Side Effects of Teriparatide
Teriparatide commonly causes nausea, dizziness, vomiting, headache, palpitations, and leg cramps, with the most significant metabolic concern being hypercalcemia, which occurs 12.9 times more frequently than placebo. 1, 2
Common Adverse Effects Leading to Treatment Withdrawal
- Gastrointestinal symptoms are the most frequent reason for discontinuation, with nausea, vomiting, and gastritis occurring 3.26 times more often than placebo (moderate certainty evidence) 2
- Withdrawal due to adverse events increases significantly with teriparatide compared to placebo—17 more events per 1000 patients at 24 months and 127 more events per 1000 patients at 36 months (moderate certainty) 1
- At 36 months, teriparatide shows a 3.1-fold increased risk of withdrawal due to adverse events compared to bisphosphonates (low certainty) 1
Neurological and Cardiovascular Effects
- Headache occurs with increased frequency (odds ratio 1.46) compared to placebo (moderate certainty evidence) 2
- Dizziness is commonly reported and contributes to treatment discontinuation 1
- Palpitations have been documented, though with lower certainty evidence 1, 2
- Orthostatic hypotension can occur, particularly with initial dosing—the FDA label specifically recommends administering the first dose under circumstances where the patient can sit or lie down 3
Metabolic and Renal Complications
- Hypercalcemia is the most significant metabolic adverse effect, occurring with markedly increased frequency (odds ratio 12.9) compared to placebo (high certainty evidence) 2
- The hypercalcemic effect is typically transient and mild, but requires monitoring after 1 month of treatment 3, 4
- Renal side effects occur 2.36 times more frequently than placebo (moderate certainty) 2
- Hypercalciuria occurs 2.44 times more frequently than placebo (moderate certainty) 2
- In patients with severe renal impairment (CrCl <30 mL/min), teriparatide exposure increases by 73% and half-life by 77% 3
Musculoskeletal Symptoms
Serious Adverse Events and Long-Term Safety
- Serious adverse events show no significant difference compared to placebo (low certainty evidence) 1
- Osteosarcoma risk: While rat studies showed increased osteosarcoma incidence, postmarketing surveillance over 9 years found no cases attributable to teriparatide in humans (high certainty evidence) 2, 3
- The FDA maintains a black box warning based on animal data, contraindicating use in patients with open epiphyses, Paget's disease, prior skeletal radiation, or bone metastases 3
Drug Interactions and Special Considerations
- Digoxin toxicity risk: Teriparatide-induced hypercalcemia may predispose patients to digitalis toxicity—monitor for signs and symptoms when used concurrently 3
- Pregnancy and lactation: No human data available; animal studies showed skeletal deviations at doses ≥60 times the human dose—discontinue when pregnancy is recognized and avoid during breastfeeding 3
Overdose Manifestations
- Cases of accidental administration of up to 800 mcg (40 times the recommended dose) have been reported, causing transient nausea, weakness/lethargy, and hypotension 3
- Delayed hypercalcemic effects, vomiting, dizziness, and headache may occur with overdose 3
- No fatalities from overdose have been reported; management includes discontinuation, serum calcium monitoring, and supportive care with hydration 3
Critical Clinical Caveats
- Treatment duration limitation: Use should not exceed 2 years over a patient's lifetime unless high fracture risk persists, based on animal osteosarcoma data 2, 3
- Calcium supplementation: Total daily calcium intake should be limited to 1500 mg to minimize hypercalcemia risk 4
- Sequential therapy requirement: Teriparatide MUST be followed by antiresorptive therapy (bisphosphonates or denosumab) after discontinuation to prevent rapid bone loss 5, 2
- Avoid concurrent bisphosphonates: Combination therapy with bisphosphonates diminishes teriparatide's anabolic potential 4, 6