simvastatin versus none allocated 20 mg simvastatin.

The risk of statin-induced serious muscle injury, including rhabdomyolysis, is <0.1%, and the risk of serious hepatotoxicity is ≈0.001%. … in randomized clinical trials, the difference in the incidence of muscle symptoms without significantly raised creatinine kinase in statin-treated compared with placebo-treated participants is <1%. … The risk of statin-induced newly diagnosed diabetes mellitus is ≈0.2% per year of treatment, depending on the underlying risk of diabetes mellitus in the population studied.

An Emax dose-response relationship was identified for the effect of atorvastatin on liver dysfunction, but the dose-response relationships for the other statins and adverse effects were inconclusive.

Hepatotoxicity occurred in 0.44% of 4075 patients on high dose atorvastatin [HDA], 0.07% of 72,336 on low dose atorvastatin [LDA], 0.09% of 44,675 on high dose simvastatin [HDS] and 0.05% of 119,732 on low dose simvastatin [LDS]. High dose was classified as 40–80mg daily and low dose 10–20mg daily. AHRs compared to LDS were 7.3 [4.2–12.7] for HDA, 1.4 [0.9–2.0] for LDA and 1.5 [1.0–2.2] for HDS.

allocation to low-intensity or moderate-intensity statin therapy resulted in a 10% proportional increase in new-onset diabetes (2420 of 39 179 participants assigned to receive a statin [1·3% per year] vs 2214 of 39 266 participants assigned to receive placebo [1·2% per year]; rate ratio [RR] 1·10, 95% CI 1·04–1·16). … allocation to high-intensity statin therapy resulted in a 36% proportional increase (1221 of 9935 participants assigned to receive a statin [4·8% per year] vs 905 of 9859 participants assigned to receive placebo [3·5% per year]; 1·36, 1·25–1·48).

Odds ratios were 1.12 (95% confidence interval [CI], 1.04-1.22; I(2) = 0%) for new-onset diabetes … representing 2.0 additional cases in the intensive-dose group per 1000 patient-years … the number needed to harm per year for intensive-dose statin therapy was 498 for new-onset diabetes.

Transient increases in liver enzymes occur in 0.5-2% of patients taking statins but are not clinically relevant; idiosyncratic liver injury due to statins is very rare and causality difficult to prove.

Patients taking Verapamil, Diltiazem, or Dronedarone Do not exceed ZOCOR 10 mg once daily. Patients taking Amiodarone, Amlodipine, or Ranolazine Do not exceed ZOCOR 20 mg once daily.

The 40 mg dose is contraindicated in patients with pre-disposing factors for myopathy/rhabdomyolysis. Such factors include: ... Asian patients. Pharmacokinetic studies show an approximate 2-fold elevation in median AUC and Cmax in Asian subjects (Japanese, Chinese, Filipino, Vietnamese and Koreans) compared with Caucasians.

A formula has been developed to predict creatinine clearance (Ccr) from serum creatinine (Scr) in adult males: (see article)(15% less in females). … The above formula gave a correlation coefficient between predicted and mean measured Ccr's of 0.83.

GFR = [(140−age) × weight]/[(72 × SCr) × 0.85 (if female)]

serum creatinine µmol/L to mg/dL, divide by 88.4

We developed new eGFR equations without race using data from two development data sets: 10 studies (8254 participants, 31.5% Black) for serum creatinine and 13 studies (5352 participants, 39.7% Black) for both serum creatinine and cystatin C.

eGFR = 142 × min(SCr/κ,1)α × max(SCr/κ,1)−1.200 × 0.9938Age × 1.012 [if female]

Ideal body weight (male) = 50 kg + 2.3 kg for each inch over 5 feet; ideal body weight (female) = 45.5 kg + 2.3 kg for each inch over 5 feet.